Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma

AIM: We report a case of mantle cell lymphoma masquerading as a marginal zone cell lymphoma. METHODS AND RESULTS: In the initial manifestation in the palatine tonsils, the neoplastic cells were found to grow exclusively within the marginal zones of secondary follicles which showed a preserved mantle zone. The few immunostains performed showed a B-cell phenotype including an immunoglobulin light chain restriction. The extranodal manifestation, the growth pattern, and the immunophenotype led to the diagnosis of an extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL). The specimen from the relapse occurring 8 months later exhibited diffuse monomorphous cells co-expressing B-cell antigens and CD5, CD43 and cyclin D1, leading to the diagnosis of mantle cell lymphoma. Re-investigation of the initial biopsy revealed that the neoplastic cells within the marginal zones had a mantle cell lymphoma immunophenotype expressing cyclin D1, the immunoglobulin heavy chains IgD and IgM and partly CD5. Both lesions harboured identical clonal immunoglobulin gene rearrangements proving that they represented different manifestations of the same lymphoma. CONCLUSION: This case emphasizes the importance of broad immunohistological investigation of B-cell NHLs involving the marginal zone.     

Primary marginal zone B-cell lymphoma of appendix

Primary lymphomas of appendix are extremely rare tumors. The first case of primary lymphoma of appendix was reported by Warren in the year 1898. Incidence of primary lymphoma of appendix is 0.015% of all gastrointestinal lymphomas. This is a report of primary marginal zone B-cell lymphoma of appendix which presented as appendicular mass. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.     

Proliferation of marginal zone cells mimicking malignant lymphoma

An enlarged axillary lymph node from a 58-year-old woman showed a proliferation of marginal zone cells in nodules or large band-forming aggregates within the cortex. The marginal zone cells also infiltrated the adjacent fatty tissue. They showed polytypic surface immunoglobulins (IgM++, IgG+, kappa+, lambda+). Their immunophenotype (IgD-, CD23-, KiB3-) differed from that of the small lymphocytes of the mantle zone. They were also positive for alkaline phosphatase. The lesion is reactive and must be differentiated from low-grade malignant lymphomas, especially centrocytic lymphoma.     

脾B细胞边缘区淋巴瘤的临床病理观察

目的 分析和总结脾边缘区B细胞淋巴瘤(SMZL)的临床病理特点、探讨其诊断与鉴别诊断要点.方法 对8例原发性SMZL的临床资料行回顾性分析总结、组织切片的形态观察和免疫组织化学EliVision法染色分析,并对部分病例行基因重排克隆性检测,获得4例随访资料.结果 8例SMZL的中位年龄为61.5岁(36～75岁),男女比例为1.7:1.患者均因脾大就诊,5例伴血象异常,白细胞和血小板均低于正常,其中2例全血细胞下降.脾切除后3例血象全部或部分恢复正常.3例福达华联合化疗后,2例完全缓解,1例死亡.随访4例的平均生存期21.5个月(6～60个月).在病理形态上,8例脾脏均呈白髓结节状增生,其中6例由经典的两种细胞组成,其分布表现为结节中央密集而深染的小淋巴细胞,周围为不典型单核细胞样细胞.2例增生结节全部由形态一致的不典型单核细胞样细胞组成.红髓区片状浸润8例.肿瘤细胞CD20+(8例);bcl02+(6/6),IgD+(2/4),CD5+(1/4),CD43-(516),cyclin D1-和bcl-6/CD10-(6/6).核增殖指数<15%.结论 SMZL为惰性淋巴瘤,以脾大伴血象异常为主要临床表现.脾切除治疗有效,FCD化疗可完全缓解,预后较好.病理形态以白髓结节状增生为主,呈不典型单核细胞样细胞形态,大部分标本结节中央见较小密集的淋巴细胞,同时存在红髓区片状浸润.诊断需除外其他小B细胞淋巴瘤和脾白髓增生.     

Blastic transformation of splenic marginal zone B-cell lymphoma

To our knowledge, blastic transformation of splenic marginal zone lymphoma, a recently characterized low-grade lymphoproliferative disorder, has not been reported previously. In this regard, we report the unique case of a 70-year-old woman whose untreated splenic marginal zone lymphoma underwent blastic transformation 3 years after diagnosis. Her hematologic medical history started in 1988 as thrombocytopenia refractory to steroids associated with atypical lymphoid infiltrate in the bone marrow. She underwent splenectomy in 1989, which revealed splenic marginal zone lymphoma. One year later, the patient developed lymphadenopathy noted in the chest, axillary, abdominal, and retroperitoneal lymph nodes. Because she was asymptomatic, treatment was limited to a conservative supportive regimen. The nodal lymphoma cells had features associated with marginal zone lymphoma and expressed B-cell monotypic kappa light chain. She was readmitted for the last time 2 years later with findings of 16% blasts in the peripheral blood and massive infiltration of the bone marrow by large blastoid cells. The blasts showed dispersed chromatin and prominent nucleoli, and possessed a moderate amount of clear cytoplasm. The blasts, like the previous nodal and splenic lymphomas, had a CD20-, CD19-, IgM-positive phenotype, but lacked reactivity for CD5, CD10, and CD23. The patient displayed clinical remission after treatment with vincristine and prednisone, but died of aspiration pneumonia 1 month later. These observations suggest that, similar to the other low-grade lymphoproliferative disorders, an untreated splenic marginal zone lymphoma may undergo high-grade blastic transformation.     

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.     

Burkitt lymphoma following splenic marginal zone lymphoma. evidence for two independent B-cell clones

We report the progression of splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes to Burkitt lymphoma with the presence of a t(8;14)(q24;q32) followed by a highly aggressive course. While the initial indolent lymphoma had an IgM lambda immunophenotype the Burkitt lymphoma was IgM kappa-positive. Immunoglobulin heavy chain gene (IGH) sequence analysis showed no identity between the two clones. We conclude that Burkitt lymphoma can occur in patients with SMZL, although not necessarily of identical clonal origin.     

Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract.

Extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B-cell lymphomas: 18 extranodal marginal zone B-cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro-intestinal tract with a diffuse large B-cell component (giMZBLplusLBCL), and 27 diffuse large B-cell lymphomas of the gastro-intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)-negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13-p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto-oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto-oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups.     

原发淋巴结边缘区淋巴瘤临床病理分析

目的：研究淋巴结MZL形态特征、诊断要点和鉴别诊断,为临床治疗和预后提供依据,方法：采用常规制片、免疫组化ABC法标记,光镜观察。结果：10例淋巴结MZL男性6例,女性4例,以淋巴结缓慢增大为特征,而无肝脾肿大,外周血未见异常。病理形态分为：边缘区增生型2例,结节型4例,弥漫型2例和母细胞样型2型。细胞类型：CCL细胞型5例,MBC型6例,淋巴浆细胞型2例,母细胞样型2例,10例均经免疫组化证实。结论：淋巴结MZL与MALT型淋巴瘤形态、免疫表型和起源相似。由于淋巴结组织结构特点,MZL有特殊性。     

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.     

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.     

Coexistence of tumorlet and marginal zone B-cell lymphoma in the lung

Extranodal marginal zone lymphoma (EMZL, MALT lymphoma) and carcinoid are neoplasms occurring most frequently in the gastrointestinal tract and respiratory system. Although each of them occurs relatively frequently and separately, the simultaneous appearance of these two neoplasms is exceptionally rare, and only a few cases in the gastrointestinal tract have been described so far. We report a case of a 70-year-old female with the simultaneous presence of MALT lymphoma and tumorlet in the middle lobe of the right lung. To the best of our knowledge, this is the first report of such a collision tumor at the same anatomical site.     

Hodgkin-like transformation of a marginal zone B-cell lymphoma of the larynx

Primary larynx lymphomas, specifically of the mucosa-associated lymphoid tissue, are a rare but documented phenomenon. Transformation of any type of lymphoma that has the presence of Reed-Sternberg cells is unusual in lymph nodes and exceptional in extranodal sites. Herein, we report the first case (to the best of our knowledge in a review of the English literature [MEDLINE 1966-2001]) in which both of these unusual findings are present; that is, an extranodal marginal zone B-cell lymphoma of laryngeal mucosa-associated lymphoid tissue with Hodgkin-like transformation. The patient is a 78-year-old man who presented with intermittent shortness of breath, progressive dysphagia, and intermittent hoarseness. On examination, a large mass of the left supraglottic larynx was identified with a "ball-valve" effect into the laryngeal inlet with inspiration. Examination of the neck showed no palpable masses. Histologic examination of the incisional biopsy showed replacement of the submucosa by sheets of atypical monocytoid B cells (CD20+, CD79a+, lambda+, CD3-) characterized by nuclear atypia, mitotic activity, plasmacytoid differentiation, and restricted for lambda light chains. Dutcher bodies were easily identified. Interspersed throughout the neoplastic lymphoid population were numerous Reed-Sternberg cells and variants immunoreactive for CD30 and CD15 and nonreactive for CD45RB. The patient was treated with 44 cGy to the neck and larynx and was alive and free of disease at last contact, 2.6 years after the original presentation.     

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.     

