In the current study, we describe a case of concomitant IPMN and NET of the pancreas. summarizes the clinicopathological features of the 15 previously reported cases of concomitant IPMN and NET (3
) as well as the present case. This condition mainly affects middle-aged females (average age, 63.1 years; range, 40–76 years; male/female ratio, 5:11). The main symptoms are abdominal or back pain (8 cases), no symptoms (5 cases) or weight loss (5 cases). A hormone production symptom (hypoglycemia) was observed in only one case. The most common degree of dysplasia of IPMN was low grade, however, high-grade dysplasia was also present (2 cases). The size of the NETs were not particularly large (average, 15.1 mm; range, 3–30), however, the clinical behavior was not always indolent. Metastasis of the NET was observed in 3 cases and one of these cases succumbed to NET; the histopathology of this case was NEC (NET G3). The preoperative clinical diagnosis was variable; IPMN in 7 cases and concomitant in 6 cases. Therefore, detailed pathological analysis of the resected pancreas tissue is required to indicate adequate treatment since metastasis of the NET may occur in some patients with concomitant IPMN and NET, even in those with small-sized lesions.
Clinicopathological features of concomitant IPMN and NET of the pancreas.
Somatostatin is an acidic polypeptide that inhibits cell proliferation and differentiation (10
). The physiological action of somatostatin is initiated by its interaction with a family of receptors consisting of five different subtypes, SSTR1-5 (11
). Somatostatin analogs (including octreotide) bind to the SSTRs, particularly SSTR2a, which is the most widely expressed subtype in NETs (4
). A previous study revealed that somatostatin analogs significantly lengthen the time to tumor progression in patients with metastatic midgut NETs (12
). Therefore, immunohistochemical analysis of SSTR2a expression in NETs is required to examine the suitability for somatostatin receptor analog treatment. Although the metastatic rate is low in NET G1, the analysis of SSTR2a expression is useful for identifying the utility of an optional treatment for the unexpected metastasis of NETs.
Expression of the intermediate filaments, peripherin and α-internexin, in NETs of the appendix and rectum has been previously reported (13
). We have previously characterized the expression patterns of neuronal intermediate filament proteins in the NETs of various organs (13
). While peripherin (a type III intermediate filament protein expressed in normal peripheral nerves) is expressed in all NET G1 of the rectum, the frequency of its expression is low in NET G2 of the rectum (13
). By contrast, the expression of α-internexin (a type IV intermediate filament protein normally found in the central nervous system) is observed in all NET G1 of the appendix and approximately half of rectal NET G1. All appendiceal NET G1 co-express peripherin and α-internexin (14
). Since neither peripherin nor α-internexin expression was observed in this case of NET G1 of the pancreas, it appears that intermediate filament protein expression varies with NET origin.
It is well known that IPMNs are associated with a high incidence of extrapancreatic malignancies, which proceed, coexist with or succeed IPMN (approximately 25–30% of IPMN cases) (15
). Colorectal and gastric carcinomas are the most common extrapancreatic carcinomas (15
In conclusion, although patients with IPMN have a favorable prognosis with a 5-year survival rate of almost 100% (16
), concomitant pancreatic NET and extrapancreatic malignancies may occur, therefore, systemic surveillance of extrapancreatic neoplasms and detection of concomitant NETs of the pancreas are necessary for patients with IPMN.