Risk factors for progression of appendiceal neuroendocrine tumours: low‐stage tumours <5 mm appear to be overwhelmingly indolent and may merit a separate designation

Abstract

Aims Appendiceal well‐differentiated neuroendocrine tumours (NETs) are usually incidental and clinically benign. Several studies have reported different risk factors for nodal metastasis. The aim of this study was to investigate our appendiceal NETs (App‐NETs) to determine the factors associated with malignant behaviour. Methods and results For 120 App‐NETs, we reviewed the clinical presentation and follow‐up, including serum chromogranin A (CgA) levels, and compiled several microscopic variables. Pathological factors were compared with nodal status and time to biochemical recurrence (elevated serum CgA level) by the use of Cox regression. We also reviewed similar App‐NET data in the Surveillance, Epidemiology, and End Results (SEER) Programme. Among our 120 cases, seven patients had positive lymph nodes, and nine developed subsequent elevation of CgA levels; none developed distant metastases or died of disease. Only three patients had grade 2 NETs; none had nodal disease, and one developed an elevated CgA level. Increasing tumour size was associated with an increased risk of nodal disease [odds ratio (OR) 4.99, P = 0.0055). All seven node‐positive cases were ≥13 mm. Factors associated with elevated CgA levels included age (OR 1.04, P = 0.041), pT4 disease (OR 10.22, P = 0.033), and nodal disease (OR 24.0, P = 0.012), but not size (OR 2.13, P = 0.072). Of the 1492 reported App‐NETs in the SEER database with data on tumour size, 137 (9%) were pN1; only five of these (4%) were coded as being <5 mm. Conclusions Small (<5 mm) App‐NETs that do not invade the serosa or mesoappendix appear to be overwhelmingly benign and low‐grade, requiring neither Ki67 staining nor synoptic reporting. Given their indolent behaviour, different nomenclature or staging may be more appropriate for these NETs.

Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy

“…Tubular NETs: These tumors represent < 10% of all aNETs[ 8 ] and must be distinguished from adenocarcinoma NOS and goblet cell adenocarcinoma[ 14 ].…”

“…After a CRH, residual disease or lymph node involvement is present in 0% to 40% of cases[ 2 , 8 , 28 ]. A recent review by Webb et al [ 11 ] of patients in the National Cancer Database treated with surgery found that, unlike other types of appendiceal neoplasms, in aNET, the presence of regional LNM does not reduce overall survival.…”

“…Tumor size: Some recent studies suggest that size is the main factor related to the occurrence of LNM[ 1 , 8 , 15 , 29 , 30 ]. As stated above, controversy arises in aNETs that are greater than 2 cm and those from 1 to 2 cm, which represent from 3% to 7% and from 20% to 25% of cases, respectively[ 8 , 28 ]. The 10-year survival rate according to size is 100%, 92%, and 91% for < 1 cm, 1 to 2 cm, and > 2 cm, respectively[ 31 ].…”

“…The main purpose of a CRH is to complete the regional lymph node dissection. These nodes are involved in 6% to 9% of cases[ 8 ]. Both the North American Neuroendocrine Tumor Society[ 9 ] and European Neuroendocrine Tumor Society (ENETS)[ 10 ] guidelines suggest a tailored approach to these patients based on features such as tumor size, margin status, mesoappendix infiltration, vascular and lymphatic invasion, and tumor grade.…”

“…In tumors between 1 and 2 cm, CRH should be considered when there are affected margins in tumors located at the base, when there is invasion of the mesoappendix that measures greater than 3 mm, or when there are other risk factors. However, several studies have challenged these recommendations, mainly in tumors smaller than 2 cm, arguing that CRH offers no benefits in terms of survival in tumors smaller than 2 cm[ 8 , 11 ]. Furthermore, in addition to the potential postoperative complications, a colectomy could lead to a poorer quality of life for these patients.…”