Appendiceal Neuroendocrine Carcinoma Sized 18 mm with Metastasis in one of 36 Lymph Nodes

Introduction

Tumors originating from neuroendocrine cells of the gastrointestinal tract, lung or pancreas are rare, both in adults and children. Differentiated gastroenteropancreatic neuroendocrine tumors – carcinoids, according to the traditional terminology – represent the largest subgroup [1]. The appendix represents the most common site for these tumors, especially in children, and they are the most common malignant appendiceal tumors, accounting for about 50% of cases [1] [2]. Around 0.3–1% of malignant tumors are found in appendectomy specimens [1] [2] [3], which translates as 2.5–5 cases/100000 persons per year [4].

While other neuroendocrine tumors often cause symptoms such as diarrhea, bronchospasm, or flushing [5], most neuroendocrine tumors of the appendix manifest as appendicitis and are thus usually diagnosed after appendectomy, even if positive for serotonin, gastrin or other neuroendocrine compounds [6]. Histologically, most are classified as either classical or atypical [2], with a lower incidence of malignant tumors such as mixed adenocarcinomas which have a worse prognosis [1] [2]. The histological classification system currently in use is the AJCC/UICC (American Joint Cancer Committee/Union Internationale contre le Cancer) TNM system (2009), which primarily separates highly differentiated neuroendocrine tumors from highly differentiated neuroendocrine carcinomas and dedifferentiated carcinomas [7] [8].

Neuroendocrine tumors of the appendix originate from the enterochromaffin cells at the base of the Lieberkühn crypts [3] and infiltrate the submucosa, the muscularis propria, and the serosa, finally invading the mesenteric lymph nodes [5]. Analyzing 900 cases of neuroendocrine tumors of the appendix in adults, Landry et al. found lymph node metastases in 137 patients (24%), and distant metastases in 89 (10%) [8]. While tumors with diameters of less than 1 cm or with diameters between 1 and 2 cm had an equal prognosis, the prognosis for tumors exceeding 2 cm was worse [8]. In adults, therefore extended dissection and lymph node revision are generally recommended in all cases where tumor diameters exceed 2 cm.

In children and adolescents, other limits might be appropriate. The GPOH-MET97 trial, a German prospective interdisciplinary multicenter trial of malignant endocrine tumors in children and adolescents, currently recommends extended surgery in cases where the diameter exceeds 1.5 cm, but the discussion is still ongoing [9] [10] [11].

The prognosis for neuroendocrine tumors of the appendix is excellent with a 5-year survival rate of 99% [3]; however, in view of the potential for invasion and metastasis, careful staging with consideration of the therapeutic options is mandatory.

We report here on a 12-year-old boy with an appendiceal neuroendocrine carcinoma with a diameter of 18 mm and metastasis in one of 36 lymph nodes.

• References

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