Correspondence

Primary primitive neuroectodermal tumour ofthe urinary bladder

Sir : With reference to the recent article in Histopathol-ogy entitled ‘Primary peripheral primitive neuroecto-dermal tumour of urinary bladder’1, I present here yetanother interesting and unique case of peripheralprimitive neuroectodermal tumour (PNET) of theurinary bladder which was seen in 38-year-old femalepatient with Hodgkin’s disease.

A 38-year-old female patient was referred to ourinstitution with bilateral cervical and mediastinallymphadenopathy. Lymph node biopsy confirmed thediagnosis of Hodgkin’s disease of mixed cellularity type.The patient received radiotherapy and chemotherapyand was apparently disease-free until 3 years later,when she noticed gross haematuria. Cystoscopic biopsyrevealed a high-grade malignant tumour. The patientunderwent radical cystectomy and total hysterectomywith bilateral salpingo-oophorectomy.

Grossly, a polypoidal and focally necrotic tumourmeasuring 120 × 70 × 35 mm was present in theanterior and both lateral walls. It was infiltrating thefull thickness of the bladder. Histology revealed sheets ofclosely packed small round to ovoid cells with interven-ing thin fibrovascular stroma (Figures 1a and b). Thenuclei displayed finely granular chromatin with occa-sional prominent chromocentres. Mitotic activity was0–3 per high-power field. Apoptosis was also noted. Thetumour infiltrated the full thickness of the bladder andextended into perivesical tissues. Endometrium andbilateral adnexa were unremarkable for the age of thepatient. Pelvic nodes were uninvolved.

Immunohistochemical studies with antibodies toMIC2 gene product uniformly decorated the membraneof the tumour cells (Figure 2). Neurone-specific enolaseand vimentin were also positive in the majority ofthe cells. Epithelial (cytokeratin, epithelial membraneantigen) and lymphoid (leucocyte common antigen)markers were non-reactive. S100 protein and desminwere also negative. Thus immunohistochemistry con-firmed the presence of PNET occurring in the urinarybladder.

Second malignancy developing following the treat-ment of Hodgkin’s disease is well recognized. Acute ornon-lymphocytic leukaemia occurs in the first few yearsafter treatment, most probably as a consequence ofchemotherapy, whereas with longer follow-up a higherthan expected risk for the development of solid tumoursis evident. Exposure of alkylating agents or radiation,immunosuppression due to treatment, genetic predis-position and immunological deficits associated withHodgkin’s disease may contribute to the development ofthe second malignancy2,3. A striking similarity observedin these two cases. The case reported by Banerjee et al.1

was seen in the immunosuppressed renal transplantrecipient; whereas our case occurred in a treated case ofHodgkin’s disease. Deranged immunological mechan-isms due to primary disease or prior treatment seem tobe the causative factors for the occurrence of PNET atsuch an uncommon site in these cases.

S.Desai

Tata Memorial Hospital, Dr. Ernest BorgesMarg, Parel, Mumbai, India

Histopathology 1998, 32, 477–485

q 1998 Blackwell Science Limited.

Figure 1. Sheets of monomorphic tumour cells with intervening thinfibrovascular septa (haematoxylin and eosin). Figure 2. Tumour cells are immunoreactive to MIC2.

1. Banerjee SS, Eyden BP, Mcvey RJ, Bryden AAG, Clarke NW. Primaryperipheral primitive neuroectodermal tumour of urinary bladder.Histopathology 1997; 30; 486–490.

2. Mauch PM, Kalish LA, Marcus KC et al. Second malignancies aftertreatment for laparotomy staged IA-IIIB Hodgkin’s disease: Long-term analysis of risk factors and outcome. Blood 1996; 87; 3625–3632.

3. Swerdlow AJ, Barber JA, Horwich A, Cunningham D, Milan S,Omar RZ. Second malignancy in patients with Hodgkin’s diseasetreated at the Royal Marsden Hospital. Br. J. Cancer 1997; 75; 116–123.

