Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems.

Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary system are tumors comprising oncocytic cells, in which three types of fusion genes involving -PRKACA/-PRKACB were recently identified. IOPNs infrequently combine with other histological subtypes of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and intraductal papillary neoplasms of the bile duct (IPNBs). This study aimed to confirm the sensitivity/specificity of the fusion genes for IOPNs and to examine their significance in other oncocytic lesions. An RT-PCR, followed by DNA sequencing, was undertaken to examine the fusions in 18 histologically diagnosed IOPNs, including four combined IOPNs. Moreover, in two IOPN cases, invasive carcinomatous lesions were separately examined on their fusion status. Oncocytic thyroidal (n = 10), renal (n = 10), and salivary gland (n = 3) lesions and IPMNs (n = 9)/IPNBs (n = 4) with focal oncocytic changes were examined as controls. Fluorescence in situ hybridization using PRKACA break-apart probes was conducted for the combined IOPN cases. Target sequencing of KRAS exon2/3 and GNAS exon 8/9 was performed for IOPN cases. Fusions were detected in all IOPN cases including invasive lesions/none of the control cases. The fusion event was confirmed also in non-IOPN component in one of the four combined cases. Regarding mutation events, 5.6%/0% of IOPNs were KRAS-mt/GNAS-mt, respectively, and both components of combined IOPNs were all KRAS-wt/GNAS-wt. In conclusion, our study confirmed the sensitivity and specificity of these fusions for IOPNs. Here, we analyzed the roles of these fusion genes in combined IOPNs, proposing the possibility of IOPN development via IPMNs/IPNBs. Further studies with more combined cases are warranted.

Precursor Lesions of Gallbladder Carcinoma: Disease Concept, Pathology, and Genetics.

Understanding the pathogenesis and carcinogenesis of gallbladder adenocarcinoma is important. The fifth edition of the World Health Organization's tumor classification of the digestive system indicates three types of preinvasive neoplasm of the gallbladder: pyloric gland adenoma (PGA), biliary intraepithelial neoplasia (BilIN), and intracholecystic papillary neoplasm (ICPN). New terminologies have also been introduced, such as intracholecystic papillary-tubular neoplasm, gastric pyloric, simple mucinous type, and intracholecystic tubular non-mucinous neoplasm (ICTN). Pancreatobiliary maljunction (PBM) poses a markedly high risk for bile duct carcinoma, which was analyzed and investigated mainly by Asian researchers in the past; however, recent studies have clarified a similar significance of biliary carcinogenesis in Western countries as well. In this study, we reviewed and summarized information on three gallbladder neoplastic precursors, PGA, BilIN, and ICPN, and gallbladder lesions in patients with PBM.

A Case of Untreated Myeloid Sarcoma of the Pancreas Head Region: Diagnostic Process of AML Subtyping in an Autoptic Case.

This study describes an autopsy case of pancreatic/peripancreatic myeloid sarcoma in a 70-year-old man, initially presenting with obstructive jaundice. Pathologically, diffuse infiltration of round cells containing atypical nuclei with marked cleavage was observed mainly in the pancreas head, peripancreatic lymph nodes, spleen, bilateral lung, and bone marrow. Immunohistochemically, the tumor cells were negative for CD20, CD79a, CD3, CD5, c-kit, CD34, and TdT and positive for myeloperoxidase, CD33, CD68, and CD163. Flow cytometry of the peripheral blood showed underexpression of CD11c and aberrant expression of CD56 in the monocyte subset. The peripheral blood smear showed an increase in monocytes and atypia in neutrophils and monocytes, as well as enlarged platelets and polychromatic erythroblasts. Hence, it was suggested that the myeloid sarcoma was derived from the acute transformation of chronic myelomonocytic leukemia. Myeloid sarcoma is an extramedullary-mass-forming hematologic malignancy that is difficult to diagnose, especially when the initial presentation is a pancreatic mass. However, early diagnosis is important for appropriate therapy. Although bone marrow examination could not be performed because of the patients' severe condition, the pathological specimen obtained with autopsy helped subtype the patient's leukemia. The immunohistochemical features of this case merit attention.