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.     

淋巴结单核细胞样B细胞反应性结节性增生

1．病例简介：患者女,30岁。发现右侧颈部淋巴结肿大2d。无发热及其他不适,故未行特殊检查。临床诊断：右颈部淋巴结肿大。     

Follicular lymphoma with monocytoid B-cell proliferation: molecular assessment of the clonal relationship between the follicular and monocytoid B-cell components

Although a number of studies have recognized that follicular lymphomas may be accompanied by a prominent proliferation of monocytoid B-cells, the clonal relationship between these components has not been adequately assessed. Using laser capture microdissection, we isolated the follicular and monocytoid B-cell components from four well-characterized cases of follicular lymphoma with prominent monocytoid B-cells. DNA from each component was analyzed using polymerase chain reaction (PCR)-based methods to assess for clonal rearrangements of the immunoglobulin heavy chain gene (IgH) and for the presence of the bcl-2 gene major breakpoint region/joining region (MBR/JH) DNA fusion products by conventional PCR and fluorescence melting curve analysis. Evidence of clonal identity was established in the follicular and monocytoid B-cell components of three cases by demonstration of IgH gene rearrangements of identical size using IgH PCR, by comparison of complementarity determining region III (CDRIII) DNA sequences, or by detection of bcl-2 MBR/JH fusion products of identical size and/or melting temperature. Molecular analysis of the fourth case revealed a monoclonal and MBR/JH-positive follicular component accompanied by a polyclonal and MBR/JH-negative monocytoid B-cell proliferation. We conclude that the follicular and monocytoid B-cell components of this variant of follicular lymphoma are clonally identical in the majority of cases. However, in a minority of these cases, the monocytoid B-cell component is reactive. Larger studies that assess the prognostic significance of follicular lymphoma with monocytoid B-cells will benefit from molecular studies that assess the clonal relationship of both components.     

Hodgkin's disease, lymphocyte-predominant type: immunoreactivity with B-cell antibodies

Utilizing the monoclonal antibodies L26 (a new antibody possessing immunoreactivity with B-lymphocytes in paraffin-embedded tissue), LN1, LN2, and Leu-M1, 44 cases of Hodgkin's disease (HD) were examined for the presence of immunoreactivity in Reed-Sternberg (R-S) cells by the avidin-biotin-peroxidase complex (ABC) technique. In 16 cases of lymphocyte-predominant Hodgkin's disease (LPHD), the L&H variants of R-S cells exhibited a different pattern of staining compared to R-S cells in other histologic types (total, 28 cases: 11, mixed cellularity; 8, nodular sclerosing; 6, lymphocyte depleted; 3, unclassified). L&H variants in LPHD were immunoreactive for L26 and LN1 in 15 and 14 cases, respectively, whereas R-S cells in the remaining types were negative or rarely positive (3, L26; 2, LN1). Leu-M1 was strongly positive in 27 of 28 cases of non-LPHD versus only 4 of 16 in LPHD. LN2 was reactive in virtually all cases (43 of 44). These findings suggest the possibility that the R-S cells of LPHD are derived from a different lineage than R-S cells in other histologic types of HD or that the latter have somehow lost the ability to express the antigens defined by L26 and LN1. Finally, based on immunologic and morphologic findings in this study, the similarities seen between the nodular and diffuse subtypes of LPHD are felt to favor a close relationship between the two subtypes.     

Varied B-cell immunophenotypes of Hodgkin/Reed-Sternberg cells in classic Hodgkin's disease