Prostate-specific antigen and the salivarygland

Sir : A recent article by Simpson and Skalova describedtwo cases of metastatic carcinoma of the prostatepresenting as a parotid tumour1. They referred to astudy by van Krieken2, describing positive staining byprostate markers in tumours of the salivary glands.Simpson and Skalova were unaware of other studiesreproducing these results.

I would like to draw attention to a study reportedsome 12 years ago3, describing staining of striated ductcells of the salivary gland and myeloid cells withprediluted (kit) rabbit antisera to prostate-specificantigen. One pleomorphic adenoma was also positive.Understandably this study was reported in a localscientific journal and would probably not appear inmost computerized literature searches.

This aberrant staining was found to disappear whenthe antisera was further diluted: 1/16 for salivary glandstaining and 1/8 for myeloid cells. Positive stainingremained in a poorly differentiated prostatic carcinomaat these dilutions. The cross-reacting antibodies weretherefore found to be a minor component of theantibody preparation.

Since then, this staining has failed to recur withsubsequent lots of antibody. This also has been found bySimpson and Skalova.

It is therefore important to routinely test new lots ofantiserum on normal tissues to check for unexpectedstaining. Salivary gland and bone marrow (myeloidcells) should be included in the quality control of PSAantisera.

T.Henwood

Department of Anatomical Pathology, Royal Prince AlfredHospital, Camperdown, Australia

1. Simpson RHW, Skalova A. Metastatic carcinoma of the prostatepresenting as parotid tumour. Histopathology 1997; 30; 70–74.

2. Van Krieken JWM. Prostate marker immunoreactivity in salivary

gland neoplasms, a rare pitfall in immunohistochemistry. Am. J.Surg. Pathol. 1993; 17; 410–414.

3. Scott GS, Henwood AF. Crossreactivity in immunoperoxidase:prostate specific antigen. Aust. J. Med. Lab. Sci. 1984; 5; 73–75.

Squamoid eccrine ductal carcinoma

Sir : Related to the recent report on squamoid eccrineductal carcinomas by Wong et al.1, we want to commenton our recent experience with a case of malignanteccrine neoplasm showing extensive squamous differ-entiation in a 41-year-old-man.

The tumour was located on the right knee and hadbeen present for < 10 years. One month prior toexcision, the size of the lesion decreased from20 × 20 mm to 10 × 5 mm and a yellow fluid dischargecould be seen on the surface. The clinical examinationshowed no evidence of lymph node or systemicmetastases.

Histologically the tumour was poorly circumscribedand showed an infiltrative growth (Figure 1a) with deepextension into the dermis near the subcutaneous fat.Only focal continuity with the overlying epidermis wasfound. The neoplasm showed prominent squamousdifferentiation resembling moderately well differen-tiated squamous cell carcinoma (Figure 1b) as well asfocal ductal differentiation including a cuticular lumi-nal border reminiscent of eccrine ducts (Figure 1c). Theinvasion front was characterized by sheets and islandsof atypical keratinocytes with squamous eddies, horncysts, and the occasional presence of intercellularbridges. Tumour cells were surrounded by a desmo-plastic stromal reaction. Another outstanding featurewas the presence of in situ squamous cell carcinomawithin the eccrine sweet ducts or glands found at theperiphery of the tumour masses. At higher magnifica-tion, tumour cells showed nuclear pleomorphism andmitoses (1 per 10 high-power fields).

Immunohistochemical stains showed strong luminalreactivity with a polyclonal anti-CEA antibody (Figure1d), and EMA immunostaining in areas with apparentductal differentiation. The tumour cells were negativefor S100 protein but we observed reactivity in residualmyoepithelial peripheral cells and dendritic cells withinthe tumour islands. Immunostaining for GCDFP-15 wasnot found in tumour cells whereas normal eccrineglands were strongly positive.

Squamous differentiation in the eccrine sweat glandcarcinomas had been already reported by Swanson et al.in 1986. In regard to the age at presentation, althoughWong et al.1 pointed out that squamoid ductal carcin-oma, as most eccrine carcinomas, occur in elderlyindividuals, our patient was aged 41 at the time of

478 Correspondence

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

diagnosis. The fact that the neoplasm had been presentfor 10 years with no dramatic increase in tumour size,and no regional or systemic dissemination, speaks infavour of an indolent clinical behaviour. The clinical

characteristics of our case are similar to that reported byPena and Suster4 as malignant eccrine poroma withsquamous differentiation. The follow-up in our case is,however, too short to evaluate the recurrence rate.

Correspondence 479

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 1. a, Low-power view of the neoplasm invading the dermis and showing a prominent luminal component (immunoperoxidase, CEA,× 25). b, A detail of the squamous differentiation (H & E, × 400). c, Both luminal and squamous components can be seen in this area (H &E, × 400). d, Apical CEA immunostaining of ductal differentiation (immunoperoxidase, CEA × 400).

Thus, in addition to emphasize, as Wong et al.1 did,the convenience of grouping eccrine ductal carcinomaswith predominantly squamous differentiation as adistinct subtype, our case indicates that these neo-plasms may occur in younger patients than previouslyreported, and that a cystic ductal component (probablyrelated to tumour compression) may account forvariations in tumour size. The latter feature meritsparticular attention, given the longstanding clinicalevolution of our case, as well as other eccrinecarcinomas reported in the literature4.

J.HerreroC.Monteagudo

E.Jorda*A.Llombart-Bosch

Departments of Pathology,and *Medicine (Dermatology),Hospital Clinico Universitario,

University of Valencia, Spain

1. Wong T-Y, Suster S, Milmi MC. Squamoid eccrine ductalcarcinoma. Histopathology 1997; 30; 288–293.

2. Swanson PE, Cherwitz DL, Neumann MP, Wick MR. Eccrine sweatgland carcinoma: an histologic and immunohistochemical study of32 cases. J. Cutan. Pathol. 1987; 14; 65–86.

3. Urso C, Paglierani M, Bondi B. Histologic spectrum of carcinomaswith eccrine ductal differentiation (sweat-gland ductal carcin-omas). Am. J. Dermatopathol. 1993; 15; 435–440.

4. Pena J, Suster S. Squamous differentiation in malignant eccrineporoma. Am. J. Dermatopathol. 1993; 15; 492–496.

Proteinaceous deposits and lipidichistiocytosis in follicular lymphoma

Sir : Accumulation of amorphous hyaline, non-amyloidsubstances is an occasional finding in malignantlymphomas, usually of follicle centre-cell origin. Suchproteinaceous deposits are generally sparse, mostlylocated inside the neoplastic follicles, and are rarely soabundant as to mask the underlying lymphoma. Werecently found prominent proteinaceous percipitatesand lipidic histiocytosis in a lymph node with a low-grade lymphoma. The rarity of this association, notpreviously reported to our knowledge, prompted thefollowing report.

A 72-year-old woman presented with enlarged lymphnodes 4 years after an initial diagnosis of follicularcentre-cell lymphoma, and subsequent clinical remissionwith six cycles of polychemotherapy (cyclophosphamide,farmorubicin, eldesine and methylprednisolone). An

axillary biopsy yielded one lymph node with a hetero-geneous, greyish-tan cut surface. Histology showed alow-grade lymphoma and confluent nodular deposits ofa periodic acid–Schiff positive, Congo red negativesubstance (Figure 1a). These amorphous deposits wererimmed by numerous foamy macrophages with Oil RedO-positive cytoplasmic lipid (Figure 1b). The depositswere labelled polyclonally for k and l light chains, to alesser extent for a and g light chains, and shared theimmunophenotype of the neoplastic cells: CD20þ,CD79aþ, CD10þ, CD5¹. Weak, paradoxical stainingfor CD3 was observed. Ultrastructurally, extracellularaccumulation of microvesicular structures and frag-mented cell membranes, scattered cytoplasmic andnuclear debris, lipid globules and pseudomyelin struc-tures were observed. On re-evaluation, sparse pro-teinaceous deposits were present in the neoplasticfollicles of the initial lymph node biopsy, beforetreatment.

