Massive hyperplasia of marginal zone B-cells with clear cytoplasm in the lymph node: a case report

An enlarged axillary lymph node from a 63-year-old woman showed proliferating marginal zone B-cells arranged in a vague nodular pattern or in band-forming aggregates throughout the cortex. Marginal zone B-cells, which also infiltrated the adjacent fatty tissue, had round or slightly indented nuclei of medium size and a moderate amount of clear cytoplasm. Immunohistochemically, these cells were CD20+, CD79a+, Bcl-2+, sIgD-, CD5-, CD10-, CD21-, CD23-, CD45RO-, Bcl-6-, and cyclin D-. A portion of the cells were sIgM- and CD43-positive. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. Systemic bacterial infection appears to be the cause of marginal zone B-cell hyperplasia. This unusual marginal zone B-cell hyperplasia should be differentiated from low-grade B cell lymphomas, and particularly from nodal marginal zone B-cell lymphomas.     

Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.     

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.     

Florid monocytoid B-cell hyperplasia resembling nodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue type. A histological and immunohistochemical study of four cases

A pale ring of medium-to-large cells surrounding the follicles, namely a marginal zone distribution pattern, is the key criterion for diagnosing nodal marginal zone B-cell lymphoma (NMZBL). The tumor cells of NMZBL occasionally exhibit the morphology of monocytoid B-cells (MBC). However, this condition can be difficult to distinguish from MBC hyperplasia in reactive conditions. We describe the histopathological and immunohistochemical findings of four cases exhibiting florid MBC hyperplasia and resembling NMZBLs. The patients consisted of three males and one female (age range 48–64 years) who had asymptomatic lymphadenopathy in the head and neck area. Histologically, a pale ring surrounding more than 75% of the lymphoid follicles characterizes the lesion. The lymphoid follicles usually had hyperplastic germinal centers, and progressive transformation of germinal center was noted in two cases. The pale ring was composed of medium-to-large cells with indented or round nuclei and relatively abundant pale clear cytoplasm. Numerous plasma cells were observed in one case. The overall histomorphological findings in these four cases were similar to those of NMZBLs. However, immunohistochemical investigations demonstrated that MBCs were CD43− and bcl-2−. Moreover, immunohistochemistry, polymerase chain reaction, and flow cytometry studies demonstrated the polytypic nature of B-lymphocytes. Recognition of this unusual MBC hyperplasia in reactive lymph node lesions is important to avoid confusion with NMZBLs.     

Histological variety of floral variant of follicular lymphoma

To further clarify the histopathological findings of the floral variant of follicular lymphoma (FVFL), we studied 13 Japanese cases. Two histological subtypes of neoplastic follicles of FVFL have been described: (i) A macrogerminal center pattern where the mantle zone lymphocytes were invaginated into the neoplastic germinal center, often reminiscent of a floral design. (ii) A microgerminal center pattern where the massive invasion of mantle zone lymphocytes resulted in almost complete breakage of the neoplastic follicles. In the former pattern, the neoplastic germinal center usually contained large clusters of tumor cells, whereas in the latter, small clusters of up to 20 tumor cells or isolated tumor cells were observed in the neoplastic germinal centers. Moreover, occasional tumor cells showed a lymphocytic and/or histiocytic Reed-Sternberg cell (L&H cells)-like morphology. Both types of neoplastic follicles were observed to a varying degree in most cases. The macrogerminal center pattern was predominant in nine cases (70%), whilst the microgerminal center pattern was predominant in only four cases (30%). Three lesions (23%) had a marginal zone component. Immunohistochemistry showed that atypical follicular center cells, including L&H cells, were CD3-, CD5-, CD10+, CD20+, CD43-, bcl-2+, cyclinD1-. The overall histological findings of the macrogerminal center are similar to those of florid progressive transformation of germinal center (PTGC), whilst the microgerminal center pattern is similar to that of nodular lymphocyte-predominant Hodgkin lymphoma. Initially, the differential diagnosis between FVFL and florid PTGC was emphasized. However, the present study indicates that nodal marginal zone B-cell lymphoma possessing floral follicles and nodular lymphocyte-predominant Hodgkin lymphoma should be added to the differential diagnosis of FVFL. The germinal center B-cell nature of FVFL is most clearly recognizable by immunohistochemistry, though histological appearance alone may cause some diagnostic problems.     

