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  • 1
    Electronic Resource
    Electronic Resource
    CD45RA+ immunophenotype in mycosis fungoides: clinical, histological and immunophenotypical features in 22 patients (2001)
    Copenhagen : Munksgaard International Publishers
    Journal of cutaneous pathology 28 (2001), S. 0 
    Details
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) usually characterized by a T-helper memory phenotype (CD3+, CD4+, CD8−, CD45R0+). Aberrant phenotypes are more commonly seen in the tumor stages. CD45RA expression has so far been documented in only a few cases of CD8+ or TCRγδ+ CTCL and in some pagetoid reticulosis cases.Methods: Two hundred and fifteen MF patients were immunophenotyped in our laboratory between January 1992 and June 2000 and 22 cases of CD45RA+ MF (8.7%) were identified by immunohistochemical analysis.Results: The majority of these CD45RA+ patients (20/22) showed a patch-plaque stage disease and an indolent clinical course, as expected in early-stage MF. The remaining 2 patients presented with stage IIB and IVA MF, and were characterized by an aggressive clinical course, with systemic spread. The immunohistochemical analysis revealed that CD45RA+ neoplastic cells belonged to the memory compartment, displaying a CD62L−, CD11a+, CD29+ phenotype. Most patients showed aberrant phenotypes, with a loss of T-cell lineage markers and expression of cytotoxic molecules or gamma-delta chain of the T-cell receptor.Conclusions: Our data show that CD45RA+ MF is a rare variant of CTCL and shares with the classic MF cases both the clinical features and disease course, even if it is characterized by a higher incidence of immunopathological abnormalities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0560.2001.280704.x
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  • 2
    Electronic Resource
    Electronic Resource
    Treatment of advanced mycosis fungoides/Sézary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 150 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Purine analogues [fludarabine monophosphate (FAMP); deoxycoformycin and 2-chlorodeoxyadenosine) and extracorporeal photochemotherapy (ECP) have been suggested to be active agents in advanced cutaneous T-cell lymphoma (CTCL) patients.Objectives  To explore further the clinical efficacy and safety of FAMP monochemotherapy in advanced CTCL and to evaluate if the sequential association of ECP to FAMP in selected patients may improve the response rate (RR) and/or lengthen the remission duration.Patients and methods  Forty-four CTCL patients [17 Sézary syndrome (SS); 26 mycosis fungoides (MF), stage IIB–IV or with peripheral blood involvement; one MF associated with lymphomatoid papulosis (LyP)] were enrolled in this pilot cohort study. All the patients received FAMP 25 mg m−2 5 days monthly; 19 patients (43·2%) underwent ECP after FAMP was discontinued. The majority of patients with erythrodermic CTCL or peripheral blood involvement underwent the combined FAMP–ECP schedule.Results  After a median follow-up of 4·2 years, the overall FAMP RR was 29·5% (13/44); a higher RR was obtained in SS (35·3%) than in MF patients (25·9%). According to the treatment group, the RR of the FAMP–ECP group (63·2%) was significantly higher than that of the FAMP monotherapy group (24%; P = 0·021). No statistically significant difference was found in time-to-progression (TTP) or survival by therapy group, even if the TTP of the patients treated with the FAMP–ECP combination therapy was higher (median 13 vs. 7 months). A decrease or a normalization in the CD4+CD26– circulating subset was observed in responding patients, paralleling the reduction in the circulating Sézary cells.Conclusions  FAMP confirms its clinical activity as a single agent in SS; conversely, FAMP results do not compare favourably with other therapeutic approaches for advanced stage MF patients. The sequential association of ECP after FAMP seems to increase the RR, even if future randomized studies are needed to confirm these results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.05712.x
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  • 3
    Electronic Resource
    Electronic Resource
    CD56-positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease (1997)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 137 (1997), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas: the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis: azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR β-chain gene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.1997.19952076.x
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  • 4
    Electronic Resource
    Electronic Resource
