Monocytoid B-cell Research Articles

A Clinical Analysis of Two Indolent Lymphoma Entities: Mantle Cell Lymphoma and Marginal Zone Lymphoma (Including the Mucosa-Associated Lymphoid Tissue and Monocytoid B-Cell Subcategories): A Southwest Oncology Group Study

The objectives of this study were (1) to determine the clinical presentation and natural history associated with two newly recognized pathologic entities termed mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), including the mucosa-associated lymphoid tissue (MALT) and monocytoid B-cell subcategories, and (2) to determine whether these entities differ clinically from the other relatively indolent non-Hodgkin's lymphomas with which they have been previously classified. We reviewed the conventional pathology and clinical course of 376 patients who had no prior therapy; had stage III/IV disease; were classified as Working Formulation categories A, B, C, D, or E; and received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) on Southwest Oncology Group (SWOG) studies no. 7204, 7426, or 7713. All slides were reviewed by the three pathologists who reached a consensus diagnosis. Age, sex, performance status, bone marrow and/or gastrointestinal involvement, failure-free survival, and overall survival were compared among all the categories. We found that (1) MCL and MZL each represent approximately 10% of stage III or IV patients previously classified as Working Formulation categories A through E and treated with CHOP on SWOG clinical trials; (2) the failure-free survival and overall survival of patients with MZL is the same as that of patients with Working Formulation categories A through E, but the failure-free survival and overall survival of the monocytoid B-cell patients were higher than that of the MALT lymphoma patients (P = .009 and .007, respectively); and (3) the failure-free survival and overall survival of patients with MCL is significantly worse than that of patients with Working Formulation categories A through E (P = .0002 and .0001, respectively). In conclusion, patients with advanced stage MALT lymphomas may have a more aggressive course than previously recognized. Patients with MCL do not have an indolent lymphoma and are candidates for innovative therapy.

Chronic lymphocytic leukemia with an interfollicular architecture: avoiding diagnostic confusion with monocytoid B-cell lymphoma.

Certain low grade B-cell lymphoproliferative disorders can be mistaken for each other morphologically, particularly when there is partial lymph node involvement. We encountered two cases of chronic lymphocytic leukemia, in which the interfollicular growth pattern and the pale appearance of the neoplastic proliferation in the lymph nodes led to a misclassification as monocytoid B-cell lymphoma. The correct diagnosis was established, however, when the lymph node morphology was carefully reexamined, with the knowledge of the clinical history, peripheral blood findings, and bone marrow data. The immunophenotype of the neoplastic cells in the peripheral blood (CD5, CD23, weak fluorescence intensity of surface immunoglobulin and CD22) and the lymph node immunohistochemistry (weak L26 staining, strong MT1 positivity) confirmed the diagnosis of chronic lymphocytic leukemia. These two cases demonstrate the necessity of a systematic approach to lymph node morphology and the utility of a multiparameter approach in the diagnosis of lymphoproliferative disorders.

Response to radiation in chemotherapy-refractory monocytoid B-cell lymphoma: A case report

A 39-year-old man had monocytoid lymphoma including a large retroperitoneal mass, retrocrural and porta hepatic adenopathy with localized pain, but no B symptoms. The tumor did not respond clinically or radiographically to CHOP or mini-ICE chemotherapy but has responded dramatically to radiotherapy. The patient's disease remains controlled 3 years after treatment. This case documents radioresponsiveness in a chemotherapy-refractory monocytoid lymphoma.

Detection of immunophenotypic abnormalities in paraffin-embedded B-lineage non-Hodgkin's lymphomas.

The authors analyzed the frequency of immunophenotypic abnormalities in 1,474 cases of routinely fixed, paraffin-embedded B-lineage non-Hodgkin's lymphomas. B-lineage was determined by immunoreactivity for CD20 (L26, 92%); CD45RA (4KB5, an additional 3%) or immunoglobulin (Ig) light chain restriction (remaining 5%). CD45RA was found to be especially helpful on Bouin's-fixed or decalcified tissue and Ig staining was most helpful in plasmacytoid lesions. Coexpression of the T-cell marker CD43 (Leu-22) was the most common immunophenotypic abnormality, seen in 60% of mantle cell lymphomas (MCL), 39% of CLL/small lymphocytic lymphomas, 16% of diffuse large cell lymphomas (DLCL), but only 5% of follicular lymphomas (FL). Antibodies to CD45RO (A6 and UCHL1) and CD3 (polyclonal) were useful in distinguishing infiltrating T cells from B cells coexpressing CD43. Ig light chain restriction was the next commonest immunophenotypic abnormality, which was identified in 67% of plasmacytoid diffuse small cell lymphomas, 43% of MCLs, 35% of monocytoid B-cell lymphomas and 28% of FLs. Overexpression of bcl-2 oncogenic protein was observed in 71% of FLs (n = 96), but not in a control group of reactive follicular hyperplasias (n = 34). Combining two criteria increased the sensitivity of immunodiagnosis in certain circumstances.

Monocytoid B Cells

Neoplastic monocytoid B-cells (MBCs) are present in different amounts in several types of non-Hodgkin's lymphomas (NHLs), including monocytoid B-cell lymphoma (MBCL), splenic marginal zone lymphoma (SMZL), mucosa-associated lymphoid tissue (MALT) low-grade B-cell lymphomas, and follicular centroblastic-centrocytic (CB-CC) lymphomas. In an attempt to clarify the relationships between different groups of tumors with a significant monocytoid component, we studied six primary lymph node MBCL, three SMZL, seven MALT lymphomas, and four CB-CC with monocytoid differentiation. Their clinical, morphological, immunohistochemical and molecular features were compared. The results show wide overlapping between MALT and MBCL in terms of morphology, immunophenotype, and molecular features. Follicular colonization was a characteristic finding in both groups. Some MBCL revealed mucosal involvement during the course of the disease, suggesting a possible MALT origin. Our data support the suggestion that the use of the term MBCL should be discontinued in cases with mucosal involvement, as they are probably examples of lymph node involvement brought about by MALT lymphomas. Although SMZL have some overlapping features with MBCL and MALT lymphomas, some of the clinical and morphological specific findings justify their distinction from the other groups. The CB-CCs with monocytoid differentiation frequently harbored t(14;18), lacking any significant differentiating features from conventional follicular CB-CC lymphomas. Additional studies are needed to define the molecular features of MBCL and other marginal zone tumors.

UCL3D3 and UCL4D12 reactivity in small B-cell neoplasms with special emphasis on monocytoid B-cell lymphoma

Two recently described monoclonal antibodies, UCL3D3 and UCL4D12, have been reported to have some specificity for mantle zone B lymphocytes and marginal zone/follicular center B lymphocytes, respectively, in the spleen. Forty-nine B-cell neoplasms, including 20 cases of monocytoid B-cell lymphoma (MBCL), were studied by frozen section immunohistochemistry with these antibodies to evaluate their utility. Tonsil, lymph node, and reactive spleen also were studied with the antibodies. Although a wide overlap was observed among the different lymphomas, a majority of cases of MBCL and half of cases of hairy cell leukemia (HCL) reacted with both markers, suggesting both marginal/follicular and mantle cell antigen expression. None of four cases of mantle cell lymphoma reacted with the proposed mantle cell marker UCL3D3, whereas three of these cases immunoreacted with UCL4D12. This marker is known to react with a subpopulation of follicular center cells and possibly with marginal zone lymphocytes. A comparison of nodal and extranodal neoplasms failed to show a significant difference in the pattern of immunoreactivity with these antibodies. Tonsil and lymph node controls showed some mantle zone staining with both antibodies, and there was a slight overlap in mantle and marginal zone staining of the spleen controls. These findings suggest an immunologic similarity between some cases of HCL and MBCL. However, the findings also would suggest that these antibodies, particularly UCL4D12, have less specificity than has been previously assumed, and UCL4D12 may not have practical utility in the evaluation of low grade B-cell lymphomas.

Monocytoid B-cells occurring in Hodgkin's disease.

