Biomedical subjects

Tony Petrella

Publications and source records attributed to Tony Petrella.

12 recordsLinked to original sources

PubMed2006

CD56-positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer.

BACKGROUND: Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. METHODS: A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. RESULTS: Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal-type extranodal natural killer/T-cell lymphoma; and (4) "classical" cases of cutaneous T-cell lymphoma (CTCL) with co-expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2-72 months), whereas all patients with CD56+ CTCL were alive at the last follow-up. CONCLUSION: Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders.

Adolescent↗

PubMed2006

Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d'Etude des Lymphomes de l'Adulte (GELA) study.

Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P = .02). Only 50% of patients achieved complete remission with a 5-year event-free survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Time-dependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.

Adult↗

PubMed2006

Granulomatous hepatitis and hemophagocytic syndrome after bacillus Calmette-Guerin bladder instillation.

Intravesical instillations of bacillus Calmette-Guérin are frequently used for treating superficial bladder carcinoma which is considered a safe treatment. We describe an unusual complication with hemophagocytosis and granulomatous hepatitis. Prompt diagnosis and treatment with corticosteroids, anti-tuberculous agents and intravenous immunoglobulins led to a rapid recovery.

Adjuvants, Immunologic↗

PubMed2005

Immune response and alteration of pulmonary function after primary human metapneumovirus (hMPV) infection of BALB/c mice.

Human metapneumovirus (hMPV), a recently identified virus, causes upper and lower respiratory tract diseases. In this study, we show that BALB/c mice inoculated with hMPV exhibited significant morbidity on 1--2 days post-infection, when airway obstruction was found. Increased airway hyper-responsiveness to metacholine was found on day 4 concurrent with lung viral replication. Both IgG1 and IgG2a hMPV-specific antibodies were found in sera, while interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were found in bronchoalveolar lavage. Lung histology showed parenchymal pneumonia and increased lymphocytic infiltration. We present here an animal model that may be helpful in studying hMPV pathogenesis and evaluating the effects of vaccines.

Airway Obstruction↗

PubMed2005

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.

Adult↗

PubMed2004

CD10 expression in diffuse large B-cell lymphomas does not influence survival.

CD10 expression is considered as a marker of centrofollicular-derived diffuse large B-cell lymphomas (DLBCL). The aim of our study was to determine retrospectively among 98 patients with DLBCL, enrolled in the LNH93 trial of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) and homogeneously treated with high-dose cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP)], the expression of CD10 using immunohistochemistry and its correlation with morphological features and clinical parameters. Of the 98 patients studied, 33 (34%) expressed CD10. There was no correlation among clinical parameters, International Prognostic Index risk groups and CD10 expression, with the exception of lactic dehydrogenase levels, which were lower in CD10-negative cases (P=0.005). There was no significant correlation between CD10 expression and morphological subtyping of DLBCL. Indeed, centrofollicular-derived DLBCL may present with numerous immunoblasts or as an immunoblastic lymphoma. Overall survival rate and event-free survival were not significantly different according to CD10 expression (P=0.44 and P=0.34 respectively). Therefore, it appears that CD10 expression does not influence survival or event-free survival in DLBCL.

Biomarkers, Tumor↗

PubMed2004

Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation).

