Yukie Tashiro

Immunohistochemical study of mucin carbohydrates and core proteins in human ovarian tumors

Many of the cancer-associated antigens recently have been identified as mucin antigens. However, there are no detailed studies describing the expression of carbohydrates and core proteins of mucin antigens in ovarian tumors. In this study we examined the expression of carbohydrate antigens, which are associated with the earliest steps in mucin glycosylation (Tn and sialosyl-Tn), and the expression of the mucin core protein antigens associated with the MUC1 gene product (mammary-type apomucin) and the MUC2 gene product (intestinal-type apomucin) in 123 ovarian epithelial (mucinous and serous) tumors. In normal ovarian tissues neither Tn, sialosyl-Tn, nor intestinal-MRP antigens (MUC2 gene product) were expressed, except for positive sialosyl-Tn staining of stromal capillaries, while the MUC1 gene product, DF3 antigen, was expressed in the cell apex of the germinal coelomic epithelium when it had plump, slightly elongated, or pseudostratified nuclei. In the benign adenomas Tn and sialosyl-Tn antigens were detected in a small number of mucinous adenomas and rarely in serous adenomas. In contrast, expression of both Tn and sialosyl-Tn antigens was observed in all the adenocarcinomas and in a considerable number of borderline malignancies. DF3 antigen was expressed in many benign serous tumors but not so frequently in benign mucinous tumors; however, it was frequently expressed in the adenocarcinomas and borderline malignancies of both mucinous and serous types. Intestinal-MRP antigen expression increased with the transition of the mucinous tumors from a benign to malignant state, although it was never detected in the serous tumors. Coexpression of DF3 and intestinal-MRP antigens was seen in borderline malignancies and carcinomas of the mucinous tumors. In conclusion, simultaneous expression of Tn and sialosyl-Tn antigens is a highly effective tumor marker in both mucinous and serous tumors of the ovary. Coexpression of DF3 and intestinal-MRP antigens may indicate the malignant potential of ovarian mucinous tumors.

EPSTEIN-BARR VIRUS-POSITIVE MULTIPLE EARLY GASTRIC CANCERS AND DYSPLASTIC LESIONS : A CASE REPORT

Epstein‐Barr vlrus (EBV) has been implicated as a causal virus of gastrlc cancer with episomal monoclonality, elevated antibodles and a unlque morphologlc expression in the early intramucosal stage, but the infection mechanisms have not been demonstrated. EBV has been shown only in the cancerous lesions by the highly sensltlve EBVencoded small RNA in situ hybridization (EBER‐ISH) method, not in the dysplastic mucosa adjacent to the cancer. A case is presented of multiple EBV‐positive gastric cancer and dysplastic epithelium observed In a 52‐year‐old man. Serlai cut sections of the gastrectomy specimen showed four small cancerous lesions, three of which were EBER‐posltlve, and three EBER‐positive, minute, non‐cancerous dysplastic lesions. The three cancerous lesions were intramucosal cancer, with one having minimal submucosal invasion forming 8 lymphoeplthelioma‐like histology. All of these EBER‐posltlve cancerous and dysplastic lesions showed Intense CD8T‐lyrnphocytic Infiltration. There was no such findings in the EBV‐negative cancerous lesion. It was concluded that EBV infection may occur in the epitheilal cells of atrophic gastric mucosa, and progress to cancer with monoclonal expansion through the EBV‐positive dysplastic change. Cytotoxlc T‐lymphocytic reactions can occur even in the dysplastic lesions. Multifocal EBV infection in the gastric mucosa may occur and, if necessary, total gastrectomy Is recommended in such a case.

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.

Distinct morphologic, phenotypic, and clinical-course characteristics of indolent peripheral T-cell lymphoma

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD20 was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor γ chain and/or α-β chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered.

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.

Clinicopathological analysis of 17 primary cutaneous T‐cell lymphoma of the γδ phenotype from Japan

Primary cutaneous γδ T‐cell lymphoma (PCGD‐TCL) is an aggressive lymphoma consisting of clonal proliferation of mature activated γδ T‐cells of a cytotoxic phenotype. Because primary cutaneous γδ T‐cell lymphoma is a rare disease, there are few clinicopathological studies. In addition, T‐cell receptor (TCR) γδ cells are typically immunostained in frozen sections or determined by TCRβ negativity. We retrospectively analyzed 17 primary cutaneous T‐cell lymphomas of the γδ phenotype (CTCL‐γδ) in a clinicopathological and molecular study using paraffin‐embedded sections. Among 17 patients, 11 had CTCL‐γδ without subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) features and six had CTCL‐γδ with SPTCL features. Immunophenotypically, some significant differences were found in CD8 and CD56 positivity between our patient series of CTCL‐γδ patients with SPTCL features and SPTCL‐γδ patients described in the previous literature. A univariate analysis of 17 CTCL‐γδ patients showed that being more than 60 years old, presence of visceral organ involvement, and small‐to‐medium cell size were poor prognostic factors. In addition, the 5‐year overall survival rate was 42.4% for the CTCL‐γδ patients without SPTCL features and 80.0% for those with SPTCL features. Consequently, there was a strikingly significant difference in overall survival among SPTCL, CTCL‐γδ with SPTCL features and CTCL‐γδ without SPTCL features (P = 0.0005). Our data suggests that an indolent subgroup may exist in CTCL‐γδ. Studies on more cases, including those from other countries, are warranted to delineate the clinicopathological features and the significance in these rare lymphomas.

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.