Molecular profiling of a primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid

J Cutan Pathol. 2020 Sep;47(9):860-864. doi: 10.1111/cup.13733. Epub 2020 Jun 15.


Primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next-generation sequencing. The patient is an 85-year-old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet-ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next-generation sequencing revealed a CDH1 mutation, which is known to confer signet-ring morphology in other carcinomas. Pathogenic mutations in NTRK3, CDKN1B, and PIK3CA were also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.

Keywords: adnexal neoplasm; cancer; cutaneous neoplasm.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Antigens, CD / genetics*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biopsy
  • Cadherins / genetics*
  • Carcinoma, Signet Ring Cell / diagnosis
  • Carcinoma, Signet Ring Cell / genetics*
  • Carcinoma, Signet Ring Cell / therapy
  • Combined Modality Therapy
  • Eyelid Neoplasms / genetics*
  • Eyelid Neoplasms / pathology
  • High-Throughput Nucleotide Sequencing / methods
  • Histiocytes / pathology
  • Humans
  • Keratin-7 / metabolism*
  • Male
  • Mutation
  • Radiotherapy, Adjuvant / methods
  • Receptors, Androgen / metabolism*
  • Skin Neoplasms / pathology
  • Surgical Flaps
  • Treatment Outcome


  • Antigens, CD
  • Antineoplastic Agents, Hormonal
  • CDH1 protein, human
  • Cadherins
  • Keratin-7
  • Receptors, Androgen