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.     

Splenic marginal zone lymphoma: a case report and review of the literature

Splenic marginal zone lymphoma is a recently described primary splenic lymphoproliferative disorder that mainly affects older individuals. We report the case of a 22-year-old woman with morphologic and immunophenotypic findings consistent with splenic marginal zone lymphoma. This woman is one of the youngest patients ever described with this disease. The patient presented with complaints of left-sided abdominal fullness and was noted to have splenomegaly on physical examination. Laboratory evaluation revealed pancytopenia and a serum M component. The spleen was removed and weighed 1550 g. Histology showed prominent white pulp with an expanded marginal zone. The neoplastic cells were marginal zone-type cells with small to intermediate-sized nuclei with occasional conspicuous nucleoli and moderate amounts of pale to amphophilic cytoplasm. Immunophenotypic analysis revealed a B-cell population (CD20 positive) with kappa-light-chain restriction. The patient was treated with adjuvant therapy, but developed progressive disease less than 2 years after initial diagnosis.     

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.     

Hairy cell leukemia variant with features of intrasinusoidal bone marrow involvement

Hairy cell leukemia variant (HCL-V) is a rare lymphoproliferative disorder. We report a case of HCL-V with an intrasinusoidal pattern of bone marrow involvement without interstitial or diffuse infiltration that is typical of HCL and its variant. The peripheral blood and bone marrow aspirates demonstrated abnormal lymphoid cells with cytoplasmic projections that were weakly positive for tartrate-resistant acid phosphatase cytochemical staining. Immunostaining of the bone marrow biopsy specimen showed that these cells were strongly positive for CD20, located within bone marrow sinusoids, and weakly positive for DBA44. By flow cytometry, these cells were positive for CD19, CD20, CD11c, and CD103, exhibited lambda light chain restriction, and were negative for CD25. The patient was initially diagnosed as having splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma (SMZL) (World Health Organization designation) and treated with fludarabine followed by splenectomy with simultaneous liver biopsy. The pathologic analysis of the spleen revealed infiltration of red pulp by the critical cells without white pulp involvement, which is characteristic of HCL and HCL-V but not of SLVL (SMZL). This case illustrates an atypical marrow presentation of HCL-V and emphasizes the need to correlate all clinical and pathologic data, including tissue biopsy, in reaching a diagnosis.     

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.     

A case of splenic lymphoma with marked diffuse nodular fibrosis and calcification,complicated with severe autoimmune hemolytic anemia

A splenic lymphoma, possibly of a splenic marginal zone lymphoma, marked by small nodular splenic calcified fibrosis and complicated by intractable autoimmune hemolytic anemia, was studied by immunohistochemical, molecular genetic, and ultrastructural analyses. The patient was a 57-year-old Japanese man who had moderate splenomegaly, and who had undergone splenectomy for improvement of severe autoimmune hemolytic anemia and to rule out malignancy in the spleen. In the resected spleen, proliferative atypical lymphoid cells were observed both in the red and white pulp with diminished germinal centers and irregularly widened marginal zones with peculiar dimorphic pattern. Ultrastructural study revealed no hairy cells or villous lymphocytes. Diffuse nodular hyalinous fibrosis surrounding the small arterioles in the white pulp overlapped with frequent calcification was a unique histologic feature in this case. Degenerative connective tissue, extracellular matrix, or collagen fibers surrounding the arterial sheath in the white pulp caused by some immunological abnormalities associated with this splenic lymphoma could be assumed to be the predisposing factor for this excessive fibrosis and dystrophic calcification in the spleen.     

Fine-needle aspiration biopsy findings in marginal zone B cell lymphoma

Marginal zone B cell lymphomas (MZBCLs) represent a category of non-Hodgkin's lymphoma which may arise in a wide variety of extranodal organs where they are termed low grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT). MZBCLs may involve primarily lymph nodes and or spleen where they are designated monocytoid B cell lymphoma or splenic marginal zone lymphoma, respectively. Recognition of this category of lymphoma, in particular, extranodal MALT lymphoma, is clinically significant in determining optimal therapy. Although there have been recent case reports describing the cytologic findings in low grade MALT lymphoma in various extranodal organs, this category of lymphoma has not been widely recognized or discussed in the cytology literature. The cytologic findings in seven fine-needle aspirations and two bronchial washings of histologically confirmed marginal zone lymphoma (five extranodal MALT lymphomas and four nodal marginal zone lymphomas) are described. In all of the cases, the cytologic specimens showed a polymorphous proliferation comprising a predominant population of intermediate sized lymphoid cells with centrocyte-like or monocytoid features, transformed cells, and variable numbers of plasma cells. These findings, while highly suggestive of MALT lymphoma in extranodal proliferations, may be more difficult to distinguish from reactive conditions in lymph nodes.     

Monoclonal antibodies against mouse splenic stromal cells

A panel of rat monoclonal antibodies directed against mouse splenic stromal cells were isolated. These monoclonal antibodies were Immunohistochemically divided into four groups which reacted with non-lymphoid cells of the murine spleen; (1) in the white pulp, (11) at the marginal zone, (111) in the red pulp, and (IV) on the endothelium of splenic blood vessels. These monoclonal antibodies were studied Immunohistochemically In lymphoid organs by means of light and electron microscopy. Monoclonal antibodies SS-4 (group I) reacted with fibroblastic reticulum cells that were distributed only in the white pulp of the spleen and In the follicular areas of lymph nodes. The SS-4 staining cell, In clustered splenic stromal cells, formed colonies which Included a small number of Thy-1 positive lymphocytes. Therefore, we concluded that SS4 staining stromal cells comprise the lymphoid cornpartment. In contrast, monoclonal antibodies SS-1, SS-3 and SS-5 (group II) reacted with dendritic shaped cells in the marginal zone of the spleen. Examination of splenic extra-medullary hematopolesis in mice rescued by bone marrow transplantation after lethal irradiation revealed that SS-3 and SS-5 reacted with dendritic shaped stromal cells in clonal nodules of engrafted marrow in the red pulp. SS-3 and SS-5 staining cells could not be observed in physiologic hematopoiesis of non-transplanted mice. It was suggested that SS3 and SS-5 staining stromal cells are Involved in primitive hematopoiesls. Monoclonal antibodies SS2, SS-6 and SS-7 (group 111) mainly reacted with dendritic cells and macro-phages in the red pulp. Monoclonal antibodies SS-8 and SS-9 (group IV) reacted with endothelial cells of blood vessels and sinuses. These findings of heterogeneity in mouse splenic stromal cells are further evidence that specific micro-envlronments are composed by speclalired stromal cells.     

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。     

CD27 distinguishes two phases in bone marrow infiltration of splenic marginal zone lymphoma

AIMS: To investigate CD27 expression in splenic marginal zone lymphoma (SMZL), an indolent low-grade B-cell lymphoma with constant involvement of the bone marrow, especially with an intrasinusoidal pattern. It is not clear if the neoplastic clone is composed of virgin or somatically mutated B cells. CD27 is reported to be a hallmark of memory B cells. METHODS AND RESULTS: We evaluated 64 bone marrow biopsy specimens (BMBs) from 36 patients with SMZL for the expression of CD27. For comparison, splenectomy specimens of patients with traumatic splenic rupture or with SMZL were used. All BMBs showed lymphomatous infiltration. When located in the marrow sinusoids, neoplastic cells were CD27- in all cases and therefore corresponded to naive B cells. In nodular/interstitial infiltration, the cells were CD27+ and therefore corresponded to memory B cells. No difference in immunohistochemical expression of B and T antibodies was found between intrasinusoidal and interstitial/nodular infiltration. CD27 was constantly expressed in the splenic marginal zone of normal spleen, surgically removed for trauma, and in seven out of 10 spleens with SMZL. CONCLUSION: We propose the existence of two different phases of neoplastic progression with, first, expansion of a virgin B clone in the bone marrow and, following exposure to antigen, a re-colonization of the bone marrow.     

SPLENIC MARGINAL ZONE EXPANSION IN B-CELL LYMPHOMAS OF GASTROINTESTINAL MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) IS REACTIVE AND DOES NOT REPRESENT HOMING OF NEOPLASTIC LYMPHOCYTES

It has been suggested that lymphocytes of mucosa-associated lymphoid tissue (MALT) arise from marginal zone cells and that MALT-derived lymphomas may spread to other extra-nodal sites by homing to marginal zones in different tissues.¹ Marginal zone expansion has been observed in spleens removed during surgery for gastrointestinal MALT lymphoma, which was sufficiently extreme in some cases to suggest neoplastic involvement. To investigate this phenomenon, polymerase chain reaction (PCR) amplification of immunoglobulin heavy chain gene fragments was performed to demonstrate B-cell clonality in gastrointestinal MALT lymphomas and spleens from 11 patients. Monoclonal PCR products were obtained from 9 of the 11 gastrointestinal tumours but from none of the accompanying spleens. One additional spleen, for which the accompanying gastric lymphoma tissue was unavailable for review, yielded a monoclonal product. However, obvious lymphoma deposits were present in this specimen, in addition to marginal zone enlargement. It is concluded that splenic marginal zone expansion accompanying gastrointestinal MALT lymphoma is correctly interpreted as being reactive. Splenic involvement by MALT lymphoma is uncommon and does not show preferential colonization of the marginal zone to suggest homing of MALT-derived cells to this site.     

