[A case of non-acquired immunodeficiency syndrome-defining lung adenocarcinoma in a multidrug-resistant human immunodeficiency virus-positive patient].

We report a case of non-acquired immunodeficiency syndrome-defining lung adenocarcinoma in a multidrug-resistant human immunodeficiency virus (HIV)-positive patient. The patient was a 47-year-old Japanese woman who received salvage combination anti-retroviral therapy with darunavir plus ritonavir plus raltegravir plus tenofovir/emtricitabine in May 2009. She was diagnosed with lung adenocarcinoma (T3N3M1, stage IV) in November 2010 and was not found to possess any activating mutations in the epidermal growth factor receptor gene. Therefore, 6 courses of carboplatin plus pemetrexed and 3 courses of gemcitabine followed by erlotinib were administrated, and therapy was changed to home medical care. The only drug-related adverse event was grade 1 neutropenia, and drug interaction between the simultaneously administered anti-retroviral and chemotherapeutic agents was not confirmed. The patient battled lung adenocarcinoma for 1 year after the diagnosis and died of cancer progression in October 2011. Her performance status was stable and the CD4 (+) lymphocyte count and HIV load were well controlled throughout the course of treatment. In conclusion, the agents used for this patient show high tolerability and can be used as an effective treatment strategy for lung cancer occurring in HIV-positive patients.

A case report of angioimmunoblastic T cell lymphoma (AITL) with localization of neoplastic clear cells in the outer zone of germinal centers.

Angioimmunoblastic T cell lymphoma (AITL) is characterized by the presence of atypical lymphocytes with clear cytoplasm and follicular dendritic cells, arborization of high endothelial blood vessels, and infiltration by inflammatory cells, such as epithelioid histiocytes, eosinophils, immunoblasts, and plasma cells. The neoplastic clear cells are localized around the high endothelial blood vessels or interfollicular areas. Recent reports have suggested that these neoplastic clear cells originate from helper T cells in germinal centers, based on their expression of CD10, PD-1, and CXCL13. We experienced a case of AITL which is histologically unique. A 61-year-old male presented to our hospital (Ogaki Municipal Hospital) with edema of his lower legs. Inguinal lymph node biopsy revealed that neoplastic clear T cells were mainly localized in the outer zone of germinal centers, specifically within the follicular dendritic cell (FDC) meshwork. Moreover, these cells were positive for CD3, CD4, CD10, CD43, CD45RO, PD-1, and weakly positive for CXCL-13. This is the first report showing that the neoplastic clear T cells were localized in the outer zone of germinal centers morphologically as well as immunohistochemically. In conclusion, this case report further supports the notion of germinal center helper T cell origin of neoplastic clear cells in AITL.

Epstein-Barr virus-associated lymphoproliferative disorder presenting with classical Hodgkin lymphoma and developing as peripheral T-cell lymphoma 9 years later: a case report of composite lymphoma.

We describe a patient who was diagnosed with classical Hodgkin lymphoma (CHL) at 67-years-old and peripheral T-cell lymphoma, not otherwise specified (PTCL) at 76-years-old, and died 5 months later. Both tumors showed prominent epithelioid cell reaction admixed with neoplastic cells. Hodgkin and Reed-Sternberg cells in the swollen lymph node were positive for CD30 and EBV-encoded RNA (EBER). PTCL cells in the skin tumor were positive for cytoplasmic CD3ε, CD4 and EBER. A rearrangement band of the T-cell receptor gene was detected in the skin tumor. This case is the first documented EBV-associated composite lymphoma composed of CHL and PTCL. The patient may show the possibility that both EBV infection and/or immunodeficiency induce the development of CHL and PTCL.

Coexistence of primary pulmonary Hodgkin lymphoma and gastric MALT lymphoma associated with Epstein-Barr virus infection: a case report.