In contrast with various forms of lymphadenitis, the presence of reactive monocytoid B-cells (MBCs) has only rarely been reported in Hodgkin's disease (HD). In order to analyse their occurrence in HD, we reviewed 120 cases before or after treatment. MBCs were identified morphologically and immunohistochemically in 8 cases (nodular paragranuloma, n = 2; nodular sclerosis, n = 2; and interfollicular mixed cellularity HD, n = 4). Acute toxoplasmic, cytomegalovirus, or Epstein-Barr virus (EBV) infections were excluded by serological tests and immunohistochemistry. MBCs were negative by immunostaining for EBV encoded latent membrane protein, while Sternberg-Reed and Hodgkin's cells expressed positivity in 50% of cases. MBCs were only identified in cases with partial or incomplete lymph node infiltration by HD together with an activated B-zone of residual non-infiltrated tissue. The relation of MBCs and HD infiltrates followed three distinct patterns: large HD infiltrates without any connection to MBC foci; small areas containing various numbers of Sternberg-Reed and Hodgkin's cells at the border between MBC foci and surrounding lymphoid tissue; and HD infiltrates within at least some MBC clusters. The data obtained suggest that MBCs occurring in HD represent a transient phenomenon associated with a B-zone activation irrespective of treatment and that they are usually not histogenetically related to HD.

Malignant Lymphomas of B-Cell Lineage with Marked Tissue Eosinophilia

Tissue eosinophilia is commonly seen in Hodgkin's disease and non-Hodgkin's lymphomas of T-cell lineage. In contrast, eosinophilia is infrequent in non-Hodgkin's lymphomas of B-cell origin. We describe five-B-cell lymphomas with exuberant tissue eosinophils. According to the Working Formulation, three were classified as large-cell immunoblastic, one as small lymphocytic lymphoma/chronic lymphocytic leukemia, and one as low-grade, not further subclassified, with features of monocytoid B-cell lymphoma. Immunophenotypic studies in each case revealed B-cell lineage; neoplastic cells expressed monotypic immunoglobulin light chain (four of five cases) or pan-B-cell antigens (five of five cases) and were negative for T-cell antigens. Southern blot hybridization in one case revealed immunoglobulin gene rearrangements, further confirming B-cell lineage. Eosinophilopoiesis is stimulated by interleukin 5 (IL-5), and Epstein-Barr virus (EBV) has been shown to upregulate IL-5 production. Therefore, both EBV infection and IL-5 expression were investigated as possibly pathogenetic mechanisms for the eosinophilia. However, both in situ hybridization studies for EBV mRNA and IL-5 mRNA were negative in the neoplastic cells. In one tumor, IL-5 was abundant in the cytoplasm of the eosinophils, a pattern similar to that seen in five cases of Hodgkin's disease studied with the same technique. Although rare, marked tissue eosinophilia may be associated with B-cell non-Hodgkin's lymphomas. Immunophenotypic or molecular genetic analyses are needed to make the correct diagnosis.

Uncommon clinical presentation of a lymphocytic lymphoma of intermediate differentiation in a patient with systemic sclerosis

The association of systemic sclerosis (SSc) and non-Hodgkin lymphoma is a rare event and its pathogenetic mechanism remains to be clarified. We describe a previously unreported association of SSc with a lymphocytic lymphoma of intermediate differentiation (IDL), involving the gastrointestinal tract, gallbladder and one salivary gland. Whereas the morphological, immunological and cytogenetic features were typical of IDL, the extensive extranodal involvement and the association with an autoimmune disorder were suggestive of two other lymphomas of mantle lineage: mucosa-associated lymphoid tissue (MALT) lymphoma and monocytoid B-cell lymphoma (MBCL).

