Importance of TKI treatment duration in treatment-free remission of chronic myeloid leukemia: results of the D-FREE study.

Treatment-free remission (TFR) is a new goal for patients with chronic myeloid leukemia in chronic phase (CML-CP) with a sustained deep molecular response (DMR) to treatment with tyrosine kinase inhibitors (TKIs). However, optimal conditions for successful TFR in patients treated with second-generation (2G)-TKIs are not fully defined. In this D-FREE study, treatment discontinuation was attempted in newly diagnosed CML-CP patients treated with the 2G-TKI dasatinib who achieved BCR-ABL1 levels of ≤ 0.0032% (MR4.5) on the international scale (BCR-ABL1IS) and maintained these levels for exactly 1 year. Of the 173 patients who received dasatinib induction therapy for up to 2 years, 123 completed and 60 (48.8%) reached MR 4.5. Among the first 21 patients who maintained MR4.5 for 1 year and discontinued dasatinib, 17 experienced molecular relapse defined as loss of major molecular response (BCR-ABL1IS > 0.1%) confirmed once, or loss of MR4 (BCR-ABL1IS > 0.01%) confirmed on 2 consecutive assessments. The estimated molecular relapse-free survival rate was 16.7% at 12 months. This study was prematurely terminated according to the protocol's safety monitoring criteria. The conclusion was that sustained DMR for just 1 year is insufficient for TFR in CML-CP patients receiving dasatinib for less than a total of 3 years of treatment.

Clinical Efficacy and Safety of Arbekacin against Pneumonia in Febrile Neutropenia: A Retrospective Study in Patients with Hematologic Malignancies.

BACKGROUND: Arbekacin (ABK) is an aminoglycoside that exhibits anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa activities. Therefore, for patients with febrile neutropenia (FN) and concurrent pneumonia suspected to be caused by MRSA, ABK may be sufficiently effective even as a single agent. MATERIALS AND METHODS: Patients with hematologic malignancies treated with ABK who met the following criteria were included: 1) fever during neutropenia or functional neutropenia, 2) FN complicated by pneumonia, and 3) possible infection by antimicrobial-resistant Gram-positive cocci. RESULTS: This study encompassed 22 episodes involving 19 patients, of which, 15 (68.2%) were successfully treated with ABK. Of the nine episodes showing inadequate response to other anti-MRSA drugs, eight were successfully treated with ABK. Grade 2 or worse adverse events included acute kidney injury (13.6%) and increased transaminase levels (9.1%). CONCLUSION: The present study demonstrated that ABK is effective and safe in patients with FN and concurrent pneumonia caused by antimicrobial-resistant Gram-positive cocci. ABK may also be effective in patients who are unresponsive to other anti-MRSA drugs. Therefore, ABK may be beneficial in the treatment of pneumonia caused by antimicrobial-resistant Gram-positive cocci in patients with FN.

Bendamustine plus rituximab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma.

This single-arm phase 3 study was conducted to confirm the results of our phase 2 study of bendamustine (B)-rituximab (R) in patients with relapsed/refractory diffuse large B cell lymphoma (rrDLBCL). The primary endpoint was overall response rate (ORR). Autologous stem cell transplantation-ineligible rrDLBCL patients with ≤ 2 prior chemotherapy regimens received R 375 mg/m2 IV on day 1 and B 120 mg/m2/day IV on days 2 and 3 every 21 days up to 6 cycles. Thirty-eight patients with a median age of 74 years (range, 43-86) received BR. The ORR and complete response rates were 76.3% and 47.4%, respectively. With a median follow-up of 19.5 months including long-term follow-up, median progression-free survival was 11.9 months. Median OS was 29.2 months. Discontinuation of treatment due to Gr3-5 TEAE was observed among 13 of 38 patients (34.2%). One patient with cytomegalovirus enterocolitis died during follow-up. This BR regimen was confirmed to be effective and tolerable in studied patients. ClinicalTrials.gov Identifier: NCT03372837 registered on 14 December 2017, NCT04354402 registered on 21 April, 2020.

Prognostic impact of trisomy 21 in follicular lymphoma.

