Appendiceal Well-Differentiated Neuroendocrine Tumors: A Single-Center Experience and New Insights into the Effective Use of Immunohistochemistry.

Abstract

Background. Appendiceal well-differentiated neuroendocrine tumor is the most common histological type of appendiceal tumor. The majority of tumors are found incidentally at the tip of the appendix, with few exceptions. Due to its primarily indolent nature, this entity presents unique pathological challenges, particularly in the appropriate use of immunohistochemistry which this study aims to clarify. Patients and methods. Patients diagnosed at University Health Network (Canada) between 2005-2019 were selected and reviewed. Results. We identified 70 patients and sex distribution was female 60%; median age 36.5 years. Among them, 63 patients underwent appendectomy, and seven had initial right hemicolectomy for non-appendix lesions. Mean tumor size was 5.0 mm. Tumor extent was submucosa (15%); muscularis propria (34%); subserosa or mesoappendix (42%); visceral peritoneum (8%). All were clinically non-functional and negative for nodal and distant metastasis. Ninety percent of tumors were WHO Grade 1; 10% were WHO Grade 2. Immunohistochemically, an average of six stains were performed per patient. Nearly all tumors were positive for chromogranin A, synaptophysin, CAM5.2, and CDX2. MIB-1 staining was < 3% in 58/63 tumors. Other immunohistochemical stainings performed were hormonal markers (serotonin, glucagon, pancreatic peptide, peptide YY). Subsequent right hemicolectomy was performed on five patients. All were followed up (median 4 years 8 months), and all were alive without recurrence except for one patient who died of another comorbidity. Conclusion. Tumors that are small, localized, and of low grade can be reasonably exempt from an extensive immunohistochemical panel in the absence of non-typical clinical and morphological features.