Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a distinct clinicopathologic and molecular entity?

The presence of circulating villous lymphocytes (VLs) in lymphoma patients usually points to splenic marginal zone B-cell lymphoma (SMZL), even if the VLs can be found occasionally in other small B-cell lymphomas. However, those cells are variably described, and detailed cytologic characterization is often lacking. We identified lymphoma cases with numerous basophilic VLs among the large group of splenic lymphoma with VLs, and for further delineation, 37 cases with this particular cytology were analyzed. Patients, predominantly older men, presented with moderate lymphocytosis and splenomegaly without pancytopenia. The monoclonal B cells expressed IgM + D, IgM + G, IgM or IgG, as well as CD76 and CD11c, frequently CD103, and rarely CD123. Spleen sections were peculiar, with atrophic white pulp and a monomorphic diffuse lymphoma infiltration in a congested red pulp. Bone marrow infiltration was interstitial and intrasinusoidal without extensive fibrosis. Cytogenetic analysis showed a frequent absence of clonal aberrations (68%). Most cases (79%) were IgH mutated, with an overrepresentation of V(H)3 and V(H)4 gene families. These results, as well as the clinical evolution, show that those lymphoma cases represent a homogeneous group distinct from SMZL and reminiscent of hairy cell leukemia variant, perhaps corresponding to a separate lymphoma entity.     

Splenic lymphoma with circulating villous lymphocytes/splenic marginal-zone lymphoma.

Splenic lymphoma with villous lymphocytes (SLVL) represents a low-grade B-cell non-Hodgkin's lymphoma (NHL) that histologically is indistinguishable from splenic marginal-zone lymphoma (SMZL). Characteristic features of SLVL are splenomegaly, moderate lymphocytosis, nodular and intrasinusoidal pattern of bone marrow infiltration, serum monoclonal band, slow benign course, and response to splenectomy. The diagnosis is made by the morphology of the circulating villous cells and their immunophenotype, which is distinct from that of chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), diseases with which SLVL may be confused. When treatment is indicated, splenectomy is the treatment of choice, but some patients may require additional chemotherapy to control progression. In those circumstances, fludarabine may be the agent of choice. Despite its unique features, which, compounded, suggest that SLVL is a clinicopathologic entity, there are no specific chromosome abnormalities and problems of differential diagnosis with other B-cell NHLs, chiefly mantle-cell lymphoma (MCL), remain in a minority of patients.     

Intrasinusoidal bone marrow infiltration and splenic marginal zone lymphoma: a quantitative study

Intrasinusoidal infiltration (ISI) is a pattern of invasion that is rarely found on bone marrow (BM) biopsies, and is considered as a hallmark of splenic marginal zone cell lymphoma (SMZL). We analysed BM biopsies showing intrasinusoidal infiltration from 54 consecutive patients with different types of lymphoma to verify if ISI quantity was a diagnostic criterion for SMZL. There were 35 primary splenic lymphoma (PSL) and 19 non-PSL; 28 SMZL, three non-splenic MZL, six mantle cell, six small lymphocytic, four follicular, four diffuse large B cell, one peripheral T cell, one lymphoplasmacytic and one anaplastic large-cell lymphoma. The quantity of BM infiltrate was assessed on CD45, CD20 and CD3 stained sections. The mean percentage of total (TI) and intrasinusoidal (ISI) lymphocytes was calculated in 10 areas for each case. TI quantity was 21.57 in PSL and 35.05 in non-PSL (P = 0.04). ISI quantity was 5.23 in PSL and 7.62 in non-PSL (P = 0.08), 5.83 in SMZL and 2.83 in other types of PSL (P = 0.12), 4.46 in non-splenic MZL and 8.21 in other types of non-PSL (P = 0.28). No difference in ISI quantity was found among the lymphoma subtypes, either in PSL (P = 0.74) or non-PSL (P = 0.3). The data demonstrate that ISI quantity in BM biopsies is not a reliable diagnostic parameter for SMZL.     

Composite splenic marginal zone lymphoma and classic Hodgkin lymphoma -- an unusual combination

The simultaneous occurrence of Hodgkin lymphoma with a variety of B-cell Non-Hodgkin lymphomas (composite lymphoma) has been described. We report the first case of composite Hodgkin lymphoma and splenic marginal zone lymphoma occurring simultaneously in the same lymph node of a 64-year-old man who presented with cervical and axillary lymphadenopathy and massive splenomegaly. He had a peripheral blood lymphocytosis and a bone marrow infiltrated by small lymphocytes. However, cervical lymph node biopsy showed classic Hodgkin lymphoma. His splenomegaly showed only a partial response to six cycles of ABVD chemotherapy so he underwent splenectomy with biopsy of remaining nodes. Histology of the spleen and nodes showed splenic marginal zone lymphoma. Review of the original biopsy confirmed the presence of both diseases in the original lymph node.     

