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U Tirelli

Publications and source records attributed to U Tirelli.

At least 145 records · Page 8Linked to original sources

Morphologic patterns and molecular pathways of AIDS-related head and neck and other systemic lymphomas.

Head and neck manifestations of human immunodeficiency virus (HIV) infection include lymph nodal and extranodal localization of non-Hodgkin's lymphoma (NHL). A histopathologic characteristic common to head and neck NHLs and to all the other systemic lymphomas in HIV patients is the frequent occurrence of cases displaying pleomorphic features and some overlap between established histologic subtypes. This article highlights the difficulties in defining HIV-related NHLs correctly, and proposes a specific pathologic categorization of these disorders accounting for their pathogenic aspects as gathered from molecular data.

Acquired Immunodeficiency Syndrome↗

Age and serum lactate dehydrogenase level are independent prognostic factors in human immunodeficiency virus-related non-Hodgkin's lymphomas: a single-institute study of 96 patients.

PURPOSE: The role of classical pragnostic factors (ie, age, performance status [PS], stage, extranodal involvement, and serum lactate dehydrogenase [LDH] level) included in the International Index for diffuse large-cell non-Hodgkin's lymphoma (NHL) of the general population is presently unknown in the setting of human immunodeficiency virus (HIV). To assess the prognostic value of these factors in HIV-related NHL, we reviewed the cohort of patients with HIV-related NHL diagnosed and treated with combination chemotherapy (CT) at our institution. PATIENTS AND METHODS: Ninety-six patients with systemic HIV-related NHL diagnosed and treated with combination CT regimens between September 1987 and December 1993 at the Centro di Riferimento Oncologico, Aviano, Italy, were studied. All clinical and laboratory data were evaluated by univariate and multivariate analyses, using overall survival as the end point. RESULTS: Complete remission (CR) occurred in 48% of patients; the overall median survival and disease-free survival times were 7 and 13 months, respectively. Among the classical and HIV-related prognostic factors, the following had a statistically significant influence on survival: PS > or = 2, elevated LDH level, age greater than 40 years, a CD4 cell count less than 100/microL, active opportunistic infections at diagnosis of NHL, and B symptoms. Multivariate analyses showed that only age, serum LDH level, and CD4 cell count were independent predictors of shortened survival. The increased hazard for patients greater than 40 years of age was 1.6 (95% confidence interval [CI], 1.2 to 2.3), for patients with increased LDH it was 1.8 (95% CI, 1.01 to 3.1), and for patients with a CD4 cell count less than 100/microL it was 1.7 (95% CI, 1.01 to 2.9). CONCLUSIONS: Our study shows that in addition to HIV-related prognostic factors, ie, CD4 cell count less than 100/microL, classical prognostic factors such as age and serum LDH level are independent prognostic factors and should be included in the design of future clinical trials of HIV-related NHL.

Adult↗

Malignant lymphomas in patients with HIV infection.

During the last two decades, the occurrence of non-Hodgkin's lymphoma (NHLs) has been increasing both in the general population, in which their incidence doubled, and in people with human immunodeficiency virus (HIV) infection, in whom a 100-fold increase has been observed since the onset of the AIDS epidemic. HIV infected patients are living longer owing to advances in antiretroviral therapy and treatment of prophylaxis against opportunistic infections but because of their immunodeficiency they are at high risk of cancers, especially NHL. The natural history of cancers in patients with HIV infection differs from that of the general population. Unusual aspects of tumor localization, growth behaviour and therapeutical response, distinguish tumors in patients with from those without HIV infection. The pathologic and virological aspects of HIV-related tumors are peculiar and a pathological classification of HIV associated systemic lymphomas based on the morphological features of the two main types, i.e. blastic and anaplastic cell lymphomas has been formulated. The treatment of HIV-related neoplasms is controversial as it is not clear whether conventional therapy and in particular chemotherapy is able to modify the natural history of these malignancies in HIV setting. Moreover the treatment of HIV-related tumors presents several problems, due to the aggressive behaviours of tumors and because of immunosuppressive chemotherapy employed in patients with immunodeficiency.