We describe a 66-year-old woman with Epstein-Barr virus-associated lymphoproliferative disorder with lung and gastric tumors. We identified two lung tumors measuring 13 and 20 mm in diameter that consisted of CD30-, CD15-, and CD20-positive Hodgkin- and Reed-Sternberg-like cells and heterogeneous cellular infiltrates in a pronounced nodular pattern, with necrosis and vasculitis, diagnosed as nodular sclerosis classical Hodgkin lymphoma. A gastric tumor showed low-grade extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Neoplastic cells in all tumors expressed Epstein-Barr virus-encoded RNA based on in situ hybridization. The present case is a rare composite lymphoma arising from different extranodal organs, associated with EBV infection. Her medical history included gamma-knife therapy for clinical diagnosis with a suspicion of cerebral lymphoma.

Primary cardiac B-cell lymphoma presented as heart tamponade and atrioventricular block: a case report.

BACKGROUND: Primay cardiac lymphoma is rare, and its diagnosis is not determined until autopsy. CASE: A 49-year-old man presented with heart tamponade and atrioventricular block. Bloody pericardiac effusion showed a monotonous proliferation of atypical large mononuclear cells, which demonstrated a lambda light-chain monoclonality by the fluorescence-activated cell-sorter method and clonal rearrangement bands by Southern blot analysis of the IgH gene. Transvenous biopsy excised from the right atrial tumor was diagnosed as diffuse large B-cell lymphoma. He underwent chemotherapy and permanent pacemaker implantation and is alive and well. CONCLUSION: Liquid cytology of cardiac effusion was very useful for rapid diagnosis, leading to a better prognosis.

Sphingosine 1-phosphate potentiates human lung fibroblast chemotaxis through the S1P2 receptor.

Migration of fibroblasts plays an essential role in tissue repair after injury. Sphingosine 1-phosphate (S1P) is a multifunctional mediator released by many cells that can be released in inflammation and after injury. This study evaluated the effect of S1P on fibroblast chemotaxis toward fibronectin. S1P alone did not affect fibroblast migration, but S1P enhanced fibronectin-directed chemotaxis in a concentration-dependent manner. The effect of S1P was not mimicked by dihydro (dh) S1P or the S1P(1) receptor agonist SEW2871. S1P augmentation of fibroblast chemotaxis, however, was completely blocked by JTE-013, an S1P(2) antagonist, but not by suramin, an S1P(3) antagonist. Suppression of the S1P(2) receptor by small interfering (si)RNA also completely blocked S1P augmentation of fibroblast chemotaxis to fibronectin. S1P stimulated Rho activation and focal adhesion kinase (FAK) phosphorylation, and these were also significantly inhibited by the S1P(2) receptor antagonist (JTE-013) or by S1P(2) siRNA. Further, the potentiation of S1P signaling was blocked by the Rho-kinase inhibitor Y-27632 in a concentration-dependent manner. Inhibition of FAK with siRNA reduced basal chemotaxis toward fibronectin slightly but significantly, and almost completely blocked S1P augmented chemotaxis. These results suggest that S1P-augmented fibroblast chemotaxis toward fibronectin depends on the S1P(2) receptor and requires Rho and Rho-kinase, and FAK phosphorylation. By augmenting fibroblast recruitment, S1P has the potential to modulate tissue repair after injury. The pathways by which S1P mediates this effect, therefore, represent a potential therapeutic target to affect tissue repair and remodeling.

Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human.

c-Maf translocation or overexpression has been observed in human multiple myeloma. Although c-maf might function as an oncogene in multiple myeloma, a role for this gene in other cancers has not been shown. In this study, we have found that mice transgenic for c-Maf whose expression was direct to the T-cell compartment developed T-cell lymphoma. Moreover, we showed that cyclin D2, integrin beta(7), and ARK5 were up-regulated in c-Maf transgenic lymphoma cells. Furthermore, 60% of human T-cell lymphomas (11 of 18 cases), classified as angioimmunoblastic T-cell lymphoma, were found to express c-Maf. These results suggest that c-Maf might cause a type of T-cell lymphoma in both mice and humans and that ARK5, in addition to cyclin D2 and integrin beta(7), might be downstream target genes of c-Maf leading to malignant transformation.

