Molecular Profiling of Syringocystadenocarcinoma Papilliferum Reveals RAS-Activating Mutations

Arch Pathol Lab Med. 2024 Feb 1;148(2):215-222. doi: 10.5858/arpa.2022-0474-OA.

Abstract

Context.—: Syringocystadenocarcinoma papilliferum (SCACP) is a rare adnexal carcinoma and the malignant counterpart of syringocystadenoma papilliferum (SCAP), which is commonly located on the head and neck and may arise in association with a nevus sebaceus. RAS mutations have been identified in both SCAP and nevus sebaceus.

Objective.—: To evaluate the clinicopathologic and molecular features of SCACPs, which have not been previously explored.

Design.—: We obtained 11 SCACPs from 6 institutions and reviewed the clinicopathologic features. We also performed molecular profiling using next-generation sequencing.

Results.—: The cohort comprised 6 women and 5 men with ages ranging from 29 to 96 years (mean, 73.6 years). The neoplasms occurred on the head and neck (n = 8; 73%) and extremities (n = 3; 27%). Three tumors possibly arose in a nevus sebaceus. A total of 4 cases showed at least carcinoma in situ (adenocarcinoma, n = 3; squamous cell carcinoma [SCC], n = 1), and 7 cases were invasive (SCC, n = 5; mixed adenocarcinoma + SCC, n = 2). A total of 8 of 11 cases (73%) had hot spot mutations consisting of HRAS (n = 4), KRAS (n = 1), BRAF (n = 1), TP53 (n = 4), ATM (n = 2), FLT3 (n = 1), CDKN2A (n = 1), and PTEN (n = 1). All 4 cases with HRAS mutations occurred on the head and neck, whereas the KRAS mutation occurred on the extremity.

Conclusions.—: RAS-activating mutations were detected in 50% of the cases, of which most (80%) involved HRAS and occurred on the head and neck, which shows overlapping features with SCAP, supporting that a subset may arise as a result of malignant transformation and likely an early oncogenic event.

MeSH terms

  • Adenocarcinoma*
  • Carcinoma, Squamous Cell* / pathology
  • Female
  • Humans
  • Male
  • Mutation
  • Nevus* / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Skin Neoplasms* / pathology
  • Sweat Gland Neoplasms* / genetics
  • Sweat Gland Neoplasms* / pathology

Substances

  • Proto-Oncogene Proteins p21(ras)