Journal of the Italian Society of Anatomic Pathology and Diagnostic

Cited in Index Medicus/MEDLINE, BIOSIS Previews, SCOPUS

Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology,Italian Division of the International Academy of Pathology

Vol. 105 December 2013

REVIEW

329 Computed tomography-histologic correlations in lung cancer I. Ariozzi, I. Paladini, L. Gnetti, M. Silva, D. Colombi, M. De Filippo, N. Sverzellati

ORIGINAL ARTICLES

337 Tumours of the skin adnexa: a case series with focus on multiple segmental forms M. D’Andrea, C. Reggiani, D. Fasano, C.M. Betts, F. Montanari, A. Lanzoni, M. Reggiani,

M.P. Foschini

342 Role of on-site microscopic evaluation of kidney biopsy for adequacy and allocation of glomeruli: comparison of renal biopsies with and without on-site microscopic evaluation

S.M. Gilani, D. Ockner, H. Qu

CASE REPORTS

346 Adenocarcinoma arising in a tailgut cyst: a case report S. Rammeh, S. Ben Abdelkrim, M.H. Ben Hadj Khalifa, R. Letaief, M. Mokni

349 Breast cholesterol granuloma: a report of two cases with discussion on potential pathogenesis

J. Bezić, M. Piljić-Burazer

353 Synchronous occurrence of pulmonary adenocarcinoma and pleural diffuse malignant mesothelioma

H. Imenpour, G.P. Ivaldi, A. Brianti, G. Pastorino, S. Biggi, L. Auriati, C. Simonassi

357 Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?

F. Limaiem, A. Khadhar, F. Hassan, S. Bouraoui, A. Lahmar, S. Mzabi

361 Letter to the Editor V. Eusebi

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Società Italiana di Anatomia Patologica e Citopatologia Diagnostica,Divisione Italiana della International Academy of Pathology

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Cited in Index Medicus/MEDLINE, BIOSIS Previews, SCOPUS

Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology,Italian Division of the International Academy of Pathology

Vol. 105 December 2013

Società Italiana di Anatomia Patologica e Citopatologia Diagnostica,Divisione Italiana della International Academy of Pathology

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CONTENTS

Review

Computed tomography-histologic correlations in lung cancerI. Ariozzi, I. Paladini, L. Gnetti, M. Silva, D. Colombi, M. De Filippo, N. Sverzellati

The multidisciplinary approach is ideal in the management of patients with lung cancer. Multidisciplinary evaluation strengthens the differential diag-nosis of aspecific radiological findings, indeed. Notably, the differential diagnosis of early stage lung cancer is a current challenge of CT imaging because the earlier the detection, the lower the accuracy of radiological fea-tures.This is particularly true for the most common subtype of lung cancer, adenocarcinoma, because it shows various radiological features. Such vari-ety is also reflected by the 2011 classification of lung cancer, that likely affected the diagnostic agreement between radiologist and clinician. This review discusses the common issues of lung cancer diagnosis by paired radiological-histologic interpretation of CT findings.

Original articles

Tumours of the skin adnexa: a case series with focus on multiple seg-mental formsM. D’Andrea, C. Reggiani, D. Fasano, C.M. Betts, F. Montanari, A. Lan-zoni, M. Reggiani, M.P. Foschini

Objective. Skin adnexal tumours (SAT) as a whole are rare tumours, and most of our current knowledge on SAT is from single case reports or small series focused on single histotypes. The purpose of this paper is to review a series of benign and malignant SAT diagnosed in a 20-year period. Methods. All consecutive cases of SAT diagnosed between January 1992 and Dicember 2011 were retrieved. All slides were reviewed and diagnosed according to currently accepted criteria.Results. 281 consecutive cases of SAT were found. The majority of cases (94.3%) were benign, the most frequent histotypes were eccrine spirade-noma, hidrocystoma, eccrine poroma, syringoma, sebaceous adenoma and trichofolliculoma. Benign SAT affected adult males more frequently (M/F = 153/112) (mean age 59 years). Recurrences were rare (2/265). Three cases of multiple segmental spiroadenoma were observed. Malignant SAT con-situted only 5.7% of all cases comprising sebaceous carcinoma, extrama-mmary Paget disease and apocrine carcinoma. There was a slight female predilection (M/F = 7/9) (mean age 72 years), although patients were older than those affected by benign SAT. All neoplasms were small and no recur-rences were recorded.Conclusion. SAT are rare and most frequently benign. Correct diagnosis and complete surgical removal are important.

Role of on-site microscopic evaluation of kidney biopsy for adequacy and allocation of glomeruli: comparison of renal biopsies with and without on-site microscopic evaluationS.M. Gilani, D. Ockner, H. Qu

Evaluation of kidney core biopsies ideally begins with on-site microscopic examination for adequacy and allocation of tissue for light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). How-ever, some renal biopsies are not microscopically evaluated by a patholo-gist at the time of procedure, and are allocated without on-site evaluation. This study compares the actual outcome of these two techniques.We reviewed the reports of patients who underwent kidney biopsy for medical causes in the past two years. Eighty-eight biopsies had on-site microscopic evaluation by pathologists, and 70 biopsies did not undergo on-site evaluation.For biopsies without on-site evaluation, no glomeruli were seen in 5 (7.14%) cases for LM, 11 (15.71%) cases for IF and 6 (8.57%) cases for EM. In cases with on-site evaluation, the absence of glomeruli was identi-fied in 1 (1.13%) case for LM, 3 (3.4%) for IF and 3 (3.4%) for EM. The biopsies with on-site microscopic evaluation had 5.68% of the cases con-sidered as inadequate, while 22% of biopsies without on-site evaluation were considered inadequate. The biopsies with on-site evaluation tended to have more glomeruli obtained during the procedure (p < 0.0005).Without on-site evaluation, the likelihood of getting an inadequate speci-men compared to on-site evaluation is nearly four times greater.

Case reports

Adenocarcinoma arising in a tailgut cyst: a case reportS. Rammeh, S. Ben Abdelkrim, M.H. Ben Hadj Khalifa, R. Letaief, M. Mokni

Tailgut cyst (TGC), also called retrorectal hamartoma, is a rare congeni-tal lesion arising from persistent remnants of the postanal gut. Malignant transformation of TGC is exceedingly uncommon. We report herein the clinicopathologic features and the follow-up of a new case of a TGC with adenocarcinomatous transformation occurring in a 61 year-old woman.

Breast cholesterol granuloma: a report of two cases with discussion on potential pathogenesisJ. Bezić, M. Piljić-Burazer

Breast cholesterol granuloma is a very rare lesion that can clinically and radiologically mimic breast carcinoma. Herein, we report two cases of breast cholesterol granulomas along with clinical, radiological, cytologi-cal and histological findings. We also discuss the potential pathogen-esis of this rare breast nodular lesion, suggesting its relation not only to mammary duct ectasia but also to the rupture of a breast macrocyst.

Synchronous occurrence of pulmonary adenocarcinoma and pleural diffuse malignant mesotheliomaH. Imenpour, G.P. Ivaldi, A. Brianti, G. Pastorino, S. Biggi, L. Auriati, C. Simonassi

We report a rare case of diffuse malignant pleural mesothelioma synchro-nous with a localized adenocarcinoma of lung in a 68-year old man with a suspicious history of asbestos exposure. Computed tomography revealed a sub-pleural mass in the lower lobe and an irregular dense area of medium lobe of right lung with thickening of pleura encasing the lung parenchyma and homolateral pleural effusion 1 cm thick. The patient underwent sur-gery and a right medium and lower lobectomy was performed. Upon fro-zen sections, intraoperative diagnosis was adenocarcinoma with a poorly differentiated component of lung infiltrating the pleura. The postoperative histological definitive diagnosis with an important contribution of immu-nostaining was synchronous pulmonary adenocarcinoma and pleural dif-fuse malignant epithelioid mesothelioma.

Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?F. Limaiem, A. Khadhar, F. Hassan, S. Ben Slama, A. Lahmar, S. Bouraoui, S. Mzabi

A 77-year-old female patient with a medical history significant for hypertension and epilepsy presented with right breast pain of 6-months duration. Examination revealed a hard sub-areola tender mass with irregular borders associated with mild right nipple retraction. Mam-mography showed a 2.2 x 2.4 cm stellate mass of the right breast. Ultrasound-guided core biopsies of the tumour were performed. Patho-logical examination revealed a grade II infiltrating ductal carcinoma. The patient underwent right radical mastectomy with homolateral axillary lymphadenectomy. Histological examination of the surgical specimen revealed grade II infiltrating ductal carcinoma concomitant with granulomatous lobular mastitis. To the best of our knowledge, the coexistence of granulomatous lobular mastitis and ductal carcinoma has been described only twice in the English language literature. The theory that chronic inflammation leads to cancer is well documented. Whether our patient had developed cancer from granulomatous lobular mastitis or otherwise is a matter of debate until more cases are encoun-tered and more research is done in the area of breast cancer patho-genesis with regards to it arising from granulomatous lobular mastitis.

pathologica 2013;105:329-336

Introduction

Primary cancers of the lung encompass several histo-logical entities that arise from various pulmonary com-ponents. A multidisciplinary approach is now recom-mended for diagnosis and treatment planning because it integrates radiologic and histologic data.Since its inception, imaging has been included in the management of patients with lung cancer. Currently, computed tomography (CT) is the radiological gold stan-dard because it grants very high sensitivity for detection of lung cancer. Of note, the increasing use of thin-sec-tion collimation allows the identification of very small and subsolid nodules that were previously undetectable. The advantage of early detection, however, is weakened by a decrease in specificity that raised concerns about differential diagnosis and management of these findings. In this scenario, comprehensive and multidisciplinary approach is ideal. In particular, such a synergy is made easier by the increasing familiarity of non-radiologist specialists with imaging features.The aim of this review is to summarize the main CT

features and histologic correlation of the most common lung cancers arising from the epithelial surface of bron-chi and alveoli.

Basic computed tomography signs of lung cancer

Primary lung cancer usually appears on computed to-mography (CT) as a subsolid nodule, solid nodule or mass. A pulmonary nodule is defined as a sharply-de-fined circular opacity that is 2 to 30 mm in diameter. Solid nodules are those composed of soft tissue that completely obscures the lung parenchyma 1. In distinc-tion, subsolid nodules (SSNs) are defined as areas of increased lung attenuation through which normal pa-renchymal structures such as pulmonary vessels can be seen 1. A pulmonary mass is any pulmonary, pleural, or mediastinal lesion seen as an opacity greater than 3 cm in diameter (without considering contour, border, or density characteristics) 1. A pulmonary mass usually im-plies a solid or partly solid opacity.

Review

Computed tomography-histologic correlations in lung cancer

I. ARIOZZI, I. PALADINI, L. GNETTI*, M. SILVA, D. COLOMBI, M. DE FILIPPO, N. SVERZELLATI Dipartimento di Scienze Chirurgiche, Sezione di Radiologia, Università di Parma; * Department Onco-Ematologico Internistico,

Sezione di Anatomia Patologica, Azienda Ospedaliero-Universitaria di Parma, Italy

Key words

Lung cancer • CT • Histology • Differential diagnosis

Summary

CorrespondenceNicola Sverzellati, Section of Diagnostic Imaging, Department of Surgical Sciences, University of Parma, via Gramsci 14, 43126 Parma, Italy - E-mail: [email protected]

The multidisciplinary approach is ideal in the management of patients with lung cancer. Multidisciplinary evaluation strength-ens the differential diagnosis of aspecific radiological findings, indeed. Notably, the differential diagnosis of early stage lung can-cer is a current challenge of CT imaging because the earlier the detection, the lower the accuracy of radiological features.This is particularly true for the most common subtype of lung cancer,

adenocarcinoma, because it shows various radiological features. Such variety is also reflected by the 2011 classification of lung cancer, that likely affected the diagnostic agreement between radiologist and clinician. This review discusses the common issues of lung cancer diag-nosis by paired radiological-histologic interpretation of CT find-ings.

I. ArIozzI et Al.330

Benign versus malignant CT features of pulmonary nodules

Pulmonary nodules may have various etiologies, includ-ing neoplasm, infection and inflammation, vascular, and congenital abnormalities. Still, the overall likelihood of malignancy for a pulmonary nodule is low 2 3. First, it is essential to establish if nodules are multiple with specific distribution within the pulmonary second-ary lobule (e.g. perilymphatic or centrilobular). Multiple small incidental nodules are considered independently when lacking a distinctive relationship to structures within the secondary lobule. Otherwise, the description of correlation between nodule distribution and non-neo-plastic etiology is beyond the scope of this article 4.Accepted predictors of malignancy for a lung nodule are as follows: upper-lobe location, size > 20 mm, ill-defined or spiculated margins, air bronchograms, inho-mogeneous central attenuation, cavitation with nodular wall thicker than 15 mm 2 5 6. Moreover, round nodules are more likely to be malignant than triangular or flat-shaped nodules. The latters may be intrapulmonary lymph nodes or granulomas 7 8. Of note, intrapulmonary lymph nodes are increasingly recognized as a benign cause of solitary pulmonary nodule on CT. Notably, lymph node has generally perifissural or subpleural location (< 15 mm from pleural surface), usually with coffee-bean shape and thin, linear opacity of connection to pleural surface (Fig. 1) 8-11.Calcification and fat tissue can both be detected on CT. Completely calcified nodules are almost invariably be-nign. Otherwise, malignant calcification is rare and is usually stippled or eccentric 3. The detection of fat den-sity in a pulmonary nodule strongly suggests hamarto-ma 13 14. Subsolid nodules (SSNs) include both pure ground glass nodules (pure GGNs) and part-solid ground-glass nod-ules (part-solid GGNs). Of note, the likelihood of ma-lignancy is greater in SSN than solid nodule. In a lung cancer screening setting, 63% incidence of malignancy was reported for part-solid GGNs (Fig. 2), whereas it was lower for pure GGNs and solid nodules (18% and 7%, respectively) 15. Hence, the solid component of SSN is the radiological feature with the strongest association with malignancy 15 16. Both pure GGNs and part-solid GGNs may be transient because they may reflect infectious or inflammatory process. Therefore, a conservative approach with initial follow-up is recommended 17-19. On the other hand, per-sistency is a malignant feature for SSN. Moreover, fea-tures suggesting malignancy of larger SSNs also include lobulated margins, pleural tags, air bronchograms, and internal lucencies 20-22. However, it was demonstrated that CT features cannot reliably differentiate benign ver-sus malignant persistent SSNs 23 24.Interval change in size and density of SSN should be thoroughly assessed before surgical approach. Of note, in a lung cancer screening setting, the progression rate of SSN toward clinically relevant disease was extreme-

Fig. 1. typical ct features of intrapulmonary lymph node: in the left lower lobe there is a lentiform shaped small perifissural nod-ule connected to a thin interlobular septum.

Fig. 2. invasive adenocarcinoma in a 57-year-old male. (a) thin-section ct image shows a 20-mm ground glass nodule with a sol-id component in the right lower lobe. (b) the photomicrograph of the corresponding histologic specimen shows a predominant lepidic growth pattern mixed with a papillary component (original magnification, X10; hematoxylin-eosin stain).

B

A

331Computed tomography-histologiC Correlations in lung CanCer

ly low. These data support active surveillance of small SSN, indeed. However, the optimal balance between prompt resection and the need to limit overtreatment is still a matter of debate 25.Cautiously, pulmonary nodule is classified as an indeter-minate, possibly malignant lesion if no definite benign morphologic finding is seen. Then, the management de-pends on size and density, namely: i) if solid and larger than 8 mm, the nodule should be evaluated by other non-invasive (e.g. PET) or invasive procedures; if solid and smaller than 8 mm, it should be followed-up according to predetermined time intervals as suggested by major international guidelines 26; ii) SSNs could also be fol-lowed-up, but surgery is generally suggested for persis-tent ones because of their high likelihood of malignancy 25 (Tab. I).

CT-histologic correlations of subsolid nodules and invasive mucinous adenocarcinoma

SSNs may represent a variety of disorders ranging from inflammatory abnormalities to lung neoplasm. Evolu-tion of the SSN over time is the most accurate feature for differential diagnosis between benign and malignant finding (Figs. 2, 3). Otherwise, other CT features of SSN may allow narrowing the diffferential diagnosis. Neoplastic pure GGN reflects focal incomplete oblit-eration of airspace. Notably, pure GGN may associate either to haemorrhagic tumor or to “lepidic” growth pat-tern of neoplastic cells lining over alveolar wall (Fig. 2).

Nevertheless, these pure GGNs may be caused by benign abnormalities, such as inflammation, edema, fibrosis, partial collapse of alveoli, focal benign haemorrhage, infectious load (macrophages, pus, debris, colonization from bacteria, virus, and fungi). Neoplastic part-solid GGN is seen in minimally-inva-sive (MIA) or invasive adenocarcinoma. Notably, the solid component is usually central and represents the invasive portion of the neoplasm, whereas, the ground glass opacity is usually peripheral and reflects areas of lepidic growth (Fig. 2). Contributors to solid component may be various, namely: alveolar collapse, deposition of inflammatory cells and fibroblast, fibrosis and fibrotic scar. Furthermore, the amount of ground glass compo-nent directly correlates with the likelihood of mutation of epidermal growth factor receptor (EGFR). Accord-ingly, the 2011 Multidisciplinary Classification of Ade-nocarcinoma focused on the strong relation between CT findings and hystology 27. Non-mucinous adenocarcino-ma shows indeed a direct correlation between size of the solid component on CT and tumoral invasion on histol-ogy. According to radiologic-histologic correlation, the 2011 classification implies T staging to be calculated on the diameter of solid component, whereas in previous classification the whole nodule was measured, including the ground glass component. Hence, two main thresh-olds were suggested for the size of solid component: di-ameter < 3 mm defines adenocarcinoma in situ (AIS), diameter 3-5 mm defines minimally invasive adenoca-rinoma (MIA), and diameter > 5 mm defines invasive non-mucinous adenocarcinoma 28 29

(Tab. II). However, this correlation is less strong in mucinous adenocarci-

Tab. I. Management of pulmonary nodule (adapted from reference 25).

