Endoscopic ultrasonography in gastric lymphomas: appraisal on reliability in long‐term follow‐up

The reliability of endoscopic ultrasonography (EUS) in follow‐up management of gastric lymphomas has not been clearly validated. We conducted a retrospective analysis on 23 patients, 12 affected by mucosa‐associated lymphoid tissue (MALT) lymphoma, eight by diffuse large B‐cell lymphoma, and three by high‐grade lymphoma with low‐grade component, all treated with a stomach‐conservative approach. One hundred and twenty matched evaluations with both EUS and endoscopy with biopsy (E‐Bx) were performed, according to validated guidelines and clinical judgment. At a median follow‐up of 87 months ranged between 9.5 and 166 months, the analysis of progression‐free survival and disease‐free survival showed a strict relationship between the persistence of EUS abnormalities and the clinical outcome in patients with MALT lymphoma (p = 0.0079; p = 0.02) but not in patients with high‐grade lymphoma. In conclusion, EUS evaluation does not seem reliable in follow‐up management of high‐grade lymphomas, although it could have a great clinical impact in the management of MALT lymphoma. Copyright © 2011 John Wiley & Sons, Ltd.     

Gastric MALT lymphoma: From concept to cure

Gastric MALT lymphomas are clinically and histologically quite distinct from comparable low-grade B-cell lymphomas of lymph nodes. Their histology suggests that immunological mechanisms might be operative in their growth. Given that there is normally no lymphoid tissue in gastric mucosa and that Helicobacter pylori (H. pylori), the only common bacterial antigen in the stomach, results in the accumulation of gastric MALT, the possibility that this organism is implicated in the pathogenesis of gastric lymphoma has been extensively investigated. It appears that most, but not necessarily all, gastric MALT lymphomas arise in MALT acquired in response to H. pylori infection and develop by stepwise accumulation of genetic abnormalities. Early molecular events in the evolution of gastric MALT lymphoma from acquired MALT include trisomy 3, t(11;18)(q21;q21), genetic damage leading to genetic instability, as indicated by the so-called replication error repair (RER) phenotype, and both p53 and c-mycmutations. At this stage in their development, the growth of the lymphomas is driven by contact between the neoplastic B cells and H. pylori specific intra-tumoral T cells. Eradication of H. pyloricauses the tumour to enter a latent phase resulting in clinical regression. Later events, such as t(1;14)(p22;q32), appear to be linked to a capacity for autonomous growth, loss of sensitivity to H. pylori and dissemination of the lymphoma beyond the stomach and gastric lymph nodes. Cloning of the breakpoint in t(1;14) has allowed the identification of a new tumour suppresser gene, bcl10. High grade transformation of MALT lymphoma has been associated with p53 inactivation, deletions of p16 and t(8;14).     

Helicobacter pylori and the t(11;18)(q21;q21) Translocation in Gastric Low-grade B-Cell Lymphoma of Mucosa-associated Lymphoid Tissue Type