Waldeyer ring lymphomas. A clinicopathological study of 79 cases

Waldeyer ring lymphomas belong to a category of tumours which has not yet been fully defined. Their relation to mucosa-associated lymphoid tissue (MALT) and other extranodal lymphomas remains largely unknown. We performed a clinicopathological retrospective study of 79 patients, and compared them with a series of MALT and nodal lymphomas. Tumours from the nasopharynx and palatine tonsil showed similar histological profiles, with a predominance of large B-cells. Centroblastic lymphomas constituted the largest group (n = 45), followed by those of centrocytic type (9) with smaller groups of centroblastic-centrocytic (5) and Hodgkin's lymphomas (2). Three monocytoid B-cell lymphomas were identified. Only one case could be classified as MALT lymphoma. The frequency of bcl-2 expression in large B-cell tumours of Waldeyer's ring has an intermediate range between large B-cell lymphomas occurring in mucosal and nodal locations. Epitheliotropism was present in all low-grade cases, and was therefore not a useful marker in the identification of potential MALT lymphomas in contrast with other mucosal sites. Comparative survival studies showed significant overall differences between Waldeyer ring lymphomas, MALT and nodal cases. These disappeared after taking stage and histological grade into account. We conclude that Waldeyer ring lymphomas show distinctive features, mainly in terms of histological distribution and immunophenotype. The key factor determining their behaviour could be their different spreading capability. These findings suggest that extranodal lymphomas are heterogeneous, and indicate the need for additional efforts to clarify this.

The cytological spectrum of the monocytoid B-cell reaction: recognition of its large cell type.

To analyse the cytological features of benign monocytoid B-cells, we investigated, histologically and immunohistochemically, 78 reactive lymphadenopathies expressing monocytoid B-cell reactions. Within a broad cytological spectrum of reactive monocytoid B-cells, two cytological types can be recognized: 1 the common type composed of medium-sized cells with irregular or bean-shaped nuclei and inconspicuous nucleoli, and 2 the large cell type composed of cells considered to represent large transformed monocytoid B-cells, with less pleomorphic round nuclei with vesicular chromatin and moderately basophilic, prominent nucleoli. In between these variants transitional forms showing evolution to large transformed monocytoid B-cells occurred. While monocytoid B-cell reactions in 70.5% of all cases were composed predominantly of the common type of monocytoid B-cells, in 29.5% of cases the large transformed cells prevailed. The two distinctive cytological types of reactive monocytoid B-cells seem to have their neoplastic counterparts in monocytoid B-cell lymphoma, including its large cell variant.

Cytogenetic studies of composite lymphomas: Monocytoid B-cell lymphoma and other B-cell non-Hodgkin's lymphomas

Monocytoid B-cell lymphoma (MBCL) is a newly recognized, morphologically and immunologically distinct, low-grade B-cell neoplasm that may exist as a pure morphologic entity or as a component of a composite lymphoma. To determine whether cytogenetic abnormalities exist in cases of MBCL, fresh tissue from four lymphoma specimens in which MBCL was a substantial component were analyzed by classic cytogenetics; no pure MBCL cases were available for study. One monoclonal neoplastic population was found in each case by immunophenotyping studies and classic cytogenetics. Clonal cytogenetic abnormalities included −X or +X, t(14;18)(q32;q21), del(6q), t(11;14)(q13;q32), dup(12q), dup(1q), t(2;3)(q13;q29), and der(8)t(8;9)(p11.2;q13). The abnormal clone usually reflected the underlying lymphomatous process, namely, follicular lymphoma [t(14;18)], mantle cell lymphoma [t(11;14)], or small lymphocytic lymphoma (partial trisomy 12). There were no cytogenetic abnormalities common to all neoplasms. Taken together, the cytogenetic and immunologic data suggest that although MBCL may exist as a pure entity, it also may commonly represent a morphologic variant or a component of other primary lymphomatous processes.

Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features.