Second-line triple therapy in failures with vonoprazan-based triple therapy for eradication of Helicobacter pylori.

Gastric acid inhibition during treatment is important for the eradication of Helicobacter pylori (H. pylori) infection. A novel potassium-competitive acid blocker, vonoprazan (VPZ), has been demonstrated to achieve high eradication rates; however, the efficacy of second-line treatment in failures of VPZ-based triple therapy has not been well studied. The aim of the current study was to determine the efficacy of VPZ in a first-line regimen for H. pylori eradication, and the efficacy of a second-line regimen using metronidazole (MTZ) in failures with the first-line regimen. Of 580 subjects enrolled in the study, 524 patients completed first-line treatment (275 patients who received VPZ and 249 patients who received LPZ). First-line regimens consisted of a combination of clarithromycin (CAM) 200 or 400 mg twice a day, amoxicillin (AMPC) 750 mg twice a day, and either LPZ 30 mg or VPZ 20 mg twice a day, administered orally for 7 days. CAM and VPZ/LPZ were replaced with metronidazole (MTZ) 250 mg and rabeprazole 10 mg in the second-line regimens. The eradication of H. pylori was assessed by the H. pylori stool antigen test. The overall first-line eradication rate with VPZ was significantly higher than that with LPZ [91.0% (250/275) vs. 84.7% (211/249), respectively, P=0.030]. The dose of CAM (400 vs. 800 mg) did not affect the eradication rate in either the VPZ or LPZ regimens. The overall eradication rates of the second-line regimens with MTZ did not differ significantly between the VPZ-failure and LPZ-failure groups [87.0% (20/23) vs. 87.9% (29/33), respectively, P=0.700]. Therefore, VPZ was significantly more effective than LPZ for first-line treatment. In patients with failure of first-line eradication therapy, successful results of second-line eradication therapy did not differ between the VPZ- and LPZ-failure groups. In conclusion, VPZ-based triple therapy should be recommended for eradication of H. pylori.

c-Maf expression in angioimmunoblastic T-cell lymphoma.

The oncogene c-Maf was recently found to be overexpressed in approximately 50% of multiple myeloma cases, and a role for c-Maf in promoting cyclin D2 expression has been postulated. We previously examined c-Maf expression in various T-cell lymphomas by reverse-transcription polymerase chain reaction and found extremely elevated c-Maf levels in angioimmunoblastic T-cell lymphoma (AILT). In this study, we examined T-cell lymphomas for c-Maf and cyclin expression immunohistochemically. Of 93 cases of T-cell lymphomas we investigated in the current study, c-Maf expression was seen in 23 out of 31 cases of AILT, 3 out of 11 of adult T-cell leukemia/lymphoma, 4 out of 19 of peripheral T-cell lymphoma, unspecified [PTCL(U)], and 0 out of 11 cases of mycosis fungoides, 0 out of 11 of anaplastic large cell lymphoma, and 1 out of 10 of extranodal NK/T-cell lymphoma, nasal type. Double immunostaining in AILT revealed that the majority of c-Maf-positive cells were also positive for CD43 (MT1), CD45RO (UCHL-1), and CD4 but were negative for CD20 (L26). Additionally, cyclins D1 and D2, which stimulate cell cycle progression, were overexpressed in a large number of the c-Maf-positive AILT samples. Quantitative reverse-transcription polymerase chain reaction analysis also showed that c-Maf was overexpressed in 8/31 cases of AILT, 0/19 cases of PTCL(U), 0/11 cases of anaplastic large cell lymphoma, 0/10 cases of extranodal NK/T-cell lymphoma, nasal type, and 2/8 cases of multiple myeloma, presenting significant difference between AILT and PTCL(U) (P=0.016, chi test). These findings strongly suggest that CD4-positive neoplastic T cells in AILT show c-Maf expression and provide new insight into the pathogenesis of AILT suggesting c-Maf to be a useful diagnostic marker for AILT.

Diffuse large B-cell lymphoma initially manifesting in the bone marrow.

