Marginal Zone Mucosa-associated Lymphoid Tissue Research Articles

Chinese expert consensus on the diagnosis and management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (2023 edition)

Ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) is a common malignant tumor that affects the ocular adnexal region. The incidence of OAML is increasing due to the aging population. The tumor invades the ocular adnexal region, which can result in abnormal ocular appearance and function, thereby reducing the quality of life. Currently, there is no standardized diagnosis and management guideline for OAML. To enhance the standardization of diagnosis and management in OAML, a collaborative effort was undertaken by esteemed organizations in China. The Cellular Immune Therapy Committee of China Association for Promotion of Health Science and Technology, the Ocular Tumor Committee of Chinese Medical Doctor Association for Ophthalmologist Branch, the Imaging Medicine Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare, the Tumor and Microecology Professional Committee of China Anti-cancer Association, and the Lymphoma Immunotherapy Committee of Beijing Cancer Prevention Society jointly convened a panel of experts to develop the inaugural "Chinese Expert Consensus on the Diagnosis and Management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (2023 edition)"..

Long-term survival outcomes of patients with primary ocular adnexal MALT lymphoma: A large single-center cohort study.

Primary ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (OAML) is a rare subtype of non-Hodgkin's lymphoma, and no consensus has been defined concerning the optimal treatment strategies. This study aims to investigate the associations of disease characteristics and different treatments with long-term outcomes of patients with localized OAML. A large retrospective cohort study was conducted in a single-center of China, and 166 patients with newly diagnosed primary localized OAML were enrolled. Detailed data of disease characteristics at diagnosis and treatments were collected for all patients. We compared treatment response and progression-free survival (PFS) among patients with different characteristics and treatments. Of the 166 patients, 52 received complete resection of neoplasm, whereas 114 had residual lesion after surgery. Among the 114 patients, 61 underwent watchful waiting and 53 received further treatment including localized radiotherapy, chemotherapy, or combined radiotherapy and chemotherapy. Median follow-up was 49 months. A total of 31 patients had disease progression or relapse, including four patients with such event more than five years after initial treatment. The 5-year PFS was 73.9%, 70.6%, and 85.9%, whereas the 10-year PFS was 69.3%, 59.2%, and 79.3%, among patients with complete resection of neoplasm, patients in the watchful waiting group and patients with further treatment, respectively. Patients with further treatment had longer PFS, compared with patients in the watchful waiting group (p=0.011). Bilateral involvement at diagnosis was associated with significantly inferior PFS (p=0.029), whereas age, IPI score, or TNM staging were not associated with PFS. No serious adverse reaction was reported among patients with further treatment. Bilateral involvement was associated with poor prognosis. Among patients with residual lesions after surgery, further treatment was associated with improved survival. Patients with OAML might experience disease progression or relapse more than five years after initial treatment.

Treatment and prognosis of primary ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma: a report from a single center

目的探讨局限于眼附属器黏膜相关淋巴组织结外边缘区淋巴瘤（OAML）患者应用不同初始治疗方案对长期预后的影响。方法对2008年4月至2019年4月首都医科大学附属北京同仁医院血液科收治的109例初发OAML患者进行疗效评估及随访，对初始治疗方案与预后进行分析。结果36例患者经手术完全切除病灶，73例术后存在残留病灶，其中37例选择观察等待，36例选择治疗，治疗方案包括局部放疗和系统性治疗（化疗、免疫化疗、放化疗联合等），选择系统性治疗患者未发生严重不良反应。中位随访时间61（10～142）个月，单眼受累患者5年、10年无进展生存（PFS）率分别为78.2％和76.0％，双眼受累患者5年、10年PFS率分别为64.4％和23.5％，单眼、双眼受累患者PFS的差异有统计学意义（P＝0.010）。残留病灶观察组患者和残留病灶治疗组患者5年PFS率分别为71.4％和90.1％，10年PFS率分别为63.5％和75.1％，两组患者PFS率的差异有统计学意义（P＝0.046）。OAML患者超过5年仍有疾病进展风险。结论双眼受累OAML患者预后差，治疗可以降低复发或进展风险。系统性治疗可作为OAML患者的一线治疗选择之一。OAML需要长期随访。

Diagnostika a endoskopická intervence u raritního MALT lymfomu proximálního jejuna