In lymph nodes, extracellular accumulation ofamorphous, non-amyloid substances, distinct from themore common fibrohyalinosis, may be seen in variousdiseases, such as follicular centre-cell lymphoma1,2,dysimmune disorders3, and plasma-cell dyscrasias4,5.These latter associations suggest that such substancesmay represent abnormal byproducts of an immunereaction. The deposits generally show the same mono-clonal immunoglobulin4, or share the same immuno-phenotype2 as the underlying lymphoma. They mayexpress various immunoglobulin light chains2,5. Ultra-structural observations describe extracellular accumu-lation of fibrillar1, amorphous non-fibrillar3–5, ormicrovesicular2 material. Chittal2 stated that a dereg-ulation of cell-wall synthesis, with abnormal productionand externalization of cell membranes could explain theaccumulation of microvesicular membranous mate-rial2. Extensive cellular destruction, with subsequent

480 Correspondence

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 1. Excision biopsy of lymph node showing, a, extensive nodu-lar deposits of proteinaceous, lightly eosinophilic material. b, Oil RedO showing numerous histiocytes with lipidic content, crowded atthe periphery of the deposits.

resorption of lipids may be responsible for the lipidichistiocytosis seen in our case.

T.LefrancqS.Michalak

L.Benboubker

Hopital Bretonneau et Trousseau,Tours, France

1. Rosas-Uribe A, Variakojis D, Rappaport H. Proteinaceous precipi-tate in nodular (follicular) lymphomas. Cancer 1973; 31; 534–542.

2. Chittal SM, Caveriviere P, Voigt J-J et al. Follicular lymphoma withabundant PAS-positive extracellular material. Immunohistochem-ical and ultrastructural observations. Am. J. Surg. Pathol. 1987; 11;618–624.

3. Osborne BM, Butler JJ, Mackay B. Proteinaceous lymphadenopathywith hypergammaglobulinemia. Am. J. Surg. Pathol. 1979; 3; 137–145.

4. Morinaga S, Watanabe H, Gemma A et al. Plasmacytoma of thelung associated with nodular deposits of immunoglobulins. Am. J.Surg. Pathol. 1987; 11; 989–995.

5. Aihara H, Tsutsumi Y, Ishikawa H. Extramedullary plasmacytomaof the thyroid with follicular colonization and stromal deposition ofpolytypic immunoglobulins and major histocompatibility antigens.Possible categorization in MALT lymphoma. Acta Pathol. Jpn 1992;42; 672–683.

An unusual granulomatous form of chronicpyelonephritis mimicking tuberculosis

Sir : An unusual form of chronic pyelonephritis asso-ciated with nephrolithiasis, resembling renal tubercu-losis is reported in a 30-year-old woman. For 3 years,the patient suffered from recurrent urinary infectionsand episodes of lithiasis of the left kidney, treated bylithotripsy. No other organism besides E. coli was foundon urine cultures. The intravenous urography and renalultasonography revealed a staghorn calculus(40 × 20 mm) in the calyces, and the pelvis of the leftkidney, and in the upper portion of the ureter. The loss ofleft renal function was demonstrated on the renalscintigraphy. Consequently, a left nephroureterectomywas performed.

Macroscopically, the kidney weighed 140 g and wassmall (80 × 50 × 30 mm). On section, only a thinperipheral layer of the renal parenchyma was stillrecognizable. The remainder of the kidney was replacedby multiple fibrous scars in cortical and medullaryregions and disseminated foci of yellow necrosis varyingin size. The pelvicalyceal system was distorted, dilatedand surrounded by abundant lipomatosis.

Microscopically, the scars contained many partly

caseating granulomas, formed by epithelioid and multi-nucleate giant-cells of Langhans’ type (Figure 1).Numerous calcifications and calcium oxalate crystalsidentified by polarized light were also found and oftensurrounded by granulomas with giant-cells of foreignbody type (Figure 2). A few oxalate crystals weredetected in giant inflammatory cells. In between thegranulomas, focal thyroidization, glomerular and peri-glomerular sclerosis was observed. The interstitiumcontained deposits of PAS-positive Tamm–Horsfallprotein, and showed an intense lymphoid infiltrate.Macrophages were rare and there were no xanthomacells.

