[Show abstract][Hide abstract] ABSTRACT: Twenty-six Japanese cases of type II enteropathy-associated T-cell lymphoma (EATL) were examined. Multiple tumors throughout the small intestine were found in 15 patients (58%) and duodenal and colonic mucosal lesions in 8 and 6 cases, respectively. Histologically, intramucosal tumor spread and a zone of neoplastic intraepithelial lymphocytes (IELs) neighboring the main transmural tumors were detected in 20 (91%) and 17 (77%) of the 22 cases examined, respectively. Inside and outside of the IEL zone, some degree of enteropathy with many reactive small IELs and villous atrophy was detected in 11 cases (50%). Immunohistologically, many CD56/CD8-positive small IELs were found in the enteropathic lesions of 4 (36%) and 7 (64%) of these 11 cases. Lymphoma cells expressed tyrosine kinase receptor c-Met, serial p-MEK1/2, c-Myc, and Bcl2 in 18 (78%), 21 (91%), 11 (42%), and 19 (73%) of the total cases, respectively. By fluorescence in situ hybridization, chromosomal loci 7q31 (c-Met) and 8q24 (c-Myc) were amplified in 11 (65%) and 12 (71%) of the 17 cases analyzed. Gain of 7q31 and c-Met expression were significantly (p < 0.01) higher than in peripheral CD8-positive T-cell or CD56-positive NK-cell lymphomas. Enteropathy was seen near the IEL zone in type II EATL, and activation of the c-Met, MEK-MAPK pathway and c-Myc-Bcl2-mediated cell survival may play important roles in lymphomagenesis, converting enteropathy to type II EATL. Seven cases in the early clinical stages I and II-1 showed significantly (P < .01) better prognoses than did those in the advanced stages. Early detection of the mucosal lesions and tumors may improve patient prognosis.
Human pathology 06/2014; 45(6). DOI:10.1016/j.humpath.2013.10.038 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had Sjögren's syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case in each of these two groups was complicated by chronic HCV-seropositive hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory processes associated with HCV infection or autoimmune disease may play independent roles in the lymphomagenesis of hepatic B cells.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2012; 460(4):379-87. DOI:10.1007/s00428-012-1199-x · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To elucidate the clinicopathological findings of primary intestinal enteropathy-associated T cell lymphoma (EATL) in Japan, a non-endemic area for coeliac disease.
Of the 24 cases, four (17%) had large-cell lymphoma (type I), and the remaining 20 (83%) had medium-sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56-positive. Only one (4%) case showed typical CD56- and CD8-negative and CD30-positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy-like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy-like lesions in five (24%) cases expressed T-bet, with no cases of CD30-positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele.
Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs.