Mesenteric Tumor Deposits in Midgut Small Intestinal Neuroendocrine Tumors Are a Stronger Indicator Than Lymph Node Metastasis for Liver Metastasis and Poor Prognosis

Abstract

Background Mesenteric tumor deposits (MTDs) are not included in the American Joint Committee on Cancer (AJCC) staging system for midgut small intestinal neuroendocrine tumors (NETs). We examined the prognostic significance of MTDs associated with midgut NETs. Materials and Methods H&E slides from 132 resected jejunal/ileal NETs were reviewed for AJCC tumor stage, lymph node (LN) metastasis, MTDs, and hepatic metastases. MTDs were defined as discrete irregular mesenteric tumor nodules discontinuous from the primary tumor. Clinical or pathological evidence of metastases and survival data were abstracted from electronic medical records. Results The cohort included 72 males and 60 females with a median age of 60 years. LN metastasis, MTDs, and liver metastasis were present in 80%, 68%, and 58% of patients, respectively. Female sex and presence of MTDs were independent predictors of liver metastasis. The odds ratio for hepatic metastasis in the presence of MTDs was 16.68 (95% CI, 4.66–59.73) and 0.81 (95% CI, 0.20–3.26) for LN metastasis. Age, MTDs, and hepatic metastasis were associated with disease-specific survival (DSS) in univariate analysis. Primary tumor histologic grade, pT3/T4 stage and LN metastasis were not associated with DSS. Multivariate analysis of liver metastasis-free survival stratified by tumor grade showed that MTDs were associated with adverse outcomes. The hazard ratio for MTDs was 4.58 (95% CI, 1.89 – 11.11), compared to 0.98 (95% CI, 0.47 – 2.05) for LN metastasis. Conclusion MTDs, but not LN metastasis, in midgut neuroendocrine tumors are a strong predictor for hepatic metastasis and are associated with poor DSS.

Mesenteric tumour deposits arising from small‐intestine neuroendocrine tumours are frequently associated with fibrosis and IgG4‐expressing plasma cells

“…Signs and symptoms of small‐bowel obstruction/ischaemia may also occur in small‐intestine NET patients when large MTDs cause kinking of the bowel and encasing of large mesenteric vessels. Additionally, patients with MTDs frequently have liver metastasis, and they can develop carcinoid syndrome when there are extensive liver metastases. Radiographically, both entities appear as a soft‐tissue mesenteric mass with radiating fibrotic bands in a stellate pattern; however, MTDs tend to encase and invade mesenteric vessels, whereas sclerosing mesenteritis often spares mesenteric fat immediately surrounding vessels, producing a ‘fat ring sign’ .…”

“…Seventy patients with MTD(s) arising in small‐intestine NET were identified from our pathology archives between 1 January 1996 and 1 July 2017; 66 of these had at least one MTD block available for immunohistochemical (IHC) staining. MTDs were defined as discrete tumour nodules within mesenteric soft tissues with an irregular growth pattern . Lesions resulting from direct contiguous spread by the primary lesion or extranodal extension were excluded.…”

“…MTDs were defined as discrete tumour nodules within mesenteric soft tissues with an irregular growth pattern. 5,6 Lesions resulting from direct contiguous spread by the primary lesion or extranodal extension were excluded. Patient electronic medical records were reviewed for demographic information, including age, sex, and clinical history.…”

“…They are frequently associated with lymph node metastasis and mesenteric tumour deposits (MTDs), both of which alter the overall stage in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for small‐intestine NETs . MTDs are defined as discrete but irregular mesenteric tumour nodules discontinuous from the primary neoplasm; they are associated with frequent liver metastasis and a poor prognosis . In addition, MTDs are frequently associated with dense fibrosis, which can lead to entrapment of adjacent large mesenteric vessels and nerves.…”

“…[3][4][5] MTDs are defined as discrete but irregular mesenteric tumour nodules discontinuous from the primary neoplasm; they are associated with frequent liver metastasis and a poor prognosis. 5,6 In addition, MTDs are frequently associated with dense fibrosis, which can lead to entrapment of adjacent large mesenteric vessels and nerves. Because of this dense fibrotic response to tumour, MTDs can radiographically simulate IgG4-related sclerosing mesenteritis, complicating diagnosis by imaging and necessitating tissue diagnosis.…”