Is Multifocality an Indicator of Aggressive Behavior in Small Bowel Neuroendocrine Tumors?

Abstract

Objectives Many patients with small bowel neuroendocrine tumors (SBNETs) have multifocal tumors (MFTs), but the frequency of MFTs has varied widely across SBNET studies. It is also unclear whether patients with MFTs have more advanced disease or worse clinical course than those with unifocal SBNETs (UFTs). We set out to determine the frequency of multifocal and unifocal SBNETs, compare clinicopathologic factors, somatostatin receptor (SSTR2) expression, and survival. Methods Clinicopathologic variables from 179 patients with surgically managed SBNETs were collected. Statistical comparisons were made using Welch’s t-test, Wilcoxon test and Fisher’s exact test. Survival was assessed using the Kaplan-Meier method. SSTR2 expression was analyzed by qPC, and Ki-67 expression by immunohistochemistry. Results MFTs were found in 45% of patients with SBNETs. Clinicopathologic factors such as grade, TNM stage, presence of distant metastases, mean SSTR2 expression, success of imaging modalities, preoperative and postoperative hormone levels were not significantly different between multifocal and unifocal groups. Progression-free and overall survival were also not significantly affected by multifocality. Conclusions Clinicopathologic features and survival of patients with MFTs and UFTs are remarkably similar. Although the etiology of MFTs is unclear, patients with MFTs do not have a more aggressive clinical course than patients with unifocal SBNETs.

Should Ki67 immunohistochemistry be performed on all lesions in multifocal small intestinal neuroendocrine tumours?

“…studied 68 SI‐NET patients (50 with unifocal and 18 with multifocal disease), concluding that multifocal disease occurred in younger patients (in contrast to findings in our study) and conferred a worse prognosis on multivariate, stage‐adjusted analysis . In contrast, two other more recent and larger series of SI‐NETs are concordant with our findings that tumour focality has no bearing on SI‐NET recurrence or prognosis . (It should be noted that our high proportion of grade 1 SI‐NETs, relatively short follow‐up and relatively few deaths from disease in our cohort make it difficult to assert that unifocal and multifocal disease have different prognoses based solely on our findings.)…”

“…(It should be noted that our high proportion of grade 1 SI‐NETs, relatively short follow‐up and relatively few deaths from disease in our cohort make it difficult to assert that unifocal and multifocal disease have different prognoses based solely on our findings.) The former, but not the latter, study also found a higher rate of nodal metastasis in multifocal SI‐NETs.…”

“…Our study is somewhat unique, in that we found a very high proportion of grade 1 tumours in our SI‐NET cohort. All but six of our 207 SI‐NETs were grade 1, for a rate of 97%; other studies have reported rates from 58% to 86% . Our grade distribution may have admittedly skewed some results, as upgrading a patient to grade 2 or grade 3 disease was unlikely if almost no lesions were grades 2 or 3.…”

“…7 In contrast, two other more recent and larger series of SI-NETs are concordant with our findings that tumour focality has no bearing on SI-NET recurrence or prognosis. 6,20 (It should be noted that our high proportion of grade 1 SI-NETs, relatively short follow-up and relatively few deaths from disease in our cohort make it difficult to assert that unifocal and multifocal disease have different prognoses based solely on our findings.) The former, 6 but not the latter, 20 study also found a higher rate of nodal metastasis in multifocal SI-NETs.…”

“…All but six of our 207 SI-NETs were grade 1, for a rate of 97%; other studies have reported rates from 58% to 86%. 6,[19][20][21] Our grade distribution may have admittedly skewed some results, as upgrading a patient to grade 2 or grade 3 disease was unlikely if almost no lesions were grades 2 or 3. The reason for the grade distribution in our cohort is unclear.…”