Rare Case of Appendiceal Signet-ring Cell Carcinoma Mimicking Advanced Ovarian Cancer

The incidence of primary carcinoma of the appendix is extremely low, affecting approximately 1–2/100,000 people each year in the United States.[] The signet-ring cell subtype is particularly rare, comprising 4% of all appendiceal carcinomas.[] Symptoms of appendiceal cancer are often nonspecific and most commonly present as right lower quadrant abdominal pain; it can mimic several diseases originating from the pelvic cavity, such as acute appendicitis, ovarian cancer, or other diseases related to the adnexa. Hence, primary cancers of the appendix are frequently diagnosed after surgery for appendicitis, presumed ovarian malignancies, or other reasons.[] In this article, we present a patient with an initial diagnosis of advanced right ovarian cancer. She underwent suboptimal debulking surgery because of extensive disseminated peritoneal metastasis. The final pathology revealed primary signet-ring cell carcinoma of the appendix. CASE REPORT A 68-year-old multiparous woman with no known medical or surgical history complained of abdominal distension for 1 month. She denied a loss of body weight, easy satiety, vomiting, abdominal pain, constipation, bloody stool, pencil stool, or irregular vaginal bleeding. On pelvic examination, a mass greater than the size of a fetal head was palpated over the right lower quadrant of her abdomen. Ultrasound displayed a cystic mass arising from the right pelvic cavity with a solid component measuring 15.8 cm × 10 cm [Figure 1]. Due to the impression of ovarian cancer, computed tomography (CT) was performed, and blood was drawn for tumor markers. The CT scan showed peritoneal seeding and a right ovarian tumor densely adhered to the uterus, bowel, and omentum [Figures 2 and 3]. No gastrointestinal tract tumor was suspected and no lymphadenopathy was detected. Elevated tumor markers, namely carcinoembryonic antigen (CEA; 750.3 ng/mL), cancer antigen 125 (CA125; 841.6 U/mL), and carbohydrate antigen 19-9 (CA19-9; 7328.3 U/mL), were noted. Since no gastrointestinal tract lesion was identified by CT scan, panendoscopy and colonoscopy were omitted. She underwent cytoreductive surgery for advanced ovarian cancer. During surgery, the adhesion between the appendix and ovarian tumor was inseparable, and an appendectomy was performed. The contralateral ovary was also involved. A frozen section of the ovarian tumor [Figure 4] was identified as a signet-ring cell tumor. Malignancy originating from the gastrointestinal tract was impressed. Because of extensive peritoneal carcinomatosis, suboptimal debulking surgery was conducted. Subsequent panendoscopy and colonoscopy both resulted in negative findings. The final pathology report revealed appendiceal adenocarcinoma of a signet-ring type [Figure 5] with bilateral adnexa, uterus, and omentum metastasis. The appendiceal tumor was immunopositive for CK7 [Figure 6] and CDX-2 [Figure 7]. After surgery, she received six courses of chemotherapy with irinotecan hydrochloride trihydrate, folinic acid, and fluorouracil. When her CEA level had decreased to 17.8 ng/mL, she rejected further treatment. Eight months after the last course of chemotherapy, she presented to the emergency room (ER) with dyspnea, abdominal distension, and bilateral leg edema. A thorough examination revealed massive ascites with spontaneous bacterial peritonitis and acute renal failure. She opted for palliative treatment and died of septic shock 10 days after her admission to the ER.

The incidence of signet-ring cell carcinoma of the appendix is less than 5% of all appendiceal tumors, and the clinical symptoms are indistinguishable from those arising from the right lower quadrant abdominal cavity. The most common clinical complaint is abdominal pain in the lower right quadrant, which is similar to that of acute appendicitis.[] Preoperative detection can be used to design an appropriate surgical resection, but making an accurate diagnosis is not often possible before surgery.[] Radiologic techniques, such as CT of the appendix, are nonspecific for appendiceal cancer.[] Cho proposed that patients with concentric hypoechoic mucosal thickening and certain clinical presentations, such as potential ovarian or peritoneal metastasis or submucosal infiltrative tumors, including signet-ring cell carcinoma, should be examined to obtain another diagnosis.[] Appendiceal sonography may be done when large pelvic tumors arising from the right pelvic cavity are seen. If the ultrasound image of the appendix shows a concentrically thickened wall with a hypoechoic submucosal and muscle layer, then signet-ring cell carcinoma should be considered in the differential diagnosis. No specific CT findings distinguish signet-ring cell carcinoma from other histological types, except those that indicate a spread to adjacent organs (76%) at presentation.[] An accurate diagnosis and precise staging warrant a right hemicolectomy, a suitable surgical treatment.[] Because of its aggressive behavior, close follow-up is necessary after cytoreductive surgery and chemotherapy. Our patient complained of abdominal fullness, which is nonspecific for appendiceal tumors. The correct diagnosis was determined only after debulking surgery, which was initially performed for ovarian malignancy. Although she received six courses of chemotherapy, the disease failed to respond. This clinical circumstance is consistent with the knowledge of signet-ring cell carcinoma, and a preoperative diagnosis remains a challenge for appropriate surgical planning. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

- 1. McCusker ME, Coté TR, Clegg LX, Sobin LH. Primary malignant neoplasms of the appendix: A population-based study from the surveillance, epidemiology and end-results program, 1973-1998 Cancer. 2002;94:3307–12 - 2. McGory ML, Maggard MA, Kang H, O'Connell JB, Ko CY. Malignancies of the appendix: Beyond case series reports Dis Colon Rectum. 2005;48:2264–71 - 3. Kelly KJ. Management of appendix cancer Clin Colon Rectal Surg. 2015;28:247–55 - 4. Fusari M, Sorrentino N, Bottazzi EC, Del Vecchio W, Cozzolino I, Maurea S, et al Primary signet ring cell carcinoma of the appendix mimicking acute appendicitis Acta Radiol Short Rep. 2012;1 arsr. 2012.120017 - 5. Ko YH, Jung CK, Oh SN, Kim TH, Won HS, Kang JH, et al Primary signet ring cell carcinoma of the appendix: A rare case report and our 18-year experience World J Gastroenterol. 2008;14:5763–8 - 6. Cho YJ, Kim HJ, Jang SK, Yeon JW, Kim KH, Paik SY. Signet-ring cell carcinoma of the appendix: A case report with an emphasis on sonographic findings Ultrasonography. 2016;35:164–7 - 7. Zhou ML, Yan FH, Xu PJ, Zhang LJ, Li QH, Ji Y. Mucinous cystadenoma of the appendix: CT findings Chin Med J (Engl). 2006;119:1300–3 - 8. Deans GT, Spence RA. Neoplastic lesions of the appendix Br J Surg. 1995;82:299–306