Early-stage splenic diffuse large B-cell lymphoma is highly associated with hepatitis C virus infection

Splenic marginal zone lymphoma (SMZL) and splenic diffuse large B-cell lymphoma (DLBCL) are the most common types of lymphomas involving the spleen. Geographic variation in hepatitis C virus (HCV) seroprevalence is characteristic of splenic lymphomas. In Italy, HCV seroprevalence was higher in patients with SMZL and splenic DLBCL than in patients with all types of lymphoma. In Japan, HCV seroprevalence was higher in patients with splenic DLBCL than in patients with all types of lymphoma; however, HCV seroprevalence in patients with SMZL was similar to that in patients with all types of lymphoma. In this study, clinicopathological data of 74 splenic lymphoma cases between 1988 and 2011 collected from the Department of Pathology at National Taiwan University Hospital were analyzed. Serology for HCV infection was available for 41 cases. Splenic DLBCL and SMZL accounted for 36% (n = 27) and 42% (n = 31) of splenic lymphomas, respectively. Microscopically, most cases of DLBCL (26/27) presented with circumscribed tumor and most cases of SMZL (28/31) presented with white pulp expansion. HCV seroprevalence in patients with DLBCL and SMZL was 44% and 10%, respectively (7/16 vs. 2/20, p = 0.020). The pattern identified in this study is closer to that in Japan than in Italy. HCV seroprevalence in patients with early-stage (I/II) and late-stage (III/IV) DLBCL was 100% and 10%, respectively (6/6 vs. 1/10, p < 0.001). Early-stage DLBCL is clinically considered a form of primary splenic lymphoma rather than a systemic lymphoma with splenic involvement. High HCV seroprevalence in patients with early-stage DLBCL suggests a role of HCV in the pathogenesis of primary DLBCL.     

Relationship between hairy cell leukemia variant and splenic lymphoma with villous lymphocytes: Presentation of a new concept

An unusual case of low-grade B-cell lymphoproliferative disorder with peripheral lymphocytosis and splenomegaly followed for 4 1/2 years is reported. During this period, the phenotype of the tumor cells in the blood changed from that of hairy cell leukemia (HCL)/chronic lymphocytic leukemia (CLL) to HCL/prolymphocytic leukemia (PLL), to PLL. The lymphoid population in the blood showed a mixture of hairy cells, villous lymphocytes, small lymphocytes, and prolymphocytes, corresponding to the phenotypes at various stages. Although relatively specific markers for CLL, HCL, and PLL, such as CD5, CD11c, CD22, CD25, and FMC-7, were positive at various stages, all these markers have also been demonstrated in a large study series of splenic lymphoma with villous lymphocytes (SLVL). In addition, the histologic pattern of the bone marrow biopsy and splenectomy specimen were not typical for HCL. This case can therefore be classified either as HCL variant or as SLVL. As SLVL assumes various cytologic and histologic patterns, which overlap with different lymphoproliferative disorders, especially HCL variants, this entity appears to represent a heterogeneous group of lymphomas/leukemias that may evolve into each other. The absence of activation of c-myc and bcl-2 oncogenes as well as mutation of p53 tumor suppressor gene, together with the presence of only one single rearranged band for both heavy chain and κ light chain genes in our case suggest that these morphologically different lymphoid tumors may belong to the same family. © 1996 Wiley-Liss, Inc.     

Simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL)

We report a unique case of 83-year-old Caucasian male with the initial simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). The patient presented with absolute lymphocytosis in the blood, asymptomatic generalized lymphadenopathy, and mild splenomegaly. The diagnosis of CLL was suggested from the blood film, but subsequent flow cytometric (FC) analysis on peripheral blood mononuclear cells (PBMNC) revealed two distinct abnormal clones of mature B cells. A small subpopulation (7%) of lymphoid cells expressed CD20, CD11c, FMC-7, CD103, CD25, and kappa surface light chain, consistent with HCL. The larger subpopulation (75%) of lymphoid cells expressed CD19, CD20, CD23, CD5, and lambda light chain, consistent with CLL. The expression of different immunoglobulin light chains on the circulating CLL (lambda) and HCL (kappa) cells suggested two, independent, malignant B-cell clones. Interestingly, FC analysis of bone marrow (BM) cells done 6 months later revealed bright lambda light chain expression on the HCL cells. Despite administration of several different courses of chemotherapy, the HCL subpopulation was not eliminated from the BM but remained stable between 7% and 10% of total BM lymphoid cells. The CLL, responsible for most of clinical symptoms in our patient, responded to combination chemotherapy with fludarabine and cytoxan, and later to monotherapy with rituximab.     

