Hiroshi Shirahama

Expression of Sulfomucins in Normal Mucosae, Colorectal Adenocarcinomas, and Metastases

We have examined the expression of specific mucin antigens in tissue sections from 92 cases of colorectal carcinoma, using sulfomucin‐specific monoclonal antibody (MAb) 91.9H. The expression of sulfomucins was high in normal mucosae and much lower in primary colorectal carcinoma, in metastatic lesions in lymph nodes or in liver. The intracellular localization of sulfomucins was also different among these tissues. In normal mucosae, MAb 91.9H binding was seen in the supranuclear area, presumably Golgi complexes, the luminal surface, and secretory products. In primary colorectal carcinomas and in their metastatic lesions, MAb 91.9H was preferentially localized in the cell surface and substances attached to the luminal surface of glandular structures. Analysis of the lysates of normal and tumor tissues showed that very‐high‐molecular‐weight components contained the antigenic epitopes. The intensity of MAb 91.9H binding was lower in tumors at advanced stages than in tumors at early stages. These high‐molecular‐weight components were apparently reactive with MAb FH6 specific for sialyl‐Lex (s‐Lex) structures. Histological specimens with low levels of MAb 91.9H reactivity often exhibited relatively high levels of MAb FH6 reactivity. These two mucins may have reversed expression during carcinogenesis and carcinoma progression, and this change may be related to metastatic potential.

18FDG PET for grading malignancy in thymic epithelial tumors: Significant differences in 18FDG uptake and expression of glucose transporter-1 and hexokinase II between low and high-risk tumors: Preliminary study

PURPOSE To evaluate (18)F-fluorodeoxyglucose (FDG) uptake to predict the malignant nature and analyze the correlation between FDG uptake and expression of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in thymic epithelial tumors. MATERIALS AND METHODS Eleven patients with a thymic epithelial tumor who underwent FDG PET/CT before therapy were reviewed. The thymic tumors were classified by the WHO histological classification and Masaoka clinical staging. Comparison of maximum standardized uptake value (SUV(max)) of the lesion was made between the low-risk (Type A, AB and B1) and high-risk {Type B2, B3 and C (thymic cancer)} groups and among clinical stages. Expression of Glut-1 and HK-II was analyzed immunohistochemically. RESULTS All 11 tumors showed FDG uptake visually. SUV(max) was significantly higher in the high-risk group (n=5, 5.24 ± 2.44) than the low-risk group (n=6, 3.05 ± 0.55) (P=0.008). Staining scores of both Glut-1 and HK-II were significantly higher in the high-risk group than in the low-risk group (Glut1: P=0.034 and HK-II: P=0.036). There were no significant differences in SUV(max) (P=0.11), Glut-1 (P=0.35) and HK-II scores (P=0.29) among clinical stages. SUV(max) was significantly correlated to each of the staining scores of Glut-1 (ρ=0.68, P=0.031) and HK-II (ρ=0.72, P=0.024). CONCLUSION These preliminary results support the previously published view that SUV(max) may be useful to predict the malignant nature of thymic epitherial tumors and suggest that the degree of FDG uptake in the thymic epitherial tumors is closely related to the amount of Glut-1 and HK-II in the tumor.

Effect of Clinicopathologic Factors on Visibility of Colorectal Polyps with FDG PET

OBJECTIVE The objective of our study was to clarify which clinicopathologic factors affect the FDG PET visibility of colorectal polyps. MATERIALS AND METHODS We used statistical methods in a retrospective examination of factors affecting the visibility of 87 colorectal polyps in 50 patients who underwent PET for cancer screening. RESULTS PET depicted 37% (32/87) of polyps. Univariate analysis revealed significant associations between polyp visibility and polyp size, histologic grade (p < 0.001 each), type (p = 0.004), and patient age (p = 0.049) but not sex or polyp location. The visualization rate increased with increases in polyp size (< or = 5 mm, 12%; 6-10 mm, 47%; > or = 11 mm, 59%) and severity of dysplasia (indefinite or low-grade dysplasia, 13%; high-grade dysplasia, 67%; polyp with early carcinoma, 75%) and was higher for pedunculated polyps (59%) than for nonpedunculated polyps (27%). Multivariate analysis showed that histologic grade was the strongest factor (p < 0.001) among three independent factors (histologic grade, type, and age). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for visualization of high-grade or early carcinoma polyps to be removed were 71%, 87%, 78%, 82%, and 80%. Maximum standardized uptake values did not differ significantly between visualized polyps with indefinite or low-grade dysplasia and visualized polyps with high-grade dysplasia or early carcinoma. CONCLUSION Histologic grade is the strongest independent factor in FDG PET visibility of colorectal polyps. FDG PET visibility may be helpful for predicting whether a polyp should be removed or observed. FDG PET findings also may suggest the need to alter the treatment of patients with colorectal polyps.

