VH gene analysis of Burkitt's lymphoma in children from north-western Iran

Cases of Burkitt's lymphoma (BL) from north-western Iran were investigated for the usage and somatic mutational pattern of their immunoglobulin variable region genes. Potentially functional V_H genes were amplified from 6/12 of the tumour masses and all of these were derived from the V_H3 family, with 4/6 being derived from the most commonly used V_H3 family member, V_3-23. All of the tumour sequences were mutated from their germline counterparts, to varying degrees, with a mean level of 5.8%, indicating that the cell of origin had encountered the germinal centre. Intraclonal sequence heterogeneity was also evident in 4/6 of the lymphomas, showing that the tumour cells had undergone further somatic mutation following neoplastic transformation. Analysis of the five potentially functional mutated V_H sequences showed a significant clustering of replacement mutations in the complementarity-determining region 2, consistent with a role for antigen in selection of tumour cell sequences. The pattern of extensive somatic mutation, and intraclonal variation, in these mainly EBV+ve tumours, was similar to that previously reported in V_H sequences of EBV+ve endemic BL (eBL) and EBV−ve sporadic BL (sBL), with the mean level of somatic mutation lying between those reported for eBL (7.7%) and sBL (4.0%). However, V_H gene bias and the distribution of mutations in the Iranian cases showed features which differed from those reported for endemic or sporadic BL.     

Subcutaneous dissemination pattern in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma

Background

Mucosa-associated lymphoid tissue (MALT) lymphoma is among the most common forms of extranodal lymphomas, but little is known about subcutaneous involvement in patients with non-primary cutaneous marginal zone lymphomas.

Design and Methods

Patients with MALT lymphoma diagnosed and treated at our institution between 1999 and 2010 were analyzed for subcutaneous deposits from MALT lymphoma diagnosed in another organ. Histological, clinical and genetic findings were assessed.

Results

Among 216 patients with MALT lymphoma, 12 had subcutaneous deposits from MALT lymphoma (5.5%). In two patients, these lesions were present at diagnosis, while they constituted the site of relapse at an interval between 5 to 144 months in the remaining cases. Interestingly, nine of the 12 patients with subcutaneous deposits had originally been diagnosed with MALT lymphoma of the ocular adnexa (total number=51; 20%), and the other three had MALT lymphoma in the breast (total number=5; 60%). None of the patients with gastric (n=86), salivary gland (n=32) or pulmonary (n=19) MALT lymphomas had subcutaneous involvement during a median follow-up time of 87 months (range; 4 to 119 months).

Conclusions

Our data show that subcutaneous MALT lymphoma involvement is a rare event in patients with prior non-cutaneous extranodal marginal zone lymphoma. However, it seems to be almost exclusively associated with MALT lymphoma of the ocular adnexa and the breast, suggesting as yet undefined interactions between potentially embryonically related organ systems.     

Clonal history of a human follicular lymphoma as revealed in the immunoglobulin variable region genes

Summary. The variable region genes used to encode the immunoglobulin expressed by tumour cells of a patient with follicular lymphoma have been identified and sequenced. Initially, a lymph node biopsy was analysed and revealed usage of V_H and V_κ genes which had numerous substitutions as compared with the closest germ line genes. The pattern of mutations in V_H was consistent with a role for positive selection by antigen. In addition, there was evidence in both V_H and V_κ sequences for clonal heterogeneity.
After 5 years, which included treatment with chemotherapy, the patient relapsed with tumour cells present in the blood. Analysis of the V-genes used by the emerging tumour revealed a single homogeneous sequence for both V_H and V_L, which, in each case, matched closely one of the sequences in the original lymph node biopsy.
These results indicate that selection. possibly mediated by antigen, can operate on a cell destined to give rise to lymphoma, and that intraclonal variation can occur after the neoplastic event. However, in this case, late relapse in the blood is dominated by a single clone.     

Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori: Scratch and win

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with Helicobacter pylori infection and, in the great majority of patients, regresses after eradication. H. pylori-negative MALT lymphoma occurs in a small minority of cases in which treatment is based on surgery or chemoradiotherapy. In the search for H. pylori based on histology and the C¹³ urea breath test, this report describes a case with a series of false-negative results, thus confirming the possibility of a lower detectability of H. pylori in patients with MALT gastric lymphoma and supporting the use of additional tests in evaluating such pathology, including polymerase chain reaction. Additionally, treatment with CD20 monoclonal antibody (rituximab) is suggested as an alternative to surgery or treatment with chemotherapy or radiotherapy in patients with truly H. pylori-negative gastric MALT lymphoma.     

