CD23 expression in mantle cell lymphoma: clinicopathologic features of 18 cases

The distinction between small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and mantle cell lymphoma (MCL) has important clinical implications. Typically, SLL/CLL is CD23+, whereas MCL is CD23-. However, CD23 is expressed in a subset of MCLs, and the clinicopathologic features of patients with these neoplasms are not well described. We report 18 CD23+ MCLs, detected by flow cytometry in all cases (dim intensity, 16; bright intensity, 2), 5 (28%), also positive by immunohistochemical analysis. There were 13 men and 5 women (median age, 56 years), 5 of whom died (median survival, 46 months). Seventeen (94%) had bone marrow involvement. Lymphadenopathy (14 cases [78%]), splenomegaly (11 cases [61%]), and leukemic involvement (10 cases [56%]) were common. Five cases (28%) had blastoid morphologic features. The frequency of CD23 expression by MCL is method-dependent, being typically dim and most commonly detected by flow cytometry. In this small study group, bone marrow and leukemic involvement were relatively common.     

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.     

Characteristic CD103 and CD123 expression pattern defines hairy cell leukemia: usefulness of CD123 and CD103 in the diagnosis of mature B-cell lymphoproliferative disorders

By using flow cytometry, we studied CD103 and CD123 expression by the malignant cells in 300 B-cell lymphoproliferative disorder (BC-LPD) cases, including 114 hairy cell leukemia (HCL), 20 HCL variant (HCLv), 9 splenic marginal zone lymphoma (SMZL; in 5, only CD103 was evaluated), 133 chronic lymphocytic leukemia (CLL), 3 follicular lymphoma (FL), and 21 mantle cell lymphoma (MCL). All HCLs expressed uniform CD103 and bright CD123. Among the 20 HCLv cases, 20 (100%) were CD103+ and 8 (40%) were CD123+ (partial or dim). CD103 was negative in all MCL, FL, CLL, and SMZL cases. CD123 was positive in 1 (25%) of 4 SMZL, 3.8% of CLL (5/133), 7 (33%) of 21 MCL, and 1 (33%) of 3 FL cases. CD103 is specific for HCL and HCLv. CD123 expression is more widespread in BC-LPDs but is useful in conjunction with CD25 to differentiate HCLv from HCL. These findings support the usefulness of CD123 and CD103 to aid in the differential diagnosis of BC-LPDs.     

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.     

Mantle cell lymphoma--a clinicopathological study of 13 cases

Mantle cell lymphoma is an uncommon non-Hodgkin's lymphoma. In a period of four years, 13 cases of mantle cell lymphoma were diagnosed in our department, comprising 3.1% of all non-Hodgkin's lymphoma diagnosed. The mean age of presentation was 52 years with a slight male preponderance. The disease was nodal in twelve and extra-nodal in tonsil in one. Five patients had bone marrow involvement. Five cases showed a nodular pattern on lymph node biopsy while the remaining eight had a diffuse pattern. Immunophenotyping showed positivity for CD20 and cyclin D1. Despite certain morphological similarity to other low-grade lymphomas, mantle cell lymphoma has a characteristic appearance of its own. It is more aggressive than other low-grade lymphomas and hence needs to be accurately diagnosed.     

B-cell lymphomas with coexpression of CD5 and CD10

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.     

Characterization of incidentally identified minute clonal B-lymphocyte populations in peripheral blood and bone marrow

We describe 69 patients in whom small clonal B-cell populations were detected incidentally in blood and bone marrow samples by flow cytometric studies. In 20 patients (29%), non-Hodgkin lymphoma (NHL) subsequently was diagnosed 0 to 40 months (median, 0.1 month) from initial flow cytometric studies. In 49 patients (71%), there was no evidence of NHL after 0.5 to 72 months (median, 16 months). Patients without overt NHL had a higher absolute WBC count than patients with NHL (2,260/microL vs 1,470/microL [2.26 vs 1.47 x 10(9)/L]; P < .01). Otherwise, there were no clinical or hematologic differences between the 2 groups. We identified 70 clonal populations in the 69 patients, ranging from 0.05% to 4.5% (median, 1.28%) of events. The mean percentage of clonal B cells was similar for the 2 groups. The populations were CD5-/CD10- in 34 cases; CD5+, chronic lymphocytic leukemia-like in 19; CD5+, indeterminate in 9; CD10+ in 3; hairy cell leukemia-like in 3; and CD5+, mantle cell lymphoma-like in 2. There were no immunophenotypic differences in patients with and without overt NHL.     

p27(Kip1) immunostaining for the differential diagnosis of small b-cell neoplasms in trephine bone marrow biopsies.

