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.


TERMINOLOGY


Abbreviations



  • Invasive apocrine carcinoma (IAC)


Definitions



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


ETIOLOGY/PATHOGENESIS


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

Full access? Get Clinical Tree

Get Clinical Tree app for offline access
%d bloggers like this: