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The utility of the in situ detection of T-cell receptor Beta rearrangements in cutaneous T-cell-dominant infiltrates.

The diagnostic assessment of cutaneous T-cell infiltrates is problematic for dermatopathologists. A variety of conditions, including lymphomatoid hypersensitivity reactions and lymphomatoid lupus erythematosus, can demonstrate lymphoid atypia and phenotypic changes that can mimic cutaneous T-cell lymphoma (CTCL). A similar issue revolves around lymphoid dyscrasias, which includes parapsoriasis, atypical pigmentary purpura, pityriasis lichenoides chronica, indeterminate lymphocytic lobular panniculitis, and lymphomatoid papulosis, which can progress to CTCL. A reverse transcription (RT) in situ PCR assay for T-cell receptor beta rearrangements (TCRbeta) was used to assess T-cell clonality in formalin-fixed, paraffin-embedded tissues. In 7 of 8 cases of classic CTCL, the RT in situ PCR assay for TCRbeta rearrangement showed monoclonality; the other was biclonal. Further, in cases with multiple lesions over time, the same T-cell clone could be detected including in those patients whose biopsies showed large-cell transformation. Monoclonality was also demonstrated in each of 2 cases of cutaneous lymphomatoid papulosis. Demonstration of oligoclonality (and one case of biclonality) by RT in situ PCR was confined to those cases that either represented prelymphomatous conditions such as large plaque parapsoriasis or pityriasis lichenoides or lesions of drug-induced lymphomatoid hypersensitivity that all demonstrated clinical regression. In conclusion, RT in situ PCR for TCRbeta, which can be done on formalin-fixed biopsies and allows direct correlation of the molecular data with the histology, is a useful adjunctive test in the differentiation of CTCL from its mimics.

Adult↗

Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma.

Eighty-two patients with either mycosis fungoides (MF) or parapsoriasis en plaques were treated with psoralens ultraviolet A light (PUVA). Clinical and histologic parameters were followed for a period from 6 months to 10 years. Complete clinical clearing of lesions was observed in 51 patients (62%) and most of them were in limited-plaque MF group or parapsoriasis en plaque. The mean total dose of PUVA for complete clearing was less for early MF. Thirty-one patients (38%) relapsed and responded to additional PUVA. Patients in early stages of the disease remained clear for up to 68 months after the first course of PUVA. Post-treatment skin biopsies with early MF showed histologic clearing. A new combination therapy for MF is presented in 15 patients. Recombinant interferon alpha-2a (Roferon-A), administered intramuscularly combined with PUVA were tested in a phase I trial. Interferon doses were from 6-30 million units three times weekly. Disease stages ranged from I-B to IV-B. Complete responses were obtained in 12 of 15 patients, and partial responses seen in 2 of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 23 months (range, 3 to 25 months). All responding patients have been maintained on therapy. The dose-limiting toxicities were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). Interferon plus PUVA appear to be highly effective regimens for the treatment of patients with cutaneous T-cell lymphomas.

Adult↗

Cornified envelopes in congenital disorders of keratinization.

A morphological and biochemical analysis was made of cornified envelopes isolated from patients with different congenital disorders. Nomarski contrast microscopy of the envelopes showed that their morphology was not greatly altered in several types of keratoderma and parapsoriasis, but it was grossly modified in ichthyotic disorders. The various types of ichthyoses, keratoderma palmoplantare, KID syndrome and parapsoriasis showed, after cyanogen-bromide cleavage, peptide patterns similar to those obtained from healthy subjects. In contrast, envelopes from patients with Darier's disease, congenital pachyonychia and erythrokeratoderma variabilis showed markedly different peptide patterns.

Adolescent↗

Malignant melanoma associated with mycosis fungoides.

2 cases of malignant melanoma in 2 male patients, 68 and 63 years old, associated with mycosis fungoides and parapsoriasis en plaques, respectively, are reported. The parapsoriasis later on developed into mycosis fungoides. A pathogenetic linkage based on decreased cellular immunity in mycosis fungoides is suggested.

Aged↗

Toll-like receptors 2, 4 and 9 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome).

The aim of this work was to study Toll-like receptors (TLRs) 2, 4 and 9 expression patterns in parapsoriasis and in cutaneous T-cell lymphoma (CTCL): Mycosis fungoides (MF) and Sézary syndrome (SS) at different stages of the illness. The expression of TLRs was examined by immunohistochemistry on paraffin-embedded biopsies. Normal skin, atopic dermatitis and psoriasis, were used as controls. In cutaneous lesions of inflammatory diseases (atopic dermatitis, psoriasis) the expression of TLR2, TLR4 and TLR9 was low compared to normal skin. In parapsoriasis the expression of the three TLRs was similar to control. By contrast, in MF skin we observed a strong intensity of labelling with the three TLRs in the epidermis. Concerning SS, the expression of TLR2, TLR4 and TLR9 was intermediate between inflammatory lesions and MF. Thus, the development of skin lesions in MF appears associated with an increase of TLR2, TLR4 and TLR9 expression by keratinocytes in cutaneous lesions, which could play a role in the chronic activation of T lymphocytes in the skin.

Biopsy↗

Use of polymerase chain reaction in the detection of clones in lymphoproliferative diseases of the skin.

Early-stage mycosis fungoides shows similar clinical symptoms and histological and immunophenotypical features to several benign lymphoproliferative skin disorders. We analyzed T cell receptor gamma gene rearrangement by polymerase chain reaction in the search for monoclonal lymphoid subpopulations in skin infiltrates. Totally, 283 skin biopsies (paraffin-embedded and frozen material) from patients with different malignant and reactive skin diseases were investigated. Using primers for the T cell receptor gamma chain gene, monoclonality was detected in 59 out of 66 (89%) cases of pleomorphic cutaneous lymphoma, in 60 out of 78 (77%) patients with mycosis fungoides, in 11 out of 22 (50%) cases of parapsoriasis en plaques, in five out of 35 (14%) cases of pseudolymphoma, in six out of 15 (40%) patients with lymphomatoid papulosis, and in none out of 64 patients with inflammatory skin diseases. The results show that clonal T cell population can be detected in the majority of patients with cutaneous T cell lymphoma, but the findings have to be correlated with the histological and morphological features.

Clone Cells↗

[The excimer laser in dermatology and esthetic medicine].

First reports about the use of the excimer laser in dermatology date back to 1997. It is seen as an improvement on conventional phototherapy and photochemotherapy because of the lower cumulative UV-dose involved, the shorter time frame required for treatment and the option of targeting individual lesions without affecting the surrounding healthy skin. In addition to the indications of psoriasis vulgaris, vitiligo and atopic eczema (for which there is now FDA approval in the US), the spectrum of possible uses for the excimer laser is growing rapidly, especially in the field of light-sensitive dermatoses. Case studies so far have ranged from post-operative hypopigmentation to acne vulgaris and from alopecia areata to parapsoriasis en plaque. The foremost priorities in the future will be to evaluate reproducible therapeutic regimens with realistic prospects of success in large-scale studies; assess potential iatrogenic risks in treatment; develop pathogenetic models for the mechanism of action; and define therapeutic approaches to new indications. This paper summarizes the publications to date and discusses our observations and experiences.

Acne Vulgaris↗

[Parakertosis variegata after pityriasis lichenoides et varioliformis acuta].

We report on a 34-year-old male patient who developed generalized parakeratosis variegata lesions 4 years after suffering from pityriasis lichenoides et varioliformis acuta. For further investigation of a possible interrelationship between these two diseases of the parapsoriasis group and their relationship to the T-cell type of cutaneous non-Hodgkin-lymphoma, histological, immunohistological and molecular-biological techniques were applied. We were able to demonstrate typical morphological features common to both diseases, and a polyclonal T-cell infiltrate in both. It is concluded that pityriasis lichenoides et varioliformis acuta and parakeratosis variegata are separate entities without monoclonal rearrangement or signs of malignancy.

Adult↗

Home ultraviolet phototherapy of early mycosis fungoides: preliminary observations.

Thirty-one patients with early mycosis fungoides (MF) and three patients with parapsoriasis en plaques were treated with ultraviolet phototherapy (280 to 350 nm) at home using a commercially available light source containing four Westinghouse FS40 lamps. A complete clinical and histologic remission of disease, lasting for a median duration in excess of 18 months, was achieved in nineteen patients (61%) with MF. Although higher complete response rates generally are achieved with other therapeutic modalities, ultraviolet phototherapy with its minimal adverse effects may be indicated for selected patients. Controlled studies are encouraged to evaluate the full potential of conventional phototherapy in the management of MF.

Adult↗

Evaluation of a 1-h exposure time to mechlorethamine in patients undergoing topical treatment.

BACKGROUND: Mechlorethamine is frequently used in the treatment of cutaneous lymphoma, but its application is limited in 30-80% of cases because of cutaneous intolerance. Reducing the concentration to avoid this side-effect has been only modestly successful. OBJECTIVES: To investigate whether a shorter application period could reduce the frequency of intolerance. METHODS: In an open prospective study in 39 patients with cutaneous T-cell lymphoma or parapsoriasis, mechlorethamine was applied according to the usual practices of the participating physicians (number of weekly applications, treatment confined to lesions or performed over the entire body) and then washed off after 1 h in all cases. RESULTS: Cutaneous intolerance was observed in 19 of 39 patients (49%). Six of these patients showed allergic contact dermatitis to mechlorethamine after a mean period of 9.3 weeks, while the other 13 developed irritant contact dermatitis after a longer period. Cutaneous intolerance did not differ significantly according to the number of applications per week or the extent of body area treated. The therapeutic response rate was 69%, and no difference in therapeutic efficacy was noted between daily and intermittent applications. CONCLUSIONS: Comparison with published studies showed no significant difference in the number of cases of cutaneous intolerance after short-term application, although their occurrence was delayed. Therapeutic response was decreased appreciably by short-term application as compared with results in the literature.

Administration, Topical↗

Chromosomal abnormalities in relation to clinical disease in patients with cutaneous T-cell lymphoma: a 5-year follow-up study.

BACKGROUND: Patients with cutaneous T-cell lymphoma (CTCL) show chromosomal aberrations in skin and blood lymphocytes. OBJECTIVES: To evaluate the significance of peripheral blood clonal or non-clonal chromosomal abnormalities in comparison with the clinical course of cutaneous T-cell lymphoma patients. PATIENTS/METHODS: Five patients with large-plaque parapsoriasis (LPP) or with follicular mucinosis, eight with mycosis fungoides and two with Sézary syndrome were followed for an average of 54 months. G-banding and enzyme-detected in situ hybridization (EDISH) were used to identify aberrations in chromosomes 1, 6, 8, 9, 11, 13/21, 15 or 17, that had previously showed frequent aberrations. RESULTS: The aberration rates of all chromosomes studied differed between patients with active disease and healthy or photochemotherapy-treated controls by EDISH or G-banding (P < 0.01 to P < 0.05). Patients in complete remission differed from healthy controls for aberrations of chromosomes 1, 6 and 11, and from patients with active, progressing disease for chromosomes 1, 6, 8, 11 and 17 (P < 0.01 to P < 0.05, EDISH or G-banding). All 11 samples representing active, progressing disease showed elevated levels of chromosome 8 aberrations in EDISH. The change in chromosomal aberration rate and clinical condition between two consecutive samples agreed for chromosomes 1, 8, 9 and 15 (G-banding) and for chromosome 17 (G-banding and EDISH; kappa > 0.5-0.6). Six of seven patients (five CTCL, one LPP patient) with clonal chromosomal aberrations by G-banding showed continuously active disease and four of them, but none of the other patients, died within 30 months of the detection of the clone. CONCLUSIONS: The rate of chromosomal aberrations associates with the activity of CTCL, and has prognostic significance. Aberrations of chromosomes 1, 6 and 11, although increasing with activity of the disease, seem to be a hallmark of existing disease, detectable even in remission. Aberrations of chromosomes 8 and 17 especially associate with active or progressive disease.

Adult↗

[Therapy of pruritus associated with skin diseases with the serotonin receptor antagonist ondansetron].

BACKGROUND: Pruritus is often a stressing symptom and a therapeutic challenge. We report our experience with the serotonin receptor antagonist ondansetron in the symptomatic treatment of pruritus accompanying various skin diseases. PATIENTS AND METHODS: The influence of ondansetron (8-12 mg orally per day) on pruritus was assessed in twelve patients with various skin disorders. The intensity of pruritus was quantitated daily by a visual analogue scale over the time period of one week before, during, and one week after treatment. RESULTS: Ondansetron decreased pruritus intensity in prurigo simplex (four patients), asteatotic eczema (two patients), parapsoriasis en plaques, and pruritus of unknown origin (one patient each). One of two patients with atopic dermatitis experienced relief, whereas no benefit was observed in urticaria factitia and notalgia paraesthetica (one patient each). CONCLUSIONS: Ondansetron may ameliorate the concomitant pruritus of some dermatologic diseases.

Administration, Oral↗

Identification of the testis-specific protein 10 (TSGA10) as serologically defined tumour-associated antigen in primary cutaneous T-cell lymphoma.

BACKGROUND: The number of identified tumour-associated antigens for cutaneous lymphoma is still very restricted, which limits the elucidation of the tumour immunology of these malignancies and the development of specific immunotherapies and immunodiagnostics. OBJECTIVES: To identify new serologically defined antigens associated with cutaneous lymphoma. METHODS: A phage expression library of the human testis transcriptom was established and immunoscreened with sera from 100 patients with cutaneous lymphoma and nine with parapsoriasis, and 81 age-matched control donors. Positive expression clones were sequenced to identify the respective antigen. RESULTS: The testis-specific protein 10 (TSGA10) was identified as an antigen recognized by sera of two patients with Mycosis fungoides but not by sera from healthy donors. By reverse transcription-polymerase chain reaction analysis, TSGA10 was found expressed in all cutaneous lymphoma samples tested, various tumour cell lines, testis, peripheral blood mononuclear cells, skin, isolated lymphocytes, keratinocytes and fibroblasts. TSGA10 overexpression had previously been reported for other cancers. CONCLUSIONS: TSGA10 is a new tumour-associated antigen of cutaneous lymphoma.

5' Untranslated Regions↗

Eosinophilic histiocytosis. A subset of lymphomatoid papulosis.

A 43-year-old male with a 23-year history of small-plaque-type parapsoriasis developed a chronic recurrent self-healing papulonodular and tumoral cutaneous eruption. The microscopic findings were consistent with eosinophilic histiocytosis. Immunohistochemical and ultrastructural studies revealed a population of T lymphocytes, eosinophils and monocyte-macrophage cells in the dermal infiltrate. These findings confirm the similarities between eosinophilic histiocytosis and lymphomatoid papulosis suggesting that the former may be a clinicopathologic variant of the latter.

Adult↗

[Differential diagnostic studies using the dermatoscope in selected diseases].

The Zeis dermatoscope can be used beyond its known applications for precise and detailed skin surface examinations of different types of dermatosis. Differential diagnostic problems are solved by comparative observation of efflorescence and efflorescence fields of similar appearance. The examination series presented, the results of which are discussed in detail, is concerned mainly with surface examinations of parapsoriasis en plaques, seborrhea en plaques and the clinically similar early forms of mycosis fungoides. Also mentioned are examinations of lichen sclerosus et atrophicus and circumscribed scleroderma, lichen planus, Hutchinson-Dubreuilh freckle and similarly appearing facial verruca seborrhoica, as well as fresh dispersions of foreign bodies. The didactic value is underlined by color photographs taken of diseased skin and nails with the dermatoscope at various magnifications. Finally, a description is given of possible instrument extensions.

Dermatitis, Seborrheic↗

Pityriasis lichenoides and lymphomatoid papulosis.

The clinical features, histopathology, immunopathology, and management of pityriasis lichenoides and lymphomatoid papulosis are discussed, with particular emphasis on the pediatric aspects of these conditions. The difficulties in logically separating pityriasis lichenoides into an acute (pityriasis lichenoides et varioliformis acuta) and a chronic (pityriasis lichenoides chronical) form are addressed. The development of lymphoreticular malignancy in patients with lymphomatoid papulosis has been well documented, but pityriasis lichenoides has characteristically been regarded as a benign condition. However, recent reports of the development of large plaque parapsoriasis in patients with pityriasis lichenoides have led to a reconsideration. Some of these patients were in the pediatric age group. Although there are significant clinical, histopathological, and immunopathological differences between pityriasis lichenoides and lymphomatoid papulosis, the demonstration of similar clonal T cell receptor gene rearrangements and the confirmation of the potentially premalignant nature of both suggests that there may indeed be an interrelationship between these two controversial entities. Close follow-up of patients with both of these conditions is recommended, with observation being discontinued only when the patient has been free of lesions for several years.

Child↗

[Comparative analysis of the cell composition of the infiltrate in malignant lymphoma of the skin].

Electron microscopy was used to investigate skin biopsy specimens in 20 patients with different clinicomorphological types of T-cell skin lymphomas (TCSL) over time. At early stages prognosis was based on the level of macrophage and fibroblast differentiation in the infiltrate: the more mature nonlymphoid elements were, the graver was a course of disease. Therefore patch and papulous variants of primary cutaneous reticulosis (atrophic parapsoriasis and mycosis fungoides with follicular mucinosis) were classified as TCSL of a low and medium degree of malignancy. The classical and beheaded forms of mycosis fungoides were attributed to a medium and high degree of malignancy.

Biopsy↗

[Preliminary results of Re-PUVA therapy in cutaneous T-cell lymphomas].

Eight patients with T-cell-lymphoma of the skin (6 mycosis fungoides, 2 parapsoriasis variegata) were treated with Tigason in combination with PUVA-therapy. The daily dose of Tigason was 50-100 mg. There was complete regression of skin lesions in three patients, partial regression in three patients, and an improvement in two patients.

Combined Modality Therapy↗