The chromosomal abnormalities associated with follicular lymphoma (FL) prognosis are not fully elucidated. Here, we evaluated the pattern of chromosomal abnormalities in FL, and clarified the correlations between the cytogenetic features and clinical outcome. Cytogenetic analysis was performed using standard methods of Giemsa-banding at diagnosis for 201 FL patients admitted to our hospitals between 2001 and 2013. The identified chromosomal abnormalities were: t(14;18)(q32;q21) (59·2%), +X (17·9%), del(6)(q)/-6 (16·9%), +7 (14·4%), abnormality of 1q12-21/1q (12·9%), del(13)(q)/-13 (11·9%), abnormality of 3q27 (10·4%), abnormality of 10q22-24 (10·0%), +12/dup(12)(q) (10·0%), abnormality of 1p21-22/1p (9·0%), +18 (9·0%), del(17)(p)/-17 (5·0%), and a complex karyotype (54·7%). Patients with trisomy 21 had a significantly shorter progression-free survival (P = 0·00171) and overall survival (OS) (P < 0·001) than those without trisomy 21; additionally, patients with trisomy 21 in the rituximab-treated cohort also had a significantly shorter OS (P = 0·000428). Multivariate analysis identified trisomy 21 as an independent risk factor in our cohorts with or without t(14;18) (P = 0·015). In conclusion, the presence of trisomy 21 was an independent risk factor for in FL. Chromosomal analysis of FL patients at diagnosis can provide useful information about their expected survival.

Bortezomib maintenance therapy in transplant-ineligible myeloma patients who plateaued after bortezomib-based induction therapy: a multicenter phase II clinical trial.

In the era of novel therapeutic agents for multiple myeloma (MM), both the significance of achieving the plateau phase and the efficacy of subsequent maintenance therapy remain unclear. In the present study, we evaluated the efficacy and safety of bortezomib maintenance therapy (biweekly for 1 year) in transplant-ineligible MM patients who plateaued after bortezomib-based induction therapy. Of 36 evaluable patients, the overall response rate during induction therapy was 61%, with a stringent complete response in 6%, a complete response in 6%, a very good partial response in 17%, and a partial response in 33%. Twenty patients achieved the plateau phase and subsequently received bortezomib maintenance therapy. Median progression-free survival from the induction and maintenance therapies was 13.8 months (95% confidence interval, 11.4-23.7 months) and 10.7 months (95% confidence interval, 3.7-10.7 months), respectively. During maintenance therapy, there were no cases with grade ≥ 2 peripheral neuropathy, nor was there any improvement in the quality of the response. In conclusion, although maintenance therapy with biweekly bortezomib for up to 1 year was feasible, plateau-oriented bortezomib induction therapy followed by bortezomib maintenance therapy was not adequate in newly diagnosed transplant-ineligible MM patients.

Clinical management and outcomes of completely resected stage I follicular lymphoma.

Recent studies have revealed the clinical and biological features of stage I follicular lymphoma (FL), but information about patients with stage I FL who underwent total resection after tissue biopsy is limited. Among 305 FL patients diagnosed between 2001 and 2013, clinical stage I disease was observed in 36 patients. Of these, 18 patients underwent total resection after diagnostic tissue biopsy. We used 18F-fluorodeoxyglucose positron emission CT for staging assessment in 13 of 18 patients (72.2%). The median age was 56.5 years. Six patients (33.3%) were male. The soluble interleukin-2 receptor alpha concentration was significantly lower than in patients with residual disease. Among these 18 patients, 7 patients (38.9%) were treated with a "watch-and-wait" (WW) policy, 7 (38.9%) were treated with involved-field irradiation, and 4 (22.2%) received systemic chemotherapy. Patients with resected disease were treated with significantly different strategies from those with residual disease (p = 0.0026). Five patients experienced relapse during follow-up (median follow-up: 48.2 months). All relapses were distant from the primary site, irrespective of treatment strategy. Among all stage I patients, disease resection was not a significant factor for survival (p = 0.9294). Collectively, the choice of treatment strategy was significantly influenced by patient status. Resection status was not significantly associated with survival after several treatment strategies.

The standard international prognostic index for predicting the risk of CNS involvement in DLBCL without specific prophylaxis.

Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1.3, 4.6, 8.8, and 12.7% in the low-, low-intermediate-, high-intermediate-, and high-risk groups, respectively (p <.001). This result is comparable with that of the CNS-IPI. Patients with breast involvement tended to have lower risk according to the standard IPI but showed frequent CNS involvement, similar to patients with testis involvement. The standard IPI is also a useful predictor of CNS involvement. Patients with breast/testis involvement would be candidates for prophylaxis regardless of the standard IPI risk.

Retrospective analysis of prognostic factors for WaldenstrÓ§m macroglobulinemia: a multicenter cooperative study in Japan.

Although population-based cancer registries have reported lower incidence of WaldenstrÓ§m macroglobulinemia (WM) in East Asia than in Western countries, previous retrospective analyses have found the clinical features of WM to be similar in these two populations. To clarify the characteristics of Japanese WM patients, we retrospectively analyzed clinical and laboratory characteristics, treatments, outcomes, and prognostic factors in 93 patients with WM. Based on the Second International Workshop on WM (IWWM-2) criteria, symptomatic WM was found in 73 (78.5%) and asymptomatic WM in 20 (21.5%) of cases examined. The median overall survival (OS) was similar to that in reports from Western countries. Patients receiving treatment regimens including rituximab exhibited significantly better survival than those not given rituximab. Although prognostic factors for WM in Western countries may not apply to Japanese patients, our finding that newly diagnosed WM patients with pleural effusion have a poorer prognosis suggests that this may be a novel predictor of adverse prognosis in symptomatic WM.

Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma.

We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.

Prognostic importance of the soluble form of IL-2 receptorα (sIL-2Rα) and its relationship with surface expression of IL-2Rα (CD25) of lymphoma cells in diffuse large B-cell lymphoma treated with CHOP-like regimen with or without rituximab: a retrospective analysis of 338 cases.

We evaluated the prognostic significance of the serum level of the soluble form of interleukin-2 receptorα (sIL-2Rα) and investigated its association with CD25 expression on tumor cells in diffuse large B-cell lymphoma (DLBCL). Three hundred and thirty-eight adult patients with newly diagnosed DLBCL were eligible for this retrospective study. 32.2% of patients were treated with CHOP-like regimen and 67.8% with R-CHOP-like regimen. CD25 expression on the surface of tumor cells was evaluated in 143 cases and its relationship with sIL-2Rα level was also investigated. Both overall survival (OS) and progression-free survival (PFS) were poorer in patients with higher sIL-2Rα, in both R-CHOP and CHOP groups. sIL-2Rα > 1,000 U/mL and performance status (PS) ≥ 2 were independently associated with poorer OS, and sIL-2Rα > 1,000 U/mL, age > 60 years, and ≥ 2 extranodal sites were independently associated with poorer PFS in the R-CHOP group. The sIL-2Rα level was higher in the CD25-positive group than in the CD25-negative group in stage 3 or 4 disease (p = 0.010). Multiple linear regression analysis showed CD25 expression to be independently correlated with sIL-2Rα levels. High sIL-2Rα is an important risk factor for survival in DLBCL treated with not only CHOP-like, but also R-CHOP-like regimens, regardless of the tumor's expression of CD25.

Primary hepatic and hepatosplenic diffuse large B-cell lymphomas with intrasinusoidal and interstitial lymphomatous infiltration.

Primary hepatic and hepatosplenic diffuse large B-cell lymphomas (DLBCLs) are rare cancers and form nodules in most instances. However, very rare cases can diffusely infiltrate the whole liver without nodules. The general clinicopathological features of these lymphomas have not been reported to date. In our current study, we attempted to elucidate the features of these lesions through our direct observations and by reviewing the current literature. We describe the characteristics of 2 patients with hepatic and hepatosplenic DLBCL by autopsy. The lymphoma cells showed diffuse infiltration of the liver, red pulp of the spleen, and bone marrow with intrasinusoidal and interstitial lymphomatous infiltration of the organs. We discuss our observations in relation to previously reported DLBCLs with a similar pathology.

[Retrospective survey on the clinical features of non-Hodgkin lymphomas in Gunma Prefecture, Japan].

We retrospectively investigated pathological types, clinical backgrounds, treatments and prognoses in 726 adult patients with newly diagnosed malignant lymphoma in Gunma Prefecture. They consisted of 679 patients with non-Hodgkin lymphoma (B-cell type, 603; T- and NK-cell type, 76) of which 376 patients had diffuse large B-cell lymphoma (DLBCL) and 47 patients with Hodgkin lymphoma. When comparing the prognosis of DLBCL between patients receiving rituximab (R-CHOP group; n=212) and not using rituximab (CHOP group; n=126), both 3-year overall survival (73.5% vs 61.7%, p=0.010) and 3-year progression-free survival (65.1% vs 45.8%, p<0.001) were statistically better in the R-CHOP group compared to the CHOP group. Our results suggest that more than half of patients were DLBCL and the rituximab-containing regimen results in an improved prognosis for DLBCL patients.