The reported regression of mucosa‐associated lymphoid tissue (MALT) type gastric low‐grade Bcell lymphoma following treatment for Helicobacter pylori (H. pylori) infection has not yet been comprehensively analyzed, especially in relation to the recently identified c‐IAP2‐MALT1/MLT gene alteration resulting from the t(11;18)(q21;q21) chromosomal translocation found in MALT lymphoma. The relationship between MALT lymphomas and H. pylori was investigated in 30 patients who received an antibacterial treatment. Patients were followed up by means of endoscopy and biopsy. Molecular genetic analyses focused on the presence or absence of the immunoglobulin heavy chain (IgH) gene and/or MALT1/MLT gene alteration resulting from t(11;18)(q21;q21) translocation. H. pylori was positive in 26 of the 30 patients. The overall success rate of cure of H. pylori infection was 96% (25/26). Thirteen patients (52%) showed complete remission (CR) of lymphoma, nine (36%) partial remission (PR), and three (12%) registered no change (NC). Statistical analysis revealed significant differences between CR and PR/NC patients in age (< 60 or 60), in lymphoma location (single or multiple sites) and in the presence or absence of gene rearrangement before eradication (P< 0.05). Endoscopy showed a cobblestone appearance only in PR cases and polypoid features predominantly in NC cases. Two NC patients with polypoid gross appearance showed rearrangements involving either c‐IAP2 or MALT1 gene in Southern blot analysis, while none of seven other resected patients with non‐polypoid superficial gross appearance showed rearrangement. Gastric MALT lymphoma could be pragmatically subdivided into three groups, CR (MALT‐A), PR (MALT‐B), and NC (MALT‐C) on the basis of the reaction to eradication of H.pylori. We speculate that MALT‐A may represent an incipient neoplasm or dysplasia, MALT‐B a neoplasm activated by antigenic stimulation of H. pylori, and MALT‐C a lymphoma independent of H. pylori. Polypoid lesions in MALT‐C were associated with c‐IAP2‐MALT1/MLT gene alteration resulting from t(11;18)(q21;q21). This classification is thought to be clinically significant for deciding the most appropriate mode of treatment of MALT‐type lymphoproliferative disorders.     

BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue

Extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) is an indolent B‐cell lymphoma, which is often localized in the stomach. It is characterized by typical morphology, immunology, cytogenetics and expression profile. The coexistence of a large B‐cell lymphoma and a MALT lymphoma in the gastrointestinal tract is defined as a composite lymphoma (ComL) and, as we have previously shown, is almost always the consequence of secondary transformation of MALT lymphoma. Here, we have analyzed a panel of seven MALT lymphomas, seven ComL and thirteen large cell variants of marginal zone B‐cell lymphomas (MZBL) using FISH for the detection of rearrangements of IGH, MALT1, BCL6, BCL10 and FOXP1 and immunohistochemistry for Bcl6, Bcl10 and FoxP1. Translocations involving IGH were found in 10/27 lymphomas including two cases with IGH‐BCL6 fusion and one with IGH‐BCL10 fusion; in 7/10 cases, the translocation partner was not identified. Bcl10 and FoxP1 protein expression was heterogeneous throughout the series. Genetic rearrangements of BCL6 and Bcl6 protein expression were found almost exclusively in the large cell components of the ComL and the large cell extranodal MZBL (p = 0.2093 and p = 0.0261, respectively). These findings suggest Bcl6 as a marker for transformation of MALT lymphoma.     

粘膜相关淋巴组织(MALT)型淋巴瘤的临床特点和处理

粘膜相关淋巴组织(MALT)型淋巴瘤是非霍奇金恶性淋巴瘤中一个独立的亚型，有其独特的临床病理特点。它是结外低度恶性B细胞淋巴瘤中最常见的一型。此型淋巴瘤病人常有慢性感染病史或自身免疫性疾病。MALT淋巴瘤是一种惰性病变，可较长时间局限于局部。局部治疗有效。胃MALT淋巴瘤最常见。本文以胃MALT淋巴瘤为重点，对MALT淋巴瘤的临床特点和处理作一个综述。     

Malignant lymphoma of mucosa-associated lymphoid tissue of the lacrimal gland: case report and review of literature

Mucosa-associated lymphoid tissue (MALT) lymphomas are increasingly recognized as a distinct clinical-pathologic entity among the non-Hodgkin's lymphomas. It usually presents as a localized disease process in extranodal tissues or organs such as stomach, salivary gland, thyroid gland, and not infrequently in orbital adnexa. Radiotherapy has an important role in the management, although long-term clinical results specifically addressing localized MALT lymphomas are lacking. We report a case of localized MALT lymphoma of the lacrimal gland, with successful treatment by radiation therapy (total dose 25 Gy) with 3 years of clinical follow-up. A review of the published literature was undertaken to assess the role of radiotherapy in the treatment of this disease involving orbital tissues, specifically, the lacrimal gland. Based on previous reports of patients with orbital lymphomas (low grade) and pseudolymphomas, of which many will now be recognized as MALT lymphomas, radiotherapy has an excellent local control rate and would be the treatment of choice. However, long-term results of pathologically confirmed cases of MALT lymphomas need further study because occasional relapses at distant sites can occur.     

