Dermal infiltrates of cutaneous T-cell lymphomas with epidermotropism but not other cutaneous lymphomas are abundant with langerin⁺ dendritic cells.

BACKGROUND: The Langerhans cell (LC) hypothesis suggests that cutaneous T-cell lymphomas (CTCL) are diseases of chronic T-cell stimulation by LC-mediated antigen presentation. OBJECTIVE: To investigate a broad panel of CTCL and cutaneous B-cell lymphomas (CBCL) for the spatial association of langerin(+) dendritic cells (DC) with T and B cells in the skin, respectively. METHODS: Fifty-five specimens of CTCL and 10 of CBCL were double-stained with monoclonal antibodies against langerin and CD3 or CD20, respectively, and evaluated by confocal laser scan microscopy. RESULTS: Dermal infiltrates in mycosis fungoides (n = 38), primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (n = 3) and primary cutaneous peripheral T-cell lymphoma, unspecified (n = 3) were characterized by a high frequency of dermal langerin(+) DCs. These cells were exclusively present in the malignant infiltrates. No direct co-localization of CD3 and langerin could be resolved. Dermal langerin(+) cells were detected only in one of six primary cutaneous anaplastic large cell lymphomas (C-ALCL), characterized by epidermotropism. In other C-ALCL cases (five of six), in lymphomatoid papulosis (n = 3), subcutaneous panniculitis-like T-cell lymphoma (n = 2), and all variants of CBCL no dermal langerin(+) DCs could be found. CONCLUSIONS: Langerin(+) DCs are abundant in the dermal infiltrates of T-cell lymphomas with specific involvement of the epidermis. This might indicate that immature LC and neoplastic T cells interact and gives rise to further studies to characterize the phenotype of the langerin(+) cell population described here and its role in the pathology of CTCL.

Somatostatin receptor scintigraphy in primary cutaneous T- and B-cell lymphomas.

BACKGROUND: Monitoring and repeated staging is of substantial importance in many patients with primary cutaneous T-cell lymphomas (CTCL). For primary cutaneous B-cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis. AIM: To evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog (111)In-pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL. METHODS: Twenty-two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of (111)In-pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions. RESULTS: Of the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sézary syndrome, had a positive (111)In- pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B-cell lymphoma - leg type, but again not in all apparent sites of lymphoma. CONCLUSIONS: Based on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST-R in the staging of patients with cutaneous lymphomas.

Rituximab monotherapy for primary cutaneous B-cell lymphoma: response and follow-up in 16 patients.

BACKGROUND: We have carried out a retrospective analysis to evaluate the therapeutic value of the anti-CD20 antibody rituximab in 16 consecutive patients with primary cutaneous CD20+ B-cell lymphomas. PATIENTS AND METHODS: Sixteen patients (4 females, 12 males) with a median age of 54 years received systemic therapy with rituximab 375 mg/m(2) once weekly for four or six consecutive weeks. Eleven patients had primary cutaneous follicle center cell lymphoma and five patients had a primary cutaneous marginal zone B-cell lymphoma. RESULTS: Of the 16 patients with PCBCL, 14 patients (87.5%) achieved complete remission (CR). In two patients, partial remission was obtained and additional focal radiotherapy was applied, which resulted in final CR. Five to 14 (35%) patients with CR relapsed, in an interval between 6 and 37 months. There were no severe side-effects. CONCLUSIONS: On the basis of our results, single-agent treatment with i.v. rituximab appears to be feasible and safe and results in a high rate of durable remissions. Judging from our data, it appears to be an attractive treatment option and should be directly compared with local radiotherapy.

Photodegradation of folic acid during extracorporeal photopheresis.

BACKGROUND: Photodegradation of folic acid (FA) by ultraviolet (UV) radiation is a well-documented photochemical reaction, and decreased serum levels of FA have been found in patients receiving photochemotherapy (psoralen plus UVA). During extracorporeal photopheresis (ECP) leucocytes and plasma are subjected to 8-methoxypsoralen (8-MOP) plus UVA. OBJECTIVES: To investigate whether ECP leads to the photodegradation of FA in the extracorporeal system. METHODS: In 30 patients undergoing ECP on two consecutive days the FA levels were measured in the extracorporeal collected plasma prior to and after UVA exposure. Healthy donor plasma was exposed to 8-MOP and increasing doses of UVA in vitro. In five patients serum folate levels were determined before and after ECP. RESULTS: We found a mean reduction of 44% and 46% on the first and second day of treatment, respectively. This effect could be reproduced in vitro: the irradiation of healthy donor plasma with UVA led to a dose-dependent reduction of FA of up to 54.75% at 16 J cm(-2). This was independent of the presence of 8-MOP and the base concentration of 5-methyltetrahydrofolate; minimal changes were observed for vitamin B(12) and homocysteine, not undergoing photodegradation. Serum folate levels did not change significantly before and after ECP. CONCLUSIONS: We conclude that extracorporeal exposure of plasma to UVA during ECP leads to photodegradation of FA. Further investigations are required to determine the biological effects of folate photoproducts and whether clinically relevant loss of FA might be a consequence of ECP.

Half-side comparison study on the efficacy of 8-methoxypsoralen bath-PUVA versus narrow-band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis.

In patients with severe chronic atopic dermatitis (AD), both photochemotherapy [psoralen ultraviolet A (PUVA)] and narrow-band (TL-01) UV B phototherapy have been reported to be very effective. As no data exist on the relative therapeutic efficacy of these two regimens, we performed a randomized investigator-blinded half-side comparison study on 12 patients with severe chronic AD. Half-side irradiation with threshold erythemogenic doses of 8-methoxypsoralen bath-PUVA and narrow-band UVB was performed three times weekly over a period of 6 weeks. The severity of the disease was assessed separately for the paired halves of the patients' bodies by a modified SCORAD score at baseline and after 2, 4 and 6 weeks of treatment. Ten of the 12 patients completed the trial. All but one showed marked improvement or complete remission with both treatments. The mean baseline SCORAD score decreased by 65.7% by the bath-PUVA treatment and by 64.1% by the narrow-band UVB treatment (P = 0.48). No serious adverse reactions to either of the two regimens were observed. Our data confirm the high efficacy of bath-PUVA and narrow-band UVB phototherapy in the treatment of patients with chronic severe AD. Both regimens appear to be equally effective when administered in equi-erythemogenic doses.