PURPOSE: We report on our experience in the treatment of T1 and T2 mycosis fungoides (MF) with total skin electron beam therapy (TSEBT), with respect to relapse-free rate, overall survival rate, and management of recurrence. METHODS AND MATERIALS: Between 1975 and 2001, 141 patients with MF were referred to the radiotherapy department for treatment by TSEBT. A total of 57 patients were staged as having T1 or T2 disease (24 T1 and 33 T2 patients). A total of 25 received topical therapy before irradiation. Treatment was delivered through a 6-MeV linear accelerator to a mean total dose of 30 Gy, 2 Gy/day, 4 days/week, for 4 weeks. Close follow-up was initiated without adjuvant therapy. Median age was 61 years (range, 19-84), and median follow-up was 114 months (range, 14-300). RESULTS: Three months after completion of TSEBT, the overall response rate was 94.7%. A complete response was achieved in 87.5% of T1 and 84.8% of T2 patients. Thirty-one patients (54.4%) experienced a skin failure (8 with T1 and 23 with T2 disease) within 1 year. Eighteen patients of 31 received a reirradiation as salvage therapy (6 localized treatment with segmental fields of electron beam irradiation and 12-second TSEB delivering 24 Gy in 12 fractions). Two were treated by topical steroids, and 11 received combination therapy with PUVA (2/10), topical (10/10) or systemic (4/10) chemotherapy, or interferon (7/10). After a second course of TSEBT (4 T1 and 10 T2 patients), the 5-year freedom from relapse rate was 70% vs. 39% in patients having received other modalities. For the whole group, 5-year DFS was 50%. The 5/10/15-year OS were 90%/65%/42%, respectively. In univariate analysis, T1 (p = 0.03), CR after first TSEBT (p = 0.04), and age younger than 60 (p < 0.001) were significant prognostic factor for OS. In multivariate analysis, age younger than 60 years was statistically associated with improved OS (p = 0.001); T stage and completion of CR remained under threshold of significance (p = 0.059 and p = 0.063, respectively). During the mean 86-month period of follow-up from relapse, a second recurrence was observed in 29% of patients. CONCLUSIONS: TSEBT is highly effective in early-stage MF without adjuvant therapy. Management of relapses with local radiotherapy or second TSEBT is feasible, time-saving, and cost-effective.

Adult↗

PubMed2004

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.

Adult↗

PubMed2004

[Hematodermic CD4/CD56 neoplasm].

Hematodermic CD4/CD56 neoplasm is a recently described entity. This name has been initially proposed by the French Study Group on Cutaneous Lymphomas which established the primary anatomoclinical and pathogenic and cytogenic bases of the disease in 1999. This descriptive and provisional name allowed conceptualizing the entity by its main clinical and phenotypical characteristics. The first case in the literature goes back to 1994. Since that time, several other cases have been published. The expression of CD56 led most of the authors to propose an NK-cell lineage origin. In the last WHO classification of lymphomas, the entity was indexed under the name of "blastic NK-cell lymphoma". However, the authors underlined that there were currently no clues to the etiology of blastic NK-cell lymphoma and that the precise lineage of this disease was still unresolved. At the clinical level the main characteristics of the disease are the skin tropism and the occurrence of a leukemic phase at any time during the course of the disease. The median age is 59 but pediatric cases do exist. At the morphological level skin biopsy shows a monomorphous cell proliferation simulating a pleomorphic T cell cutaneous lymphoma. The diagnosis is based on phenotypic criteria which require frozen tissue. Currently, the main characteristics are the expression of CD4 and CD56 antigens while the main defined lineage specific markers are negative (B-cell, T-cell, NK-cell and myeloid-cell lineages). The origin of the tumor cells still remains uncertain but the plasmacytoid dendritic cell is presently a very serious candidate. The tumor cells share a great phenotypical homology and particularly the expression of the CD123 antigen. Functional homologies have also been demonstrated with tumor cells in vitro. Outcome of CD4/CD56 hematodermic neoplasms is very bad. The median time of survival is 14 months irrespective of the treatment given. Conventional chemotherapies used for the treatment of aggressive lymphomas or acute myeloid leukemias are quickly inefficient.

Adolescent↗

PubMed2004

TCL1 and CLA expression in agranular CD4/CD56 hematodermic neoplasms (blastic NK-cell lymphomas) and leukemia cutis.

