Superficially invasive cervical squamous cell carcinoma metastatic to ovarian endometriotic cyst wall, a case report and brief review of the literature

Intraoperative pathologic evaluation revealed dark red cyst wall fragments, 7 cm in aggregate, and an unremarkable fallopian tube (Fig. 1a). The frozen section diagnosis was ovarian endometriosis (Fig. 1b), confirmed by evaluation of permanent sections. Among multiple additional permanent sections, several sections demonstrated atypical stratified epithelium in the subepithelial stroma within the cystic wall. The atypical cells had large, hyperchromatic nuclei, irregular nuclear contours, prominent nucleoli, scant cytoplasm, and numerous mitoses, consistent with malignant cells (Fig. 2a-c). The total size of malignant epithelium was approximately 15 mm. The remainder of the specimen was entirely submitted for microscopic examination and demonstrated ovarian tissue with endometriosis and an unremarkable fallopian tube. No evidence of teratoma was identified.

By immunohistochemistry (IHC), the malignant cells were diffusely positive for CK7, CK5/6, p63, and p16, and negative for CK20, WT1, GATA3, ER, and PR. p53 demonstrated wild-type staining pattern. Ki67 proliferation index was approximately 50%. (Fig. 3a-h).

Based on the morphologic features and immunohistochemical stain findings, the case was diagnosed as ovarian transitional cell carcinoma-like high-grade serous carcinoma. A differential diagnosis of metastatic urothelial carcinoma of the urinary tract was entertained; however, no lesions were identified in the urinary tract by ultrasound or computerized tomography (CT) scan. To rule out squamous cell carcinoma arising from teratoma, the entire specimen was examined. No evidence of teratoma was identified. The patient sought external pathology consultations from two large regional medical centers, both of which agreed with the original diagnosis.

Total hysterectomy and right salpingo-oophorectomy with pelvic lymph node dissection and omentectomy were performed. Grossly, the uterus, cervix, right ovary and fallopian tube were unremarkable (Fig. 4a). Microscopically, the right ovary, right fallopian tube, and other specimens revealed no evidence of malignancy. Interestingly, representative sections of the cervix revealed high-grade squamous intraepithelial lesion (HSIL). Eventually the cervix was entirely submitted for microscopic examination. Additional cervical sections demonstrated HSIL with focal superficially invasive squamous cell carcinoma. The depth of invasion was 4.0 mm and a horizontal extent was 6.0 mm involving only one of total 12 sections of the cervix. No lymphovascular invasion was identified. Examination of the right ovary revealed no evidence of teratoma. The FIGO tumor stage was IA2 (Fig. 4b-c). Prior to hysterectomy, testing for high-risk HPV was performed on the cervical cytology specimen by hybrid capture2 (HC2) method (Qiagen Inc., USA), and was positive (935 RLU; reference range: < 1.00RLU).

The original diagnosis of transitional cell carcinoma-like high-grade serous carcinoma was questioned. To correlate the findings in the ovary and cervix, DNA extraction was performed from the ovarian sections with carcinoma. The DNA extraction and purification was performed according to the manufacturer’s instructions using GenElute™ FFPE DNA Purification Kit (MilliporeSigma, Burlington, USA). Testing for high-risk HPV was performed by HC2 method was positive (141.3 RLU; reference range: < 1.00 RLU).

To further support the diagnosis of metastatic carcinoma, analysis of the patient’s peripheral blood for circulating tumor cells (CTC) was performed. Several malignant, triploid, CD45-negative epithelial cells were identified, suggestive of the presence of carcinoma cells in the peripheral blood (Fig. 4d).

The final diagnosis was metastatic cervical squamous cell carcinoma involving ovarian endometriosis.