Nodule Type Management Recommendation Additional remarks

Solitary Pure GGN

< 5 mmNo additional follow up required

obtain contiguous 1mm to confirm that nodule is truly a pure ggN

≥ 5 mm initial follow-up at 3 months to confirm persistence, then annual ct surveillance for a minimum of 3 years

FDg pEt is of limited value, potentially misleading, and therefore not recommended

Solitary part-solid nodules initial follow-up at 3 months to confirm persistence.

if persistent and solid component <5mm, yearly ct surveillance for a minimun of 3 years.

if persistent and solid component ≥ 5 mm, biopsy or surgical resection

consider pEt/ct for part-solid nodules > 10mm

Multiple subsolid nodules

pure ggNs ≤5 mm Follow-up ct at 2 and 4 years consider alternative cause of multiple ggNs ≤ 5mm

pure ggNs > 5mm without dominant lesion(s)

initial follow-up ct at 3 months.if persistent, yearly ct surveillance for a minimun of 3 years

FDg pEt is of limited value, potentially misleading and therefore not recommended

Dominant nodule with part-solid or solid component

initial follow-up at 3 month to confirm persistence. if persistent biopsy or surgical resection is recommended especially for lesions with > 6 mm solid component

consider lung sparing surgery for patients with dominant lesion(s) suspicious for lung cancer


noma because the solid component may represent both the neoplastic invasion and the alveolar collapse related to mucinous obstruction 16 28-31.Multiple SSNs are more likely preinvasive lesions, whereas invasive adenocarcinoma more commonly looks like a solitary SSN. A number of molecular stud-ies have demonstrated that multifocal SSNs are more likely synchronous primary cancers rather than intrapul-monary spread of disease. Furthermore, non-malignant multiple SSNs are also seen in pulmonary infections (e.g. viral), eosinophilic lung diseases, drug toxicity, radiation-induced pulmonary disease, and inhalational pulmonary disease from cigarette smoke or organic and inorganic dust.The main CT features of invasive adenocarcinoma with predominant lepidic growth can be related to the histo-logic abnormalities as follows: 1) ground glass opac-ity caused by replacement, tumoral growth or lepidic growth of either cuboidal or columnar cells, without invasion of the stroma 16 30 32; 2) consolidation related to active fibroblasts and tumor cells proliferation evolv-ing into areas of retained mucous and alveolar collapse (consolidation can even evolve to a lobar swelling and a bulging of the interlobar fissure) 16 33; 3) crazy pav-ing pattern described as diffuse ground-glass attenua-tion with superimposed interlobular septal thickening and intralobular lines related to interstitial infiltration by tumor cells or inflammatory component (more fre-quently observed in the mucinous multifocal disease) 34; 4) tree-in-bud opacities (uncommon feature) represent-ing bronchiolar dilatation and filling of mucus or fluid, resembling a branching or a budding tree 35. Besides, invasive adenocarcinoma may associate with CT fea-tures, such as: bubble-like radiolucencies 30 33, the open bronchus sign (larger membranous bronchioles within areas of lung consolidation) 7 22, the angiogram sign (seen as enhancing branching pulmonary vessels in a

homogeneous low-attenuating large consolidation of lung parenchyma) 29 31 33. The histological type of invasive adenocarcinoma can be roughly predicted by CT 16 22 33. In particular, the muci-nous type commonly appears as areas of extensive con-solidation, ground glass or crazy paving representing the tumour growth along alveolar wall or alveolar space filled with mucin (Fig. 4). On the other hand, the non-mucinous type manifests as a solitary SSN, reflecting a tumoural growth along alveolar wall with preserved underlying framework 16 22. Mihara et al. 32 also found a correlation between three bronchioloalveolar subtypes (globet cells, Clara cells and type 2 pneumocyte sub-type) and their CT patterns, but an attempt of such a dis-tinction in clinical practice is likely unreliable.A number of lung abnormalities have been associated with the adenocarcinoma, such as: tuberculous scarring, lung fibrosis, congenital pulmonary airway malforma-tion (CPAM). Because they may represent precursor lesions of adenocarcinoma, the prompt recognition of these findings should grant timely histologic diagnosis. Moreover, it has been suggested that an unstable epithe-lial component within the wall of congenital cyst may be responsible for the development of adenocarcinoma. Also, areas of metaplasia within fibrosis or malforma-tion may evolve to dysplastic lesions 36-38.

CT features of the other main histological subtypes of lung cancer

The four major histological types of lung cancer (e.g. squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma) commonly show different CT features 39 40.Squamous cell carcinoma usually grows in the main, lo-bar or segmental bronchi as an endobronchial mass that

Fig. 3. atypical adenomatous hyperplasia in a 53-year-old female. (a) thin-section ct image shows a 6-mm well-defined pure ground-glass nodule without any solid component. (b) photomicrograph shows thickened alveolar walls covered by a single layer of moderately atypical cuboidal pneumocytes (original magnification, X10; haematoxylin-eosin statining). the cells consist of rounded, cuboidal, low columnar with round to oval nuclei.

BA


spreads by infiltration of the bronchial wall and rapid invasion into lymphatic system 41 42. At the first CT diag-nosis, squamous cell adenocarcinoma appears as a large, rounded solid mass that may cavitate and invade hilar and mediastinal structures, typically with lymph node involvement 43. Only about 30% of squamous cell car-cinoma occur as solitary nodule or mass at the lung pe-riphery. Secondary signs of bronchial obstruction (e.g. atelectasis, obstructive pneumonia, mucous plugs, etc.) are frequently associated to squamous cell carcinoma that is often indistinguishable from the surrounding col-lapsed parenchyma.Adenocarcinoma appears as a peripheral solitary nod-ule or mass in 75% of cases, more commonly in the up-per lobes. Yet, adenocarcinoma may also grow on main

airways as a central mass with mediastinal lymph node enlargement, thus mimicking squamous cell carcino-ma 41 44.Small cell carcinoma mostly originates from the main or lobar bronchi as a voluminous hilar or para-hilar mass associated with parenchymal invasion and massive me-diastinal lymph node enlargement 41 45. Therefore, CT features of small cell carcinoma may overlap findings of squamous cell carcinoma 46.Large cell carcinoma occurs as a voluminous peripheral mass (> 40 mm) with irregular margins, in more than 60% of cases. It is generally larger in size than adeno-carcinoma at the time of diagnosis. Cavitation and calci-fication are rare. Of note, early extrapulmonary metasta-ses are frequently observed at first diagnosis 41 47.

Tab. II. adenocarcinoma histopathologic-ct correlation (adapted from references 27 28).

Histopathologic findings small biopsy/citology: IASLC/ATS/ERS 2011 Classification of Lung Adenocarcinoma

CT findings

Preinvasive lesions

Atypical adenomatous hyperplasia (aah) pure ground-glass nodule, typically <5 mm in diameter, although these lesions can be as large as 1 to 2 cm.

Adenocarcinoma in situ (aiS) Mostly nonsolid nodule, slightly more opaque than aah.

Nonmucinous aiS pure ground glass nodule >5 mm in diameter. it may also appear as part-solid ggN for the presence of alveolar collapse.

Mucinous aiS Solitary solid nodule.

Mixed mucinous/nonmucinous overlap ct features of mucinous and non-mucinous

Minimally invasive adenocarcinoma (Mia) the lepidic growth portion is seen as hazy ground glass component, whereas the invasive portion is solid and ussually with diameter <5 mm. alveolar collapse, inlammatory cells, fibroblast, fibrosis, and fibrotic scar appear as solid area.

Nonmucinous Mia (usually) Either pure ggN or part-solid ggN with a small solid component ≤ 5mm.

Mucinous Mia (rare) Mucin may contribute to a solid, part-solid or predominantly solid appearance of the tumor at ct.

Mixed mucinous/nonmucinous Mia overlap ct features mucinous/nonmucinous.invasive adenocarcinoma Morphologic adenocarcinoma pattern clearly presentlepidic predominant pattern Usually manifest as a solid or part solid noldule, only rarely

appears as pure ggNs.acinar predominant patternpapillary predominant patternMicropapillary predominant patternSolid predominant patternadenocarcinoma with (describe pattern present) and clear cell features

Solid or predominantly solid nodule or mass with a small non solid component.

adenocarcinoma with (describe pattern present) and signet ring featuresMorphologic adenocarcinoma pattern not present: non small cell carcinoma, favor adenocarcinomaVariants of invasive adenocarcinomainvasive mucinous adenocarcinoma aspecific appareance: single or multifocal (sometimes

multilobar) solid, part-solid or ground glass nodules or masses, frequently centrilobular or bronchocentric. consolidation and air bronchogram are also seen.

colloid typically seen as solid or predominantly solid.

Fetal (low and high grade)

Enteric


Bronchial carcinoid

Bronchial carcinoids may be typical or atypical. Both types of carcinoid appear as a spherical or ovoid nod-ule or mass with a well-defined and slightly lobulated border. However, atypical carcinoids have been reported to be larger than typical carcinoids, with mean diameter of 3.6 cm and 2.3 cm, respectively 48. Calcifications oc-cur in up to 30% of lesions showing punctate or diffuse pattern 49. Both typical and atypical carcinoids show high contrast enhancement due to the abundant vascular stroma and the numerous thin-walled blood vessels 50. The majority of carcinoids belongs to the typical sub-type (80-90% of cases) 51

. Notably, typical carcinoid is usually seen as an endobronchial nodule in the main, lobar, or segmental airways or as a hilar-perihilar mass associated with bronchial narrowing, deformation, ob-struction, and even secondary signs of airway obstruc-tion such as atelectasis or obstructive pneumonia (Fig. 5). Peripheral lesions are more likely associated with the atypical subtype 52 53.

Mimickers of lung cancer on CT

Many diseases may appear as pulmonary nodule, mass or irregular consolidation on CT. Thus, these CT abnor-malities may be non-specific of malignancy when other signs of neoplastic lesion are lacking (e.g. contiguous or-gans invasion, metastases etc.). Irregular consolidation or masses resembling lung tumors may also occur in infec-tions, autoimmune diseases, and inflammatory disorders. Differential diagnosis is made even more difficult by as-pecific and overlapping clinical findings 54 55.Consolidation without obvious cavitation, as well as few large nodules may be all forms of radiological presen-tation of granulomatosis with polyangiitis, previously known as Wegener disease (Fig. 6). Such a vasculitis may

Fig. 5. typical carcinoid in a 43-year-old individual. ct scan shows a nodule obstructing the right lower lobe bronchus and atelecta-sis in the right upper lobe.

Fig. 4. Mucinous adenocarcinoma (formerly bronchioloalveolar carcinoma) in a 54-year-old woman. (a) thin-section ct image shows patchy consolidation with air bronchogram, ground glass opacity, crazy paving pattern (arrow), and scant nodules. (b,c) photomicrographs (original magnification, X10, X4; hematoxylin-eosin stain) show mucin-containing tumor cells along the alveolar walls. the alveolar spaces are filled with mucin, as well.

B

A

C


also cause airway involvement, with stenosis of large air-ways that might be misinterpreted as lung cancer 56.Occasionally, a large solitary nodule or mass with ir-regular margins may be seen in organizing pneumonia, prompting invasive investigations for lung cancer 57 58. Also exogenous lipoid pneumonia can manifest with ir-regular mass-like opacities. In this case, superimposed fibrosis on CT can make differential diagnosis with lung cancer more difficult. A striking diagnostic CT clue for lipoid pneumonia is fat attenuation within the pulmo-nary lesion 14 59. Pulmonary infections such as cryptococcosis, actinomy-

cosis, histoplasmosis or nocardiosis may present as large masses or nodules mimicking lung cancer. In the pres-ence of specific anamnestic data, the radiologist may suggest infectious differential diagnosis 60.IgG4-related lung disease may also cause misdiagnosis of pulmonary findings because it may appear as large solid or subsolid nodules, with ground glass opacity (Fig. 7). Such a spectrum of appearance may particularly overlap adenocarcinoma with lepidic growth pattern 61 62.

Fig. 6. ct through the upper lobes obtained in a 35-year-old male with known granulomatosis with polyangiitis. two pulmonary nodules mimicking lung cancer are seen in the right upper lobe.

Fig. 7. thin-section ct scan in a 76-year-old female with igg4-related lung disease demonstrates a solid spiculated nodule in the right upper lobe. Spiculations of the nodule mimick a lung cancer features.

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pathologica 2013;105:337-341

Introduction

Skin adnexal tumours (SAT) constitute a wide spectrum of lesions differentiating towards epithelial adnexal structures. SAT are classified according to their pre-sumed origin into those with apocrine, eccrine, follicular and sebaceous differentiation. Almost all of these types of tumours can have benign and malignant counterparts. Even though the histopathological criteria to define the biological behaviour are well established 1 2, SAT form a wide morphological spectrum of lesions, that can some-times cause difficult histological diagnosis. Only a few recently published papers in the literature considered appendageal tumours as a single group, while most of our current knowledge on SAT is derived from single case reports or small series focusing on a simple histotype.

The purpose of this paper is to review a series of benign and malignant SAT diagnosed over a 20- year period.

Methods

All cases of skin adnexal tumours diagnosed between 1 January 1992 and 31 December 2011 at the Section of Anatomic Pathology of the Department of Biomedical Sciences and Neuromuscular Disorders at Bellaria Hos-pital were retrieved.The medical and surgical records of the cases were ana-lyzed, and all original slides were reviewed and diag-nosed according to current criteria 1 2. To establish the incidence of SAT, the number of cases retrieved was compared with the total number of non-melanocytic skin epithelial tumours, including squa-

ORiginal aRticle

Tumours of the skin adnexa: a case series with focus on multiple segmental forms

M. D’ANDREA1, C. REGGIANI2, D. FASANO3, C.M. BETTS4, F. MONTANARI3, A. LANZONI5, M. REGGIANI5, M.P. FOSCHINI1

1 Department of Biomedical and Neuromotor Sciences, University of Bologna, Section of Anatomic Pathology “M. Malpighi”, at Bellaria Hospital, Bologna, Italy; 2 Department of Dermatology, University of Modena, Italy; 3 Operative Unit of Plastic Surgery,

Bellaria Hospital, Bologna, Italy; 4 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 5 Operative Unit of Dermatology, Bellaria Hospital, Bologna, Italy

Key words

Skin adnexa • Eccrine spiroadenoma • Multiple segmental eccrine spiroadenoma

Summary

CorrespondenceMaria Pia Foschini, Department of Biomedical and Neuromotor Sciences, University of Bologna, Section of Anatomic Pathology, Bellaria Hospital, via Altura, 3, 40139 Bologna, Italy - Tel. +39 051 6225523 - Fax +39 051 6225759 – E-mail: [email protected]

Objective. Skin adnexal tumours (SAT) as a whole are rare tumours, and most of our current knowledge on SAT is from sin-gle case reports or small series focused on single histotypes. The purpose of this paper is to review a series of benign and malignant SAT diagnosed in a 20-year period. Methods. All consecutive cases of SAT diagnosed between January 1992 and Dicember 2011 were retrieved. All slides were reviewed and diagnosed according to currently accepted criteria.Results. 281 consecutive cases of SAT were found. The major-ity of cases (94.3%) were benign, the most frequent histotypes were eccrine spiradenoma, hidrocystoma, eccrine poroma, syr-

ingoma, sebaceous adenoma and trichofolliculoma. Benign SAT affected adult males more frequently (M/F = 153/112) (mean age 59 years). Recurrences were rare (2/265). Three cases of multiple segmental spiroadenoma were observed. Malignant SAT consi-tuted only 5.7% of all cases comprising sebaceous carcinoma, extramammary Paget disease and apocrine carcinoma. There was a slight female predilection (M/F = 7/9) (mean age 72 years), although patients were older than those affected by benign SAT. All neoplasms were small and no recurrences were recorded.Conclusion. SAT are rare and most frequently benign. Correct diagnosis and complete surgical removal are important.

M. D’AnDreA et Al.338

mous and basal cell carcinomas, diagnosed in the same time interval.

Results

281 cases were retrieved and constituted the basis of the present study. Patients consisted of 160 males (56.93%) and 121 females (43.07%), with an age from 12 to 99 years (mean age 62.82 years). The incidence of SAT was

evaluated among non-melanocytic epithelial tumours of the skin. In the same time interval, besides the 281 SAT cases, 7567 basal cell carcinomas and 1459 squa-mous cell carcinomas were diagnosed. Therefore, SAT constituted 3.01% of a total of 9026 cases of epithelial tumours of the skin. Clinical data are summarized in Tables I and II.The vast majority of SAT cases were benign (265 cases, 94.3%), while only 16 (5.7%) malignant cases were ob-served.

Tab. I. clinical data of benign Sat.

Histotype No. cases M\F Age range (mean±SD)

Diameter range(mean±SD)

Recurrences&

multiple nodulesSpiradenoma 55 32/23 21-90

(52.55±16.3)0.2-3 cm

(1.2±1.08cm)1 recurrence after 6 years

3 multiple noduleshidrocystoma 52 30/22 22-84

(58.02±16.0)0.2-2.5 cm

(0.81±0.47cm)-

Eccrine poroma 45 21/24 31-80(60.02±13.3)

0.3-3.7 cm(0.90 ±0.65 cm)

1 recurrence after 7 months

Syringoma 41 21/20 32-93(55.62±15.9)

0.2-3.2 cm(0.95±0.70 cm)

-

Sebaceous adenoma 24 21/3 32-84(68.29±13.9)

0.4-3.2 cm(0.64±0.57 cm)

-

trichofolliculoma 21 14/7 21-89(59.47±21.2)

0.3-1.5 cm(0.54±0.34 cm)

-

trichoblastoma 17 9/8 12-82(62.82±19.1)

0.3-3.5 cm(1.1±0.86 cm)

trichilemmoma 10 5/5 24-79(55.4±18.7)

0.4-2.2 cm(0.85±0.54 cm)

-

Tab. II. clinical data of malignant Sat.

Histotype No.cases

M/F Age range(median±SD)

Diameter range(median±SD)

Recurrences

Sebaceous carcinoma 6 2/4 39-86(65.83±18.1)

1.3-2.4 cm(1.74±0.56 cm)

-

EMpD 6 1/5 62-99(78.33±14.8)

0.2-1.5 cm(01.06 ±0.58 cm)

-

apocrine carcinoma 4 4/0 61-86(73.33±12.5)

1-1.7 cm(1.35±0.49 cm)

-

legend: No. cases=number of cases; M=male; F=female.

EMpD=extra-mammary paget disease.

Tab. III. Sites of benign lesions.

Torso Scalp Face Axilla Back Limbs Periocular Skinhidroc. - 7 23 2 3 3 9 5Syring. 2 2 21 1 3 4 6 2poroma 5 5 7 3 3 21 - 1Spirad. 9 7 4 - 14 17 2 2tricobl. 2 1 9 1 1 3 - -trichil. 1 5 2 - - 2 - -tricof. - 2 15 - - 4 - -Seb. ad - 1 15 - 2 - 3 3total 19 30 96 7 26 54 20 13

Legend: ad=adenoma; ca=carcinoma; Seb=sebaceous; apo=apocrine; tricof=tricofolliculoma; trichil=trichilemmoma; tricobl=tricoblastoma; Spirad=spiradenoma; Syring=syringoma; hidroc=hidrocistoma.

339Skin adnexal tumourS

Benign SATThe most frequent histotypes of benign SAT (94.3%), in descending order were: spiradenoma (55 cases), hi-drocystoma (52 cases), eccrine poroma (45 cases), syr-ingoma (41 cases), sebaceous adenoma (24 cases) and trichofolliculoma (21 cases). Most cases of benign SAT affected adult patients, the mean age being 59.20 years, ranging from 12 to 99 years. Only one case was observed in a patient younger than 18, specifically a 12-year-old girl presenting with a trichoblastoma. In almost all cases there was a slightly greater incidence in males (M/F = 153/112). Only eccrine poroma (M/F = 21/24) affected female patients more frequently than males.

All cases had been diagnosed and removed when they were small in size. Mean diameter was 0.9 cm, with a range from 0.2 cm to 3.7 cm. The largest diameter ob-served was in a case of eccrine poroma, while the small-est were cases of eccrine spiradenoma, hydrocystoma and syringoma.Sites of lesions are summarized in Table III and Fig-ure 1. Cases of benign SAT were localized as follows: head and neck (146 cases, 51.9%), limbs (54 cases, 19.2%) and back (26 cases, 9.3%).Recurrences appeared in only two cases (0.71%). One case, a male with eccrine spiradenoma, presented a local recurrence 6 years after the first surgery. The neoplasm was in close proximity to surgical margins at the time of first presentation. The second case was a male patient with a eccrine poroma who presented a recurrence 7 months after first surgery, and in this case also the mar-gins were involved by the neoplasm after first removal.

