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Background Recurrent hydrocephalus may occur as a complication of neurosarcoidosis with chronic inflammation. We present a case that required a combination of multistage endoscopic diversion of the cerebrospinal fluid pathway and shunt surgery. Case Description A 34-year-old man presented with progressive nausea and vomiting. Magnetic resonance imaging revealed hydrocephalus with leptomeningeal enhancement along the base of the fourth ventricle and the bilateral foramina of Luschka. Concurrent endoscopic third ventriculostomy and biopsy were performed. The diagnosis was neurosarcoidosis. Immediately after the procedure, the endoscopic third ventriculostomy stoma was occluded, and a right ventriculoperitoneal shunt was urgently performed. However, left unilateral hydrocephalus developed during the late phase of immunosuppressive therapy for neurosarcoidosis. Endoscopic septostomy with repositioning of the ventricular catheter was indicated. Intraoperative findings included a white pasty tissue with nodules that covered the ventricular wall close to the foramen of Monro and sealed the side holes of the catheter. Chemotherapy with a tumor necrosis factor–α inhibitor was initiated after the surgical procedure. The patient had an uneventful course without recurrence of hydrocephalus for >6 months. Conclusions Endoscopic diversion of the cerebrospinal fluid pathway should be actively considered for treating hydrocephalus without a shunt and performing biopsy simultaneously. Even if a subsequent shunt is needed, complex hydrocephalus can be avoided with a combination of endoscopic techniques.

Central nervous system (CNS) infections due to filamentous basidiomycetes are extremely rare. We encountered a case of epidural abscess due to Schizophyllum commune that extended from sinusitis. A 53-year-old Japanese man presented at our hospital with a headache. Computed tomography (CT) of the cranium and sinuses showed ethmoid and sphenoid sinusitis with no intracranial abnormalities. The patient was diagnosed with acute sinusitis and underwent antibiotic treatment. However, the symptoms deteriorated, and the patient came to our hospital again with consciousness disturbance. CT scan of the cranium and sinuses showed no improvement of sinusitis after antibiotic therapy and an epidural abscess emerged in the middle cranial fossa. Therefore, emergency craniotomy and endoscopic sinus fenestration were performed. Filamentous fungal elements were observed in both rhinorrhoea and epidural abscess. The symptoms improved after the operation and administration of liposomal amphotericin B. The clinical isolate was identified as S. commune by a molecular-based method. To our knowledge, this is the first report of epidural abscess due to this fungus. Although rare, clinicians should be aware that S. commune could be a causative agent of CNS infections.

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

Cholangiolocellular carcinoma (CLC) is classified into the following two subtypes: (a) pure biliary subtype without hepatocellular carcinoma (HCC) component and (b) hepatobiliary subtype with HCC component. The possibles of cell origin of the former subtype are cholangiole, interlobular duct, and ordinary intrahepatic bile duct (septal or larger duct). The cell origin of the latter type may be HCC. The Japanese General Rules for the Clinical and Pathological Study of Primary Liver Cancer described the features of pure biliary type. Whereas World Health Organization Classification 2010 put an emphasis on the features of hepatobiliary subtype. CLC of the true meaning which must have originated from cholangiole may be identified by the following criteria: the size of the cancer duct (smaller than 15 μm), positivity for c-Kit, and absence of an ordinary ICC component.

Author(preprint), We previously showed that mature hepatocytes could transdifferentiate into bile ductular cells when placed in a collagen-rich microenvironment. To explore the mechanism of transdifferentiation, we examined whether inflammatory cytokines affected the phenotype of hepatocytes in a three-dimensional culture system. Spheroidal aggregates of rat hepatocytes were embedded within a type I collagen gel matrix and cultured in the presence of various cytokines. In the control, hepatocytes gradually lost expression of albumin, tyrosine aminotransferase, and hepatocyte nuclear factor (HNF)-4α, while aberrantly expressed bile ductular markers, including cytokeratin 19 (CK 19) and spermatogenic immunoglobulin superfamily (SgIGSF). Among the cytokines examined, tumor necrosis factor (TNF)-α inhibited expression of albumin and HNF-4α, both at mRNA and protein levels. After culturing for 2 weeks with TNF-α, hepatocytic spheroids were transformed into extensively branching tubular structures composed of CK 19- and SgIGSF-positive small cuboidal cells. These cells responded to secretin with an increase in secretion and expressed functional bile duct markers. TNF-α also induced the phosphorylation of Jun N-terminal kinase (JNK) and c-Jun, and the morphogenesis was inhibited by SP600125, a specific JNK inhibitor. Furthermore, in chronic rat liver injury induced by CCl(4) , ductular reaction in the centrilobular area demonstrated strong nuclear staining of phosphorylated c-Jun. Our results demonstrate that TNF-α promotes the ductular transdifferentiation of hepatocytes and suggest a role of TNF-α in the pathogenesis of ductular reaction.

Author, We previously demonstrated that mature rat hepatocytes transdifferentiate to bile ductular cells when cultured in a three-dimensional collagen-rich matrix. Here, we show that the phenotype of transdifferentiated hepatocytes can be reversed by modulating culture conditions. Spheroidal aggregates of hepatocytes were cultured within a collagen gel matrix in the presence of serum and tumor necrosis factor-α. Spheroids transformed into ductular structures composed of small cuboidal cells, lost the expression of hepatocytic markers, whereas aberrantly expressed bile ductular markers. The transdifferentiated cells were then retrieved from the gels, plated on surfaces coated with a basement membrane-like material, and cultured in serum-free media. Cells spontaneously formed spheroidal aggregates and recovered hepatocytic phenotype. Dexamethasone (Dex), which suppressed the phosphorylation of ERK and Jun N-terminal kinase, facilitated the recovery, and the combination with interleukin-6 or oncostatin M resulted in the recovery of hepatocyte nuclear factor 4 α protein expression and the typical hepatocytic morphology, and a decrease in the expression of bile ductular markers. A cDNA microarray analysis revealed that the hepatocyte-specific mRNA expression profile was recovered in these cells. Our results demonstrate that hepatocytes are able to recover their phenotypes following bile ductular transdifferentiation, suggesting that hepatocytic and bile ductular phenotypes may be mutually reversible.

Author, Orthovanadate (OV), an inhibitor of protein tyrosine phosphatases, affects various biological processes in a cell-type-specific manner. In this study, we investigated the effect of OV on hepatic stellate cells (HSCs). When primary rat HSCs were cultured in the presence of 10% serum, they spontaneously lost characteristic stellate morphology, proliferated, and were transformed into an activated state with the formation of abundant stress fibers and increased expression of both alpha-smooth muscle actin and collagen type I mRNA. OV treatment inhibited proliferation and activation of HSCs and partially reversed the phenotype of activated HSCs. Among the signaling molecules investigated, phosphorylation of the Src protein at tyrosine 416 was the most striking in OV-treated HSCs. Treatment of cells with Src family inhibitors partially abrogated the effects of OV. Furthermore, transfection of v-Src into activated HSCs induced a stellate morphology similar to that in the quiescent state. We then examined whether OV could effectively suppress HSC activation in vivo after liver injury induced by either carbon tetrachloride or dimethylnitrosamine. OV significantly reduced the appearance of alpha-smooth muscle actin-positive cells and decreased collagen deposition, concomitant with an improvement in liver function. Our study showed for the first time that OV was able to suppress the activation of HSCs, possibly through the modulation of Src activity, and attenuated fibrosis after chronic liver injury.

Background The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Methods Ninety‐four HCC lesions no larger than 8 cm from 94 patients were immuno‐histochemically studied using two hepatocyte markers (Hep par 1 and α‐fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c‐Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0–5.0 cm; S3, 5.0–8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. Results The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c‐Kit). Conclusion Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.

Down syndrome with transient myeloproliferative disorder (TMD) is often associated with perinatal liver fibrosis. The authors recently encountered an autopsy case of this disease with a characteristic severe perisinusoidal liver fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse fibro-inflammatory diseases. The purpose of the present report was to examine the involvement of OPN in development of the Down syndrome-associated liver fibrosis. Histology indicated severe perisinusoidal fibrosis and ductular arrangements of hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a feature of TMD associated with Down syndrome, was not evident. On immunohistochemistry expression of OPN was observed in hepatocytes often having ductular arrangements and infiltrating macrophages. In contrast, a small number of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were present in the liver. Numerous activated hepatic stellate cells (HSC) expressing alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A recent report indicated that OPN could directly activate the HSC. Thus, it is suggested that OPN produced by hepatocytes and macrophages induces activation of the HSC, and leads to the development of perisinusoidal liver fibrosis.

The feasibility of defining early cholangiocarcinoma has not been adequately evaluated. The surgical outcomes of patients who had undergone pancreatoduodenectomy (PD) for pathological T1 (pT1) distal cholangiocarcinoma (DCC) were evaluated to determine whether it is possible to define early DCC. The clinicopathological data of 18 patients with pT1 DCC who had undergone PD were reviewed retrospectively. Depth of fibromuscular (fm) layer invasion was divided into two categories: fm1 and fm2 (without adventitia fascia invasion and with adventitia fascia invasion). Comparative analyses were performed according to the depth of invasion. Disease-specific survival rates of patients with five mucosal tumors and 13 fm-invasive tumors were 80 and 61.9 % at 5 years and 80 and 41.2 % at 10 years, respectively. There was no significant difference in disease-specific survival rates between the two groups (P = 0.244). Disease-specific survival rates of patients with 7 fm1-invasive tumors and 6 fm2-invasive tumors were 85.7 and 40 % at 5 years and 85.7 and 0 % at 10 years. A significant difference in disease-specific survival rates was observed between mucosal tumors and fm2-invasive tumors (P = 0.043), and disease-specific survival rates of mucosal tumors and fm1-invasive tumors were similar (P = 0.968). Defining early DCC as carcinoma confined to the fm of the bile duct might be inappropriate; early DCC should be limited to the mucosal carcinoma.

To elucidate the mechanism of apoptosis of liver sinusoidal endothelial cells (SECs), we examined the phosphorylation status of Bad and its upstream signaling molecules during apoptosis in culture and after ischemia-reperfusion injury. Rat SECs were isolated by the immunomagnetic method, and 2 days after culture, most SECs underwent apoptosis, which was associated with decreased tyrosine phosphorylation of cellular proteins. Addition of orthovanadate (OV), a protein tyrosine phosphatase inhibitor, sustained cellular protein phosphorylation and strongly inhibited apoptosis. Bad was dephosphorylated at Ser-112 and Ser-136 during apoptosis, but the phosphorylation status of Bad was maintained in the presence of OV. OV activated the Akt, extracellular signal-regulated protein kinase, and p38 mitogen-activated protein kinase pathways, which are involved in Bad phosphorylation. In the absence of OV, depletion of Bad by RNA interference conferred resistance to apoptosis. Hepatic injury after ischemia-reperfusion was alleviated by OV treatment, with significant inhibition of SEC apoptosis. SEC apoptosis in vivo was associated with dephosphorylation of Bad, Akt, and extracellular signal-regulated protein kinase, which was blocked by OV treatment. Our data suggest that maintenance of Bad phosphorylation is important in the prevention of SEC apoptosis and that the anti-apoptotic property of OV might have therapeutic utility.

Metastasis from renal cell carcinoma (RCC) to the testis is rare. This case report presented an extremely rare case of simultaneous bilateral testicular metastases from RCC in a 65-year-old man who had experienced indolent scrotal enlargement over a period of several months. Scrotal ultrasonography showed 4.0- and 2.0-cm-sized masses in the left and right testes, respectively. Contrast-enhanced computed tomography identified multiple tumors in the kidneys, the pancreas and the left adrenal gland. Left orchiectomy and pathological examination were performed and indicated testicular metastasis from clear cell RCC. The patient underwent complete surgical resection of all residual lesions. Postoperative follow-up examination without adjuvant therapy identified no recurrence over 11 months. This study also reviewed existing literature and determined that retrograde venous spread from the primary kidney tumor to the testis may be an important pathway for testicular metastasis from RCC. In conclusion, RCC can result in testicular metastases not only unilaterally, but also bilaterally, as was observed in the present case.

Growing evidence revealed that liver sinusoidal endothelial cells (SEC) play several important roles in physiology and pathology of the liver. It has been well understood that their structural characteristics, such as the membrane sieve and lack of basement membrane, facilitate direct contact of soluble and insoluble serum substances with hepatic parenchymal cells, resulting in enhancement of hepatic metabolic activity. In addition, SEC is now regarded as a member of the scavenger endothelial cells, which have potential to eliminate a variety of macromolecules from the blood circulation by receptor-mediated endocytosis. It is reported that molecules preferentially eliminated by SEC are denatured or modified proteins such as advanced glycation end products, extracellular matrix components including hyaluronic acid, and some lipoproteins. The nature of the scavenger receptors corresponding to these molecules remains to be clarified. Recently, it was noted that SEC has an antigen-presenting function similar to dendritic cells. Taken together, it is suggested that SEC, cooperating with Kupffer cells and hepatic dendritic cells, may partake of immunoregulatory functions in the liver. SEC also plays a pivotal role in the pathological process of ischemia-reperfusion injury following liver surgery and liver transplantation. Thus, it is of importance to elucidate the mechanisms of apoptosis and proliferation of SEC. Recent results on the regulation of growth and apoptotic signaling of SEC are discussed.

Background/Aims : To develop a specific isolation method of hepatic sinusoidal endothelial cells (SEC), we applied the immunomagnetic method using a monoclonal antibody (SE-1) that recognizes a membranous antigen expressed only in rat SEC. Methods : Cells were isolated by incubating mixed non-parenchymal cells, which were obtained by collagenase digestion of the liver, with SE-1-conjugated superparamagnetic polystyrene beads. The conventional Percoll method was also performed in parallel to compare with the immunomagnetic method. The isolated cells were cultured on glass coverslips coated with type I collagen in the presence of various growth factors for 6 days. Results : Approximately 98% of the isolated cells were positive for SE-1 and the contamination of Kupffer cells or stellate cells was less than 1%. The purity was significantly better than that obtained by the Percoll method. The cultured cells showed typical SEC features, such as sieve plates and uptake of acetylated low-density lipoprotein. Although the cells continuously underwent apoptotic cell death after 2 days, they started robust cell growth after 3 days and were well maintained during the culture period. Conclusions : Our simple and specific isolation method enables us to culture SEC with high purity and should be useful for the biological analysis of SEC.

Evaluation of the malignant potential of a pheochromocytoma (PCC) remains controversial. PCC is regarded as a neuroendocrine tumor (NET), and the classification of NETs has gradually been defined over the last decade, particularly for gastroenteropancreatic NET. The present study describes a case of locally advanced, carcinoma-like, nonfunctional PCC, which may be regarded as neuroendocrine carcinoma (NEC) rather than a malignant PCC. A 72-year-old man was referred to Saitama Red Cross Hospital (Saitama, Japan), presenting with a 2-month history of right flank pain. Computed tomography revealed a right adrenal gland tumor, which measured 6.0 cm in diameter, invading the hilum of the right kidney, liver and inferior vena cava (IVC). Radical surgery was performed with en bloc resection of the right kidney, and adjacent parts of the liver and IVC. Immunohistochemical examination demonstrated that all of the resected tissues were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, cluster of differentiation 56 and Ki-67, and the specimen had a Ki-67 index of 80%. A diagnosis of carcinoma-like PCC or NEC of the adrenal gland was confirmed. Reports of NEC of the adrenal gland are extremely rare in the literature, and classification of PCC as a NET has not yet been fully discussed. The present case may therefore contribute to the classification of NETs in the adrenal gland.

Reported herein is an autopsy case of mast cell leukemia, a rare form of systemic mastocytosis, complicated with portal hypertension. A 52-year-old woman presented with urticaria-like skin symptoms, anemia, and thrombocytopenia. Atypical mast cells (CD2+, CD25+, CD117+) with toluidine blue metachromasia were found in the peripheral blood and on bone marrow aspiration smears. Chemotherapy with cytosine arabinoside and idarubicin was ineffective and the patient died of multi-organ failure with rapidly progressing hepatosplenomegaly and large-volume ascites 3 months after admission. At autopsy the bone marrow, spleen, liver, and lymph nodes were extensively infiltrated by atypical tumor cells with occasional bi- or multi-lobated nuclei. They were positive for mast cell tryptase and possessed an activating mutation of the c-kitgene (D816V). Ascites (2200 mL) and non-ruptured esophageal varices with submucosal hemorrhage indicated the presence of severe portal hypertension. Although there was no evidence of liver cirrhosis, the hepatic sinusoids were clogged with tumor cells, with a tendency to be more severe in the perivenular areas, and the lumens of central veins were obliterated by tumor cell infiltration. The present case demonstrates that non-cirrhotic portal hypertension due to blocking of sinusoidal and venous flow could be a serious complication in mast cell leukemia.

There have only been a few reports on lansoprazole-associated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimicking ulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis. Consequently sulfasalazine 2 g/d was started. The patient’s diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Five months later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea. Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.

Down syndrome with transient myeloproliferative disorder (TMD) is often associated with perinatal liver fibrosis. The authors recently encountered an autopsy case of this disease with a characteristic severe perisinusoidal liver fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse fibro-inflammatory diseases. The purpose of the present report was to examine the involvement of OPN in development of the Down syndrome-associated liver fibrosis. Histology indicated severe perisinusoidal fibrosis and ductular arrangements of hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a feature of TMD associated with Down syndrome, was not evident. On immunohistochemistry expression of OPN was observed in hepatocytes often having ductular arrangements and infiltrating macrophages. In contrast, a small number of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were present in the liver. Numerous activated hepatic stellate cells (HSC) expressing alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A recent report indicated that OPN could directly activate the HSC. Thus, it is suggested that OPN produced by hepatocytes and macrophages induces activation of the HSC, and leads to the development of perisinusoidal liver fibrosis.

We investigated the mechanism of phenotypic plasticity of hepatocytes in a three-dimensional organoid culture system, in which hepatocytic spheroids were embedded within a collagen gel matrix. Hepatocytes expressed several bile duct markers including cytokeratin (CK) 19 soon after culture and underwent branching morphogenesis within the matrix in the presence of insulin and epidermal growth factor. Cultured hepatocytes did not express Delta-like, a specific marker for oval cells and hepatoblasts. Furthermore, hepatocytes isolated from c-kit mutant rats (Ws/Ws), which are defective in proliferation of oval cells, showed essentially the same phenotypic changes as those isolated from control rats. The bile duct-like differentiation of hepatocytes was associated with increased expression of Jagged1, Jagged2, Notch1, and several Notch target genes. CK19 expression and branching morphogenesis were inhibited by dexamethasone, a mitogen-activated protein kinase kinase 1 (MEK1) inhibitor (PD98059), and a phosphatidyl inositol 3-kinase inhibitor (LY294002). After being cultured for more than 3 weeks within the gels, hepatocytes transformed into ductular structures surrounded by basement membranes. Our results suggest that hepatocytes might have the potential to transdifferentiate into bile duct-like cells without acquiring a stem-like phenotype and that this is mediated through specific protein tyrosine phosphorylation pathways.

