Breast – Cyto-Histo Correlations of Fibroepithelial Lesions

Charles D. Sturgis, M.D.Associate Professor of Pathology

Mammary Fibroepithelial LesionsLecture Outline

Review of normal

Lesions:- Hamartoma- Fibroadenoma- Tubular adenoma- Lactating adenoma- Phyllodes Tumor

TDLU

Microanatomy of the Fibroglandular Component of the Female Breast

Benign mammary ductHistology 48F

Benign Ductal EpitheliumFocus on Epithelium

Benign Ductal EpitheliumFocus on Myoepithelium

“Benign Signet Ring ME Cell”

Breast Lobule inHistology and

Cytology

Image from scrape preparation ofnon-neoplasticbreast tissue

Benign mammary lobuleFNA Papanicolaou stain

60X

Hamartoma

Disorganized but benign appearing masses composed of cells indigenous to the particular site.

Focal malformations that resemble a neoplasm, grossly and even microscopically, but result from faulty development in an organ.

Comprised of abnormal mixtures of tissue elements or an abnormalproportion of elements normally present at that site.

Well circumscribed mass lesions developing at various body sites comprised of overgrown and sometimes disorganized mixtures of

mature tissue types native to the particular organ / anatomic location.

Mammary Hamartoma

4.8% of benign breast tumors (WHO, 2012, Chapter 11).

Term first applied by Arrigoni et al to breast lesions in 1971.Surg Gynecol Obstet 1971;133(4):577-582

Called “adenolipoma” & “lipofibroadenoma” by some.

Well circumscribed and sometimes encapsulated lobulatedlesions with ducts / lobules / fibrous tissue / adipose tissue

in varying amounts.

May contain areas of PASH and smooth muscle / myoid stroma.

Associated with Cowden syndrome (germline PTEN mutations).

RUOQ

41F10 yr history of painless lump

Gradually increasing in size over timeNo history of

trauma/surgery/radiationNo nipple discharge

12 x 10 cmNo skin fixation

Well circumscribed by imaging

WHO states: Differentiation of hamartomas from fibroadenomas may be difficult on needle biopsy and is often impossible on fine needle aspiration.

Tel-Aviv, Israel

Fibroadenoma

Benign fibroepithelial neoplasm arising from TDLUHyperplastic lesion of the specialized (intralobular) stroma

Usually seen in patients 20 to 35 years of ageTypically single, 20% multipleMay enlarge during pregnancy

Usually stabilize in size between 2 and 3 cmFirm, well circumscribed, sharply demarcated, freely mobile

“Marble” in the breast of a young woman

Malignant transformation reported in less than 0.1% of cases

Fibroadenoma

Ultrasound

Gross Cut Surface

Growth PatternsIn Adult Type Fibroadenomas

Intracanalicular PatternPericanalicular Pattern

Pericanalicular: Expanded stoma with ducts retaining rounded profiles.Intracanalicular: Elongated duct-like structures with slit-like lumens

Patterns descriptive; may coexist; have no clinical significance.

Histology of Fibroadenoma

Fibroadenoma

Cytomorphologic Features

Cellularity variable, possibly as high or higher than carcinomasCohesive groupings arranged in branching or antler-like patternMyoepithelial cells detectable in cohesive epithelial fragments

Apocrine change possible

Naked oval / bipolar nuclei in background / adjacent to epithelium(Myoepithelial and/or stromal in origin)

Well demarcated stromal fragments with spindle cells

Cytology of Fibroadenoma

Cytology of Fibroadenoma

Normocellular stroma for contrast Fibroadenoma stroma

20F 3 cm Breast Mass

Benign Ductal EpitheliumFocus on Epithelium

Benign Ductal EpitheliumFocus on Myoepithelium

Cytology of Fibroadenoma

Histologic “Types” of Fibroadenoma

AdultMyxoid

ComplexJuvenileApocrine

Myxoid

Apocrine

Cytologic “Types” of Fibroadenoma

AdultMyxoid

ComplexJuvenileApocrine

Apocrine

Myxoid

Fibroadenoma with hyalinized stroma and dystrophic calcifications - 62F

Fibroadenoma with intrinsic invasive carcinoma / UDH / ADH - 46F

Invasive ductal carcinoma - 53F

Tubular Adenoma

Considered by most to be a variant of pericanalicular fibroadenomaProminent / florid adenosis-like epithelial appearance

Clinical / imaging features indistinguishable from fibroadenoma

“Softer” than FA on palpation and tan rather than “white” surface

Well circumscribed

House small round tubules lined by uniform epithelial cells with surrounding myoepithelium throughout

Tubular lumina generally empty

2015

Histology of Tubular Adenoma

Histology of Tubular Adenoma

H&E p63

Cytology of Tubular Adenoma

Lactating Adenoma

Rounded mobile mass arising in setting of pregnancy / lactation

Have been reported in non-pregnant patients on high doseexogenous steroid hormones, antipsychotic and

antihypertensive medications

May be hyperplastic or neoplastic in etiology

Histologically localized collections of lobules showinglactational changes – can include hemorrhage and infarction

Benign lesions that are biopsied to exclude malignancy

Lactating Adenoma

36F7 weeks post partum

Cytomorphologic Features

Highly cellularIntact lobules possibly identified

Areas of dyscohesion

Large hyperchromatic granular nucleiProminent nucleoli

Fragile bubbly cytoplasmNaked nuclei

Background with vacuoles, granular debris and even necrosis

Lactating Adenoma

Cytology of Lactating Adenoma

Cytology of Lactating Adenoma

Phyllodes Tumor

Primary stromal neoplasms of the breastMedian age at diagnosis 45, (older than fibroadenomas),

although can occur in adolescentsSeparated from FA by morphology and not size

Less than 1% of all breast neoplasms

Classical clinical settingLarge, irregularly lobulated, rapidly growing, painless mass

in an older woman

Lesions may be labeled as benign vs indeterminate vs malignant

Phyllodes Tumor

Histomorphologic Features

Benign PTsWell circumscribed

Stromal hypercellularity and integral benign glandular elementsLeaf-like or club-like epithelial-lined expanses of mesenchyme

Enhanced intracanalicular growth patternHemorrhage and necrosis possible

Few to no mitoses

Borderline PTSStroma typical of low grade fibrosarcoma

Intermediate numbers of mitoses

Malignant PTsInfiltrative growth, frankly sarcomatous

More than 10 mitoses per 10 HPFHeterologous elements not uncommon

WH0 2012 Lakhani et al…

p. 145

Definition of Stromal OvergrowthAbsence of epithelial elements in one low-power

microscopic field (containing only stroma).Based on 10X objective and 4X ocular (40X).

Definition of Stromal ExpansionAbsence of epithelial elements in one intermediate-power microscopic field (containing only stroma).

Based on 10 x objective and 10X ocular (100X).

Histology of Phyllodes Tumor

Benign PTs

Malignant Phyllodes Tumor8 cm RUOQ

58 F

R-XCCL

Histology of Phyllodes Tumor

Malignant Phyllodes Tumors

______________________________

HeterologousElements

Osteosarcomatous area, 52F Chondrosarcomatous area, 52F

Liposarcomatous area, 51F

Phyllodes Tumor

Cytomorphologic Features

Dimorphic population of epithelial and stromal cells

Helping to differentiate from FAHigh stromal cellularity

Single intact mesenchymal cellsStromal atypia

Mesenchymal cells longer and more wavy with plump nuclei

Capillaries may traverse stroma

Cytology of Phyllodes Tumor

Normocellular stroma for contrast

Cytology of Phyllodes Tumor

Cytology of Phyllodes Tumor

Vol 42, Issue

5, pages 405-

415 May

2014

24 of 932 breast FNAs with erroneous or

inconclusive diagnoses over a 7 year

period.

Emphasize search for and recognition of

cellular stromal fragments in

fibroepithelial lesions.

Authors from:American University of Beirut, Lebanon

&Cleveland Clinic Lerner College of Medicine, U.S.A.

Differentiation Between Phyllodes Tumors and Fibroadenomas Based on Mammographic Sonographic and MRI FeaturesDuman L., Gezer N.S., Balcı P., Altay C., Başara I., Durak M.G., Sevinç A.İ.

Dokuz Eylul University, Izmir, Turkey

Background: This study was performed to compare the mammographic, sonographic, and magnetic resonance imaging (MRI) characteristics of phyllodes tumors and fibroadenomas, which may resemble each other. Methods: Preoperative mammograms, B-mode and Doppler sonograms, and dynamic breast MRIs of 72 patients with pathologically proven fibroadenomas and 70 patients with pathologically proven phyllodes tumor were evaluated in this retrospective study. Statistical significance was evaluated using chi-square and Fisher's exact tests. Correlations in lesion size among radiological methods were examined by Pearson's correlation analysis. Results: The features that differed on mammogram were size, shape, and margin of the mass. Sonograms showed significant differences in size, shape, margin, echo pattern, and vascularization of the mass. Pearson's correlation analysis showed strong agreement among radiological methods in terms of assessment of size. Tumor size ≥ 3 cm, irregular shape, microlobulated margins, complex internal echo pattern, and hypervascularity were significant findings of phyllodes tumors. Internal cystic areas on MRI were frequently associated with phyllodes tumors.Conclusion: Mammographic, sonographic, and MRI findings of fibroadenomas and phyllodes tumors could help radiologists to ascertain imaging-histological concordance and guide clinicians in their decision making regarding adequate follow-up or the necessity of biopsy.

Breast Care 2016;11:123-127

MRI of 41F: T2-weighted turbospin echo sequence with fatsuppression showed hyperintensecystic areas. Histopathologyindicated a borderline phyllodestumor.

Nuanced differentiations

may not always be

mandatory.

2016

FA with phyllodal features Benign PT Borderline PT

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