bcl-10蛋白异常表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的诊断价值

目的探讨bcl-10蛋白表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）的诊断价值。方法收集140例不同部位的MALT淋巴瘤,包括胃38例、眼眶35例、肠16例、皮肤15例、涎腺15例、肺14例、甲状腺3例、其他部位4例。对照：10例扁桃体反应性滤泡增生（RFH）、5例眼眶的淋巴组织增生和143例非MALT淋巴瘤、不同类型的非霍奇金淋巴瘤（NHL）,包括20例NK／T细胞淋巴瘤、20例滤泡性淋巴瘤（FL）、20例间变性大细胞淋巴瘤（ALCL）、20例淋巴结内弥漫大B细胞淋巴瘤（DLBCL）、10例原发胃DLBCL、13例淋巴结边缘区淋巴瘤（NMZL）、12例套细胞淋巴瘤（MCL）、11例脾脏边缘区淋巴瘤（SMZL）、6例血管免疫母细胞性T细胞淋巴瘤（AITL）、6例外周T细胞淋巴瘤（PTCL）、3例B．小淋巴细胞淋巴瘤（B-SLL）、1例淋巴浆细胞性淋巴瘤（LPL）和1例浆细胞瘤。免疫组织化学EnVision法检测bcl-10蛋白;免疫组织化学双标记法检测CD20与bcl-10的共表达。结果在扁桃体RFH中,bel-10蛋白呈中等强度表达于生发中心B细胞质中,套细胞不表达,边缘区细胞和副皮质区T细胞呈弱表达。在眼眶淋巴组织增生中,2例bel-10阴性,3例主要呈淋巴滤泡生发中心B细胞质阳性,与扁桃体RFH的表达类似。在非MALT淋巴瘤的其他类型NHL中,除3例（3／10）原发胃DLBCL呈胞核阳性外,其余均未见胞核表达;在不同NHL中的胞质阳性分别为：结内（12／20）和胃（7／10）DLBCL、FL和ALCL（16／20）、PTCL（5／6）、AILT（6／6）、NMZL（13／13）、SMZL（11／11）、B-SLL（3／3）和浆细胞瘤（1／1）,11例MCL呈胞质可疑阳性,20例NK／T细胞淋巴瘤和1例LPL阴性;在部分淋巴瘤中可见肿瘤性细胞表达而反应性小淋巴细胞不表达：MALT淋巴瘤之bcl-10的总表达率为92．1％（129／140）,其中54．3％（76／140）胞质阳性,37．9％（53／140）胞核阳性;但不同部位之胞核阳性率有所不同。在MALT淋巴瘤中,bcl-10蛋白核强表达最常见于眼眶（25．7％,9／35）;除出现异常bcl-10胞核表达外,约20％有反应性滤泡的病例呈生发中心失表达。双标记显示bcl-10阳性细胞为CD20阳性细胞,但CD20阳性细胞多于bcl-10阳性细胞。结论（1）淋巴细胞增生性病变中bcl-10蛋白普遍表达,细胞质表达可出现在多数NHL和反应性增生中,但在淋巴瘤中呈肿瘤细胞表达而反应性细胞不表达,提示bcl-10异常可能与部分淋巴瘤的形成有关;（2）细胞核内bcl-10异常表达主要见于MALT淋巴瘤;眼眶、肺等部位的胞核强阳性和生发中心阴性的特殊模式,对MALT淋巴瘤的诊断及其与反应性病变的鉴别诊断有一定辅助意义。     

B-cell lymphoma with hyaline vascular Castleman disease-like features: a clinicopathologic study

Hyaline vascular Castleman disease (HV-CD) is a localized benign mass characterized by follicular hyperplasia with atrophic germinal centers, mantle zone hyperplasia, hyaline deposits, and vascular proliferation. Before establishing a diagnosis of CD, several B-cell lymphomas (BCLs) must be considered, including follicular lymphoma (FL), mantle cell lymphoma (MCL), and nodal marginal zone lymphoma (NMZL). Conversely, BCLs with prominent atrophic germinal centers and hyaline vascular penetration may closely resemble HV-CD, leading to misdiagnosis. We report 6 cases of BCL with prominent HV-CD-like features, including FL (2 cases), MCL, NMZL (2 cases), and interfollicular large B-cell lymphoma. Histologically, all were initially considered to be HV-CD before additional tests revealed a neoplastic B-cell proliferation. We highlight the clinicopathologic features of these cases in comparison with cases diagnostic of HV-CD. In contrast with HV-CD, BCLs with HV-CD-like features are more likely to manifest clinically with systemic symptoms or generalized lymphadenopathy. Careful histopathologic examination, supported with immunohistochemical studies, flow cytometric immunophenotyping, and judicious use of cytogenetic and molecular analyses, allows identification of the masked neoplastic process. A multifaceted approach, integrating clinical, histologic, and ancillary tests, can help avoid this diagnostic pitfall.     

