TNM stage and grade in predicting the prognosis of operated, non-functioning neuroendocrine carcinoma of the pancreas--a single-institution experience.

OBJECTIVE: To evaluate the prognostic significance of TNM and grading categories in curatively resected non-functioning neuroendocrine pancreatic carcinoma (nfnepC). METHOD: Eighteen nfnepC were retrospectively analyzed for differences in survival. RESULTS: (1) There was a correlation between pT (P = 0.026), respectively pM categories (P = 0.016) and survival. (2) G categories and length of survival were closely correlated (P = 0.0036). (3) Disease stages I-IV had a significant effect on survival (P = 0.051). (4) The WHO classification in well and poorly differentiated carcinomas proved to be the most conclusive predictive factor (P = 0.0009). (5) Subgroups with significantly different prognoses determined by histological grade were present within disease stage II. CONCLUSIONS: The retrospective analysis showed a good correlation between survival and pT, pM, tumor stage, G categories, and WHO classification in well and poorly differentiated carcinomas. Including histological differentiation in the staging system or carrying it out separately in well and poorly differentiated carcinomas, could enhance the predictive potential of TNM-based disease stages.

Ductulo-insular pancreatic endocrine neoplasms: clinicopathologic analysis of a unique subtype of pancreatic endocrine neoplasms.

Pancreatic neoplasms with mixed ductal and endocrine components are a heterogeneous group of tumors. The least recognized of these are pancreatic endocrine tumors (PETs) displaying benign-appearing tumor-associated ductules. To characterize these ductulo-insular pancreatic endocrine tumors (DI-PETs), we reviewed a series of 92 resected PETs. To be considered as a DI-PET we required the presence and tight intermingling of ductules with the dominant endocrine component (including the presence of ductulo-insular units). A total of 15 PETs fulfilled our criteria (16.3%). The average age of the DI-PET patients was similar to typical PETs (54 years vs 56 years). These tumors were smaller and more often insulin positive than typical PETs (p <0.05). Diffuse stromal fibrosis was more frequent in DI-PETs (11 of 15; 73.3.7%) compared with PETs (8 of 72; 11.1%) (p <0.05). The tumor-associated ductules were composed of cuboidal cells with dense eosinophilic cytoplasm and round nuclei without atypia or mitoses. They were positive for cytokeratin 7 and cytokeratin 19 and lacked any neuroendocrine markers. Reversibly, the endocrine component was negative for cytokeratin 7 and cytokeratin 19 and positive for neuroendocrine markers. Ultrastructural examination of ductulo-insular units confirmed a dual ductal and endocrine differentiation with amphicrine differentiation in one case. Follow-up was available in 12 cases with an average follow-up of 70.1 months (range 25-203 months). Ten patients are currently alive, and two patients died 81 and 158 months after surgery. We conclude that DI-PETs are not uncommon and that they are biologically similar to other PETs. We also hypothesize that the ductal cells develop by transdifferentiation of the endocrine cells.

Cellular composition and anatomic distribution in nonfunctioning pancreatic endocrine tumors: immunohistochemical study of 30 cases.

OBJECTIVE: To investigate the cytological pattern and distribution in nonfunctioning pancreatic endocrine tumors. METHODS: Using labeled streptavidin-biotin (LSAB), immunohistochemical staining for insulin, glucagon, somatostatin, pancreatic polypeptide and gastrin was performed on 30 nonfunctioning pancreatic endocrine tumors from 30 patients. The cellular composition and anatomic distribution in these tumors were analyzed. RESULTS: Of 30 tumor tissues, 22 (73.3%) were found to contain cells immunoreactive to 1-4 kinds of peptide hormones; 17 (56.7%) showed positive staining for more than one peptide and up to 4 peptides; and 8 (26.7%) showed negative immunoreaction to all antiserum applied. No tumor was found to contain immunoreactive gastrin. Among 17 multihormonal tumors, 4 contained 2 kinds of peptide hormones, 8 had 3 kinds, and 5 harbored 4 kinds of peptide hormones. In addition, the difference in the number and type of positive endocrine cells between the tumors arising from the head of the pancreas and those arising from the body and tail of the pancreas were statistically significant (P < 0.05). CONCLUSIONS: Immunohistochemically, the high positive rate to peptide hormones suggests that the nonfunctioning pancreatic endocrine tumors are actually not nonfunctioning; they are asymptomatic pancreatic endocrine tumors. Moreover, an uneven distribution of positive endocrine cells in the nonfunctioning pancreas endocrine tumors within the pancreas was identified.