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

• Published in: The American journal of surgical pathology Vol. 41; no. 5; pp. 685 - 695
• Main Authors: Rambau, Peter F, McIntyre, John B, Taylor, Jennifer, Lee, Sandra, Ogilvie, Travis, Sienko, Anna, Morris, Don, Duggan, Máire A, McCluggage, W Glenn, Köbel, Martin
• Format: Journal Article
• Language: English
• Published: United States Copyright Wolters Kluwer Health, Inc. All rights reserved 01-05-2017
• Subjects: Adolescent; Adult; Aged; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biopsy; Carcinoma, Endometrioid - chemistry; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - pathology; Diagnosis, Differential; DNA Mutational Analysis; 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
• ISSN: 0147-5185; 1532-0979
• DOI: 10.1097/PAS.0000000000000812

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.