Large cell variants of CD5+, CD23- B-cell lymphoma/leukemia

CONTEXT: Mantle cell lymphoma (MCL), and its leukemic phase, constitute a well-studied hematologic malignancy with known overall survival, prognostic indicators, morphologic findings at diagnosis and in bone marrow, and known incidence of the bcl-1 immunoglobulin gene rearrangement. Large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype (CD5+, CD23-), including but not limited to blastic MCL, prolymphocytoid MCL, blastic mantle cell leukemia, and prolymphocytic mantle cell leukemia, are not as well characterized. Although blastic MCL is known to be associated with a shorter overall survival than conventional MCL, the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype have not been described as fully as conventional MCL. OBJECTIVE: The purpose of the present study was to describe the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype. DESIGN: Nineteen cases of large cell variants of CD5+, CD23- B-cell lymphoma/leukemia are reviewed and described in regard to morphology, bone marrow morphological findings, Cyclin D1 immunostaining, and bcl-1 analysis. Clinical data were not available owing to the varied clinical sources of the specimens. SETTING: Tertiary-care academic institution. RESULTS: Lymph node involvement in blastic CD5+, CD23- B-cell lymphoma was diffuse (100%) with a nodular component (33%) or focal mantle zone pattern (10%). Bone marrow involvement in blastic CD5+, CD23- B-cell lymphoma was seen in only 27% of cases and was composed predominantly of small, slightly irregular lymphocytes. Cyclin D1 was demonstrated in 60% of the 15 cases analyzed and more sensitive in B5-fixed tissue. Bcl-1 (performed in 5 cases) was not detected in the 4 cases of blastic CD5+, CD23- B-cell lymphoma analyzed and was detected in the case of the prolymphocytoid MCL. Cyclin D1 was demonstrated in all 4 bcl-1 negative cases and was negative in the bcl-1 positive prolymphocytoid MCL. CONCLUSION: Careful analysis of clinical data, morphology, immunophenotype, Cyclin D1 expression, and molecular analysis are required to differentiate the unusual large cell variants of MCL from other processes.     

Composite mantle cell and follicular lymphoma. A case report

We describe the association of 2 types of small B-cell lymphomas with different morphologic and immunophenotype patterns inside the same lymph node. Morphologically distinct zones were detected and studied with immunohistochemistry analyses. Most of the areas examined were characteristic of classic mantle cell lymphoma (CD20+, CD5+, cyclin D1+) with nodular and mantle zone areas. However, other areas had the morphologic and immunohistochemistry pattern of follicular lymphoma (CD20+, CD10+, Bcl2+). The diagnosis of both lymphomas was confirmed by polymerase chain reaction detection of both Bcl-1 MTC and Bcl-2 MBR rearrangements. DNA degradation in fixed tissue prevented a complete polymerase chain reaction analysis of immunoglobulin heavy chain rearrangements, but a single immunoglobulin H rearrangement was detected at the FR3 locus. These findings confirm the presence of a monoclonal cell population but do not demonstrate the same clonal origin for both lymphoma populations.     

Hyperplasia of mantle/marginal zone B cells with clear cytoplasm in peripheral lymph nodes. A clinicopathologic study of 35 cases

We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.     

骨髓活检组织淋巴瘤的病理诊断和分型

目的 探讨组织形态改变、免疫组织化学、基因重排在淋巴瘤骨髓侵犯的病理诊断和分型中的作用。材料与方法 对62例甲醛固定、石蜡包埋的骨髓活检组织,分别做了组织学、EnVision法观察和免疫球蛋白重链(IgH)基因和TCRγ基因重排检测。结果 慢性淋巴细胞性白血病／小淋巴细胞淋巴瘤(CLL／SLL)的异型淋巴细胞呈小梁间结节状或散在分布,有时可见假滤泡结构。滤泡型淋巴瘤(FCL)表现为结节性小梁旁或小梁间的浸润,结节内小淋巴样细胞松散聚集。淋巴浆细胞性淋巴瘤(LPL)主要为小梁间弥散浸润,在小而圆的淋巴细胞间可见散在数量不等的浆细胞样淋巴细胞。边缘区淋巴瘤(MZL)则见模糊的或界限不清的小梁间或小梁旁结节,一些细胞胞质透明。套细胞性淋巴瘤(MCL)异型细胞小到中等大小,缺乏副免疫母细胞和假滤泡。毛细胞性淋巴瘤(HCL)瘤细胞胞膜多清晰,胞质丰富透明,常形成荷包蛋样表现。霍奇金病可见大核瘤细胞,核仁明显。T-非霍奇金淋巴瘤(NHL)浸润骨髓主要为小梁间间质性散在或弥漫分布,胞质多透明,核有芋艿样或脑回状改变,DLBL造血细胞间体积大的瘤细胞散在或弥漫分布。CD3对T细胞来源、CD20和CD79对B细胞来源淋巴瘤有鉴别诊断价值,cyclin D1和(SD5阳性对MCL具有诊断性价值,bcl-2和CD10阳性则对FCL具有诊断性意义,而CLL／SLL除了(SD20和CD79阳性外,也可CD5和CD23阳性。HCL的瘤细胞CD25强阳性。CD15、CD30和Fascin也适用于骨髓霍奇金病的诊断。骨髓中CLL／SLL,LPL,MZL及DLBL的IgH重排率(80％、60％、66．7％、70％)及T—NHL的TCRγ重排率(66．7％)较高。结论 综合组织形态改变、免疫组织化学和IgH／TCRγ重排检测,有助于淋巴瘤骨髓侵犯的诊断和分型,有助于发现骨髓中为数不多的淋巴瘤细胞。     

