Yuki Fukumura

Histopathologic characteristics of autoimmune pancreatitis based on comparison with chronic pancreatitis.

Objectives: To clarify the histopathologic characteristics of autoimmune pancreatitis (AIP), based on comparison with both chronic alcoholic pancreatitis (CAP) and chronic obstructive pancreatitis (COP). Methods: Three AIP patients, 17 CAP patients, and 19 COP patients were studied histopathologically. Results: There was a dense lymphoplasmacytic infiltrate, especially within and around the pancreatic ducts, and fibrosis associated with AIP, while there was fibrosis accompanied by mild inflammatory infiltration in both CAP and COP. Inter- and intralobular fibrosis admixed with acinar atrophy was observed in both AIP and COP, while interlobular fibrosis combined with a “cirrhosis-like” appearance was found in CAP. Obliterative phlebitis was found in AIP, while thrombosis of the splenic vein was exhibited in CAP. Conclusion: Autoimmune pancreatitis was histologically characterized by dense lymphoplasmacytic infiltrate combined with fibrosis, acinar atrophy, obliterative phlebitis, and ductal involvement.

Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve

Aim:  The rate of oocyte decline follows a biphasic pattern, characterized by acceleration between 32 and 38 years old. Ovarian reserve is also affected by external factors, including ovarian disease and iatrogenic damage. The aim of this study was to histologically evaluate the impact of ovarian endometriomas, laparoscopic cystectomy, and age on follicle reserve in healthy ovarian tissues and in surgically resected cyst walls.

Detection of Epstein–Barr virus-encoded small RNA-expressed myofibroblasts and IgG4-producing plasma cells in sclerosing angiomatoid nodular transformation of the spleen

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare inflammatory tumor-like lesion composed of vascular nodules and non-neoplastic stroma including spindle cells and inflammatory cells. The focus of our study was on the stromal proliferating process in SANT. Nine cases of SANT were examined. All cases showed α-smooth muscle actin (α-SMA) and vimentin on the spindle cells but not CD21, CD31, CD34, CD68, desmin, S100, human herpes virus-8, or anaplastic lymphoma kinase-1. In one case, 20–30% of the myofibroblasts in Epstein–Barr-virus (EBV)-positive spindle cells were detected using double-labeling immunohistochemistry for α-SMA and EBV-encoded small RNA in situ hybridization. A quantitative analysis of IgG and IgG4-positive plasma cells (pPCs) in SANT was performed. The median densities of IgG-pPCs and IgG4-pPCs in SANT were approximately four-fold and 13-fold higher than those in the normal spleens, respectively. In addition, there was a statistically significant increase of IgG4/IgG-pPCs ratio in SANT in comparison to the control specimens. In conclusion, the fibrogenesis in a subset of SANT may be associated with EBV-infected myofibroblasts in an overlapping immune reaction indicated by the presence of infiltrating IgG4-pPCs. Further investigation is needed to elucidate the association between SANT and IgG4-related sclerosing disease.

Congenital fibromuscular dysplasia involving multivessels in an infant with fatal outcome

We report the unusual case of a 2-month-old boy with systemic fibromuscular dysplasia (FMD). He presented with congenital renovascular hypertension due to stenosis of the right renal artery, and later developed renal infarction on the contralateral side resulting in renal failure. The boy subsequently died of intracranial haemorrhage at the age of 14 months. During the course, hemiconvulsion caused by a Moyamoya disease-like vascular lesion was noted. Stenotic lesions of both the abdominal aorta and its branches were also revealed by angiography. Post-mortem examination confirmed that the coronary, splenic and mesenteric arteries were also affected and their histological findings were compatible with FMD. To our knowledge, this is the first congenital case of FMD demonstrating a rapidly progressive course resulting in a fatal outcome. In this case, multivessels in both intracranial and extracranial arteries were involved. Conclusion:our case suggests that the nature of fibromuscular dysplasia is congenital in origin and its aetiology, at least in some cases, is a systemic abnormality of vascular development.

Expression of Transforming Growth Factor β1, β2, and β3 in Chronic, Cancer-Associated, Obstructive Pancreatitis

Abstract Context.—Myofibroblasts are considered to play central roles in pancreatic fibrosis. The potent fibrogenic capacities of transforming growth factor βs (TGF-βs) have been emphasized in vitro and in animal studies. However, the roles of TGF-βs in human chronic pancreatitis have not been fully clarified. Objective.—To investigate whether expressions of TGF-βs are related to myofibroblast distribution in chronic, cancer-associated, obstructive pancreatitis (COP). Design.—Histopathologic studies using hematoxylin-eosin and Elastica-Masson trichrome and immunohistochemical studies using antibodies against α-smooth muscle actin (SMA); CD68; TGF-β1, -β2, and -β3; and TGF-β soluble receptor type II were performed in 19 COP cases and 6 controls. By classifying COP tissues into 3 fibrosis phases by the amount of collagen deposits, immunoreactivities for TGF-βs, histopathologic changes, and myofibroblast distribution were examined for each fibrosis phase. Results.—Six cases were categorized in the early stag...