The authors studied 56 cases of diffuse low-grade B-cell lymphoma using frozen tissue sections and a large panel of monoclonal antibodies that distinguish subsets of normal B cells. They compared the immunophenotypes with the histologic subtypes defined by the Rappaport classification, Working Formulation, and Kiel classification to correlate antigen expression with the morphologic subtypes defined in these classification schemes and to define the contribution of immunophenotype to clinically relevant subclassification. All categories in all classifications showed some heterogeneity of antigen expression; however, antigen expression correlated better with four major subgroups defined by the Kiel classification: (1) CD5+ CD10- CD23+ CD43+: chronic lymphocytic leukemia (CLL); (2) CD5+ CD10-/+CD23- CD43+: centrocytic (mantle cell) lymphoma; (3) CD5- CD10+/- CD23-/+ CD43-: centroblastic/centrocytic (CB/CC) lymphoma; and (4) CD5- CD10- CD23-/+CD43-/+: immunocytoma, mucosa-associated lymphoid tissue (MALT)-type, and monocytoid B-cell lymphoma. These subgroups had distinctive clinical features. Patients with centrocytic lymphoma were predominantly male (5.5:1) and had a significantly worse probability of survival than those with either CLL or MALT-type lymphoma (P = 0.001). The group with CB/CC lymphoma had an equal male-female ratio and an intermediate prognosis. Most patients with MALT-type and nodal monocytoid B-cell lymphomas were female (2:1); the disease-free survival for patients with extranodal MALT-type lymphoma was significantly better than that for all patients with other lymphoma subtypes except CB/CC (P < 0.01). The group with non-MALT immunocytoma had a slight male predominance, a high frequency of monoclonal gammopathy, and an intermediate prognosis. In differential diagnosis, CD23 was useful in distinguishing B-cell CLL from centrocytic lymphoma (P < 0.0001); CD5 (P < 0.0001), CD6 (P < 0.005), and CD43 (P < 0.0001) distinguish centrocytic lymphoma from CB/CC lymphoma; and CD10 (P < 0.005), CD43 (P = 0.06), Leu-8 (P = 0.08), and Ig heavy chain (P = 0.01) may help distinguish CB/CC lymphoma from immunocytoma, monocytoid B-cell lymphoma, and MALT-type lymphoma. Differences in antigen expression and clinical features among these Kiel classification subgroups suggest that they represent distinct biologic entities. The Working Formulation categories do not delineate these diseases clearly.

Monocytoid B-cell lymphoma with a distinctive clinical presentation

Monocytoid B-cell lymphoma (MBCL) is a recently described non-Hodgkin's lymphoma. Patients with MBCL usually present with localized or generalized lymphadenopathy; peripheral blood and bone marrow involvement is rare. Patients with leukemic manifestations typically have advanced disease with extensive lymph node and bone marrow involvement. We report a distinctively unusual case of MBCL with peripheral blood and splenic involvement at presentation and with no evidence of peripheral lymph node disease. This case emphasizes the fact that malignancies of monocytoid B cells should be viewed as a spectrum of disease that ranges from leukemia to lymphoma. This feature is similar to other low-grade B-cell neoplasms, such as chronic lymphocytic leukemia/small cell lymphoma, lymphocytic type.

Monocytoid B-Cell Lymphoma

Monocytoid B-cell lymphoma is a distinct clinicopathologic entity occurring primarily in the lymph nodes of elderly patients. Its unique features compared with other low-grade lymphomas are also its characteristic morphologic features. These are its rare leukemic conversion and infrequent bone marrow involvement, and its relatively common association with autoimmune disease. Although MBCL is believed to be a low-grade, indolent type of lymphoma, its progression to high-grade lymphoma warrants close follow-up of patients.

Monocytoid B-cell lymphoma: Its relationship to and possible cellular origin from marginal zone cells

Monocytoid B-cell lymphoma, the neoplastic counterpart of the monocytoid B cells, is a now well-recognized variant of low-grade, malignant B-cell lymphomas. However, monocytoid B-cell lymphomas state of differentiation, its cellular origin, and its relationship to other B-cell compartments are still obscure. We investigated an unusual case of monocytoid B-cell lymphoma with generalized disease at presentation, including infiltration of the abdominal lymph nodes, spleen, liver, and bone marrow, as well as involvement of the peripheral blood. The tumor showed the typical sinusoidal and perifollicular growth pattern in the lymph nodes. In the spleen the main infiltrate was confined to the marginal zone. These features and the characteristic immunoreactivity of the tumor cells (KiM1P+, KiB3−) in our case suggest that monocytoid B cells and their neoplastic counterparts are closely related to and probably derived from marginal zone cells.

