Immunohistochemical study of endocrine cells in ductal adenocarcinoma of the pancreas

Abstract

To clarify whether scattered endocrine cells in pancreatic ductal adenocarcinoma are neoplastic or not, we immunohistochemically studied 29 cases of invasive pancreatic ductal adenocarcinomas, 17 with metastases, for chromogranin A, insulin, glucagon, pancreatic polypeptide, serotonin, gastrin, laminin, and Ki-67. Endocrine cells were found in primary sites in 24 cases (82.3%), where endocrine cells showed at least a visibly close location to adjacent islet cells. Although endocrine cells in neoplastic glands were within the neoplastic basement membrane, endocrine cells were not seen in invasive sites beyond the pancreas where islets were not present. Endocrine cells in neoplastic glands were reactive for two or three of the islet hormones in all cases, and different types of hormonal reactivity was recognized in the same neoplastic gland or the same cluster of neoplastic glands in 22 (91.7%) cases, thus suggesting a close relation with islets. Ki-67 did not stain any endocrine cells in ten of the adenocarcinomas studied. In three (10.3%) cases, endocrine cells were found in the intraductal extensions. They may have pre-existed in non-neoplastic ducts. In 17 cases with metastatic sites, all but one had no endocrine cells in the metastases. Serotonin-positive cells were found in one metastatic lymph node in one case. We concluded that most endocrine cells seen in ductal adenocarcinomas of the pancreas are non-neoplastic and are derived from the surrounding islets. Some neoplastic endocrine cells may exist, though their frequency is low.

Advanced gastric endocrine cell carcinoma with distant lymph node metastasis: a case report and clinicopathological characteristics of the disease

“…At present, the presence of cytoplasmic argyrophilia and structural neurosecretory granules helps in the diagnosis of gastric ECC, but it has also been reported that several tumors had no such features [7,13,14,18]. Therefore, immunohistochemically positive staining for several neuroendocrine markerschromogranin A, synaptophysin, synaptic vesicle protein, Leu 7 (CD57), neuron-specific enolase (NSE), protein gene product (PGP 9.5), neural cell adhesion molecule (NCAM; CD56), and cytokeratin -is helpful in determining the histology of ECC, in contrast to negative staining for CEA [7,19]. We realize that preoperative diagnosis using these immunohistochemical markers is important for gastric ECC, because its aggressive biological behavior toward distant lymph nodes is occasionally beyond our ability to detect, as occurred in our patient.…”

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

“…Of note, 40-80% of pancreatic adenocarcinomas entrap neuroendocrine islets, which may lead to over-diagnosing MiNEN ( Fig. 2 d) [10,46,47] . Similarly, 5-10% of pancreatic NEN may entrap non-neoplastic ductules, and these "ductuloinsular" NEN should not been mistakenly diagnosed as MiNEN [10,48,49] .…”

Neoplastic Endocrine Differentiation of Pancreatic Ductal Adenocarcinoma in a Metastatic Lymph Node: Report of a Case

“…Recent studies suggest that most of these cells are tumor-associated, but non-neoplastic because they lack cellular atypia and account for only a small percentage. [1][2] In contrast, NED of pancreatic DAC is rare, and very few cases have been described. [3][4][5][6][7] This case is unusual and distinct from previous cases in that the main pancreatic tumor was composed purely of moderately differentiated DAC without endocrine differentiation, and NED was observed in a metastatic peripancreatic lymph node.…”

“…Non-neoplastic, tumorassociated, scattered endocrine cells are commonly found in pancreatic DACs. [1][2][3][4][5][6][7][8][9][10][11] Kamisawa et al 10 investigated 79 cases of pancreatic DAC immunohistochemi- cally, testing for chromogranin A, neuron-specifi c enolase Leu-7, and synaptophysin, and found that 29% contained scattered endocrine cells, accounting for less than 10% of the neoplastic cells. Similarly, Tezel et al 11 investigated 44 cases of pancreatic DAC immunohistochemically, using antibodies against chromogranin A, neuron-specifi c enolase, synaptophysin, CD57, and neural cell adhesion molecule, and found that 45% showed endocrine-like differentiation.…”

“…[1][2][3][4][5][6][7][8][9][10][11] Recent studies suggest that most of these cells are non-neoplastic. 1,2 In contrast, neoplastic endocrine differentiation (NED) of pancreatic DAC is rare, and only few cases have been described. [3][4][5][6][7] We recently detected NED in a metastatic lymph node from pancreatic DAC.…”