A 47-year-old female presented to the emergency room with complaints of ongoing abdominal pain for 2 weeks. The patient had no medical problems and had not had any surgical procedures in the past.
At presentation, the patient’s computed tomography (CT) scan of the abdomen and pelvis showed bilateral complex adnexal masses measuring approximately 17 and 14 cm in greatest dimension and a large amount of abdominal and pelvic ascites. The findings were suspicious for neoplastic disease and the patient subsequently underwent exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oopherectomy.
The frozen section of the specimen obtained during the procedure favored metastatic tumor described as signet ring cell carcinoid. Hence, an appendectomy was also performed. The cytology of ascitic fluid drained during the procedure showed rare clusters of atypical cells suspicious for carcinoma.
The final pathology was consistent with adenocarcinoma ex-goblet cell carcinoid, signet ring cell type. The size of the tumor was 2.2 cm in the greatest dimension predominantly in the distal half of the appendix with extension into the proximal half. Extensive lympho-vascular invasion and focal peri-neural invasion was identified. Pathologic staging was consistent with pT3 (tumor invading through the muscularis propria into the sub-serosa or mesoappendix), pNx (no lymph nodes were identified in the specimen), and M1b (non-peritoneal metastases present in the ovaries and fallopian tubes). Immunohistochemistry was positive for CDX2, CD56, CEAP (focally), synaptophysin, Cam 5.2, and pancytokeratin with Ki 67 being over 10%. Mucicarmine and periodic acid-Schiff (PAS) stains confirmed presence of intracytoplasmic mucin in signet ring cells (Fig. 1). Additional staining was performed including beta-catenin (negative), MUC-1, and MUC-2 (positive). Mutation testing for BRAF V600, KRAS at codons 12 and 13, and NRAS was reported negative.
Treatment & use of biomarker
Given the aggressive nature of reported cases and metastatic nature of the disease, a decision was made to treat the patient with adjuvant chemotherapy with a fluorouracil-based regimen. The patient’s CA-125 level at the time was 41 units/ml and carcinoembryonic antigen (CEA) level was 1 ng/ml. A PET-CT scan done to complete staging showed a focal area of non-specific hypermetabolic uptake adjacent to the appendectomy bed likely related to post-surgical changes. No other regions of pathologic FDG uptake were seen.
The patient was started on chemotherapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) and follow-up imaging 4 and 8 months after diagnosis did not show any evidence of disease. Her CA 125 level at 4 months was down to 14 units/ml, and 16 units/ml at 8 months. The patient completed 16 cycles of chemotherapy without any complications and a decision was made to observe her thereafter. Sixteen months into diagnosis, she remains without any evidence of disease. It is planned to monitor her periodically with a CA 125 level and radiologic imaging.