The Utility of Immunohistochemistry in the Differential Diagnosis of Gynecologic Disorders

Abstract

Context Immunohistochemistry has assumed an increasing role in the identification and characterization of gynecologic disorders including lesions with deceptively bland morphology, uncommon and underdiagnosed neoplasms, and neoplasms with specific genetic alterations associated with overexpression or loss of expression of specific proteins. The diagnostic accuracy has been significantly improved owing to the discovery and increasing experience with the tumor-associated biomarkers, and the increasing demand for precise tumor classification to assess suitability for the expanding therapeutic modalities including clinical trials. Objective To differentiate lesions of the gynecologic tract through the use of effective immunohistochemical panels. Data Sources Literature review and authors' personal practice experience. Conclusions The application of diagnostic and prognostic immunohistochemical panels has enabled pathologists to better guide therapeutic decisions and to better predict the clinical outcome. It is now well established that the use of ancillary testing, including immunohistochemistry, has a significant power in the identification, differentiation, and classification of reactive, premalignant, and malignant gynecologic disorders. This article discusses the utilities and pitfalls of the commonly used immunohistochemical markers in the context of overlapping morphologic features encountered in the uterus, ovaries, and fallopian tubes.

Abdominopelvic washings in gynecologic pathology: A comprehensive review

“…62 It is prudent to rule out a metastasis of a mucinous tumor to the ovary or peritoneum in cases of mucinous neoplasms. 43 Strong and diffuse p16 positivity likely points to an endocervical primary, but will not stain rare HPV-negative endocervical carcinomas that have metastasized to the ovary. Pseudomyxoma peritonei is often associated with an appendiceal primary tumor, and can be divided into disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, with the former typically following an protracted clinical course, and the latter with a poor prognosis.…”

“…Cytokeratin antibodies alone cannot be used to differentiate between adenocarcinoma and mesothelial cells, because mesothelium expresses many cytokeratins that are also expressed in carcinomas, including those arising from the female genital tract. [43][44][45][46][47][48] Mesothelium has also been shown to stain for estrogen receptor (ER) and progesterone receptor (PR). [40][41][42][43][44] Conversely, immunohistochemical markers expressed in adenocarcinoma but not in mesothelial cells include MOC-31, Ber-Ep4, and Leu-M1.…”

“…43 WT-1 is also negative in endometrioid adenocarcinoma, which can be in the differential for highgrade serous carcinoma. Expression of WT-1 can be useful in determining whether a high-grade serous carcinoma is from endometrial versus extrauterine origin, as high-grade serous carcinomas of the ovary, peritoneum, and fallopian tube typically express WT-1, while serous carcinomas originating from the endometrium should be negative for WT-1.…”

“…Cases of pseudomyxoma peritonei can lead to confusion as to the origin of the mucinous neoplasm, and these scenarios are not uncommon in clinical practice. 43,99 Colorectal carcinoma should express stronger CK20 positivity than CK7 positivity, with diffuse CDX-2 positivity, and pancreatobiliary carcinomas will show loss of DPC-4 expression in approximately 50% of cases. 96 The presence of rather scant clusters of bland epithelial cells in a background of mucin favors disseminated peritoneal adenomucinosis, while cellular fluids with numerous epithelial cell clusters demonstrating moderate to severe atypia typically correspond to peritoneal mucinous carcinomatosis (Fig.…”

“…Pseudomyxoma peritonei is often associated with an appendiceal primary tumor, and can be divided into disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, with the former typically following an protracted clinical course, and the latter with a poor prognosis. 43,100 Low-grade appendiceal mucinous neoplasms stain with a similar immunoprofile as colorectal carcinomas. 9).…”