Agranular CD4/CD56 hematodermic neoplasm (CD4/CD56 HN), also termed blastic natural killer cell lymphoma, is characterized by a peculiar immunophenotype and high skin tropism. The lineage of origin is not known, and a plasmacytoid dendritic cell derivation has been proposed. CD4/CD56 HN generally is diagnosed by using tumor skin biopsy, with the most important differential diagnosis being myelomonocytic leukemia cutis. We evaluated the expression of 2 plasmacytoid dendritic cell antigens, T-cell leukemia 1 (TCL1) and cutaneous lymphocyte-associated antigen (CLA), in 29 cases of CD4/CD56 HN and 18 cases of myelomonocytic leukemia cutis. TCL1 and CLA were expressed in 26 (90%) of 29 CD4/CD56 HN cases vs TCL1 expression in 3 (17%) and CLA expression in 14 (78%) of 18 leukemia cutis cases. Furthermore, CLA antiserum displays a peculiar small-dot staining pattern in CD4/CD56 HN. These results suggest that TCL1 and CLA are good markers for CD4/CD56 HN tumor cells and add support for a plasmacytoid dendritic cell origin. The high skin tropism of CD4/CD56 HN might be related to the skin-homing property of CLA.

Adult↗

PubMed2002

'Agranular CD4+ CD56+ hematodermic neoplasm' (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes.

In 1999, we reported seven cases of an unusual hematologic malignancy with primary cutaneous presentation that appeared as a distinct clinicopathologic entity characterized by medium-sized tumor cells with a peculiar CD3- CD4+ CD56+ CD43+ HLA-DR+ cell surface phenotype. Because the origin of tumor cells was not clear and they exhibited a nonlineage-specific phenotype, we hypothesized that such tumors likely originated from hematologic-myeloid precursor cells and were tentatively assigned the designation "agranular CD4+ CD56+ hematodermic neoplasms." In the present study we report 14 cases (seven already reported and seven additional cases) of these tumors, and simultaneously we present now a rare population of cells that we have identified in the peripheral blood of healthy volunteers treated with Flt3 ligand. These cells express all the characteristic markers of CD4+ CD56+ hematodermic neoplasms. This population appears to be related to plasmacytoid monocytes because they also expressed CD68 and bright levels of CD123. To confirm the relationship between these normal cells and CD4+ CD56+ hematodermic neoplasms, we conducted an extensive comparative phenotypic study. Results show that these two cell types are indeed related because they share many phenotypic features, including the presence of CD4, CD56, CD43, CD68, and HLA-DR and the absence of other T, B, NK, or myelomonocytic markers. More importantly, we found that the bright expression of CD123 by immunohistochemistry is a distinctive characteristic of CD4+ CD56+ hematodermic neoplasms because all (n = 14) cases expressed this marker, whereas only two specimens in a control panel comprising 30 samples of related tumors expressed comparable levels of CD123. We therefore propose that oncogenic transformation of NCAM-expressing plasmacytoid monocyte-like cells may lead to "agranular CD4+ CD56+ hematodermic neoplasm."

Adult↗

PubMedDate not supplied

Skin manifestations in CD4+, CD56+ malignancies.

CD4+ CD56+ hematologic neoplasms were recently individualized. We report three cases of CD4+ CD56+ malignancies with cutaneous lesions in three cases and also bone marrow involvement in two cases. Two patients relapsed 2 and 3 months after polychemotherapy. Two patients died within 3-10 months. A constant immunophenotype was observed with the co-expression of CD4 and CD56, the absence of B and T-cell markers. The salient fact of this report is the presence of T-cell clonal rearrangement. The clinical and pathological features closely resemble the specific cutaneous manifestations in acute leukemia with monocytic differentiation, especially the granulocytic sarcoma. Because of the positivity of the CD56, natural killer cell proliferations were discussed. Since 1994, 50 cases of CD4+, CD56+ cutaneous neoplasms have been reported with specific clinical, cytologic and immunohistochemical features. The diagnosis is more difficult when the cutaneous location is exclusive; on the contrary, the cytological features of the blood and medullar cells with cytoplasmic vacuoles and pseudopodia are characteristic of this hematologic neoplasm. The presence of CD123 antigen in most of the cases is an argument for a plasmacytoid dendritic cell proliferation and it is also a good marker for primary cutaneous lesions.

Aged↗