A systematic review and meta-analysis of thymic mucosa-associated lymphoid tissue lymphoma

BackgroundMucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is a rare disease. The present meta-analysis aims at accumulating current evidence to explore the clinical characteristics, treatments, and prognoses of thymic MALT lymphoma.MethodsWe searched seven databases for studies published between the start date of database establishment and September 15, 2021. We included studies of patients with histological diagnoses and excluded those without data specifically on thymic MALT lymphoma. The quality was analyzed using an assessment tool. All data were tabulated. Pooled proportion was obtained using random-effects model. Statistical analysis was performed on R statistic software.ResultsOverall, 52 case reports and 13 case series were eligible. The quality of case reports was inferior to that of case series in terms of selection (P<0.001). Based on the analysis of patients in the case reports, age, gender, concurrent diseases, and tumor size did not differ between limited-stage and advanced-stage cases. Surgery is the mainstay to treat thymic MALT lymphoma. The surgical approach and extent did not influence the occurrence of events. Patients at Ann Arbor stage I were prone to not receiving postoperative therapy (P=0.011), though it may not reduce the occurrence of events (P=0.637). The five-year overall survival (OS) rate and five-year progression-free survival (PFS) rate were 97.2% and 88.4%, respectively. Patients with advanced-stage disease were more likely to suffer events (P=0.009).ConclusionsThymic MALT lymphoma is an extremely rare disease with a favorable prognosis. Currently available evidence is insufficient to draw solid judgments about treatment and prognosis. However, patients may benefit if thymectomy is chosen as the primary treatment. In some patients, lymph node sampling or dissection should be considered. In addition, if the patient is at an advanced-stage, postoperative therapy should be considered.     

Aggressive non-Hodgkin's lymphoma after successful eradication of Helicobacter pylori and regression of gastric lymphoma of mucosa-associated lymphoid tissue

A 57-year-old woman presented to our clinic with low-grade gastric lymphoma of mucosa-associated lymphoid tissue (stage IE) and Helicobacter pylori infection. She received a 2-week course of omeprazole and clarithromycin, resulting in eradication of H. pylori and histological disappearance of the lymphoma. However, 9 months later (May 1996), multiple mass lesions were found around the pancreas and hepato-duodenal ligament on abdominal computed tomography. Inguinal lymph node biopsy revealed aggressive nodal type B-cell non-Hodgkin's lymphoma, diffuse large cell type. She received chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone, but failed to achieve remission and died in December 1996. There was no evidence of recurrent gastric lymphoma. This case emphasizes the importance of performing follow-up examinations to detect other neoplasms in patients with gastric lymphoma of mucosa-associated lymphoid tissue. Received Aug. 21, 1997; accepted Mar. 27, 1998     

Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: “pure MALT lymphoma,” “MALT lymphoma with high-grade component” (mixed), and “pure DLBCL.” Seventy-six patients were included in our study—26 with pure MALT, 22 with MALT with high-grade component (“mixed”), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45% for DLBCL. On univariate analysis, DLBCL histology, age, performance status, serum albumin, lactate dehydrogenase, bone marrow, number of extranodal sites, stage, and IPI score were prognostic for inferior survival. On multivariate analysis, DLBCL histology remained significantly prognostic for inferior survival, independent of chemotherapy regimen (hazard ratio (HR) 6.66, 95% confidence interval (CI) 2.01–21.41, p = 0.001). Mixed histology was not prognostic for inferior survival (HR 1.13, 95% CI 0.28–4.54, p = 0.868). Other factors prognostic for inferior survival were serum albumin <37 g/L (HR 3.22, 95% CI 1.11–13.22, p = 0.034) and treatment with non-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy (HR 4.89, 95% CI 1.67–14.36, p = 0.004). In conclusion, the clinical characteristics of mixed histology MALT lymphoma are similar to low-grade MALT lymphoma and significantly different from pure DLBCL. The prognosis of mixed histology MALT lymphoma is significantly better than pure DLBCL, independent of IPI and chemotherapy regimen, and pure DLBCL histology is independently prognostic of inferior survival outcome.     

Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature

A primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) is very rare. We found a solitary mass 27 mm in size in the left lobe of the liver of a 58-year-old Japanese man with a history of hepatitis-C infection. Based on the results of imaging studies, the tumor was diagnosed as a hepatocellular carcinoma (HCC). The left lobe of the liver was lobectomized and microscopic findings showed that the tumor was a hepatic MALT lymphoma, while immunohistochemistry showed it to be positive for CD20 and CD79a. In a fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning (FDG-PET CT) before surgery, the tumor was revealed to have a high standardized uptake value (SUV) for FDG. The patient received chemotherapy after surgery. To the best of our knowledge, 45 cases had been reported with a mean age for all patients of 61.4 years. The pathogenesis remains unclear, although half of the patients had a past history of chronic inflammatory liver disease. Surgical resection was performed in most cases and some patients received postoperative chemotherapy or radiotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.     

