Even with routine immunohistochemical evaluation, distinguishing classic Hodgkin lymphoma (CHL) from diffuse large B-cell lymphoma (DLBCL) or anaplastic large cell lymphoma (ALCL) can be difficult. In these cases, the transcription factors (B cell-specific activator protein [BSAP], octamer-binding transcription factor 2 [Oct-2], and B-cell Oct-binding protein 1 [BOB.1]) and the pan-B-cell markers (CD20, CD22, and CD79a) may aid in clarifying the diagnosis. In 57 cases of CHL, 5 cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), and 33 cases of non-Hodgkin lymphoma (25 DLBCL and 8 ALCL) we found the transcription factor phenotype BSAP+ and either Oct-2- or BOB.1- to be predictive of CHL; BSAP+/Oct-2+/BOB.1+ was predictive of NLPHL or DLBCL, while BSAP- was predictive of ALCL. Expression of all 3 pan-B-cell markers was seen only in NLPHL and DLBCL; positivity for a single B-cell marker was present only in CHL. Thus, together, the transcription factors and pan-B-cell markers might be useful in the differential diagnosis of CHL.
Leprosy provides a useful model for understanding immunoregulatory mechanisms in man. The disease forms a spectrum in which the immunologic response of the patient correlates with the clinical and histopathologic classification (1-3). At one end of the spectrum, patients with tuberculoid leprosy have one or several skin lesions in which bacilli can rarely be identified . CD4+ T lymphocytes predominate in these lesions (4-7) and respond to Mycobacterium leßrae in vitro (8). At the other end of the spectrum, patients with lepromatous leprosy have diffuse infiltration of skin and nerves with bacilli-laden macrophages. CD8+ cells predominate in lepromatous lesions and function as antigen-specific Ts cells in vitro (9, 10). The CD4+ lymphocytes derived from these lesions are unresponsive to M. leßrae . Imposed upon this spectrum are the so-called "reactional states" of reversal reaction and erythema nodosum leprosum (ENL)' that are of immunologic interest in understanding mechanisms of immunoregulation in man.The reversal reaction syndrome is associated with a marked rise in lymphocyte transformation to M. leßrae antigens in vitro, and is therefore thought to be a delayedtype hypersensitivity (DTH) reaction against M. leßrae antigens (11)(12)(13)(14)(15). Clinically, the condition is often associated with reduction or elimination of bacilli in lesions and sometimes followed by upgrading of the clinical and histological classification toward the tuberculoid pole. The pathogenesis of ENL reactions is somewhat controversial, thought to be due to immune complex deposition in the lesions (16-18) and/or increases in cell-mediated immunity (19,20).
Bone marrow involvement is reported in approximately 25% of patients with newly diagnosed acquired immunodeficiency syndrome-related lymphoma (ARL). Studied were 291 patients with ARL, diagnosed and treated at one medical center between 1984 and 1998. Clinical, immunologic, and pathologic characteristics of patients with bone marrow involvement were compared with those of patients without marrow involvement. Bone marrow involvement was present in 55 patients (19%). Small noncleaved lymphoma was diagnosed in 38% of the entire group and was the most common pathologic subtype in patients with bone marrow involvement (55% versus 34%; P ؍ .008). Analysis of complete blood counts revealed a median hemoglobin level of 10.6 g/dL in both marrow-positive and marrownegative groups. In contrast, a platelet count lower than 100 000/L was more common in patients with bone marrow involvement (27% versus 11%; P ؍ .02). Patients with marrow involvement were more likely to have leptomeningeal (cerebrospinal fluid [CSF]) lymphoma than patients whose marrows were uninvolved (24% versus 7%; P < .001) and were also more likely to have high lactate dehydrogenase (LDH) (P ؍ .002), bone involvement (P < .001), and/or systemic B symptoms including fever, night sweats, and/or weight loss (P ؍ .05). Median survival did not differ between marrow-positive and marrow-negative groups. On multivariate analysis, factors associated with decreased survival of marrow-positive patients included greater than 50% involvement (P ؍ .002), systemic B symptoms (P ؍ .008), and high-grade histologic type (P ؍ .035). Marrow involvement in ARL correlates with small noncleaved pathology, thrombocytopenia lower than 100 000 mm 3 , high LDH, and lymphomatous involvement of the CSF. Survival is statistically shorter in patients with greater than 50% marrow involvement, high-grade pathology, and/or systemic B symptoms. (Blood. 2001;98:2358-2363)
We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.
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