Humans↗

Characteristics of EBV-infected cells in HIV-related lymphadenopathy: implications for the pathogenesis of EBV-associated and EBV-unrelated lymphomas of HIV-seropositive individuals.

The present study was performed with the aim of better defining the possible role of Epstein-Barr-virus (EBV)-infected cells in the pathogenesis of HIV-related lymphadenopathy syndrome (LAS). In addition, since LAS has been considered as a pre-lymphomatous lesion, we also wished to elucidate the possible contribution of EBV-carrying cells present in LAS tissues to the development of HIV-associated malignant lymphomas. To this end, we have characterized EBV-infected cells in LAS lymph nodes in terms of EBV DNA prevalence, tissue distribution in relation to HIV-carrying cells, virus sub-type, expression of latent and replicative antigens, and presence of clonal EBV episomes. When compared with HIV-unrelated lymphadenopathies (4/10, 40%), LAS showed a higher prevalence of EBV DNA (14/20, 70%). Comparable values of EBV prevalence were detected in LAS with follicular hyperplasia (12/16, 75%) and with follicular involution (4/4, 100%). All EBV+ non-neoplastic lymph nodes from HIV-seronegative patients carried type-I EBV, whereas LAS specimens showed almost equivalent distribution of the 2 EBV sub-types. Of the 14 EBV-carrying LAS, 4 (29%) were positive by Southern-blot analysis for the BamHI-W region of the virus genome but negative for the presence of monoclonal EBV episomes. In situ hybridization revealed a remarkably higher load of EBV-infected cells in LAS than in HIV-unrelated lymphadenopathies. In LAS lymph nodes, EBV-carrying cells were identified as isolated, cytologically normal elements, sometimes with immunoblastic morphology, usually scattered throughout the interfollicular areas. By contrast, the expression of HIV p24 was restricted to germinal center cells. All the EBV+ LAS samples were negative for the expression of EBV-encoded latent (LMP-1 and EBNA-2) and replicative proteins (BZLF-1, BHLF-1, EA-D, EA-R and VCA). In addition, amplification of the immunoglobulin heavy-chain genes using 2 different polymerase-chain-reaction protocols showed evidence of B-cell clonal expansion in 2/20 (10%) LAS, one EBV- case, and one sample with low numbers of EBV-infected cells. These results suggest that (i) EBV-carrying cells are probably not involved in the development of LAS, either directly or indirectly; (ii) type-2-EBV-infected cells are present in LAS lymph nodes from the early phases of HIV infection; (iii) EBV-carrying LAS per se probably does not constitute a lesion at high risk for subsequent development of EBV+ lymphomas; (iv) it is unlikely that a high viral load or strong EBV-mediated antigenic stimulation plays a contributory role in the development of EBV-unrelated lymphomas of HIV-seropositive individuals.

AIDS-Related Complex↗

Head and neck lymphomas associated with human immunodeficiency virus infection.

OBJECTIVE: To focus on clinicopathologic data of non-Hodgkin's lymphomas (NHLs) of the head and neck area (with lymph nodal or extranodal localization) arising in patients with immunodeficiency virus (HIV) infection. PATIENTS: Among 73 evaluable patients for presenting symptoms, of a total of 82 with HIV-related NHLs whose conditions were diagnosed at the Centro di Riferimento Oncologico, Aviano (Italy), between September 1984 and May 1992, 15 (21%) had primary, solitary head and neck (P-HN) lymphoma and 13 (18%) had systemic head and neck (S-HN) lymphoma arising from this region. RESULTS: Ten (67%) of 15 patients with P-HN NHL had stages I and II, whereas all patients with S-HN NHL had stages III and IV. Twenty-seven of 28 patients had extranodal disease at presentation, the principal sites being Waldeyer's ring and soft tissues. There were only high-grade (14 cases) or intermediate-grade (three cases) NHLs, the most frequent histotypes being small noncleaved cell, Burkitt's type, and large-cell immunoblastic. Seven of 11 cases in the miscellaneous group of the working formulation were classified as Ki-1+ anaplastic large-cell lymphoma. By immunophenotypic and genotypic characterization, a B-cell derivation was suggested for 21 of 28 NHLs. After combination chemotherapy with or without radiotherapy, a complete remission was observed in seven (58%) of 12 patients with P-HN lymphoma and in only two patients with S-HN lymphoma. Median survival was 9.8 months for the patients with P-HN lymphoma and 8.3 months for the other patients. Thirteen patients died, the most common causes of death being opportunistic infections (five cases) and progression of lymphoma (four cases). CONCLUSIONS: Most HIV-infected patients with head and neck NHL had severe immunodeficiency, extranodal disease, aggressive histologic findings, and a poor treatment response.