Immunophenotyping of low-grade B-cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification

Results of immunophenotypic examinations of peripheral blood and/or bone marrow (BM), involved in low-grade B-cell non-Hodgkin's lymphomas, were compared with the results of cytomorphological and histopathological examinations in 133 adult patients. 69 cases of chronic B-lymphocytic leukaemia (B-CLL), 16 centrocytic (CC) lymphomas, 14 centroblastic-centrocytic (CB/CC) lymphomas, 15 immunocytomas (IC), 10 cases of hairy cell leukaemia (HCL), four prolymphocytic leukaemias (PLL), two B-CLL in transformation, one splenic lymphoma with villous lymphocytes (SLVL), one hairy cell leukaemia variant (HCL-V), and one lymphocytic lymphoma (LC) were classified according to the Kiel and /or FAB classification. Leukaemic disease was found in 105 cases. The following markers were used for immunocytology (APAAP technique) of blood and/or BM smears: CD 19, CD 5, CD 10, CD 11c, CD 14, CD 21, CD 22, CD 23, CD 25, CD 38 and TdT. All cases tested showed CD 19, but no TdT expression. Every case of HCL had a distinct phenotype with expression of CD 11c, CD 22 and CD 25 and the lack of CD 5 and CD 23 antigens. In all other NHL cases a very heterogenous expression of CD-antigens with no significant correlations to the cytomorphological subtypes was found. The expression of CD 5 is a frequent but inconstant finding in lymphoproliferative diseases other than B-CLL, so 50% of CB/CC, 75% of CC and 80% of IC were CD 5 positive. Our results indicate that, with the exception of HCL, the diagnostic relevance of immunophenotyping for the classification of cytomorphologically and histopathologically defined subtypes in blood and/or BM is of very limited value.     

A case of T-cell lymphoma with Sézary cells in the blood and bone marrow accompanied by peripheral T and B lymphocytosis.

A case of T-cell lymphoma occurred in a man, aged 66, whose symptoms started as itching and the appearance of 1-2 cm indurated plaques with central pustules on the skin of the trunk and face. A few months later generalized lymphomas and splenomegaly were present. Investigations of the lymphocytic subpopulations in situ in fresh frozen sections of lymphomas and skin showed only T cells. Samples of blood and bone marrow disclosed lymphocytosis and Sézary cells. Both T and B lymphocytes were definitely increased in the blood. The value of tissue studies in analyzing lymphocytic subpopulations is emphasized as a differential diagnostic aid in classifying lymphomas. A relationship between the T-cell neoplasia and the T and B lymphocytosis to mycosis fungoides and the Sézary syndrome is discussed.     

Splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a specific low-grade small B-cell lymphoma that is incorporated in the World Health Organization classification. Characteristic features are splenomegaly, moderate lymphocytosis with villous morphology, intrasinusoidal pattern of involvement of various organs, especially bone marrow, and relative indolent course. Tumor progression with increase of blastic forms and aggressive behavior are observed in a minority of patients. Molecular and cytogenetic studies have shown heterogeneous results probably because of the lack of standardized diagnostic criteria. To date, no definitive therapy has been established. Therapeutic options include treatment abstention, splenectomy, splenic irradiation, and chemotherapy.     