Prognostic impact of extranodal involvement in diffuse large B-cell lymphoma in the rituximab era.

BACKGROUND: Extranodal involvement is considered a poor prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL); however, the prognostic impact of specific sites of involvement has not been fully elucidated. METHODS: The authors retrospectively analyzed 1221 patients treated uniformly with standard R-CHOP therapy between 2003 and 2006. Patients with distinct forms of DLBCL such as intravascular lymphoma, primary effusion lymphoma, pyothorax-associated lymphoma, primary central nervous system lymphoma, and intraocular lymphoma were also excluded. The authors evaluated 26 extranodal sites of involvement with respect to prognostic impact. The median age was 64 years (range, 15-91 years). RESULTS: Univariate analysis revealed that patients with involvement of specific extranodal sites had significantly worse overall survival (OS) than did patients without such involvement; these sites included nasal cavity, paranasal sinus, lung, pleura, small intestine, peritoneum, liver, pancreas, stomach, spleen, adrenal gland, testis, bone, bone marrow, peripheral blood, skin, and subcutaneous tissue. Patients with Waldeyer ring involvement had significantly better OS. Multivariate analysis revealed that patients with the involvement of the pleura (P < .001), small intestine (P = .015), peritoneum (P = .002), adrenal gland (P < .001), testis (P = .005), bone marrow (P < .001), and peripheral blood (P = .002) had significantly worse OS, whereas those with Waldeyer ring involvement had significantly better OS (P = .038). Subgroup analysis with the nodal and/or Waldeyer patient group also showed prognostic impact of Waldeyer ring by multivariate analysis (relative risk, 0.3; P = .04). CONCLUSIONS: Extranodal involvement affects the prognosis of patients undergoing R-CHOP therapy for DLBCL.

Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era.

Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further.

TCL1A gene involvement in T-cell prolymphocytic leukemia in Japanese patients.

T-cell prolymphocytic leukemia (T-PLL) is a rare type of peripheral T-cell leukemia. In this study, we examined the clinical and biological characteristics of 11 Japanese patients with T-PLL. Median age was 74 years, with male predominance. Median lymphocyte frequency was 85.3% in blood. Physical characteristics were splenomegaly (36.4%), tiny lymph adenopathy (63.6%), skin lesion (9.1%) and pleural effusion (27.3%). Median survival was 30.1 months, despite treatment with various chemotherapeutic modalities. Although complex chromosomal abnormalities were observed in 5 of 11 cases (45.5%), typical 14q32 and Xq28 abnormalities were not detected. TCL1A mRNA expression was observed in 6 of 11 cases (54.5%) on real-time quantitative PCR. In 5 of these 6 cases, flow cytometric analysis and/or immunohistochemistry confirmed the expression of TCLA1 protein. Split signals for the TCL1 region on fluorescence in situ hybridization confirmed rearrangement in 3 out of 7 cases evaluated. These cases corresponded to cases that were positive for TCL1A expression, suggesting that rearrangement of the TCL1 region induced high expression of TCL1A gene. In summary, a substantial number of T-PLL cases in Japan had abnormal expression of TCL1A, probably due to rearrangement of TCL1 region. Expression and/or rearrangement of TCL1A may, therefore, be a useful marker for diagnosing T-PLL, regardless of chromosomal abnormalities.

Atypical lymphoplasmacytic and immunoblastic proliferation of autoimmune disease : clinicopathologic and immunohistochemical study of 9 cases.

