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.     

Marginal zone and mantle cell lymphomas: assessment of cytomorphology in subtyping small B-cell lymphomas

The diagnosis of malignant lymphomas by fine-needle aspiration biopsy (FNAB) is increasing in utilization. The cytomorphologic distinction among the small B-cell lymphomas may be quite difficult. We are unaware of anyone who has compared directly mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) in FNAB. Our major goal was to examine the cytomorphologic attributes of MCL and MZL and to look for features distinctive of or suggestive of either neoplasm. Seven immunophenotypic MCL and seven immunophenotypic MZL aspirates were evaluated for a number of cytomorphologic features in direct smears. Features favoring MCL include a relatively monomorphic cellular population, prominent nuclear membrane contour irregularities, and mitotic figures. Conversely, a polymorphic cellular population suggested MZL. However, due to extensive overlap of specific cytologic features, the two lymphomas cannot be definitively distinguished based solely on cytomorphology. Although there are cytomorphologic attributes suggestive of either MCL or MZL, considerable overlap exists. Based on an individual case basis, the distinction cannot be made reliably by morphology alone; ancillary studies, e.g., immunophenotyping, are essential.     

Primary extranodal marginal zone lymphoma of the endometrium: report of four cases and review of literature

Primary extranodal marginal zone lymphoma of the endometrium (PEMZL-EM) is exceedingly rare and has not been well characterized. Herein, we study the clinicopathological, cytogenetic and molecular features of four cases, the largest case series reported to date. The median age of the four patients was 59 years. Clinical presentations included abnormal vaginal bleeding (three cases) and incidental finding (one case). There were no constitutional symptoms in any of the cases. None of the patients had evidence of lymphoma in any other anatomic sites including bone marrow. Histologically, the lymphoma was characterized by a nodular proliferation of small lymphocytes admixed with occasional immunoblasts and variable number of plasma cells, which was restricted to the endometrium in most cases. Lymphoepithelial lesions were not identified in any of the cases. All cases displayed the immunophenotype of marginal zone B-cell lymphoma. Cytogenetics and FISH studies revealed absence of characteristic chromosomal translocations. Molecular analysis demonstrated immunoglobulin heavy chain gene rearrangement in all cases, two of which were found to use IgVH3-30 gene by DNA sequencing. Three of the four patients were still alive after a median follow-up of three years. PEMZL-EM predominantly affects postmenopausal women and is characterized by distinct histological patterns, lack of specific genomic alterations, and indolent clinical course.     

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.     

Follicular lymphoma mimicking marginal zone lymphoma in lymph node: a case report

Nodal follicular lymphoma (FL) is typically composed of follicular or nodular proliferation of small cleaved lymphoid cells, presumably derived from germinal center (GC) B cells. The hallmark of FL is t(14;18)(q32;q21) chromosomal translocation, which juxtaposes anti-apoptotic gene BCL2 to immunoglobulin heavy chain (IGH) promoter. Reflecting this background, FL cells are immunohistochemically positive for BCL2 as well as GC B cell markers CD10 and BCL6. It is known that low grade B-cell lymphomas, including FL, chronic lymphocytic leukemia/small lymphocytic lymphoma, and marginal zone lymphoma, are sometimes associated with marginal zone differentiation or plasmacytic differentiation. The marginal zone differentiation obscures the morphological differences among these, providing diagnostic challenges for histopathologists. In this paper, we present a case of FL, originally mimicking marginal zone lymphoma in the axillary lymph node. Subsequent bone marrow biopsy showed paratrabecular infiltration of small to medium-sized lymphoid cells. Immunohistochemical analysis of the bone marrow biopsy together with histopathology and flow cytometry of the axillary lymph node led to a final diagnosis of FL with marginal zone differentiation in the axillary lymph node and its bone marrow infiltration. Our case illustrates and reconfirms the importance of clinicopathological correlation which leads to a correct diagnosis.     

Clinicopathologic,enzyme and hisotchemical studies of centrocytic (mantle cell) lymphoma: Comparison with other types of low-grade B cell lymphoma bases on the updated Kiel classification

