Oral Plasmablastic Lymphoma: A Rare Manifestation of HIV-Related Neoplasm-A Brief Clinical Study.

Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency virus-positive patients. Though the oral cavity is a common site for PBL, this condition is not commonly reported in the literature as an oral manifestation. Most oral PBLs presented as an asymptomatic swelling, frequently associated with ulcerations and bleeding. No standard treatment is yet advocated for oral PBL. Five-year survival rate was recorded not more than 33.5%. This presentation emphasizes on oral manifestation of plasmablastic lymphoma (PBL) as a rare entity, which was provisionally diagnosed for carcinoma (CA) oral cavity. A simple presentation of ulcerated growth in the upper jaw was excised for histopathologic evaluation. Subsequently, it turned out to be a rare oral manifestation of HIV-related lymphoma. It is imperative to understand simple oral presentation as a manifestation of an underlying systemic condition. With this interest, this case presentation is published with a literature review.

Human Immunodeficiency Virus Associated Plasmablastic Lymphoma Involving Bones and Peritoneum in a 4-Year-old Child.

In children with underlying Human Immunodeficiency virus infection and AIDS, hematolymphoid cancers, especially non-hodgkin lymphomas are common. Plasmablastic lymphoma is one such non-hodgkin lymphomas arising from the head and neck region (especially sinonasal) but extremely rare. We describe the clinical course in a 4-year-old boy who presented with a solitary bony swelling of the right knee joint, which on diagnostic work-up turned out to be plasmablastic lymphoma. With combination chemotherapy, intrathecal chemotherapy, and early institution ofHighly active anti-retroviral therapy, the child continues to be in remission.

Hematologic cancers in individuals infected by HIV.

HIV infection increases cancer risk and is linked to cancers associated to infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. Lymphomas represent one of the most frequent malignancies among individuals infected by HIV. Diffuse large B-cell lymphoma remains a leading cancer after the introduction of combined antiretroviral therapy (cART). The incidence of other lymphomas including Burkitt lymphoma, primary effusion lymphomas, and plasmablastic lymphoma of the oral cavity remain stable, whereas the incidence of Hodgkin lymphoma and Kaposi sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman disease has increased. The heterogeneity of lymphomas in individuals infected by HIV likely depends on the complexity of involved pathogenetic mechanisms (ie, HIV-induced immunosuppression, genetic abnormalities, cytokine dysregulation, and coinfection with the gammaherpesviruses Epstein-Barr virus and KSHV) and the dysregulation of the immune responses controlling these viruses. In the modern cART era, standard treatments for HIV-associated lymphoma including stem cell transplantation in relapsed/refractory disease mirror that of the general population. The combination of cART and antineoplastic treatments has resulted in remarkable prolongation of long-term survival. However, oncolytic and immunotherapic strategies and therapies targeting specific viral oncogenes will need to be developed.

[Human immunodeficiency virus and lymphoma]. / Virus de l'immunodéficience humaine et lymphome.

Lymphomas remain a leading cause of morbidity and mortality for HIV-positive patients. The most common lymphomas include diffuse large B-cell lymphoma, Burkitt lymphoma, primary effusion lymphoma, plasmablastic lymphoma and Hodgkin lymphoma. Appropriate approach is determined by lymphoma stage, performans status, comorbidities, histological subtype, status of the HIV disease and immunosuppression. Treatment outcomes have improved due to chemotherapy modalities and effective antiretroviral therapy. This review summarizes epidemiology, pathogenesis, pathology, and current treatment landscape in HIV associated lymphoma.

DUSP22-IRF4 rearrangement in AIDS-associated ALK-negative anaplastic large cell lymphoma.