Intrasinusoidal bone marrow infiltration: a common growth pattern for different lymphoma subtypes

We report a retrospective immunohistochemical study on bone marrow biopsies of 43 patients with different types of lymphomas showing unusual intrasinusoidal infiltration. Most of these patients presented with splenomegaly (74.4%) and peripheral lymphocytosis (83%). In 20/43 patients, lymphoid infiltrates were not detectable on haematoxylin-eosin sections. After immunohistochemistry on bone marrow biopsies and blood and bone marrow smear examinations, the following diagnoses were made: splenic marginal zone lymphoma with villous lymphocytes (SLVL) in 24 patients, large granular lymphocyte (LGL) leukaemia in 14 patients, hepatosplenic T-cell lymphoma in two patients, anaplastic large cell lymphoma in two patients and intravascular large B-cell lymphoma in one patient. In the presence of intrasinusoidal infiltrates of small lymphocytes, a B-cell phenotype (CD20+, CD76/DBA44+/-) was associated with splenic marginal zone lymphoma whereas intrasinusoidal CD3/CD45RA-positive T-cell infiltrates were strongly suggestive of LGL leukaemia. Intrasinusoidal bone marrow infiltration appears to be a common feature of distinct lymphoma subtypes. Immunohistochemical analysis is essential to detect intrasinusoidal medullary infiltrates (which may be minimal) and should be systematically performed in patients with splenomegaly and peripheral lymphocytosis.     

Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) "SMZL-specific subsets" (n=5), composed only of 12 SMZL (9 HCV-from our series); ii) "Non-Hodgkin’s lymphoma-like subsets" (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) “CLL-like subsets” (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV-unrelated epitopes or an antigenic trigger common to other indolent lymphomas.     

Frequency of MYD88 L256P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasm

Objective/backgroundB-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasmacytic lymphoma (LPL)/Waldenström’s macroglobulinemia (WM), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and hairy cell leukemia (HCL). In this study, we analyzed the frequency of MYD88 L265P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasms.MethodsA total of 110 consecutive cases of B-cell neoplasms showing peripheral blood and/or bone marrow infiltration were included. MYD88 L265P mutation was detected by polymerase chain reaction amplification of exon 5 of MYD88 gene, followed by restriction fragment length polymorphism analysis.ResultsAmong the 110 cases, the major group was of CLL (54.5%, n = 60), followed by HCL. Other cases included MCL, LPL, DLBCL, SMZL, NMZL, FL, and BL. MYD88 L265P mutation was seen in 21 (19.1%) cases of B-cell neoplasm, whereas 89 (80.9%) cases were negative for MYD88 L265P mutation. It was most commonly seen in LPL/WM cases followed by HCL, SMZL, CLL, and MCL cases. No case of DLBCL, FL, and BL showed MYD88 L265P mutation. Statistically significant difference was seen for hemoglobin level in CLL cases, with MYD88 L265P mutated cases showing higher mean hemoglobin levels than MYD88 wild-type cases (p = .001). For other parameters, no statistically significant difference was noted between mutated and unmutated cases.ConclusionMYD88 L265P mutation is seen in various B-cell neoplasms; it is most commonly seen in LPL/WM cases but not specific for it.     

A narrow deletion of 7q is common to HCL, and SMZL, but not CLL

To further characterise the genetic background of the two closely related B-lymphocytic malignancies hairy cell leukaemia (HCL), and splenic marginal zone lymphoma (SMZL) we have identified characteristic copy number imbalances by comparative genomic hybridisation (CGH). Based on these findings, areas of special interest were fine mapped, and relevant probes constructed for use in interphase-fluorescence in situ hybridisation (FISH) investigations. Thus, using the CGH data from 52 HCL and 61 SMZL patients, we identified the characteristic profiles of copy number imbalances for both diseases. These were a gain of 5q13-31 (19%) and loss of 7q22-q35 (6%) for HCL, and gain of 3q25 (28%), loss of 7q31 (16%), and gain of 12q15 (16%) for SMZL. A partial loss of 7q unusual for low-malignant B-cell diseases was found to be common to the two diseases. This loss was therefore fine mapped with BAC/PAC clones. Fine mapping revealed that in SMZL the minimal lost region covers 11.4 Mb spanning from 7q31.33 to 7q33 located between sequence tagged site (STS)-markers SHGC-3275 and D7S725. This area was distinct from the commonly deleted 7q region of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML). A FISH probe specific for the 7q region was constructed. Using this probe in an interphase-FISH investigation we showed the minimal lost 7q-region of HCL and SMZL to be one and the same. In one HCL case, this investigation furthermore showed the extent of the deleted region to be below the detection limit of CGH, whereas interphase-FISH screening of 36 chronic lymphocytic leukaemia (CLL) cases showed no deletion of the 7q area. In conclusion, we have identified characteristic profiles of copy number imbalances in HCL and SMZL and fine mapped the minimal extent of a commonly lost 7q area of special interest. We hypothesise that this region may contain (a) gene(s) important for the pathology of HCL and SMZL.     

Clinical and prognostic significance of monoclonal small cells in the peripheral blood and bone marrow of various B-cell lymphomas.

