Invasive Micropapillary Carcinoma of the Breast

Epidemiology:

• Pure micropapillary carcinomas are rare (1-2% of invasive breast cancers)
• Areas with a micropapillary pattern in up to 8% of invasive breast cancers
• Age similar to ER+ NST

Common sites:

Gross features:

• No specific gross features
• Palpable mass (vast majority)
• Dense, irregular mass with indistinct margins and microcalcifications (mammography)
• Hypoechoic usually with or without posterior acoustic shadowing

Histologic features:

• > 90% micropapillary architecture on representative sections
• If 51-90% is micropapillary, it is:
• Mixed invasive carcinoma NST and invasive micropapillary carcinoma
• If 50% or less micropapillary, then you can say “invasive carcinoma NST with micropapillary features”
• Small, hollow or morula-like clusters of cancer cells
• Surrounded by clear stromal spaces reminiscent of lymphatic channels (but not lined by endothelial cells)
• Fixation artifact maybe
• Reverse polarity (“inside-out”) growth pattern
• Apical pole of the cells faces the stroma and not the luminal surface
• No fibrovascular core
• Cuboidal-to-columnar cells
• Eosinophilic cytoplasm, dense or finely granular
• Apocrine features in some
• Nuclei variable pleomorphism but rarely pronounced
• Mitotic activity low to moderate
• Nottingham grade 2-3 (up to 75%)
• Necrosis rare
• Brisk lymphocytic infiltrate is rare

Immunophenotype:

Marker:	Sensitivity:	Specificity:
MUC1 (clear demonstration of reverse polarity
ER positive	Vast majority	Not specific
PR positive	Vast majority	Not specific
HER2 variable	Conflicting results

Molecular features:

• Luminal A or B subtype by gene expression microarray
• Rarely “basal” expression pattern
• May have a distinct pattern of gains and losses by microarray compared to NST:
• Gains:
• 8q
• 17q
• 20q
• Deletions:
• 6q
• 13q
• Amplifications:
• MYC (8q) (33%)
• CCND1 (11q) (8%)
• FGFR1 (17%)

Other features:

• Lymphotropic
• Lymphatic invasion significantly more frequent
• Lymph node mets significantly more frequent
• Prognosis – not established if it is an independent prognostic factor

References:

• Lakhani SR et al., eds. WHO Classification of Tumours of the Breast, 4^th ed. (2012)