All the histological stains (Gram, PAS, Grocott, Ziehl–Neelsen, auramine rhodamine) for bacterial, parasiticand fungal germs were negative. No bacteria weregrown from the tissue culture and PCR for mycobacter-ial genome, on paraffin-embedded tissue, was negative.

This is an unusual chronic pyelonephritis withpseudotuberculous pattern of which only two cases, to

Correspondence 481

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 1. Granulomas showing a central caseous necrosis. Inset:epithelioid and giant cells of the Langhans type in a granuloma.

our knowledge, have been reported1,2. Differentialdiagnosis with the caseous and ulcerative form oftuberculosis was considered. In the present case,repeated urinary cultures were negative and no bacteriawere detected by histochemical staining on microscopicexamination or by PCR. Xanthogranulomatous pyelo-nephritis and malakoplakia were excluded due to theabsence of xanthoma cells in the former and Michaelis–Gutmann bodies in the histiocytes in the later. On theother hand, although it is true that the presence ofnecrotizing granulomatous lesions lessens the possibi-lity of sarcoidosis, the latter is often a diagnosis ofexclusion.

Other aetiological factors have to be discussed in thegenesis of this kind of pyelonephritis. The Tamm–Horsfall protein can potentially cause a cell mediatedimmune response3, but it has limited ability to directlyinduce a necrotizing granulomata. In our case, we didnot observe any morphological correlation between thegranulomas and immunohistochemical positiveTamm–Horsfall protein. Granulomatous and necroticinflammation could be secondary to a peculiar viru-lence of urinary germs. Indeed Kovats showed that E.coli endotoxins can alter renal tissue antigens4. Becauseof the rarity of this pseudo-tuberculous pyelonephritisand the frequent incidence of E. coli infections, suchinfections are probably not responsible for this disease.Induction of granulomatous reaction by calciumoxalate crystals or nephrocalcinosis has been suggestedby some authors1,5 and similar changes were describedin the ureter following disintegration of urinary stonesusing lithotripsy6. In our case, the patient was subjectedto lithotripsy at one stage of her management. Renalscars contained rich deposits of calcium phosphate andcalcium oxalate and some of the calcium oxalate

crystals were found in multinucleated giant cells. Thiswould seem the most logical explanation for the foreignbody reaction and necrotizing granulomata in our case.

In conclusion, chronic pyelonephritis associated withnephrocalcinosis may have a pseudotuberculous pat-tern. We propose that its pathogenesis is related to thepresence of calcium oxalate crystals which could besecondary to lithotripsy.

H.BouzoureneN.BouzoureneM.-L.Francke

Lausanne Institute of Pathology,Lausanne,

Switzerland

1. Hoorens A, van der Niepen P, Keuppens F, Vanden Houte K, KloppelG. Pseudotuberculous pyelonephritis associated with nephrolithia-sis. Am. J. Surg. Pathol. 1991; 16; 522–525.

2. Valerdis Casasola S, Parra Muntaner L, Garcia Alonso J. Pseudo-tuberculous pyelonephritis. Archivos Espanoles de Urologica 1994;47; 172–174.

3. Sato K, Oguchi H, Yoshie T, Koiwai T. Tubulointerstitial nephritisinduced by Tamm–Horsfall protein sensitization in guinea pigs.Virchows Archiv B Cell Pathol. 1990; 58; 357–363.

4. Kovats TG. The role of endotoxin in autoimmune processes.Naturwissenschaften 1961; 48; 572–578.

5. Gonzalez JEG, Caldwell RG, Valatitis J. Calcium oxalate crystals inthe breast. Pathology and significance. Am. J. Surg. Pathol. 1991;15; 586–591.