Discordant lymphomas, in particular nodal large-cell lymphomas with marrow small-cell lymphoma, were discovered recently, and the prognosis of patients with such disease has been discussed. The small cells were reported to be small lymphocytic or small cleaved lymphoma cells. We have detected, by kappa-lambda imaging (KLI) with delta-curves, using a flow cytometer, small lymphoma cells in the peripheral blood (PB) and bone marrow (BM) of 41 untreated patients with various B-cell lymphomas expressing surface Ig (sIg+BCL), and evaluated their clinical and prognostic significance. Small cells were found in approximately 90% (37 of 41) of sIg+BCL patients when either PB or BM was analyzed and, overall, the presence of small cells correlated well with the disease activity. However, in some patients, a few cells remained in the PB (16%) or BM (27%) even when they were in remission, whereas in others, the cells were presented in the PB or BM several months before relapse. These results suggest that the detection of small cells in PB or BM by KLI may be helpful for screening and monitoring patients with sIg+BCL. When the patients were subdivided into three groups (normal, low, and high amplitude), according to the abnormal grade criteria of the delta-curves, which were based on the results of both PB-KLI and BM-KLI, the survival of the high-amplitude group tended to be shorter than that of the normal group (P = .068), which was particularly marked when the follow-up period exceeded 2 years. Moreover, as the group grading worsened (normal less than low less than high), the complete response rates deteriorated (100%, 71%, and 60%, respectively) and the respective relapse rates after complete remission increased (17%, 40%, and 67%). Thus, the determination of the proportion of small lymphoma cells in PB and BM by KLI may be useful for predicting the prognoses of patients with sIg+BCL.     

Reassessment of small lymphocytic lymphoma in the era of monoclonal B-cell lymphocytosis

Background

In the 2008 World Health Organization classification, small lymphocytic lymphoma is defined as a neoplasm with the tissue morphology and immunophenotype of chronic lymphocytic leukemia, but with absence of leukemia. Minimal criteria of tissue involvement to separate small lymphocytic lymphoma from monoclonal B-cell lymphocytosis have not been defined.

Design and Methods

We reviewed the clinicopathological features of 36 patients with extramedullary tissue biopsies containing chronic lymphocytic leukemia-type cells and less than 5×10⁹/L peripheral blood monoclonal B cells. Pathological features (extent and patterns of involvement, architectural preservation, presence of proliferation centers) as well as cytogenetic and radiological findings were examined in relation to clinical outcome.

Results

The biopsies were performed to evaluate lymphadenopathy in 20 patients and for other reasons (most frequently staging of a non-hematologic neoplasm) in 16 patients. At latest follow-up (median 23 months), 21 untreated patients had no or stable lymphadenopathy, 3 had regressed lymphadenopathy, and 12 had developed progressive lymphadenopathy and/or received therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma. Features associated with progression/treatment included lymph nodes 1.5 cm or greater on imaging studies (P=0.01) and presence of proliferation centers in the biopsied tissue (P=0.004). Neither the size nor extent of involvement of the excised lymph node correlated with progression/treatment.

Conclusions

Our findings suggest that biopsies containing chronic lymphocytic leukemia-type cells, but lacking proliferation centers and with non-enlarged or only slightly enlarged lymph nodes on imaging, represent a very indolent disease that may best be considered a tissue equivalent of monoclonal B-cell lymphocytosis rather than overt small lymphocytic lymphoma. We propose that such cases be designated as tissue involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma-like cells of uncertain significance.     

Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

Background

Cases of mantle cell lymphoma with indolent behavior have been reported, but are poorly identified by current clinical risk models. Early studies found peripheral blood involvement to be an adverse prognostic factor; however, cases of a seemingly indolent variant of mantle cell lymphoma, characterized by peripheral blood involvement and minimal nodal disease, have been incompletely described, particularly with regard to bone marrow findings. We report a series of leukemic phase mantle cell lymphomas with a non-progressive or slowly progressive course.

Design and Methods

Cases presenting with mantle cell lymphoma limited to the peripheral blood/bone marrow from 2000–2010 were identified. Diagnoses were established by morphology, flow cytometric analysis and requisite evidence of IGH-CCND1@ by fluorescence in-situ hybridization or t(11;14)(q13;q32) by cytogenetics. Patients with lymphadenopathy, splenomegaly and gastrointestinal symptomatology were excluded.

