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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.

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.

Notes: Soluble interIeukin-2 receptor (sIL-2R) serum levels were evaluated in Sézary syndrome (SS). mycosis fungoides. non-epidermotropic T-cell lymphomas. inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow-up of 17 SS patients showed that serum SIL-2R correlated with the clinical course of the disease and with other haematologicai parameters (ahsolute numher of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematoiogical disorders, highly enriched resting Sézary cells were unahle to release sII-2R. and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastie sIL-2R source. To further support this hypothesis, the highest sIT.-2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced.

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.

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.

Notes: T and B lymphocyte populations were evaluated in 56 patients with malignant melanoma. Active rosettes (T-Ea) were decreased only in metastatic patients, while the total T population (T-Et) was decreased in all stages. In addition the metastatic patients presented significant decreases in IgD and IgM subpopulations. An increase in null cells was noted in metastatic patients. Regular controls over a period of 2 years showed that T-Ea levels were closely linked to the clinical picture. Patients whose values were constant remained cancer free, while a reduction heralded the appearance of clinical and/or radiological signs of metastasis.

Notes: Angioimmunoblastic lymphadenopathy with dysproteinaemia is reported (AILD) in four patients with different skin pictures. As the disease progresses two main forms predominate: papulonodular and erythroderma. In all cases the histological picture of the skin mirrors that of the lymph-node.Our results point to an increase in the peripheral blood, lymph-nodes and skin of T and sub-sequently of B lymphocytes suggesting that a proliferation of helper T cells and hence activation of the B-cell subpopulation may be involved in the pathogenesis of some cases of AILD.

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.