Lymph nodes from 21 cases of malignant lymphoma of a centrocytic (mantle cell) type, (ML, cc (mc)) were examined. All the cases had monoclonal surface immunoglobulin (sig) M and/or D, but were negative for CD 10 (CALLA), and CD11c (LeuM5). Lymphoma cells with CD25 (anti-Tac)+, CD5 (Leu1)+, and alkaline phosphatase (ALPase)^-in eight cases showed bone marrow involvement (10–66% of the nucleated cells; mean 32± 18%) but with no leukemic changes. These eight cases has a similar phenotype and were distributed by the lymphoma cells to the examined B-chronic lymphocytic leukemia. Seven cases showed an infiltration of CD25^-, CD5+, and AL Pase^- lymphoma cells, in which only two cases showed focal bone marrow involvement.There was a close relationship between CD25 expression and bone marrow invasion by the lymphoma cells in ML, cc(mc). Three of the six CD25^- and CD5^- cases presented zonal proliferation of AlPase+ lymphoma cells with round nuciee and a high anti-proliferating cell nuclear antigen/cyclin (PCNA/c) rate in the mantle zone and paracortex, accompanied by a prominent interdigitating dendritic and histiocytic cell reaction. Examined CD25^-, CD5^- and ALPase+ lymphoma showed a neoplastic counterpart of so-called marginal zone lymphocytes, which was different from other cases of ML, cc (mc). Lymphoma cells in ML, cc(mc), except for those of the so-called marginal zone lymphoma, might be derived from slgM+, D+/^-, CD25+/^-, CD5+^/-, ALPase^-, CD10^- and ^CD11c- lymphocytes present in the mantle zone and primary lymph follicles. Other types of lowgrade B cell neoplasms that were examined had different tumor cell markersfor ig, CD5, CD10, CD11c, a higher PCNA/c rate, and prominent dendritic cells and histiocytic reaction when compared with those of ML, cc (mc).     

Marginal zone variant of mantle cell lymphoma: CD5-negative cyclin D1-positive variant posing a diagnostic dilemma

Described herein is an unusual case of mantle cell lymphoma (MCL) histologically mimicking marginal zone lymphoma (MZL). An 83-year-old man presented with multiple adenopathies and a hilar mass encroaching on the right lung. A transbronchial biopsy showed small blue cells suspicious for small cell carcinoma. On further analysis the cells were predominantly small cleaved and CD20 positive, suggesting follicular lymphoma, grade 2. An axillary lymph node biopsy showed germinal centers surrounded by monocytoid B cells. Flow cytometry was negative for CD5 and CD23 and the diagnosis of MZL was considered. Because of the aggressive clinical behavior, including extensive necrosis on imaging studies, immunohistochemistry for cyclin D-1 was performed and was positive. Bone marrow was extensively involved and it showed t(11;14), in addition to other complex cytogenetic abnormalities. Differentiating MCL from MZL has prognostic and therapeutic implications, particularly when considering the potential role of targeted therapy and cell cycle modulators.     

Floral leukemic cells transformed from marginal zone lymphoma

There are three clinicopathological entities of marginal zone lymphoma (MZL), including extranodal or mucosa-associated lymphoid tissue (MALT) lymphoma and MZL of nodal (NMZL) or splenic (SMZL) type. Of these, leukemic presentation, usually as small or villous lymphocytes, is more common in SMZL, while leukemic change in NMZL is rare, and the morphology has not been characterized. We present a stage 4 MZL involving lymph node, spleen, and bone marrow with two relapses after chemotherapy. The leukemic cells at the second relapse revealed irregular nuclear contours with multilobated nuclei (so-called flower cells or floral cells) mimicking the neoplastic cells in adult T-cell leukemia/lymphoma (ATLL). The absence of leukemic change and splenic hilar lymphadenopathy at initial presentation, expression of IgD by tumor cells, and cytogenetic changes of +7 suggested that this tumor might be a NMZL. Although the cytomorphologic features of floral leukemic cells might suggest ATLL, thorough clinical and laboratory workup helped to reach a correct diagnosis. Our findings broaden the cytological spectra of leukemic cells in MZL and illustrate the importance of immunophenotyping.     

Paediatric marginal zone lymphoma and hyperplasia

Marginal zone lymphomas (MZL) are low-grade B-cell lymphomas arising from post-germinal memory B-cells occurring in adults with a slight female predilection. They are sub-categorized into nodal (NMZL), extra-nodal/mucosa-associated lymphoid tissue (MALT) and splenic (SMZL). MALT lymphomas are the most common (70%) followed by SMZL (20%) and NMZL (10%). Histologic transformation into aggressive B-cell lymphoma can rarely occur. MZL is extremely uncommon in the paediatric population and unlike in adults, is predominantly nodal. Paediatric NMZL (pNMZL) is an indolent, low-grade lymphoma with unique clinical and morphologic features. In contrast paediatric MALT lymphoma and SMZL are extremely uncommon and resemble their adult counterparts. Paediatric marginal zone lymphomas must be differentiated from paediatric-type follicular lymphoma (PFL) and marginal zone hyperplasia (MZH) of lymph nodes and mucosa-associated lymphoid tissue. This review summarizes the pathogenesis, morphology, genetic features of paediatric MZL and marginal zone hyperplasia. Recognition of these entities is important to avoid unnecessary therapy.     