We histologically and immunohistochemically studied 37 cases of diffuse large B-cell lymphoma (DLBCL) initially manifesting in the bone marrow (BM). We also compared these cases with the Asian variant of intravascular large B-cell lymphoma (AIVL). Histologically, the neoplastic cells of the BM mostly had large and round nuclei and formed clusters. Immunohistochemically, all cases were positive for B-cell markers. Factor VIII staining revealed neoplastic cells within the sinusoids of BM in 8 cases; however, these cells accounted for fewer than 20% of the overall neoplastic cells. In several cases, the neoplastic cells infiltrated liver, spleen, kidneys, lungs, stomach, and adrenal glands with a mainly leukemic and infrequently intravascular pattern. Although our cases share some clinical features with AIVL, we consider DLBCL initially manifesting in the BM to be a unique entity because the neoplastic cells proliferate mainly in BM, with infrequent involvement of the sinusoids and occasional leukemic infiltration in various organs.

Osteosarcoma arising in the breast.

We report on a 49-year-old woman with osteosarcoma arising in the breast. She had undergone two consecutive excision biopsies for right breast tumors at ages 40 and 42 years. The tumors were diagnosed as a fibroadenoma and a benign phyllodes tumor, respectively. At age 46 years, she noticed a gradually enlarging mass in the same breast. After 3 years, at age 49 years, total mastectomy was performed. The tumor occupied the entire breast and measured 12x9x8.5 cm. The tumor cells were spindle-shaped and pleomorphic, with large, irregular nuclei and distinct nucleoli. Many tumor cells had characteristics of osteoblastic and chondroblastic elements producing osteoid, osseous, and cartilaginous intracellular substances. Pathologic mitoses and apoptotic cells were frequent. Neoplastic cells had infiltrated the skin. Blood and lymph vessel invasion was present. Tumor cells expressed vimentin, osteopontin, vascular endothelial growth factor, CD10, and alkaline phosphatase, but did not express keratin. Chemotherapy was not effective. The patient died of multiple pulmonary metastases 9 months after mastectomy.

Quantitative analysis of herpesvirus load in the lymph nodes of patients with histiocytic necrotizing lymphadenitis using a real-time PCR assay.

The cause of histiocytic necrotizing lymphadenitis (HNL) has been ascribed to viral infection, but its pathogenesis still remains unknown. Real-time PCR assays are useful not only for their sensitivity of detection but also for the quantitation of viral DNA with a wide linear range. We accordingly used this technique to estimate for each patient the viral load of the following members of the herpesvirus family: Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus (HHV) types 6, 7, and 8. Samples of patients diagnosed as reactive lymphadenopathy (RL) were included for control. Thirty percent (6/20 cases) and 63% (12/19 cases) of the HNL and RL patients were positive for EBV, and the mean of the detectable EBV viral load of the HNL and that of the RL patients were 463 and 355 (copies/mug DNA), respectively. By in situ hybridization, EBV-encoded RNA could be detected in the lymph tissue samples with more than 14.3 copies/mug of EBV DNA. No significant difference was detected between the number of HNL patients with HHV6 DNA (3/20, 15%) or HHV7 DNA (2/20, 10%) and RL controls. CMV and HHV8 were not detected in the DNA from any patient. In this study, we were unable to definitively identify the causative herpesvirus for HNL; however, 1 HNL case had an extremely large copy number of HHV6-DNA and displayed positive immunostaining for the HHV6 early/late antigen in lesional areas of the node, suggesting that HHV6 infection may be associated with some cases of HNL.

Loss of O6-methylguanine-DNA methyltransferase protein expression is a favorable prognostic marker in diffuse large B-cell lymphoma.

