What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors

Abstract

Ovarian carcinomas represent a heterogeneous group of neoplasms consisting of separate entities with distinct risk factors, precursor lesions, pathogenesis, patterns of spread, molecular profiles, clinical course, response to chemotherapy, and outcomes. The histologic subtype and the related molecular features are essential for individualized clinical decision-making. The fifth edition of the World Health Organization classification of tumors of the female genital tract divides ovarian carcinomas into at least five main and distinct types of ovarian carcinomas: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. Molecular pathology has improved the knowledge of genomic landscape of ovarian carcinomas identifying peculiar alterations for every histologic subtype. It is well-known that high-grade and low-grade serous carcinomas are separate entities with entirely different morphologic and molecular characteristics. TP53 and BRCA mutations are typical of high-grade serous carcinoma, whereas BRAF and KRAS mutations frequently occur in low-grade serous carcinoma. Endometrioid and clear cell carcinomas are frequently associated with endometriosis. Endometrioid tumors are characterized by β-catenin alterations, microsatellite instability, and PTEN and POLE mutations, while ARID1A mutations occur in both endometrioid and clear cell carcinomas. Mucinous carcinomas are uncommon tumors associated with copy-number loss of CDKN2A and KRAS alterations and metastasis from other sites should always be considered in the differential diagnosis.

Keywords: histopathology; immunohistochemical profile; molecular pathology; ovarian cancer tissue biomarkers; ovarian carcinoma.

Figure 1

(A) Histologic appearance of classic high-grade serous carcinoma (HGSC) (hematoxylin and eosin, H&E, ×100); (B) Solid, pseudoendometrioid, transitional cell carcinoma-like (SET) variant of HGSC (hematoxylin and eosin, H&E, ×100).

Figure 2

(A) Histologic appearance of low-grade serous carcinoma showing tumor cells with uniform nuclei and inconspicuous mitotic activity (hematoxylin and eosin, H&E, ×100); (B) Psammoma bodies are frequent in low-grade serous carcinoma (hematoxylin and eosin, H&E, ×100).

Figure 3

(A) and (B) Histologic appearance (hematoxylin and eosin, H&E) of low-grade endometrioid carcinoma with squamous differentiation (×100 and ×200, respectively).

Figure 4

(A) Histologic appearance of clear cell carcinoma with tubulocystic pattern, tumor cells are polygonal to cuboidal and flattened with clear cytoplasm; (hematoxylin and eosin, H&E, ×200); (B) Papillary pattern shows small and regular papillae, frequently hyalinized (hematoxylin and eosin, H&E ×100).