Composite splenic marginal zone lymphoma and mantle cell lymphoma arising from 2 independent B-cell clones

We report the first case of composite lymphoma involving both mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes. Morphological, immunohistochemical, immunophenotyping, as well as detailed genetic studies (fluorescence in situ hybridization, IGVH gene sequencing), were performed and confirmed the existence of 2 independent, unrelated tumor clones. The MCL component expressed IgMD lambda, was CD5+, harbored a t(11;14)(q13;q32) involving CCND1, and showed an unmutated VH1-18 gene rearrangement. The SMZL component expressed IgMD kappa, was CD5-, showed a t(10;14)(q24;q32) and an unmutated VH3-7 gene rearrangement. Interestingly, this t(10;14) targeted the NFKB2 gene. Only a single other case of SMZL with t(10;14)/NFKB2 has been reported. Taken together, these data indicate that the MCL and SMZL arose as a consequence of independent malignant transformation events within an antigen-naive B-cell population. This case highlights the importance of a multidisciplinary approach and tissue diagnosis in these complex situations.     

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.     

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.     

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.     

Floral variant of follicular lymphoma containing marginal zone B-cell component. Report of two cases

We here report two unusual cases of floral variant of follicular lymphoma containing marginal zone B-cells. Histologically, the neoplastic follicles consisted of three distinct layers. The inner layer was composed of neoplastic germinal centers exhibiting a floral design and the middle layer had unusually prominent mantle zones. The outer zone of neoplastic follicles was surrounded by a pale cuff of marginal zone B-cells. Immunohistological study demonstrated that both the germinal center and marginal zone component lay within the follicular dendritic cell network. The germinal center component was CD10+ and bcl-2+. However, a portion of the marginal zone component weakly expressed bcl-2 but not CD10. Nodal marginal zone B-cell lymphoma (NMZBL) occasionally possesses "floral" lymphoid follicles. Follicular lymphoma with marginal zone differentiation is a high-risk variant of follicular lymphoma. In diagnostic practice, the differential diagnosis between the floral variant of follicular lymphoma containing marginal zone B-cells and the "floral variant" of NMZBL is important.     

Marginal zone lymphoma

The term marginal zone lymphoma includes a collection of different diseases with some shared morphologic and pathogenic features, but distinctive clinical presentation, immunophenotype, molecular abnormalities, and treatment recommendations. This review describes the main features of splenic marginal zone lymphoma, nodal marginal zone lymphoma, and extranodal marginal zone lymphoma, mucosa-associated lymphoid tissue type.     

Marginal zone cell lymphoma--an update on recent advances

The marginal zone represents one of the distinct compartments of the B-cell area in lymphoid tissues. It is especially well developed in the spleen and in Peyer's patches of the gut, but not in lymph nodes, with the exception of the ones in the mesenterium. However, the pronounced proliferation of so-called 'monocytoid B-cells' that may be seen in some inflammatory conditions of the lymph node may be regarded as a nodal reactive marginal zone cell expansion. The cellular compositions of the marginal zone and the monocytoid B-cell proliferation are similar and both show a heterogeneous population of B-cells, of which the functions are being slowly unravelled. Neoplasms originating in the marginal zone have been recognized in the past and are listed in the REAL classification as marginal zone B-cell lymphomas including extranodal MALT-type lymphomas, splenic marginal zone lymphomas and nodal (monocytoid) marginal zone lymphomas. Marginal zone cell lymphomas display a broad morphological spectrum, which is reflected by the heterogeneity of the cellular composition and the variation in the growth pattern of the lymphoma, but is independent of the anatomical site. All three marginal zone cell lymphomas share immunophenotypic, genetic and chromosomal similarities which will be discussed. The morphologic features are dealt with only briefly as they have been extensively discussed elsewhere.     

A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases

AIMS: To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. METHODS AND RESULTS: The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). CONCLUSION: NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.     

Primary splenic marginal zone lymphoma with florid granulomatous reaction--a case report and review of literature

Splenic marginal zone lymphomas (SMZL) constitute about 20% of primary splenic NHLs. We report a case of primary SMZL with a florid granulomatous reaction which obscured the underlying lymphoma. Although granulomas have been described in splenic non-Hodgkin lymphoma, it can be extensive and mask the underlying lymphoma. A careful search for the cytoarchitectural features of SMZL is warranted in such a case.     

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.