Although aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) is a favorable prognostic marker in patients with diffuse large B-cell lymphoma (DLBCL), MGMT protein expression has not been thoroughly examined. The aim of this study was to evaluate the clinical implication of MGMT protein expression and its correlation with promoter hypermethylation of the gene. We investigated MGMT protein expression by immunohistochemical analysis of 63 DLBCL patients who received cyclophosphamide as part of multidrug regimens. In addition, promoter methylation of the MGMT gene was analyzed by a methylation-specific polymerase chain reaction assay, and correlations with chemotherapeutic effect and prognosis were statistically evaluated. Immunohistochemical assay results for MGMT protein were negative in 30.2% of patients with newly diagnosed DLBCL. Immunostaining results were closely correlated with the methylation status of the promoter. Promoter DNA methylation of the gene was not detected in 34 (81.0%) of 42 tumor samples determined to be MGMT-positive DLBCL by immunostaining and was detected in 15 (88.2%) of 17 cases of MGMT-negative DLBCL. Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in MGMT-negative patients than in MGMT-positive patients (5-year OS, 81.3% versus 56.6% [P = .0375]; 5-year DFS, 66.3% versus 39.9% [P = .0121]). The combined rate for complete response (CR) plus unconfirmed CR was significantly higher in MGMT-negative patients (15/19, 79.0%) than in MGMT-positive patients (25/44, 56.8%) (P = .0488). A multivariate analysis showed that absence of MGMT expression was an independent prognostic factor for OS (relative risk, 4.09; P = .0258). Lack of MGMT protein expression is associated with aberrant promoter DNA methylation and appears to be a useful marker for predicting the survival of DLBCL patients.

Promoter hypermethylation of the DNA-repair gene O6-methylguanine-DNA methyltransferase and p53 mutation in diffuse large B-cell lymphoma.

The gene for the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which is closely related with cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation in several human cancers, including malignant lymphoma. Promoter hypermethylation of the MGMT gene is a favorable prognostic factor in diffuse large B-cell lymphoma (DLBCL). Although inactivation of the MGMT gene is closely related to p53 gene mutations in several cancers, the relationship between p53 gene mutation and MGMT inactivation in malignant lymphoma has not been thoroughly examined. We studied the correlation between MGMT hypermethylation and p53 mutation in DLBCL and their impacts on patient prognosis. In a retrospective cohort study, we used a methylation-specific polymerase chain reaction technique to analyze the methylation status of the promoter region of the MGMT gene in 116 DLBCL patients who received cyclophosphamide as part of multidrug combination chemotherapies. Denaturing high-performance liquid chromatography and direct sequencing were used to search for p53 gene mutations in exons 5 through 9 in 96 of the 116 samples. Disease-free survival and overall survival were estimated by the Kaplan-Meier method. Multivariate survival analyses were performed with the Cox proportional hazards model. Forty-five (38.8%) of 116 DLBCL patients showed MGMT promoter hypermethylation. The presence of MGMT hypermethylation was associated with better overall survival (P = .036). MGMT promoter hypermethylation was a prognostic factor that was independent of established prognostic factors, such as age, disease stage, serum lactic dehydrogenase level, and the number of extranodal disease sites (hazard ratio, 2.43; 95% confidence interval, 1.28-4.61; P = .007). p53 mutations were detected in 19 (19.8%) of 96 patients and were identified as a risk factor in the complete remission rate and overall survival (P = .0040, and P = .027, respectively). A correlation between MGMT hypermethylation and p53 mutation or p53 G:C-to-A:T mutation was not observed (P = .88, and P = .31, respectively). MGMT promoter hypermethylation and p53 mutation are useful prognostic markers in DLBCL. The impact of MGMT inactivation on p53 mutation in DLBCL is unclear.

Clinicopathological features and prognostic factors of Japanese patients with "peripheral T-cell lymphoma, unspecified" diagnosed according to the WHO classification.

Clinicopathological features of 36 patients, male: 58.3%; median: 68 years, with "peripheral T-cell lymphoma, unspecified" diagnosed by the WHO criteria were reviewed. Majority (69.4%) had stage IV disease with frequent involvements into bone marrow, spleen, liver, and skin. According to the IPI, 72.2% were categorized as high or high-intermediate risk group. CR and PR were achieved in 12 and 10 out of 31 patients treated by CHOP-based chemotherapy, respectively. One- and two-year overall survivals were 60.6 and 25.0%, respectively. Performance status, serum LDH, and B symptom were significant prognostic factors. Survival of CD4-/CD8+ cases, corresponding to cytotoxic T-cell lymphoma, was significantly worse than that of CD4+/CD8-.

