Breast-nonmalignant - Adenomyoepithelioma

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Breast-nonmalignant

Benign (usually) tumors / tumor like-changes

Adenomyoepithelioma

Reviewer: Hind Nassar, M.D., Johns Hopkins Medical Centers (see Reviewers page)

Revised: 29 July 2010, last major update July 2010

Definition

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● Tumor composed of variable number of myoepithelial cells around small epithelial lined spaces

● First recognized in the breast by Hamperl (Curr Top Pathol 1970;53:161)

Terminology

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● Other breast myoepithelial lesions are myoepitheliosis and myoepithelioma

● The terminology "adenomyoepithelial adenosis" is no longer used

● Page recommends that cases with malignant histology not be called adenomyoepithelioma but be defined by the histology of the malignant component (Am J Surg Pathol 2005;29:1294)

Epidemiology

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● Uncommon, mean age 60 years

● Rare in male breast

Sites

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● Usually occurs in the peripheral portion of the breast, but can be central

● No predilection for either breast

Etiology

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● Considered a variant of intraductal papilloma

Clinical features

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● Usually presents as a mass

● Usually benign, although may recur locally

● Benign appearing tumors rarely metastasize to lung (Arch Pathol Lab Med 2006;130:1349)

● Malignant tumors are usually low grade; may metastasize to lung, brain, jaws, lymph nodes

Prognostic factors

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● Mitotic rate > 3 MF/10 HPF is associated with recurrence

● High mitotic rate, atypia, necrosis and infiltrative borders favor malignancy

Case reports

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● Cellular tumor (Am J Surg Pathol 1983;7:863)

● 48 year old woman with tumor containing collagenous spherulosis (J Clin Path 2004;57:83)

● 56 year old woman with intracystic tumor (Breast Cancer 2007;14:429)

Malignant tumors

● Benign tumor recurring as malignant myoepithelioma (J Med Imaging Radiat Oncol 2009;53:234)

● 50 year old woman with tumor transforming to osteosarcoma and carcinoma and causing death (Am J Surg Pathol 1998;22:631)

● 69 year old woman with malignant myoepithelial component and p53 mutation (Pathol Int 2006;56:211)

● 71 year old woman (Arch Pathol Lab Med 2000;124:632)

● 75 year old woman (Arch Pathol Lab Med 2004;128:235)

● 77 year old woman whose tumor had matrix production (Pathol Res Pract 2007;203:599)

● 80 year old woman (Eur J Gynaecol Oncol 2009;30:234)

Treatment

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● Complete local excision

● May recur with incomplete excision

Gross description (Macroscopy)

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● Well circumscribed, usually small (mean 1-2 cm), but can be up to 8 cm

● Firm

● May have satellite nodules

Gross images

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Unusually large bisected tumor with central Intracystic nodule

cavity with bosselated contour (AFIP)

Micro description (Histopathology)

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● Well circumscribed, may be encapsulated or multinodular

● Proliferation of epithelial and myoepithelial cells

● Aggregated lobules of glands with tall lining epithelium with scant cytoplasm and hyperchromatic nuclei surrounded by myoepithelial cells with clear cytoplasm

● Epithelial cells usually form glandular spaces

● Myoepithelial cells can be dominant and may be spindle-shaped, clear or polygonal

● Apocrine metaplasia may be present, also adenomyoepitheliomatous hyperplasia

● Variants include spindle cell type (epithelial-lined spaces may be sparse, resembles leiomyoma), tubular variant (ill-defined margins, may resemble tubular adenoma), lobulated variant (nests of myoepithelial cells surround compressed epithelial lined spaces)

● Malignant appearing cases have local invasion, high mitotic rate, severe atypia (Am J Surg Pathol 1992;16:868)

Micro images

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Proliferation of epithelial and myoepithelial cells

Proliferation of epithelial and myoepithelial elements

Myoepithelial cells are difficult to identify Various images and stains

Large glands with open lumina S100 stains myoepithelial cells

and apocrine metaplasia

With collagenous spherulosis

AFIP images:

Intraductal bands of pale myoepithelium Myoepithelial cells with clear cytoplasm crowd

separate adenomatous ductal epithelium glandular epithelium and expand into stroma

Overgrowth of myoepithelium in two nodules Myoepithelial cells in small clusters

separated by stromal band have replaced most ductal elements

Foci of glands with luminal secretions Isolated myoepithelial cells with

clear vacuolated cytoplasm

Transition between adenomatous and myomatous growth

AE1+ glandular cells, (myoepithelial Myoepithelial cells are focally actin+

cells are negative

Epithelial cells are CK7+ Myoepithelial cells are CK5/6+

Benign histology but malignant behavior

Benign appearing tumors that Lung metastases with benign histology

metastasized to lung

Malignant histology

Mitotic activity Various images Keratin+ epithelium

Fig A: biphasic growth with dark areas of hyperchromatic cells with high N/C ratio and pale zone of large polygonal pale cells with ill-defined cytoplasm and vesicular nuclei

Fig B: mitotic figure (arrow)

Fig C: AE1-AE3 staining of epithelial component

Fig D: S100 staining of myoepithelial component

Cytology description

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● Moderate to highly cellular with large clusters of epithelium and myoepithelium

● Tubular structures occasionally found

● Myoepithelium appears as small clusters or dispersed cells with epithelioid morphology, intranuclear or intracytoplasmic vacuoles, often naked bipolar nuclei

● Mild to moderate nuclear atypia present

● Metachromatic fibrillary stroma occasionally found

● No mitotic figures, no necrosis

● Often classified incorrectly as fibroadenoma, suspicious for malignancy or malignant (Cancer 2006;108:250)

Cytology images

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Various images

Branching groups of benign ductal and Metachromatic fibrillary stroma

myoepithelial cells resemble fibroadenoma, accompanying cells, inset-myoepithelial cells

inset shows tubular structures surround hyaline globule, resembling

collagenous spherulosis (Pap stain)

Ductal cells shows moderate atypia (nuclear Diff-Quik shows myoepithelial cells with

pleomorphism, irregular nuclear contours, vacuolated cytoplasm, spindled myoepithelial

occasional prominent nucleoli), arrow points cells and naked bipolar nuclei, arrow

to myoepithelial cell (Pap stain) points to inclusion in myoepithelial cell

Myoepithelial cells as single cells with intact

cytoplasm, some plasmacytoid, others

are clear cells

Virtual Slides

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Benign tumor with case report

Positive stains

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Epithelial component:

● keratin (AE1-AE3), CEA; variable ER

Myoepithelial component:

● p63 (AJSP 2001;25:1054), S100, smooth muscle myosin heavy chain

Negative stains

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● PR

Electron microscopy descriptions

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● Myoepithelial features (classic) include myofibrils with dense bodies, pinocytotic vesicles, desmosomes or tight junctions, patchy basement membrane

Molecular / cytogenetics description

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● Case report with t(8;16)(p23;q21) (Cancer Genet Cytogenet 2005;156:14)

Differential Diagnosis

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● Adenosis tumor: no prominent myoepithelial component

● Intraductal papilloma: no prominent myoepithelial component

● Invasive carcinoma (on core biopsy): unequivocal evidence of invasion

● Nipple adenoma: no prominent myoepithelial component

● Tubular adenoma: very well circumscribed (tubular variant is not), myoepithelial cells are inconspicuous or rare

Additional references

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● Hum Path 1987;18:1232, Stanford University

End of Breast-nonmalignant > Benign tumors / changes > Adenomyoepithelioma

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