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Secretory Carcinoma of the Breast


Secretory carcinoma is a rare but distinct subtype of breast carcinoma. Although it was initially described as a carcinoma of young children, most cases have been reported in adults of both sexes. Most cases are in young women, with a median age of 25 years. They usually present as a slow-growing, painless, well-circumscribed, mobile and palpable mass.

Microscopically, secretory carcinoma is composed of epithelial cells arranged in microcystic, follicular, ductal, and solid patterns. Hyalinized fibrous tissue is frequently identified centrally, and papillary architecture is sometimes seen at the periphery of the tumor. The characteristic histomorphology is the presence of a large amount of intracellular and luminal eosinophilic secretion that stains positive for periodic acidSchiff after diastase digestion (PAS-D).  Most tumors stain positive for S100 consistently, and negative for estrogen receptor, progesterone receptor, and HER2/neu (ie, triple negative). In addition, some secretory carcinomas express basal-cell markers, including cytokeratins 5/6, 14, and 17; c-Kit (CD117); epidermal growth factor receptor; and vimentin. Recent studies have shown a characteristic molecular feature: a balanced t(12;15) translocation that results in an ETS variant 6 with neurotrophic tyrosine kinase receptor type 3 (ETV6-NTRK3) fusion gene encoding a chimeric tyrosine kinase.

Axillary lymph node metastasis is uncommon, especially if tumors are less than 2 cm. Although rare events of axillary lymph node or distant metastases have been documented, the prognosis is generally excellent. The methods of surgical treatment and the role of adjuvant therapy, particularly for young patients, remain controversial.

Main differential diagnosis includes Cystic hypersecretory hyperplasia, Lipid-rich (lipid-secreting) carcinomas, Glycogen-rich carcinomas and apocrine carcinomas.

======= Summary ===========

  • Most occurs in young women
  • Microcystic and follicular patterns
  • PAS-D positive secretion characteristic
  • Consistently S100-positive
  • Positive for basal-cell markers.
  • t(12;15) result in ETV6-NTRK3 fusion gene
  • Excellent prognosis.

Reference / Suggested Readings

Tavassoli FA et al.: Secretory carcinoma of the breast. Cancer 45(9):24042413, 1980.

Rosen PP et al.: Secretory carcinoma of the breast. Arch Pathol Lab Med 115(2):141-4, 1991.

Tognon C. et al: Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell  2:367-376, 2002.