Diagnostic features of gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue may be difficult to distinguish from florid gastritis and other small B-cell lymphomas. The following review details a practical summary of the morphologic features, immunohistochemical markers, and molecular tests that currently provide for an accurate diagnosis in daily practice.     

眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤临床病理分析

目的 探讨眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤(marginal zone B cell lymphoma of mucosa-associated lymphoid tissue)(简称为MALT淋巴瘤)的临床病理特征、治疗及预后.方法 对15例眼结膜MALT淋巴瘤患者的临床病理资料进行回顾性分析及随访,复查和完善HE及免疫组化染色切片,4例进行Ig基因重排克隆性分析.结果 (1)15例患者中,男性5例,女性10例,中位年龄42岁,病史平均20个月.(2)病理形态:黏膜下大量密集淋巴样细胞弥漫浸润,并有模糊淋巴滤泡样结节.浸润细胞多为小～中等大小的淋巴样细胞及单核样B细胞.(3)免疫表型:浸润细胞CD20、CD79a、BCL-2均(+),CD3、CD5、CD10、Cyclin D1、TdT均(-).(4)Ig基因克隆性分析:4例均呈单克隆.(5)随访:随访时间2～35个月,截止随访日期,所有患者均生存,且病变无复发.结论 眼结膜MALT淋巴瘤好发于中年女性,结膜红肿突起为主要特征,镜下以小细胞样边缘带B细胞为主,具有典型MALT淋巴瘤的免疫表型和惰性临床经过,预后良好.     

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.     

Extranodal marginal zone lymphoma occurring along the trachea and central airway

Extranodal marginal zone lymphoma is a low-grade B cell lymphoma that presents with an indolent clinicopathologic nature. Although this tumor can occur in various sites, including the gastrointestinal tract and lungs, it develops and spreads extremely rarely along the trachea and central airway. We report a case of extranodal lymphoma of mucosa-associated lymphoid tissue with tracheobronchial involvement. An 83-year-old woman presented with a cough and dyspnea. Bronchoscopic evaluation confirmed diffuse, multiple nodular lesions in both the trachea and large bronchi, and she was diagnosed with an extranodal marginal zone lymphoma of the tracheobronchial tree. After systemic chemotherapy, she survived for more than 18 months.     

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.     

Monocytoid B-cell lymphoma, a tumour related to the marginal zone

Monocytoid B-lymphocytes are a B-cell subset present in subcapsular sinuses in some cases of lymphadenitis. We describe a case of lymphoma of this cell type. The tumour shows a distinctive morphology characterized by concentric strands of tumour cells around lymphoid follicles with hyperplastic germinal centres and conserved mantle zones. Electron microscopy of these cells shows short cellular processes as well as moderate development of endoplasmic reticulum. The phenotype of the tumour was monoclonal IgM-kappa, distinct from other node-based B-cell subpopulations and suggesting a possible relationship to the lymphocytes of the marginal zone present peripheral to lymphoid follicles of the spleen. Morphological features that suggest a relationship with hairy cell leukaemia are contrasted by phenotypic differences and the ultrastructural absence of ribosomic lamellar complexes.     

CT-guided needle biopsy in the diagnosis of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a rare combination

We represent a rare case of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The patient was a 66-year-old male presented with 1 month history of recurrent cough and hemoptysis. Chest CT showed solitary ground-glass opacity (GGO) in the upper lobe of the right lung and mediastinal lymph node enlargement in station 3p. A CT-guided transthoracic needle biopsy was performed. Tissue specimens of the GGO revealed a typical adenocarcinoma. Histopathologic diagnosis of mediastinal lymph node was extranodal marginal zone lymphoma of MALT. Because of its rarity, extranodal marginal zone lymphoma of MALT should be considered in the differential diagnosis when we encounter mediastinal lymphadenopathy in patients with lung adenocarcinoma.     

