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PubMed2000

Mycosis fungoides: classic disease and variant presentations.

Mycosis fungoides is a peripheral non-Hodgkin's T-cell neoplastic process, representing the most common type of primary cutaneous malignant lymphoma. Neoplastic lesions classically show skin predilection and characteristic clinical and histologic features in patch, plaque, and tumor stages. In addition, several clinicopathologic variants of mycosis fungoides have been delineated, including poikiloderma atrophicans vasculare (parapsoriasis variegata), Sézary syndrome, granulomatous mycosis fungoides, hypopigmented mycosis fungoides, folliculocentric mycosis fungoides, syringotropic mycosis fungoides, and Woringer Kolopp disease. We will review the salient features of patch, plaque, and tumor stage mycosis fungoides in this article and follow with a discussion of these variant clinicopathologic presentations and of therapeutic modalities.

Diagnosis, Differential↗
PubMed1999

Meningeal involvement by a transformed mycosis fungoides following Hodgkin's disease.

A 58-year-old man had long-standing lesions of presumed large plaque parapsoriasis. Following treatment for nodal Hodgkin's disease (HD), these became more infiltrated, with a diagnosis of mycosis fungoides (MF). A few months later, nodules appeared on the right leg, which was lymphoedematous after inguinal irradiation for HD. Histopathological examination showed CD3+, CD30-, CD15- large pleomorphic lymphocytes, leading to the diagnosis of transformed MF. The cutaneous lesions were successfully treated with topical nitrogen mustard and interferon alfa-2b then methotrexate, but his general health worsened with depression and malaise, without specific neurological symptoms or extracutaneous spreading of the lymphoma. Cerebral computed tomographic scan revealed a cerebellar subdural collection, arachnoid cyst and quadriventricular hydrocephaly, initially considered to be non-specific. After a few weeks, clinical symptoms of intracranial hypertension appeared, and a cerebrospinal fluid (CSF) examination revealed meningeal involvement by the lymphoma. These cells were CD3-negative and the diagnosis was confirmed by polymerase chain reaction (PCR) study, which revealed an identical clonal rearrangement of the T-cell receptor gamma gene between cutaneous biopsies and the CSF. Repeated intrathecal injections of methotrexate and cranial irradiation were performed and the patient was still alive after 13 months. This case illustrates the possible meningeal involvement of MF that may be preceded by atypical and mild neurological or psychiatric symptoms, which may be dissociated from the evolution of the cutaneous lesions. Moreover, PCR study may be useful for both diagnosis and monitoring.

Follow-Up Studies↗
PubMed2001

Modulation of substance P and somatostatin receptors in cutaneous lymphocytic inflammatory and tumoral infiltrates.

BACKGROUND: The expression of receptors for neuropeptides in the skin is modified in skin diseases. OBJECTIVE: We studied the cutaneous expression of substance P (SP) and somatostatin (SOM) receptors (SPR and SSTR, respectively) in skin affected by cutaneous inflammatory or tumoral T-cell infiltrates because these two neuropeptides are the ones most involved in inflammation. METHODS: We revealed expression of these receptors using a binding in situ technique that gave highly specific results. Skin biopsies were incubated with biotinylated neuropeptides (SP or SOM). RESULTS: In normal skin, SSTR were observed on blood vessels, smooth muscle fibres and sweat glands. SSTR expression was modified only when expressed by keratinocytes in Ofuji papuloerythroderma and by plasmocytes in plasmocytoma. SPR distribution was not modified in subjects with atopic dermatitis or lupus. The expression of SPR in the epidermis was diminished in Ofuji papuloerythroderma and parapsoriasis and absent in mycosis fungoides. CONCLUSIONS: These results suggest that malignant lymphocytic infiltrates can inhibit SPR expression on keratinocytes.

Humans↗
PubMed1994

Value of PCR detection of TCR gamma gene rearrangement in the diagnosis of cutaneous lymphocytic infiltrates.

In this study, we analyzed the reliability and usefulness of the polymerase chain reaction (PCR) for the detection of T-cell receptor (TCR)gamma gene monoclonal rearrangement. We first tested for the specificity and sensitivity of this strategy, against the classical criteria of Southern blot analysis (SBA). Of the 27 samples tested, results agreed in all but two. Broader analysis of these cases demonstrated the high specificity (absence of false positives) of the PCR strategy, together with its limited sensitivity (10% of false negatives). The usefulness of this PCR approach was then tested on a panel of 28 biopsy specimens of cutaneous lymphocytic infiltrates. Monoclonal TCR gamma rearrangement was detected in seven of eight cases of early stage mycosis fungoides (MF), one of two Sezary syndrome (SS) cases, two of two non-MF T-cell lymphoma, and two of three lymphomatoid papulosis. Monoclonality was not detected in any of the 11 benign cases (parapsoriasis and inflammatory dermatosis). Results obtained with this new molecular strategy provide additional support for the hypothesis of a monoclonal origin for most early stage T-cell MF. They also suggest the heterogeneous nature of some lymphomatoid papulosis lesions. Therefore, due to the difficulty in detecting T-cell monoclonality by immunohistochemical techniques, PCR can be a useful alternative strategy to SBA. It could also be used as a complementary technique in the routine diagnosis of T-cell cutaneous infiltrates.

Adolescent↗
PubMed2002

Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues.

Cutaneous T-cell lymphoproliferative disorders (CTCLs) remain a subject of confusion and controversy. In this review, the authors discuss diagnostic criteria and classification, including the role of immunohistochemistry and gene rearrangement studies. In addition, cutaneous T-cell pseudolymphomas, the current status of parapsoriasis and other premalignant syndromes, and the clinicopathological variants of mycosis fungoides are discussed. CD30-positive lymphoproliferative disorders and a number of rare variants of CTCL including granulamatous slack skin, subcutaneous (panniculitic) T-cell lymphoma, gamma-delta cutaneous lymphoma, NK/NK-like T-cell lymphoma, and primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphoma are also considered.

Gene Rearrangement↗
PubMed2004

Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.

Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

Clone Cells↗
PubMed1977

Heliotherapy of pityriasis lichenoides chronica.

Fifteen patients with pityriasis lichenoides chronica (parapsoriasis guttata) were treated with sunlight irradiation during the summer months at seaside resorts under the supervision of the authors. Complete clearing occurred in 1 of the patients, almost complete clearing in 8, definte improvement in 4, temporary clearing in 2. All patients responded beneficially and no worsening was noted in these 15 cases. In an additional six cases who were instructed to expose themselves to sunlight similar results were obtained.

Adolescent↗
PubMed1980

Therapeutic evaluation of the oral retinoid Ro 10-9359 in several non-psoriatic dermatoses.

Forty-five patients suffering from various genodermatoses and erythematous, scaling, non-psoriatic dermatoses were treated orally with the aromatic derivative of retinoic acid, Ro 10-9359 (Tigason). In the genodermatoses the best results were obtained in ichthyosis, keratodermias and Darier's disease (95.6% good to excellent). Among the erythematous scaling diseases, treatment was effective in lichen planus, parapsoriasis and pityriasis rubra pilaris (53.3% good to excellent results). In comparison with therapies previously employed Ro 10-9359 was more effective. No serious side-effects were noted.

Administration, Oral↗
PubMed1992

HTLV-1-negative pleomorphic T-cell lymphoma of the skin: the clinicopathological correlations and natural history of 15 patients.

The peripheral T-cell lymphomas represent a heterogeneous group and include, besides mycosis fungoides and Sézary syndrome, large-cell anaplastic lymphoma. We report 15 cases from our files that fulfil the histological criteria of pleomorphic T-cell lymphoma with primary skin involvement. Most of the cases were elderly with a male-to-female ratio of 1.5:1. The HTLV-1 serology was negative. The clinical features of these patients differed from those with mycosis fungoides and Sézary syndrome, in that eczematous and precursor lesions such as parapsoriasis en plaque were lacking apart from one exception. All the patients with small-cell pleomorphic T-cell lymphomas were alive, although three of the nine patients with medium-to-large tumour cells have died. Pleomorphic T-cell lymphoma should be regarded as a distinct entity among the lymphoproliferative disorders of the skin.

Adult↗
PubMed1989

Cutaneous and ocular side-effects of PUVA photochemotherapy--a 10-year follow-up study.

To record the potentially serious side-effects of melanoma and non-melanoma skin cancers and ocular damage following long-term PUVA chemotherapy, we re-examined 198 of 242 patients. These comprised: 90 with psoriasis, 27 with parapsoriasis, 19 with cutaneous T-cell lymphoma, 23 with vitiligo, eight with cutaneous mastocytosis, 16 with atopic dermatitis, three with prurigo nodularis, two with polymorphous light eruption and 10 with pruritus of chronic renal failure on dialysis, treated between 1977 and 1987 in our department. During the 10-year period, 11 patients died of unrelated disease. None of the patients reviewed had previous skin cancer or had been treated with arsenic, methotrexate or ionizing irradiation before PUVA treatment. None of the patients were children under 16 years of age. The mean age was 54.5 years, the sex ratio 102:96 (M:F). The mean cumulative dose of UVA for the whole group was 169.5 J/cm2. One patient with psoriasis, psoriatic arhropathy, ankylosing spondylitis and Crohn's disease, who was on azathioprine for 6 years, developed squamous-cell carcinoma on the left lower leg. Another patient with pustular psoriasis, who received PUVA treatment to her palms and soles only, developed malignant lentigo of Hutchinson on the right lower leg. PUVA lentigines were found in about 20% of patients. All patients had a yearly ophthalmological examination. None of them developed cataracts, lens opacities or had impairment of their visual acuity.

Adolescent↗
PubMed1995

Densitometry of Pautrier's microabscess cells in cutaneous T cell lymphoma.

BACKGROUND: Epidermotropic lymphoid T cell infiltrates are part of a continuous spectrum of lesions ranging from "benign" parapsoriasis to frank cutaneous T cell lymphoma (CTCL, mycosis fungoides). Either the clinical or histologic differentiation between these entities prove often difficult and the prognosis may be difficult to assess. PATIENTS AND METHODS: We studied 15 patients, men aged 50 to 81 years, mean +/- SD 68 +/- 12 years, with patch-plague CTCL. Sections from punch biopsies from active lesions were stained with Feulgen reagent, coupled with a "twin" adjacent hematoxylin and eosin (H&E)-stained section and analyzed with a VIDAS Zeiss-Kontron Image Analyzer. At least 50 dermal infiltrating cells and 50 epidermotropic Pautrierian cells per specimen were counted and the biopsies were repeated periodically. RESULTS: Nine patients with aneuploid Pautrierian cell DNA patterns dis well after conventional phototherapy (dermal cell ploidy was irrelevant), whereas six patients with euploid Pautrierian cell DNA patterns had to be treated aggressively (IFN + retinoids, COP). Clinical and histopathologic aspects of the first group were comparable to those of the second group. CONCLUSIONS: The classical cytophotometric aphorism seems to be reversed in this sample: "The more abnormal the ploidy of epidermotropic Pautrierian cells, the better the prognosis." Euploid epidermotropic cell prove more efficient in invading the skin and other areas and this efficiency may be reflected in more aggressive trends in the evolution of the lymphoma. Thus, DSM analysis of epidermotropic cells could prove very useful as an inexpensive tool for routine CTCL grading.

Abscess↗
PubMed2003

Atrophying tinea versicolor: a clinical and histological study of 12 patients.

BACKGROUND: We describe 12 patients with an atrophying dermatitis in whom the biopsy findings were compatible with tinea versicolor. DESIGN: We encountered 12 skin biopsies from 12 patients in whom a clinically atrophying dermatosis was associated with light microscopic (LM) evidence of atrophy and epidermal colonization by Pityrosporum sp. Formalin-fixed, paraffin-embedded tissue sections were cut at 5 microns and stained with H&E, alcian blue-PAS and PAS-diastase preparations. RESULTS: Five men and seven women aged 17-73 years in whom lesions characterized as atrophic plaques, patches or macules prompted clinical differential diagnoses including parapsoriasis or mycosis fungoides (MF), anetoderma, lupus erythematosus, and steroid atrophy. A LM examination showed epidermal colonization with pityrosporum hyphae and spores accompanied by variable epidermal and dermal atrophy characterized by rete-ridge effacement, subepidermal fibroplasia, pigment incontinence and elastolysis. CONCLUSIONS: Atrophying cutaneous lesions comprise part of the clinical spectrum of tinea versicolor for which we propose the term 'atrophying tinea versicolor'. The pathogenetic basis is unclear but could be the sequela of delayed type hypersensitivity and the release by T-helper lymphocytes of leukotrienes which perturb collagen metabolism and/or keratinocyte growth. Lesions may be mistaken clinically for MF or other atrophying dermatoses.