Adult↗

Genotypic and immunohistological demonstration of the progression of an unusual reactive-like B-cell lymphoproliferative disorder to a high grade diffuse lymphoma.

In the present study the clinical and pathological evolution of a reactive-like B-cell lymphoproliferative disorder with an unusually high content of T cells is described. Immunogenotypic analysis showed that the same phenotypically atypical B-cell clone, characterized by the unusual presence of an immunoglobulin (Ig)K gene rearrangement, with the heavy chain (IgH) gene in germline configuration, was invariantly present in all phases of the disease. The disorder showed an indolent course for a long period of time during which the clonal B-cell population coexisted with an abundant, reactive T-cell component in different locations of the disease. These findings, together with the observation of spontaneous progression and regression phases of the disorder and its responsiveness to corticosteroids, suggest that functional interactions between the B-cell clone and the polyclonal infiltrating T cells probably were involved in the pathogenesis of the disease. After the administration of the antiblastic treatment, a progressive reduction of the reactive T-cell component was observed with the concomitant evolution to a diffuse large cell (immunoblastic) B-cell lymphoma and the appearance of an IgH gene rearrangement. The biological characteristics and the clinical evolution of the case described here are similar to those reported for the so-called "T-cell-rich B-cell lymphomas" (TCRBCLs). These findings suggest that the T-cell-rich pattern may identify a group of B-cell lymphoproliferations with common pathogenetic mechanisms and clinical behavior.

Adult↗

AIDS-related Burkitt's lymphoma. Morphologic and immunophenotypic study of biopsy specimens.

In patients infected with HIV, high-grade B-cell non-Hodgkin's lymphomas (NHL), including the small noncleaved cell (SNCC) category, exhibit pleomorphic features, which makes precise definition difficult. Sixty-nine pathologic specimens with HIV-related systemic lymphomas, including 42 SNCC, 20 immunoblastic lymphomas (IBL), and 7 cases with features "intermediate" between SNCC and IBL were morphologically and immunophenotypically investigated. The host immune status was also analyzed in 57 of 69 patients. In 29 representative SNCC lymphomas, in 9 IBL cases, and an additional 3 intermediate lymphomas, both p53 protein overexpression and the association of Epstein-Barr virus (EBV) genetic information were assessed. Small noncleaved cell lymphomas included tumors exhibiting features of the 2 established subtypes (27 Burkitt's and 15 non-Burkitt's). In the seven intermediate cases, cells showed features intermediate between SNCC with plasmablastic differentiation and immunoblasts plasmacytoid. Immunoblast-like cells were also present. p53 protein overexpression and EBV association were found in a proportion of SNCC (14 of 29; 7 of 29) and intermediate (3 of 3; 2 of 3) lymphomas. Conversely, IBL cases were consistently p53 negative, but showed a high EBV association (7 of 9). All the evaluated patients with intermediate lymphomas had a considerably lower mean (76.6 per mm3 +/- 77.4 SD) and median (54 per mm3) number of CD4+ lymphocyte count than SNCC patients (mean 227.9 per mm3 +/- 186.9 SD, median 193 per mm3), thus mirroring IBL patients (mean 95.3 per mm3 +/- 82.8 SD, median 81 per mm3). All data provide evidence that lymphomas showing intermediate features constitute a distinct subgroup from either SNCC or IBL.