Summary: Extranodal lymphoma from the marginal zone mucosa-associated lymphoid tissue (MALT lymphoma) is one of the primary extranodal non-Hodgkin‘s lymphomas with low degrees of malignancy but with the risk of spreading to distant locations in the body. B-lymphomas are sometimes associated with other diseases (eg. Helicobacter pylori and Campylobacter jejuni infections or inflammatory bowel disease). B-lymphomas may manifest with a variety of clinical signs, from dyspeptic syndrome with malabsorption and weight loss to ileus or massive gastrointestinal bleeding. Dia­gnosis is based on the clinical condition and the results of laboratory tests and imaging techniques, while endoscopy is the essential procedure for visualizing the tumor mass and collecting a bio­psy sample to determine the definitive histopathological dia­gnosis. MALT lymphoma treatment is managed by oncologists and includes chemotherapy and/or radiotherapy, with resection indicated in rare cases. In this case report we present an elderly female patient who was referred to our IBD centre for non-specific abdominal pain with a positive fecal occult blood test. Computed tomography (CT) examination was used before endoscopy and showed an infiltration of the splenic flexure by an unspecified mass, a subsequent colonoscopy showed intact mucosa of the colon, including the terminal ileum. In the second reading of the CT scan the location of the infiltrate was identified more specifically as the area of the proximal jejunum and jejunal mesentery. Subsequent upper endoscopy revealed a stenosing exulcerated tumor in the proximal jejunum, with the stenosis impassable even for a pediatric colonoscope. The dia­gnosis of MALT lymphoma was confirmed by a histological examination of the bio­psied tissue. A follow-up upper endoscopy was performed after the patient had completed her oncological treatment (chemotherapy in combination with radiotherapy), showing the presence of stenosis at the proximal jejunum, still impassable for the endoscope. In clinical terms, the patient experienced weight loss, which was to some extent caused by intermittent pseudo-obstruction when on a solid diet, therefore we decided to enrich her oral intake with high-calorie sip feed. The next follow-up CT scan of the abdomen showed a regression of the infiltrate, but the stenosis of the proximal jejunum, about 7 centimeters long, persisted. To respect the patient‘s wishes, no surgical resection of the stenotic section of the intestine was performed, but we proceeded with endoscopic dilatation of the stenotic section of the jejunum with a balloon. After the first two endoscopic dilatations of the stenotic area the patient experienced a temporary improvement in solid food tolerance. Because of restenosis, a third endoscopic dilatation was performed, with the development of complications that included short-term circulatory instability with abdominal pain and eventually required an urgent surgical solution. Key words: marginal zone B-cell lymphoma – stenosis – dilatation – intestinal perforation – jejunum – MALT

Successful Radiotherapy of a Rectal MALT B Lymphoma in an Adolescent

Purpose: We report the case of an adolescent with a rectal MALT lymphoma manifesting with hematochezia who was treated successfully with radiotherapy. Pediatric gastrointestinal (GI) malignancies are very rare. Of these, lymphomas are the most common. In adults, primary GI non-Hodgkin lymphomas (NHL) account for 4-20% of all NHL. WHO classifies NHL as Burkitt's, diffuse large B cell, mantle cell, follicular cell, and extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (MALT). Colorectal lymphomas are very rare (10-20% of GI NHL and 0.2-0.6% of all colonic malignancies), and only 10-25% localize in the sigmoid and rectum. MALT lymphomas represent 5% of NHL and the majority occur in the stomach. MALT rectal lymphomas are extremely rare and have been treated with surgery, chemotherapy, antibiotics, or radiation therapy. A 16-year-old male presented with a history of painless hematochezia and constipation for 2 months. Past medical and family history were unremarkable. Rectal exam revealed redundancy of the posterior rectal mucosa and gross blood on the glove. The physical exam was otherwise normal. Colonoscopy was normal except for mild nodularity of the rectosigmoid, with cobblestoning of the first 5 cm of the rectum and the presence of two hypertrophic anal papillae. Biopsies of the first 5 cm of rectum, including the anorectal junction, showed an infiltrate of large atypical B cells CD20+, Pax 5+, CD 79a+, CD43+, MUM1+, BCL2+, BCL6+, CD5-, CD10-, BCL1-. Plasma cells were CD20- showing cytoplasmic IgA kappa restriction. CD79a was strongly expressed in plasmacytic cells and poorly in B cells. Ki67 proliferation index was low to moderate. EBER-ish was negative. The findings were consistent with marginal zone lymphoma with plasmacytic differentiation. PET scan showed a hypermetabolic uptake in the anal region (SUV 11.4). CT of the chest, abdomen and pelvis was negative. The patient received 24 GCE involved field proton beam radiotherapy in 12 fractions to the anorectal lesion. Pelvic and inguinal nodes were not irradiated. Repeat PET scan 5 months after radiotherapy showed decreased anal hypermetabolic uptake (SUV 4.4). Colonoscopy after 6 months showed mild nodularity of rectosigmoid. The anorectal margin had mild erythema and nodularity. Rectal biopsies showed benign lymphoid aggregates and the anorectal junction mucosa was normal. He reported occasionally minor anorectal bleeding when constipated. To our knowledge this is the first pediatric case of a rectal MALT lymphoma that was induced into remission by low dose proton beam radiotherapy. Although very rare, anorectal malignancies should be considered in the differential diagnosis of hematochezia in children and adolescents.

TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-κB

Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

Diagnostic accuracy of PET/CT in patients with extranodal marginal zone MALT lymphoma

(18)Fluoro-2-deoxyglucose ((18)FDG) positron emission tomography (PET) is widely used for initial staging and follow-up in patients with malignant lymphoma. While earlier studies suggested a limited role for PET in extranodal marginal zone mucosa-associated lymphoid tissue (MALT) lymphoma patients due to their non-FDG avidity, more recent reports have suggested that the issue is controversial. In the present study, we evaluated the diagnostic accuracy of PET integrated with CT (PETCT) in patients with MALT lymphoma and assessed its reliability in clinical staging and monitoring response. Thirty-three patients with biopsy proven MALT lymphoma in 37 sites, who underwent PET/CT at diagnosis, were enrolled. Medical records, PET/CT findings and data obtained by other diagnostic procedures were reviewed. Common sites of MALT lymphoma were the stomach (18), lung (5), orbit (4), and parotid gland (3). PET/CT detected active disease in 18 of 33 patients (54.5%) at diagnosis. Sensitivity in gastric MALT (38.9%) was lower when compared with non-gastric MALT (75%). PET/CT detected active disease in 100% patients with advanced disease (stage III-IV) but only in 42.3% with early stage disease (I-II). The incidence of gastric FDG uptake was higher in patients showing gastric ulcer on gastroscopy than in subjects with minimal or no macroscopic findings. Of the 33 patients in the study cohort, 12 had a follow-up PET/CT which detected relapse in three patients. These data suggest that PET/CT is a useful tool for both, initial staging and follow-up after therapy in patients with MALT lymphoma. Its sensitivity depends on disease location and stage at initial diagnosis.

Heterogeneity of protein kinase C β2 expression in lymphoid malignancies

Aims: Protein kinase C (PKC) β is an important regulator of lymphoid survival and its expression has been shown to be altered in lymphomas. The aim was to determine the expression of PKC β2 in various subtypes of lymphoproliferative diseases by immunohistochemistry.Methods and results: One hundred and forty archival samples representing various subtypes of lymphoproliferative diseases were analysed. Certain subtypes, such as mantle cell, lymphocytic or follicular lymphoma, were found to express PKC β2 in > 90% of the samples. In follicular lymphomas, the follicular lymphomatous areas were constantly labelled, whereas residual germinal centres remained negative. In follicular hyperplasia, PKC β2+ cells were found in the mantle and marginal zones. Most angioimmunoblastic T‐cell lymphomas, lymphoblastic T‐cell lymphomas and marginal zone/mucosa‐associated lymphoid tissue (MALT) lymphomas were labelled with anti‐PKC βII antibody, but the pattern of expression was more heterogeneous in these subtypes. A minority of diffuse large B‐cell lymphomas were stained and most plasma cell malignancies were negative. None of the cases of Hodgkin's disease and anaplastic large cell lymphoma expressed PKC β2.Conclusions: PKC β2 expression varies significantly among lymphoproliferative diseases. In our series, the highest level of expression was found in mantle cell lymphomas and chronic lymphocytic lymphoma.

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases.

The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34-91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis. Twelve patients developed cutaneous or extracutaneous recurrences, and five died from malignant lymphoma 7-84 months (median 36) after diagnosis. Histological examination showed features of marginal zone/mucosa-associated lymphoid tissue (MALT)-type lymphoma in 12 cases. Three of these had transformed to diffuse large B-cell lymphoma (DLBCL) in relapse biopsies. The remaining cases were seven primary DLBCLs and two cases tentatively classified as follicle centre cell (FCC) lymphoma. The neoplastic B cells showed similar phenotypes and genotypes in most cases (CD20+, CD79+, CD5-, CD10-, cyclin D1-, bcl-2+, bcl-x-, bax-, t(14;18)-negative). p53 protein was expressed in five cases, and four harboured mis-sense or loss-of-function mutations in the p53 gene. Deletion or promoter region hypermethylation of the p16INK4a gene was detected in two patients with DLBCL. The level of retinoblastoma protein expression and the proliferative fraction were significantly higher in DLBCL (> 50%) than in MALT- or FCC-type lymphomas (< 10%). Features associated with an unfavourable prognosis were the presence of multiple skin lesions at diagnosis, transformation from MALT-type lymphoma to DLBCL, and possibly p16INK4a aberrations. It is concluded that most CBCLs are dissimilar from FCC lymphomas and seem to be more closely related to marginal zone/MALT-type lymphomas. It is also suggested that there are fundamental differences between DLBCL and other histological categories of CBCL, indicating that cutaneous DLBCL is a separate entity with an increased growth potential and genetic features similar to DLBCL originating in other anatomical sites.