Results

Patients (n=8, median age 60.5 years) were asymptomatic with mild lymphocytosis (8.7×10⁹/L; range, 4.5–14.2×10⁹/L) and cytology typical of mantle cell lymphoma. Flow cytometric analysis showed that all expressed CD5, CD19, CD20, variable CD23, and a striking kappa immunoglobulin light chain restriction (7/8 cases). Bone marrow biopsy at diagnosis showed interstitial single or small lymphoid aggregates with similar patterns of CD20 and cyclin D1 immunostaining which were not readily discernable by hematoxylin and eosin stain. SOX11 was negative (4/5) or only weakly expressed (1/5). The median follow-up was 27 months (range, 5–109 months) and all patients, but one, are alive with no clinical evidence of disease. The prevalence of indolent mantle cell lymphoma presenting only with lymphocytosis, among all mantle cell lymphomas diagnosed during the same period, was 3%.

Conclusions

Leukemic mantle cell lymphoma limited to blood and bone marrow is an indolent variant characterized by mild-moderate lymphocytosis, interstitial low-level bone marrow involvement, simple karyotype, kappa light chain expression, cyclin D1 expression with lack of SOX11, and slow or absent clinical progression. Some cases may represent a mantle cell lymphoma counterpart to chronic lymphocytic leukemia – phenotype monoclonal B-cell lymphocytosis. Recognition of this variant could inform treatment decisions and possibly avoid unnecessary treatment.     

Splenic lymphoma with circulating villous lymphocytes: Report of seven cases and review of the literature

Splenic lymphoma with villous lymphocytes (SLVL) is a relatively new entity with only a few reports published. We report seven cases of SLVL with detailed clinicopathologic and comprehensive immunophenotypic studies to further characterize this lymphoma, which is frequently confused with hairy cell leukemia and other low-grade B-cell lymphoid neoplasms. The diagnostic criteria we used include 1) prominent splenomegaly, 2) insignificant or no lymphadenopathy, 3) lymphocytosis without leukopenia, 4) presence of circulating villous lymphocytes, 5) characteristic cytologic and histologic features, and 6) specific phenotypic and cytochemical findings. Our studies show that SLVL does not represent a pure entity but rather a morphologically heterogeneous group of low-grade lymphomas with various cytologlc and histologic features. Although immunophenotyping is helpful in differential diagnosis, multiparameter studies are necessary to confirm the diagnosis. In our series, only two patients died of SLVL, who probably developed transformation to a higher-grade lymphoma. © 1994 Wiley-Liss, Inc.     

Leukemic phase of intermediate non-Hodgkin's lymphoma with cells showing different matured stages in invaded various organs.

A 56-year-old male was admitted to our hospital with lymphocytosis (16.4 x 10(9)/l; 79% lymphocytes including 50% small lymphocytes), generalized lymphadenopathy, massive splenomegaly, and heavily infiltrated bone marrow. Immunophenotype analysis of the neoplastic cells in the bone marrow revealed that they were B cells (CD20 + CD19 + Ia1 + sIgM+) positive for CD10. By contrast, the cells in the lymph node were CD20 + CD19 + Ia1 + sIgM+ but negative for CD10. The patient was tentatively diagnosed as having lymphosarcoma cell lymphoma, however, the final diagnosis was leukemic phase of intermediate lymphocytic lymphoma. We concluded that CD10+ neoplastic cells in the bone marrow and peripheral blood had differentiated to CD10- cells.     

脾边缘带淋巴瘤的临床及肿瘤细胞特征的研究

目的 提高对脾边缘带淋巴瘤（SMZL）的认识和诊疗水平,方法 报告1例典型SMZL,外周血,骨髓及脾脏标本分别采用光镜,相差显微镜,扫描电镜,免疫组化染色,流式细胞术,G显带核型分析及PCR技术研究其肿瘤细胞的生物学特征。结果 本例患者肿瘤细胞为B淋巴细胞,不伴有绒毛,表达CD20,HLA-DR、CD45RA和bcl-2,无异常核型,肿瘤细胞主要浸润脾脏白髓致边缘带明显扩大,脾门淋巴结受累,骨髓和外周血与脾脏有相同的单克隆IgH重排基因,治疗7个月后转为多克隆重排,结论 脾大,外周血或骨髓淋巴细胞比例增高而无淋巴结肿大和白细胞增高患者应疑及SMZL,单克隆IgH基因重排有助于SMZL的诊断,对可疑病例应尽早切脾以明确诊断及防止恶性转化。