Rheumatic manifestations of neoplasia

Recent literature on the rheumatic manifestations of neoplasia has again focused on the increased association of Sjögren's syndrome and rheumatoid arthritis with lymphoproliferative malignancies and leukemias. A series of 13 patients with monocytoid B-cell lymphoma, a recently described variant of low-grade B-cell lymphoma, and Sjögren's syndrome was reported. The skeletal manifestations of leukemias are extensively reviewed emphasizing that osteoarticular manifestations may predate the hematologic disease. A case of monoarthritis of the knee as a manifestation of chronic leukemia is presented in which synovial biopsy revealed a leukemic infiltrate. Recent studies looking at the association of polymyositis and dermatomyositis with malignancy challenge this link. Two cases of malignancy presenting with polyarthritis are reviewed, and in both cases the polyarthritis resolved with removal of the tumor. A case report and a series of synovial sarcomas are also reviewed. Hodgkin's disease can initially present with skeletal involvement; six cases are reviewed.

Ｍｏｎｏｃｙｔｏｉｄ Ｂ‐Ｃｅｌｌ Ｌｙｍｐｈｏｍａ 本邦４７例の臨床病理学的検討並びにいわゆるＭＡＬＴ ｌｙｍｐｈｏｍａとの異同について

In order to characterize whether a recently proposed monocytoid B-cell lymphoma (MBCL) is a distinct clinicopathologic entity, cases were collected from the two lymphoma files (K.N. and H.N.). The diagnosis of MBCL was based primarily on the described criteria, but several other limitations were also applied to increase the accuracy of case selection. By clinicopathologic features of 47 cases collected together with review of the literature, it is confirmed that a low-grade non-Hodgkin's lymphoma (NHL) which is difficult to be characterized based on the currently used classification systems does exist. However, the clinicopathologic features of MBCL were more heterogeneous than initially thought. Although MBCL and low-grade B-cell NHL arising from the mucosa-associated lymphoid tissue should be separated for the managements of patients with these NHLs, several lines of evidence indicate that these two NHLs are hematopathologically identical. It is stressed that NHLs should be classified based on the cells of origin, but not on the organs or systems involved.

Lack of evidence of Epstein-Barr virus in hairy cell leukemia and monocytoid B-cell lymphoma

An association between the Epstein-Barr virus (EBV) and hairy cell leukemia (HCL) has been reported. Due to the similarities between HCL and monocytoid B-cell lymphoma (MBCL), an association between EBV and MBCL has been postulated. To address these issues we studied 27 spleens from cases with HCL and 13 tissue specimens from cases with MBCL from various sites for evidence of EBV DNA and RNA by in situ hybridization. Using a genomic EBV internal repeat probe and an oligonucleotide probe directed against the EBER1 gene, we were unable to identify EBV DNA or RNA, respectively, in the tumor cells of any of the cases. The results of our study suggest that EBV may not be strongly linked with either HCL or MBCL.

The morphological spectrum of monocytoid B-cell lymphoma and its relationship to lymphomas of mucosa-associated lymphoid tissue.

We report 10 cases of monocytoid B-cell lymphoma, five of which had extranodal lymphomas of mucosa-associated lymphoid tissue (MALT) type. In one patient the MALT lymphoma in the salivary gland was microscopic. In another, the small bowel lymphoma, which preceded the monocytoid B-cell lymphoma by 11 years, showed different clonal immunoglobulin gene rearrangements. Attention is drawn to the extreme degree of plasmacytic differentiation and epithelioid cell infiltration that may occur in monocytoid B-cell lymphoma. In addition to the cytological and immunophenotypic likeness of monocytoid B-cells and centrocyte-like cells, monocytoid B-cell and MALT lymphomas share a number of micro-anatomical and behavioural characteristics. These include the sharp separation of the monocytoid B-cells and plasma cells, follicular colonization and progression to high-grade lymphoma. It is suggested that the frequent association of monocytoid B-cell lymphoma with Sjögren's syndrome may be due to the fact that the salivary glands drain to cervical lymph nodes that are part of the systemic, rather than the mucosal, lymphocyte circulation pathway.