Radiation therapy for localized low-grade non-Hodgkin's lymphomas

The most common low grade B-cell non-Hodgkin's lymphomas are follicular lymphomas, and extranodal marginal zone lymphomas, also known as mucosa-associated lymphoid tissue (MALT) lymphomas. Localized presentations of follicular lymphoma occur in 20-30% of cases, while for MALT lymphomas, stage I-II disease presentations occur in 70-90%. These are radiation-sensitive lymphomas. Following moderate dose local radiation treatment (30-35 Gy) for these stage I and II low grade lymphomas, the clinical results indicate long-term local control and possible cure. While local control is achieved with minimal morbidity with involved-field radiation therapy, a significant proportion of patients relapse with systemic disease outside of radiation fields. For follicular lymphoma, this occurs in approximately 50% of patients after 15 years, and for non-gastric MALT lymphoma, 30-40% after 10 years. Although patients with relapsed systemic disease are not curable with chemotherapy, the disease often behaves in an indolent fashion and prolonged survival is observed. For gastric MALT lymphomas, radiation therapy is indicated in patients whose lymphoma did not respond to Helicobacter pylori eradication therapy, or in gastric lymphoma not related to this microorganism. The subject of causative agents responsible for non-gastric MALT lymphomas is under active study and the identification of putative microorganisms will lead to improved treatment strategies for these unusual lymphomas, similar to the success in gastric lymphomas over the last decade.     

Primary diffuse large B cell lymphoma of the stomach: analysis of somatic mutations in the rearranged immunoglobulin heavy chain variable genes indicates antigen selection.

Gastric low grade MALT lymphomas show a pattern of somatic mutations in their rearranged immunoglobulin genes, indicative of antigen selection. This provides evidence for antigen stimulation in the lymphomagenesis. Gastric diffuse large B cell lymphomas develop secondary to low grade MALT lymphoma or de novo. To study whether antigen-selection is also a feature of primary diffuse large B cell lymphomas, we analysed somatic mutations in the rearranged immunoglobulin heavy chain (IgH) variable genes (VH). The rearranged VH genes of six cases of gastric primary diffuse large B cell lymphoma were amplified from genomic or complementary DNA by a VH gene family-specific polymerase chain reaction method. The PCR products were directly sequenced and were compared to published germline sequences to analyse somatic mutations. Similarly to low grade MALT lymphomas 5/6 primary diffuse large B cell lymphomas show a pattern of somatic mutation in their rearranged VH genes, indicative of antigen selection and suggesting a role for antigens in lymphomagenesis. One case showed bi-allelic VH gene rearrangements, which were non-functional due to extensive deletions. Antigen selection could not be demonstrated or excluded. Antigen selection is a common feature in most analysed primary diffuse large B cell lymphomas, although some heterogeneity in the mechanisms involved in the lymphomagenesis of gastric primary diffuse large B cell lymphomas has not been excluded entirely (case 4).     

Transformation of MALT lymphoma to pure plasma cell histology following treatment with the anti-CD20 antibody rituximab

Mucosa associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma arising from marginal-zone B-cells which are closely related to plasma cells. As opposed to the large majority of plasma cells, MALT lymphoma cells express CD20, and the anti-CD20 antibody rituximab has been reported as active treatment in patients with MALT lymphoma. We present a patient with MALT lymphoma involving stomach and lung which transformed to a pure plasma cell tumor after therapy with rituximab. This observation again supports the close association between the cell of origin of MALT lymphoma and plasma cells, suggesting that “plasmacytoma of the GI-tract” as anecdotally reported may in fact be a MALT lymphoma with extreme plasmacytic differentiation. In addition, our findings suggest that MALT lymphomas with plasmacytic differentiation might have a different 18F-FDG uptake as compared to classical MALT lymphoma.     

Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.     