Nodal marginal zone lymphoma associated with extensive epithelioid histiocytes

Nodal marginal zone lymphoma (NMZL) is a rare type of non-Hodgkin lymphoma. In this report, we describe a similar condition affecting female 53-year-old presented with generalized lymphadenopathy and high LDH level. The patient underwent excision of cervical lymph node and bone marrow biopsy. Histopathological examination of the excised lymph node revealed florid infiltrate by epithelioid histiocytes, which greatly underscores the neoplastic process directing the diagnosis towards reactive lesions such as toxoplasmosis, marginal zone hyperplasia or monocytoid B-cell hyperplasia. Careful histopathological examination of interfollicular and parafollicular regions helped in recognition of the pale monomorphic neoplastic cells that showed immunoreactivity for CD20 and Bcl-2 and lacked expression for CD5, CD10 and CD23. The involvement of bone marrow by the same type of cells has excluded the possibility for reactive conditions. The recognition of NMZL is sometimes difficult when benign components predominate such as the presence follicular hyperplasia and epithelioid cell clusters. However, full clinical data including LDH level and asking for bone marrow biopsy were greatly helpful in identifying the correct lesion.     

Mantle cell lymphoma

Mantle cell lymphomas comprise 2 to 8% of non-Hodgkin's lymphoma in the United States. They occur in older adults with a distinct male predominance, who present with generalized lymphadenopathy, and often have disseminated disease at the time of diagnosis. Pathologically, mantle cell lymphomas are characterized by a proliferation of small lymphocytes, with irregular nuclei, clumped chromatin, and sparse cytoplasm that can grow in nodular or diffuse patterns in lymph nodes, that localize to the splenic white pulp and that produce interstitial, paratrabecular, and intertrabecular lymphoid aggregates in the bone marrow. Phenotypically, mantle cell lymphomas are B cell neoplasms that express pan B cell lineage antigens, CD5 and CD43, and that are negative for CD10 and CD23. On a genetic level, many cases of mantle cell lymphomas have the t(11;14)(q13;q32) that causes overexpression of cyclin-D1, a protein that can be demonstrated by immunohistochemistry in many examples of mantle cell lymphoma and that can be exploited diagnostically to distinguish mantle cell lymphomas from other low-grade B cell lymphoproliferative disorders. The differential diagnosis of mantle cell lymphoma includes small B cell lymphoma, lymphoplasmacytic lymphoma, nodal, extranodal, and splenic marginal zone lymphomas, and follicular small cleaved cell lymphoma. In most instances, these disorders can be separated from one another by morphology, distinctive immunophenotypic profiles, and genetic features.     

Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+. Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.     

B-cell cutaneous lymphoid hyperplasia representing progressive transformation of germinal center: a report of 2 cases

Cutaneous lymphoid hyperplasia (CLH) is a reactive polyclonal benign lymphoproliferative process predominantly composed of B cells or T cells, either localized or disseminated. The authors report histomorphologic, immunophenotypic, and genotypic findings of 2 cases of B-cell CLH demonstrating progressive transformation of germinal center (PTGC). Histologically, most of the lymphoid follicles were PTGCs with a few hyperplastic germinal centers. PTGC was characterized by enlarged but well-circumscribed follicles without clear demarcation of the germinal center and mantle zone, which contained a predominance of small lymphocytes and variable numbers of centrocytes, centroblasts, and immunoblasts. However, there were no centroblasts and immunoblasts resembling lymphocytic and/or histiocytic Reed-Sternberg cell variants in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in either lesion. These unusual CLHs should be differentiated from the primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular lymphoma, particularly "floral variant," or NLPHL. To avoid overdiagnosis and overtreatment, immunophenotypic and genotypic studies are required along with careful morphologic examination.     

