Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors

Abstract

Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

Fig. 1

Endometrioid carcinoma showing squamous morule and low-grade endometrioid glandular differentiation.

Fig. 2

High-grade serous carcinomas with SET features (originally diagnosed as FIGO grade 3 endometrioid carcinoma) showing solid architecture.

Fig. 3

High-grade serous carcinomas with SET features (originally diagnosed as FIGO grade 3 endometrioid carcinoma) showing pseudo-endometrioid growth pattern.

Fig. 4

High-grade serous carcinomas with SET features (originally diagnosed as FIGO grade 3 endometrioid carcinoma) showing transitional cell-like architecture.

Fig. 5

High-grade serous carcinomas with SET features (originally diagnosed as FIGO grade 3 endometrioid carcinoma) showing numerous tumor-infiltrating lymphocytes.

Fig. 6

Low-grade endometrioid carcinoma exhibiting papillary architecture.

Fig. 7

Low-grade endometrioid carcinoma exhibiting and sex cord-like pattern.

Fig. 8

High-grade (FIGO grade 3) endometrioid carcinoma with a predominantly solid growth pattern.

Fig. 9

High-grade (FIGO grade 3) endometrioid carcinoma with focal low-grade endometrioid glandular differentiation.

Fig. 10

Immunohistochemistry - p53 expression in endometrioid carcinoma.

Fig. 11

Immunohistochemistry - p53 expression in OSC-SET.

Fig. 12

Null pattern of p53 expression in an OSC-SET. Note the rare non-neoplastic cells that display weak p53 expression; this serves as a positive internal control.

Fig. 13

Immunohistochemistry - WT-1 expression in endometrioid carcinoma.

Fig. 14

Immunohistochemistry - WT-1 expression in OSC-SET.

Fig. 15

Rare WT-1 positive cells in a low-grade endometrioid carcinoma.