Breast – Malignant, Males, Children - Micropapillary carcinoma

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Breast-malignant, males, children

Micropapillary carcinoma

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Reviewer: Daniel Visscher, M.D., University of Michigan Hospitals, February 2009 (see Reviewers page)

Revised: 29 September 2009

Last major update: September 2009

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 Path 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

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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, causing detachment of tumor cells from stroma, promoting their spread and leading to early nodal metastases (Mod Path 2004;17:1045)

● Sialyl Lewis X/CD15s, the ligand of E-selectin, also exhibits reversed cell polarity in these tumors (Int J Surg Pathol 2008 Jul 8 [Epub ahead of print])

● Tumor infiltrating lymphocytes usually lack cytotoxic phenotype (Mod Path 2008;21:1101)

Treatment and prognosis

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● Very aggressive with poor prognosis (Adv Anat Path 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 Path 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 Path 2001;14:836, AJCP 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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● 59 year old woman (Case of the week #4)

● 66 year old man (Can J Surg 2005;48:156)

Gross description

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● Mean tumor size 2 cm, range 0.1 to 10 cm

● Lobulated outline

Microscopic description

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● Well formed, angular, 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, no lymphocytic inflammation

Micro images

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Low power Well defined margins

High power Tumor cell nests within Nested pattern with intervening

fine reticular stroma clear spaces

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

Tumor cells have coarse chromatin, Angiolymphatic invasion

prominent nucleoli, frequent mitotic figures

With adjacent colloid carcinoma Infiltrating ductal carcinoma with

focal micropapillary features

Various images Tumor infiltrating lymphocytes With siliconoma

Nodal metastases

MUC1 stain #1 #2 - highlights tumor cell clusters #3-in breast and bladder tumors

and surrounding clear spaces

Other images: 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)

Cytology images

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Cell block shows micropapillary/ Tumor micropapillae with abortive

pseudoacinar pattern branching, but no fibrovascular cores

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%), GCDFP-15 (30%)

Negative stains

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● MUC2, CK5, CK20, c-kit/CD117

● EGFR (Archives 2005;129:1277), WT1 (usually)

Molecular / cytogenetics

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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, MYC (8q24) amplification (J Pathol 2008;215:398)

Electron microscopy

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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 Path 2008;39:666)

● Metastatic micropapillary carcinoma (breast primaries are ER+, mammaglobin+, PAX8/WT1-, other primaries have different patterns, Am J Surg Pathol 2009 Feb 20 [Epub ahead of print])

● Extensive lymphovascular invasion by a primary or metastatic breast carcinoma

Additional references

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● Mod Path 1999;12:499, AJCP 2004;121:857, AJR 2002;179:927, Stanford University

End of Breast – Malignant, Males, Children > Micropapillary carcinoma

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