Fujihiko Suzuki

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.

Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis

IntroductionA protein analysis using a mass spectrometry indicated that there are serum proteins showing significant quantitative changes after the administration of infliximab. Among them, connective tissue growth factor (CTGF) seems to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, this study was conducted to investigate how CTGF is associated with the disease progression of RA.MethodsSerum samples were collected from RA patients in active or inactive disease stages, and before or after treatments with infliximab. CTGF production was evaluated by ELISA, RT-PCR, indirect immunofluorescence microscopy, and immunoblotting. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, a bone resorption assay and osteoclasts specific catalytic enzymes productions.ResultsThe serum concentrations of CTGF in RA were greater than in normal healthy controls and disease controls. Interestingly, those were significantly higher in active RA patients compared to inactive RA patients. Furthermore, the CTGF levels significantly were decreased by infliximab concomitant with the disease amelioration. In addition, tumour necrosis factor (TNF)α can induce the CTGF production from synovial fibroblasts even though TNFα can oppositely inhibit the production of CTGF from chondrocytes. CTGF promoted the induction of the quantitative and qualitative activities of osteoclasts in combination with M-CSF and receptor activator of NF-κB ligand (RANKL). In addition, we newly found integrin αVβ3 on the osteoclasts as a CTGF receptor.ConclusionsThese results indicate that aberrant CTGF production induced by TNFα plays a central role for the abnormal osteoclastic activation in RA patients. Restoration of aberrant CTGF production may contribute to the inhibition of articular destruction in infliximab treatment.

Age-related phenomena in the lumbar intervertebral discs. Lipofuscin and amyloid deposition.

In 69 lumbar intervertebral discs from 69 autopsies, lipofuscin was seen in discs from individuals older than 50 years of age and amyloids in the discs of individuals older than 40 years of age. In 261 intervertebral disc tissue specimens collected at the time of surgery for disc herniation, lipofuscin was seen in the discs of individuals older than 20 years of age and amyloids in the discs of individuals older than 15 years of age. It is speculated that amyloids and lipofuscin are a sign of aging in the intervertebral disc as in other tissues. Furthermore, amyloids and lipofuscin were seen in the operated discs of young individuals than in the autopsy cases.

Pancreatic, hepatic, splenic, and mesenteric mucinous cystic neoplasms (MCN) are lumped together as extraovarian MCN

Mucinous cystic neoplasms (MCN) of the pancreas are mucin‐producing cystic tumors with an ovarian‐like stroma (OLS). In the present study MCN were obtained from 27 patients. These MCN were derived from 22 pancreas, three livers, spleen, and mesentery. MCN in various organs have common clinicopathological profiles, being unilocular or multilocular cystic tumors, with a fibrous capsule and lined by mucin‐secreting epithelium associated with an underlying subepithelial OLS. The OLS showed strong positivity for α‐smooth muscle actin (α‐SMA) and vimentin and weak, focal positivity for desmin. Both estrogen receptors and progesterone receptors were expressed in the nuclei of OLS cells. In addition, 20 ovarian MCN and 13 normal ovaries were studied with particular attention to the stroma. The stroma of ovarian MCN was strongly immunopositive for α‐SMA and vimentin and focally positive for desmin, whereas normal ovarian stroma was immunonegative for both α‐SMA and desmin. The OLS of MCN mentioned here was similar to the septa of ovarian MCN but not to ovarian stroma. In conclusion, MCN in various organs should be lumped together as ‘extraovarian’ MCN. The OLS was identified on the basis of myofibroblastic proliferation both in response to neoplastic development and dependent on hormones.

Histopathologic and Immunohistochemical Studies on the Mechanism of Interlobular Fibrosis of the Pancreas

OBJECTIVE To elucidate the mechanism of interlobular fibrosis of the pancreas, which is categorized as chronic alcoholic pancreatitis. METHODS Forty pancreatic tissue samples from patients with ampullary carcinomas, which cause various degrees of stricture of the main pancreatic duct, and 20 patients with chronic alcoholic pancreatitis were studied histopathologically and immunohistochemically. RESULTS Fibrosis was observed in 23 of 40 patients with ampullary carcinomas and was classified into 3 categories: mild changes (10 cases), moderate changes (9 cases), and marked changes (4 cases). In the mild change cases, mild fibrosis was diffusely distributed in the interlobular areas, with scant immunoreactivity of anti-alpha-smooth muscle actin (alpha-SMA) and an expansive lobular appearance, whereas moderate and marked change cases showed interlobular and intralobular fibrosis with marked anti-alpha-SMA immunoreactivity and lobular atrophy. By quantitative analysis, the mild change cases showed both higher MIB1-positive and lower apoptotic acinar cell ratios than those of moderate and marked changes. Anti-alpha-SMA immunoreactivity in the patients with chronic alcoholic pancreatitis was found in interlobular fibrosis. Hence, mild changes in cases of ampullary carcinomas had histologic findings similar to chronic alcoholic pancreatitis, except for excessive fibrosis cases with patchy distribution. CONCLUSION Incomplete obstruction of the main pancreatic duct caused the beginning of interlobular fibrosis, which is categorized as chronic alcoholic pancreatitis.