Multiple segmental formsThree of 55 cases of eccrine spiradenoma (1.06% of all SAT and 5.5% of eccrine spiroadenoma) presented as multiple segmental forms, appearing as multiple nodules affecting one region. Multiple segmental eccrine spirade-noma (MSES) affected two females (aged 32 and 73) and one male (aged 22). The two female patients presented multiple nodules located, respectively, in the right arm and scalp, thus presenting a zosteriform appearance 3. On the contrary, the male patient developed multiple nodules located in the torso and back, thus developing a derma-tomal presentation 4. On histology all lesions were com-posed of multiple dermal nodules, had well defined bor-ders and were constituted by clusters of small, basophilic cells, intermingled with lymphocytes (Fig. 2). The nod-ules ranged in greatest axis from 146 microns to 15 mm. In the female patient presenting nodules in the right arm, the nodules appeared over a two year period.

Malignant SATThe malignant SAT observed herein were composed of, in descending order: sebaceous carcinoma (SC) (6 cases), ex-

tra-mammary Paget disease (EMPD) (6 cases) and apo-crine carcinoma (AC) (4 cas-es). Patients presenting ma-lignant SAT were older that those affected by the benign forms, with a mean age of 72.58 years (range 39 to 99 years). In SC and EMPD, a slightly greater incidence in female patients (M/F = 3/9) was observed. On the con-trary, AC affected male pa-tients only (M/F = 4/0). All cases of malignant SATs were small in size and radi-cal surgical excision was achieved. The mean diam-

Fig. 1. Schematic representation of sites of benign and malignant Sats.

Fig. 2. Multiple segmental eccrine spiroadenoma: a: upon histology it shows multiple nodules vary-ing in size. B: in this case, nodules appeared over a two year period.

A

B

M. D’AnDreA et Al.340

eter was 1.33 cm (range 0.2 cm to 2.74 cm). The larg-est diameter was seen in sebaceous carcinoma and the smallest in EMPD. Malignant SATs were located (Tab.IV and Fig. 1) as follows: head and neck region (7 cases, 43.7%), torso (5 cases, 31.3%), axilla (3 cases, 18.7%) and limbs (1 cases, 6.3%). No recurrences were recorded among the cases of malignant SATs.

Discussion

The appendageal tumours constitute a small percent-age 5-7 of all tumours of the skin. The present series ob-served during a period of 20 years consists of 281 cases, corresponding to 3.01% of non-melanocytic lesions of skin. Samalia 6 analyzed adnexal skin tumours in Zaria (Niger), and found only 52 cases of SAT among 5642 cutaneous tumours (0.92%) (melanocytic and non-men-alocytic tumours of skin) during a period of 15 years. Holtherhues et al. in the Netherlands 7 evaluated the in-cidence of SAT during a 16 year period (from 1989 to 2005) and observed an incidence of 0.35% among all cu-taneous neoplasms. The higher incidence of SAT in the present series is, most probably, a consequence of the fact that we considered only non-melanocytic tumours (basal cell carcinoma and squamous cell carcinoma). In the present series, the majority of SAT were benign (94%) and the most frequent forms were those arising from the sweat glands, and specifically: spiradenoma, hidrocystoma, eccrine poroma, syringoma, sebaceous adenoma and trichofolliculoma. This is consistent with the data in the literature 5-7. According to previously published data 5-6, the most fre-quent sites affected by benign SAT were the head and neck area and limbs. Accordingly, in present series more than half of the benign SAT were located to head and neck area (face, periocular area and scalp), while other frequent localizations were the limbs, back and torso.The gender predilection was different among the single histotypes. There was almost always a slight predomi-nance in males (54.44%) except for eccrine poroma 8 9 (M/F = 21/24) in which a slight female predominance was observed. In the literature, for neoplasm onset in sweat glands both male and female are equally affected 10-13. Recurrences of benign SAT have been rarely reported in the literature 14 15. In the present series only 2 cases (0.74% of all SAT) recurred months and years after sur-

gery. In both cases, the initial tumour had not been com-pletely excised at presentation. Three cases of MSES were observed. Since the origi-nal description appeared in 1956 16, less than 40 cas-es 3 17 18 of MSES have been described, and therefore their incidence remains unknown. In the present se-ries, they constituted only 1.11% of all SAT and 5.5% of eccrine spiroadenoma.MSES present as multiple cutaneous nodules, having a zosteriform or dermatomal appearance 3 4. They affect mainly adult patients, but paediatric cases have been re-corded 18. In addition, rare forms of familial cases have been documented 19. In the present cases, no family his-tory was available. The two female patients presented a zosteriform type of distribution, while the male patient presented a dermatomal type of distribution. In one of the present cases, the nodules appeared over a period of two years. The appearing lesions were considered mul-tiple forms and not true recurrences, as in all the samples small nodules were present very close to the surgical margins. None of the present cases presented malignant transformation.Malignant SAT were rare and constituted only 6% of the present series. They were composed of SC, EMPD and AC. According to previously published data 20-24, the most frequent sites affected by malignant SAT were the torso and head and neck region. They affected pa-tients with a higher mean age than benign SAT (72 vs 59 years, respectively), with a slight female predominance. In none of the 15 cases herein observed were recurrences and/or metastasis recorded. This is most probably a con-sequence of the small dimension of tumours at presenta-tion combined with radical surgical excision.

Conclusions

SAT are rare cutaneous tumours, constitute only about 3% of non-melanocytic tumours of the skin and have a wide spectrum of morphological features. The majority of SATs are benign, although complete surgical exci-sion is of upmost importance to avoid local recurrences. MSES are rare variant of SAT, appearing in about 1% of cases. Knowledge of these rare forms is important to achieve correct surgical treatment. Malignant SATs are rare, and, if correctly diagnosed and completely re-moved surgically, can have a good prognosis.

Tab. IV. Sites of malignant lesions.

Torso Scalp Face Axilla Back Limbs Periocular Skinapo ca. - - 1 3 - - - -EMpD 4 1 - - - 1 - -Seb. ca 1 2 3 - - - - -total 5 3 4 3 0 1 0 0

Legend: ca: carcinoma; apo: apocrina; Seb: sebaceous; EpMD: Extra Mammary paget Disease

341Skin adnexal tumourS

References

1 LeBoit PE, Burg G, Weedon D, et al. Pathology and genetics of Tumours of Skin. World Health Organization Classification of Tu-mors. IARC press, Lyon, 2006.

2 Patterson JW, Wick MR. Non Melanocytic Tumours of Skin. Armed Forces Institute of Pathology (AFIP). Atlas of Tumor Pathology, Series 4, Washington DC, ARP Press, Silver Spring (Maryland), 2006.

3 Gupta S, Jain VK, U. Singh, et al. Multiple eccrine Spirad-enomas in Zosteriform distribution in a child. Pediatr Dermat 2000;17:384-6.

4 Yoshida A, Takahashi K, Maeda F, et al. Multiple vascular eccrine spiradenoma: a case report and published work review of multiple eccrine spiradenomas. J Dermatol 2010;37:990-4.

5 Obaidad NA, Alsaad KO, Ghazarian D. Skin adnexal neoplasms - part 2: an approach to tumours of cutaneous sweat glands. J Clin Pathol: 2007;60:145-59.

6 Samalia MO. Adnexal skin tumors in Zaria, Nigeria. Ann Afr Med 2008;7:6-10.

7 Holterhues C, de Vries E, Louwman MW, et al. Incidence and trends of cutaneous malignancies in the Netherlands, 1989-2005. J Invest Dermatol 2010;130:1807-12.

8 Jayaraman M, Janaki VR, Yesudian P. Case report: eccrine poro-ma. Indian J Dermatol, Venereol Leprol 1996;62:310-1.

9 Ferrari A, Buccini P, Silipo V, et al. Eccrine poroma: a clin-ical-dermoscopic study of seven cases. Acta Derm Venereol 2009;89:160-4.

10 Sarabi K, Khachemoune A. Hidrocystoma - a brief review. Med Gen Med 2006;8:57.

11 Nam J, Lee G, Kim W, et al. Eccrine hidrocystoma in a child: an atypical presentation. Ann Dermat 2010;22:69-72.

12 Agrawal A, Kumar A, Sinha AK, et al. Chondroid syringoma. Sin-gapore Med J 2008;49:e33.

13 Kaleeswaran AV, Janaki VR, Sentamilselvi G, et al. Eccrine spi-radenoma. Indian J Dermat Venereol Leprol:2002;68:236-7.

14 Burns T, Breathnach S, Cox N, et al. Rook’s Textbook of Derma-tology, 8th Ed. Wiley-Blackwoll 2010.

15 Delfino S, Toto V, Brunetti B, et al. Recurrent Atypical Eccrine Spiradenoma of the Forehead. In vivo 2008;22:821-4.

16 Kersting DW, Helwig EB. Eccrine spiradenoma. A.M.A. Arch Derm 1956;73:199-227.

17 Englander L, Emer JJ, McClain D, et al. A rare case of mul-tiple segmental eccrine spiradenoma. J Clin Aesthet Dermatol 2011;4(4):34-8.

18 Gordon S, Styron BT, Haggstrom A. Pediatric segmental eccrine spiradenomas: a case report and a review of the literature. Pedri-atr Dermatol 2013;30:e285-6.

19 Poorten MCT, Barrett K, Cook J. Famialial eccrine spiradenoma: a case report and review of literature. Dermatol Surg 2003;29:411-4.

20 Ruiz-Villaverde R, Elosequi Martinez F, Luque Barona RJ, et al. Primary cutaneous cribriform apocrine carcinoma on an atypical location. Eur J Dermatol 2010;20:832-3.

21 Hartman R, Chu J, Pathel R, et al. Extramammary Paget disease. J Dermathol Online 2011;17:4.

22 Sawada Y, Bito T, Kabashima R, et al. Ectopic extramammary Paget’s disease: case report and literature review. Acta Dermo Venereol 2010;90:502-5.

23 Bhat IP, Madhukara J, Elizabeth J, et al. Multifocal extra-oc-ular sebaceous carcinoma. Indian J Dermat Venereol Leprol 2011;77:403.

24 Sung D, Kaltreider SA, Gonzales-Fernandez F. Early onset seba-ceous carcinoma. Diagn Pathol 2011;6:81.

pathologica 2013;105:342-345

Introduction

Kidney biopsy is the gold standard in the evaluation of renal diseases. It plays an indispensable role in the definitive diagnosis and guidance of treatment of renal disease. Light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM) are the most impor-tant tools for this process. Ideally, the evaluation should start with an on-site microscopic examination for the ad-equacy and proper distribution of the specimen for light microscopy, immunofluorescence and electron micros-copy 1, followed by the systemic evaluation of glomeru-li, tubules, interstitium and vasculature. To obtain an ad-equate specimen is the first step in this complex process. Adequacy of the specimen is determined by the number of glomeruli present in the core 2. However, this inva-sive procedure carries rare but genuine risks of serious complications. The adequacy should be obtained with minimal passes in order to minimize risk. On-site evalu-

ation provides real-time guidance to the biopsy operator. Without onsite microscopic examination, the adequacy is determined solely based on number of the cores. The purpose of this study is to assess the efficacy of on-site microscopic evaluation of medical kidney biopsies for adequacy and allocation of glomeruli and comparison of both techniques.

Materials and methods

This study was started after the approval of the Institu-tion Review Board (IRB). We retrospectively reviewed the data of the adult patients who underwent native kidney biopsies from 2009 to 2010 for medical causes. Transplant kidney biopsies were excluded. Pathology reports of 158 kidney biopsies were examined and data was compared between patients with and without on-site microscopic evaluation. At one facility, kidney core

ORiginal aRticle

Role of on-site microscopic evaluation of kidney biopsy for adequacy and allocation of glomeruli: comparison of renal biopsies with and without

on-site microscopic evaluationS.M. GILANI, D. OCKNER, H. QU

St. John Hospital & Medical Center, Detroit MI, USA

Key words

Kidney biopsy • Onsite evaluation • Glomeruli • Adequacy

Summary

CorrespondenceSyed M. Gilani, Department of Pathology, St. John Hospital & Medical Center, Detroit, MI, USA - E-mail: [email protected]

Evaluation of kidney core biopsies ideally begins with on-site microscopic examination for adequacy and allocation of tissue for light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). However, some renal biopsies are not micro-scopically evaluated by a pathologist at the time of procedure, and are allocated without on-site evaluation. This study compares the actual outcome of these two techniques.We reviewed the reports of patients who underwent kidney biopsy for medical causes in the past two years. Eighty-eight biopsies had on-site microscopic evaluation by pathologists, and 70 biopsies did not undergo on-site evaluation.

For biopsies without on-site evaluation, no glomeruli were seen in 5 (7.14%) cases for LM, 11 (15.71%) cases for IF and 6 (8.57%) cases for EM. In cases with on-site evaluation, the absence of glomeruli was identified in 1 (1.13%) case for LM, 3 (3.4%) for IF and 3 (3.4%) for EM. The biopsies with on-site microscopic evaluation had 5.68% of the cases considered as inadequate, while 22% of biopsies without on-site evaluation were considered inad-equate. The biopsies with on-site evaluation tended to have more glomeruli obtained during the procedure (p < 0.0005).Without on-site evaluation, the likelihood of getting an inad-equate specimen compared to on-site evaluation is nearly four times greater.

343On-site evaluatiOn Of kidney biOpsy

biopsies are evaluated at the site of procedure by pathol-ogist, using a dissecting or standard light microscope. At the other facility, kidney biopsies did not undergo on-site microscopic evaluation and were allocated by the radiologist. Eighty-eight (55.69%) patients had on-site microscopic evaluations performed by a patholo-gist, and 70 (44.30%) did not receive any microscopic evaluation at the time of the procedure. At the time of the procedure, specimens were evaluated under the mi-croscope by the pathologist and it was then allocated accordingly for LM, IF and EM. On average, the large portion of the specimen (predominantly cortex) was submitted in formalin for subsequent light microscopic evaluation, while a small portion of cortex was placed in the Michel’s media for immunofluorescence analy-sis. A very small portion of the cortex was allocated in the glutaraldehyde fixative for EM. On contrary, the specimen in the cases with no on-site microscopic eval-uation was divided for LM, IF and EM and transported in formalin, Michel’s media and glutaraldehyde fixa-tive, respectively. However, the allocation of the speci-men was done randomly without microscopic evalu-ation. We divided the patients into two groups (with and without microscopic evaluation). We collected the following data including age, gender, light microscopy, immunofluorescence and electron microscopy reports.

For the adequacy of the sample there are no definitive criteria. We defined the sample as adequate if at least one non-sclerotic or partially sclerotic glomerulus was present in the sample for light microscopy, immunofluo-rescence and electron microscopy. The sample was de-fined as inadequate if there was absence glomerulus or the presence of only completely sclerotic glomeruli. Af-ter collecting the data we have compared the adequacy of the sample between the above-mentioned groups. The data was also compared between LM, IF and EM of both groups. Statistical analysis was performed by using Chi-square analysis and Student’s T-test or ANOVA when appropriate. P-values <0.05 were considered statistically significant.

Results

A total of 88 patients (48 females and 40 males) with on-site microscopic evaluation were analyzed. Only 1 (1.13%) case for light microscopy which was female was classified in the category of inadequate due to absence of glomeruli. Three (3.4%) cases for immunofluorescence and 3 (3.4%) of electron microscopy had no glomeruli. In all 88 cases, approximately 37 glomeruli per case were obtained after on-site microscopic evaluation.

Tab. I. comparison of both groups for the inadequacy of glomeruli.

Groups Total cases LM(Absent/

Inadequate)

IF (Absent /

Inadequate)

EM(Absent /

Inadequate)

Total number of cases

cases withon-site microscopicevaluation

88 1 3 3 7

cases withouton-site evaluation

70 5 11 6 22

lM, light microscopy; iF, immunofluorescence and EM, electron microscopy

Tab. III. comparison of inadequacy between light microscopy cases with and without on-site evaluation.

% of inadequate cases (if adequacy is one glomerulus)

% of inadequate cases (if adequacy is 5 glomeruli)

% of inadequate cases (if adequacy is 10 glomeruli)

cases with on-site microscopic evaluation

5.68% 5.6% 25.0%

cases without on-site microscopic evaluation

22.85% 28.57% 52.85%

Tab. II. overall comparison of both groups & EM; electron microscopy).

Groups Total cases Total number of cases with absent glomeruliEven if absent in either

LM or IM or EM

Total percentage of cases

cases with on-site microscopic evaluation

88 n = 5 5.68%

cases without microscopic evaluation70 n = 16 22.85%

(lM; light microscopy, iF; immunofluorescence & EM; electron microscopy)

S.M. Gilani et al.344

On the other hand, 70 patients (39 females and 31 males) without on-site microscopic evaluation were examined, and approximately 23 glomeruli per case were obtained. Five (7.14%) cases for light microscopy, 11 (15.71%) cases for immunofluorescence and 6 (8.57%) cases for electron microscopy were classified as inadequate with no glomerulus (Tab. I). The mean number of non-sclerotic glomeruli observed was 26.88 + 15.56 (mean + SD, n = 88) for the on-site microscopic evaluation group, and 17.99 + 12.35 for the group without on-site evaluation (n = 70, p < 0.0005). If we define the absence of glomerulus in any sample for either light or immunofluorescence or electron mi-croscopy as an inadequate sample, the differences were more striking on the overall comparison of both groups. The group with on-site microscopic evaluation had only 5.68% cases with no glomeruli and the group without on-site microscopic evaluation had 22% of cases absent non-sclerotic glomeruli (Tab. II). By increasing the cut-off for adequacy of glomeruli for light microscopy to 5 glomeruli, we found 5.6% cases with on-site evaluation were inadequate compared to 28.5% for cases without on-site microscopic evaluation. Similarly, by increasing the cut-off value for adequacy up to 10 glomeruli, we observed that 25.0% cases with on-site microscopic evaluation were inadequate versus 52.8% cases without on-site evaluation (Tab. III). No significant differences were found considering gender or age.

Discussion

Kidney core needle biopsy is an important method to di-agnose medical and transplant diseases pertaining to the kidney. In our study, we found that on-site microscopic evaluation of kidney biopsies was helpful in getting an adequate number of glomeruli for the LM, IF and EM compared to cases with no on-site microscopic evalua-tion. For light microscopy there is no definitive criteria for adequacy of glomeruli. In the literature, different numbers for adequacy have been suggested 3-4. To over-come this issue, we have also compared the adequacy of glomeruli for light microscopy between both above-men-tioned groups by increasing the adequacy to 5 and then 10 glomeruli. By increasing the cut-off for adequacy of

glomeruli for light microscopy to 5 glomeruli, 5.6% cases with on-site evaluation were inadequate com-pared to 28.5% for cases without on-site microscopic evaluation. If adequacy of glomeruli is increased up to 10 glomeruli as described by a few authors in the literature, then the difference is even more strik-ing. The cases with on-site evalua-tion (25%) were categorized as in-adequate in comparison to 52.85% cases without on-site evaluation. We emphasized the onsite evalua-tion of the needle core because it is more likely to obtain an adequate specimen. On-site evaluation is more likely to keep the core in-tact, which is essential in observ-ing the disease distribution pattern, such as subcapillary or paramedul-lary distribution. This helps in the proper and adequate distribution of the specimen for LM, IF and EM, increasing the overall diagnostic yield. Many investigators have in-

Fig. 1. a. on-site evaluation of renal core biopsy; the section shows mainly cortex having glomeruli (original magnification x 40). B, c & D. Sections show glomeruli (arrow) (original magnification x 100).