Peripheral T-cell lymphoma with involvement of the expanded mantle zone

Peripheral T-cell lymphoma (PTCL) with a nodular architecture is rare. Recently, two variants have been described with infiltration of the B-cell follicle, one variant that localizes to the marginal zone with a so-called perifollicular growth pattern, and a variant that localizes to the germinal center. These lymphomas have a CD4+ phenotype and may express Bcl-6. We have studied five similar cases of PTCL with involvement of the B-cell follicle. However, our cases differ from the cases previously described by their predominant and frequently patchy involvement of the expanded mantle zone of the B-cell follicle at onset. Later biopsies in three of the cases show diffuse infiltration of the lymph node, without features of angioimmunoblastic TCL (AILT). All cases expressed Bcl-6 in addition to CD4. Cytogenetics was available in four of the cases but revealed no recurrent chromosomal aberrations or changes associated with other types of PTCL. No mutations of the BCL-6 gene were observed. Together, the cases seem to have an intermediately aggressive clinical behavior. Whether our cases are part of a spectrum of PTCLs that encompasses previously described variants with predominant marginal zone or germinal center infiltration or they represent a separate T-cell lymphoma type remains to be demonstrated by a study of more of such cases.     

Splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is an indolent lymphoproliferative disease accounting for approximately 1% of all lymphomas. SMZL presents with marked splenomegaly, and often accompanied by circulating atypical 'villous lymphocytes' and is also known as splenic lymphoma with villous lymphocytes. Histologically, the spleen in SMZL is characterised by a nodular infiltrate based on pre-existing white pulp but also involving the red pulp. Within the white pulp, the infiltrate has a biphasic morphology comprising an inner zone of small lymphocytes and a peripheral (marginal) zone of larger lymphoid cells. Usually the splenic lymph nodes and bone marrow are also involved by a vaguely nodular infiltrate of similar nature. Immunophenotypically, the tumor cells has a mature B-cell phenotype and frequently express IgM and IgD but typically lack CD5, CD23, CD43, CD10, Bcl-6 and cyclin D1. Analysis of immunoglobulin heavy-chain gene variable regions suggest that some cases of SMZL arise form postfollicular B cells but others from na?ve B cells. Genetic studies have shown abnormalities of a number of chromosomes however 7q31-32 allelic loss appears to be characteristic. Histological differential diagnosis include a number of entities such as lymphoid hyperplasias, other marginal zone lymphomas, mantle cell lymphoma, follicular lymphoma, and B-CLL.     

High-resolution genome-wide array comparative genomic hybridization in splenic marginal zone B-cell lymphoma

Splenic marginal zone B-cell lymphoma is characterized by high genetic heterogeneity, and hepatitis C virus infection seems to be involved in a subset of patients. The aims of the analysis were to identify potential genetic alterations related to hepatitis C virus status, IgV_H gene mutational status, and prognostic categories identified in a multicenter study (Blood 2006;107:4643). Genome-wide array comparative genomic hybridization at a 100-kilobase (kb) resolution was performed in 34 patients with splenic marginal zone B-cell lymphoma, 12 of whom were hepatitis C virus positive. Array-comparative genomic hybridization experiments revealed no copy number alterations in 10 patients (4 were hepatitis C virus positive). A median of 5.6 and 3.8 copy number alterations were detected in hepatitis C virus–positive and in hepatitis C virus–negative patients, respectively. The most frequent copy number alterations involved chromosomes 7 and 17 (21% and 24%, respectively). Except for Xp gain (P = .01), no differences in common alterations were found between hepatitis C virus–positive and hepatitis C virus–negative cases. Unmutated status of the IgV_H gene was related to del(7q) (P = .04) and dup(12q) (P = .03). The high-risk group identified according to the new splenic marginal zone B-cell lymphoma prognostic score was associated with del(7q) (P = .01) and del(17p) (P = .02). Hepatitis C virus–positive splenic marginal zone B-cell lymphoma patients have no specific chromosome alterations. Patients with poor prognosis are characterized by distinctive imbalances.     

淋巴结边缘区B细胞淋巴瘤的临床病理特征

目的探讨原发性淋巴结边缘区B细胞淋巴瘤（NMZL）的形态特点、免疫表型特征、鉴别诊断及预后。方法对10例原发于淋巴结的NMZL进行光镜观察,免疫组织化学EliVision法染色,参照Ann Arbor临床分期,并进行了3～29个月随访。结果10例就诊时均精神状况良好,但大多（6／7）临床分期较高（Ⅱ或Ⅲ期）。NMZL大多呈模糊结节的生长方式（5／10）。细胞的形态以中心细胞样细胞为主（7／10）,少数以单核细胞样细胞为主（2／10）或小淋巴细胞样细胞为主（1／10）。大多（8／10）伴有浆样细胞和（或）浆细胞。肿瘤细胞增殖指数范围5％～50％。7例滤泡树突细胞（FDC）网以萎缩变小为主,3例FDC网不同程度增生。7例得到随访（平均12个月）,其中6例临床分期为Ⅱ或Ⅲ期。3例存活1年以上。结论原发性NMZL少见,肿瘤细胞生长方式独特,细胞形态多以生发中心细胞样细胞为主。需与淋巴浆细胞淋巴瘤、结外边缘区淋巴瘤累及淋巴结及T区增生等鉴别。肿瘤细胞较易播散,诊断时大多临床分期较高,预后可能较差。