Patients with AIDS have increased risk of developing lymphomas, such as anaplastic large cell lymphoma (ALCL), which generally carry a poor prognosis. The DUSP-IRF4 genetic rearrangement in ALCL confers a favourable prognosis in HIV-negative patients; it is unknown how this interacts clinically with HIV/AIDS. A man aged 53 years presented with subcutaneous nodules on the scalp and axillae, and diffuse lymphadenopathy. Biopsy of subcutaneous nodule and lymph node showed large atypical anaplastic lymphocytes which were CD30+ and anaplastic lymphoma kinase-negative, consistent with primary systemic ALCL. In addition, he was found to be HIV-positive and diagnosed with AIDS. Genetic testing of the tissue revealed a DUSP22-IRF4 rearrangement. Complete remission was achieved with HyperCVAD and subsequent brentuximab vedotin monotherapy. We report a case of AIDS-associated primary systemic ALCL with a DUSP22-IRF4 rearrangement. AIDS-associated ALCL is an aggressive lymphoma, with a poor prognosis. However, the presence of the genetic rearrangement, previously unseen in this disease, drastically altered the disease course. This case highlights the value of genetic testing and identifies DUSP22-IRF4-associated ALCL in the setting of HIV-associated lymphoproliferative disorders.

Human Immunodeficiency Virus-Associated Lymphoproliferative Disorders.

HIV infection is associated with an increased risk for developing B-cell lymphoproliferative disorders. The spectrum of disease differs in HIV-infected versus HIV-uninfected persons, with aggressive B-cell non-Hodgkin lymphomas constituting a higher proportion of all lymphoproliferative disorders in the HIV-positive population. Although antiretroviral therapy (ART) has significantly changed the landscape of lymphomas arising in HIV-infected persons, population growth and aging are reflected in the steady increase in non-AIDS-defining cancers. In the ART era, outcomes for HIV-infected lymphoma patients are similar to those of HIV-negative patients. This article reviews the diagnostic features and summarizes current biologic understanding of HIV-associated lymphomas.

HIV-related lymphomas in adults served in the public health network: An observational study.

Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.

The clinical features and prognosis of 100 AIDS-related lymphoma cases.

To improve outcomes and risk assessment, we systematically analyzed the clinical features of patients with acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) and identified survival-associated factors. Data were collected from 100 patients diagnosed with ARL at the Henan Provincial Infectious Disease Hospital in China. The progression-free survival (PFS) duration and 2-year overall survival (OS) rate were determined. A multivariate analysis was used to evaluate the associations between survival and the following variables: sex, age, histological subtype, Ann Arbor stage, lactate dehydrogenase (LDH) level, primary site, baseline CD4+ count, use of chemotherapy, and age-adjusted international prognostic index IPI (aaIPI). The timing of combined antiretroviral therapy (cART) relative to chemotherapy was also assessed. The PFS duration and 2-year OS rate were significantly higher in the chemotherapy vs. the non-chemotherapy group (P < 0.001), but did not differ significantly between patients who received chemotherapy before vs. simultaneously as cART (P > 0.05). Age, aaIPI, chemotherapy, LDH level, and the Burkitt/Burkitt-like lymphoma subtype were significant prognostic factors for 2-year OS; the other factors were not associated with prognosis. Our results show that cART plus chemotherapy significantly improves the survival of patients with ARL and identifies several prognostic factors.

Burkitt's lymphoma nodular cystic hepatosplenic, in HIV patient. Case report / Linfoma de Burkitt hepatoesplénico quístico nodular, en paciente con VIH. Reporte de caso

Background: Patients with human immunodeficiency virus (HIV) are more likely to develop cancer. Malignant lymphomas are the main cancer group seen in these patients. Diffuse large B-cell lymphoma including central nervous system lymphoma and Burkitt's lymphoma account for 90% of HIV-related non-Hodgkin's lymphomas. Clinical case: A 22-year-old man with fever up to 39 ° C, malaise, excessive tiredness and night sweats, loss of 8 kg of weight, abdominal pain in the right hypochondrium, all 5 months before hospitalization. Hemoglobin: 9.5 g/dL, leukocytes 5.13 x 103/mm3, platelets 124 000 cel/mm3; albumin 2.9 g/dL, alanine aminotransferase 28 IU/L, aspartate aminotransferase 105 IU/L; HIV reactive, beta 2 microglobulin: 20 000 ng/mL. Viral load for HIV 100 034 cp/mL, CD4: 76 cel/mcL (5%). It was performed abdominal ultrasound and denoted cysts in the liver and spleen. Abdominal-pelvic computed tomography with hepatosplenomegaly, retroperitoneal and inguinal adenopathies and free fluid in abdominal cavity. Splenectomy was performed and Burkitt's lymphoma was reported in the histopathological study. Conclusion: HIV predisposes patients to any type of cancer. Intra-abdominal findings should be a warning of lymphoma suspicious and may occur from infiltration of the small intestine, solid organ and soft tissues.

