Morphologic Reproducibility, Genotyping, and Immunohistochemical Profiling Do Not Support a Category of Seromucinous Carcinoma of the Ovary

Am J Surg Pathol. 2017 May;41(5):685-695. doi: 10.1097/PAS.0000000000000812.

Abstract

The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The morphologic diagnosis of seromucinous carcinomas is not very reliable and it does not exhibit a distinct immunophenotype or genotype. The molecular features overlap mostly with endometrioid and low-grade serous carcinomas. Our data suggest the category of seromucinous carcinoma be discontinued as ancillary molecular tests can assign cases to one of the major histotypes.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Carcinoma, Endometrioid / chemistry
  • Carcinoma, Endometrioid / diagnosis*
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry*
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Mutation
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Cystic, Mucinous, and Serous / chemistry
  • Neoplasms, Cystic, Mucinous, and Serous / diagnosis*
  • Neoplasms, Cystic, Mucinous, and Serous / genetics
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Observer Variation
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Phenotype
  • Predictive Value of Tests
  • Reproducibility of Results
  • Terminology as Topic
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor