Hitoshi Yamazaki

A hepatic sclerosed hemangioma with significant morphological change over a period of 10 years: a case report

IntroductionLiver cavernous hemangioma is the most common noncystic hepatic lesion, and a hemangioma that undergoes degeneration and fibrous replacement is called a hepatic sclerosed hemangioma.Case presentationA 63-year-old Japanese man was admitted for detailed investigation of a liver tumor. Tumor markers carcinoembryonic antigen, alpha-fetoprotein, and CA19-9 levels in the peripheral blood were not elevated at any time. Plain computed tomography showed an approximately 1.5cm low density mass in the periphery of segment 8, which was marginally enhanced on contrast-enhanced dynamic computed tomography. On magnetic resonance imaging, the tumor was hypointense on T1-weighted image and hyperintense on T2-weighted image. The tumor was suspected to be an atypical hemangioma, metastatic, hepatocellular carcinoma, or cholangiocellular carcinoma. Segmental hepatectomy was performed. Histological examination of the resected tumor specimen revealed a sclerosed hemangioma with marked hyalinization and sparse stromal fibrosis. Immunochemically, the tumor cells were positive for CD34 and alpha smooth muscle actin. Electron microscopically, the residual hemangioma consisted of numerous caveolae and vesicles in endothelial cells in irregular shapes and sizes. Immunostaining for caveolin-1 showed decreased or no caveolin-1 reactivity in the hyalinized lesions of the sclerosed hemangioma, but abundant caveolin-1 reactivity in the residual cavernous hemangioma. Of interest, computed tomography images of the tumor obtained 10xa0years earlier at our hospital depicted a 3cm typical cavernous hemangioma.ConclusionsHepatic sclerosed hemangioma is a rare condition. Comparison of radiological findings of the lesion over a period of 10xa0years was valuable in providing insight for the evolutional process from liver cavernous hemangioma to hepatic sclerosed hemangioma.

Mixed angiosarcoma, clear cell adenocarcinoma and mature teratoma elements in an ovarian tumor: A case report and literature review

Malignant transformation of a mature teratoma in the ovary is a rare event, with an approximate rate of only 1–2%. Here, we report an ovarian tumor with a unique combination of epithelial and non‐epithelial malignant components, including mature teratoma elements. A 59u2003year‐old postmenopusal woman underwent total hysterectomy and bilateral salpingo‐oophorectomy to remove a huge solid mass of the right ovary. The ovarian tumor was 16 × 12 × 4.5u2003cm in dimensions, composed of red‐brown and greyish‐white tissue with several cystic areas. Microscopically, atypical cells immunopositive for both CD31 and CD34 formed irregular ectatic vascular patterns with a high MIB‐1 labeling index in red‐brown areas. In contrast, tubule‐cystic and papillary structures were lined by HNF‐1β‐immunopositive atypical cuboidal and hobnail cells with clear cytoplasm in greyish‐white areas. In addition, normal‐looking epithelial and stromal components, including mature squamous, cuboidal and ciliated epithelial cells, and adipose tissues, were observed in red‐brown areas, suggesting an ovarian tumor combining angiosarcoma, clear cell adenocarcinoma, and mature teratoma features. We could demonstrate identical X‐chromosome inactivation patterns among all three components by human androgen receptor gene (HUMARA) assays, pointing to complex inter‐relationships regarding their pathogenesis. These observations suggest that a malignant tumor composed of two characteristic phenotypes arose in mature teratoma.

Relation between ultrastructural localization, changes in caveolin-1, and capillarization of liver sinusoidal endothelial cells in human hepatitis C-related cirrhotic liver.

Most vascular endothelial cells are continuously exposed to shear stress in vivo. Caveolae are omega-shaped membrane invaginations in endothelial cells (ECs) and are enriched in cholesterol, caveolins, and signaling molecules. This study was designed to elucidate the ultrastructural localization and change in caveolin-1 expression within human liver sinusoidal endothelial cells (LSECs) during the progression of cirrhosis caused by hepatitis C, using tissue sections prepared via perfusion-fixation. Normal control liver specimens and hepatitis C–related Child-Pugh A and C cirrhotic liver specimens were studied. Caveolin-1 in the liver sinusoids was examined via immunohistochemistry, Western blotting, and immunoelectron microscopy. In control liver tissue, caveolin-1 was localized on caveolae mainly in arterial and portal endothelial cells of the portal tract and was also found on vesicles and some fenestrae in LSECs around the central vein. In cirrhotic liver tissue, aberrant caveolin-1 expression was observed on caveolae-like structures in LSECs. Caveolin-1 was especially overexpressed in late-stage cirrhosis. This study demonstrates that caveolin-1 is strongly expressed within caveolae-like structures and associated vesicles within LSECs of the hepatitis C–related cirrhotic liver. These findings suggest a direct association of caveolin-1 in the process of differentiation of LSECs in cirrhosis-mediated capillarization.

Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen

AIM To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors. METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion (MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion (MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage (36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NY-ESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1 (MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

Prostatic stromal sarcoma with neuroectodermal differentiation

AbstractProstatic stromal sarcoma is a fairly rare tumor that constitutes approximately 0.1–0.2% of all prostatic cancers. Detailed characteristics of the tumor are still unclear due to its rarity.We describe a case of prostatic stromal sarcoma in a 63 year-old man who suffered from urinary obstructive symptoms. Palliative transuterine resection was performed and the preliminary histopathological diagnosis was neuroendocrine carcinoma. After chemotherapy, total pelvic exenteration was performed. Histopathologically, the tumor was composed of monotonously proliferating small to medium-sized round cells, which existed in compact islands with loose or dense fibrovascular networks. Immunohistochemically, the tumor cells were widely positive for vimentin, CD56, CD99 and focally positive for synaptophysin, CD10, progesterone receptor, desmin and CD34, but negative for EMA, cytokeratin, estrogen receptor, S-100 and myoglobin. Most of the previously reported tumors exhibited positive stainability for CD10 and progesterone receptor. In addition to these markers, expressions of CD56, CD99 and synaptophysin were characteristically detected in our case. To the best of our knowledge, we present the first case of prostatic stromal sarcoma with characteristic immunohistochemical staining properties. Although the biological characteristics of this rare tumor have not yet been elucidated, these findings suggest prostatic stromal sarcoma can potentially show neuroectodermal differentiation.Virtual slideThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/7291874028051262

Increases in endothelial caveolin-1 and cavins correlate with cirrhosis progression.

BACKGROUND AND AIMSnCaveolin-1 is associated with flat caveolar domains, invaginated smooth plasmalemmal vesicles, and caveolae. Polymerase 1 and transcript release factor (PTRF) (cavin 1) and serum deprivation protein response (SDPR) (cavin 2) are required for the invagination of caveolae, and PRKCDBP (protein kinase C, delta-binding protein; cavin 3) is required for caveolae budding to form caveolar vesicles. To investigate whether cavins are involved in hepatic sinusoidal angiogenesis and remodeling during progression to cirrhosis, normal control liver specimens and early and late cirrhotic liver specimens were studied.nnnMATERIALS AND METHODSnCavin-1, cavin-2, and cavin-3 proteins and their gene expression were examined using immunohistochemistry (IHC), Western blotting, and laser capture microdissection (LCM)-polymerase chain reaction (PCR) during progression of cirrhosis caused by hepatitis C. According to the perfusion, fixation methods were designed to reevaluate the precise ultrastructural localizations and changes of cavin-1 and cavin-2 expression on liver sinusoidal endothelial cells (LSECs) facing the sinusoidal blood flow.nnnRESULTSnFor IHC, cavin-1 and cavin-2 expressions were found to be upregulated in small angiogenic LSECs with collagen deposition in the perisinusoidal space as well as in the vascular endothelial cells of the remarkably proliferated portal venules, hepatic arterioles, and arterial capillaries within the fibrotic septa of late-stage cirrhotic liver. Cavin-3 was mainly localized in large vessels, and it was detected only scantly on the central vein and hepatic sinusoids in the control liver. In late-stage cirrhotic liver, the intensity of cavin-3 was enhanced mainly on proliferative large vessels in regenerated nodules and in the peripheral regions of nodules and fibrous septa. On conducting immunoelectron microscopy, in the control liver tissue, cavin-1 was found to be localized on the caveolae of hepatic arterial and portal venous endothelial cells, but it was scantly localized on hepatic sinusoidal lining cells, and cavin-2 was found mainly on vesicles in LSECs. In the cirrhotic liver tissue, aberrant cavin-1 and cavin-2 expressions were observed on caveolae-like structures in LSECs. Significant overexpressions of cavin-1 at the protein and messenger RNA (mRNA) levels in a cirrhotic liver were demonstrated by Western blotting and LCM-PCR.nnnCONCLUSIONSnCavin-1 and cavin-2 are strongly expressed within caveolae-like structures and associated vesicles within LSECs of the hepatitis C-related cirrhotic liver. Cavin-1 would play a critical role in regulating aspects of caveolin-1 in LSECs. Moreover, these findings suggest a direct association of cavin-1 and cavin-2 with the process of differentiation and transformation of LSECs inducing hepatic sinusoidal capillarization related to the progression of cirrhosis.

Co‐registered positron emission tomography/computed tomography and gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid magnetic resonance imaging features of multiple angiosarcoma of the liver

Hepatic angiosarcoma is a very rare disease, accounting for only 2% of primary liver malignancy. An 82‐year‐old man was admitted to our hospital because of jaundice and weight loss. Computed tomography (CT) and magnetic resonance imaging (MRI) showed diffuse and multiple space‐occupying lesions. On gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced MRI, the tumor was not enhanced intensely in the arterial phase following contrast injection, and was then gradually enhanced homogeneously. In the delayed phase and hepatobiliary phase, the tumor was completely washed out. Whole‐body 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET)/CT fusion scanning confirmed metabolic activity with maximum uptake value of 3.64 in the lesions. A liver biopsy showed spindle‐shaped tumor cells proliferating along sinusoids, with elongated and hyperchromatic nuclei. Immunohistochemical studies showed tumor cells positive for von Willebrand factor and CD34. These findings were consistent with angiosarcoma of the liver. This case report is the first description of co‐registered FDG‐PET/CT images and Gd‐EOB‐DTPA‐enhanced MRI of primary hepatic angiosarcoma.

A Case of Inflammatory Pseudotumor of the Liver Mimicking Hepatocellular Carcinoma on EOB-MRI and PET

A 71-year-old man was referred to us for investigation of a liver mass and adenomyomatosis of gallbladder. Findings on ethoxybenzyl diethylenetriamine-enhanced MRI (EOB-MRI) led to a presumptive diagnosis of a 1.5u2009cm hepatocellular carcinoma (HCC) in the right posterior lobe of the liver. Transcatheter arterial chemoembolization and radiofrequency ablation of the tumor were attempted. After 2 months, CT scan and EOB-MRI showed that the tumor had enlarged to 3u2009cm. Positron emission tomography (PET) confirmed abnormal metabolic activity with a high standardized uptake value of 7.3 in the lesion. These findings could indicate malignancy such as well-differentiated HCC or cholangiocarcinoma or a benign lesion such as hepatic abscess. Histopathological examination of a liver biopsy revealed a granuloma with many inflammatory cells, leading to a diagnosis of inflammatory pseudotumor of the liver. We report a rare case of hepatic inflammatory pseudotumor with enhancement on EOB-MRI and increased uptake on PET, mimicking HCC.

Aquaporin-1 is associated with arterial capillary proliferation and hepatic sinusoidal transformation contributing to portal hypertension in primary biliary cirrhosis

Although aquaporins (AQPs) in normal hepatobiliary system have been studied, little is known about AQP localization and changes in the hepatic microvascular system including sinusoids in cholestatic liver. The present study aimed to clarify the localization of AQP-1 in the microvessels in normal human liver and in primary biliary cirrhosis (PBC). Human normal liver (control) and PBC liver specimens were obtained. Immunohistochemistry, Western blotting, in situ hybridization (ISH) and electron microscopic examination for AQP-1 were conducted. In control liver and stages I–II PBC liver, AQP-1 immunoreactivity was mainly localized in portal venules, hepatic arterioles and bile ducts in the portal tract, but was hardly detected in the sinusoids. However, AQP-1 expression was enhanced in the proliferated bile ductules in PBC. In stages III–IV PBC liver tissues, AQP-1 was aberrantly expressed in proliferated arterial capillaries opening into the sinusoids at the peripheral edge of regenerating hepatic nodules and in the fibrotic septa. Overexpression of AQP-1 at protein and mRNA levels was demonstrated by Western blot and ISH, respectively. Angiogenetic and fibrotic responses are probably induced by AQP-1, leading to enhanced pouring of arterial blood into the sinusoids; thus, contributing to progression of portal hypertension in PBC.

Participation of aquaporin-1 in vascular changes and remodeling in cirrhotic liver

The pathophysiology of arterial capillary proliferation accompanying fibrosis in human cirrhosis remains unclear. However, evidence regarding the molecules participating in the pathophysiological process has been accumulating. Water channel proteins known as aquaporins (AQP)s, notably AQP-1, appear to be involved in the arterial capillary proliferation in the cirrhotic liver.