6. Dretler SP, Young RH. Stone granuloma: a cause of ureteralstricture. J. Urol. 1993, 150; 1800–1802.

Large cell carcinoma of lung with osteoclast-like giant cells

Sir : Non-neoplastic multinucleated giant cells havebeen described infrequently in a number of extraosseousmalignancies, such as in the breast1, thyroid2 andstomach3. Occurrence in the lung is very rare4–6. Thesetumours are characterized by the presence of a variablenumber of benign appearing multinucleated giant cellsclosely associated with malignant epithelial component.These giant cells morphologically resemble those foundin giant cell tumour of bone, and are named osteoclast-like giant cells. The diagnosis of these tumours is usuallyobvious in resection specimens. In small biopsies orcytology specimens, they can cause diagnostic problemsin terms of differential diagnosis. We would like to reporta case of large cell carcinoma with osteoclast-like giantcells present in the primary lung lesion and lymph nodemetastasis.

A 58-year-old man had a history of squamous cell

482 Correspondence

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 2. Calcifications surrounded by granulomas of the foreignbody type.

carcinoma of the right tonsil treated with radiationtherapy and right radical neck dissection three yearsago. Recent chest X-ray showed a mass in the upper lobeof his right lung. Fine needle aspiration biopsy showednumerous mononuclear inflammatory cells and multi-nucleated giant cells. A few groups of malignant cellswere noted in the cell block. The right upper lobectomyspecimen showed a 14 mm hard tan tumour with anadjacent 7 mm satellite nodule. Microscopically, itshowed a large cell carcinoma with no evidence ofsquamous differentiation. In the surrounding stroma,there was a heavy lymphoplasmacytic infiltrateadmixed with many multinucleated giant cells (Figure1). Mononuclear and binucleated forms were alsopresent. Metastatic carcinoma with similar giant cellswas present in one peribronchial lymph node. Immu-nohistochemically, the tumour cells showed strongpositive staining for cytokeratin (CAM 5.2) and were

negative for histiocytic markers CD68 (KP1), alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme. Areverse pattern of staining was noted in the giant cells(Figure 2). The overall features were that of a large cellcarcinoma with a peculiar giant cell reaction.

On review of the literature, only three similar caseshave been reported in the lung4–6. Two of them aremetaplastic squamous cell carcinomas4,5. The thirdcase is an undifferentiated carcinoma with focaladenocarcinoma differentiation6. Although our patienthad a previous history of tonsillar squamous cellcarcinoma, the present tumour most likely representsa primary lung carcinoma because it has differenthistological appearance from the tonsillar carcinoma,and there is no evidence of extrapulmonary metastaticdisease.

Carcinoma with osteoclast-like giant cells should bedistinguished from giant cell carcinoma where the giantcells are bizarre, malignant-looking and epithelial innature. Granulomatous foci present in inflammatoryconditions such as sarcoidosis or tuberculosis alsocontain giant cells. The differential diagnosis is usuallyobvious in resected specimen. However, small biopsiesmay be difficult to interpret and fine needle aspiratesmay be confusing3. In our patient, the presence ofbenign multinucleated giant cells in a background ofmononuclear inflammatory cells in the fine needleaspiration smears is misleading and suggests aninflammatory process. Malignant cells become evidentonly in the cell block. Awareness of this rare neoplasmand a high level of suspicion are helpful in avoidingmisinterpretation.

There has been much controversy about the originand nature of these tumour-associated giant cells.Epithelial, histiocytic or mesenchymal metaplasia hasbeen suggested. Previous immunohistochemical andultrastructural studies on tumours in other sites haveshown that they are of histiocyte/macrophage lineage1–

3. In lung carcinomas, Oyasu et al.4 found ultrastruc-tural features resembling histiocytes in the giant cells.Nakahashi et al.6 suggested that the giant cells werereactive in nature, as they were benign looking andshowed phagocytosis. In our case, the positive immu-noreactivity for histiocytic markers suggests a histio-cyte/macrophage phenotype. The giant cells appear tobe an integral part of the host response and are presentin the primary tumour as well as in the lymph nodemetastasis. The mechanism of this peculiar stromalreaction is unknown. Histiocytes may be recruited bysoluble factors produced by the tumour cells and fuse toform giant cells. The biological significance of thesegiant cells in lung carcinoma is to be determined. Inbreast carcinoma where the largest number of cases

Correspondence 483

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 1. Osteoclast-like giant cells are present admixed with tumourcells. A dense lymphoplasmacytic infiltrate is present in the stroma.