Atypical lymphoplasmacytic immunoblastic proliferation (ALPIB) is a rare lymphoproliferative disorder (LPD) associated with autoimmune disease (AID). To further clarify the clinicopathologic, immunohistological, and genotypic findings of ALPIB in lymph nodes associated with well-documented AIDs, 9 cases are presented. These 9 patients consisted of 4 patients with systemic lupus erythematosus, 3 patients with rheumatoid arthritis, and one case each with Sjögren's syndrome and dermatomyositis. All 9 patients were females aged from 25 to 71 years with a median age of 49 years. Four cases presented with lymphadenopathy as the initial manifestation. In 4 patients, immunosuppressive drugs were administered before the onset of lymph node lesion. However, none of the 9 patients received methotrexate therapy. The present 9 cases were characterized by : (i) prominent lymphoplasmacytic and B-immunoblastic infiltration ; (ii) absence of pronounced arborizing vascular proliferation ; (iii) absence of CD10(+) "clear cells" ; (iv) presence of hyperplastic germinal center in 7 cases ; (v) immunohistochemistry, flow cytometry, and polymerase chain reaction demonstrated a reactive nature of the T- and B-lymphocytes ; and (vi) on in situ hybridization, there were no Epstein-Barr virus -infected lymphoid cells in any of the 9 cases. Overall 5-year survival of our patients was 83%. The combination of clinical, immunophenotypic, and genotypic findings indicated that the present 9 cases can be regarded as having an essentially benign reactive process. Finally, we emphasized that ALPIB should be added to the differential diagnostic problems of atypical LPDs, particularly lymph node lesions of IgG4-related diseases.

Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis.

The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients.

Reactive lymphoid hyperplasia with giant follicles associated with a posttherapeutic state of hematological malignancies. A report of eight cases.

AIMS AND BACKGROUND: To further clarify the clinicopathological, molecular genetic and karyotypic findings of reactive lymph node hyperplasia with giant follicles (RLHGF) associated with a posttherapeutic state of hematological malignancies, we studied eight such cases. METHODS: Using formalin-fixed, paraffin-embedded sections, histological, immunohistochemical, in situ hybridization (ISH), and polymerase chain reaction (PCR) were performed. RESULTS: Six patients had a history of malignant lymphoma (diffuse large B-cell lymphoma [DLBCL] = 4, marginal zone B-cell lymphoma = 2), and two had acute myeloid leukemia (AML). Six patients initially presented with lymphadenopathy of the head and neck area and the remaining one presented with swelling of the tonsil. All seven cases demonstrating analyzable metaphases showed a normal karyotype. Histologically, all eight lesions were characterized by numerous enlarged, bizarre-shaped coalescing lymphoid follicles with follicular lysis. Immunohistochemical and flow cytometry study demonstrated the reactive nature of the B cells in all eight lesions. However, three of our eight cases demonstrated immunoglobulin heavy-chain (IgH) gene rearrangement on PCR study. Different clonal bands were detected in the initial lymphomatous tissue and RLHGF in one of the studied cases. There was no development of B-cell lymphoma or recurrence of B-cell lymphoma in any of the three lesions demonstrating IgH rearrangement. There were no human herpes virus type-8+ or human immunodeficiency virus type-1+ cells in any of the eight lesions. ISH demonstrated Epstein-Barr virus (EBV)-encoded small RNA (EBER)+ cells in only two lesions. PCR analyses demonstrated that there was no Toxoplasma gondii DNA in any of the eight lesions. CONCLUSIONS: As suggested in RLHGF posttransplant, RLHGF arising after therapy for hematological malignancies is also a consequence of chronic stimulation in the setting of immune deregulation rather than various infectious agents. It is important for pathologists and clinicians to be aware of this type of lesion in diagnostic practice.

B-cell lymphoma associated with Sjögren's syndrome among Japanese patients: a clinicopathologic and immunohistochemical study of 15 cases.

To clarify the clinicopathological findings of B-cell lymphoma associated with Sjögren's syndrome (SJS) among Japanese Patients, 15 individuals with this disease were studied. The patients, 14 females and one male, ranged in age from 41 to 73 years with a median age of 56 years. These lymphomas arose not only in the salivary gland (n=4) but also in other mucosal extranodal sites (n=5). Histologically, six cases were marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) type, three cases were diffuse large B-cell lymphoma (DLBCL) + MALT type lymphoma, two cases were nodal MZBL and one case each was small lymphocytic lymphoma, Burkitt's lymphoma, CD10(+) DLBCL and DLBCL + nodal MZBL. Using in situ hybridization, numerous Epstein-Barr virus(+) tumor cells were detected only in the case of Burkitt lymphoma. There were no human-herpes type 8(+) tumor cells in any of the 15 cases. There was no API2-MALT1 fusion transcript in any of the eight cases examined. B-cell lymphoma associated with SJS also frequently affected extranodal organs in patients from Japan as well as from patients in Western countries. The majority of B-cell lymphomas in patients with SJS also appear to be low-grade MZBLs or high-grade lymphomas probably derived from MZBL both in Western countries and in Japan.