Table 3.

Pathologic-molecular correlations in gynecologic cancers and their implications for patient management

Histopathologic finding(s)	Ancillary pathologic test(s) (IHC/ISH)	Associated molecular abnormality	Intervention/Management implications
Endometrial: Lower uterine segment location; endometrioid or undifferentiated histotype; mucinous differentiation; tumor-infiltrating lymphocytes; peri-tumoral lymphocytes Ovarian: endometrioid or clear cell histotype; tumor- infiltrating lymphocytes	Immunohistochemistry for MLH1, MSH2, MSH6, PMS2; MLH1 promoter methylation analysis	DNA mismatch repair deficiency due to: 1) germline mutations in MLH1, MSH2, MSH6, PMS2 or EPCAM 2) somatic mutations or MLH1 promoter methylation	1) Genetic counseling and family screening for Lynch syndrome 2) Consider immune therapy e.g. checkpoint inhibitors for recurrent disease
Endometrial: High grade; frequent lymphovascular space invasion; endometrioid, clear cell, undifferentiated or carcinosarcoma histotype; conspicuous tumor- infiltrating lymphocytes and/or peri-tumoral lymphocytes; morphologic heterogeneity/ambiguity; bizarre/giant tumor cell nuclei Ovarian: endometrioid histotype; morphologic heterogeneity		POLE mutations	Consider immune therapy e.g. checkpoint inhibitors for recurrent disease Consideration of avoidance of overtreatment in adjuvant setting
Ovarian: Variant (solid, endometrioid, and transitional cell carcinoma, SET-like) morphology; tumor-infiltrating lymphocytes; necrosis		Homologous recombination deficiency e.g. BRCA1/2 mutations	Consider germline BRCA1/BRCA2 testing and PARP inhibitor therapy in recurrent setting
Ovarian: Serous borderline tumors with eosinophilic cells; cuboidal and columnar cells that line papillae and bud from their surfaces	BRAF VE1 immunohistochemistry	MAPK pathway activation	Presence of V600E BRAF mutation may portend improved prognosis