The distinction between mantle cell lymphoma (MCL) and other small B-cell non-Hodgkin lymphomas (NHL) is important because MCL has a more aggressive clinical course. In bone marrow (BM) biopsy specimens, this distinction can be particularly difficult. Although cyclin D1 immunostaining and molecular detection of the t(11;14) translocation are highly specific markers for MCL, they fail to detect a proportion of cases. We have recently described that MCL typically lacks detectable expression of the cyclin-dependent kinase inhibitor p27(kip1) protein by immunostaining, which is expressed at high levels in most small B-cell NHL inversely correlated to the proliferation rate. We therefore examined whether p27(kip1) immunostaining could be a useful adjunct for the differential diagnosis of small B-cell NHL infiltrates in the BM. Trephine BM biopsy specimens of 96 patients, including well-characterized MCL (19 cases), B-cell chronic lymphocytic leukemia (27 cases), follicular lymphoma (18 cases), hairy cell leukemia (22 cases), and marginal zone lymphoma (10 cases) as well as 10 reactive BM, including five with benign lymphoid aggregates were investigated. In addition, the presence of a t(11;14) translocation involving the major translocation cluster was studied by PCR in all MCL. All cases of B-cell chronic lymphocytic leukemia, follicular lymphoma, and marginal zone lymphoma revealed a strong p27(kip1) nuclear staining in the majority of neoplastic cells. Fourteen (78%) cases of MCL were p27(kip1)-negative in the tumor cells, whereas four cases revealed a weak nuclear positivity. Seventeen (77%) cases of hairy cell leukemia were also either completely negative for p27(kip1) or showed a faint positive staining in a minority of the neoplastic cells. Nine of 19 cases (47%) of MCL showed a bcl1 rearrangement involving the major translocation cluster region. These findings demonstrate that p27(kip1) immunostaining is a valuable additional marker for the differential diagnosis of small B-cell NHL infiltrates in BM biopsies. The reduction or lack of p27(kip1) protein expression in MCL, as well as in hairy cell leukemia, might be an important event in the pathogenesis of these disorders.     

逆转录聚合酶链反应检测石蜡包埋组织中细胞周期蛋白D1 mRNA对套细胞淋巴瘤的诊断价值

目的 探讨用逆转录聚合酶链反应（RT-PCR）法和竞争性RT-PCR法检测套细胞淋巴瘤（MCL）石蜡包埋组织中细胞周期蛋白D1（cyclin D1）蛋白和mRNA在常规病理工作中的可行性及其诊断和鉴别诊断价值。方法 收集淋巴结内MCL38例、对照组包括结内小B细胞淋巴瘤58例（B小淋巴细胞性淋巴瘤14例,淋巴浆细胞性淋巴瘤3例,滤泡性淋巴34例,淋巴结边缘区B细胞淋巴瘤7例）和淋巴结反应性增生病例20例,用免疫组织化学EnVision法和RT-PCR法、竞争性RT-PCR法检测cyclin D1蛋白及其mRNA的表达,以看家基因PGK作为内对照检测RNA。结果 （1）38例结内MCL中,cyclin D1蛋白阳性率为71．1％（27／38）,对照组均为阴性。（2）116例标本中,可检出内对照PGK基因mRNA表达103例（88．8％）。38例MCL中PGK阳性36例（94．7％）。（3）38例结内MCL中,34例可检出cyclin D1 mRNA表达,去除PGK和cyclin D1 mRNA均阴性的2例,MCL中cyclin D1 mRNA表达的阳性率为94．4％（34／36）。对照组中B小淋巴细胞性淋巴瘤1例检出cyclin D1 mRNA表达,其余病例均未检出cyclin D1 mRNA表达。PCR结果全部经测序证实。（4）用竞争性RT-PCR,38例结内MCL中27例可检出cyclin D1 mRNA高表达,去除2例PGK也为阴性的病例,MCL中cyclin D1 mRNA高表达率为75．0％（27／36）。对照组小B细胞恶性淋巴瘤及淋巴结反应性增生无1例有cyclin D1 mRNA高表达。结论 RT-PCR方法和竞争性RT-PCR方法可在石蜡包埋组织中检测cyclin D1 mRNA的表达,均可用于MCL的诊断。     

Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases

Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.     

Progressive leukemic non-nodal mantle cell lymphoma associated with deletions of TP53, ATM,and/or 13q14

Leukemic, non-nodal mantle cell lymphoma (MCL) is a relatively indolent disease characterized by asymptomatic leukemic presentation, non-nodal disease distribution, and slow disease progression, particularly in comparison to that of classic nodal MCL. We studied 3 cases of leukemic, non-nodal MCL in which TP53, ATM, and/or 13q14 deletions were identified. All three patients had disease progression leading to treatment requirements in two of the patients at 5 and 18 months after initial diagnosis. The third patient also clinically progressed 25 months after initial diagnosis but was lost to follow up despite recommendation for initiation of therapy. We present these cases as potential evidence that while leukemic non-nodal MCL is typically an indolent disease compared to classically defined mantle cell lymphoma, cytogenetic heterogeneity exists and cases with TP53, ATM, and/or 13q14 deletions may have a relatively aggressive clinical course.     