肺黏膜相关淋巴组织边缘区B细胞淋巴瘤及良性淋巴组织增生性疾病的临床病理分析

目的 研究肺原发性黏膜相关淋巴组织边缘区B细胞(MALT)淋巴瘤及良性淋巴组织增生性疾病的临床病理形态、免疫组织化学表型和B细胞重链基因重排,比较肺MALT淋巴瘤和良性淋巴组织增生性疾病的差异.方法 回顾性的分析原发性肺MALT淋巴瘤13例,7例肺良性淋巴组织增生性疾病资料.对标本行常规HE染色,EnVision免疫组织化学染色(抗体包括AE1/AE3、CD20、CD79α、CD3、CD5、CD10、CD21、bel-2、bcl-6、cyclinD-1)及免疫球蛋白重链IgH基因重排检测.结果 13例肺MALT淋巴瘤,细胞成分多样,分别由不同比例的小淋巴细胞样细胞、中心细胞样细胞、单核样B细胞组成,常伴有浆细胞分化.肿瘤细胞以弥漫性和滤泡边缘区排列为主,常见反应性淋巴滤泡和滤泡中心的植入.肿瘤细胞呈串珠状直接侵犯肺泡间隔和沿支气管血管束向周边及肺膜扩散.MALT淋巴瘤中,均未见坏死.9例可见肿瘤细胞侵犯血管壁,6例可见胸膜累及,2例肺门淋巴结侵犯.9例肺MALT淋巴瘤可见淋巴上皮样病变,免疫组织化学显示上皮细胞内的淋巴细胞CD20阳性,CD3阴性.7例肺良性淋巴组织增生性疾病,2例可见淋巴上皮样病变,免疫组织化学显示,其淋巴上皮样病变内的淋巴细胞,部分CD20阳性,部分CD3阳性.9例肺MALT淋巴瘤进行了免疫球蛋白重链IgH基因重排,8例阳性;7例良性淋巴组织增生性疾病均为阴性.结论 肺MALT淋巴瘤在细胞组成和排列上与其他部位结外MALT淋巴瘤相同,肿瘤细胞呈串珠状直接侵犯肺泡间隔和沿支气管血管束向周边及肺膜扩散.在肺内淋巴上皮样病变常见于MALT淋巴瘤,并有助于诊断,但并非其特异性病变,一些肺的反应性淋巴组织增生也可出现,用免疫组织化学有助于区别两种病变.免疫球蛋白重链IgH基因重排可以帮助鉴别肺MALT淋巴瘤和良性淋巴组织增生性疾病.     

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type in Waldeyer's ring

Amongst a total of 329 cases of low-grade B-cell lymphoma of Waldeyer's ring, we identified 12 cases that corresponded histomorphologically to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. These lymphomas are characterized by an extrafollicular growth pattern, often with a marginal zone-like arrangement, and by the centrocyte-like morphology of the tumour cells. They have not been described previously in this location. They predominantly affected the palatine tonsil. Ten cases were primary lymphomas of Waldeyer's ring. In two cases there was a simultaneous high-grade component. Two cases showed regional spread to cervical lymph nodes, but there was no widespread nodal involvement at the time of diagnosis. Immunohistochemically, all cases displayed B-cell markers and light chain restriction. Tropism of tumour cells for the epithelium was a consistent finding. In two cases involvement of Waldeyer's ring was secondary; in one of them the primary tumour was a gastric low-grade B-cell lymphoma of MALT type and in the other a high-grade B-cell non-Hodgkin's lymphoma of the stomach. These findings indicate that low-grade B-cell lymphomas of MALT type occurring in Waldeyer's ring should be included amongst the tumours of the MALT system. We surmise that in Waldeyer's ring such tumours are derived from the marginal zone, as has already been postulated for similar gastric tumours.     

Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with rheumatoid arthritis

The majority of thymlc lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) In the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Hlstologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and Infiltrated Hassan's corpuscles (lymphoepithellal lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma In the thymus. This is the first report of low-grade B cell lymphoma In the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, It is suggested that the RA played an Important role in the development of malignant lymphoma in this case.     

Lymphomas of mucosa-associated lymphoid tissue arising in the urinary bladder

The clinical, histological and immunohistochemical findings in five primary lymphomas of the urinary bladder are reported. One patient had both lymphoma and transitional cell carcinoma of the bladder. All of the lymphomas showed histological features of mucosa-associated lymphoid tissue (MALT) lymphomas with centrocyte-like cells in all cases. One patient with pre-existing cystitis glandularis showed lymphoepithelial lesions. Biopsies from four patients contained reactive germinal centres and, in two of these, there was follicular colonization by tumour cells. In three patients, repeat biopsies, over several years, showing the changes of MALT lymphoma, were diagnosed as cystitis. We suggest that a large proportion of primary lymphomas of the bladder are lymphomas of MALT and that the characteristic morphological and immunohistochemical features of these tumours should be sought in biopsies containing large numbers of lymphoid cells.     

眼眶原发性MALT淋巴瘤临床病理观察

目的 探讨眼眶原发性黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)临床病理特点及影响预后因素。方法 复习7例眼眶原发性MALT淋巴瘤临床病理资料及病理切片,并用免疫组化S—P法重新标记瘤细胞。结果 5例位于泪腺及结膜,2例位于眼肌,7例均为IE期。瘤细胞以边缘区B细胞为主,混有少量浆细胞及母细胞化的淋巴细胞。位于泪腺及结膜者可见淋巴上皮病变及生发中心植入现象。瘤细胞表达CD45、CD20、IgM、bcl-2及单一的轻链,CD3、CD5、CD10、cyclin D1、CK均阴性。7例均作手术治疗;1例辅以放疗,2例结合化疗。7例随访4～139个月,均存活。结论 眼眶原发性MALT淋巴瘤好发于泪腺及结膜,预后与临床分期有关,与治疗方法关系不大。     

Primary malignant lymphoma of the thyroid-a tumour of mucosa-associated lymphoid tissue: review of seventy-six cases

Seventy-six cases of primary thyroid lymphoma have been reviewed employing the Kiel classification. These lymphomas are almost entirely of follicle centre cell origin, occur predominantly in elderly females, and are frequently associated with lymphocytic thyroiditis or Hashimoto's disease. The overall prognosis is variable, with long-term survival in a substantial number of cases following thyroidectomy and radiotherapy. Results of histological examination including immunoperoxidase studies are described. It is proposed that thyroid lymphoma represents a neoplasm of mucosa-associated lymphoid tissue (MALT), and the implications of this are discussed.     

