Lymph node-based disease and HHV-8/KSHV infection in HIV seronegative patients: report of three new cases of a heterogeneous group of diseases

Abstract

We describe three cases of lymph proliferative diseases characterized by the presence of lymphoma cells expressing the KSHV/HHV-8 antigen with or without EBV expression. The patients were HIV seronegative without serous effusions. One case was diagnosed as KSHV-germinotropic lymphoproliferative disorder due to the presence of atypical plasmablasts involving germinal centers. These plasmablasts were positive for MUM1 and vIL6, co-expressed EBV and LNA-1 of HHV-8/KSHV, and showed a polyclonal pattern of Ig gene rearrangements on PCR. The disease was localized and the prognosis was good. In two other cases, a diagnosis of KSHV/HHV-8-related diffuse large cell B-lymphoma morphology was made. The lymphoma cells were anaplastic or frankly pleomorphic, expressed KSHV but not EBV, and were positive for CD20, MUM1, PAX-5, and vIL6. In both cases the prognosis was poor. On the basis of the features observed, we raise three considerations: (1) KSHV-related lymphoproliferative disorders represent a distinctive and heterogeneous group of diseases with variable clinico-pathologic findings and immunophenotypes (BCL6-/MUM1+/CD138- and BCL6+/MUM1+/CD138- or BCL6-/MUM1+/CD138+). (2) Although the pathogenic mechanism of HHV8 in lymphomagenesis is unclear, the presence the viral DNA in lymph nodes of HIV- patients is not a simply opportunistic infection, but is directly implicated in the pathogenesis of KSHV-related diseases; the activation of IL-6 receptor signalling may play an important role in most cases. (3) The different prognoses among different diseases with KSHV etiology may be related to the fact that the pathogenic potential appears to be constrained by a competent immune system.

The Role of Human Herpesvirus 8 Molecular Characterization in the Management of HIV Infected Patients Diagnosed with Malignancies Associated with Its Infection

“…Now, there is a controversy around the participation of HHV-8 in NHL. In this sense, some authors have also agreed that HHV-8 DNA detection in the lymph node would be considered not only as opportunistic infection but also as an agent involved in malignant lymphoproliferation [25]. Furthermore, rare HHV-8 positive solid lymphomas have been described as extra-cavitary PELs forms [26] and Engels and colleagues have previously reported a similar case of NHL from Ugandan pediatric patient [27].…”

HHV8/EBV Coinfection Lymphoproliferative Disorder: Rare Entity with a Favorable Outcome

“…As in our case, no additional therapy was done after the lymphadenectomy in 2 cases, with a favorable course after 2 and 7 years, respectively [ 1 , 4 ]. This attitude raises questions about the accurate benefit of an adjuvant treatment in the management of this entity.…”

“…The causal relationship between HHV8 and lymphoproliferative disorder is not yet clearly elucidated [ 5 ]. According to some authors, HHV8+ lymphoproliferation may originate from B-cells at different stages of differentiation [ 4 , 5 , 7 , 9 , 10 ]. Moreover, it was suggested that the maturation stage of HHV8+ B-cells and the type of viral infection (latent or lytic) might define the pathological features of the lymphoproliferation [ 10 ].…”

“…An isolated lymphadenopathy was the initial presentation in 6 cases [ 2 , 4 – 7 ]. For the other cases, enlarged lymph nodes were associated with systemic symptoms in one case [ 1 ], to a leg swelling and paraesthesia in one case [ 2 ], and to ruptured aneurysm not related to the lymphoproliferative disorder in the third case [ 3 ].…”

Fat graft for reducing pain in chronic wounds

“…Numerous factors must be kept in mind 6 : diabetes, vascular diseases, autoimmune diseases, and other conditions can impair healing up to amputation 1 . The regenerative property of the fat was discovered several years ago: Rigotti already in 2007 understood that lipofilling improved scars in patients undergoing to radiation therapy 7 . It was thought that this effect was mediated by stem cells derived from fat 8 .…”