Splenic small B‐cell lymphoma with predominant red pulp involvement: a diffuse variant of splenic marginal zone lymphoma?

AIMS: Splenic marginal zone lymphoma (SMZL) has been characterized by a micronodular pattern of infiltration, biphasic cytology, follicular replacement and the presence of marginal zone differentiation. Here we describe four cases with some distinctive features, such as diffuse splenic infiltration, lack of micronodules, marginal zone cytology, p53 inactivation and cutaneous involvement. METHODS AND RESULTS: In the course of a review of cases of SMZL, we recognized the existence of a subset of four cases of splenic B-cell lymphoma, with predominantly red pulp involvement, absence of follicular replacement, and a monomorphous population of tumoral cells resembling marginal zone B-cells, with scattered nucleolated blast cells. The immunophenotype (bcl2+, CD5-, CD10-, CD43-, CD23-, cyclin D1-, IgD- (3/4)) was consistent with SMZL. Bone marrow infiltration (4/4) and peripheral blood involvement (2/4) showed similar findings to those described for SMZL in these locations. However, unlike classical SMZL, 2/4 had cutaneous involvement, and 4/4 cases showed either p53 mutation or anomalous p53 staining (p53+, p21-). CONCLUSIONS; In spite of a diffuse pattern of splenic infiltration, cutaneous involvement and p53 alterations, these cases have findings that overlap with those corresponding to classic SMZL (symptomatology, morphology of bone marrow, lymph nodes, peripheral blood involvement, and immunophenotype). We suggest that these cases be considered a putative variant of SMZL.     

Malignant lymphoma of the spleen in Japan: A clinicopathological analysis of 115 cases

Primary splenic lymphoma is rare, but malignant lymphoma often produces a lesion in the spleen as part of systemic disease. The frequency of splenic malignant lymphoma in Japan is unknown. We classified 184 specimens of the spleen according to the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition (2008). Of the 184 specimens, 115 were determined to be lymphoid neoplasm (62.5%). The most common subtype of lymphoid neoplasm was diffuse large B-cell lymphoma (DLBCL) (46 cases), followed by splenic marginal zone lymphoma (SMZL) (28 cases), follicular lymphoma (11 cases), splenic B-cell lymphoma, unclassifiable (SBL-U) (6 cases) and peripheral T-cell lymphoma, not otherwise specified (4 cases). In the SBL-U subtype, 5 of 6 cases were splenic diffuse red pulp small B-cell lymphoma, and one case was the hairy cell leukemia variant. Analysis of clinical features revealed that patients with DLBCL had a higher age, high lactate dehydrogenase and tumor formation in the spleen. On the other hand, it was found that patients with SMZL had splenomegaly but no discrete tumor formation. Most of the patients with SBL-U presented with thrombocytopenia, bone marrow involvement, and advanced stage. Our study revealed the frequency and clinical features of splenic malignant lymphoma in Japan.     

Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase

In mice homozygous for the 'viable motheaten' ( me^v ) mutation, numbers of macrophage progenitor cells, particularly monocytes, were markedly increased in the bone marrow and spleen. Increased mobilization of these precursor cells to peripheral tissues and their differentiation to macrophages were evidenced by striking increases in macrophage numbers. Immunohistochemical double staining of tissue sections and flow cytometry analyses of single cell suspensions from these mice demonstrated CD5 (Ly-1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstrated in the peritoneal cavity of the me^v mice and developed in the omental milky spots. The development of marginal metallophilic and marginal zone macrophages was poor in the splenic white pulp and related macrophage populations were absent in the other lymphoid tissues. The numbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic medulla, lymph nodes, and the other peripheral lymphoid tissues were decreased. However, increased numbers of dendritic cells accumulated in the lungs, liver, and kidneys. These abnormalities in development and differentiation of macrophages and dendritic cells may be ascribed to the deficiency in haematopoietic cell SHP-1 tyrosine phosphatase or may be a secondary consequence of abnormal microenvironments, (either constitutive or in response to inflammatory stimuli) in the haematopoietic and lymphopoietic organs and tissues of these mice.     

Low-grade B-cell lymphomas of the splenic marginal zone: a clinicopathological and immunohistochemical study of 14 cases

We have studied 14 cases of low-grade, splenic marginal zone, B-cell non-Hodgkin's lymphoma. The clinical presentation in all cases was with splenomegaly and, in 10 cases, circulating neoplastic lymphoid cells in the peripheral blood with involvement of bone marrow. In all cases the splenic white pulp was hyperplastic with expansion of marginal zones and varying degrees of infiltration of germinal centres by neoplastic cells. The cells were a mixture of medium sized lymphocytes with moderate amounts of cytoplasm and finely dispersed nuclear chromatin, together with occasional blast cells with small nucleoli. Satellite red pulp aggregates of tumour cells centred on small epithelioid cell clusters were seen in all cases. These appear to be a characteristic and diagnostically important feature of splenic marginal zone lymphoma. The tumour cells expressed CD20, CD45RA, bcl-2 and the antigens detected by MB2. All cases expressed IgM with light chain restriction. In addition, IgD was expressed in four cases. The follicular dendritic cell network was disrupted in those follicles which were infiltrated by tumour cells. A network of stromal myoid cells, at the periphery of the marginal zone, identified by expression of α-smooth muscle actin, was preserved. Alpha-smooth muscle actin positive dendritic cells were also seen within and around satellite tumour nodules in the red pulp.     

Primary marginal zone lymphoma of the thymus accompanied by chromosomal anomaly 46,X,dup(X)(p11p22)

We report a case of primary marginal zone lymphoma in the thymus of a 34-year-old woman. She was initially suspected of having a mediastinal plasmacytoma because of the presence of dominantly proliferating plasmacytic cells in a small fragment obtained by thoracoscopic biopsy, and an elevated level of serum monoclonal IgA. However, histology of the tissue obtained by a subsequent open surgical biopsy revealed diffuse proliferation of atypical monocytoid B-lymphocyte-like cells, which showed prominent plasmacytic differentiation and a close association with thymic epithelial cells consistent with the histology of a marginal zone lymphoma of the thymus. These lymphoma cells were positive for CD19, CD20, IgA, and kappa, and negative for CD5, CD10, and other T/NK-cell and myelomonocyte antigens. Both G-banded and spectral karyotyping analyses revealed the lymphoma cells carried a chromosomal anomaly, 46,X,dup(X)(p11p22). Although large cell type B-cell lymphoma in the thymus (mediastinal diffuse large B-cell lymphoma), which is categorized as a definite subtype in revised European-American classification of lymphoid neoplasms and the new World Health Organization classification, is not infrequent, primary marginal zone lymphoma of the thymus is extremely rare. To our knowledge, this is the first case report of primary marginal zone lymphoma of the thymus with a detailed chromosomal analysis.     

The CD45 isoform B220 identifies select subsets of human B cells and B-cell lymphoproliferative disorders

The B220 isoform of CD45, a pan B-cell marker in mice, is expressed by only a subset of human B cells that do not express the memory B-cell marker CD27, suggesting that it is a differentiation-specific isoform of CD45. We examined normal human peripheral blood B cells, secondary lymphoid tissue, and a range of human B-cell lymphoproliferative disorders for the expression of B220 by flow cytometric immunophenotyping and immunohistochemical staining. We found that a subset of human B cells in peripheral blood is positive for B220 by flow cytometric immunophenotypic analysis. In reactive lymphoid tissues, B220 is expressed by B cells occupying the mantle zones and by a subpopulation of germinal center cells, but, in contrast, marginal zone B cells in the spleen do not express B220. Of 94 cases of B-cell lymphoproliferative disorders, 33 (35%) were positive for B220 by flow cytometric immunophenotypic analysis, including most cases of marginal zone lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma. In contrast, all cases of precursor B lymphoblastic leukemia/lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma were negative for B220. Immunohistochemical staining for B220 correlated with flow cytometric analysis for all cases studied by both methods. Our data demonstrate that B220 is expressed in a select subset of normal, reactive B cells in a pattern that is consistent with a marker of naive B cells. However, this restricted expression pattern is not seen in B-cell lymphoproliferative disorders. Discordance between the B220 expression patterns of normal mantle and marginal zone B cells and their respective neoplastic counterparts may aid in the distinction between normal and neoplastic proliferations at these anatomical sites.     

Absence of TCL1A expression is a useful diagnostic feature in splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a low-grade lymphoma showing a rather nonspecific immunophenotype. Gene expression profiling studies suggested that TCL1A could be a marker of SMZL, but reported data are conflicting. We evaluated TCL1A expression in a series of spleen and bone marrow samples involved by SMZL and correlated the findings with other immunophenotypical, morphological, and clinical data. In addition, we evaluated the expression of TCL1A in a series of spleens and lymph nodes involved by lymphomas that might mimic SMZL (13 nodal marginal zone lymphomas (NMZL), 39 follicular lymphomas (FL), 30 B-cell chronic lymphocytic leukemias (B-CLL), 31 mantle cell lymphomas (MCL), 1 lymphoplasmacytic lymphoma) and 15 bone marrow specimens involving hairy cell leukemia (HCL). TCL1A staining was negative in 24/31 cases of SMZL (77?%); 27/31 MCL and all B-CLL were positive for TCL1A; 32/34 cases of nodal FL (96?%) and all five splenic FL were positive for TCL1A, although at a lower intensity. Eight of 13 NMZL were positive for TCL1A, often showing a heterogeneous staining pattern. All HCL samples were strongly positive for TCL1A. No correlation was found between the pattern of splenic infiltration, TCL1A expression, and the clinical course. TCL1A-positive SMZL showed a higher rate of DBA44 staining compared to the negative ones, and this difference was statistically significant (Fisher test, single-tailed, p?=?0.0397). Our data support the use of TCL1A in the panel of diagnostic markers used in the differential diagnosis of splenic low-grade B-cell lymphoma; a possible prognostic value, however, needs a larger series to be established.     

Evidence that Candida albicans binds via a unique adhesion system on phagocytic cells in the marginal zone of the mouse spleen.

We recently demonstrated by using an ex vivo adhesion assay that Candida albicans yeast cells exhibit a unique binding affinity for the marginal zone of the spleen. This binding event provides a working model for studying mechanisms of organ dissemination of the fungus from the blood. By using the ex vivo assays reported here, we showed by bright-field and electron microscopic techniques that mouse spleen marginal zone cells capable of ingesting India ink particles are also involved in yeast cell attachment. During splenic clearance of yeast cells from the circulation in vivo, C. albicans is also associated exclusively with marginal zone cells capable of ingesting India ink. The ability to ingest the ink particles is not necessarily related to yeast cell adherence, because the fungal cells did not bind to phagocytic cells in the splenic red pulp. In fact, the marginal zone phagocytic cells appear to have a unique binding system, because yeast cells also did not bind to phagocytes in other tissues, such as the thymus and peritoneum, or to seven different myeloid cell lines. In addition, antibodies to a number of well-characterized murine adhesion molecules, such as leukocyte integrins, LECAM-1, and CD44, had no effect on binding. On the basis of these results, we propose that splenic marginal zone phagocytes express a novel adhesion system that involves either a unique adhesion molecule or previously described adhesion molecules with unique binding activities.     

Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes

The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been generated against human mesothelioma cells and recognizes a biochemically unknown membrane epitope. We have accidentally found that the HBME-1 reacts with scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To evaluate its reactivity pattern, we have performed a consecutive immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n?=?40), as well as in malignant lymphoproliferations (n?=?427), including hairy cell leukemia (HCL) (n?=?72), HCL variant (HCL-v) (n?=?13), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n?=?8), splenic B cell marginal zone lymphoma (SMZL) (n?=?59), and splenic B cell lymphoma/leukemia, not further classifiable on bone marrow morphology (SBCL) (n?=?37) cases. The staining pattern of HBME-1 was compared to DBA.44. HBME-1⁺ villous lymphocytes were constantly detected in low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence staining, HBME-1⁺ lymphocytes showed a CD20⁺/CD79a⁺/IgM⁺ B cell phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1 reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases were positive in 12 % of the cases. A small minority (4 %) of the other B cell lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In conclusion, our study has established that HBME-1 reacts with a minor subset of B lymphocytes and a small proportion of B cell lymphomas, which has not been described previously. We suggest that HBME-1 can be a useful marker in the diagnosis of HCL and other indolent lymphoproliferations of villous B lymphocytes.