Fig. 2. a. Renal core biopsy with medulla (original magnification x 40). B. Section shows core biopsy with medullary component (original magnification x 100).

345On-site evaluatiOn Of kidney biOpsy

vestigated the efficacy of image-guided biopsies and the adequacy of specimens. The majority of medical kidney diseases require EM evaluation, and proper allocation of the glomeruli for EM is very essential to establish a di-agnosis 5-6, which can be achieved through on-site evalu-ation of kidney core biopsies. Mahoney et al. noted that image guided percutaneous biopsies in transplant patients are useful 7. Patel et al. also emphasized the relevance of ultrasound-guided kidney biopsies 8. In our experience, teamed with radiologists, on-site evaluation of the speci-men by the pathologist improves the rate of adequacy.

Conclusions

Without onsite evaluation of the kidney core biopsies at the time of procedure the chances of getting an in-adequate sample is four times greater compared to the specimen with on-site evaluation. On-site microscopic evaluation plays a key role in assessment of adequacy and proper allocation of the glomeruli for further evalu-ation. Based on our study, we recommend evaluation of the kidney biopsy specimens by the pathologist under microscope at the time of procedure.

References

1 Walker PD, Cavallo T, Bonsib SM. Ad Hoc Committee on Renal Biopsy Guidelines of the Renal Pathology Society, Practice guide-lines for the renal biopsy. Mod Pathol 2004;17:1555-63.

2 Pasquariello A, Innocenti M, Batini V, et al. Theoretical calcu-lation of optimal depth in the percutaneous native kidney biopsy to drastically reduce bleeding complications and sample inad-equacy for histopathological diagnosis. Nephrol Dial Transplant 2000;22:3516-20.

3 Fogo AB. Approach to renal biopsy. Am J Kidney Dis 2003;42:826-36.

4 al Rasheed SA, al Mugeiren MM, Abdurrahman MB, et al. The

outcome of percutaneous renal biopsy in children: an analysis of 120 consecutive cases. Pediatr Nephrol 1990;4:600-3.

5 Rivera A, Magliato S, Meleg-Smith S. Value of electron micros-copy in the diagnosis of childhood nephrotic syndrome. Ultrastruct Pathol 2001;25:313-20.

6 Haas M. A reevaluation of routine electron microscopy in the exami-nation of native renal biopsies. J Am Soc Nephrol 1997;8:70-6.

7 Mahoney MC, Racadio JM, Merhar GL, et al. First Safety and ef-ficacy of kidney transplant biopsy: Tru-Cut needle vs sonographi-cally guided Biopsy gun. AJR Am J Roentgenol 1993;160:325-6.

8 Patel MD, Phillips CJ, Young SW, et al. US-guided renal trans-plant biopsy: efficacy of a cortical tangential approach. Radiology 2010;256:290-6.

pathologica 2013;105:346-348

Introduction

Tailgut cyst (TGC), also called retrorectal hamartoma, is a rare congenital lesion arising from persistent remnants of the postanal gut. Complications of TGCs include benign reactive lesions associated with infection and inflammation, and malignant transformation 1 2. We de-scribe here the clinicopathologic features of a new case of TGC associated with focal malignant transformation.

Case report

A 61-year-old woman with uneventful past medical and surgical history presented with pelvic and perineal pain of 3 months’ duration. Digital rectal examination showed a tender, extrinsic, well defined presacral mass compressing the rectum. On the remainder of physical examination, there was no abnormality. Sigmoidoscopy was normal. Abdominal computed tomography (CT) scan demonstrated a well-demarcated hypodense, cystic lesion, measuring 7x5 cm (Fig. 1). On MRI, the mass re-pressed the rectum without invading the rectal wall and the other locoregional structures (Fig. 2). Exploratory laparotomy revealed a cystic mass affixed to the sacrum. The lesion was partially resected. The surgical specimen showed a cystic mass with haemorrhagic content. Mi-croscopic examination revealed that the wall of the cyst was lined by benign stratified squamous, stratified cili-ated columnar epithelium (Fig. 3) and transitional cells.

Interrupted bundles and wisps of smooth muscle were present, separated from the epithelium by a thin layer of inflammatory fibrous tissue. There was no distinct nerve plexus. Focal areas of adenocarcinomatous changes in the cyst wall consisting of small foci of carcinomatous glands were noted (Fig. 4). The patient’s postoperative recovery was uncomplicated. The patient was lost to follow-up and did not receive any further therapy. Ten months later, she presented with perineal pain and a re-lapse confirmed by CT scan was detected. The mass, measuring 7 cm, was adherent to the posterior wall of the rectum (Fig. 5) and to the anal sphincter muscles. The resection was partial and complicated by a rectal fistula. The patient refused abdominoperineal amputa-tion and underwent adjuvant radiation [50 Gy]. She died 18 months later for local recurrence.

Discussion

TGCs are unusual lesions arising in the retrorectal, presacral space and considered to be of developmental origin arising from remnants of the tail gut 1. Various names have been used to describe this entity, such as retrorectal cyst-hamartoma, cyst of the postanal intes-tine, mucin-secreting developmental cyst, tailgut vestige and rectal cyst 2. Hjermstad and Helwig 1 suggested the term tailgut cyst because of its unambiguity. TGCs oc-cur in all age groups and are three times more common in women than in men. Nearly half of patients are as-

case RepORt

Adenocarcinoma arising in a tailgut cyst: a case reportS. RAMMEH, S. BEN ABDELKRIM, M.H. BEN HADJ KHALIFA*, R. LETAIEF*, M. MOKNI

Department of Pathology, Farhat Hached University Hospital, Sousse, Tunisia; * Department of Surgery, Farhat Hached University Hospital, Sousse, Tunisia

Key words

Tailgut cyst • Retrorectal hamartoma • Developmental cyst • Malignant transformation

Summary

CorrespondenceSoumaya Ben Abdelkrim, Farhat Hached Hospital, 4000, Sousse, Tunisia - Tel. +216 73 210 355 - Fax +216 73 210 355 - E-mail: [email protected]

Tailgut cyst (TGC), also called retrorectal hamartoma, is a rare congenital lesion arising from persistent remnants of the postanal gut. Malignant transformation of TGC is exceedingly uncommon.

We report herein the clinicopathologic features and the follow-up of a new case of a TGC with adenocarcinomatous transformation occurring in a 61 year-old woman.

347AdenocArcinomA Arising in A tAilgut cyst: A cAse report

Fig. 1. ct showing a retrorectal mass of liquidian density.

Fig. 2. t2-weighted MRi of the perineal region showing an en-capsulated retrorectal mass with a heterogeneous liquidian hy-persignal. New formations are seen in the lower part of the mass.

Fig. 3. cystic wall lined by benign stratified ciliated columnar cells (haematoxylin and eosin staining, original magnification x 40).

Fig. 4. Focal area of carcinomatous transformation in the cyst wall which is lined by normal columnar cells (haematoxylin and eosin staining, original magnification x 40). Below and to the right: detail of carcinomatous glands (haematoxylin and eosin staining, original magnification x 200).

Fig. 5. ct shows the mass invading the posterior wall of the rectum.

ymptomatic, and the other half present with symptoms resulting from local mass effects (constipation, rectal fullness, lower abdominal pain, dysuria, etc.), with a pal-pable retrorectal mass at digital rectal examination, or a complication. Loco-regional inflammatory processes frequently complicate this lesion and can cause perirec-tal fistulae, bleeding and malignant degeneration, which are the major complications of developmental cysts 1-3. TGCs have specific radiological and histopathological features that distinguish them from other similar forma-tions 3. Radiologically, differential diagnoses include der-moid cyst, epidermoid cyst, teratoma, rectal duplication cyst and anal gland cyst. The presence of calcification is suggestive of a dermoid cyst or teratoma. Rectal duplica-tion cysts often communicate with the rectal lumen and

S. Rammeh et al.348

are anterior to the rectum. Anal gland cysts have a lower loca-tion than TGCs and are typically close to the anal sphincter 4. Histologically, various epithe-lial cell types line the cyst, but identification of transitional or glandular-type epithelium with or without stratified squamous components is essential for diag-nosis. The other histologic req-uisites for the diagnosis are ab-sence of a well-defined muscu-lar coat containing a myenteric plexus and serosa. These criteria differentiate retrorectal cysts from epidermoid (stratified squamous epithelium only), dermoid (stratified squamous epithelium with skin adnexal structures) and duplication cysts which are lined by epithelium similar to that of the gastrointestinal and respiratory tracts and which have a distinctive feature consisting in two layers of muscular bundles containing a nerve plexus 5.Malignant transformation is rare. The largest series of 53 cases was reported by Hjermsted and Helwig 1; they found only 1 case associated with malignant transfor-mation. A recent report of a large series of the Mayo Clinic including 31 patients showed a 13% risk of ma-lignant transformation (adenocarcinoma in three cases and carcinoid in one case) 6. In an extensive review of the world literature, Tampi and colleagues in 2007 7 found only 16 cases with adenocarcinomatous malig-nant transformation and reported another case; Spada

References

1 Hjermstad BM, Helwig EB. Tailgut cyst: a report of 53 cases. Am J Clin Pathol 1988;89:139-47.

2 Ottery FD, Carlson RA, Gould H, et al. Retrorectal cysthamarto-mas: CT diagnosis. J Comput Assist Tomogr 1986;10:260-3.

3 Krivokapic Z, Dimitrijevic I, Barisic G, et al. Adenosquamous car-cinoma arising within a retrorectal tailgut cyst: report of a case. World J Gastroenterol 2005;11:6225-7.

4 Graadt van Roggen JF, Welvaart K, de Roos A, et al. Adenocarci-noma arising within a tailgut cyst: clinicopathological description and follow up of an unusual case. J Clin Pathol 1999;52:310-2.

5 Jang SH, Jang KS, Song YS, et al. Unusual prerectal loca-tion of a tailgut cyst: A case report. World J Gastroenterol 2006;12:5081-3.

6 Mathis KL, Dozois EJ, Grewal MS, et al. Malignant risk and sur-gical outcomes of presacral tailgut cysts. Br J Surg 2010;97:575-9.

7 Tampi C, Lotwala V, Lakdawala M, et al. Retrorectal cyst hamar-toma (tailgut cyst) with malignant transformation. Gynecol Oncol 2007;105:266-8.

8 Spada F, Pelosi G, Squadroni M, et al. Neuroendocrine tumour arising inside a retro-rectal tailgut cyst: report of two cases and a review of the literature. Ecancermedicalscience 2011;5:201.

9 Rogers A, Simpson E, Atherstone A. Adenocarcinoma in a retro-rectal cystic hamartoma: a case report and literature review. S Afr J Surg 2007;45:148-50.

10 Jarboui S, Jarraya H, Ben Mihoub M, et al. Retrorectal cys-tic hamartoma associated with malignant disease. Can J Surg 2008;51:E115-E116.

11 Vinciguerra GL, Mercantini P, La Torre M, et al. Transitional cell carcinoma of the retrorectal space arisen in tailgut cyst: a case report and review of the literature. Int J Surg Pathol 2013 Jul 1. [Epub ahead of print]

12 Chhabra S, Wise S, Maloney-Patel N, et al. Adenocarcinoma as-sociated with tail gut cyst. J Gastrointest Oncol 2013;4:97-100.

13 Charalampakis V, Stamatiou D, Christodoulakis M, et al. A large presacral tailgut cyst with a carcinoid tumor in a male: report of a case. Surg Today 2013 Jan 10. [Epub ahead of print]

14 Kanthan SC, Kanthan R. Unusual retrorectal lesion. Asian J Surg 2004;27:144-6.

Tab. I. cases of malignant transformation of tgc reported in the literature.

References Number of cases

Histological subtype

tampi c et al., 2007 7 17 adenocarcinomasRogers a et al., 2007 9 1 adenocarcinomaJarboui S et al., 2008 10 1 adenocarcinomaMathis Kl et al., 2010 6 4 3 adenocarcinomas and 1 carcinoid tumourSpada F et al., 2011 8 16 Neuroendocrine tumoursVinciguerra gl et al., 2013 11 1 transitional cell carcinomachhabra S et al., 2013 12 1 adenocarcinomacharalampakis V et al., 2013 13 1 carcinoid tumourKanthan Sc et al., 2004 14 1 low-grade endometrioid adenocarcinomathis report 1 adenocarcinoma

and colleagues 8 reported 2 cases of TGCs with neu-roendocrine malignant transformation and found 14 other cases of carcinoid tumors arising in TGCs in the literature. Malignant transformation mainly involves the neuroendocrine or glandular epithelium; recently, a transitional cell carcinoma that arose in a tailgut cyst was reported for the first time 11. Table I details the cases of malignant transformation of TGC reported to date. Differential diagnosis of such cases includes extension of a locoregional carcinoma, and metastatic disease 4.Prognosis of malignant TGC varies from case to case, but depends on the status of the surgical margins and tumour histology. There is no standardized postopera-tive chemotherapy protocol because of the few reported cases. Further reports and studies are required to better define the management of this entity 4 6.

pathologica 2013;105:349-352

Introduction

Breast cholesterol granuloma is an uncommon nodular breast lesion that can be encountered in pathohistologi-cal evaluation of screening-detected abnormalities sus-picious for malignancies. Its pathogenesis is still un-clear. In the literature, breast cholesterol granuloma is commonly related to mammary duct ectasia accompa-nied with the rupture of ectatic ducts 1 2. However, in the majority of cases with duct ectasia, rupture of the ectatic ducts generates only an inflammatory reaction known as periductal mastitis. The tumorous mass containing inflammatory cells and cholesterol crystals, known as cholesterol granuloma, is rarely found.Herein, we present two typical cases of breast choles-terol granuloma along with clinical, radiological, cy-tological, and pathohistological imaging findings. We also discuss a potential pathogenesis of this rare tu-morous breast lesion, proposing its relation not only to mammary duct ectasia, but also to the rupture of breast macrocysts.

Case report

Clinical and radiological findings

Case 1A 55-year-old asymptomatic woman presented with a suspicious nodular lesion in the right breast discovered on routine ultrasonographic examination, with no pal-pable abnormality on physical examination. The lesion was nodular and hypoechoic, with a maximum diameter of 7 mm, and located peripherally on the border of later-al breast quadrants (Fig. 1). A mammogram, performed a few months before ultrasonographic examination, showed no visible abnormality except a large cyst on the site of the subsequently discovered ultrasonographic abnormality of the right breast. The patient denied any significant traumatic event of the breast tissue after pre-vious mammography. Fine needle aspiration cytology (FNAC) was recommended.

Case 2Routine ultrasonographic examination of the breasts of a 57-year-old asymptomatic woman showed round hy-poechoic lesion with slight acoustic shadow, located centrally on the border of lateral quadrants of the right breast. The maximum diameter of the lesion was 6 mm.

case RepORt

Breast cholesterol granuloma: a report of two cases with discussion on potential pathogenesis

J. BEZIć, M. PILJIć-BURAZERInstitute of Pathology, Forensic Medicine and Cytology, Clinical Hospital Center, Split, Croatia

Key words

Breast • Cholesterol granuloma • Duct ectasia • Macrocyst

Summary

CorrespondenceJoško Bezić, Institute of Pathology, Forensic Medicine and Cytology, Clinical Hospital Center Split, Spinčićeva 1, 21 000 Split, Croatia - Tel. +385 21 556 512 - Fax +385 21 389 510 - E-mail:[email protected]

Breast cholesterol granuloma is a very rare lesion that can clini-cally and radiologically mimic breast carcinoma. Herein, we report two cases of breast cholesterol granulomas along with clinical, radiological, cytological and histological findings. We

also discuss the potential pathogenesis of this rare breast nodular lesion, suggesting its relation not only to mammary duct ectasia but also to the rupture of a breast macrocyst.

J. Bezic, M. PiLJic-BURAzeR350

A mammogram performed one month before the ultra-sonographic examination showed numerous cysts in the parenchyma of the both breasts measuring 5-10 mm in the greatest diameter. FNAC was recommended.

Cytological findingsThe FNA specimens of nodules were obtained us-ing 21-gauge needles. Brownish viscous content was yielded in both cases. The contents were immediately smeared onto glass slides, air-dried and May-Grünwald-Giemsa stained. The cytological smears in both cases showed numerous giant multinuclear cells with occa-sional histiocytes and ductal epithelium (Fig. 2). Extir-pation followed by pathohistological evaluation of the nodules was recommended.

Pathohistological findingsExcisional biopsies of the detected lesions were per-formed. On gross examination, both lesions were pre-sented as well circumscribed brownish nodules, of soft consistency, with maximum diameters of 6 mm (Fig. 3). The surrounding breast tissue was grossly unremarkable in both cases. The tissues were fixed in neutral buffered formalin and embedded in paraffin for routine histo-logical examination. The slides were stained with hae-matoxylin and eosin. Histologically, the nodules were composed of sheets of histiocytes with ample eosino-philic cytoplasm. Some of the histiocytes were giant and multinuclear, while at the periphery of the nodules mild lymphocytic infiltrate was noticed. Additionally, mas-sive cholesterol deposition in the form of cholesterol crystals arranged in irregular arrays was observed in both cases (Figs. 4 and 5). The granuloma in case 1 addi-

Fig. 3. gross surgical specimen of breast cholesterol granuloma.

Fig. 4. Breast cholesterol granuloma with massive deposition of cholesterol crystals (hE, 20x).

Fig. 1. Ultrasonography of breast cholesterol granuloma.

Fig. 2. Multinucleated giant cells and ductal epithelium (Mgg, 400x).

351Breast cholesterol granuloma

tionally contained numerous siderophages accompanied with marked fibrous proliferation. The residual epithe-lial component was not recognizable in either nodule. Based on these findings, a pathohistological diagnosis of cholesterol granuloma was made for both cases. In case 1, the surrounding breast tissue was histologically unremarkable, while in case 2 mildly dilated ducts sur-rounded by fibrous proliferation and both lymphocytic and histiocytic infiltration was observed. This finding was consistent with duct ectasia and periductal mastitis (Fig. 6).