Synchronous mucosa-associated lymphoid tissue (MALT) lymphomas involving bilateral orbits and breasts: a rare clinical entity

Primary orbital and primary breast lymphomas comprise very small subgroups of extranodal lymphomas. Clinical presentation at both these sites together is extremely rare. We describe a case of bilateral orbital and bilateral breast mucosa-associated lymphoid tissue (MALT) lymphomas with bilateral pre-auricular lymph nodal metastasis. The case history, staging and management for this unusual entity are discussed.     

18F‐FDG uptake and its clinical relevance in primary gastric lymphoma

We studied the clinical relevance of ¹⁸F‐fluorodeoxyglucose (¹⁸F‐FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty‐two patients with primary gastric lymphoma were analysed: 32 diffuse large B‐cell lymphomas (DLBCL) and 10 extranodal marginal zone B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up‐staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down‐staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax ≥ median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow‐up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual ¹⁸F‐FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual ¹⁸F‐FDG uptake observed during follow‐up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd.     

Apoptosis in lymphocytic leukemias and lymphomas

Most current classifications of lymphoid neoplasms define the tumors based on the cell of origin, phenotype, genetic abnormalities, and clinical features. Here it is proposed that human lymphocytic tumors can be categorized based on the propensity and capacity of the tumor cells to undergo apoptosis. The first category is defined by malignant cells that are resistant to apoptosis due to expression of anti-apoptotic factors such as bcl-2 and cellular inhibitors of apoptosis (IAPs). These tumors would include CLL and follicular lymphomas, as well as some malignancies in which the tumor cells are infected by viruses that co-opt cell survival pathways, such as human T-cell leukemia/lymphoma virus (HTLV)-1. The second category, in which the malignant cells are apoptosis-prone, would include tumors arising in the context of impaired cytotoxic T-cell function. These neoplasms would include some human immunodeficiency virus (HIV)-related lymphomas such as Burkitt's lymphoma, and post-transplantation lymphomas. The third category would include neoplasms of intermediate sensitivity to apoptosis, some of which are associated with infection such as mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach. Although this classification is tentative, it should evolve in parallel with our understanding of pathogenic mechanisms in lymphoid neoplasia, and provides a novel framework with which to consider the appropriateness of specific therapeutic strategies. Distinctions among lymphocytic tumors in terms of the likelihood of response to therapies such as antisense to bcl-2 related proteins, inhibitors of NF-kappa B activity, and new approaches aimed at bolstering the host's immune response, would cross standard classifications based on the T or B-cell origin of the tumor cells.     

肾脏黏膜相关淋巴瘤2例报道并文献回顾

背景与目的：原发肾脏的黏膜相关组织淋巴瘤十分罕见,目前世界报道不足50例。本文介绍2例肾脏黏膜相关淋巴瘤的形态学特点和免疫表型特征,旨在使临床和病理对这种低度恶性的B细胞肿瘤的特点有所了解。方法：收集病史资料,形态学评价根据HE切片,用免疫组化法检测肿瘤细胞的表型,使用的抗体包括CD20、CD79、CD5、CD10、CD43、CD23、BCL10和Cyc linD1。结果：2例患者均为女性,年龄分别为48岁和55岁,临床上均有慢性肾盂肾炎病史。B超和CT检查发现肾脏肿块,行全肾切除。大体检查可见肿块位于肾髓质,呈境界不清的暗红色;镜检见肾盂至肾实质弥漫淋巴样细胞浸润,以小淋巴细胞、中心细胞样细胞、淋巴浆细胞和浆细胞浸润为主,可见肿瘤细胞浸润肾小管和肾球囊形成淋巴上皮病变和反应性淋巴滤泡,但没有显著滤泡殖入;免疫组化显示增生细胞以B淋巴细胞为主,散在分布反应性T细胞,肿瘤细胞CD20、CD79 a阳性,CD43弱阳性,CD5、CD10、BCL10、CD23和Cyc linD1均为阴性。结论：原发肾脏黏膜相关淋巴瘤临床极为罕见,临床表现和辅助检查与肾细胞癌不易鉴别,但组织学特点符合经典黏膜相关淋巴瘤的所有特征,免疫表型有助于病理诊断。     