A common clonal origin of nodal marginal zone B-cell lymphoma and plasma cell myeloma demonstrating different immunophenotypes: a case report of composite lymphoma.

We demonstrated an 83-year-old male case of composite lymphoma. Before 18 years, he was diagnosed with nodal marginal zone B-cell lymphoma in the cervical lymph node. Peripheral blood showed anemia and IgA (kappa)-type monoclonal gammopathy (IgA; 3,625 mg/dL). Bone marrow aspiration biopsy exhibited plasma cell myeloma, in which atypical plasma cells were positive for cytoplasmic IgA (kappa) and atypical lymphoid cells intermingled were positive for CD20. In contrast, cervical lymph node biopsy revealed nodal marginal zone B-cell lymphoma, in which lymphoma cells were positive for cytoplasmic IgG (lambda). Southern blotting analysis of the IgH gene showed same clonal rearrangement band in both lymph node and bone marrow samples and additional band in the bone marrow. Sequence analyses of the IgH gene showed an identical sequence of CDR3 in both samples. Thus, we demonstrated a common clonal origin of composite lymphoma comprising nodal marginal zone B-cell lymphoma and plasma cell myeloma. Nodal marginal zone B-cell lymphoma recurred in cervical lymph node and involved into the bone marrow, differentiating into plasma cell myeloma in which Ig isotype switched and monoclonal gammopathy developed. Sequence analysis of the IgH gene was a powerful tool for determination of clonal origin.

Epstein-Barr virus-positive Hodgkin/Reed-Sternberg-like B cell in non-hodgkin lymphoma: nucleotide sequence of the amplified immunoglobulin heavy-chain variable region gene by the single-cell polymerase chain reaction technique.

We examined nucleotide sequences of Epstein-Barr virus (EBV)-positive Hodgkin/Reed-Sternberg (HRS)-like B cells in a case of diffuse large B-cell lymphoma (DLBCL) and a case of adult T-cell lymphoma (ATL) for single-cell polymerase chain reaction of the immunoglobulin heavy-chain gene variable region (VH gene). HRS-like B cells were scattered in the area irrelevant to the lymphoma infiltrates of DLBCL and in the lymphoma area of ATL. HRS-like B cells were positive for CD20 and CD30 but negative for CD15. EBV presented in HRS-like B cells in both cases but not in any lymphoma cells. VH genes of five HRS-like B cells analyzed in DLBCL were polyclonal and showed in-frame sequences with 0% to 2.8% somatic mutation frequency. In an ATL, VH genes of five HRS-like B cells analyzed were polyclonal and somatically mutated. Four cells carried in-frame rearrangements with 3.5% to 17.7% mutation frequency. One of the VH genes has a one-codon deletion. From the fifth cell, an out-of-frame rearrangement with an insertion and a deletion was obtained. Thus, we showed polyclonal EBV-positive HRS-like B cells in both DLBCL and ATL and that whereas EBV-positive, HRS-like B cells in DLBCL exhibited unmutated and mutated VH gene, those in ATL were found to have a somatically mutated VH gene with/without deletions and/or insertions. The HRS-like B cells may appear because of active EBV infection in a patient who is immunosuppressed from the primary lymphoma.

Cytotoxic T-cell lymphoma arising in Behçet disease.

The case of a 49-year-old man with peripheral T-cell lymphoma arising in Behcet disease (BD) is reported. A diagnosis of incomplete BD was made, and the patient was treated with immunosuppressive agents for 9 months. A left perirenal mass emerged, and a computed tomography-guided needle biopsy of the tumor revealed the infiltration of small- and medium-sized lymphoma cells. The cells were positive for CD3, CD8, CD45RO, CD43, granzyme B, and T-cell intracellular antigen-1. A diagnosis of non-Hodgkin's lymphoma (diffuse medium, T-cell) was made. A left orbital mass also appeared. Standard combination chemotherapy diminished the perirenal and orbital lesions. Lymphoma cell infiltration in the esophagus was detected after chemotherapy, and the patient died of massive bleeding from the gastrointestinal tract. Non-Hodgkin's lymphoma is rarely associated with BD, and only 7 cases have been reported in the literature. We have summarized the published case reports of malignant lymphoma arising in BD. To our knowledge, this case report is the first to describe cytotoxic T-cell lymphoma arising in Behçet disease.