Figure 2. The mononuclear and multinucleated giant cells showstrong positive staining for CD68, while the adjacent carcinoma cellsare negative.

have been reported, the presence of giant cells does notappear to have any prognostic significance1.

C.S.LeungI.Morava-Protzner

Department of Laboratory Medicine,Sunnybrook Health Science Centre,

University of Toronto, Toronto,Ontario, Canada

1. Tavassoli FA, Norris HJ. Breast carcinoma with osteoclast-like giantcells. Arch. Pathol. Lab. Med. 1986; 110; 636–639.

2. Gaffey MJ, Lack EE, Christ ML et al. Anaplastic thyroid carcinomawith osteoclast-like giant cells. A clinicopathologic, immunohisto-chemical, and ultrastructural study. Am. J. Surg. Pathol. 1991; 15;160–168.

3. Stracca-Pansa V, Menegon A, Donisi PM et al. Gastric carcinomawith osteoclast-like giant cells. Report of four cases. Am. J. Clin.Pathol. 1995; 103; 453–459.

4. Oyasu R, Battifora HA, Buckingham WB et al. Metaplasticsquamous cell carcinoma of bronchus simulating giant celltumour of bone. Cancer 1977; 39; 1119–1128.

5. Love GL, Daroca PJ. Bronchogenic sarcomatoid squamous cellcarcinoma with osteoclast-like giant cells. Hum. Pathol. 1983; 14;1004–1006.

6. Nakahashi H, Tsuneyishi M, Ishida T et al. Undifferentiatedcarcinoma of the lung with osteoclast-like giant cells. Jpn J. Surg.1987; 17; 199–203.

The double muscularis mucosa in ulcerativecolitis: is it all new?

Sir : The presence of a double muscularis mucosa hasbeen described in the context of inflammatory boweldisease and in the presence of Barrett’s oesophagus. Theorigin of this ‘doubling’ is uncertain and a number ofpossibilities have been raised. In the previouslydescribed cases, one of the bands showed both theinner circular and outer longitudinal muscle layers andthe other band was a single muscle layer. We describe adouble muscularis mucosa in a colectomy specimenfrom a patient with ulcerative colitis. Both bands in thiscase show the inner circular and outer longitudinalmuscle layers.

A 35-year-old male with long-standing ulcerativecolitis had a total colectomy for symptoms which werepoorly responsive to medical treatment. Macroscopi-cally, the large bowel had total colitis with loss ofmucosal folds and granularity but with little ulceration.There was no thickening of the bowel wall nor was thereany fat wrapping. Histologically, there was mildly activechronic total ulcerative colitis with no dysplasia. Themost striking abnormality was the presence of a doublemuscularis mucosa. Both of these layers of muscularis

mucosa consisted of two layers of muscle. Both layerswere regular, fairly uniform in thickness and presentthroughout the sections taken. There was very littlecrypt atrophy in the overlying mucosa. There were veryfew inflammatory cells in the two layers of themuscularis mucosa or between them. No lymphogland-ular complexes were seen in the submucosa.

The muscularis mucosa has two layers of muscle; aninner circular layer and an outer longitudinal layer,which are usually poorly demarcated. The presence of adouble muscularis mucosa in ulcerative colitis has beennoted previously1–3. There are three views to its origin.The double muscularis mucosa noted by Mapstone andDixon appeared to have one upper layer at the level ofthe shortened crypt bases and a second lower layerwhich was composed of two muscle layers. They havesuggested that this second upper layer of the muscularismucosae is formed from pericrypt fibroblasts in responseto severe inflammation and injury.

