A 46-year-old Chinese woman, gravida 1 para 1, presented with lower abdominal pain for 5 days and dysmenorrhea for 2 years. Trans-vaginal ultrasound, magnetic resonance image (MRI) and computerized tomography (CT) indicated the presence of uterine adenomyosis and bilateral ovarian endometriotic cysts. There were no abnormalities were found in her bilateral lungs and other abdominal/pelvic organs. The preoperative serum CA-125, carcinomatous embryonic antigen (CEA), and CA-153 were 263.1 U/mL (normal < 35 U/mL), 13.9 U/mL (normal< 5 U/mL) and 33.1 U/mL (normal < 25 U/mL), respectively. She denied her personal and familial history of any cancers and related diseases.
After admission, an abdominal cystectomy of the right ovary was initially performed. The intraoperative frozen section was carried out. Unexpectedly, the frozen section showed an ovarian adenocarcinoma in the wall of the endometriotic cyst. The laparotomy exploration found no abnormalities in other abdominal/pelvic organs including stomach, colon, rectum, appendix, pancreas, and liver. There were no any visible tumorlets in the abdominal/pelvic cavity. The patient eventually underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and omentectomy. The patient was eventually assessed as a stage IC ovarian carcinoma because the tumor partly adhered to the surrounding organs. She recovered smoothly from her surgery. She received 5 courses of TP (paclitaxel + cisplatin) chemotherapy, but she had to abandon her last chemotherapy because of the severe myelo-suppression.
The patient was followed up regularly in our outpatient clinics. The serum CA-125, CEA and CA-153 gradually returned to normal levels within 22 days after her surgery. However, her serum CEA began to elevate (6.3 U/mL) at 6 months after her surgery and rose up to 62.1 U/mL at 7 months. MRI showed a right pelvic mass measuring 9.5*5.7 cm and no abnormalities in the abdominal organs. The patient was transferred to a tertiary hospital for further treatment. The gastrointestinal endoscopic examination with multiple biopsies showed no abnormalities in the stomach, terminal ileum, colon and rectum. A relaparotomy was carried out. The intraoperative findings included a large tumor adhering to the right pelvic wall and the ileum wall, and multiple small grey nodules along the small intestinal mesentery. Other abdominal organs, such as stomach, colon, appendix, pancreas and liver, looked unremarkable. The pelvic tumor and partial ileum were removed. The patient refused to adjuvant therapies including chemotherapy and radiotherapy. She was alive with disease for13 months after her first surgery at present.
Grossly, the right ovarian cyst for frozen section measured 18 × 15 × 14 cm. It had a smooth outer surface with occasional rough areas consistent with the adhesions to the surrounding organs. The unilocular cyst was filled with thick, chocolate-like fluids. The inner cystic wall was uneventful except the attachment of some blood clots. There was a small mural nodule with a size of l.0 × 0.5 × 0.2 cm protruding into the lumen. The nodule had a white and solid cut surface. The texture was soft. The right ovary was partly hemorrhagic due to the cystectomy. The left ovary measured 5.0 × 5.0 × 4.5 cm. It had some cystic areas containing dark brown hemorrhagic materials. The uterus measured 10*9*5 cm. The myometrium of the posterior wall was thickened. The cut surface was trabeculated and contained hemorrhagic foci. The endometrium measured 0.2–0.3 cm and looked unremarkable. The uterine cervix and bilateral fallopian tubes were grossly normal.
The mural nodule was histologically continuous with the endometriotic epithelium [Fig. 1a, b]. It showed an invasive growth pattern that were characterized by solid nests with occasional cribriform structures, crowded small irregular glands in sheets and scattered single cells [Fig. 1c, d]. The neoplastic cells in solid nests or in single harbored a typical signet-ring appearance as large mucinous vacuoles and atypical crescentic nuclei [Fig. 1c, e]. The glands were lined by columnar cells with abundant cytoplasmic mucin, significant nuclear atypia, and occasional mitotic figures. The intracellular mucin was Alcian Blue (pH 2.5) positive [Fig. 1f]. The stroma was desmoplastic and had occasional extracellular mucin deposits. There was no lymphovascular invasion or surface involvement of the ovary. The remaining cystic wall showed a typical morphology of an endometriosis that was composed of endometrial epithelium and stroma with hemosiderin-laid macrophages [Fig. 1a, b]. The epithelium adjacent to the tumor showed atypical features (“atypical endometriotic cyst”) that were characterized by cellular crowding, stratification, small papillary formation with eosinophilic cytoplasmic changes, and variable cytological atypia with increased nuclear to cytoplasmic ratio, enlarged hyperchromatic nuclei, and conspicuous nucleoli [Fig. 1g, h]. The surface epithelium was cytologically bland in most areas.
Immunohistochemistry demonstrated that the tumor cells were strongly and diffusely positive for CK 7 [Fig. 2a], CEA and p16, and focally positive for CA125, MUC-6 and p53 (DO-7). They were negative for phosphate and tension homology deleted on chromosome ten (PTEN), estrogen receptor (ER), progesterone receptor (PR), CK19, CK20 [Fig. 2b], PAX-8 [Fig. 2c], and CDX2. They did not show loss of hMLH1 and hMSH2 expression. The atypical endometriotic epithelium was positive for PAX-8 [Fig. 2d]. The final pathological diagnosis of the right ovary was poorly differentiated mucinous carcinoma with signet ring cells and concurrent endometriotic cyst with atypical features.
Other pathological findings included endometriotic cysts of the left ovary and uterine adenomyosis. The endometrium showed proliferating-phase alterations. The remaining right ovary, bilateral fallopian tubes, and uterine cervix were pathologically unremarkable. The omentum and pelvic lymph nodes were free of tumor.
The gross feature of the recurrent tumor from her second operation was unavailable in detail. Pathological review of the slides indicated that the recurrent tumor was consisted of poorly-differentiated adenocarcinoma in the fibrous stroma resembling to the original ovarian carcinoma. The tumor involved the outer intestinal muscular proper, but the intestinal mucosa remained normal after careful and extensive sampling. The excision margins were free of tumor.