Biopsy↗

Testicular germ cell tumors and human immunodeficiency virus infection: a report of 26 cases. Italian Cooperative Group on AIDS and Tumors.

PURPOSE: Besides tumors that are diagnostic of AIDS, such as non-Hodgkin's lymphoma, Kaposi's sarcoma, and invasive carcinoma of the cervix, other tumors have been described in the human immunodeficiency virus (HIV) setting. Some case reports on testicular cancer in HIV-infected patients have appeared in the literature. We present a retrospective study on 26 cases of testicular germ cell tumors (TGCTs) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT) between November 1986 and September 1994. PATIENTS AND METHODS: Twenty-six patients with TGCT and HIV-infection from the GICAT were retrospectively analyzed. RESULTS: Fourteen patients had seminoma and 12 had nonseminoma. Four patients underwent only orchidectomy, one patient received only chemotherapy, nine patients were treated with postsurgical chemotherapy, 10 patients (38%) received postsurgical radiotherapy, one patient received postsurgical chemotherapy plus radiotherapy, and one patient was lost for follow-up evaluation immediately after diagnosis. The complete response (CR) rate was 95%. Relapse occurred in 32% of patients. The median follow-up time was 33 months. The mortality rate was 37%. Causes of death were neoplasia in three of nine patients, AIDS in five of nine patients, and fortuitous event in one of nine patients. The overall 3-year survival rate was 65%, and the 3-year disease-free survival rate was 65%. Severe hematologic toxicity was observed in seven of 15 patients. CONCLUSION: HIV-infected patients with testicular cancer should be offered standard oncologic therapy, irrespective of their HIV status, since the majority can be cured of their tumor and have a good quality of life. Use of concomitant prophylaxis for opportunistic infections is recommended.

Adult↗

CD30 (Ki-1)-positive anaplastic large-cell lymphomas in 13 patients with and 27 patients without human immunodeficiency virus infection: the first comparative clinicopathologic study from a single institution that also includes 80 patients with other human immunodeficiency virus-related systemic lymphomas.

PURPOSE: CD30 (Ki-1)-positive anaplastic large-cell lymphoma (Ki-1 ALCL) rarely has been described in patients with human immunodeficiency virus (HIV) infection. The purpose of this study was to characterize further the clinicopathologic features of Ki-1 ALCL in patients with HIV infection and, for the first time, to make a comparison with Ki-1 ALCL in patients without HIV infection. PATIENTS AND METHODS: From September 1987 to April 1993, 93 patients with HIV infection and systemic non-Hodgkin's lymphoma (NHL) were treated at the Cancer Center of Aviano, Italy; in 13 (14%), the diagnosis was of Ki-1 ALCL subtype. This group of patients was compared with the remaining 80 patients who had other HIV-related NHL and with another group of 27 patients with Ki-1 ALCL who were without a diagnosis of HIV infection. RESULTS: There was no case of a T-cell phenotype in the 13 HIV-positive Ki-1 ALCL patients, whereas there was such a phenotype in six of 27 (22%) HIV-negative Ki-1 ALCL patients. In regard to the general characteristics of the two groups with Ki-1 ALCL, more patients with stage IV, two or more extranodal sites at presentation, treatment-related leukopenia, and opportunistic infections as the cause of death were observed in the HIV-positive Ki-1 ALCL group. When these variables were compared with those of the other HIV-related NHL group, such differences were not present. CONCLUSION: Ki-1 ALCL is not a rare clinicopathologic entity among NHL in patients with HIV infection. The differences observed within the two Ki-1 ALCL groups of patients may be because of factors related to the HIV infection alone.

Adult↗

Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologic features of 114 patients from the Italian Cooperative Group on AIDS and Tumors.