Peripheral T-cell lymphoma with a nodular growth pattern

Peripheral T-cell lymphomas (PTCL) with nodular growth patterns are very rare, with only 17 cases reported previously. Here, we report a case of PTCL with a nodular growth pattern. The patient was an 81-year-old Japanese woman who complained of malaise, fever and generalized lymph node swelling. Cervical lymph node biopsy was performed, and histological examination revealed proliferation of medium- to large-sized atypical lymphoid cells with indented to irregular nuclei, distinct nucleoli and clear cytoplasm. The nodular growth pattern of the lymphoma cells was obvious. On immunohistochemistry, the atypical lymphoid cells proved to be of T-helper cell origin (CD2+CD3CD4+CD5+CD7+ CD8-CD10-CD25-CD30-CD57-). Polymerase chain reaction analysis of the T-cell receptor gamma-chain revealed a monoclonal rearrangement band. This unusual growth pattern should be distinguished among PTCL, as such cases could be confused with reactive nodular hyperplasia, nodular lymphoma, mantle cell lymphoma and marginal zone lymphoma with nodular colonization.     

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.     

B-cell non-Hodgkin lymphomas in Uganda: an immunohistochemical appraisal on tissue microarray

The most common non-Hodgkin lymphomas in Uganda are neoplasms of B-cell derivation. The field of B-cell lymphoma immunophenotype has rapidly progressed because of the increasing availability of markers applicable to routine sections. Although the latter have allowed the identification of distinctive lymphoma entities in the developed countries, such approach has not yet been used in Uganda. One hundred twenty-nine formalin-fixed, paraffin-embedded tissue samples from the Department of Pathology of Makerere University were used for tissue micro-array (TMA) construction. Four-micrometer-thick sections were cut from TMAs and stained with hematoxylin and eosin and Giemsa. They were also used for immunohistochemistry and in situ hybridization. According to morphology and immunohistochemistry, lymphoid neoplasms were classified as Burkitt's lymphoma (BL) (95 cases), diffuse large B-cell lymphoma (19 cases), mantle cell lymphoma (4 cases), and B-cell lymphoblastic lymphoma (1 case). In BL, a homogeneous phenotype (CD10(+), Bcl-6(+), Bcl-2(-), MUM1/IRF4-, and Ki-67 approximately 100%) and a stable Epstein-Barr virus integration were found. A distinctive and unusual feature was the frequent plasma cellular differentiation, along with the positivity for CD30 and CD138 (recorded in 35 and 43 cases, respectively). According to our findings, most non-Hodgkin B-cell tumors in Uganda are endemic BLs followed by diffuse large B-cell lymphomas. The rest consist of rare but clinically important entities such as mantle cell lymphoma and B-cell lymphoblastic lymphoma. The availability of TMAs and immunohistochemistry has enabled us to precisely categorize tumors that have so far been diagnosed in Uganda as "high-grade/aggressive" lymphomas on the basis of cell morphology alone.     

Nodal marginal zone B-cell lymphoma with prominent follicular colonization - difficulties in diagnosis: a study of 15 cases

Aims:  While colonization of reactive follicles is well described in mucosa-associated lymphoid tissue lymphoma, this is not fully appreciated in nodal marginal zone B-cell lymphoma (NMZL). The aim was to address how to recognise this feature/entity and to discuss diagnostic difficulties faced by histopathologists in dealing with such lesions and their biological implications.
Methods and results:  Fifteen NMZLs with prominent follicular colonization are described, 14 of which were referrals from other hospitals. All cases had a follicular pattern and showed prominent 'follicular colonization'. In many follicles the colonization was partial, and follicles also had a reactive germinal centre component. The phenomenon of follicular colonization was highlighted by immunohistochemistry. The benign follicle centre cells expressed CD20, CD10 and Bcl-6 and were negative for Bcl-2 and MUM1. In contrast, the colonizing marginal zone lymphoma cells expressed CD20, Bcl-2 and often MUM1 and were negative for Bcl-6 and CD10. Partially colonized follicles showed a 'moth-eaten' appearance on CD10, Bcl-2, Bcl-6 and MUM1 immunohistochemistry. In none except one was the referring diagnosis NMZL.
Conclusion:  Recognizing and appreciating follicular colonization in a subset of NMZLs, appropriate use of immunohistochemistry and knowledge of immunohistological features can aid in making the correct diagnosis.     

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.