    Keratinocytes express dipeptidyl-peptidase IV (CD26) in benign and malignant skin diseases (1996)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 134 (1996), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using Immunohistochemlcal techniques. A sporadic focal CD26 positivity was found in normal skin, whereas increased expression of CD26 was observed both in cutaneous T-cell lymphomas and in inflammatory skin diseases, e.g. psoriasis, lichen planus and spongiotic dermatitis, in the basal and spinous layers, CD26 keratinocyte staining was not specific for a single disease, but seems to be associated with the presence of a reactive or neoplastic infiltrate in the epidermis. We propose that the CD26molecule may function as a keratinocyte activation antigen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.1996.d01-900.x
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  • 5
    Electronic Resource
    Electronic Resource
    Disseminated Kaposi's sarcoma associated with idiopathic CD4+ lymphocytopenia and low dose steroid therapy (2005)
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 30 (2005), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A case of disseminated Kaposi sarcoma in a 76-year-old woman treated with low-dose steroids for a seronegative polyarthritis is described. HIV serology was negative, whereas PCR for HHV-8 was positive. The patient presented with a profound reduction in the peripheral blood CD4+ cell count and a decrease in serum immunoglobulins and was diagnosed as having idiopathic CD4+ lymphocytopenia. The clinical picture was characterized by limited cutaneous lesions with typical features of KS associated with widespread visceral involvement and unusually aggressive behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.2005.01795.x
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  • 6
    Electronic Resource
    Electronic Resource
    T-cell receptor γ gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome) and benign inflammatory disease: correlation with clinical, histological and immunophenotypical findings (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  A dominant T-cell clone can be detected by polymerase chain reaction (PCR) in 40–90% of cutaneous samples from patients with cutaneous T-cell lymphoma (CTCL).Materials and methods  From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sézary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64·5%) and CTCL in 194 (35·5%). T-cell receptor (TCR)-γ gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T-cell lineage antigen loss, using univariate and multivariate logistic regression analyses.Objective  To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T-cell clonality.Results  A clonality was demonstrated in 83·5% of CTCL and in 2·3% of BID (P 〈 0·001). A significantly higher percentage of clonal cases was associated with the cutaneous T-score (71·4% in T1, 76·1% in T2 and 100% in nodular and erythrodermic MF samples) and with the presence of a T-cell lineage antigen loss (93·9% vs. 77·4%). Moreover, clonality was closely related to an increase in the histopathological score (51·3% in the samples with a score 〈 5, compared with 92% in the lesions with ≥ 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score ≥ 5. The multivariate logistic regression showed that the density and extent of the cell infiltrate, the degree of epidermotropism and the presence of cytological atypia share an independent predictive value for clonality in T1/T2 samples, even if the highest odds ratios (3·6) were associated with the density of the cell infiltrate. The disease course of T1/T2 patients was analysed according to the PCR findings. All the PCR-negative patients showed a long-standing stable disease course; on the other hand, a disease progression occurred in 12/87 (13·8%) positive patients.Conclusions  The multiplex PCR/HD analysis is associated with a high diagnostic accuracy (92·7%) in CTCL patients. The finding of a clonal T-cell rearrangement is more closely associated with the histological pattern (in particular with the density and extent of the cell infiltrate) rather than with the MF cutaneous T-score or immunophenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06649.x
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  • 7
    Electronic Resource
    Electronic Resource