Adolescent↗
PubMed1996

T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders. We investigated the variable region (V beta) of the T-cell receptor (TCR) repertoire in CTCL and compared it to the V beta repertoire in normal and eczematous skin. We used a panel of 21 anti-V beta antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13 Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL nor classified). Six biopsies of normal skin and 6 of eczematous skin lesions served as controls. We determined the frequency of the V beta in normal and inflamed skin and compared it to the percentage of the respective V beta in the malignant clone of the CTCL patients. The percentage of the V beta positive CD4+ cells in relation to the total number of T cells in normal skin and inflamed skin differed from the distribution of the V beta families in the peripheral blood mononuclear cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%). We identified the following clones: 1 V beta 3.1 (16MF), 7 V beta 5.1 (1 CD8+ CTCL, 1 CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V beta 6.7 (1 SS), 7 V beta 8.1/8.2 (2 CTCL not classified, 1 PLEO, 2 MF, 2 SS), 1 V beta 12.1 (1 PLEO), 3 V beta 17.1 (2 CTCL not classified, 1 MF), 2 V beta 22.1 (1 CTCL not classified, 1 MF), 1 TCR delta (SS). The frequency of the malignant clone V beta usage corresponded well to the repertoire of V beta in eczematous skin but not to the repertoire in PBMC. In 6 patients, the malignant clone was mainly localized in the epidermis. In 17 cases, the clone-specific cells were distributed in epidermis and dermis equally. A retrospective analysis showed that preferential epidermal homing of the clone was associated with a non-aggressive clinical course. The V beta usage of CTCL and eczema suggests a special cutaneous microenvironment which might be co-created by certain (bacterial?) superantigens. A preferential epidermal homing of the clone might have prognostic implications.

Adolescent↗
PubMed1996

Correlation between clonotypic T-cell receptor beta chain variable region (TCR-V beta) gene expression and aberrant T-cell antigen expression in cutaneous T-cell lymphoma.

Immunohistochemical studies can augment the clinicopathologic diagnosis of cutaneous T-cell lymphoma (CTCL). Our goal was to determine whether a panel of 11 T-cell receptor (TCR) beta chain variable region (V beta) monoclonal antibodies (moAbs) could consistently identify clonal T-cell populations within CTCL skin infiltrates, and whether these cell exhibited aberrant T-cell antigen expression. Biopsies from 24 CTCL and 3 parapsoriasis patients were analyzed. Of the 27 patients, 4 (15%) demonstrated T-cell clonality by restricted TCR-V beta moAb staining. The V beta + restricted cells expressed aberrant antigen profiles. Overall, aberrant antigen profiles were detected in 18/24 (75%) CTCL. Patients. V beta 18 moAb crossreacted with a 85 kD protein produced by basal and suprabasal keratinocytes. We conclude: 1) Restricted TCR-V beta expression correlated with aberrant T-cell antigen profiles: 2) In the absence of a complete panel of TCR-V beta moAbs, localization of aberrant T-cell antigen expression can be useful in identifying malignant T-cells within CTCL skin infiltrates; 3) The detection sensitivity and specificity of the currently available TCR-V beta moAbs may limit their utility to consistently detect clonal T-cell populations in CTCL skin biopsies; 4) A 85 kD protein present on basal and suprabasal keratinocytes is recognized by V beta 18 moAb and may be related to immune function(s) of the epidermis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Development of cutaneous pseudolymphoma following ciclosporin therapy of actinic reticuloid.

The patient is a 57-year-old man with actinic reticuloid, who despite systemic prednisone, azathioprine, topical steroid, and sun-protective cream had to stay indoors in the summer of 1986. In February 1987 he was started on ciclosporin (CS), 5.5 mg per kg body weight, and skin symptoms did not develop as usual in spring and summer 1987. Following 4 months of successful therapy, he developed an indolent tumor on his right chin and parapsoriasis en plaque on the lower arms and legs. Histological examinations of the tumor showed an intense lymphoid infiltrate of a pseudolymphomatous type. The tumor regressed partly following discontinuation of CS, but additional radiation therapy had to be administered. His clinical symptoms of actinic reticuloid reappeared. Eight months after CS treatment he developed a malignant T cell lymphoma with metastasis in the regional lymph nodes on the neck. CS should not be used in diseases with potential premalignant features even though its therapeutic efficacy in actinic reticuloid was impressive.

Cyclosporins↗
PubMed1987

Retinoids in cutaneous T cell lymphomas.

Sixteen patients - 12 with cutaneous T cell lymphoma (CTCL), 1 with Sézary syndrome, 1 with actinic reticuloid, and 2 with parapsoriasis variegata - were treated with either a new, potent arotinoid alone or with combined etretinate (Tigason) and PUVA therapy (Re-PUVA). 92% of all patients showed a minor up to a distinct response of their skin lesions within 12.6 +/- 7.4 weeks. More than 50% of the skin lesions cleared in 67% of the patients. After discontinuation of the retinoid therapy, relapses occurred in all cases within 3-10 weeks. There was no difference between the therapeutic efficacy of arotinoid alone and the Re-PUVA regimen, but the latter was less toxic.

Antineoplastic Agents↗
PubMed2000

Historical perspective on the use of retinoids in cutaneous T-cell lymphoma (CTCL).

Vitamin A and its analogues influence differentiation and proliferation and may also alter immune responses. Limited clinical efficacy of these compounds given alone or as part of a combination therapy has been shown in various types of cutaneous T-cell lymphoma (CTCL), including mycosis fungoides, Sézary syndrome, and prelymphomatous disorders such as parapsoriasis en plaques. Compounds used mostly in small, nonrandomized trials are isotretinoin (13-cis-retinoic acid), etretinate, acitretin, and all-trans-retinoic acid. Clinical responses have been found despite persistent residual disease with atypical lymphocytes in various compartments. The exact mechanism of action of retinoids in CTCL is unclear and depends on the presence of retinoid receptors on the tumor cells, which is variable in different forms of CTCL. Therapies combining retinoids with psoralen-ultraviolet A or with interferons may have a synergistic effect, which deserves confirmation through randomized trials in the future.

History, 20th Century↗
PubMed1999

Telomerase activity and telomere length in lymphocytes from patients with cutaneous T-cell lymphoma.

BACKGROUND: Telomeres shorten with successive cell divisions in normal somatic cells. Telomerase is a ribonucleoprotein enzyme associated with cellular proliferation and plays an important role in maintaining the stability of chromosomes and the length of DNA telomeres. Telomerase activity has been detected in tissues from many human tumors, but is not present in the majority of normal tissues. Thus, measurement of telomerase activity and telomere length may contribute to understanding the mechanism of tumorigenesis and provide useful diagnostic or prognostic information. The aim of this study was to investigate the telomerase activity and telomere length from patients with cutaneous T-cell lymphoma (CTCL). METHODS: Eighteen skin-homing T-cell lines were established from skin biopsies and 10 peripheral blood mononuclear cells (PBMC) were isolated from patients with various stages of CTCL together with 22 PBMC from healthy donors. For each sample an identical amount of cellular protein was measured quantitatively for telomerase activity using the telomerase polymerase chain reaction-enzyme-linked immunosorbent assay based on the telomeric repeat amplification protocol method. Telomere length was assayed using a commercial kit. RESULTS: Eight of ten PBMC and 16 of 18 skin-homing T-cell lines from patients with CTCL showed moderate to strong telomerase activity. Freshly obtained PBMC from healthy donors showed weak levels of telomerase activity. A shorter telomere length was found in cell lines and PBMC from patients with CTCL compared with healthy controls. Four skin-homing T-cell lines going into growth crisis showed sharply reduced telomerase activity. CONCLUSIONS: The results of the current study indicate that both skin-homing T-cells and PBMC from CTCL have high telomerase activity and short telomere length. These changes are similar to the changes observed in the majority of malignant cells including other types of T-cell lymphoma. It is interesting to note that even in the very early stages of CTCL such as parapsoriasis (which is a clinically benign disease) the changes already are present, indicating that a significantly high level of telomerase activity frequently occurs in CTCL and may be an important event in tumorigenesis. Telomerase activity and telomere length are useful markers for CTCL risk assessment.

Aged↗