Rapidly progressive Lennert's lymphoma terminating in fulminant hepatic failure.

A 65-year-old male with rapidly progressive Lennert's lymphoma terminating in fulminant hepatic failure is presented. Staging radiological studies revealed that he had cervical and mediastinal lymph node swellings and multiple nodular lesions in the spleen. Lymph node biopsy specimens showed the proliferation of epithelioid cells interspersed with large blastic lymphocytes. These lymphocytes were CD3+, CD45RO (UCHL-1) +, CD4-, CD8+, CD56-, CD30-, CD15-, T-cell intracellular antigen-1+, granzyme B+ and perforin+, suggestive of the cytotoxic T-cell lineage. Under the diagnosis of Lennert's lymphoma, he was treated with standard CHOP chemotherapy. After two courses of the chemotherapy, despite the decreased size of cervical lymph nodes, high-grade fever and constitutional symptoms appeared. As multiple low-density nodules were observed in the liver by computed tomography, needle biopsy was performed. The biopsy specimens showed the proliferation of CD3+, CD4- and CD8+ lymphoma cells. Thereafter, the liver function deteriorated rapidly, and disseminated intravascular coagulation emerged. He died of rapidly progressive hepatic failure. This case is another example demonstrating that at least some of the Lennert's lymphomas phenotypically correspond with cytotoxic T-cell lymphomas, as was previously suggested by us [Am. J. Surg. Pathol. 24 (2000) 1627]. It should be also emphasized that Lennert's lymphomas containing cytotoxic proteins may have a fulminant clinical course, which cannot be rescued by the conventional chemotherapy.

The association between tumour necrosis factor-alpha gene polymorphism and the susceptibility to rugal hyperplastic gastritis and gastric carcinoma.

OBJECTIVES: Some subjects infected by Helicobacter pylori have enlarged folds in the gastric body, the precise mechanism of which remains obscure. The aim of this study was to clarify the association of tumour necrosis factor-alpha (TNFA) gene polymorphism with susceptibility to hyper-rugosity. We also examined the association of TNFA polymorphism with gastric carcinoma. SUBJECTS AND METHODS: Four hundred and seventy-two subjects (male/female = 351/121, aged 26-81 years) without gastric carcinoma (control group), and 300 patients (male/female = 218/82, aged 32-91 years) with gastric carcinoma. Barium meal roentgenograms were performed in 396 subjects in the control group and fold width was measured at the greater curvature of the middle portion of the gastric body. Fasting plasma anti-H. pylori IgG titres, pepsinogens (PGs) I and II were analysed, and TNFA -857 promoter polymorphism was distinguished by the 5' nuclease polymerase chain reaction assay and polymerase chain reaction restriction fragment length polymorphism using HincII in both groups. RESULTS: Adjusted odds ratios of TNFA -857 T/T genotype and H. pylori seropositivity for hyper-rugosity (fold width = 6.0 mm) were 6.7 (95% confidence interval (CI) 1.5-28, P < 0.01) and 18.2 (95% CI 4.2-78, P < 0.0001), respectively. There were no significant differences in any genotype or allele frequencies between the control and total gastric carcinoma group. In a subgroup of gastric carcinoma patients who were negative for the PG assay, however, the odds ratio of the T allele was 1.4 (95% CI 1.0-2.0, P < 0.05). CONCLUSION: The TNFA -857 T/T genotype and H. pylori infection were strongly associated with rugal hyperplastic gastritis. The TNFA -857 T allele may promote gastric carcinoma without severe atrophy.