Clinicopathological features and risk factors of lymph node metastasis of gastrointestinal neuroendocrine neoplasms in 467 patients

Abstract

Objective To investigate the clinicopathological features and risk factors of lymph node metastasis of gastrointestinal neuroendocrine neoplasms (GI-NENs). Methods The retrospective case-control study was conducted. The clinicopathological data of 467 patients with GI-NENs who were admitted to the Fourth Hospital of Hebei Medical University from January 2006 to December 2015 were collected. Observation indicators: (1) occurrence sites and pathological classification of GI-NENs; (2) pathological characteristics of surgical specimens of GI-NENs; (3) univariate analysis and multivariate analysis affecting lymph node metastasis of GI-NENs: sex, age, tumor location, tumor diameter, pathological classification, pathological stage and tumor invasive depth. The univariate analysis and multivariate analysis were respectively done using the chi-square test and Logistic regression model. Results (1) Occurrence sites and pathological classification of GI-NENs: of 467 patients with GI-NENs, tumors of 304, 15, 7, 14 and 127 patients were located at stomach, duodenum, small intestine, colon and rectum, respectively. Tumor diameter was 0.3-12.0 cm, with an average diameter of 2.2 cm. Of 467 patients with GI-NENs, G1 and G2 of neuroendocrine tumors (NETs), G3 of neumendocfine carcinomas (NECs) and mixed adenoneuroendocfine carcinomas (MANECs) were respectively detected in 209, 64, 146 and 48 patients. Lymph node metastasis rate of GI-NENs was 31.48%(147/467). (2) Pathological characteristics of surgical specimens of GI-NENs: NETs were high-differentiated NENs. Cells of NETs were solid and nest-, trabeculum- and tubular-shaped, and consisted of small or medium cells, with moderate amount or massive cytoplasms, round or oval nucleus, particle-shaped chromatin, unobvious nucleolus and positive endocrine markers. There were abundant of small blood vessels and surrounding fibrous stroma in peripheral tumor cell nests. NECs were low-differentiated NENs and included small cell carcinoma and large cell NEC. Cells of small cell carcinoma were small round or oval and looked similar to lymphocytes, with few amount cytoplasms, fine granular-shaped or hyperchromatic nucleus and common mitosis figures. Cells of large cell NEC were large and greater than 3 lymphocytes, arrayed in organoid- or chrysanthemum-shape, with massive cytoplasms, coarse particle-shaped chromatin, obvious nucleus, clear mitosis figures and large laminar-shaped necrosis. There were different positive expressions of endocrine markers between small cell carcinoma and large cell NEC. MANECs had the characteristics of glandular cavity formation of traditional adenocarcinoma and NENs. Results of immuno-histochemical staining in 467 patients showed that Ki-67 of 467 patients was positive; CD56 in 379 of 428 with CD56 test was positive; synaptophysin (Syn) in 416 of 422 with Syn test was positive; cytokeratin (CK) in 354 of 396 with CK test was positive; chromogranin (CgA)in 264 of 388 with CgA test was positive; neuron specific enolase (NSE) in 287 of 346 with NSE test was positive. (3) Univariate analysis and multivariate analysis affecting lymph node metastasis of GI-NENs: results of univariate analysis showed that sex, tumor location, tumor diameter, pathological classification, pathological satge and tumor invasive depth were related factors affecting lymph node metastasis of patients with GI-NENs (χ2=20.654, 18.182, 26.788, 184.709, 163.738, 195.391, P<0.05). Results of multivariate analysis showed that pathological classification and pathological stage were independent influenced factors affecting lymph node metastasis of patients with GI-NENs (HR=2.129, 7.171, 95% confidence interval: 1.273-3.561, -2.327-22.098, P<0.05). Conclusions GI-NENs are mostly located on the stomach and rectum. Results of immunohistochemical staining could help diagnosis of GI-NENs. Pathological classification and pathological stage are independent influenced factors affecting lymph node metastasis of patients with GI-NENs. Key words: Neuroendocrine neoplasms; Gastrointestinal tract; Pathology; Lymph node metastasis