CXCL12 is a costimulator for CD4+ T cell activation and proliferation in chronic lymphocytic leukemia patients.

Activated T cells from patients with chronic lymphocytic leukemia (CLL) provide survival and proliferative signals to the leukemic clone within lymphoid tissues. Recruitment of both, CLL cells and T lymphocytes, to this supportive microenvironment greatly depends on CXCL12 production by stromal and myeloid cells. CXCL12 also supplies survival stimuli to leukemic B cells, but whether it exerts stimulatory effects on T lymphocytes from CLL patients is unknown. In order to evaluate the capacity of CXCL12 to increase CD4(+) T cell activation and proliferation in CLL patients, peripheral blood mononuclear cells were cultured with or without recombinant human CXCL12 or autologous nurse-like cells, and then T cell activation was induced by anti-CD3 mAb. CXCL12 increases the proliferation and the expression of CD25, CD69, CD154, and IFNγ on CD3-stimulated CD4(+) T cells from CLL patients, similarly in T cells from ZAP-70(+) to ZAP-70(-) patients. Autologous nurse-like cells establish a close contact with CD4(+) T cells and increase their activation and proliferation partially through a CXCR4-dependent mechanism. In addition, we found that activated T cells in the presence of CXCL12 enhance the activation and proliferation of the leukemic clone. In conclusion, CXCL12 production by lymphoid tissue microenvironment in CLL patients might play a key dual role on T cell physiology, functioning not only as a chemoattractant but also as a costimulatory factor for activated T cells.

Biallelic deletion 13q14.3 in patients with chronic lymphocytic leukemia: cytogenetic, FISH and clinical studies.

BACKGROUND AND OBJECTIVE: Monoallelic deletion of 13q14.3 (13q14x1) is the most common abnormality in chronic lymphocytic leukemia (CLL). As a sole alteration, it predicts a favorable outcome. Biallelic 13q14.3 (13q14x2) deletion or concomitant 13q14x1/13q14x2 has been scarcely evaluated in the literature. We present the clinical, cytogenetic and fluorescence in situ hybridization (FISH) analysis of six CLL patients with normal karyotypes and 13q14x2 and their comparison to cases with 13q14x1 as a single abnormality. PATIENTS AND METHODS: A total of 103 CLL patients were studied. Cytogenetic and FISH analysis were performed on stimulated peripheral blood lymphocytes. Specific fluorescence DNA probes for CLL were used. RESULTS: Six out of 103 (5.8%) patients showed normal karyotypes and 13q14x2. It was observed as a single alteration in one patient and combined with 13q14x1 in five cases. Biallelic clones were larger than monoallelic ones in 3/5 patients (60%). The comparison of clinical and hematological data between 13q14x1 and 13q14x2 groups showed progression of the disease in all 13q14x2 patients respect to 12/32 (37.5%) cases with 13q14x1 (P = 0.008), significant differences in the distribution by Rai stage (P = 0.042) and a tendency of a higher lactate dehydrogenase level in 13q14x2 patients (P = 0.054). Treatment free survival for 13q14x2 group was 28.5 months, shorter than those observed in patients with 13q14x1 alone (49 months). CONCLUSIONS: Our data would suggest that 13q14x2 could represent a more aggressive FISH anomaly than 13q14x1 alone, probably as a consequence of clonal evolution and/or due to the complete inactivation of this critical region by mean of more complex mechanisms.

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.

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.

Non-Hodgkin lymphomas of the oral cavity in AIDS patients in a reference hospital of infectious diseases in Argentina: report of eleven cases and review of the literature.

INTRODUCTION: Extranodal non-Hodgkin lymphoma (NHL) were commonly described in AIDS patients and are related with an atypical morphology and aggressive clinical course. MATERIALS AND METHODS: In this single institutional study we evaluated the epidemiological, clinical, immunological, virological, histopathological and the outcome of eleven HIV/AIDS patients with oral cavity lymphomas (OCL). RESULTS: Nine were males and seven intravenous drug abusers. The median of age was 33 years and the median of CD4 T cell counts at the time of diagnosis was 97 cell/µL. The majority of tumors presented as large and ulcerated masses involving the gingiva, the palate and the jaw. Six of these tumors were diffuse large B-cell lymphomas (DLBCL); three were Burkitt's lymphomas and the final case was a plasmablastic lymphoma. An association with Epstein-Barr virus (EBV) was found in three of the ten tested cases by in situ hybridization (EBER 1 and 2 probes) and immunohistochemistry (LMP-1). Human herpes virus-8 (HHV-8) was detected by polymerase chain reaction (PCR) in only one neoplasm. Six patients died without specific treatment; four received chemotherapy and highly active antiretroviral therapy (HAART) and three of them presented a prolonged survival. DISCUSSION: Combination of HAART and chemotherapy should modify the poor prognosis of AIDS patients with OCL.