Oncocytic mucoepidermoid carcinoma of the parotid gland with CRTC1-MAML2 fusion transcript: report of a case with review of literature

Oncocytic mucoepidermoid carcinoma is a very rare variant of mucoepidermoid carcinoma, composed predominantly of oncocytic cells. Most previously reported cases described the difficulty in histologic differentiation from other oncocytic tumors. Here we report a case of oncocytic mucoepidermoid carcinoma of parotid gland diagnosed by the detection of CRTC1-MAML2 fusion. A 53-year-old man had a left superficial parotidectomy conducted for 3-cm-sized mass. The resected tumor was composed almost exclusively of oncocytic tumor cells. With detailed histologic evaluation, scarce vacuolated tumor cells, suggestive of mucous cell of mucoepidermoid carcinoma, and one focus of tumor embolism in a vein were found, suggesting the possibility of oncocytic mucoepidermoid carcinoma. Immunohistochemically, oncocytic cells were diffusely positive for p63. Reverse transcriptase polymerase chain reaction and direct sequencing revealed CRTC1-MAML2 translocation of this tumor. To our knowledge, this report describes the first case of oncocytic mucoepidermoid carcinoma confirmed with CRTC1-MAML2 fusion. Identification of this fusion gene may help in distinguishing oncocytic mucoepidermoid carcinoma from its mimics.

Pathology of autoimmune pancreatitis and tumor-forming pancreatitis

The most frequently recognized presentation of autoimmune pancreatitis (AIP) is that mimicking pancreatic cancer. It is also known that at some stage during the disease process chronic pancreatitis clinically presents as a tumorous swelling, often suspected of being a carcinoma. In Japan, this stage has also been proposed clinically to be tumor-forming pancreatitis. Hence, tumor-forming pancreatitis shows at least two distinct types: a reparative process for centriductal acute inflammation with a background of chronic pancreatitis, which is considered to have given rise to the tumor at some stage of chronic pancreatitis, and a lymphoplasmacytic infiltration with lymphoid and fibrous proliferation in normal pancreatic tissue, which corresponds to autoimmune pancreatitis. These tumorous lesions may be changeable along the disease process.

Expression of Transforming Growth Factor β by Small Duct Epithelium in Chronic, Cancer-associated, Obstructive Pancreatitis: An In Situ Hybridization Study and Review of the Literature

Objectives: Transforming growth factor β (TGF-β) is a dominant mediator of pancreatic fibrosis. The objective of this study was to identify cellular sources of TGF-β mRNA and compare the results with previous immunohistochemical/in situ hybridization studies. Methods: In situ hybridization of TGF-β was conducted for 9 human tissues of chronic obstructive pancreatitis (COP) and 2 control specimens. By classifying these 9 COP tissues into 3 fibrosis phases by the amount of fibrotic space, histopathologic changes were examined for each fibrosis phase. Whether or not TGF-β-positive cells were closely distributed to fibrosis was also investigated in control and COP cases. Results: Three cases were categorized in early, intermediate, and advanced stages of fibrosis. Transforming growth factor β mRNA was identified for a part of small duct epithelia, that is, intercalated ductule cells, centroacinar cells, and/or metaplastic ductal structures adjacent to acinar cells. The number of TGF-β-positive cells was greater in COP cases than in controls. In controls and in the early stage of fibrosis, no fibrosis was seen near TGF-β-positive cells. Conclusions: Small duct epithelia are the main cellular sources of TGF-β in COP, and many of them may be working for COP fibrosis either directly or indirectly.

Urothelial carcinoma of the renal pelvis with rhabdoid features

Reported herein is the case of a 70‐year‐old man with high grade urothelial carcinoma (UC) with rhabdoid features of the renal pelvis. For the most part, the tumor was composed of pleomorphic, non‐cohesive round tumor cells with abundant cytoplasm. In situ high‐grade UC composed of cohesive tumor cells was seen only in a small portion. Pleomorphic dyscohesive tumor cells often showed rhabdoid features, containing eosinophilic inclusions. These pleomorphic/rhabdoid tumor cells were immunohistochemically positive for vimentin but negative for cytokeratins, CD45, CD20, CD79a, CD3, CD45RO, CD38, and CD138. Loss of heterozygosity (LOH) analysis demonstrated identical allelic losses as well as additional allelic losses for the dyscohesive and cohesive UC lesion, indicating that these two lesions originated from a single clonal lesion.

Activated perilobular, not periacinar, pancreatic stellate cells contribute to fibrogenesis in chronic alcoholic pancreatitis

The authors investigated the role of activated perilobular, not periacinar, pancreatic stellate cells, in fibrogenesis in chronic pancreatitis, based on the distribution of myofibroblasts. Twenty‐four patients with clinically diagnosed chronic alcoholic pancreatitis were studied histopathologically, immunohistochemically and quantitatively. In all cases, fibrosis was patchily distributed in the perilobular, or interlobular, areas, accompanied by a cirrhosis‐like appearance; it had extended into the intralobular area in advanced cases. Seven patients had a massive or confluent loss of exocrine tissue, resulting in extensive interlobular fibrosis; the more extensive the interlobular fibrosis, the smaller the lobules. Immunoreactivity to α‐smooth muscle actin, a myofibroblast marker, was found mostly in the same areas of the fibrosis, mainly the interlobular, and less often the periacinar, areas; the average percentage area of perilobular myofibroblasts was significantly higher than that of periacinar myofibroblasts in 20 randomly selected lobules (P > 0.001), in which the average value for the former was 38.03% (range: 13.54–61.32%; SD, 13.8%) and that for the latter was 4.85% (range 0.90–9.57%; SD, 2.22%). Fibrosis also immunostained positive for collagen types I and III. In conclusion, activated perilobular, not periacinar, pancreatic stellate cell contribute to fibrogenesis in chronic pancreatitis.