1.1. Background: Neuroendocrine Carcinoma (NEC) of the appendix is extremely rare and its clinical characteristics and treatment strategy have not been well established. Here we present a case of appendiceal NEC with very rapid progression, in which complete remission was achieved by radical surgery followed by systemic chemotherapy.
1.2. Case presentation: A 50-year-old woman presented with right lower quadrant abdominal pain and low-grade fever. She underwent laparoscopic appendectomy based on the diagnosis of acute appendicitis with mucinous cystadenoma of the appendix. The resected specimen showed a 2.5- cm tumor at the base of the appendix. Immunohistochemistry revealed diffuse staining for synaptophysin and a Ki-67 labeling index of >90%. The case was diagnosed as NEC according to the 2010 World Health Organization classification. One month after appendectomy, we performed right hemicolectomy with extended lymph node dissection for metastatic lymph nodes around the ileocolic and superior mesenteric vessels. Pathological examination revealed metastases in 27 of 42 dissected lymph nodes, including lymph nodes around the root of the superior mesenteric artery and superior mesenteric vein. One month after right hemicolectomy, metastasis to Virchow’s lymph node was detected. After six cycles of chemotherapy with etoposide and cisplatin, complete remission was achieved and was maintained at the 3-year follow-up after initial surgery.
1.3. Conclusion: Right hemicolectomy with extended lymph node dissection followed by chemotherapy with etoposide and cisplatin may be a viable treatment strategy for appendiceal NEC.
Keywords:Appendiceal neoplasms; Neuroendocrine carcinoma; Neuroendocrine tumor; World Health Organization classification
2. IntroductionThe World Health Organization (WHO) diagnostic criteria for neuroendocrine tumors (NETs) and neuroendocrine carcinoma (NEC) of the gastrointestinal tract were published in 2010 [1]. NEC is defined as a small cell or large cell carcinoma with a mitotic rate of more than 20 per 10 high power fields and/or a Ki-67 labeling index of >20%. Thus, all poorly differentiated neoplasms are classified as NEC, which constitutes a separate group from NET given its invariable high-grade malignant potential. NEC is characterized by diffuse immunostaining for synaptophysin, and only infrequent and sparse immunostaining for chromogranin A [1, 2]. Appendiceal NEC, which is distinct from mixed adenoneuroendocrine carcinoma (MANEC), is extremely rare, and its clinical characteristics are not well established. A literature review in PubMed revealed only two case reports on appendiceal NEC [3, 4]. In this report, we describe a case of appendiceal NEC with very rapid progression, in which complete remission was achieved by radical surgery followed by systemic chemotherapy
3. Case PresentationA 50-year-old woman was referred to our hospital with complaints of right lower quadrant abdominal pain and prolonged fever for over a week. Her medical history was unremarkable. On physical examination, we noted tenderness at McBurney’s point with mild rebound tenderness. Computed tomography (CT) revealed an enlarged appendix, with wall thickening and a cystic lesion at the appendiceal tip (Figure 1A, B). Under the diagnosis of acute appendicitis with mucinous cystadenoma of the appendix, she underwent laparoscopic appendectomy. During the operation, there were no findings indicative of malignancy (Figure 1C). There were no postoperative complications, and she was discharged six days postoperatively. Analysis of the resected specimen revealed wall thickening at the base of appendix, and the peripheral side was filled with mucous (Figure 1D). The cut end was intact. The tumor size was 2.5 × 2.5 cm, and microscopic observation showed tumor cells with hyperchromatic nuclei forming a sheetlike structure in the submucosa, with low- and high-grade tubulo-villous adenoma in the mucosa. The tumor invaded the muscularis propria. Immunohistochemical analysis of the tumor revealed a neuroendocrine tumor with positive staining for synaptophysin (Figure 2) and CD-56. Based on these findings, neuroendocrine neoplasm (NEN) was suspected. Chromogranin A staining was negative. The Ki- 67 labeling index was ≥90%, confirming that the tumor was a NEC according to the 2010 WHO classification. Focal squamous differentiation was observed, as well as lymphatic and venous invasion. The T-stage of the appendiceal NEN was T3 according to European Neuroendocrine Tumor Society (ENETS) staging [5] and T2 according to Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) staging [6].
4. Discussion and ConclusionsHere, we describe a rare case of appendiceal NEC. Despite having rap idly progressed through the lymphatic system, complete remission was achieved by radical surgery followed by systemic chemotherapy. Right hemicolectomy with extended lymph node dissection followed by chemotherapy with etoposide and cisplatin may be a viable treatment for appendiceal NEC. According to the Surveillance Epidemiology and End Results (SEER) database, appendiceal NEN has an incidence rate of approximately 0.15–0.6 cases per 100000 people per year, with a slight female preponderance and a mean patient age of 38–48 years [7]. Approximately 60-75% of appendiceal NENs occur in the tip of the appendix [5, 8]. Most appendiceal NENs are diagnosed incidentally during appendectomy for acute appendicitis, at a rate of 3-5/1000 appendectomies [5]. According to the WHO classification scheme, appendiceal NENs are classified as gastrointestinal NENs, and evaluated according to tumor size, mitotic index, and prolifer ative index [1]. Regarding staging, two different TNM staging systems are used: the one proposed by ENETS [5] and the one proposed by the UICC/ AJCC [6]. Whereas most NETs with localized lesions have a very good prognosis [5, 9,10], NEC has a very poor prognosis [11]. So far, very few cases of appendiceal NEC have been reported in the literature. O’Kane et al. [3] reported a case of small cell carcinoma of the appendix with multiple liver metastasis and para-aortic lymphadenopathy. Despite undergoing right hemicolectomy and palliative chemotherapy, the patient died two months after surgery. The tumor was positive for synaptophysin by immunohistochemistry, and the Ki-67 staining index was approximately 90%. Thus, the diagnosis was NEC according to the 2010 WHO classification. Tomioka et al. [4] reported a case of appendiceal NEC without any metastasis. The tumor was diagnosed after appendectomy for acute appendicitis, and a few weeks later, ileocecal resection with lymphadenectomy was performed. No regional lymph node metastasis was observed. The patient declined adjuvant chemotherapy and was disease free at five months after initial surgery. Another case reported as appendiceal NEC in 2006 does not appear to be currently classified as NEC according to the 2010 WHO classification because the tumor was a well-differentiated NET [12].
5. AcknowledgementsSM and DS designed the report and wrote the initial draft of the manuscript; HT performed the pathological diagnosis and assisted in the preparation of the manuscript; and TO, MI, and YK contributed to data collection and interpretation, and critically reviewed the manuscript. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Satoko Ejima Monma. Primary Neuroendocrine Carcinoma of the Appendix: A Case Report. Annals of Clinical and Medical Case Reports 2021