原发淋巴结套细胞淋巴瘤临床病理分析

目的：探讨原发淋巴结套细胞淋巴瘤（MCL）的临床病理与免疫组化特点。方法：收集6例淋巴结MCL,免疫组化ABC法确定肿瘤细胞特征,使用的抗体有CD45、CD20、CD79、CD45RO、CD30、CD68、TdT、CD43、CD5、cyclinD1、c-myc,IgD,IgM等。结果：光镜可将MCL分为4种亚型：套区型1例,结节型1例,弥漫型2例,母细胞化型2例。肿瘤细胞表达全B细胞标记,IgD CD43 ,cyclinD1(5/6),CD5(4/6) 。结论：MCL是一种具有特殊免疫表型的B细胞淋巴瘤,不同的组织学构型其预后可能不同,临床应与其它类型B细胞淋巴瘤鉴别,如淋巴结边缘区B细胞淋巴瘤（MZL）,滤泡性淋巴瘤（FL）及CLL／SLL等鉴别。     

Non-Hodgkin's lymphoma in Dakar: study of 107 cases diagnosed between 1986 and 1998

Non-Hodgkin's Lymphomas (NHL) are the most prevalent malignant hemopathies in Senegal. In this study we have investigated the epidemiological aspects considering the HIV infection pandemic, and evaluated the diagnosis means and evolutive features of this disease in Dakar. Between 1986 and 1998 (13 years), we collected 107 cases of NHL, all histologically confirmed. Average age of patients was 31.4 years (2-85 years) and sex ratio was 21. HIV infection was found in three out of 62 patients tested (4.8%). At moment of diagnosis, 72% of patients were in stage III or IV according to the Ann Arbor Staging System. Large cell lymphomas were predominant (67.2%), followed by small lymphocyte lymphomas (24.2%) and follicular lymphoma with 8.4% of cases. Localization of lymphomas was exclusively nodal (30.8%) or extra nodal (31.7%) or mixed (37.3%). In therapeutical field, 21.5% of patients were treated with only symptomatical means. Chemotherapy was used in 54 patients (78.2% of treated patients), surgery was performed in 6 patients (8.6%), association of radiotherapy and chemotherapy in 5 patients (7.2%) and 4 patients (5.7%) were treated with surgery + chemotherapy. The average survival time was 344 days. Four patients (3.7%) were alive 3 years after diagnosis and only 2 patients (1.8%) after 5 years.     

CD5- B-cell lymphoproliferative disorders presenting in blood and bone marrow. A clinicopathologic study of 40 patients

We studied 40 patients with CD5- B-cell lymphoproliferative disorders (B-LPDs) presenting in blood or bone marrow and 28 control patients with CD5+ B-cell chronic lymphocytic leukemia (CLL). Fifteen study patients had morphologic features typical of CLL. The 15 patients with CD5- CLL were older and had lower absolute lymphocyte counts and more advanced-stage disease at diagnosis than controls. Ten study patients had morphologic features suggesting mantle cell lymphoma (MCL); 3 were later given a diagnosis of MCL based on lymph node biopsy results. The 10 patients with CD5- MCL were older and at a more advanced stage than CLL control patients. The remaining 15 study patients were given the following diagnoses: circulating non-Hodgkin lymphoma, 5; splenic lymphoma with villous lymphocytes, 5; lymphoplasmacytoid lymphoma, 3; and CLL/pro-lymphocytic leukemia, 2. For the patients with CD5- B-LPDs with morphologic features and manifestations resembling CLL, we prefer the term CD5- CLL variant because of clinical and immunophenotypic differences. Patients with CD5- B-LPDs with atypical nuclear morphologic features may represent the leukemic phase of MCL. Since CD23 is expressed in most patients with CD5- B-LPD, its use in subclassifying these disorders seems limited.     

Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome

Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies.     

