Breast malignant, males, children - Mucinous / colloid carcinoma

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Breast malignant, males, children

Carcinoma subtypes

Mucinous / colloid carcinoma

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 14 October 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● Clusters of small uniform cells floating in lakes of extracellular mucin
● Mucin accumulation may be due to inversion of polarity in cell, with mucin secretion directed towards base of cell / stroma, rather than luminal border
● Tumor cells also produce MUC2, a distinctive mucin type (Am J Surg Pathol 2003;27:571, Hum Pathol 1998;29:1517, Histopathology 2003;42:26)
● Classified as type A (paucicellular / no neuroendocrine differentiation), type B (hypercellular / neuroendocrine differentiation) or type AB (intermediate form), although no clinical significance
● Based on molecular studies, mucinous type A is distinct from mucinous type B, and mucinous type B is part of a spectrum with neuroendocrine carcinoma (Mod Pathol 2009;22:1401)
● Pure if 90% of more mucinous / colloid component
● Cases with 75-90% mucinous / colloid component are considered a mixed variant with a prognosis worse than pure mucinous carcinoma, and dependent on the grade of the remaining carcinoma component
● Dictionary definition of colloid: (a) gelatinous material resulting from colloid degeneration in diseased tissue; (b) resembling product of thyroid gland; (c) system in which finely divided particles are dispersed within a continuous medium in a manner that prevents them from being filtered easily or settled rapidly

Terminology
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● Also called gelatinous carcinoma

Epidemiology
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● 0.5 to 3% of breast carcinomas (Cancer Radiother 2009;13:37)
● Usually older women (mean age 71 years, Breast Cancer Res Treat 2008;111:541) with slow growing tumor

Clinical features
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● Nodal metastases are rare (2-4%), but important prognostic factor (Am J Surg 2004;187:528)
● Usually no nodal metastases for tumors < 1 cm (Am J Surg 2008;196:549)
● Micropapillary architecture has no clincal significance (Int J Surg Pathol 2008;16:251, but see Breast J 2008;14:412)

Prognostic features
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● 10 year survival for pure form is > 90% (much better than ductal carcinoma NOS)
● Death may occur late, although 20 year breast cancer specific survival is still > 80%

Case reports
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● 35 year old woman with locally advanced tumor and sudden growth (Jpn J Clin Oncol 2002;32:64)
● 36 year old woman with tumor arising within fibroadenoma (Pathologica 2008;100:199)
● 42 year old woman with aggressive, HER2+ tumor (Am Surg 2008;74:113)
● 47 year old woman with vulvar tumor due to ectopic breast tissue (Arch Pathol Lab Med 2002;126:1216)
● 64 year old woman with giant (17 cm) tumor (Breast Cancer 2005;12:337)
● 74 year old man with rapidly growing retroareolar tumor in left breast (Gac Med Mex 2007;143:79)
● 86 year old man with tumor presenting as Paget’s disease of nipple (Diagn Pathol 2008;3:42)
● Woman in 60's with a breast mass (Case of the Week #11)

Treatment
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● Pure cases may not need axillary staging (Ann Surg Oncol 2002;9:161)

Gross description
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● Soft, pale, gray-blue, gelatin-like and well-circumscribed
● Frequently hemorrhagic

Gross images
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Soft, gelatinous mass AFIP

Tumor with positive margin (Fig 1A/1B)

Soft, gelatinous mass #1; #2

Micro description
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● Well-differentiated (low grade) tumor cells floating in a sea of lightly staining amorphous mucin
● Tumor cells may be solid, acinar or detached
● Often surrounded by connective tissue bands
● Recommended that at least 1/3 of tumor volume should consist of mucin, and that no areas of typical invasion should be present (Stanford Universtiy)
● No / rare mitotic figures
● Usually no in-situ epithelial component
● Note: recommended to designate tumors as pure (at least 90% mucinous component) or mixed

Micro images
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Images from Case of the Week #11




Abundant mucinous stroma containing epithelial tumor cells with at most mild atypia

AFIP images:

Clusters of tumor cells                         Alveolar and festoon            Sparse epithelial
in mucinous secretion                          patterns surrounded            component (arrow-DCIS)
surround a duct                                                                                    by mucin


Clusters of tumor cells


ER+, PR+, chromogranin+                   Tumor cells are ER+
and synaptophysin+


Grimelius staining (an agryophilic silver stain) denotes neuroendocrine differentiation

Ectopic breast tissue in vulva:
Figure 1: mucinous lakes with clusters of tumor cells and adjacent benign breast tissue
Figure 2: ER+
Figure 3: BRST1+

Various images: fig 2, 4

Cytology description
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● Highly cellular, loosely cohesive clusters and dissociated cells with intact cytoplasm and nuclei with mild atypia, no oval bare nuclei
● Also thin walled capillaries, micropapillary pattern of angulated clusters or abortive papillae and ball-like clusters (Acta Cytol 2007;51:25), abundant extracellular mucin (Malays J Pathol 2000;22:65)
● May have spindle cells at edge of nests and in background, which represent either tumor cells compressed by mucin or fibroblasts (Diagn Cytopathol 2009;37:393)
● Variable psammoma bodies (Diagn Cytopathol 2007;35:230)

Cytology images
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Fig C: FNA shows tightly                         Fig C: FNA shows carcinoma
cohesive tumor cells in                           cells embedded in mucin
mucinous background

Various images: fig 5-9

Colloid carcinoma

Virtual slides
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Mucinous / colloid carcinoma

Videos
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Mucinous / colloid carcinoma

Positive stains
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● ER, PR (< 70%) and MUC2
● Neuroendocrine differentiation (chromogranin, synaptophysin, neuron-specific enolase) in 15-50% (Am J Surg Pathol 1994;18:702)
● Mucin stains with PAS, Alcian blue and mucicarmine
● Also WT1 (65%, Mod Pathol 2008;21:1217), androgen receptor (42%, Ann Oncol 2010;21:488)

Negative stains
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● MUC1 (or low, Histopathology 2003;42:26)
● p53
● HER2 (Kaohsiung J Med Sci 2005;21:197)

Molecular description
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● Usually diploid

Electron microscopy description
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● Differences exist between cells of pure and mixed forms (Ultrastruct Pathol 2007;31:263)

Electron microscopy images
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Cytoplasmic mucigen granules

Differential diagnosis
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● Infiltrating ductal carcinoma with focal mucinous change
● Invasive micropapillary carcinoma: less extracellular mucin than mucinous carcinoma; cells have abundant eosinophilic cytoplasm, round vesicular nuclei and prominent nucleoli; extensive true angiolymphatic invasion; often psammoma bodies
● Metastatic mucinous carcinoma (rectum-Asian J Surg 2006;29:95)
● Mucinous ductal carcinoma in situ: non-invasive, myoepithelial cells (calponin+, p63+) are present
● Mucocele-like lesion: myoepithelial cells are present and adherent to strips of cells floating in mucin, also ducts extended by mucinous material
● Myxoid fibroadenoma - has compressed spaces lined by 2 layers
● Signet ring carcinoma: intracellular mucin only
● FNA: infiltrating ductal carcinoma - marked atypia (Am J Clin Pathol 2003;120:194)
● FNA: myxoid fibroadenoma - stromal fragments and oval bare nuclei in every case

End of Breast malignant, males, children > Carcinoma subtypes > Mucinous / colloid carcinoma

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