Cytogenetic evidence for the origin of neoplastic cells in CD5-positive marginal zone B-cell lymphoma

We describe an 87-year-old female patient presenting with a breast lump and axillary lymphadenopathy. Histological examination revealed the lump to be a CD5-positive extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue. Subsequent staging revealed disseminated disease including the head and neck region. Only 2 cases of CD5-positive MZBCL have undergone any form of cytogenetic analysis, and we report the first standard karyotype of such a case. This revealed partial trisomy 3,7q deletion and an additional marker chromosome. Notably, cells lacked the t(11;14) found at high frequency in mantle cell lymphoma and trisomy 12 found in B small lymphocytic lymphoma (B-SLL). These results, combined with the clinical, histological, and immunophenotypic picture, suggest a marginal zone origin for the neoplastic lymphocytes, rather than a relationship with mantle cell or small lymphocytic lymphoma.     

Peripheral T-cell lymphoma mimicking marginal zone B-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and cytologic appearances. We describe eight cases of PTCL morphologically simulating marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our institution between 1990 and 2000 and selected eight cases for study based on the following criteria: small-cell morphology with abundant, clear cytoplasm and either marginal zone involvement by the neoplastic infiltrate in lymph node biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features and ancillary studies were reviewed. Patients included six women and two men with a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed with primary nodal PTCL, and two presented with primary extranodal disease. The original diagnosis was PTCL in only four cases; three cases were diagnosed as atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion. Lymph node biopsies revealed partial effacement of the architecture with residual follicles surrounded by the neoplastic small cells. Extranodal sites included hard palate, tongue, tonsil, and submandibular glands; all but one case demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of eight cases (rearrangement of T-cell receptor gene), and three of eight had an aberrant T-cell population by flow cytometry. The differential diagnosis of atypical lymphoid infiltrates with morphologic features of marginal zone B-cell lymphoma should include PTCL. This uncommon morphological mimicry should be recognized, because PTCL is an aggressive disease regardless of morphology and should be treated accordingly.     

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。     

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.     

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.     

Primary nodal marginal zone B-cell lymphoma arising from more than one clonal neoplastic population

Primary nodal marginal zone B-cell lymphoma is an uncommon monoclonal B-cell lymphoproliferative disorder. We report a case of a 79-year-old woman who presented with generalized lymphadenopathy. Histologic and immunohistochemical examinations of biopsy sections from an axillary lymph node were consistent with nodal marginal zone B-cell lymphoma. Flow cytometry analysis showed 2 distinct clonal B-cell populations expressing lambda or kappa light chain restriction. Subsequently, genomic deoxyribonucleic acid (DNA) isolated from a paraffin-embedded lymph node section was analyzed for the presence of gene rearrangements. Polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain genes revealed 3 rearranged DNA bands, confirming the presence of more than one clonal B-cell population. These immunophenotypic and genotypic findings have not been previously described in association with this type of lymphoma. To our knowledge, this represents the first reported case of biclonal nodal marginal zone B-cell lymphoma.     

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.     

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.     

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.     

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.     

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.     

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.     

Classical Hodgkin lymphoma concurrently evolving in a patient with marginal zone B-cell lymphoma of the spleen

Combination of the splenic marginal zone B-cell lymphoma (SMZL) and classical Hodgkin lymphoma (cHL) is extremely rare. We report a unique case with concurrent SMZL and cHL. The patient was a 63-year-old man who presented with fatigue and anemia, showing a splenomegaly and retroperitoneal lymphadenopathy. A splenectomy revealed monotonous marginal zone lymphocytic infiltrates and numerous large Reed-Sternberg–like cells. Flow cytometry revealed a κ light-chain–restricted CD5 (−), CD23 (−) B-cell population. DNA polymerase chain reaction analysis confirmed the presence of clonal rearrangement of the immunoglobulin heavy-chain gene. Immunohistochemical studies revealed that the large atypical cells were CD30 (+), CD15 (weakly +), CD20 (−), CD45 (−), Pax5 (weakly +), BOB.1 (−), and Oct2 (−), indicating the coexistence of SMZL with cHL. After the chemotherapy, the patient achieved a clinical/radiologic remission, whereas cHL was detected in liver and bone marrow subsequently. The case indicates that both components of lymphoma can present concurrently as a composite form of lymphoma and both need to be treated adequately.     

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.     

CD10 positive thyroid marginal zone non-Hodgkin lymphoma

A 72 year old woman presented with swelling of the right lobe of her thyroid gland. Fine needle aspiration and flow cytometry showed a clonal population of B cells expressing CD10 and a diagnosis of follicle centre cell lymphoma was made. Subsequent excision of the thyroid showed the typical histological features of a marginal zone non-Hodgkin lymphoma. Polymerase chain reaction showed no evidence of t (14;18). Immunohistochemistry confirmed CD10 positivity and LN1 (CDw75) expression. This is only the second report of aberrant expression of CD 10 by a marginal zone 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.     

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.     

乳头黏膜相关淋巴组织型结外边缘区B细胞淋巴瘤一例

患者女,57岁,左则乳头肿大半年余,因短期内迅速增大于2002年11月就诊,患者自发病以来无发热,消瘦及明显不适,体检：左侧乳头明显肿大,表皮粗糙,腋窝及颈部未触及肿大淋巴结。