Mutation analysis of papillary tubal hyperplasia associated with ovarian atypical proliferative serous tumor and low-grade serous carcinoma

We present a patient with ovarian atypical proliferative serous tumor and low-grade serous carcinoma, related to KRAS mutation. Bilateral fallopian tubes had papillary tubal hyperplasia, providing additional evidence that it is the putative precursor of low-grade serous tumors. Mutation analysis of papillary tubal hyperplasia has not been done in previous literature.

Ovarian cancer is the most lethal gynecologic malignancy and serous neoplasm is the most common subtype. According to histology, serous neoplasm includes atypical proliferative serous tumor (APST), low-grade (LG) serous carcinoma (SC), and high-grade (HG)-SC. Recent studies strongly suggest fallopian tube epithelium to be the origin of both LG- and HG-SC rather than the ovarian surface epithelium as previously believed. HG-SC originate from precursor tubal lesions designated serous tubal intraepithelial carcinomas (STICs). Kurman et al recently identified a fallopian tube lesion as the likely precursor of LG serous tumor, and designated it as papillary tubal hyperplasia (PTH). According to Kurman et al, PTH, the putative precursor of LG serous neoplasm, is frequently associated with APST and noninvasive implants.

Here we report a female patient with ovarian APST, LG-SC, and multiple noninvasive and invasive implantations over different sites. Bilateral fallopian tubes revealed PTH.

Case Report

A 48-year-old woman experienced abdominal fullness and poor appetite for 1 month. Her history was unremarkable except for hypertension. Physical examination showed abdominal distension.

Abdominal sonography revealed massive ascites with suspicious omental cake formation, while computed tomography showed heterogeneous masses at bilateral adnexal regions, with multiple peritoneal lesions. No gastrointestinal tumor was found despite extensive endoscopic studies. Laboratory data showed elevated cancer antigen 125 at the level of 2888 U/mL. Cancer antigen 19-9 and carcinoembryonic antigen levels were within reference levels.

Intraoperative examination of a frozen section was performed. The right ovarian tumor measured 7 × 5 cm and adhered to the posterior cul-de-sac. It was friable and cystic with papillary and solid components. Histologic features of frozen section favored an APST with focal micropapillary structures of the right ovary, with noninvasive and invasive omental implantations. The patient received debulking surgery, including hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and biopsy of the peritoneum and urinary bladder.

Microscopically, the right ovary revealed a background of micropapillary serous borderline tumor with micropapillary, medusa branching, filigree patterns, cribriform confluent areas, and psammoma bodies ( Figure 1 ). Foci of LG-SC with stromal invasions were present. Multiple noninvasive and invasive implants involved the left ovary, omentum, peritoneum and the serosa of the urinary bladder. Both fallopian tubes had tubal epithelial proliferations with papillary tufting, detached clusters and abundant psammoma bodies, suggestive of PTH ( Figure 2 ). To perform mutation analysis, we used manual microdissection to harvest cells from selective areas of lesions with lesser calcification, where tumor cells occupied >50% of the overall cell population. Molecular studies revealed same KRAS mutations in the ovarian APST and LG-SC, but no mutation was detected in the PTH ( Figure 3 ). The patient has received subsequent chemotherapy and regular follow-up.