Invasive Apocrine Carcinoma

Invasive Apocrine Carcinoma

Apocrine carcinoma is a morphologically distinct type of invasive breast cancer characterized by large cells with a low nuclear to cytoplasmic ratio and abundant eosinophilic granular cytoplasm image.

The cytoplasm is abundant with a coarsely granular eosinophilic appearance image. The nuclei are large and pleomorphic with prominent nucleoli image. The growth pattern is typically solid in type.



  • Invasive apocrine carcinoma (IAC)


  • Breast carcinoma with characteristic morphologic appearance resembling apocrine sweat glands in at least 90% of tumor cells, closely linked with androgen receptor expression


Androgen Metabolism in IAC

  • Majority of breast cancers (70-80%) express androgen receptor (AR)

    • Highest expression is seen in ER/PR/HER2 positive cancers (˜ 80%), followed by ER/PR positive, HER2 negative cancers (˜ 60%) and ER/PR negative, HER2 positive cancers (˜ 50%); lowest expression is in ER/PR/HER2 negative cancers (˜ 35%)

      • HER2 may induce AR transactivation through MAP kinase pathway

    • IAC expresses AR in 56-100% of cases

      • AR expression may help distinguish IAC from basal-like cancers that are also “triple negative”

  • Expression of AR is also frequent in benign apocrine lesions

    • Growth of cutaneous apocrine glands is stimulated by androgens

  • Enhanced metabolism of testosterone precursors has been reported in IAC

  • Altered androgen metabolism may play a role in pathogenesis and tumor progression

Gene Expression Profiling

  • Molecular studies indicate that invasive apocrine carcinomas may represent distinct subgroup of breast cancers

  • IAC is characterized by gene expression pattern largely driven by expression of AR

    • Majority AR positive; AR may be potential therapeutic target

    • About 1/2 negative for ER, PR, and HER2; however, IAC does not cluster with basal-like group

    • About 1/2 negative for ER and PR but HER2 positive

      • Tumors overlap significantly with HER2 group as defined by intrinsic gene classification

      • Gene expression data suggests link between HER2 signaling and molecular apocrine phenotype

    • Gene signature includes increased expression of numerous genes with role in metabolism

Association with Benign Apocrine Lesions

  • Apocrine glands normally occur in skin

    • Breast evolved from skin appendages and, thus, has many features in common

  • Cells with functional apocrine characteristics have been described in fetal breast tissue

  • Apocrine change is commonly seen in cysts in adult breast tissue and may arise from fetal cells or from metaplasia

  • Benign apocrine lesions express AR and are negative for ER and PR

  • Apocrine change without atypia has not been consistently linked to increase in risk of breast cancer

    • Difficult to define atypia in apocrine lesions

    • Lesions with high-grade nuclei, cribriform architecture, &/or necrosis would be considered atypical

      • Additional studies will be necessary to show that these changes increase risk of invasive cancer

  • Some apocrine lesions show loss of heterozygosity and other genetic changes, supporting that some are clonal lesions and may be nonobligate precursors of apocrine carcinomas

    • Atypical apocrine proliferations are found more commonly in breasts with apocrine carcinomas

Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Invasive Apocrine Carcinoma

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