Marina Narbaitz

Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients

Diffuse large B‐cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult non‐Hodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein‐Barr virus (EBV)+ DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV+ DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T‐cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real‐time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T‐cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV+ DLBCL, with ≥20% of EBERs+ cells. These findings suggest that EBV+ DLBCL in our series was similar to the previously described in Asia and Latin‐America, displaying latency II or III expression profile and no age‐specific characteristics. Finally, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal.

Epstein-Barr virus presence in pediatric diffuse large B-cell lymphoma reveals a particular association and latency patterns: analysis of viral role in tumor microenvironment.

Non‐Hodgkins lymphoma represents 6–10% of pediatric malignancies, and diffuse large B‐cell lymphoma (DLBCL) is one of the three major subtypes. The 2008 WHO classification included a new entity, Epstein–Barr virus (EBV)‐positive DLBCL of the elderly, affecting patients >50 years. It has been demonstrated that EBV may play a role in tumor microenvironment composition, disturbing antitumor immune response and disease progression. As most studies were performed in adults, our aim was to assess EBV presence and latency pattern, as well as T‐cell microenvironment in a pediatric DLBCL series of Argentina. The study was conducted on formalin‐fixed paraffin‐embedded biopsies from 25 DLBCL patients. EBV‐encoded small nuclear early regions (EBERs) expression was performed by in situ hybridization, whereas EBV gene expression was analyzed using real‐time PCR. Epstein–Barr virus latent membrane proteins (LMP)1, LMP2A, CD3, CD4, CD8 and Foxp3 expression were assessed by immunohistochemistry (IHC). Forty percent of cases showed EBV expression, with a significantly higher incidence among patients <10 years (p = 0.018), and with immunosuppressed (p = 0.023). T‐cell subsets were not altered by EBV presence. Full EBV latency antigen expression (latency type III) was the most frequently pattern observed, together with BZLF1 lytic gene expression. One patient showed II‐like pattern (LMP1 without LMP2A expression). Based exclusively on IHC, some patients showed latency II/III (EBERs and LMP1 expression) or I (EBERs only). These findings suggest that EBV association in our series was higher than the previously demonstrated for elderly DLBCL and that EBV latency pattern could be more complex from those previously observed. Therefore, EBV could be an important cofactor in pediatric DLBCL lymphomagenesis.

Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein–Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.

Oral cavity and extra-oral plasmablastic lymphomas in AIDS patients: report of five cases and review of the literature

Plasmablastic lymphoma (PBL) is a distinct disease entity of the diffuse large B-cell lymphoma, which often occurs in HIV-positive patients. The immunophenotype of this lymphoid neoplasm is characterized by the presence of plasma cell-associated markers VS38c and CD138 antigens and the absence of B-cell markers such as CD20 and CD45. The most frequent site of involvement is the oral cavity and the jaw, while several reports describe the development of PBL in extra-oral sites including the lymph nodes, the anal canal, the soft tissue, the skin and the gastrointestinal tract as less frequent. Epstein−Barr virus is often associated with PBL pathogenesis and the neoplastic cells contain this virus genome. Here we review the epidemiological, clinical, immunological, histopathological and virological characteristics and their prognosis and outcome in a series of five patients with diagnoses of HIV/AIDS and PBL.

Endobronchial leiomyoma: an unusual non-defining neoplasm in a patient with AIDS

Smooth muscle neoplasms are more frequent in human immunodeficiency infected children than in HIV seropositive adults. Endobronchial leiomyoma is a rare benign tumor in HIV infected adult patients. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of these tumors. Here we describe an adult patient with HIV infection with atelectasis of the left upper pulmonary lobe as the first clinical expression of an intrabronchial leiomyoma. In this case, we can not show the association with EBV. Our report suggests that smooth muscle tumors as leiomyoma should be included in the differential diagnosis of endobronchial masses in AIDS patients.

Burkitt's lymphoma of the duodenum in a patient with AIDS

Non-Hodgkins lymphoma of B-cell type is the second most common neoplasm after Kaposis sarcoma, among patients with human immunodeficiency virus infection. Most non-Hodgkins lymphoma cases that are associated with acquired immunodeficiency syndrome involve extranodal sites, especially the digestive tract and the central nervous system. We report a case of primary lymphoma of the duodenum in a patient with AIDS. Upper gastrointestinal endoscopy revealed pseudopolypoid masses found in the second portion of the duodenum. A complete diagnostic study including histological, immunohistochemical and virological analyses showed high-grade B-cell Burkitts lymphoma. The Epstein-Barr virus genome was detected in biopsies by immunohistochemical and in situ hybridization.

IgA from HIV+ haemophilic patients triggers intracellular signals coupled to the cholinergic system of the intestine

IgA was obtained from HIV‐infected haemophilic patients and the intracellular signals triggered by its reaction with isolated rat intestinal strips were studied. HTV+ IgA stained intestinal microvilli with a granular immunofluorescence pattern and bound to the muscarinic acetylcholine receptor (mAChR), displacing the specific muscarinic cholinergic antagonist QNB in a non‐competitive manner. It triggered the signals that are the consequence of mAChR stimulation in die intestine. Thus, it decreased cAMP synthesis and increased guanosine 3′:5′‐cyclic monophosphate (cGMP) formation and phosphoinositide (PI) turnover of the intestine. In addition, it stimulated prostaglandin E2 (PGE2) synthesis by intestinal strips. Through its effect on PGE2 synthesis, HIV+ IgA could have a dual action. On the one hand, it could enhance immunosuppression at a local level, favouring pathogen growth and subsequent intestinal dysfunction. On the other hand, PGE2 could directly increase intestinal motility and electrolyte/fluid loss. Both effects could be involved in intestinal damage in AIDS.

Soft-tissue masses as presentation of non-Hodgkin's lymphoma in AIDS patients.

Primary soft tissue Non-Hodgkin lymphomas are very rare and account only for 0.1 % of the cases. Generally, Non-Hodgkin lymphomas of the soft tissue present as large subcutaneous masses without evidence of nodal or skin involvement. We describe four cases of primary Non-Hodgkin lymphomas of the soft tissue in patients infected with the human immunodeficiency virus. The most common site of involvement was the chest wall in all the patients; histopathological and immunophenotypic examination of the biopsy smears revealed two cases of plasmablastic lymphomas, one Burkitt and one diffuse large B-cell lymphoma. Non-Hodgkin lymphomas should be included in the differential diagnosis of soft tissue masses in human immunodeficiency virus - seropositive patients.

Central nervous system involvement in Hodgkin's lymphoma associated with Epstein-Barr virus in a patient with AIDS: case report and review of the literature

Intracranial and intraspinal involvement is a rare complication of Hodgkins disease. We report a case of a patient with diagnosis of AIDS and Hodgkins lymphoma who developed brain and spinal involvement at the time of the relapse of the neoplasm disease. Mixed cellularity histology was the subtype of Hodgkins disease in our patient; we identified the Epstein-Barr virus genome in the Reed-Sternberg cells by immunohistochemistry and in situ hybridization.

Primary extranodal non-hodgkin lymphoma of the head and neck in patients with acquired immunodeficiency syndrome: a clinicopathologic study of 24 patients in a single hospital of infectious diseases in Argentina.

Introduction Extranodal non-Hodgkin lymphomas (NHLs) are commonly described in patients with acquired immunodeficiency syndrome (AIDS) and are related with an atypical morphology and aggressive clinical course. AIDS-associated lymphomas are characterized by their rapid progression, frequent extranodal manifestations, and poor outcome. Objective The aim of this article is to remake the clinical features of head and neck (HN) NHL in patients with AIDS to facilitate early diagnosis and treatment. Methods We evaluated the epidemiologic, clinical, immunologic, virologic, and histopathologic characteristics of 24 patients with human immunodeficiency virus (HIV)/AIDS with primary HN NHL treated at a single institution between 2002 and 2012. Histopathologic diagnosis was made according to the criteria of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. Additional immunohistochemical stains were applied in all cases. Results Eighteen patients (75%) were men and the median of age was 39 years. The gingiva and the hard palate were the most common sites of the lesions (15 patients, 62.5%). Lactate dehydrogenase levels were elevated in 16 cases (84%). Bone marrow infiltration was detected only in 4 cases (16.6%). The median CD4 T-cell count was 100 cells/µL. According to the histopathologic evaluation, the most common subtype was diffuse large B-cell lymphoma (12 cases, 50%), followed by plasmablastic lymphoma (9 cases, 37.5%) and Burkitt lymphoma (3 cases, 12.5%). Conclusion HN NHL is a severe complication of advanced HIV/AIDS disease. Early diagnosis followed by chemotherapy plus highly active antiretroviral treatment is necessary to improve the prognosis and the survival of these patients.