AIMS: Recent analyses have suggested that Hodgkin's or Reed-Sternberg (HRS) cells in most cases of classic Hodgkin's disease are derived from germinal centre B-cells. However, there is controversy over which B-cell antigens are expressed in HRS cells. METHODS AND RESULTS: We studied 51 cases of classic Hodgkin's disease to immunohistochemically characterize HRS cells for pan-B-cell markers and specific markers for plasma cells. HRS cells expressed CD20 (L26) in 18 cases (35%), CD19 (B4) in nine (18%) and CD79a (mb-1) in 13 (25%). Furthermore, HRS cells were positive for CD138 (B-B4) in 24 cases (45%) and for PCA-1 in 24 (45%). In 41 (80%) cases, HRS cells expressed more than one B-cell marker. We then subclassified cases into those positive for plasma cell markers (n = 27) (group 1) and those negative for them (n = 24) (group 2). The average age in group 1 (40 years) was younger than in group 2 (54 years) (P < 0.05). The percentage of nodular sclerosis (NS) subtype in group 1 (52%) was 1.5 times greater than in group 2 (33%) (P < 0.05). With regard to Epstein-Barr virus encoded small RNA (EBER) in-situ hybridization, 14 cases (64%) were positive in group 2, but only seven cases (31%) were positive in group 1 (P < 0.025). CONCLUSION: In most cases of classic Hodgkin's disease, HRS cells expressed later stage of B-cell development. We consider that two different clinicopathological groups may correlate with the two different expressions of B-cell markers.     

Rearrangement of the beta T-cell receptor gene in a monocytoid B-cell lymphoma

We describe an unusual case of monocytoid lymphoma displaying a rearrangement of the T-cell receptor beta-chain gene associated with a rearrangement of the immunoglobulin heavy-chain gene, and of the lambda light-chain gene. This lymphoma was morphologically similar to previous cases in the literature, and was clinically of low grade. The lymphoma expressed the lambda light chain, HLA-DR, CD21, and CD22. Though the B-cell lineage of this lymphoma seems very likely, the genotypic profile raises a cautionary note regarding the supposed high stage of differentiation of monocytoid lymphomas.     

Large B-cell lymphoma with Hodgkin's features

AIMS: To describe the features of a series of nine cases of diffuse large B-cell lymphoma (DLBCL) showing morphological and immunophenotypic features that are intermediate with Hodgkin's lymphoma (HL). METHODS AND RESULTS: Most cases (6/9) presented as mediastinal tumours affecting young males, while the other three cases arose in extramediastinal locations. Histopathologically, tumours showed diffuse large cell areas in a polymorphous background, with pleomorphic cytology and the common presence of Hodgkin's and Reed-Sternberg cells. Immunophenotypically, tumours shared features of DLBCL and classical HL, with expression of CD30, CD15 (6/9), and a full B-cell profile including CD45RB, CD20, CD79a and OCT2. Epstein-Barr virus-latent membrane protein expression was found in 2/9 cases. The majority of tumours had immunohistochemical features consistent with activation of the NF-(kappa)B pathway, including nuclear location of the c-REL/p65 subunit, overexpression of phosphorylated I(kappa)B(alpha), and overexpression of NF-(kappa)B targets. Finally, 2/9 cases showed 3q27 (BCL6) rearrangement, and 1/9 had p53 gene mutations, both of which are rarely detected in classical HL. CONCLUSIONS: These findings suggest that DLBCLs with HL features constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth and peculiar characteristics could be facilitated by a particular microenvironment found in the mediastinum.     

Absence of B-cell or T-cell clonal expansion in nodular, lymphocyte predominant Hodgkin's disease

Recent studies based upon immunophenotypic data have provided strong evidence that nodular lymphocyte predominant Hodgkin's disease (NLPHD) represents an entity that is distinct from other subtypes of Hodgkin's disease (HD). In contract to other forms of HD, the predominance of B-lymphocytes in NLPHD has prompted the thesis that this lesion is actually an atypical B-cell hyperplasia or follicular center cell lymphoma. Three cases of NLPHD by restriction endonuclease analysis were studied in an attempt to identify a clonal B-cell or T-cell expansion in this disorder. DNA was extracted from these tumors and hybridized to probes for the immunoglobulin genes (C kappa, C lambda, JH) and the T-cell receptor beta chain gene. Gene rearrangements were not detectable in any of the cases. The results provide genotypic evidence that there is not a monoclonal or oligoclonal proliferation of small B-lymphocytes or T-lymphocytes in NLPHD. The possibility that the L&H Reed-Sternberg cells are monoclonal cannot be excluded because their small number is below the level of sensitivity of this technique.     

Transformation of monocytoid B-cell lymphoma to large cell lymphoma associated with crystal-storing histiocytes

We report a case of crystal-storing histiocytosis associated with large cell lymphoma in a patient with a history of monocytoid B-cell lymphoma 10 years previously. The cervical lymph node biopsy showed a diffuse proliferation of large lymphocytes with vesicular nuclear chromatin and distinct nucleoli. These lymphocytes were associated with numerous immunoglobulin lambda light-chain crystal-storing histiocytes, which morphologically resembled rhabdomyoblasts. Occasional lymphoid cells also showed large immunoglobulin crystals. This case establishes the association of crystal-storing histiocytes with lymphomas of mucosa-associated lymphoid tissue and emphasizes the need for immunophenotyping to distinguish these unusual cases from other tumors, particularly adult rhabdomyomas.     

Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma

BACKGROUND: Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells. METHODS: We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced. RESULTS: In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type. CONCLUSIONS: In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.     

The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease

Recent evidence indicates that membrane-bound immunoglobulin on B lymphocytes is associated with a molecule which comprises the products of the mb-1 and B29 genes. This molecule is a highly specific marker for B-cells, presumably because of its central functional role in antigen triggering, and has recently been clustered as CD79a at the 5th Leucocyte Workshop. Recently there has been controversy surrounding reports of B-cell antigen expression by Reed–Sternberg and related cells, and we have therefore studied 108 cases of Hodgkin's disease immunohistochemically using a novel antibody which detects mb-1 protein in paraffin sections. The results were compared with those achieved using antibody L26 to detect CD20. The mb-1 protein was present in the neoplastic cells in all 14 cases of lymphocyte predominance Hodgkin's disease studied, and CD20 immunoreactivity was also found in seven of the eight cases of this subtype studied. Of the non-lymphocyte predominance cases, 20% (19/94) expressed mb-1 and 30% (20/67) CD20 in the Reed–Sternberg cells, but the cells positive for either of these two markers usually constituted only a very small proportion of the neoplastic population. However, in occasional cases (one of 94 for mb-1 and five of 67 for CD20), more than 50% of the neoplastic cells expressed one or both B-cell antigens. These results confirm the B-cell origin of the neoplastic cells in lymphocyte predominance Hodgkin's disease, but they also indicate that, contrary to our previous study, mb-1 expression may occasionally be found in what appears, on histological grounds, to be other types of Hodgkin's disease.     

Leu 7 (CD57) reactivity distinguishes nodular lymphocyte predominance Hodgkin's disease from nodular sclerosing Hodgkin's disease, T-cell-rich B-cell lymphoma and follicular lymphoma.

Several recent reports have suggested that nodular lymphocyte predominance Hodgkin's disease (NLPHD) may be distinct from other forms of Hodgkin's disease and may be more closely related to B-cell non-Hodgkin's lymphoma. This is primarily based on immunophenotypic studies that have shown that the L & H cells in NLPHD demonstrate a B-cell phenotype. In 1989, Poppema reported that the T cells in NLPHD differ from T cells in other forms of Hodgkin's disease in that they demonstrate reactivity for Leu 7 (CD57). In this study we tested the hypothesis that Leu 7 (CD57) reactivity of small lymphocytes in NLPHD is an immunophenotypic feature that distinguishes NLPHD from nodular sclerosing Hodgkin's disease and from certain B-cell lymphomas that may histologically simulate NLPHD, namely T-cell-rich B-cell lymphoma and follicular lymphoma. Using an image analysis method, we found Leu 7 (CD57) reactivity in an average of 18.9% of the small lymphocytes in the nodules of NLPHD compared with 3.9% in nodular sclerosing Hodgkin's disease, 4.3% in T-cell-rich B-cell lymphoma, and 2.1% in follicular lymphoma. Moreover, Leu 7 (CD57)-reactive small lymphocytes often showed a distinctive pattern in NLPHD, forming a ring of cells around the large L & H cells. While scattered Leu 7 (CD57)-reactive lymphocytes were found in the other disorders, the percentage of reactive cells and the pattern of reactivity were significantly different in NLPHD. These results suggest that Leu 7 (CD57) reactivity may be used as an additional immunophenotypic criterion in distinguishing NLPHD from nodular sclerosing Hodgkin's disease, T-cell-rich B-cell lymphoma, and follicular lymphoma. The clinical and biological significance of Leu 7 (CD57) reactivity of small lymphocytes in NLPHD merits further investigation.