Introducción: los pacientes con virus de inmunodeficiencia humana (VIH) son más propensos a desarrollar cáncer. Los linfomas malignos son el principal grupo de cáncer que se observa en estos pacientes. El linfoma difuso de células grandes B, incluido el del sistema nervioso central y el linfoma de Burkitt, constituyen 90% de los linfomas no Hodgkin relacionados con VIH. Caso clínico: hombre de 22 años de edad, con fiebre de hasta 39 °C, malestar general, cansancio excesivo y sudoración nocturna, pérdida de 8 kg de peso y dolor abdominal en hipocondrio derecho, 5 meses previos a su hospitalización. Se reportó hemoglobina de 9.5 g/dL, leucocitos 5.13 x 103/mm3, plaquetas 124 000 cel/mm3; albúmina 2.9 g/dL; alanino aminotransferasa 28 UI/L, aspartato aminotransferasa 105 UI/L; VIH reactivo, beta 2 microglobulina 20 000 ng/mL. Carga viral para VIH 100 034 cp/mL, CD4 76 cel/mcL (5%). El ultrasonido abdominal mostró quistes en hígado y bazo. La tomografía abdominopélvica reportó hepatoesplenomegalia, adenopatías retroperitoneales e inguinal y líquido libre en cavidad abdominal. Se realizó esplenectomía y en el estudio histopatológico se reportó Linfoma de Burkitt. Conclusión: El VIH predispone a los pacientes a cualquier tipo de cáncer. Los hallazgos intraabdominales deben hacer sospechar de linfoma y se puede presentar desde infiltración del intestino delgado, órgano sólido y tejidos blandos.

Incidence and risk factors for relapses in HIV-associated non-Hodgkin lymphoma as observed in the German HIV-related lymphoma cohort study.

Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate.

Oral plasmablastic lymphoma as the first manifestation of AIDS.

Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes.

Stage IV advanced diffuse large B-cell lymphoma in human immunodeficiency virus infection with achieving cure by using highly active antiretroviral therapy alone: a case report.

After the introduction of highly active antiretroviral therapy (HAART), there has been a decrease in the incidence of lymphoma among the HIV-infected population and also significantly improved survival rates. We describe a remarkable case of an HIV-infected patient with advanced stage IV diffuse large B-cell lymphoma (DLBCL), completely regressed with the use of HAART alone. He remained disease-free for 6 years and he achieved cure without chemotherapy. Although several cases of low-grade lymphoma with complete regression were reported, we could not find any case of stage IV high-grade malignant lymphoma with HAART alone in complete remission for over 5 years from our review of the literature. This unique case shows the importance of HAART in improving survival and achieving cure in HIV-high-grade malignant lymphoma.

An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

Clinicopathologic characteristics of HIV/AIDS-related plasmablastic lymphoma.

Plasmablastic lymphoma is a rare and aggressive B cell lymphoma that is considered to be strongly associated with HIV infection. This article explores the histological morphology and immunohistochemical characteristics of HIV/AIDS-related plasmablastic lymphoma with the goal of improving the diagnosis and treatment of this rare tumor. According to criteria of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues (2008), six plasmablastic lymphoma cases admitted to the Shanghai Public Health Clinical Center were comprehensively analyzed with conventional hematoxylin-eosin staining, immunohistochemical staining and in situ hybridization. The morphological features of six tumors were consistent with PBL. Immunohistochemical staining showed that all six cases were negative for CD19, CD20, and CD79a, and positive for OCT-2, BOB-1, VS38c, and melanoma ubiquitous mutated 1. The Ki67 proliferation index was higher than 90% in all six cases. In situ hybridization indicated that four cases were EBER-positive. In addition, three cases had C-MYC translocation rearrangement. Our results showed that the immunophenotypes of PBL vary, which makes PBL diagnosis difficult. Therefore, morphological characteristics, immunophenotypic markers, and clinical data should be used in combination to enable an accurate diagnosis, especially in the presence of immunophenotypic variation, as this approach will facilitate timely treatment.