    The relevance of the CD4+ CD26– subset in the identification of circulating Sézary cells (2001)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 144 (2001), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary syndrome (SS) patients makes it difficult both to ascertain the presence of clonal cells and to quantify the tumour burden in the peripheral blood. In previous reports we showed that the lack of CD26 (dipeptidyl-aminopeptidase IV) is a characteristic feature of circulating Sézary cells (SC). Objectives  The purpose of this study was to ascertain, by means of high-resolution two-, three- or four-parameter flow cytometry, the relationship between CD26 expression on peripheral blood lymphocytes and peripheral blood involvement in cutaneous T-cell lymphoma patients and to assess its significance in SS diagnosis. Methods  The patient population included 52 SS patients, 151 mycosis fungoides (MF) patients at different clinical stages (including 14 with blood involvement, B1-MF), 88 patients with erythrodermic inflammatory skin diseases (EISD) and 72 healthy donors (HD). CD26+ values were available in all cases, whereas CD4+ CD26– level measurement was performed in 23 SS, 141 MF, 71 EISD and 72 HD. Results  CD4+ CD26– percentage values were higher than 30% in all but one B1-MF and higher than 40% in all SS cases, whereas HD, EISD and B0-MF patient values were always lower than 30%. A statistically significant difference was found in both CD26– and CD4+ CD26– percentage and absolute values between SS and HD, EISD and B0-MF patients. The CD26– and CD4+ CD26– percentage values (but not the absolute values) were significantly higher in B1-MF compared with HD, EISD and B0-MF patients (P 〈 0·001). Moreover, CD26– absolute values and CD4+ CD26– percentage and absolute values were significantly higher in SS than in B1-MF (P 〈 0·001). A statistically significant direct relationship was found between CD4+ CD26– percentage values and the percentage of circulating SC within the lymphoid population in SS and B1-MF (r = 0·77; P 〈 0·001). The lack of CD26 was confirmed on phenotypically clonal cells in patients with an expanded circulating TCRvβ population or a T-cell antigen loss. Sorted CD4+ CD26– cells from both SS patients and HD showed the characteristic cerebriform nuclei of SC. Conclusions  We feel that a CD4+ CD26– percentage value higher than 30% of peripheral blood lymphocytes could correctly identify the presence of peripheral blood involvement in SS and MF patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2001.04014.x
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  • 8
    Electronic Resource
    Electronic Resource
    In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid pro-drug on melanoma cells: Evaluation of antiproliferative activity and apoptosis induction (2000)
    Springer
    Clinical & experimental metastasis 18 (2000), S. 663-673 
    Details
    ISSN: 1573-7276
    Keywords: apoptosis ; butyrate ; cell cycle ; cholesteryl butyrate ; drug delivery ; melanoma ; solid lipid nanospheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G0/1-S transition block and a `sub-G0/1' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1013186331662
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  • 9
    Electronic Resource
    Electronic Resource
    Prognostic factors in Sézary syndrome: A multivariate analysis of clinical, haematological and immunological features (1998)
    Springer
    Annals of oncology 9 (1998), S. 857-863 
    Details
    ISSN: 1569-8041
    Keywords: cutaneous T-cell lymphoma ; multivariate analysis ; Sézary syndrome classification ; Sézary syndrome immunology ; Sézary syndrome prognosis ; Sézary syndrome therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Sézary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to assess by multivariate analysis the predictive value with respect to survival of a series of clinical, haematological and immunological parameters taken at SS diagnosis. Patients and methods: A cohort of 62 SS patients diagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model. Results: The median survival time was 31 months (range: 1 month–15.7+ years), and the five-year survival rate 33.5%. The following variables were found by univariate analysis to be associated with a poor prognosis at the time of SS diagnosis: previous history of mycosis fungoides (P = 0.013), high number of circulating leukocytes (P = 0.001), Sézary cells (SC) (P 〈 0.001) and CD4+ cells (P 〈 0.001), presence of large circulating SC (P 〈 0.001), above normal range LDH serum levels (P = 0.015), presence of PAS-positive inclusions in the cytoplasm of circulating SC (P 〈 0.001), high CD4/CD8 ratio (P = 0.004) and a CD7 negative circulating SC phenotype (P 〈 0.001). Among them, the stepwise multivariate analysis selected as adverse independent prognostic factors: PAS-positive cytoplasmic inclusions (P = 0.001), CD7 negative phenotype (P = 0.018) and presence of large circulating SC (P = 0.045). Conclusions: Two low-/high-risk groups have been singled out on the basis of the risk index. Patients with no or one adverse prognostic feature(s) (risk index ≤ 1; n = 31) share a slow disease course and a relatively favorable prognosis (five-year survival: 58%); on the other hand, patients with 2 or 3 adverse prognostic features (risk index 〉 1; n = 20) are characterized by an aggressive disease course not modifiable by traditional therapies (five-year survival: 5%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008397323199
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