De novo CD5 positive diffuse large B-cell lymphomas with bone marrow involvement in Korean

In CD5 positive (CD5+) mature B-cell lymphomas, newly recognized CD5+ diffuse large B-cell lymphoma (DLBCL) has been characterized by aggressive features. We studied twenty-five cases with CD5+ lymphomas involving bone marrow. Eleven cases were diagnosed as chronic lymphocytic leukemia, six cases were diagnosed as mantle cell lymphoma (MCL), and three cases with morphologic characteristics of MCL and without both the cyclin D1 expression and IGH/CCND1 rearrangement were unclassifiable. The remaining five cases, showing large to medium-sized lymphoid cells with prominent nucleoli and a moderate amount of cytoplasm, were diagnosed as DLBCL. Five DLBCL cases were positive for CD5, CD20, surface immunoglobulin, but negative for CD23. Patients with CD5+ DLBCL showed a high age of onset (median, 68 yr) and two patients expired one month after the diagnosis. Since CD5+ DLBCL forms a distinct subgroup of DLBCL, a study of CD5 expression in DLBCL would be helpful to predict prognosis and to determine future therapeutic strategy. To the best of our knowledge, this is the first report on de novo CD5+ DLBCL in Koreans.     

Distribution of lymphomas in Poland according to World Health Organization classification: analysis of 11718 cases from National Histopathological Lymphoma Register project - the Polish Lymphoma Research Group study

Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.     

Analysis of human equilibrative nucleoside transporter 1 (hENT1) protein in non-Hodgkin's lymphoma by immunohistochemistry.

The human equilibrative nucleoside transporter 1 (hENT1) is a member of the equilibrative nucleoside transporter family that mediates cellular entry of gemcitabine, cytarabine, and fludarabine. Deficiency in hENT1 confers resistance to toxicity of these drugs in a variety of model systems. Since some nucleoside analogs have a role in treating patients with non-Hodgkin's lymphoma (NHL), this study was undertaken to assess hENT1 abundance in NHL. A total of 115 cases of NHL of various subtypes and 15 reactive lymph nodes were evaluated for the presence of hENT1 protein using immunohistochemistry applied to frozen tissues. Samples were considered positive when >or=50% of neoplastic cells showed immunostaining. In reactive lymph nodes, hENT1 was confined to the germinal centers, whereas mantle zone B-cells and interfollicular T-cells were negative. In NHL, a relatively high frequency of hENT1 positivity was found in Burkitt lymphoma/leukemia (63%), diffuse large B-cell lymphoma (DLCL; 45%), and follicular lymphoma (40%). In DLCL, 26% of cases were positive for CD10, and CD10-positive DLCL cases were more likely to be hENT1 positive than CD10-negative cases (P=0.025). A lower frequency of hENT1 positivity was found in mantle cell lymphoma (13%) and peripheral T-cell lymphomas (37%). All marginal zone lymphomas (n=5), chronic lymphocytic leukemia small lymphocytic lymphomas (n=10), plasmacytoma (n=3), acute lymphoblastic lymphoma/leukemia, and anaplastic large-cell lymphomas (n=5) were negative. In conclusion, hENT1 was most frequently found in benign and malignant follicular center cells. Prospective studies to assess the value of hENT1 immunostaining in predicting resistance to nucleoside chemotherapy for NHL are warranted.     

Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.     

Immunophenotyping of non-Hodgkin's lymphoma. Correlation with relapse-free survival

In a retrospective analysis the authors studied the relation between the immunologic phenotype of B-cell non-Hodgkin's lymphoma (NHL) and disease-free survival. The phenotype included immunoglobulin isotypes; B-cell maturation/differentiation antigens of clusters of differentiation CD9, CD10, CD19-24, CD37, CD38; T-lymphocyte antigens in CD5-7; HLA-DR; peanut agglutinin binding capacity; terminal deoxynucleotidyl transferase; the activation marker CD25 (interleukin-2 receptor); and the proliferation marker transferrin receptor. The phenotype and clinical data were available for 109 patients. Two patients underwent bone marrow transplantation, and 15 patients (with low or intermediate grade NHL) did not receive treatment intended to achieve complete remission. These 17 cases were excluded from the analysis. For individual markers, CD23 expression was associated with a longer actuarial disease-free survival (50% survival in CD23-positive cases was 40 months; and in CD23-negative cases, 16 months; P = 0.01). Among the total study population of 92 patients, this finding applied in particular to those with a low-grade malignancy according to the Kiel classification (P = 0.03). In high-grade NHL (Kiel classification) the absence of CD38 or presence of CD24 on tumor cells correlated with a higher degree of disease-free survival (P values 0.009 and 0.04, respectively). For a combination of five CD markers associated with stages in physiologic B-lymphocyte maturation/differentiation (CD9, CD10, CD21-23), the lowest measure of disease-free survival was observed where NHLs were at an immature stage, and the greatest extent of survival where NHLs were associated with a resting B-cell stage (P = 0.006). These statistical significances aside, the detailed immunologic phenotyping has relatively little prognostic value when compared with that of the malignancy grade assessed by conventional histopathology.