Monocytoid/marginal zone B-cell differentiation in follicle centre cell lymphoma

We report on two cases of low grade follicle centre cell lymphoma with a pronounced parafollicular monocytoid/marginal zone B-cell component. One patient had a history of preceeding follicular high grade B-cell lymphoma of centroblastic type showing the same light chain restriction and identical immunoglobulin heavy chain gene rearrangement as the low grade lymphoma diagnosed 15 months later. Morphologically, in both cases the two constituents of the low grade tumours were clearly distinguishable. Immunohistochemically, the follicular component strongly expressed bcl-2 protein in contrast to a weak staining of the marginal zone B-cell component. Performing PCR, a rearrangement of the major breakpoint region of bcl-2 was not found. Identical light chain restriction of the follicular and the monocytoid B-cell/marginal zone components strongly indicates a clonal relationship between them. A monocytoid/marginal zone B-cell component in follicular lymphoma probably results from differentiation of the follicle centre cells and does not indicate a composite lymphoma.     

Malignant lymphoma of mucosa-associated lymphoid tissue

Lymphomas of the gastrointestinal tract, salivary glands, lung and thyroid are grouped together as tumours arising in mucosa-associated lymphoid tissue. The great majority of them are of B-cell origin but distinctive T-cell lymphomas are also recognized in the gastrointestinal tract. These lymphomas tend to remain localized for prolonged periods but, whereas the B-cell group respond favourably to local therapy, the T-cell group are associated with severe morbidity and their overall prognosis is extremely poor. Accepted histological classifications of non-Hodgkin's lymphomas are difficult to apply to these tumours. In this paper their morphological features are reviewed; recent findings based on immunohistochemistry and DNA analysis are presented; and the biological behaviour of these tumours is discussed insofar as they offer insight into mucosal immunological mechanisms.     

Plasmablastic lymphoma following combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue lymphoma: a case report and review of literature

Plasmablastic lymphoma (PBL) is an uncommon malignancy which predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. Sporadic cases have been published describing PBL in immunocompetent patients as well as in immunodeficient patients following immunosuppressive therapy or transplantation. We hereby reported a case of PBL in a 69-year-old, HIV-negative male subjected to combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue (MALT) lymphoma. The diagnosis of PBL was made with tumor cells of immunoblasts or plasmablasts morphology strongly positive for MUM-1, EMA and CD138, and partly positive for CD38, and negative for CD20, BCL-6, and CD56, and approximately 80% of which were positive for Ki-67. The case presented PBL after MALT, and a history of chemotherapy including fludarabine and rituximab led to the potential immunocompromised state. The patient died 5 months after the diagnosis of PBL.     

Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma

AIMS: Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP. METHODS AND RESULTS: Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10-) (n=12), FL (cyclin D1- CD5- CD10+) (n=14) and MALT (cyclin D1- CD5- CD10-) (n=9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P=0.0040). CONCLUSIONS: Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.     

Primary hepatic marginal zone B-cell lymphoma with mantle cell lymphoma phenotype

We report a rare case of primary hepatic lymphoma, Stage II disease, in a 48-year-old male who had a solitary hepatic tumour measuring 4×4.5×3 cm. The tumour showed a nodular growth pattern and lymphoepithelial lesions with bile ducts. Some neoplastic nodules had a non-neoplastic atrophic germinal centre and/or a thin mantle cell layer. Morphologically, the neoplastic cells were centrocyte-like cells or intermediate lymphocytes. They expressed L26(CD20)⁺/LN-1(CDw75)^±/LN-2(CD74)⁺/cyclin D1^– and had a monotypic immunoglobulin of cytoplasmic IgM () on paraffin sections. The neoplastic cells or neoplastic nodules expressed surface IgM⁺/surface IgD^±/Leu-1(CD5)⁺/DRC-1⁺/alkaline phosphatase⁺/B1(CD20)⁺/B4(CD19)^– on fresh frozen sections. We therefore diagnosed this case as primary hepatic marginal zone B-cell lymphoma with mantle cell lymphoma phenotype. We confirm that it is difficult to differentiate extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue type; MALT lymphoma) and mantle cell lymphoma.