Role of activated host T cells in the promotion of MALT lymphoma growth

Gastric mucosa-associated lymphoid tissue (MALT) B cell lymphomas contain activated helper T cells. The evidence supports the presence of mechanisms of T cell dependence underlying the development of these lymphomas. It appears that the T cells, which activate B cells, may contribute to lymphoma pathogenesis. Co-stimulatory molecules necessary for effective B cell/T cell interaction are expressed in MALT lymphomas. The studies suggest that CD40 signaling, in combination with cytokines, is essential for the development and progression of MALT lymphomas. Activated T cells of low grade gastric MALT lymphoma, while delivering full help to B cells, are apparently deficient in two cytotoxic mechanisms involved in the concomitant control of B cell growth.     

Non-Hodgkin's lymphoma of the thyroid: A retrospective review of all patients diagnosed in Nottinghamshire from 1973 to 1992

The pathological and clinical features were reviewed of all primary non-Hodgkin's lymphomas (NHL) of the thyroid gland diagnosed between 1973 and 1992 in the population (1.1 million) served by the Nottingham and North Nottinghamshire Health Authorities. Of the 43 patients with histologically proven NHL, three had low grade mucosa associated lymphoid tissue (MALT) lymphomas (Stage I_eA, 2; Stage II_eA, 1), 35 had intermediate or high grade lymphomas, Stage I_ea or II_eA (intermediate MALT, 2; high grade MALT, 14; B-cell diffuse centroblastic, 17; anaplastic large cell (Ki-1) of null cell type, 1; high grade unclassifiable, 1), and one had unclassifiable NHL Stage II_eA. One patient had Stage III_eA disease (high grade MALT) and three had stage IVA disease (high grade MALT, 2; B-cell diffuse centroblastic, 1). The median age was 68 years (range 45–86) with a female : male ratio of 6:1. For the 35 patients with intermediate or high grade thyroid NHL (Stages I_eA and II_eA) the 5- and 10-year cause specific survival was 60%. The 21 patients treated between 1985 and 1992 initially with chemotherapy (except stage I_eA (<5 cm diameter) had a 5-year cause specific survival of 69% (95% CI 48–90) compared with 46% (95% CI 19–73) for the 14 patients treated between 1973 and 1984 with initial radiotherapy (χ² = 1.62). The survival of those patients with intermediate or high grade MALT lymphomas was not significantly greater than of those patients with B-cell diffuse centroblastic NHL.     

Indolent T‐ and NK‐cell lymphoproliferative disorders of the gastrointestinal tract: a review and update

Primary gastrointestinal (GI) T‐ and NK‐cell lymphomas are usually aggressive neoplasms associated with high morbidity and mortality. Over the past two decades, however, cases of primary GI lymphoproliferative disorders (LPDs) or lymphomas of T‐ or NK‐cell derivation with indolent behavior have been reported. These LPDs are rare and they can be challenging to diagnose as they share clinical and pathological features with both, inflammatory disorders and aggressive T‐ and NK‐cell lymphomas. Primary, indolent clonal T‐cell proliferations of the GI tract, which can be CD4+, CD8+ or CD4? CD8?, have been included as a provisional entity in the newly revised World Health Organization (WHO) classification of lymphoid neoplasms and designated ‘indolent T‐cell LPD of the GI tract’. It is currently unclear whether the indolent NK‐cell LPDs represent reactive or neoplastic proliferations. In this review, we describe the clinical, morphologic, immunophenotypic and genetic features of indolent GI T‐ and NK‐cell LPDs and provide guidance in differentiating them from other inflammatory and neoplastic diseases. We believe that greater awareness of these LPDs amongst physicians and the research community will lead to timely and accurate diagnoses, stimulate investigations into the pathogenetic mechanisms underlying different entities thereby enhancing our understanding of disease biology and enable the development of effective therapeutic regimens. Copyright © 2016 John Wiley & Sons, Ltd.     

