Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile

Histopathology. 2016 Jun;68(7):1030-9. doi: 10.1111/his.12897. Epub 2016 Jan 7.

Abstract

Aims: Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of those of usual ductal hyperplasia. In this study we sought to define the molecular characteristics of infiltrating epitheliosis.

Methods and results: Eight infiltrating epitheliosis, adjacent breast lesions (one usual ductal hyperplasia, one papilloma, one micropapillary ductal carcinoma in situ and one low-grade adenosquamous carcinoma), and corresponding normal breast tissue from each case were microdissected and subjected to massively parallel sequencing analysis targeting all coding regions of 254 genes mutated recurrently in breast cancer and/or related to DNA repair. Mutations in components of the PI3K pathway were found in all infiltrating epitheliosis samples, seven of which harboured PIK3CA hotspot mutations, while the remaining case displayed a PIK3R1 somatic mutation.

Conclusions: Somatic mutations affecting PI3K pathway genes were found to be highly prevalent in infiltrating epitheliosis, suggesting that these lesions may be neoplastic rather than hyperplastic. The landscape of somatic genetic alterations found in infiltrating epitheliosis is similar to that of radial scars/CSLs, suggesting that infiltrating epitheliosis may represent one end of this spectrum of lesions.

Keywords: complex sclerosing lesions; immunohistochemistry; infiltrating epitheliosis; massively parallel sequencing.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Adenosquamous / genetics*
  • Carcinoma, Adenosquamous / metabolism
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Female
  • Fibrocystic Breast Disease / genetics*
  • Fibrocystic Breast Disease / metabolism
  • Fibrocystic Breast Disease / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Hyperplasia
  • Immunophenotyping
  • Middle Aged
  • Mutation
  • Papilloma / genetics*
  • Papilloma / metabolism
  • Papilloma / pathology
  • Sclerosis / genetics*
  • Sclerosis / metabolism
  • Sclerosis / pathology
  • Sequence Analysis, DNA

Substances

  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human