Regression of primary low-grade mucosa-associated lymphoid tissue lymphoma of duodenum after long-term treatment with clarithromycin

A 74-year-old woman was referred to our department because of epigastralgia. Endoscopic findings revealed yellowish bumpy mucosa from the bulbus to the second portion of the duodenum. The patient was admitted to our hospital for further examinations and treatment for this lesion. Endoscopic mucosal resection (EMR) was performed on part of the lesion to obtain the final diagnosis, and then mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum was diagnosed using this procedure. In this case, no evidence of Helicobacter pylori infection in the patient's stomach was detected by any of the diagnostic examinations used, such as the urea breath test, histological study, culture, and serological antibody. For this reason, the patient's duodenal MALT lymphoma was treated solely with long-term clarithromycin, which had an inhibitory action on lymphocyte activation. The lesion showed slight improved during the first 12 days of treatment, and complete regression was reached after 6 months of treatment. It is suggested that the long-term use of clarithromycin may be effective for diseases of the gastrointestinal tract associated with the lymphocyte proliferation.     

Idiopathic ulcer of the small bowel containing numerous plasma cells: case resembling mucosa-associated lymphoid tissue lymphoma

Idiopathic ulcer of the small bowel is a poorly recognized entity. Herein is reported a case of idiopathic ulcer of the jejunum containing numerous lymphoplasmacytoid infiltrates and mimicking mucosa-associated lymphoid tissue (MALT) lymphoma. An 82-year-old Japanese woman presented with nausea and vomiting. Following diagnosis of submucosal tumor, partial jejunal resection was performed. Macroscopically the resected specimen contained multiple small shallow ulcers. Histologically the lesion was composed of numerous plasma cells mixed with lymphocytes and histiocytes. Immunohistological study revealed that the plasma cells contained polytypic intracytoplasmic immunoglobulins. The patient remained free of disease after 36 months. Marginal zone B-cell lymphoma of MALT-type arising from small intestine occasionally shows prominent plasma cell differentiation. The present case demonstrates that idiopathic ulcer of the small bowel should be added to the differential diagnosis of MALT-type lymphoma of the small bowel.     

Mantle cell lymphoma with the features of mucosa-associated lymphoid tissue (MALT) lymphoma in an HTLV-I-seropositive patient

Summary A case of small lymphocytic B-cell lymphoma with seropositivity for human T-cell leukemia virus type I (HTLV-I), whose clinical features were closely related to those of mucosa-associated lymphoid tissue (MALT) lymphoma, is presented. The neoplastic cells of the lymph node were immunologically positive for CD5, in addition to several B-cell markers, but negative for CD10, and cytogenetically carried a t(11;14)(q13;q32). These findings were fully consistent with so-called mantle cell lymphoma (MCL). In addition to the lymph nodes and bone marrow, multiple extranodal sites including lacrimal and salivary glands, lung and stomach (where MALT is present) were occupied by lymphoma cells. These extranodal lesions were immunologically identical to the lymph nodes (CD5(+), CD10(–)), but histologically showed lymphoepithelial lesions (LEL) characteristic of MALT lymphoma. These findings suggest a possible relationship between MCL and MALT lymphoma, and the neoplastic cells are thought to originate from the CD5-positive B cells, which are present near the areas across the mantle and marginal zones. Furthermore, HTLV-I-infection, which appears to create an immunodeficient state or modulate the B-cell response, is thought to play a role in B-cell lymphomagenesis.     

Prevalence of Achromobacter xylosoxidans in pulmonary mucosa‐associated lymphoid tissue lymphoma in different regions of Europe

Extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) comprises 7–8% of B‐cell lymphomas and commonly originates from a background of long‐standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene–based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram‐negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies.     

胃黏膜相关淋巴组织淋巴瘤临床研究及随访

目的探讨胃黏膜相关淋巴组织淋巴瘤的临床特征及治疗策略。方法采用回顾性方法对32例经组织学确诊的胃黏膜相关淋巴组织淋巴瘤进行随访。结果32例患者中多数起病隐匿，上腹痛为主要症状，也有以消化道出血入院者。内镜下病变主要分布在胃窦部，以隆起型和溃疡型表现为主。首次胃镜检查约25％获正确诊断。本组病例幽门螺杆菌感染率约为88％。20例（62．5％）接受了手术治疗，15例（46．88％）行幽门螺杆菌根除治疗，其中，3例早期阶段患者获得组织学完全缓解。结论胃黏膜相关淋巴组织淋巴瘤的临床表现、内镜下特征和病理特点的认识有待进一步提高。对早期阶段患者幽门螺杆菌治疗当属首选。     

胃黏膜相关淋巴组织淋巴瘤临床与胃镜表现分析

目的探讨胃黏膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)淋巴瘤临床和内镜下表现特征,提高其在胃镜下的早期诊断率。方法对15例胃MALT淋巴瘤患者临床和内镜下表现特征进行回顾性分析。结果胃MALT淋巴瘤多见于40~60岁患者,男女发病率相近。临床症状无特异性,H.pylori感染率为73.33%。胃MALT淋巴瘤多位于胃窦部,66.67%表现为单个或多个溃疡,质地偏硬,蠕动性及胃腔形态无明显特异性。结论胃MALT淋巴瘤作为一类特殊的原发性胃淋巴瘤,内镜下多块、深而大的活检有助于提高确诊率。