Small cell carcinoma of the prostate with hypercalcemia

Abstract We present a case of small cell prostate carcinoma with hypercalcemia in a 75‐year‐old man. He was diagnosed as having stage T3bN1M0 adenocarcinoma of the prostate. His serum prostate‐specific antigen level was reduced to below the normal range after a combination treatment of a luteinizing hormone‐releasing hormone agonist and flutamide for prostate carcinoma. He subsequently experienced increasing fatigue, poor appetite, short time loss of consciousness and pain in his lower abdomen. His serum calcium level and carcinoembryonic antigen were increased. He died 5 months from the start of treatment. The autopsy revealed small cell carcinoma of the prostate and multiple metastasis of the lung, liver, pancreas, lymph nodes and spine.

Sarcomatoid carcinoma and carcinosarcoma of the urinary bladder

Two cases, sarcomatoid carcinoma and carcinosarcoma, of the urinary bladder are reported. A 68‐year‐old man with sarcomatoid carcinoma underwent total cystectomy and was alive and had had no recurrence after 21 months. A 78‐year‐old woman with carcinosarcoma underwent total cystectomy, but she died from increasing multiple lung metastases 4 months after surgery. The histopathological characteristics of both neoplasms are reported and discussed.

CASE REPORT: Intra‐abdominal angiosarcomatosis after radiotherapy

Background: We report a case of a 61‐year‐old Japanese woman who developed intra‐abdominal angiosarcomatosis 20 years after receiving radiotherapy for squamous cell carcinoma of the cervix.

Pre-existing histological type and developmental mechanism of mucinous noncystic carcinoma of pancreas

Eleven cases with mucinous noncystic carcinoma (MC) of the pancreas were studied by histology and mucin immunohistochemistry, to elucidate the mechanism, or route of development, and pre-existing histological type of MC of the pancreas. These MCs were observed in close approximation to, or surrounding, intraductal papillary-mucinous carcinomas (IPMCs), and were centrally situated among ductal adenocarcinomas (DAs). Hence, the 11 cases originated from 8 IPMCs and 3 DAs. The mechanism and routes to MC were divided into four types as follows: IPMC directly invaded the stroma (4 cases), over-production of mucin in IPMC expanded the branches of the pancreatic duct possibly resulting in rupture (3 cases), DA underwent extreme mucinous degeneration (3 cases), and a recurrent form, as MC, at the surgical stump of IPMC (one case). The outcomes of MC cases with IPMC had variable survival rates, while those from DA had short durations. MUC immunoreactivity in MC was divided into three categories; anti-MUC1-positive only (2 IPMCs, 2 DAs), mixed anti-MUC1 and anti-UC2-positive (3 IPMCs, one DA) and anti-MUC-positive only (3 IPMCs). Pre-existing MC histological types included both IPMC and DA. These two pre-existing types of MC involved mucin overproduction and mucinous degeneration. MUC immunoreactivity in MC revealed three patterns, which may be related to variable outcomes.

Cytodiagnosis of placental site trophoblastic tumor. A report of two cases.

BACKGROUND Placental site trophoblastic tumor (PSTT) is a rare form of trophoblastic neoplasm. Approximately 100 cases of PSTT have been reported, but we found no report on its cytodiagnosis. CASES Case 1, a 39-year-old female, came to the hospital because of abnormal genital bleeding. Case 2, a 36-year-old female came because of amenorrhea for a year. In both cases, endometrial smear and intrauterine curettage suggested trophoblastic disease, and hysterectomy was performed. Laboratory data revealed a mild increase in human chorionic gonadotropin (hCG) and beta-hCG but normal human placental lactogen (hPL). In the cytologic examination, the background contained some hemorrhagic and fibrinous areas but no necrosis. Most tumor cells stained light green, were round or polygonal, and contained abundant cytoplasm. Some were palely stained and had vacuoles. Some cells showed hyperchromatism, an irregular nucleus, fine-to-coarse chromatin granules and markedly different sizes. Most of the cells were hPL positive, and a few were hCG positive. CONCLUSION Both cases were considered benign because of rare mitoses despite cellular pleomorphism. However, careful follow-up is required. The differential diagnosis of PSTT is difficult from cytologic and biopsy specimens alone but may be achieved with additional magnetic resonance imaging findings and positive staining of hPL and hCG.