Linfoma de Burkitt primario de la cavidad oral en una paciente con sida. Reporte de un caso y revisión de la literatura / Burkitt's lymphoma of the oral cavity in a female with AIDS. Case report and literature review

Los linfomas no Hodgkin (LNH) son un grupo heterogéneo de enfermedades linfoproliferativas con elevada prevalencia en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). La inmunodeficiencia asociada al sida predispone al desarrollo de LNH, incluyendo el linfoma de Burkitt (LB). El LB es un subtipo infrecuente y agresivo de LNH con elevada frecuencia en pacientes con sida. Se asocia a una alta tasa de replicación celular (determinada por el índice Ki67) y con alta frecuencia de compromiso extranodal como forma de presentación clínica de la neoplasia. Se presenta una paciente con sida que desarrolló un LB primario de la cavidad oral y se realiza una revisión de la literatura sobre el tema (AU)

Non-Hodgkin lymphomas (NHL) are a heterogeneous group of diseases with a high prevalence in human immunodeficiency virus (HIV) infected patients. The immunosuppression associated with AIDS predisposes to develop NHL, including Burkitt's lymphoma (BL). BL is an uncommon and aggressive subtype of NHL that occurs with increased frequency among patients with AIDS. BL is associated with a high proliferative rate (Ki67 index) and compromises extranodal sites as the clinical presentation of the disease. Here we report a case of a primary BL of the oral cavity in an AIDS female patient, and a review the literature on the characteristics of oral cavity lymphomas in AIDS patients (AU)

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...

Soft-tissue masses as presentation of non-Hodgkin's lymphoma in AIDS patients / Massas de tecidos moles como apresentacao do linfoma nao-Hodgkin em pacientes com AIDS

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.

Os linfomas Não-Hodgkin primários de tecidos moles são muito raros e responsáveis por somente 0,1% dos casos. Geralmente, os linfomas Não-Hodgkin de tecidos moles se apresentam como massas subcutâneas sem evidência de comprometimento dos nódulos ou da pele. Descrevemos aqui quatro casos de linfomas Não-Hodgkin primário de tecidos moles em pacientes infectados pelo vírus da imunodeficiência humana. O local mais comum de comprometimento foi a parede torácica em todos os pacientes; os exames histopatológico e imunofenotípico do esfregaço da biópsia revelaram dois casos de linfoma plasmablástico, um linfoma de Burkitt e um linfoma difuso de grandes células B. O linfoma Não-Hodgkin deve ser incluído no diagnóstico diferencial de massas de tecidos moles nos pacientes soropositivos para vírus da imunodeficiência humana.

Inv(4)(p14q27) in a case with de novo acute nonlymphocytic leukemia.

An inversion, inv(4)(p14q27), was found as the sole karyotypic anomaly at diagnosis in the bone marrow cells from a 65-year-old male patient with an M4 acute nonlymphocytic leukemia (ANLL). To our knowledge, the breakpoints observed in this case appear to be different from other inversions of chromosome 4 previously described in ANLL. The patient we described had a poor response to chemotherapy and had a short survival.

Deleción bialética de 13q14: un nuevo factor pronóstico en leucemia linfocítica crónica? / Bialelic deletion of 13q14: a new factor in forecast chronic lymphocytic leukemia?

La pérdida monoalélica de la banda 13q14.3 (13q14x1) es la anomalía más frecuente de la leucemia linfocítica crónica (LLC), asociada a buen pronóstico. La deleción bialélica de 13q14.3 (13q14x2) es un evento escasamente evaluado. En este trabajo se analizan las características clínicas, citogenéticas y citomoleculares de 8 pacientes con 13q14x2, de un total de 95 casos (8,4% ) (4 mujeres, edad media 64,7 años; rango 47.77 años). Cinco pacientes habían fallecido al momento de este análisis. Se realizó cultivo de sangre periférica con estimulación mitogénica. Se efectuó FISH (Fluorescence in situ hybridization) empleando las sondas: centromérica del cromosoma 12 y locus específica de: D13S319 (13q14), ATM (llq22) y TP53 (17p13). Cinco casos presentaron cariotipo normal y 3 mostraron otras anomalías: + 12, i(17)(q10) y cariotipo complejo. Seis casos mostraron concomitantemente 13q14x1 y 13q14x2. El análisis por grupo de riesgo citogenético mostró progresión de la enfermedad en los casos con cariotipo normal y 13q14x2 respecto del 38,7% de los pacientes con 13q14x1 (p