Histopathologic features and expression of Bcl-2 and p53 proteins in primary gastric lymphomas

The aim of this study is to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas which were reclassified according to the concept of mucosa associated lymphoid tissue (MALT). The resected specimens from 41 patients with primary gastric lymphoma were investigated retrospectively. Immunohistochemical study was done to analyze the immunophenotype and bcl-2 and p53 proteins expression. Twenty three of the cases had tumors mainly located in the antrum. Histologically, 12 were low grade and 20 were high grade B-cell lymphoma of MALT, 9 other B-cell nonHodgkin's lymphomas. Helicobacter pylori was identified in 72% of the cases. According to Musshoff's modification, most of the MALT lymphoma cases had stage I or II disease. There was significant difference between low and high grade cases, in respect to depth of invasion in gastric wall. Immunohistochemically, the neoplastic cells in all MALT lymphomas expressed B-cell phenotype. Bcl-2 protein was found to be expressed in 59% and p53 protein expression was detected in 72% of cases. Among the B-cell lymphoma of MALT, bcl-2 positivity decreased and p53 positivity increased significantly as the histological grade advanced. So, an inverse correlation was observed between the expression of bcl-2 and p53. In conclusion, most primary gastric lymphomas are low or high grade B-cell MALT lymphomas and appear to arise in MALT acquired as a reaction to Helicobacter pylori infection. Expression of bcl-2 and p53 in gastric lymphomas may be associated with transformation from low-grade to high-grade disease.     

Thyroid Lymphoma: Recent Advances in Diagnosis and Optimal Management Strategies

Primary thyroid lymphoma is rare, composing approximately 5% of all thyroid malignancies and less than 3% of all extranodal lymphomas. It typically presents as a rapidly enlarging goiter with associated compressive symptoms. Thyroid ultrasound and fine needle aspiration cytology, using flow cytometry and immunohistochemistry, remain the main modalities used to confirm the presence of lymphoma. The increasing use of an ultrasound‐guided core biopsy to achieve an accurate diagnosis has further limited the role of surgery. An open surgical biopsy may still be required not only for definitive diagnosis but also to confirm the subtype of lymphoma. There are limited numbers of randomized or prospective trials to guide management, and controversy remains over optimal treatment. Treatment and prognosis of this disease can be dichotomized into two separate groups: pure mucosa‐associated lymphoid tissue (MALT) lymphoma and diffuse large B‐cell lymphoma (DLBCL) or mixed subtypes. Early stage (stage IE) intrathyroidal MALT lymphomas typically have an indolent course and may be treated with single‐modality surgery, radiotherapy, or a combination of both. DLBCLs are more aggressive, and survival outcomes are highest with multimodal therapy incorporating monoclonal antibodies, chemotherapy, and radiotherapy. The prognosis is generally excellent but can be varied because of the heterogeneous nature of thyroid lymphomas. The aim of this paper is to discuss the changes in diagnostic modalities and to focus on the recent alterations in the management of this rare disease, including targeted therapies as well as the more limited role of the endocrine surgeon.     

Mucosa-associated lymphoid tissue lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma has attracted attention because its concept has amalgamated the study of etiology and pathogenesis in an intriguing group of lymphomas. MALT lymphomas are a B-cell malignancy with characteristic lymphoepithelial lesions; cells are CD20-positive and CD5- and CD10-negative. The molecular changes observed include trisomy 3, t(11;18), and t(1;14) translocations. They commonly occur in the stomach, orbit, salivary glands, and thyroid. Localized disease is present in 60% to 70% of patients. Involvement of multiple extranodal sites has been observed at presentation or during the course of disease. Lymphocyte homing has been implicated in gastrointestinal MALT and may be involved in other MALT lymphomas. Local therapy, either through surgery or radiotherapy, is curative in a high proportion of patients. MALT lymphomas respond to chemotherapy, but there is no evidence that cure can be achieved, although prolonged survival is common. Long-term follow-up is essential for study of the outcomes in this disease.