Discussion

Breast cholesterol granuloma is a very rare finding in the spectrum of benign breast nodular lesions, with only dozen of cases so far reported in the English literature 1-7. Döring and Wedemeier were the first who described this entity in the female breast in 1974 8. Cholesterol granu-loma is a common disorder in the middle ear and mastoid process, with exceptionally reported cases in the testis, kidney, parotid gland, lymph nodes, thyroglossal duct and peritoneum 9-14. Typically, pathohistological char-acteristics of mammary cases do not differ from those of extramammary cases, with some exceptions as is the case with extensive osseous metaplasia and a case ac-companied by breast cancer 6 7. The main significance of this entity in breast tissue is that it may be clinically and radiologically indistinguishable from breast carcinoma. Proper diagnosis usually requires excisional biopsy and pathohistological confirmation of the benign nature of this disease 1-5.The pathogenesis of the breast cholesterol granuloma is still controversial. This entity is traditionally related to duct ectasia accompanied by the rupture of ectatic ducts. The lipid-rich material from the damaged lumina of ectatic ducts escapes into the periductal parenchyma

causing the formation of cholesterol crystals surround-ed by massive foreign body inflammatory reaction 1 2. According to this scenario, Wilhelmus et al. postulated that the cholesterol granuloma formation is “an unusual development in the advanced stage of mammary duct ectasia” 1. Osada and coworkers, in their work with lit-erature review of 8 breast cholesterol granuloma cases, found adjacent mammary duct ectasia in 5 cases 5. Our findings in case 2 confirmed that the origin of the cho-lesterol granuloma was ruptured ectatic duct. We easily identified a mild duct ectasia with periductal inflamma-tion in surrounding breast parenchyma. However, some of the reported cases of breast cholesterol granuloma were without histologically confirmed duct ectasia in surrounding breast tissue 5. Furthermore, many of the re-ported cases were situated on the periphery of breast pa-renchyma, while the duct ectasia is centrally located 5 15. Taking this into consideration, our case 1 is particularly interesting. In this patient, the granuloma was located on the periphery of breast parenchyma, with no histologi-cal finding of inflammatory reaction around surrounding breast ducts. Previous mammography showed a large cyst on the same site where the subsequent granuloma had been found. We speculate that a spontaneous rupture of the breast macrocyst into surrounding breast paren-chyma elicited the cholesterol granuloma formation. In cases of duct ectasia, periductal inflammation is prob-ably a primary lesion, causing the damage of the duct wall with consequent periductal fibrosis 16. Only in the minority of cases the leakage of lipid rich luminal mate-rial cause the formation of small histiocyte aggregates with resulting xanthogranulomatous mastitis, or excep-tionally, the formation of large histiocyte aggregates with “macrogranuloma” formation 17. Alternatively, we propose that in some rare cases with ruptured, peripher-ally located breast macrocyst the inflammatory response is cellular rather than fibrotic, which facilitates the ag-gregation of histiocytes on the site of the rupture, with

Fig. 5. Detail of the breast cholesterol granuloma with scattered cholesterol crystals surrounded by giant cells, histiocytes and in-flammatory cells (hE, 200x).

Fig. 6. Mammary duct adjacent to the granuloma in case 2: the mildly dilated duct surrounded by fibrous proliferation and both lymphocytic and histiocytic infiltration is visible (hE, 200x).

J. Bezic, M. PiLJic-BURAzeR352

formation of granuloma around precipitated cholesterol crystals. In conclusion, we confirm that centrally located cases of this rare benign nodular breast lesion represent late

stage of mammary duct ectasia. We believe that in cases of peripherally located nodules cholesterol granuloma formation may be an unusual result of the rupture of a breast macrocyst.

References

1 Wilhelmus JL, Schrodt GR, Mahaffey LM. Cholesterol granulo-mas of the breast. A lesion which clinically mimics carcinoma. Am J Clin Pathol 1982;77:592-7.

2 Reynolds HE, Cramer HM. Cholesterol granuloma of the breast: a mimic of carcinoma. Radiology 1994;191:249-50.

3 Smith GL, Hicks P, Wijesinghe DP, et al. Cholesterol granuloma of the breast presenting as an intracystic papilloma. Br J Radiol 1997;70:1178-9.

4 Ishizaki M, Ohsumi S, Takashima S, et al. Two cases of cholesterol granuloma of the breast. Breast Cancer 2001;8:158-61.

5 Osada T, Kitayama J, Nagawa H. Cholesterol granuloma of the breast mimicking carcinoma: report of a case. Surg Today 2002;32:981-4.

6 Furuhira C, Ohshima A, Shimada K, et al. A case of breast cholester-ol granuloma accompanied by cancer. Breast Cancer 2004;11:210-3.

7 Garofalo S, Casolino C, Accurso A, et al. Cholesterol granuloma of the breast with unusual ossification features (osseous metapla-sia). Pathol Res Pract 2008;204:353-6.

8 Döring L, Wedemeier G. Cholesterol granuloma of the female breast. Chirurg 1974;45:520-1.

9 Lin JL, Tseng CH, Marsidi PJ, et al. Cholesterol granuloma of right testis. Urology 1979;14:522-3.

10 Nast CC, Cohen AH. Renal cholesterol granulomas: identifica-tion and morphological pattern of development. Histopathology 1985;9:1195-204.

11 Bundgaard N, Eriksen HE, Greisen O. Inflamed adenolymphoma with cholesterol granuloma. J Laryngol Otol 1987;101:967-70.

12 Grignon DJ, Kirk ME, Haines DS. Cholesterol granulomas in lymph nodes draining a benign ovarian neoplasm. Arch Pathol Lab Med 1985;109:1124-6.

13 Aviel A, Segal M, Ostfeld E, et al. Cholesterol granuloma in a thyroglossal duct cyst: a case report. J Laryngol Otol 1983;97:379-81.

14 Al-Amer AF, Walia HS, Madda JP. Cholesterol granuloma of the peritoneum. Can J Surg 1990;33:410-3.

15 Haagensen CD. Mammary duct ectasia. A disease that may simu-late carcinoma. Cancer 1951;4:749-61.

16 Dixon JM, Anderson TJ, Lumsden AB, et al. Mammary duct ecta-sia. Br J Surg 1983;70:601-3.

17 Koo JS, Jung W. Xanthogranulomatous mastitis: clinicopathology and pathological implications. Pathol Int 2009;59:234-40.

pathologica 2013;105:353-356

Introduction

The simultaneous occurrence of various primary pleu-ropulmonary tumours is a rare condition. This might be differentiated from histologic heterogeneity of multiple localization of the same tumour that occurs frequently in the lung. There are criteria to confirm the multiplicity of primary malignant neoplasms described by Warren and Gates 1. The co-existence of malignant mesothelioma and pulmonary adenocarcinoma is very rare 2. Whereas the association of asbestos with malignant mesothelioma is definite, the development of concurrent malignant pleural mesothelioma and lung carcinoma has been in-frequently reported in asbestos-exposed individuals 3-6: only in 1.8% of 500 malignant mesotheliomas in the se-ries of Attanoos 7. In this report, we describe a rare case of synchronous diffuse malignant pleural mesothelioma and adenocar-cinoma in a case of suspicious asbestos exposure, but no clinical and pathological confirmation of evidence of asbestosis.

Case report

A 68-year-old male was admitted to the Pneumology department for fever, pain and discomfort at right hy-pochondrium. The patient was a non-smoke, retired customs agent, with suspicious contact with asbestos, who referred several episodes of pleuritis, the first time at 20 years old and the last two years ago. He had never undergone a clinical search for asbestos bodies. Tho-racic standard X ray revealed hyperdensity of the infe-rior lobe of right lung. A CT scan with contrast showed, in the right lung, a nodule in the parenchyma at the posterior region of the basal inferior lobe of 12 mm, an irregular dense parenchymal area of the medium lobe with thickening of pleura and effusion of about 1 cm thick in the same hemithorax (Figs. 1, 2). Blood work-up showed an increase in inflammatory indices with a D-Dimer of 300. The patient was subsequently admitted to the thorax surgery department and underwent inferior and medium right lung lobectomies with intraoperatory frozen sec-

case RepORt

Synchronous occurrence of pulmonary adenocarcinoma and pleural diffuse malignant mesothelioma

H. IMENPOUR1, G.P. IVALDI2, A. BRIANTI2, G. PASTORINO4, S. BIGGI4, L. AURIATI1, C. SIMONASSI2

Departments of Pathology1, Pneumology2, Radiology3, Chest Surgery4, Villa Scassi Hospital, Genova (ASL3), Italy

Key words

Synchronous pulmonary neoplasias • Adenocarcinoma • Pleural malignant mesothelioma

Summary

CorrespondenceHossein Imenpour, Anatomia Patologica, ASL 3 Genovese, Ospedale Villa Scassi, c.so Scassi, 1-16149 Genova, Italy - Tel. +39 010 8492326 - Fax +39 010 8492290 - E-mail: [email protected]

We report a rare case of diffuse malignant pleural mesothelioma synchronous with a localized adenocarcinoma of lung in a 68-year old man with a suspicious history of asbestos exposure. Com-puted tomography revealed a sub-pleural mass in the lower lobe and an irregular dense area of medium lobe of right lung with thickening of pleura encasing the lung parenchyma and homolat-eral pleural effusion 1 cm thick. The patient underwent surgery

and a right medium and lower lobectomy was performed. Upon frozen sections, intraoperative diagnosis was adenocarcinoma with a poorly differentiated component of lung infiltrating the pleura. The postoperative histological definitive diagnosis with an important contribution of immunostaining was synchronous pulmonary adenocarcinoma and pleural diffuse malignant epithe-lioid mesothelioma.

AcknowledgementsThe authors wish to thank Dr Cavazza (Reggio Emilia) for consultancy along with our laboratory staff.

H. Imenpour et al.354

tion examinations on margins of bronchial resection and the nodulectomy specimen. The bronchial margin was clean, and the nodule of inferior lobe was an adenocar-cinomatous infiltration in the sub-pleural parenchyma with prevalently tubulopapillary growth pattern associ-ated with histologically different solid epiteliomatous malignant infiltration of the above visceral pleura, en-casing the lung parenchyma and intimately mixed and formed collision tumours. This was interpreted as a less differentiated component of the adenocarcinoma by the pathologist at frozen section examination. The next two frozen section examinations of another sub-pleural seg-ment of inferior lobe and one segment of medium lobe demonstrated similar solid neoplastic infiltrations of the pleura.

Gross examination showed a nodule of 1 cm diameter with a grey cut surface in the first frozen specimen with thickening of the above pleura and in other frozen sec-tions thickening of pleura with thick septa and small nodules penetrated in the parenchyma. Formalin-fixed tissue was processed routinely, and 5 micron thick paraf-fin sections were cut and stained with haematoxilin and eosin (Figs. 3-5).These tissue blocks reflected the same aspects of fro-zen sections with more detail about the solid epithelioid pleural components. No diffuse interstitial fibrosis and no asbestos bodies were seen on light microscopy. No lymph node metastasis was seen.By immunostaining, neoplastic cells of the first nodule showed diffuse nuclear positivity for thyroid transcrip-tion factor-1 TTF1 (Clone 8G7G3/1 DAKO) (Figs. 7, 8) and were negative for calretinin (Clone DAH/calret 1DAKO) (Figs. 9, 10), while the pleural lesions with the relative septal and nodular coinfiltrating components was positive for calretinin and negative for TTF1.The patient was uneventfully discharged on the 12th day after surgery and had 6 cycles of chemotherapy with carboplatin and pemetrexed, and has had no recurrence after 7 months of follow-up and CT.

Discussion

In the literature, cases with different histologically-different malignancies in the same lung are only rarely reported. Historically, there is a case of squamous cell and oat cell carcinoma appearing in different lobes of the right lung 8, a case of squamous cell carcinoma, ad-enocarcinoma and anaplastic carcinoma, three separate primary tumours in the right lung in autopsy 9 and 53 double primary lung tumours 10. There is also case of synchronous occurrence of an intermediate small cell and a bronchiolo-alveolar carcinoma 11. Co-existing granular cell tumour and adenocarcinoma of the lung has also been documented 12. Successively, another authors have reported the cases of synchronous pleural diffuse malignant mesothelioma and pulmonary carcinoma, sometimes with significant histories of asbestos expo-sure 11-13, three cases of synchronous pulmonary carci-

Figs. 1, 2. ct scans of the chest show a nodule in the basal infe-rior lobe of the right lung and effusion and thickening of pleura encasing the lung parenchyma.

2

1

Figs. 3-5. histopathology shows the synchronous presence of pulmonary adenocarcinoma and pleural malignant mesothelioma (h&E, x100).

43 5

355SynchronouS occurrence of Pulmonary adenocarcinoma and Pleural diffuSe malignant meSothelioma

noma and pleural diffuse malignant mesothelioma from 16,000 pleuropulmonary cases of three referral centres, often with history of smoking or asbestos exposure re-ported 3, 9 cases of synchronous diffuse malignant me-sothelioma and carcinomas in asbestos-exposed individ-uals 7, minute localized malignant pleural mesothelioma coexisting with multiple adenocarcinoma 14 and 1 case of

metachronous malignant mesothelioma and pulmonary adenocarcinoma 15 (Tab. I). However, a history of as-bestos is not required for diagnosis, and patients tend to be older than those with a single tumour 14. More rarely, there is simultaneous pulmonary carcinoma and pleural malignant mesothelioma with nodular lung parenchyma coinvolvement. In these cases, patients underwent sur-

Figs. 6, 7. immunohistochemical staining for ttF-1 is positive in adenocarcinoma and negative in mesothelioma (x100).

7

6

Figs. 8, 9. immunohistochemical staining for calretinin is positive in mesothelima and negative in adenocarcinoma (x100).

9

8

Tab. I. literature review.

First author Year of publication Diagnostic indicators

hanbury W.J. 1961 1 case of squamous cell and oat cell carcinoma in different lobes of the right lungonuigbo W.i. 1962 1 case of squamous cell carcinoma, adenocarcinoma and anaplastic carcinoma in

autopsyShields t.W. 1964 53 double primary lung tumoursVerska J.J. 1968 1 case of simultaneous bronchial adenoma and bronchiolo-alveolar carcinomaDohner V.a. 1975 1 case of simultaneous pulmonary adenocarcinoma and pleural diffuse malignant

mesothelioma okumara t. 1980 2 cases of mesothelioma with lung cancerWong K. 1993 1 case of co-existing granular cell tumour and adenocarcinoma of the lung cagle p.t. 1994 1 case of concurrent mesothelioma and adenocarcinoma of the lungSuzuki Y. 1994 1 case of concurrent mesothelioma and adenocarcinoma of the lung in a patient

with asbestosisFrench c.a. 1999 1 case of synchronous pleural mesothelioma and primary lung carcinoma attanoos R.l. 2003 9 cases of synchronous diffuse malignant mesothelioma and carcinomas in

asbestos-exposed individualsallen t.c. 2006 3 cases of synchronous pulmonary carcinoma and pleural diffuse malignant

mesotheliomaMaeda R. 2009 1 case of minute localised malignant pleural mesothelioma coexisting with

multiple adenocarcinomasozbudak i.h. 2013 1 case of metachronous malignant mesothelioma and pulmonary adenocarcinoma

H. Imenpour et al.356

gery for treatment of carcinoma; non-malignant meso-thelioma was identified preoperatively. It is of interest that upon frozen section examination the mesothelioma can simulate a less differentiated carcinoma, but immu-nostaining supports definitive diagnosis. Such synchro-nous neoplasms occur rarely in patients with asbestos risk factors.

Conclusion

Pleural diffuse malignant mesothelioma coexisting with lung adenocarcinoma is rare. Knowledge of the clinical features and patient history is crucial. Immunohisto-chemical staining techniques are necessary to confirm diagnosis of a mesotheliomatous component of synchro-nous tumours.

References

1 Warren S, Gates O. Multiple primary malignant tumors: a survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.

2 Allen TC. Syncronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. Arch Pathol Lab Med 2006;130:721-4.

3 Cagle PT. Concurrent mesothelioma and adenocarcinoma of the lung in a patient with asbestosis. Mod Pathol 1993;6:438-41. Mod Pathol 1994;7:148-9.

4 Suzuki Y. Concurrent mesothelioma and adenocarcinoma of the lung in a patient with asbestosis. Mod Pathol 1993;6:438. Mod Patho 1994;7:888-9.

5 French CA, Sugarbaker DJ, Corson JM. Sincronous pleural meso-thelioma and primary lung carcinoma. Mod Pathol 1999;12:183A.

6 Okumura T, Okada M, Tsuji, et al. Mesothelioma with lung cancer complicating asbestosis. Acta Pathol Jpn 1980;30:579-90.

7 Attanoos RL. Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals. Histopathology 2003;43:387-92.

8 Hanbury WJ. Two histologically different carcinomas in tha same lung. J Path Bact 1961;81:540.

9 Onuigbo WI. Multiple carcinomata of the lung. Brit J Dis Chest 1962;56:144.

10 Shields TW, Drake CT. Bilateral primary bronchogenic carcino-ma. J Thorac Cardiovasc Surg 1964;48:401.

11 Dohner VA, Beegle RG, Miller WT. Asbestosis exposure and mul-tiple primary tumores. Am Rev Respir Dis 1975;112:181-99.

12 Muhammad AA. Co-existing granular cell tumor and adenocarci-noma of the lung: a case report and review of the literature. Respir Care 2001;46(7):702-4.

13 Wong K. Syncronous occurrence of an intermediate small cell and a bronchiolo-alveolar carcinoma of the lung. J Royal Society of Medicine 1993;86:599.

14 Maeda R, Isowa N, Onuma H, et al. Minute localized malignant pleural mesothelioma coextisting with multiple adenocarcinomas. Gen Thorac Cardiovasc Surg 2010;58:91-4.

15 Özbudak İH, Özbudak Ö, Arslan G, et al. Metachronous malignant mesothelioma and pulmonary adenocarcinoma. Turk Patoloji Derg 2013;29:83-6.

pathologica 2013;105:357-360

Introduction

Granulomatous mastitis (GM), also called granuloma-tous lobular mastitis, is an uncommon chronic inflam-matory disease of the breast. The aetiology of this disor-der is unknown, but its clinical and radiological features can mimic breast carcinoma. To the best of our knowl-edge, the coexistence of GM and ductal carcinoma has been described only twice in the English language lit-erature. In this paper, the authors report a new case of breast infiltrating ductal carcinoma coexisting with GM and discuss the pathophysiological mechanism of this rare association.

Clinical history

A 77-year-old female patient with a medical history for hypertension and epilepsy presented with right breast pain of 6-months duration. Examination revealed a hard sub-areola tender mass with irregular borders almost fixed to underlying structure. This was associated with mild right nipple retraction and a 0.7 cm non-tender

right axillary node. The mammography report noted a 2.2 x 2.4 cm stellate mass of the right breast. Results of standard laboratory analyses were within normal range. Ultrasound-guided core biopsies of the tumour were per-formed. Pathologic examination revealed a Grade II in-filtrating ductal carcinoma. The patient underwent right radical mastectomy with homolateral axillary lymph-adenectomy. Histopathological examination showed destruction of lobular architecture by granulomatous inflammation and a moderately differentiated infiltrat-ing ductal carcinoma (Grade II according to Modified Scarff-Bloom-Richardson grading system) (Figs. 1, 2). The granulomatous inflammatory reaction was centred on lobules. Granulomas were composed of epithelioid histiocytes, Langhans giant cells accompanied by lym-phocytes, and plasma cells (Figs. 3, 4). Axillary lymph nodes were not metastatic. Immunohistochemical stain-ing of tumour cells showed strongly positive nuclear staining for oestrogen and progesterone receptors and negative staining for HER-2neu protein overexpression. The final pathological diagnosis was grade II infiltrating ductal carcinoma concomitant with granulomatous lobu-lar mastitis. During her hospitalization, work-up for me-

case RepORt

Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?

F. LIMAIEM, A. KHADHAR, F. HASSAN, S. BOURAOUI, A. LAHMAR, S. MZABIUniversité de Tunis El Manar, Faculté de Médecine de Tunis, Department of Pathology, Mongi Slim Hospital, La Marsa, Tunisia

Key words

Granulomatous lobular mastitis • Breast carcinoma • Surgery

Summary

CorrespondenceFaten Limaiem, Department of Pathology, Mongi Slim Hospital, La Marsa, Tunisia - Tel. +216 96 55 20 57 - E-mail: [email protected]

A 77-year-old female patient with a medical history significant for hypertension and epilepsy presented with right breast pain of 6-months duration. Examination revealed a hard sub-areola ten-der mass with irregular borders associated with mild right nipple retraction. Mammography showed a 2.2 x 2.4 cm stellate mass of the right breast. Ultrasound-guided core biopsies of the tumour were performed. Pathological examination revealed a grade II infiltrating ductal carcinoma. The patient underwent right radi-cal mastectomy with homolateral axillary lymphadenectomy. Histological examination of the surgical specimen revealed grade

II infiltrating ductal carcinoma concomitant with granulomatous lobular mastitis. To the best of our knowledge, the coexistence of granulomatous lobular mastitis and ductal carcinoma has been described only twice in the English language literature. The the-ory that chronic inflammation leads to cancer is well documented. Whether our patient had developed cancer from granulomatous lobular mastitis or otherwise is a matter of debate until more cases are encountered and more research is done in the area of breast cancer pathogenesis with regards to it arising from granulomatous lobular mastitis.

