Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics

Abstract

The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).

Figure 1

Serous tubal intraepithelial carcinoma (STIC). (a) The morphological features of a small STIC showing papillary architecture with intraepithelial carcinoma cells, many of which are detached and are able to freely disseminate onto ovaries, pelvic, or peritoneal wall. (b) The p53 immunohistochemistry demonstrates that all intraepithelial carcinoma cells are intensely positive for p53 nuclear immunoreactivity. In contrast, the normal-appearing tubal epithelial cells flanking the STIC are negative for p53.

Figure 2

Serous tubal intraepithelial lesion (STIL). (a) The morphological features of an STIL identified in a young cancer-free BRCA mutation carrier. The epithelium shows mild nuclear and architectural atypia but not to the level of a classical STIC. (b) An immunohistochemical stain for p53 shows overexpression in several consecutive secretory cells. (c) An immunohistochemical stain for Ki-67 shows a low proliferation index.