Background/Aims H19 is a paternally imprinted gene that is believed to function as non-coding mRNA. While H19 is only faintly expressed in the normal adult liver, it is abundantly expressed during the fetal period. We explored the possibility that H19 might participate in the regulation of hepatocyte proliferation. Methods Adult male rats and mice were subjected to a two-thirds partial hepatectomy, and after various time periods, hepatocytes were isolated and analyzed for H19 gene expression. The expression was also examined in cultured rat hepatocytes. Results The expression of H19 was dramatically increased after 2 days (rat) and 4 days (mouse), peaked at 3 days (rat) and 6 days (mouse), and then gradually declined. In both species, the increase in H19 gene expression was preceded by the induction of proliferating cell nuclear antigen and DNA synthesis. An allele-specific RT-PCR analysis in the mouse showed that the paternally imprinted status of the gene was maintained after a partial hepatectomy. H19 was strongly induced in spheroid cultures after transient hepatocyte proliferation, but not in conventional monolayer cultures, in which persistent proliferation occurred. Conclusions Our results demonstrated that H19 gene expression was dynamically regulated in adult hepatocytes in close association with their proliferation.

Background: p120catenin (p120ctn), a member of the Armadillo protein family, is ubiquitously expressed and binds to classical cadherins together with other catenins to participate in the adherens junction. p120ctn has numerous isoforms generated through extensive splicing and alternative usage of translation initiation codons. Although the involvement of p120ctn in cell growth control has been postulated, little has so far been known about its expression patterns in the skin and epidermal tumors. Objective: To identify the isoforms expressed in benign and malignant keratinocytes and to analyze the expression patterns of p120ctn in epidermal tumor specimens. Methods: HaCaT, DJM-1, BSCC-93, HSC-1, HSC-5 and A431 cells along with normal skin tissue were subjected to RT-PCR to identify the expressed isoforms. For immunofluorescence study, surgical specimens including 29 squamous cell carcinomas (SSCs), 4 basal cell carcinomas (BCCs) and 4 seborrheic keratoses as well as 3 normal skin samples were stained with specific antibodies to detect p120ctn and E-cadherin. Results: RT-PCR revealed that the isoform 3A was predominantly expressed with faint expression of the isoform 4 and that there was no difference in expressed isoforms between the examined cell lines. Immunofluorescent staining indicated that the expression of p120ctn was significantly reduced in all of the examined squamous cell carcinomas and that p120ctn was frequently localized in cytoplasm. In benign tumors and normal samples, p120ctn was properly expressed in cell–cell boundaries. Furthermore, there were several SCCs where E-cadherin continued to be expressed with no expression of p120ctn. Conclusion: Reduced expression and aberrant localization of p120ctn are among the most common events during the development and/or progression of SCCs.

A rare case of rapidly growing osteosarcoma that developed in the uterine corpus of a 62-year-old woman is presented. The tumor occupied almost the entire pelvic cavity and extended into the abdominal cavity, with marked involvement of the intestines. Histopathologically, the tumor was composed of an osteoblastic component, accompanied by conspicuous bone formation, and a fibroblastic component. The tumor cells were positive for vimentin and osteocalcin, as well as desmin, alpha-smooth muscle actin and muscle-specific actin, but negative for h-caldesmon. The results indicated myofibroblastic differentiation in a part of the tumor. A review of 14 reported cases and our case of uterine osteosarcoma revealed that this tumor has a biologically aggressive nature, although its histopathological and immunohistochemical features are similar to those of osteosarcomas in soft tissue and bone. As the prognosis of patients with this tumor is poor, it is of importance to differentiate this tumor from other types of tumors arising from the uterine corpus.

Measuring nuclear brightness histography may be useful in differentiating among G1 urothelial carcinoma, urothelial dysplasia, and nonneoplastic atypical urothelium.