F. Limaiem et aL.358

tastases was negative. The patient’s course two months after the operation remained uneventful and she refused to receive adjuvant chemotherapy.

Discussion

Granulomatous mastitis is a rare, chronic, non-caseat-ing, granulomatous lobulitis of uncertain aetiology that usually affects women of a child-bearing age 1 2. Since its initial description by Kessler and Wolloch in 1972, more than 120 cases of GM have been reported in the English language literature to date 1. Most case series regarding GM are less than 20 patients and from devel-oping countries or countries with predominantly Cau-casian populations 3. GM is, pathologically, a diagnosis

of exclusion: other granulomatous inflammatory breast diseases must be first ruled out, including plasma cell mastitis, Wegener’s granulomatosis and granuloma-tous reaction secondary to sarcoidosis, ruptured cyst, duct ectasia, fat necrosis, foreign body reaction, tuber-culosis, brucellosis or other fungal or parasitic infec-tions. Some authors have speculated that the increasing incidence of GM coming from developing countries, in particular from the Mediterranean region and Asia, may be due to underdiagnosed breast tuberculosis 4-6. No consistent association has been observed with smok-ing, contrary to periductal mastitis, or with trauma to the breast, foreign material, feedingbreast-feeding or oral contraception 5. Thus, an autoimmune disease process is thought to be most likely. The autoimmune hypothesis is supported by the fact that the condition

Fig. 1. coexistence of lobulocentric lymphocytic infiltration com-posed of small mature lymphocytes and infiltrating ductal carci-noma. (haematoxylin & eosin staining; original magnification x 4).

Fig. 2. Moderately differentiated infiltrating ductal carcinoma: several elongated glands with infiltrating growth pattern. the glands were lined by mildly atypical tumour cells (haematoxylin & eosin staining, original magnification x 20).

Fig. 3. Destruction of lobular architecture by granulomatous inflammation. granulomas were composed of epithelioid his-tiocytes, langhans giant cells, lymphocytes and plasma cells (haematoxylin & eosin staining, original magnification x 20).

Fig. 4. Non caseating granulomas involving mammary lobules with langhans-type multinucleated giant cells, lymphocytes and plasma cells. (haematoxylin & eosin stain; original magnification x 40).

359LobuLar granuLomatous mastitis and ductaL carcinoma

often improves with the administration of steroids. Furthermore, erythema nodosum has been reported as an extramammary manifestation of GM. On the other hand, classic serologic tests of autoimmune disorders, such as antinuclear antibodies and rheumatoid factors, are usually to be negative 7. The suggested pathophysi-ology for this autoimmune hypothesis is through dam-age to ductal epithelium producing a leak of luminal protein-rich secretions and fat into the lobular con-nective tissue, eliciting a granulomatous reaction with lymphocyte and macrophage migration 5. Extravasated lactational secretions occurring in women with recent pregnancy and lactation may elicit such a local granulo-matous response, with local trauma or other infections as other possible triggers 8. The most common clinical presentation of GM is a unilateral firm-to-hard extra-areolar mass ranging from 0.5 to 9 cm in size 9 10. The lump may involve the overlying skin or penetrate the underlying pectoralis muscle with nipple retraction, si-nus formation and axillary lymphadenopathy clinically mimicking breast carcinoma 9-11. With its retro-areolar or central location, features of inflammation and its common occurrence in recent pregnancy and lactation, the breast mass can also be mistaken clinically for a lactating breast abscess. Routine radiological exami-nation including ultrasonography and mammography cannot differentiate idiopathic GM from carcinoma 9. Ultrasonography usually reveals inhomogeneous, ir-regular hypoechoic lesions with focal posterior shad-owing or multiple relatively circumscribed heteroge-nous hypoechoic lesions associated with a large mass 12

13. Doppler examination reveals increased vascularity of the lesions and surrounding tissues. On MRI, it is not possible to differentiate an active inflammatory process from a tumoural process. With the exception of two cases, no additional reported cases have sug-gested the possibility of an association between GM and malignancy 14 15. A literature search of any infec-tion leading to breast cancer has only revealed that the cross species viral infection by the Mouse Mammary Tumour Virus can lead to the pathogenesis of breast cancer, although this remains at a very early stage of

research 16. The theory that chronic inflammation leads to cancer is well documented 17. It is postulated that as a result of infection from an offending microorgan-ism the host’s defense mechanisms produce free radi-cals which lead to oxidative damage and nitration of DNA bases which increases the risk of DNA damage. This would eventually lead to cell dysplasia and subse-quently the development of cancer. It has been reported that nearly 15% of worldwide cancer is associated with microbial infection 18. However, breast cancer is not associated with such infections. The difficulty in differentiating breast carcinoma and GM and the possibility that GM could have led to cancer prompts us to raise the question whether current man-agement with regard to monitoring and surgical therapy is adequate and appropriate. Current practice indicates that following careful confirmation of the diagnosis of GM, initial treatment should be non-operative and that in patients with more severe symptoms, a course of prednisolone may be started. In more persistent cases, either further immunosuppressive therapies like metho-trexate or azothioprine may be used or the patient can be offered surgical management such as wide surgical exci-sion or mastectomy. Surgical excision has the advantage of fewer recurrences 7. It was reported that only 3 re-currences occurred after excision of 18 cases diagnosed with GM. Whether the need for more radical surgery is needed remains a matter of debate until it can be demon-strated that GM can lead to cancer.In summary, two different hypotheses are possible in our patient. Firstly, that the patient has developed breast carcinoma as a second separate pathology in the same breast. Secondly, she developed breast carcinoma as a result of chronic inflammation leading to dyspla-sia and subsequent malignant change. Whether the pa-tient had developed cancer from GM or otherwise is be a matter of debate until more cases are encountered and more research is done in the area of breast cancer pathogenesis with regard to it arising from GM. The result of future research can affect the diagnosis and treatment of GM, and will certainly alter the course of its management.

References

1 Kok K.Y.Y, Telisinghe P.U. Granulomatous mastitis: Pres-entation, treatment and outcome in 43 patients. The Surgeon 2010;8:197-201.

2 Van Ongeval C, Schraepen T, Van Steen A, et al. Idiopathic gran-ulomatous mastitis. Eur Radiol 1997;7:1010-2.

3 Mohammed S, Statz A, Lacross JS, Lassinger BK, et al. Granu-lomatous mastitis: a 10 year experience from a large inner city county hospital. J Surg Res 2013;184:299-303.

4 Ocal K, Dag A, Turkmenoglu O, et al. Granulomatous mastitis: clinical, pathological features, and management. Breast Journal 2010;16:176-82.

5 Akcan A, Akyildiz H, Ali Deneme M, et al. Granulomatous lobu-lar mastitis: a complex diagnostic and therapeutic problem. World Journal of Surgery 2006;30:1403-9.

6 Al-Khawari HAT, Al-Manfouhi HA, Madda JP, et al. Radiologic features of granulomatous mastitis. Breast Journal 2011;17:645-50.

7 Erhan Y, Veral A, Kara E, et al. A clinico-pathologic study of a rare clinical entity mimicking breast carcinoma: idiopathic granu-lomatous mastitis. Breast 2000;9:52-6.

8 Yau FM, Macadam SA, Kuusk U, et al. The surgical management of granulomatous mastitis. Annals of Plastic Surgery 2010;64:9-16.

9 Limaiem F, Korbi S, Tlili T, et al. Idiopathic granulomatous mas-titis mimicking breast cancer: report of two cases. Pathologica 2012;104:105-8.

10 Van Ongeval C, Schraepen T, Van Steen A. Idiopathic granuloma-tous mastitis. Eur Radiol 1997;7:1010-2.

11 Yilmaz E, Lebe B, Usal C. Mammographic and sonographic find-ings in the diagnosis of idiopathic granulomatous mastitis. Eur Radiol 2001;11:2236-40.

F. Limaiem et aL.360

12 Tuncbilek N, Karakas HM, Okten OO. Imaging of granulomatous mastitis: assessment of three cases. Breast 2004;13:510-4.

13 Han B, Choe YH, Park JM, et al. Granulomatous mastitis: mam-mographic and sonographic appearances. Am J Roentgenol 1999;173:317-20.

14 Handley WS. Chronic Mastitis and breast cancer: a family history of five sisters. Br Med J 1938;7:113-6.

15 Luqman M, Niza A.S.S, Jaszle J.S, et al. Breast carcinoma oc-

curring from chronic granulomatous mastitis. Malays J Med Sci 2012;19:82-5.

16 Stanislav I, Walter HG. Rapid spread of mouse mammary tumour virus in cultured human breast cells. Retrovirology 2007;4(73):1-15.

17 Nahoum SR. Why Cancer and inflammation? Yale J Biol Med 2006;79:123-30.

18 Zlotnik A. Chemokines and cancer. Int J Cancer 2006;119:2026-9.

pathologica 2013;105:361

Sir,I enjoyed very much reading the paper by Limaiem et al. (Pathologica 2013;105:101-3) in which the first case of hydatic cyst presenting as breast lump in a male patient was described. It is pertinent to remind read-ers that in this same journal (Gaspa & Eusebi, Patho-logica 1973;65:235-7) the first case of hydatic cyst in a

breast of a Sardinian female patient was reported. The cyst manifested as a lump that upon excision revealed a minute invasive carcinoma in the cyst capsule. The patient was followed for lenghty period, but no sign of carcinoma was evident. This appeared as the first and unique case of an early diagnosis facilitated by a parassite!

Letter to the Editor

V. EUSEBIDept. of Pathology, Ospedale Bellaria, University of Bologna

362 pathologica 2013;105:362-368

Issue 1February 2013

ORIGINAL ARTICLE1 Clinical management of thyroid nodules with inde-

terminate cytology: our institutional experience using SIAPEC cytological criteria and v600-BRAF test

G. Di Benedetto, A. Fabozzi, C. Rinaldi

CASE REPORTS5 Role of biopsy in low-grade laryngeal chondrosar-

coma: report of two cases M. Onorati, L. Moneghini, A. Maccari, M. Albertoni,

I. Talamo, F. Ferrario, G. Bulfamante, S. Romagnoli, F. Di Nuovo

8 Uterine endometrioid adenocarcinoma with extensive pilomatrixoma-like areas.

A case report S. Squillaci, R. Marchione, M. Piccolomini, M. Chiu-

dinelli, E. Fiumanò, M. Ungari

11 Recurrent ossifying fibroma of the maxillary sinus in an adult patient

D. Cabibi, R. Speciale, F. Lorusso

15 Intraparenchymal serous papillary cystadenoma of the testis: a case report

L. Olla, N. Di Naro, G. Puliga, G.A. Tolu

18 Pancreatic heterotopia of the small intestine: two case reports

F. Limaiem, I. Haddad, L. Marsaoui, A. Lahmar, S. Bouraoui, S. Mzabi

21 Molecular diagnostics of pulmonary metastasis from cervical cancer

C. Fodero, A. Cavazza, R. Bio, L. Bulgarelli, L. Campioli, T. Rubino, V. Semeraro, S. Prandi

24 Pure uterine lipoma H. Imenpour, F. Petrogalli, L. Anselmi

LINEE GUIDA28 Il carcinoma del pancreas esocrino: il referto istologico C. Capella, L. Albarello, P. Capelli, F. Sessa, G. Zam-

boni per conto del Gruppo Italiano Patologi Appa-rato Digerente (GIPAD) e della Società Italiana di Anatomia Patologica e Citopatologia Diagnostica / International Academy of Pathology, Italian Division (SIAPEC/IAP)

39 In memoriam of John G. Azzopardi V. Eusebi, T. Krausz

Issue 2April 2013

ORIGNAL ARTICLES43 On the question of cognitive limits in diagnostic his-

topathology E. Cardesi, D. Galliano

51 Histological evaluation of papillary lesions of the breast from needle biopsy to the excised specimen: a single institutional experience

S. Gilani, R. Tashjian, P. Kowalski

CASE REPORTS56 Pancreatic adenocarcinoma in duodenal ectopic pan-

creas: a case report and review of the literature A. Ginori, L. Vassallo, M.A.G.M. Butorano, F. Bet-

tarini, G. Di Mare, D. Marrelli

59 Pulse granuloma involving Meckel’s diverticulum: a case report and literature review

J.K. Karp, A. Davis, P.J. Read, A. Mashayekh, A. Bombonati, F. Palazzo

62 Sclerosing stromal tumour of the ovary: two case reports

F. Limaiem, E. Boudabous, S. Ben Slama, B. Chelly, A. Lahmar, S. Bouraoui, F. Gara, S. Mzabi

66 Diagnosis and clinical course of cardiac myxoma M. Mlika, A. Ben Youssef, R. Hamrouni, A. Ayadi-

Kaddour, T. Kilani, F. El Mezni

69 Lung metastasis from TTF-1 positive sigmoid adeno-carcinoma. Pitfalls and management

A. Remo, C. Zanella, M. Pancione, L. Astati, P. Pi-acentini, S. Cingarlini, A. Bonetti, C. Micheletto, A. Talamini, M. Chilosi, R. Vendraminelli, E. Manfrin

73 Primary tuberculosis of the adenoids in an 11-year-old male presenting with hearing loss: a case report

S. Taghipour-Zahir, M.H. Baradaranfar, A.A. Zol-faghari

76 Memoir of Antoine Zajdela L. Di Bonito

Index Volume 105, No. 1-6

363Index volume 105, no. 1-6

Issue 3June 2013

ORIGINAL ARTICLES77 Giant benign solitary fibrous tumour of the pleura

(>15 cm): role of radiological pathological correla-tions in management. Report of 3 cases and review of the literature

T. Pusiol, I. Piscioli, M. Scialpi, E. Hanspeter

83 The Cancer Screening Monitoring System: indicators for organised programmes and possible extension to spontaneous screening

P. Giorgi Rossi, A. Federici, M. Zappa

CASE REPORTS86 A complex association between derivatives from the

neural crest. A case report M. Filotico, O. Potì, S. Carluccio

90 Gangliocytic paraganglioma of duodenum metastatic to lymph nodes and liver and extending into the retro-pancreatic space

S.M. Amin, N. Wewer Albrechtsen, J. Forster, I. Dam-janov

94 A case of sclerosing angiomatoid nodular transforma-tion of the spleen

A. Giorlandino, R. Caltabiano, S. Lanzafame

98 Epithelioid fibrous histiocytoma EMA positivity: a case report

C. Floris, N. Di Naro, L. Olla, G. Puliga, D. Altea, G.A.Tolu

101 Hydatid cyst presenting as a breast lump in a male patient

F. Limaiem, S. Bouslama, I. Haddad, S. Bouraoui, A. Lahmar, S. Mzabi

104 About a challenging tumour, elastofibroma dorsi: an eight-case study

M. Mlika, N.B. Abdeljalil, S. Boudaya, A. Ayadi-Kad-dour, T. Kilani, F. Mezni

107 Leiomyomatosis peritonealis disseminata: pregnancy, contraception and myomectomy of its pathogenesis

M. Onorati, G. Petracco, P. Uboldi, S. Romagnoli, M.M. Amidani, G. Bulfamante, F. Di Nuovo

Issue 4August 2013

ORIGINAL ARTICLES111 Lymphomatoid granulomatosis: a practical review for

pathologists dealing with this rare pulmonary lym-phoproliferative process

E. Tagliavini, G. Rossi, R. Valli, M. Zanelli, A. Cadioli, M.C. Mengoli, A. Bisagni, A. Cavazza, G. Gardini

117 About the necessity of improving the current nodal classification of non-small cell lung carcinoma

M. Mlika, A. Ayadi-Kaddour, S. Boudaya, A. Marghli, T. Kilani, F. Mezni

122 Intraparenchymal leiomyoma of the breast: report of a case with emphasis on needle core biopsy-based di-agnosis

G.M. Vecchio, A. Cavaliere, F. Cartaginese, A. Lu-caccioni, T. Lombardi, R. Parenti, L. Salvatorelli, G. Magro

128 Primary mucinous carcinoma of the thyroid gland: case report with review of the literature

H. Mnif, A. Chakroun, S. Charfi, S. Ellouze, M. Ghor-bel, T. Sallemi-Boudawara

CASE REPORTS132 A solitary polypoid gastric metastasis 20 years after

renal cell carcinoma: an event to be considered, and a brief review of the literature

M. Onorati, G. Petracco, P. Uboldi, D.G. Redaelli, S. Romagnoli, M. Albertoni, F. Di Nuovo

137 Coexistence of xanthogranulomatous cholecystitis and gallbladder adenocarcinoma: a fortuitous asso-ciation?

F. Limaiem, B. Chelly, F. Hassan, I. Haddad, S. Ben Slama, A. Lahmar, S. Bouraoui, S. Mzabi-Regaya

140 Pinkus tumour: an unusual case S. Sehli Attafi, M. Jones, B. Fazaa, R. Zermani, S.R.

Rommany

142 Mammary myofibroblastoma with leiomyomatous differentiation: case report and literature review

H. Mnif, S. Charfi, N. Abid, T. Sallemi-Boudawara

Issue 5October 2013

ATTI DI CONGRESSO147 6° Congresso Triennale SIAPEC-IAP Roma, 26-30 ottobre 2013

Index volume 105, no. 1-6364

Issue 6December 2013

REVIEW329 Computed tomography-histologic correlations in lung

cancer I. Ariozzi, I. Paladini, L. Gnetti, M. Silva, D. Colombi,

M. De Filippo, N. Sverzellati

ORIGINAL ARTICLES337 Tumours of the skin adnexa: a case series with focus

on multiple segmental forms M. D’Andrea, C. Reggiani, D. Fasano, C.M. Betts,

F. Montanari, A. Lanzoni, M. Reggiani, M.P. Foschini

342 Role of on-site microscopic evaluation of kidney bi-opsy for adequacy and allocation of glomeruli: com-parison of renal biopsies with and without on-site mi-croscopic evaluation

S.M. Gilani, D. Ockner, H. Qu

CASE REPORTS346 Adenocarcinoma arising in a tailgut cyst: a case report S. Rammeh, S. Ben Abdelkrim, M.H. Ben Hadj Khali-

fa, R. Letaief, M. Mokni

349 Breast cholesterol granuloma: a report of two cases with discussion on potential pathogenesis

J. Bezić, M. Piljić-Burazer

353 Synchronous occurrence of pulmonary adenocarci-noma and pleural diffuse malignant mesothelioma

H. Imenpour, G.P. Ivaldi, A. Brianti, G. Pastorino, S. Biggi, L. Auriati, C. Simonassi

357 Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?