Gouldston and McGovern noted that the muscularismucosa is hypertrophied and in a state of contrac-tion1,4,5. They suggested that this contraction is soforceful that the inner coat pulls away from the outerlongitudinal coat forming two layers. In some of thesecases the presence of lymphocytes between the twolayers was noted. Also the outer longitudinal layer isdescribed as compact and defined whereas as the innercircular layer is less defined. Fibrosis is usually presentin the deep lamina propria and the submucosa. Thethird view is that fibrous tissue is laid down in responseto severe inflammation replacing the muscularismucosa and thereby splitting the muscularis mucosainto two layers3,4,6.

Outside inflammatory bowel disease, the doublemuscularis mucosa has been described in Barrett’s

484 Correspondence

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 1. Large bowel with inactive ulcerative colitis and a doublemuscularis mucosa.

oesophagus7. The double muscularis mucosa wasalways located below the metaplastic columnar epithe-lium. The findings from this study suggested that thedeep layer was the original, whereas the superficialmuscularis mucosa was the newly formed layer. Thedouble muscularis mucosae can cause diagnosticdifficulties on endoscopic biopsy specimens. Whenthere is inflammation between the two layers, thismay mistakenly be interpreted as submuscosal inflam-mation if the biopsy is not full thickness and bothmuscularis mucosa cannot be seen. If the deeper layer isthe true muscularis mucosa then the inflammatory cellsseen below the superficial layer (which may be the onlymuscularis mucosae included in the biopsy) would infact still be within the lamina propria. This may lead toan erroneous diagnosis of Crohn’s disease.

This case described here differs from those describedpreviously in that the normal longitudinal and circularlayers of the muscularis mucosa are seen in both bandsof the double muscularis mucosa. This change was seen

throughout the colectomy specimen. Additionally, theanatomy of both layers appears rather too well orderedand is strikingly uniform in thickness to be the result ofprevious inflammatory damage. We believe that thiscase differs from those previously described. We wouldlike to suggest that this could represent a primaryabnormality in the muscularis mucosa that happens tobe present in a patient who has ulcerative colitis,although this has not been described previously. Theoriginal biopsy from this patient, from which thediagnosis of ulcerative colitis was made, is unhelpfulin trying to establish whether the double muscularismucosa was present at that time, as it only showed onelayer of muscularis mucosa (the most superficial).

V.C.SoundyS.E.Davies*

B.F.Warren†

Department of Histopathology, Whittington Hospital,*Department of Histopathology, Royal Free Hospital,

London, and †Department of Cellular Pathology, JohnRadcliffe Hospital, Headington, Oxford, UK

1. Goulston SJM, McGovern VJ. The nature of benign strictures inulcerative colitis. New Eng. J. Med. 1969; 281; 290–295.

2. Davies SE, Levine S, Talbot IC. Fibrosis in ulcerative colitis. J. Pathol.1992; 168; 105A.

3. Lumb G. Pathology of ulcerative colitis. Gastroenterology 1961; 40;290–297.

4. Lennard-Jones JE, Lockhart-Mummery HE, Morson BC. Clinicaland pathological differentiation of Crohn’s disease and proctoco-litis. Gastroenterology 1968; 54; 1162–1170.

5. Gumaste V, Sachar DB, Greenstein AJ. Benign and malignantcolorectal strictures in ulcerative colitis. Gut 1992; 33; 938–941.

6. De Dombal FT, Watts JMcK, Watkinson G, Goligher JC. Localcomplications of ulcerative colitis: strictures, pseudopolyposis andcarcinoma of colon and rectum. Br. Med. J. 1966; 1; 1442–1447.

7. Takub K, Sasajima K, Yamashita K, Tanaka Y, Fujita K. Doublemuscularis mucosae in Barrett’s oesophagus. Hum. Pathol. 1991;22; 1158–1161.

Correspondence 485

q 1998 Blackwell Science Ltd, Histopathology, 32, 477–485.

Figure 2. Muscularis mucosa at higher power showing the bilayeredstructure of both components.