Defining the cut point between low-grade and high-grade ovarian serous carcinomas: a clinicopathologic and molecular genetic analysis

Abstract

A 2-tier grading system based on nuclear grade divides ovarian serous carcinomas into low (nuclear grade 1) and high grade (nuclear grade 3). In most instances the separation is straightforward but at times, the morphologic distinction between them can be difficult. We studied 11 ovarian serous carcinomas with features that were "intermediate" (nuclear grade 2) between low and high grade. All the cases were high staged and had a poor clinical outcome. None of the tumors showed mutations in KRAS, BRAF, and ERBB2 genes that characterize most low-grade serous carcinomas. In contrast, 10 (90.9%) of 11 cases contained nonsynonymous TP53 mutations characteristic of high-grade serous carcinomas. In summary, the molecular genetic profile and behavior of serous carcinomas with grade 2 nuclei are virtually the same as those of serous carcinomas with grade 3 nuclei, supporting the use of the 2-tier grading system for classifying ovarian serous carcinomas.

Fig. 1

Grade 1 nuclei (Gr 1) are small and uniform in size and there are few mitotic figures. Grade 2 nuclei (Gr 2) are larger compared to grade 1 but are still relatively uniform. Nuclear chromatin is coarser than in grade 1and mitotic figures are more frequent. Grade 3 nuclei (Gr 3) are highly pleomorphic and large with coarsely clumped chromatin. Numerous mitotic figures including many abnormal ones are present.

Fig. 1

Grade 1 nuclei (Gr 1) are small and uniform in size and there are few mitotic figures. Grade 2 nuclei (Gr 2) are larger compared to grade 1 but are still relatively uniform. Nuclear chromatin is coarser than in grade 1and mitotic figures are more frequent. Grade 3 nuclei (Gr 3) are highly pleomorphic and large with coarsely clumped chromatin. Numerous mitotic figures including many abnormal ones are present.

Fig. 2

Case 5 shows a micropapillary pattern (A) and tumor cells contain grade 2 nuclei (B,C). Case 3 demonstrates a slit-like growth pattern (D) and tumor cells contain grade 2 nuclei (E,F).

Fig. 2

Case 5 shows a micropapillary pattern (A) and tumor cells contain grade 2 nuclei (B,C). Case 3 demonstrates a slit-like growth pattern (D) and tumor cells contain grade 2 nuclei (E,F).