F. Limaiem, A. Khadhar, F. Hassan, S. Bouraoui, A. Lahmar, S. Mzabi

361 Letter to the Editor V. Eusebi

365

Author Index

Abbona G., 258 Abbondanza M., 282 Abdeljalil N.B., 104Abete L., 275, 276, 298, 316 Abid N., 142Accurso A., 304 Acquati F., 243 Addati T., 257, 267, 304 Agostinelli C., 150 Agostini V., 226 Airoldi I., 231 al-Hamad M., 228 Alaggio R., 232 Albarello L., 28Albertelli M., 248 Albertoni M., 132Albertoni M., 300 Albertoni M., 5Alessandrini L., 227, 258, 292, 293 Alì G., 254, 267, 308 Alia L., 291 Allaf M., 317 Altea D., 98Alvaro D., 252 Amato E., 239 Amato M., 294, 297 Amato T., 235, 236 Ambrogi M.C., 308 Ambrosini-Spaltro A., 257 Ambrosio A., 278 Ambrosio M.R., 232, 236, 278, 298,

315 Amico P., 238, 274, 317 Amidani M.M., 107Amin S.M., 90Ammirabile M., 266 Amodio G., 244 Amore F.F., 274, 315 Amoreo C.A., 208, 224, 253 Amoruso A., 296 Angeli G., 268 Angeli G.A., 310 Angelico G., 233, 287, 297, 315 Angelucci D., 265, 290, 306, 307,

310, 318 Angione V., 263 Angrisani B., 240, 259 Anichini C., 264 Anile M., 309 Anselmi L., 24Antinolfi G., 261 Antinori A., 265 Antonacci C., 225 Antoniani B., 208, 224 Antonuccio S., 304 Apollo A., 230 Aprile G., 250, 297 Arborea G., 244, 283, 289, 301, 306 Arcaini L., 234 Arciuolo D., 304 Arduini R., 261 Arena V., 304 Aretini P., 228 Argani P., 317 Ariozzi I., 329Armiraglio E., 270, 289 Armogida I., 228 Arra M., 234 Arrizza L., 255 Arrondini M., 268 Artibani W., 230, 318 Ascani S., 271, 278 Ascierto P., 176 Ascoli V., 240 Astati L., 69, 229 Augurio A., 232 Auriati L., 353

Ayadi-Kaddour A., 66, 104, 117Baccarini P., 259 Baggio S., 276 Baldovini C., 261 Baradaranfar M.H., 73Barbagli L., 278, 315 Barbanti G., 315 Baron L., 250, 281 Baronchelli C., 248 Barone A., 232, 235, 278, 298, 315 Barresi V., 216, 247, 250, 300, 314 Bartolommei S., 278 Basciu M., 211 Basilico R., 232 Basolo F., 156, 163, 301 Bassi C., 252 Bassi P.F., 313 Battolla E., 307 Beacci D., 285 Beccari S., 228 Becce M., 254 Bega O., 275, 288, 296 Bellan C., 235, 236 Bellevicine C., 241, 247, 253, 260,

261, 266 Bellezza G., 254, 278 Bellis D., 258 Bellotti A., 229 Beltrami C.A., 250, 284 Ben Abdelkrim S., 346Ben Hadj Khalifa M.H., 346Ben Slama S., 62, 137Ben Youssef A., 66Benvenuto A., 268 Berardi A.C., 289 Berloco P., 252 Berti E., 178 Bertorelle R., 293 Betta P.G., 182 Bettarini F., 56Betts C.M., 337Bevilacqua G., 228, 230 Bezić J., 349Biancalani M., 244 Bianchi C.L., 300 Bianchi D., 262 Bianco A., 241, 253, 266 Bianco S.B., 305Biggi S., 353Biglietto M., 266 Bio R., 21Birocco N., 157 Bisagni A., 111Bizzarro T., 240, 259 Blandamura S., 258, 292, 293 Blundo C.B., 305 Boccardo S., 308 Bogina G., 228 Boldrini R., 167 Bombonati A., 59Bonandini E., 258 Bonanno A.M., 260 Bonanno E., 152, 225, 282 Bondi A., 272 Bonetti A., 69Bonetti F., 228 Bongiovanni L., 271 Bonifacio D., 225 Bonifazi Pniccià A., 315 Borrelli N., 254 Borri F., 282 Borzomati D., 294 Boscaino A., 265, 266 Boschetto A., 241, 280 Bosco A., 227, 233, 274, 297, 315 Bosco D., 240, 252 Bosman F.T., 173

Botti G., 176 Bottini L., 280 Boudabous E., 62Boudaya S., 104, 117Bouraoui S., 18, 62, 137, 357Bouslama S., 101Branca G., 247, 250, 300, 314 Brancato F., 232 Bria E., 249Brianti A., 353Brisigotti M., 316 Brisigotti M.P., 248 Brucchietti R., 263 Brunelli F., 304 Brunelli M., 228, 230, 254, 315,

317, 318 Brunello E., 228 Brunetti A.E., 292 Bruno P., 261 Bruzzi P., 225 Bruzzone M., 314, 316 Bruzzone M.B., 310 Bubendorf L., 312 Buccoliero A., 275 Buccoliero A.M., 272 Buffelli F., 288, 296, 317 Bufo P., 270, 297 Buglioni S., 224, 253 Bulfamante G., 5, 107Bulgarelli L., 21Butorano M.A.G.M., 56, 260, 265,

285, 289 Cabibi D., 11, 303Cacciato Insilla A., 301 Cacciotti J., 295 Cadioli A., 111Cagiano S., 270 Calamaro P., 294, 316 Calarco A., 229, 312, 313 Calderoni G., 317 Caliò A., 236 Caltabiano R., 94, 268, 303, 315 Calvisi G., 258, 274, 297 Camerin C., 258 Campagna F.R.C., 305 Campidelli C., 298 Campioli L., 21Canavese G., 249, 293 Canessa P.A., 307 Cantile M., 176 Capasso G., 220 Capella C., 28, 164 Capelli P., 28, 247, 249, 252 Capodicasa S., 298 Capodimonti S., 234, 238 Caponio M.A., 257 Caporusso C., 268, 283, 306 Cappellesso R., 239, 258, 292 Cappiello A., 307 Capulli M., 229, 255, 263 Carbone A., 263, 304 Carbone F.S., 291 Carcangiu M.L., 149 Cardesi E., 43Cardia R., 300 Cardillo S., 285 Cardinale V., 252 Cardone C., 232, 315 Cardone R., 187 Carducci A., 260 Carini M., 318 Carlomagno C., 247 Carluccio S., 86Carmelo L., 219 Carnevali I., 243 Caroppo D., 311 Carotti U., 297

Carpino G., 252 Carr B.I., 282 Cartaginese, 122Casagrande M., 250 Cascarano M.A., 275, 296, 301 Cascone A., 303 Casini B., 224, 253 Cassano A., 249, 265 Cassaro M., 258, 299 Cassoni O., 174 Cassoni P., 249 Castaing M., 238 Castellano I., 249 Castiglione F., 272, 275 Cataldo I., 276 Catalucci A., 311 Cattaneo C., 292 Cattani M.G., 261 Cavaliere A., 122Cavaliere M.L., 266 Cavallaro G., 295 Cavalleri S., 318 Cavallini A., 282 Cavazza A., 21, 111, 185 Cazzulino C., 288 Ceccarelli M., 251 Cecconi F., 315 Celiento T., 248, 314 Cenci T., 229, 234, 235, 238, 239,

249, 265, 312, 313Cengia G.P., 248 Censi F., 233 Centrone M., 257, 267 Cerasoli V., 280 Cerbelli B., 240 Cerbone V., 220, 265 Ceriolo P., 244 Cernic S., 250, 253 Cerroni L., 150 Cerruto M.A., 318 Cesari P., 237 Cesari V., 159 Cestari R., 248 Chakroun A., 128Charfi S., 128, 142Chaux A., 230 Chelly B., 62, 137Chiacchio R., 268 Chiappetta C., 233, 256, 287, 295, 309 Chiaravalli A.M., 243 Chiarello G., 244 Chilosi M., 69, 236, 254 Chimenti M., 152 Chini T., 231 Chiominto A., 274 Chiudinelli M., 8, 311 Ciancia G., 287, 304, 305 Cicchinelli I., 258, 297 Ciccotelli M., 298 Cicinelli E., 244 Cima L., 230 Cimetti L., 199, 243 Cimminiello M., 268 Cimmino A., 288, 289 Cingarlini S., 69Cinocca S., 226, 261 Cipolloni G., 258, 297, 310 Cirese V., 194 Cirilli A., 306 Ciuffetelli V., 285 Civerra M., 301 Cives M., 283 Clemente C., 298 Cocomazzi A., 234, 239 Colantuoni V., 251 Colasante A., 232, 264, 294 Colby T.V., 179

aUthoR iNDEX

366

Colella R., 254 Coletti G., 274, 285 Collini P., 168, 206 Colombi D., 329Comin C., 275 Coppola L., 242 Coppola R., 294 Corradi G., 252 Corrado S., 238 Corsello S.M., 238 Corsi F., 283 Cosimi M.F., 288 Cossu Rocca P., 305, 316 Costa S., 204 Costarelli L., 226 Covelli C., 282, 283, 288 Cozzi I., 240 Cozzolino I., 287, 304, 305 Crescenzi B., 285 Crinò S., 260 Cristina S., 234 Croce C., 150 Croci G.A., 234 Crosetti E., 258 Crucitti P., 272 Cucchi M.C., 226 Curcio Rubertini B., 279 Cuscunà D., 301 Cutilli T., 258 D’Alessandris G.Q., 238, 239 D’Alicandro V., 208, 224, 253 D’Alo F., 235 D’Alterio A., 266 D’Amore E.S., 270D’Andrea M., 337D’Antonio A., 312 D’Antuono T., 231, 276 D’Armiento M., 271, 299 D’Elia C., 318 Dabrowska M.E., 280 Dal Mas A., 297 Dalla Palma P., 189 Dallera E., 234 Damjanov I., 90Daolio P.A., 289 Daperno M., 249, 293 Daprile R., 267, 304 David E., 293 Davis A., 59De Angelis F., 295 De Biase D., 159, 284 De Chiara A., 205 De Falco G., 236 De Feo A., 187De Filippo M., 329De Leo A., 225, 259 De Luca C., 247, 253, 260, 266 De Luca F., 236 De Luca G.De Lucia A., 302 De Maglio G., 250, 253, 284, 309 De Manzo G., 249 De Marco A.D.M., 305 De Marco V., 318 De Maria Marchiano R., 201 De Mattia D., 240 De Miglio M.R., 305, 316 De Paulis D., 311 De Pellegrin A., 263 De Rosa G., 261, 297 De Rosa N., 261 De Silvestri A., 250, 294 De Stefano A., 247 De Stefano F., 243 De Vanna A.C., 256 De Vito M., 299 Defferrari R., 168 Dei Tos A.P., 248, 288 Del Sordo R., 254, 278, 303 Del Vecchio G., 268 Del Vecchio M., 226 Dell’Endice T.S., 292, 304

Della Ragione C., 220, 265, 266 Della Rocca C., 233, 256, 287, 295,

309 Delsedime L., 221 Deriu G., 280 Despini L.D., 305 Dessanti P., 307 Detti B., 231 Di Benedetto A., 208, 224 Di Benedetto G., 1, 242Di Benedetto S., 224 Di Bernardo A., 270, 289 Di Blasi A., 251, 256 Di Carlo E., 231 Di Clemente L., 313, 314 Di Cola E., 270, 274, 285 Di Cristofano C., 233, 287, 295, 309 Di Filippo F., 224 Di Filippo L., 301 Di Giosia P., 270 Di Lallo A., 288 Di Lauro A., 257 Di Leo A., 296 Di Loreto C., 263 Di Lorito A.Di Mare G., 56Di Meo S., 231 Di Naro , 15, 98Di Nuovo F., 269, 279, 281, 287,

291, 300 Di Nuovo, 5, 107, 132Di Oto E., 284 Di Ristofano C., 256 Dima G., 291 Dimartino V., 208, 224 Diodoro M., 251 Disanto A., 260 Doglioni C., 236, 254 Donato F., 237 Donofrio V., 270 Dubini A., 236 Duregon E., 157, 166 Egarter-Vigl E., 243, 257 El Mezni F., 66Elicio G., 302 Ellouze S., 128Ena S., 305, 316 Ercolani C., 208, 224, 253 Ermellino L., 246 Errico M.E., 270 Esposito S., 231 Eusebi V., 39, 226, 227, 259, 361 Ezejiofor F.I., 232 Fabbri C., 259 Fabbri T., 279 Fabbri V.P., 284 Fabi A., 224 Fabozzi A., 1Facchetti F., 150, 236, 269 Facciolo F., 280 Fadda G., 240, 259 Falasca C., 261 Fanelli G., 228 Faraj S., 230 Fasano D., 337Fasola G., 250 Fassan M., 207, 239, 247, 249, 252,

294 Fassina A., 239, 258, 292, 293 Fazaa B., 140Fedeli F., 307 Federici A., 83Ferone D., 248 Ferrara G., 256 Ferraresi V., 251 Ferrari M., 288 Ferrario E., 162 Ferrario F. , 5Ferri A., 246 Ferri I., 254, 278 Ferro P., 307 Ficarra G., 154, 155

Filippetti M., 253 Filotico M., 86Finato N., 284 Fiocca R., 248, 271, 294, 298, 299 Fior A., 311 Fiore G., 244 Fiore M.G., 288, 296 Fiumanò E., 8Florena A.M., 271 Floris C., 98Fociani P., 246, 291 Fodero C., 21Foglia Manzillo E., 246 Fontana V., 307, 308 Fontanini G., 185, 254, 267, 308 Foreid S., 226 Fornaciari G., 255 Fornari A., 258 Fornelli A., 259 Forster J., 90Foschini M.P., 225, 226, 261, 284,

337 Franceschi E., 284 Franceschin M., 315 Franceschini M.C., 307 Franchi A., 302 Franco G., 271 Franco V., 271, 303 Fraternali Orcioni G., 271, 299 Freguia F., 284 Freguia S., 243 Frezza G.P., 284 Fujita K., 230 Fulcheri E., 244, 272, 275, 276 Fulcheri L., 258 Fuligni F., 150 Furlan D., 243 Gacci M., 318 Galimberti M., 281 Galleri D., 301 Galliano D., 43Gallmetzer F., 257 Gallo E., 224, 280 Galloro P., 220, 265 Galzio R., 311 Gambini C., 244 Gambini D.G., 305 Gara F., 62Garatti C., 311 Gardini G., 111Garufi C., 251 Gaspari G., 232 Gaudio E., 252 Gelibter A., 251 Gemini Piperni S., 255 Gennari A., 225 Genova R., 148 Gentile M., 282 Gentile R., 252 Gessi M., 217 Ghirardini A., 187 Ghiringhello B., 203 Ghorbel M., 128Giachelia M., 235 Giacometti C., 258 Giampietro J., 232 Giannatiempo R., 277 Giannini E., 225 Giannini R., 254 Giannone A.G., 271 Giannone G., 257, 267 Giansanti D., 241, 280 Giardina C., 306 Giardini R., 188 Giarnieri E., 241, 261 Gilani S., 51Gilani S.M., 342Gilioli E., 254 Ginori A., 56, 232, 260, 265, 278,

291, 293, 315Giordano M., 271, 299 Giordano S., 286

Giorgio F., 296 Giorlandino A., 94, 233, 268, 274, 315 Giorlandino AGiotta F., 304 Giovagnoli M.R., 203, 241, 261, 280 Giovenali P., 285 Giroda M.G., 305 Giuffra V., 255 Giuffrè G., 247 Gnetti L., 329Gobbo S.P., 317 Gonzalez-Roibon N., 230 Gozzetti A., 236 Grasso G., 317 Grillo F., 248, 250, 272, 276, 294, 298 Grillo F.G., 310 Grillo L., 240 Grindati A., 246 Grossi F., 308 Guadagno A., 271, 299, 316 Guadagno A.G., 310 Guardascione M., 250 Guerrieri A.M., 306 Guerriero M., 288, 301 Guglielmi A., 247 Guidotti M.C., 255 Guiotto I., 263 Gulino A., 271 Gullo I., 294 Guzzetti S., 161 Haas T.L., 239 Haddad I., 18, 101, 137Hailemariam S., 312 Hamrouni R., 66Hanspeter E., 77Hartmann A., 312 Hassan F., 137, 357Hayashi M., 317 Herz M., 260 Hicks J., 230 Hohaus S., 234, 235 Hoque M., 317 Iaccarino A., 241, 266 Iachininoto M.G., 234 Iacomino E., 311 Ianniello A.A., 287 Iannucci A., 254 Iantorno R., 232 Ieni A., 247, 250, 260, 300, 303,

314, 317Ientile D., 148 Ierardi E., 296 Ilardi G., 282 Imenpour H., 24, 353Inchingolo C.D., 286, 299, 302 Inghirami G., 254 Ingravallo G., 289, 296, 306 Iorio O., 295 Ishikawa Y., 303 Ius T., 284Ivaldi G.P., 353Jaconi M., 308 Jasani B., 228 Jones M., 140Kara E., 301 Karp J.K., 59Kasal A., 243, 257 Khadhar A., 357Kilani T., 66, 104, 117Korasidis S., 308 Kowalski P., 51Krausz T., 39La Rosa S., 164 La Starza R., 285 Laginestra M.A., 150 Lahmar A.,18, 62, 101, 137, 357Lambiase M., 239 Lanza C., 227 Lanza P., 249 Lanzafame S., 94, 268, 303Lanzoni A., 337Larghi A., 249

aUthoR iNDEX

367

Larocca L.M.Lattanzio G., 264, 269, 273, 276,

281, 284 Laudanna C., 251 Laurent S., 308 Laurino L., 225 Lavezzi A.M., 307 Lawlor R., 230 Lazzari E., 270 Lazzi S., 232, 236 Lega S., 272 Leocata L., 270 Leocata P., 258, 274, 285, 297, 304 Leomporra G., 187 Leoncini L., 232, 235, 236 Leone B.E., 292, 308 Leone G., 234, 235 Leopizzi M., 233, 287, 309 Lessi F., 228, 230 Lestani M., 306, 315Letaief R., 346Lettini T., 244, 282, 283 Libener R., 227 Liberati F., 263, 299, 311, 313, 314 Liberatore M., 276 Licata L., 300, 314 Limaiem F., 18, 62, 101, 137, 357Lio R., 265, 285 Lisanti M.P., 228 Liso V., 271 Liuzzi M., 268 Lo Mele M., 227 Lo Vasco V.R., 287 Lobello G., 278 Lombardi C.P., 240, 259 Lombardi M., 262 Lombardi T., 122Lonfo F.R., 226 Longo F.R., 233, 287, 297 Lopez Beltran A., 213 Lorenzi L., 211 Lorusso F., 11Lorusso V., 292 Losito V., 286, 299 Losurdo G., 296 Lucaccioni A., 122Luchini C., 249, 254, 276, 318 Lucioni M., 178, 234 Luconi M, 215Ludovini V., 254 Lupi C., 254 Maccallini V., 242 Maccari A., 5Maccio L., 238 Maffi A., 178 Mafficini A., 239, 247, 249 Maganza C., 272 Maglietta A., 295 Maglietta R., 295 Magnani E., 301 Magro G.Magro G., 122Maino A., 283 Mainoldi P., 261 Maione M.P., 277 Maiorana A., 154, 155, 238, 301 Maiorano E., 268 Makeda T., 150 Malaguti P., 224 Malapelle U., 241, 247, 253, 266 Malfettone A., 304 Manca A., 305, 316 Manenti S., 248 Manfrin E., 69, 228, 229, 251, 276,

