Pathological, Immunological, and Molecular Features of Hodgkin's Disease Associated with HIV Infection

Abstract

The aim of the present study was to analyze in a series of 24 HIV-positive Hodgkin's disease (HD) patients the morphological and immunological features, the presence of rearrangements in the immunoglobulin heavy chain (IgH) gene, expression of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1), and the existence of deletions in the intracytoplasmic domain of the LMP-1 gene. The results obtained were compared with those from a parallel series of 56 patients with ordinary HD. Briefly, comparison of the two series showed a predominance of unfavorable histological subtypes in HIV-positive HD patients. The mixed cellularity subtype was more frequent in HIV-positive than in HIV-negative HD patients: the difference in percentage was statistically significant (p = 0.04). Neoplastic cell-rich cases were significantly more frequent (p = 0.40) in HIV patients (59%) than in ordinary HD patients (34%). In 25% of HIV-infected and in 14% of ordinary HD patients, the neoplastic cells were CD20+, a difference that was not statistically representative. Clonal IgH rearrangements were detected in 33% of HIV-infected patients and in 23% of ordinary HD patients, a nonsignificant difference. LMP-1 expression was detected in 100% of HIV-positive patients and in 57% of ordinary HD patients (p = 0.004). A 30-base-pair deletion in the carboxy-terminal domain of the LMP-1 gene was found in 16 of 18 HIV-infected patients (89%), whereas it was identified in only 8 of 25 ordinary HD patients (32%) (p = 0.008). In conclusion, HD in HIV-infected patients as compared with HD in HIV-negative individuals is associated with morphological features of aggressivity, with a higher frequency of neoplastic cells, and with constant LMP-1 expression. The fact that LMP-1 is expressed in all HIV-infected patients suggests that EBV plays an etiological role in the pathogenesis of HIV-associated HD. Furthermore, the presence of EBV strains carrying deletions near the 3' end of the LMP-1 gene in the majority of cases may be related with the morphological and clinical aggressivity of HD in immunocompromised patients.

Latent Membrane Protein 1 Deletion Mutants Accumulate in Reed-Sternberg Cells of Human Immunodeficiency Virus-Related Hodgkin's Lymphoma

“…Twenty-nine of the 31 informative HIV-HL cases (93.5%) carried the 30-bp (28 cases) or the 69-bp (1 case) LMP-1 deletion variants, confirming also in this series the high prevalence of LMP-1 deletions previously found in patients with this disease (2,8,23) (Table 1). In 17 of the 28 cases carrying the 30-bp deletion (60.7%), faint bands corresponding to full-length LMP-1 variants were also detected, although only at low dilutions of template DNA, indicating a likely derivation from EBV-positive bystander B cells.…”

“…Interestingly, this region is highly heterogeneous across diverse isolates, showing clustered point mutations, insertions, and in-frame 30-or 69-bp deletions (3,17,30). A high prevalence of the 30-bp LMP-1 deletion mutants was reported in undifferentiated nasopharyngeal carcinoma (6,15), peripheral Tcell lymphomas (22), posttransplant lymphoproliferative disorders (25), and, particularly, in aggressive HIV-unrelated HL and HIV-HL (2,9,10,19,22), suggesting that these LMP-1 deletion mutants may have increased transforming potential. Accordingly, LMP-1 deletion forms display enhanced tumorigenicity and reduced immunogenicity compared with those of LMP-1 of strain B95.8, in animal and in vitro models (6,16,27,28).…”

Pathobiology of Classical Hodgkin Lymphoma

“…ALL/LBL = Acute lymphoblastic leukemia/lymphoblastic lymphoma; BL = Burkitt's lymphoma; DLBCL = diffuse large B-cell lymphoma; FL = follicular lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma; NHL = non-Hodgkin lymphoma; SLL = small lymphocytic lymphoma. ficiency syndrome (AIDS) [34,[58][59][60] , 7-fold in siblings ! 45 years of age [61] , 6-fold in patients who have undergone allogenic bone marrow transplantation [62] , as well as in patients with the autoimmune lymphoproliferative (Canale-Smith) syndrome [63][64][65] and multiple sclerosis [66] .…”

“…As mentioned previously, immunosuppression, and particularly AIDS, increases the risk of developing cHL [34,[58][59][60] . In immunocompromised patients, cHL is often aggressive and has a very poor prognosis, accompanied by a widespread disease and primary extranodal involvement.…”

Surgical Pathology in HIV Infection in the Era of Antiretroviral Therapy

“…Diagnostic criteria for LH are the same for either HIV or healthy individuals. However the most frequent subytype in HIV patients comprises the most unfavorable variants such as mixed cellularity and depletion of lymphocytes of the clasical HL(p<0.01), other features published are the abundance of a proliferation of the fibrohistiocyte stroma and a higher perecentage of Reed-Sternberg cells (Ree et al 1991;Bellas et al 1996). Relation between EBV infection and the origin of LH seems to be tighter in HIV infected patients than in the reamainder LH cases (Ree et al 1991).…”