Primary mediastinal large B-cell lymphoma in HIV: report of two cases
Primary mediastinal large B cell lymphoma (PMLBCL) is a subtype of diffuse large B cell lymphoma arising in the mediastinum with distinctive clinical and morphological features. Though diffuse large B cell lymphoma is one of the most common non-Hodgkin lymphoma associated with AIDS, there are no data available regarding the association of HIV and PMLBCL. We report here two cases of PMLBCL arising in AIDS patients. In both cases, PMLBCL presented in a setting of low CD4 T-cell count as rapidly enlarging mediastinal mass. The morphologic and immunophenotypic findings are characteristic of PMLBCL. One of the two patients, a 25-year-old woman who had localized disease and evidence of Epstein–Barr virus in lymphoma cells, did not respond to chemotherapy and died of disease progression 5 months after diagnosis. The second patient, a 38-year-old male with disseminated disease, responded to therapy and is disease-free after 9 months of follow-up.
KeywordsPrimary Mediastinal Large B Cell Lymphoma HIV EBV
The incidence of non-Hodgkin lymphoma (NHL) is 100–200-fold higher in HIV-infected individuals than in the general population. NHL is an AIDS-defining illness and in 3–5% of cases, the lymphoma is the initial manifestation of AIDS . The most common HIV-associated lymphomas are diffuse large B cell lymphoma (DLBCL; often primary in the central nervous system), Burkitt lymphoma, primary effusion lymphoma, and plasmablastic lymphoma of the oral cavity . Primary mediastinal large B cell lymphoma is a subtype of diffuse large B cell lymphoma arising in the mediastinum with distinctive clinical, morphologic, and genotypic features . Most patients are young adult females presenting with localized mediastinal mass and symptoms often related to local effects of the large mediastinal tumor such as superior vena cava syndrome. DLBCL is one of the most common lymphomas in the setting of HIV, but the incidence of PMLBCL in HIV is not well established. Only one reported case of HIV-associated PMLBCL has been found in the English literature . We report here two additional cases of PMLBCL arising in AIDS patients.
The World Health Organization classification of hematopoietic malignancies recognizes AIDS-associated lymphomas as a specific category to acknowledge the significant impact of HIV on the pathophysiology and prognosis of lymphomas . The pathogenetic mechanisms contributing to lymphoma genesis are complex and include chronic antigen stimulation, genetic abnormalities, cytokine dysregulation, and the role of herpes viruses: Epstein–Barr virus (EBV) and Kaposi Sarcoma Human Virus (KSHV, HHV8) . The overall survival of patients with HIV-related NHLs is inferior compared to HIV-negative patients, and in HIV, the majority of patients present with widespread disease and with higher risk for central nervous system involvement. The introduction of HAART extended the lifespan of AIDS patients and some studies indicated a decrease of the incidence of lymphomas in AIDS since widespread availability of HAART . The combination of HAART with aggressive chemotherapy, such as CHOP, not only is tolerable and effective treatment in patients with HIV and NHL but the initial good response to HAART is also associated with higher complete response rates to the chemotherapy (77% response to CHOP versus 50% in nonresponders) . The association between HIV and classical Hodgkin lymphoma is less clear, and, unexpectedly, the incidence of Hodgkin lymphoma in AIDS has increased since HAART was introduced . Of note, HIV-related Hodgkin lymphoma is associated with EBV in nearly all cases , and it has been postulated that the EBV-encoded latent membrane protein (LMP1; which is functionally homologous to activated CD40), is essential to the antiapoptotic phenotype of the Reed–Sternberg cells, replacing the CD40/CD40 ligand interaction by CD4+ T cells, which are decreased in AIDS .
Though diffuse large B cell lymphoma is one of the most common NHL associated with AIDS, there are virtually no data available about the association of HIV and PMLBCL. So far, only one case of PMLBCL has been described in the literature in the setting of AIDS . This patient, a 29-year-old woman with 12 years of history of HIV infection without prior AIDS-defining illness, presented with fever, night sweats, cough, and a CD4 count of 316/μL. HAART therapy was initiated but had to be discontinued within a few days due to development of Stevens–Johnson syndrome. Biopsies via mediastinotomy established the diagnosis of PMLBCL, with no evidence of extrathoracic disease upon staging. Chemotherapy with CHOP and granulocyte colony-stimulating factor was started; however, 6 days after the first cycle of treatment, the patient died from neutropenic sepsis.
Comparison of the clinical features of Case 1, Case 2, and the case reported by Milling et al. 2004
Case reported by Millings et al. 2004
Shortness of breath, cough, chest pain
Shortness of breath, fever, night sweats
Fever, night sweats and cough
Duration of HIV+ status
Prior therapy for HIV
CD4 count at presentation
LDH at presentation
379 IU/L (high)
886 IU/L (high)
542 IU/L (high)
Stage of disease
Bone marrow involvement
Pleural masses, pleural effusions, left lung nodule
Pleural effusion, left lung nodules, multifocal abdominal and acetabular masses
HAART, 3 cycles of EPOCH then VP-16, ifosfamide, ARA-C, mesna
HAART, 6 cycles of Rituxan-Hyper CVAD
1 cycle of CHOP and G-CSF
Death 5 months after diagnosis
No detectable disease after 9 months follow-up
Death 6 days after chemotherapy
In summary, though increased incidence of PMLBCL has not been established in AIDS due to the rarity of these cases, PMLBCL occurs in HIV and appears to present in the setting of low CD4 T-cell count as a rapidly growing mediastinal mass. A good response to a combination of HAART and chemotherapy can be obtained even in cases with widespread disease. More cases are necessary to characterize the relationship between PMLBCL and HIV and to determine the impact of EBV infection on disease pathogenesis and prognosis in the immunocompromised.
Conflict of interest
The authors have no conflict of interest.
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