311 Mangia A., 292, 304 Mani A., 269, 310 Mannelli M., 215 Marchegiani G., 252 Marchelle G., 227 Marchesin F., 284 Marchetti A., 232

Marchiò C., 224 Marchione R., 311 Marchione R., 8Marchionni L., 317 Marghli A.,117Marinelli C.Marinelli L., 240 Marino M., 184, 280 Marinucci A., 274, 304 Marra G., 295 Marras V., 305 Marrelli D., 56Marsaoui L., 18Martignoni G., 228, 230, 236, 252,

254, 315, 316, 317, 318Martini M.Marucci G., 284 Marzano A.L., 304 Marzullo A., 282, 283, 295 Masciullo V., 244 Mascolo M., 256 Mashayekh 59Masiero E., 250, 253 Massa S., 211 Massi D., 215, 264 Mastracci L., 248, 250, 272, 275,

294, 298, 314Mastracci L.M., 310 Mastrogiulio M.G., 315 Mastromauro M., 296, 301 Matteucci C., 285 Mattioli E., 246 Matturri L., 307 Maurizi A., 255 Mazzanti C.M., 228, 230 Mazzei M.A., 293 Mazzilli L., 232 Mazzocco K., 168 Mecucci C., 285 Meeker A., 230 Melchiorri L., 274, 304 Melisi D., 247 Melucci E., 208, 224, 251, 253 Meneghini G., 306 Menghi M., 254 Mengoli M.C., 111Menicagli M., 228 Mercurio C., 255, 313 Mercurio C.A., 229 Merlo D.F., 308 Merola G., 287 Merolla F., 283 Mertz K.D., 312 Messerini L., 174, 275 Messini S., 260 Mezni F., 104, 117Mian C., 257, 260 Miccoli P., 301 Micheletto C., 69Micheli P., 261 Migliora P., 268 Migliora P.M., 310 Mignogna C., 148 Miracco C., 293 Miraglia C., 289, 290 Mirella P., 270 Miscioscia P., 302 Mitilini N., 220, 265, 266 Mlika M., 66, 104, 117Mnif H., 128Mokni M., 346Molinaro L., 250, 294 Monaco R., 265 Monciatti I., 298 Moncini D., 272, 275 Moneghini L., 5Montagnani I., 272, 275 Montanari F., 337Montenegro L., 296 Monti L., 243 Montrone T., 244, 283, 306, 317 Monzoni A., 225

Mora M., 308 Morabito A., 308 Morandi L., 225, 284, 303 Moretto R., 247 Mori V., 230 Morichetti D., 271, 273, 307, 312 Morini S., 297 Mottolese M., 208, 224, 251, 253 Mourmouras V., 236, 298 Munari E., 230, 317 Muroni M.R., 305, 316 Musci G., 275, 282, 296 Musizzano Y., 244 Mussari S., 257 Mustacchi G., 225 Muzii V.F., 285 Mzabi S., 18, 62, 101, 357Mzabi-Regaya S., 137Naccarato A.G., 228, 230 Napoli A., 289, 317 Nappi O., 265, 266 Nappo G., 294 Natella V., 261 Nebuloni M., 246 Negri F., 244 Negri G., 243, 257, 260, 262 Nenna R., 286, 299, 302 Nesi G., 215, 231, 302, 318 Netto G., 230, 317 Nicastro A., 277 Niccoli C., 254, 267 Nicita G., 231 Nicola M., 178, 234 Nofrini V., 285 Nonomura N., 230 Normanno N., 239 Nottegar A., 254 Novella G., 318 Nugnes L., 277 Nuti M., 252 Nuzzolo E., 234 Ockner D., 342Olivari N., 252 Olla L., 15, 98Onetti Muda A., 294, 297 Onorati M., 5, 107, 132, 269, 279,

281, 287, 291, 300Opinto G., 268, 306 Oppressore D., 277 Orlandi A., 282 Orrù S., 305 Ortenzi V., 228, 230 Orvieto E., 227 Ottaviani F., 232 Otte O., 318 Oyama T., 303 Pacella E., 275 Pacella E.P., 310 Pacella M., 316 Padolecchia E., 262 Pagani L., 284 Pagano F., 246 Pagano L., 150, 266 Pagliarulo V., 282 Paglierani M., 215 Pagni F., 292 Paladini I., 329Palazzo F., 59Palicelli A., 262 Pallante P., 266 Pallini R., 238, 239 Palma F., 246 Palmieri D., 302 Palumbieri G., 290 Palumbo M., 265 Pancione M., 69, 229, 251 Paniccià Bonifazi A., 306 Pannone G., 270, 297 Panzacchi R., 226, 261 Papadantonakis A., 280 Papanikolaou N., 243 Papi G., 238

Papotti M., 157, 166, 258 Papucci A., 264 Paradiso A., 246 Parafioriti A., 270, 287, 289 Parenti R., 232, 122Parisi A., 276 Pasinato L., 311 Pastorino G., 353Paulli M., 150, 178, 234 Pecori S., 249 Pedicillo M.C., 270 Pegolo E., 263, 284 Pellegatti S., 229 Pelliccioni S., 254, 267 Pennacchia I., 304 Pennella A., 282, 283 Pepe F., 253, 266 Peronio L., 263 Perracchio L., 224 Perrone G., 294, 297 Persiani R., 249 Pescarmona E., 224, 280 Pession A.L., 159 Petracco G., 107, 132Petracco G., 269, 279, 287, 291 Petrogalli F., 24Petrone G., 229, 312, 313 Petroni S., 257, 267 Petrozza V., 233, 256, 287, 295, 309 Petruzzellis C., 252 Pettinato G., 271, 287, 299, 304, 305 Pezzuto F., 282, 283, 296 Piacentini P., 69Piana A., 305 Picardi A., 297 Piccaluga P.P., 150 Piccolomini M., 311 Piccolomini M., 8Pierconti F., 229, 312, 313 Pierini T., 285 Pierini V., 285 Pierotti P., 272 Pignatti E., 301 Pileri Jr A., 150 Pileri S.A., 150 Pili F., 316 Piljić-Burazer M., 349Pilotto S., 249 Pilozzi E., 218 Pimpinelli N., 150 Pinto F., 229, 312, 313 Pinzani P., 215 Piol N., 250, 294 Piovano P.L., 227 Pireddu A., 254 Pisapia P., 260 Piscioli I., 77Piscitelli D., 296, 301 Pistillo M.P., 307, 308 Pitino A., 288 Pitto F., 250, 275, 294 Pizzi S., 292 Pizzolitto S., 250, 253, 263, 284, 309 Pizzuti M., 268 Plank J., 243 Pochini M., 241, 280 Poggi G., 231, 302, 318 Poletti V., 236 Pollio A.M., 288, 301 Ponte R., 276, 314, 316 Pontecorvi A., 238, 240, 259 Pontieri F., 271 Popescu O., 267 Porcaro A.B., 230 Porcasi R., 271 Porta N., 256, 295 Posenato I., 311 Postiglione A., 265 Postiglione M., 277 Potì O., 86Potieri F., 291 Potincasa P., 288

aUthoR iNDEX

368 aUthoR iNDEX

Prandi S., 21Pretelli D., 272 Pretelli P., 275 Proietti A., 254, 267 Projetto E., 272, 275 Puggioni C., 233, 256, 287 Pulcini F., 211 Puliga G., 15, 98Punzi A., 282, 283, 289 Punzo A., 257 Pusiol T., 77, 271, 273, 307, 312 Puzzo L., 227, 232 Qu H., 342Rachiglio A.M., 239 Ragazzi M., 185 Raimondi A., 286 Raimondi P., 290 Raiti G., 263 Rammeh S., 346Ranieri G., 314 Ranieri L., 265 Raulli G., 189, 279 Read P.J., 59Redaelli D.G., 132Reggiani C., 337Reggiani M., 337Reggiani Bonetti L., 250 Reghellin D., 306, 315 Reid L., 252 Reina H., 243 Remo A., 69, 229, 251, 311 Renzulli G., 275, 301 Resta L.Riboni R., 234 Ricci C., 240, 259 Ricci R., 248, 249, 265 Ricci-Vitiani L., 238, 239 Rinaldi C., 1Rinaldo C., 280 Rindi G., 163, 248, 249 Riosa F., 263 Risio M., 174 Riva C., 199, 243 Riva G., 252Riva M., 243 Rivasi F., 243, 262 Rizzi R., 271 Rizzo A., 198, 225 Rocca B.J., 232, 236, 278, 298, 315 Rocca R., 249, 293 Rochira V., 301 Rodella R., 252, 262 Rognoni E.R., 305 Rolfi F., 237 Romagnoli S., 5, 107, 132Rommany S.R., 140Romoli S., 285 Roncati L., 154, 155, 301 Roncella S., 307 Ronchi S., 292, 308 Rosaria S.M., 150 Rosini F., 226 Ross G., 185 Rossi E., 240 Rossi E.D., 259 Rossi G., 111Rossi P. Giorgi, 83Rossi R., 244, 282 Rossoni R., 282 Rotellini M., 272 Rotondo M.I., 301 Roz E., 219, 227 Rubini A., 306 Rubini V., 246, 267 Rubino T., 21Rucci N., 229, 255 Rucco V., 306, 315 Ruco L., 210 Rugge M., 227, 294 Ruisi R., 286 Rullo D., 298, 299

Runza L.R., 305 Russo A., 277 Russo D., 256 Russo M., 247 Russo S., 253, 266 Ruzzenente A., 247 Ruzzo A., 251 Sabatino L., 251 Sacchini A., 236 Saguatti, 261, 226 G., Sahnane N., 243 Saieva C., 231 Saladino V., 231, 302, 318 Salatiello M., 253 Salemme M., 248 Sallemi-Boudawara T., 128, 142Saltarelli S., 270 Salvatorelli L., 122, 226, 227, 232,

233, 238, 297, 317Salvi S., 308 Salvia R., 252 Salvianti F., 215 Sanges F., 316 Sansò M.R., 269 Santagostino A., 268 Santangelo R., 235 Santeusanio G., 193 Santi R., 231, 302, 318 Santopietro R., 315 Santopietro R.C., 278 Santoro A., 270, 297 Santoro P., 288 Sapino A., 161, 224, 249, 293 Saponaro C., 292 Saporito C., 266 Sarocchi F., 250, 276, 294, 298, 314 Sartori G., 262 Savio A., 237, 252, 262 Scamarcio R., 268, 275, 301, 306,

317 Scambia G., 244 Scaramuzzino F., 291 Scarfì R., 247 Scarpa A., 161, 207, 230, 239, 247,

249, 252Scatena C., 215, 228 Scattone A., 282, 283 Schiavo N., 306, 315 Scialpi M., 77Scibetta N., 286, 289, 290 Scimeca M., 152, 225 Scognamiglio G., 176 Scognamillo G., 257 Scotti M.C., 281 Seghetto I., 229 Sehli Attafi S., 140Sementa A.R., 168 Semeraro R., 252 Semeraro V., 21Senetta R., 249, 293 Senore C., 174 Sensi E., 254 Sepich C.A., 230 Seraschi C., 187 Serio G., 282, 283, 296 Serra S., 305 Servadio A., 267, 308 Sessa F., 28, 164, 199, 243 Sfondrini M.M.S., 305 Sgariglia R., 247, 253, 266 Siano M., 311 Sicoli F., 249 Sidoni A., 254, 278, 303 Sikora K., 239 Silecchia G., 295 Silva M., 329Silvestris F., 283, 317 Silvestris N., 292 Simbolo M., 247, 249 Simonassi C., 353Simonato F., 258, 292, 293

Simone A., 247 Simone G., 246, 257, 267, 292, 304 Simoni M., 301 Sironi M., 225 Skrap M., 250, 284 Soda G., 257 Soddu S., 280 Sollai M., 231, 264, 302, 318 Sollima L., 270, 274, 285 Somma A., 261 Somma P., 270 Sonzogni A., 174 Sormani M.P., 225 Sorrentino C., 231 Sotgiu G., 316 Spairani C., 288 Sparano L., 252 Speciale G., 314 Speciale R., 11Sperandio N., 230, 252 Sperduti I., 251 Sperti C., 292 Squadrelli-Saraceno M., 302 Squillaci S., 8, 288, 311 Staibano S., 176, 297 Stamati R., 261 Straccia P., 240, 259 Sturiale C., 284 Succo G., 258 Suriani R., 249, 293Sverzellati N., 329Tabbò F., 254 Tacchini D., 265, 285, 289, 291 Taddei G., 275 Taddei G.L., 272, 275 Taghipour-Zahir S., 73Tagliavini E., 111, 185Talamini A., 69Talamo I., 5, 281 Tallini G., 159, 284 Taramelli R., 243 Tashjian R., 51Tedoldi C., 282 Teofili L., 234 Terrenato I., 224 Terrinazzi V., 272, 275 Terron E., 246 Teti A., 229, 255 Theunissen P., 309 Tibiletti M.G., 243 Tinelli C., 250 Tironi A., 236 Tisi M., 235 Todaro P., 260 Tognetti A., 308 Tolu G.A.15, 98Tomei S., 230 Tomezzoli A., 247 Tommasetti S., 236 Toncini C., 314, 316 Torregrossa L., 163, 301 Torrisi A., 238 Torsello A., 251 Tortora G., 247 Tot T., 196 Totaro A., 313 Toti P., 289 Trabucco X., 317 Tricoli D., 233 Tripodi S., 291, 315 Tripodo C., 150 Troncone G., 241, 247, 253, 260,

261, 266 Trovati M., 302 Trovato G., 238 Truini M., 308 Tuccari G., 247, 250, 260, 303 Tupone M.G., 231 Uboldi P., 107, 132, 279, 281, 287,

300Uccini S., 151

Ungari M., 8, 311 Unti E., 286, 289, 290 Uras M.G., 305, 316 Urso C., 264 Valentini E., 258 Valentini S., 234 Valentino A., 307 Valli R., 111van der Wal A.C., 212 van Roijnen N., 309 Varga S., 226 Vari S., 224 Varone V., 287, 304, 305 Varricchio S., 282 Vasquez E., 226, 232, 297 Vassallo L., 56, 265, 285, 289, 293,

315 Vattemi E., 257 Vecchio F.M., 304 Vecchio G.M., 122Vecchio G.M., 226, 227, 233, 238,

274, 287, 317 Vecchione A., 214 Vecchione M.L., 283 Vellone V.G., 244, 272, 275, 276,

294, 310 Vendraminelli R.,69, 229, 251 Ventura L., 229, 255, 263, 298, 299,

311, 313, 314Ventura T., 298 Venuta F., 309 Verdun di Cantogno L., 171 Vergine M., 228 Vespasiani Gentilucci U., 297 Vetrani A., 287, 304, 305 Viberti L., 162 Vici P., 224 Vighi E., 301 Vigliar E., 241, 260, 261 Villanacci V., 248, 249, 293 Villari D., 231 Vinciguerra A., 232 Vindigni C., 293, 298 Viola P.Visani M., 159 Visca P., 253 Vismara A., 269 Vitale A.R., 285, 304 Vittadello F., 243, 257, 260, 262 Viviani G., 237 Viviano M., 272 Volante M., 157, 166 Voso M.T., 234, 235 Vurchio L., 299 Wewer Albrechtsen N., 90Zagami M., 263 Zambelli C., 237, 262 Zamboni G., 228 Zamboni G., 28Zamò A., 236 Zamparese R., 270 Zanconati F., 225 Zanconato G., 276 Zanella C., 229, 251 Zanella C., 69Zanelli M., 111Zannoni G.F., 147, 244, 271 Zappa M., 83Zaralli R., 256 Zavaglia K., 228, 230 Zawada L., 246 Zeppa P., 303, 312 Zerbi P., 246 Zermani R., 140Zeuli M., 251 Zolfaghari A., 73Zorzi F., 237, 252, 262 Zorzi M.G., 271, 273, 307, 312 Zorzi R., 289 Zorzoli A., 231 Zugaro L., 313

369KEY WoRDS iNDEX

Key words index

Adenocarcinoma 353Adenocarcinoma duttale 28 Adenoids 73 Adequacy 342Benign tumour of the pleura 77Biopsy 5, 51, 142Breast 101, 122, 349Breast cancer 51Breast carcinoma 357Carcinoma 128, 137Cardiac 66 Cemento-ossifying fibroma 11Cervical cancer 21, 83Cholesterol granuloma 349Cognitive process 43Colorectal carcinoma 69 Contraception 107 CT 329Cutaneous 140Developmental cyst 346Diagnosis 56Diagnostic histopathology 43 Differential diagnosis 51, 122, 128, 329Duct ectasia 349Duodenum 18, 56, 90EBV 111 Eccrine spiroadenoma 337Ectopic pancreas 56 Elastofibroma dorsi 104EMA 98Endocrine tumour 90 Endometrial adenocarcinoma 8 Epithelioid fibrous histiocytoma 98Fibro-osseous dysplasias 11Fibroepithelioma 140 Fibrous tumour 77Gallbladder 137 Gangliocytic paraganglioma 90 Gastric obstruction 56 Glomeruli 342Granulomatous lobular mastitis 357H-caldesmon 142Histology 140, 329HPV genotyping 21 Human papillomavirus 21

Hydatid cyst 101 Hypertrophy 73Ileum 18 Immunodeficiency 111Immunohistochemistry 43, 98, 111, 122,

128Kidney biopsy 342Larynx 5 Leiomyoma 122 Leiomyomatosis 107Lipoma 24Low-grade chondrosarcoma 5 Lung 111 Lung cancer 21, 329Lung metastasis 69Lymphoma 111 Macrocyst 349Malignant transformation 56, 346Mass screening 83 Maxillary sinus 11Meckel’s diverticulum 59 Mesenchymal tumours 5Metastases to liver 90Molecular biology 69Morphology 94Mucinous carcinoma 128Multiple segmental eccrine spiroadenoma

337Myofibroblastoma 142 Myomectomy 107Myxoma 66Neoplasia intraduttale 28 Neurocristopathic complex neoplasia 86Non-small cell lung carcinoma 117Odontogenic fibro-osseous lesions 11Onsite evaluation 342Ossifying fibroma 11Ovary 62 Pancreas 28Pancreatic heterotopia 18 Papillary neoplasms 51 Papilloma 51 Performance indicators 83 Pilomatrix carcinoma 8 Pilomatrixoma 8

Pleural malignant mesothelioma 353Polypoid gastric metastasis 132 Pregnancy 107Primary 73 Pseudotumor 104Pulse granuloma 59Quality assurance 83Radiology of the pleura 77Rare tumors 15 Ratio of metastatic lymph nodes 117 Referto GIPAD 28 Renal cell carcinoma 132 Retrorectal hamartoma 346SANT 94Sclerosing stromal tumour 62 Serous papillary cystadenoma 15Serous papillary cystic tumor 15 Sex cord-stromal tumours 62Shadow cells 8Skin adnexa 337Siapec Consensus Conference Molecular

Biology 1Skin 98Small intestine 18Smooth muscle cells 142 Snare polipectomy 132Spindle cell tumors 122Spleen 94 Surgery 51, 66, 137, 357Synchronous pulmonary neoplasias 353Tables of truth 43Tailgut cyst 346Testicular neoplasms 15 Testis 15 Thyroid FNAB 1 Thyroid gland 128 TNM classification 117TTF-1 69 Tuberculosis 73Ultrasonography 101Uterine lipoma 24V600-Braf 1Xanthogranulomatous cholecystitis 137

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Journal of the Italian Society of Anatomic Pathology and Diagnostic