Dedifferentiated secretory breast carcinoma with fibrosarcomatous features harboring an ETV6-NTRK3 fusion in both components

Genes Chromosomes Cancer. 2021 Jun;60(6):447-451. doi: 10.1002/gcc.22929. Epub 2020 Dec 28.

Abstract

Secretory carcinomas are low-grade translocation-driven carcinomas occurring in patients over a wide age range. These tumors most frequently arise in the breast and salivary gland, but may occasionally arise at other anatomic sites, such as the skin, the thyroid gland or the upper or lower respiratory tract. In concert with their low-grade morphology, secretory carcinomas most often follow an indolent clinical course. However, rare cases have shown dedifferentiation (also known as high-grade transformation) and aggressive clinical behavior. To date, the dedifferentiated component in all molecularly confirmed cases of secretory carcinoma has taken the form of a high-grade carcinoma. Here we present a case of an ETV6-NTRK3 fusion-positive secretory carcinoma of the breast with sarcomatous dedifferentiation. The sarcomatous component showed an infantile or adult fibrosarcoma-like morphology including a herringbone fascicular pattern and a hemangiopericytic vascular pattern. By immunohistochemistry, the sarcomatous component showed focal CD34 immunoreactivity and loss of all of the markers expressed in the conventional secretory carcinoma component, including SOX10, S100, GATA-3, AE1/AE3 and E-cadherin. Fluorescence in situ hybridization analysis revealed that the sarcomatous component retained the ETV6-NTRK3 fusion, but also acquired homozygous deletion of CDKN2A. The tumor followed an aggressive clinical course and the patient eventually succumbed to her disease 14 months after diagnosis. The histomorphologic and molecular genetic features of this tumor are discussed, including its ability to mimic kinase-rearranged infantile or adult fibrosarcomas at extramammary sites and the theragnostic importance of its distinction from conventional metaplastic spindle cell carcinomas in the breast.

Keywords: CDKN2A homozygous deletion; ETV6-NTRK3; dedifferentiation; sarcomatous transformation; secretory carcinoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Female
  • Fibrosarcoma / genetics*
  • Fibrosarcoma / pathology
  • Humans
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*

Substances

  • ETV6-NTRK3 fusion protein, human
  • Oncogene Proteins, Fusion