Breast malignant, males, children - Micropapillary carcinoma

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Breast malignant, males, children

Carcinoma subtypes

Micropapillary carcinoma

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 6 October 2012, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● Tumor composed of small clusters of cells within clear stromal spaces resembling dilated vascular channels
● First described by Tavassoli (Mod Pathol 1993;6:660)

Epidemiology
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● Rare, < 2% of invasive breast cancers have substantial micropapillary pattern
● Mean age 59 years, range 25-92 years

Clinical features
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● Morphologically similar to micropapillary tumors of bladder, lung and major salivary glands
● May be caused by reversal of cell polarity and MUC1 expression, resulting in detachment of tumor cells from stroma, promoting their spread and leading to early nodal metastases (Mod Pathol 2004;17:1045)
● Sialyl Lewis X/CD15s, the ligand of E-selectin, also exhibits reversed cell polarity in these tumors (Int J Surg Pathol 2010;18:193)
● Tumor infiltrating lymphocytes usually lack cytotoxic phenotype (Mod Pathol 2008;21:1101)
● Increased expression of CD146 and microvessel density (Pathol Res Pract 2011;207:739)

Prognostic features
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● Very aggressive with poor prognosis (Adv Anat Pathol 2004;11:297)
● 95% have lymph node metastases at presentation
● 70% recur, 50% die of disease
● Similar prognosis as other breast carcinoma subtypes if node status, tumor size and other classic prognostic markers are considered (Hum Pathol 1999;30:1459)
● Focal component found in 6% of all breast carcinomas - these cases have same poor prognosis regardless of amount of micropapillary component (Mod Pathol 2001;14:836, Am J Clin Pathol 2006;126:740); exception is that presence of micropapillary pattern in mucinous / colloid carcinoma of breast may have no clinical significance (Int J Surg Pathol 2008;16:251)
● Presence of micropapillary features and retraction artifact in core biopsies predicts nodal metastases (Am J Surg Pathol 2009;33:202)

Case reports
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● 35 year old woman with multifocal grade III invasive micropapillary carcinoma associated with metaplastic breast carcinoma (Int J Surg Pathol 2012;20:488)
● 51 year-old woman with myoepithelial carcinoma and contralateral invasive micropapillary carcinoma of the breast (J Korean Surg Soc 2011;81:211)
● 59 year old woman with a 2 cm breast mass, who underwent lumpectomy and axillary dissection (Case of the Week #4)
● 66 year old man with pure invasive micropapillary carcinoma of breast (Can J Surg 2005;48:156)
● Series of eight cases of invasive micropapillary carcinoma of breast (Breast J 2012;18:267)
● Invasive micropapillary carcinoma of the male breast with neuroendocrine differentiation (Zhonghua Bing Li Xue Za Zhi 2011;40:704)

Gross description
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● Mean tumor size 2 cm, range 0.1 to 10 cm
● Lobulated outline

Micro description
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● Well formed, angular and avascular papillary clusters, or morula-like epithelial groups of cells without a fibrovascular core floating in aqueous or mucinous material in lymphatic-like spaces (but without a definite lining)
● Cells have abundant eosinophilic cytoplasm, round vesicular nuclei and prominent nucleoli
● Also fibrocollagenous stroma
● Extensive true angiolymphatic invasion
● Often psammoma bodies
● Variable histologic grade
● Minimal mitotic activity, no necrosis and no lymphocytic inflammation

Micro images
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Low power


High power                       Well defined margins                     Tumor cell nests within fine reticular stroma


Various images                Tumor infiltrating lymphocytes      With siliconoma


Nested pattern with intervening clear spaces                         Nodal metastases

Infiltrating ductal carcinoma with focal micropapillary features


Tumor cell clusters are surrounded by clear                          Tumor cells have some features
empty spaces, cells have abundant mildly                             of colloid / mucinous carcinoma
granular cytoplasm and nuclear clearing


MUC1 stain                       Highlights tumor cell clusters       In breast and bladder tumors

Low power

Tumor cell clusters are surrounded by clear empty spaces, cells have abundant mildly granular cytoplasm and nuclear clearing

Cytology description
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● Increased cellularity, angulated clusters, abortive papillae and isolated malignant cells
● Staghorn epithelial structures in 35% (Pathology 2007;39:401)
● May have few malignant appearing multinucleated giant cells or focal mucin (Acta Cytol 2009;53:463)
● No fibrovascular cores (Cancer 2002;96:280)

Positive stains
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● MUC1 on stroma-facing surface of cell clusters [basal], which accentuates outlines of micropapillary units to form a distinct band on this surface
● HER2 (95%), p53 (70%), bcl-2 (70%), ER and PR (20-80%) and GCDFP-15 (30%)

Negative stains
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● MUC2, CK5, CK20, c-kit/CD117, EGFR (Arch Pathol Lab Med 2005;129:1277) and WT1 (usually)

Molecular description
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● Mixed tumors have genetic profiles more similar to pure tumors than to ductal carcinoma (J Pathol 2009;218:301)
● High cyclin D1 expression, high proliferation rates and MYC (8q24) amplification (J Pathol 2008;215:398)

Electron microscopy description
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● Secretory activity in stroma-facing surface of tumor cells

Differential diagnosis
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● Metastatic ovarian papillary serous carcinoma: WT1+, GCDFP15- (Hum Pathol 2008;39:666)
● Metastatic micropapillary carcinoma: breast primaries are ER+, mammaglobin+, PAX8/WT1-, other primaries have different patterns (Am J Surg Pathol 2009;33:1037)
● Extensive lymphovascular invasion by a primary or metastatic breast carcinoma

Additional references
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● Mod Pathol 1999;12:499, Am J Clin Pathol 2004;121:857, AJR Am J Roentgenol 2002;179:927, Stanford University

End of Breast malignant, males, children > Carcinoma subtypes > Micropapillary carcinoma

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