Epstein-Barr virus-associated enteritis with multiple ulcers after stem cell transplantation : First histologically confirmed case

The present case involves unique enteritis forming multiple ulcers associated with Epstein–Barr virus (EBV). A 57‐year‐old man had undergone a reduced intensity allogeneic stem cell transplantation for a relapse of multiple myeloma following sequential autologous peripheral blood stem cell transplantation. The ileum, resected for massive melena, showed multiple irregular ulcers with occasional cobblestone‐like appearance. There was inflammation including numerous plasma cells in the ulcer bases and surrounding areas, where many EBV‐infected plasma cells were detected by double staining with EBV‐encoded small RNA‐1 (EBER‐1) in situ hybridization and CD79a, while EBV‐infected epithelial cells were not noted. The number of EBER‐1‐positive cells in the ileum (mucosa, 1451 cells/mm2; submucosa, 465 cells/mm2) was much larger than in control samples (malignant lymphoma or leukemia after allogeneic stem cell transplantation, n = 4, range 0–113 cells/mm2; malignant lymphoma after chemotherapy, n = 14, range 0–0.89 cells/mm2; colon cancer, n = 12, range 0–3.5 cells/mm2). In the mucosa near the ulcers, EBER‐1‐positive cells often surrounded and involved the glandular epithelium, forming lymphoepithelial‐like lesions. The histological findings differ from post‐transplant lymphoproliferative disorders or intestinal thrombotic microangiopathy, and this is the first case of EBV‐associated enteritis with ulcers characterized by numerous plasma cells and lymphoepithelial‐like lesions after stem cell transplantation.

Paraneoplastic vasculitic neuropathy: immunohistochemical studies on a biopsied nerve and post-mortem examination

Abstract. We studied a patient with paraneoplastic vasculitic neuropathy (PVN) associated with a carcinoma of the common bile duct. Immunohistochemical analysis of the biopsied sural nerve showed that the cellular infiltrates in the vascular lesions were composed primarily of CD8‐positive T lymphocytes and macrophages. Pathogenic significance of the T‐cell‐mediated immunological reaction was suggested. Post‐mortem examination revealed the absence of systemic vasculitis, which may be a characteristic feature of PVN. The patient responded to immunosuppressive treatment. We discuss the efficacy and the risk of immunosuppressive therapy for PVN.

Alpha-fetoprotein (AFP)-producing adrenocortical carcinoma — Long survival with various therapeutic strategies including a lung resection: Report of a case

We experienced a very rare case of late pulmonary metastasis from ACC. The patient was a 40-year-old woman who had undergone a left adrenectomy 12 years earlier. Instead of a large metastatic lung tumor with hemothorax and the existence of metastases in other organs, combined therapy of repeated resections for metastases and adjuvant therapy allowed for almost a 36-month survival following the first recurrence and a good quality of life. In addition, a blood and pathological study revealed that the tumor in this case was an alpha-fetoprotein-producing ACC, which is, as far as we could ascertain, the first case of its kind.

CD8 positive T-cell infiltration in the dentate nucleus of paraneoplastic cerebellar degeneration

Recent reports have discussed the presence of cytotoxic T cells in paraneoplastic cerebellar degeneration (PCD). We report an autopsy case of PCD associated with anti-Hu antibody, in which we revealed infiltration of CD8+ T cells in and around the dentate nucleus but not in the cerebellar cortex, in addition to severe Purkinje cell loss. Some infiltrated mononuclear cells expressed cytotoxic cell marker, Granzyme B. Decrease of neurons and reduced presynapses were demonstrated in the dentate nucleus. This is the first report that suggests the possibility of the dentate nucleus being primarily attacked followed by Purkinje cell loss in PCD.

Synchronous multicentric thymona: report of a case.

We report a case of multiple thymoma with different histological subtypes, not associated with myasthenia gravis. We describe the histological findings, especially the results of immunohistochemical staining, which support the possibility of multicentric thymoma. The validity of extended thymectomy is also discussed.

An atypical extrahepatic metastasis of the distal phalanx from hepatocellular carcinoma

A 49-year-old woman presented with severe swelling and pain of the left little finger, which had exacerbated rapidly, in October 2006. The patient had a history of hepatocellular carcinoma and metastatic lung cancer. She had undergone partial hepatectomy for the hepatocellular carcinoma in September 2001 and pulmonary resection for metastatic lung cancer in November 2005. Roentgenogram of the hand on admission showed complete destruction of the distal phalanx of the left little finger. The final pathological result of the tissue obtained by disarticulation was an extrahepatic metastasis of hepatocellular carcinoma. Extrahepatic metastasis from primary hepatocellular carcinoma to the hand is very rare and only four cases have been reported in the literature. All the patients with extrahepatic metastases from the primary hepatocellular carcinoma to the hand had poor prognoses, but the patient presented in this article exhibited an unusual clinical course. The patient is still alive 1 year after the diagnosis of extrahepatic bone metastasis of the distal phalanx.

A comprehensive expression analysis of mucins in appendiceal carcinoma in a multicenter study: MUC3 is a novel prognostic factor.

Background Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma. Methods Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma. Results The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93–24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05–34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13–10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma. Conclusions Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.