PURPOSE: To describe virologic, clinicopathologic, and therapeutic features of a large series of Italian patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: From November 1986 to March 1994, 114 cases were observed. The relationship between Epstein-Barr virus (EBV) and HD was determined by an in situ hybridization technique, immunostaining for EBV-encoded latent membrane protein-1 (LMP-1) expression, and Southern blotting. Twenty-six patients were included in a prospective study evaluating the combination of chemotherapy (CT) with zidovudine. RESULTS: Combined approach on EBV study revealed that 14 (78%) of 18 patients were EBV-associated. An almost equivalent distribution of EBV subtypes was observed in EBV-carrying cases, indicating that in the HIV setting, type 2 EBV also may be pathogenetically involved in HD development. In comparing these 114 patients with our single-institutional series of 104 HIV-negative patients with HD, we observed at presentation a younger median age (29 v 38 years); a prevalence of males (90% v 56%); and a higher percentage of stage IV disease (52% v 15%), presence of B symptoms (77% v 35%), and extranodal disease (63% v 29%). The complete remission (CR) rate (58%) and median survival (13 months) of patients treated prospectively were similar to that of patients treated with standard CT regimens. The statistically significant favorable prognostic factors for survival being the following: achievement of CR, CD4+ count greater than 250/microL, and no prior diagnosis of AIDS at onset of HD. CONCLUSION: Our virologic findings indicate that HIV-related HD is more closely associated with EBV than HD in the general population. The peculiar clinicopathologic findings, the role of some prognostic factors, and the possibility of cure of HIV-related HD have been demonstrated.

Acquired Immunodeficiency Syndrome↗

The classification of AIDS cases: concordance between two AIDS surveillance systems in Italy.

This study assessed the concordance between the transmission classification of 725 acquired immunodeficiency syndrome (AIDS) cases by the Italian AIDS Registry (the national surveillance system) and the classification of the same cases by the Italian Cooperative Group on AIDS-Related Tumors. A high degree of concordance emerged for intravenous drug users in both sexes (kappa = 0.88; 95% confidence interval [CI] = 0.84, 0.92), for homosexual men (kappa = 0.83; 95% CI = 0.79, 0.87), and for persons infected through contaminated blood or blood derivatives (kappa = 1.00). The concordance was lower among heterosexual men (kappa = 0.51; 95% CI = 0.37, 0.65) and especially among men whose risk group was not determined (kappa = 0.28; 95% CI = 0.12, 0.44). The discrepancies observed among heterosexual men indicate a need for continuing and accurate monitoring of AIDS reporting by transmission category.

Acquired Immunodeficiency Syndrome↗

Clinical evaluation of 451 patients with HIV related non-Hodgkin's lymphoma: experience on the Italian cooperative group on AIDS and tumors (GICAT).

We report the clinical experience in 451 patients with HIV related non-Hodgkin's lymphoma (HIV-NHL) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT: Gruppo Italiano Cooperativo AIDS e Tumori), a significant number of them being treated at the Aviano Cancer Center (ACC). High grade histology according to the Working Formulation, stages III-IV and B symptoms were detected in the majority of patients. The median survival was 6 months. Based on the Cox model, three factors appeared to influence survival: advanced stage, treatment received and failure to obtain complete remission (CR). In another study aimed at comparing between chemotherapy with or without G-CSF it was shown that G-CSF significantly reduced white blood cells (WBC) nadir duration, the mean delays between cycles, the mean hospitalization time for toxicity per patient treated, without increasing significantly the overall costs. Furthermore, of 77 GICAT patients treated at the ACC with (group A) or without (group B) long-lasting CR, performance status and the mean CD4+ cell count at time of NHL diagnosis were the only parameters of statistical relevance. Based on our data HIV related NHLs are highly aggressive malignancies which are associated with a poor prognosis per se, and because of the underlying HIV infection. Long-term survivals and possible cures can, nonetheless, be obtained in a subgroup of patients, who have a better performance status and a less advanced immune dysfunction related to HIV infection.

Acquired Immunodeficiency Syndrome↗