Low-grade serous carcinoma of the ovary displaying a macropapillary pattern of invasion.

Invasive micropapillary serous carcinoma (MPSC) also designated "low-grade serous carcinoma" (LGSC) of the ovary is characterized by small micropapillae that infiltrate underlying tissue (ovarian stroma). On occasion these tumors in addition to the micropapillae contain large macropapillae lined by bland epithelium. In rare cases, the entire tumor is composed of macropapillae. In these cases, the question of whether this is an invasive carcinoma or an unusual type of adenofibroma has been raised. The goal of this study was to describe this unusual macropapillary pattern of invasion in LGSC. Cases of LGSC containing macropapillae were retrieved from the files of the Johns Hopkins Hospital. In addition to a detailed morphologic analysis, the mutational status of KRAS and BRAF in the macropapillary, noninvasive, and invasive MPSC components was analyzed by nucleotide sequencing. There were 14 cases containing macropapillae (11 cases of LGSC, 2 cases of atypical proliferative serous tumor (APST) with microinvasion, and 1 case of APST with a focus of LGSC with macropapillae in perivaginal soft tissue). In 3 cases, extraovarian metastases contained macropapillae. Molecular analysis of the primary tumor components (macropapillary, noninvasive, and invasive MPSC and/or APST) was performed in 7 cases and of a lymph node metastasis with macropapillae in 1 case. The identical KRAS mutation was detected in all of the analyzed components of the primary ovarian tumors in 4 cases. In one of these cases, macropapillae in the lymph node metastasis contained a KRAS mutation identical to the primary tumor. The BRAF mutation identified in 1 case was identical in all components of the ovarian tumor. The identical mutations in the macropapillae and the other tumor components in each case indicate that they are clonally related. The finding of macropapillae within lymph nodes supports the interpretation that the macropapillary component is another manifestation of invasion in LGSC. The recognition of this pattern is important, especially in cases when a tumor is composed entirely of macropapillae.