Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology

Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.     

Leu-8/CD7 antigen expression by CD3+ T cells: comparative analysis of skin and blood in mycosis fungoides/Sézary syndrome relative to normal blood values.

Deficiencies of Leu-8 and CD7 antigens are exhibited by CD3+ T cells in the skin lesions of most patients with mycosis fungoides/Sézary syndrome. To determine whether these antigenic abnormalities are limited to involved skin, we studied Leu-8/CD7 expression in 21 skin lesions of mycosis fungoides/Sézary syndrome obtained from 16 patients and compared them with their peripheral blood leukocytes obtained concurrently. There was no correlation between Leu-8/CD7 values in skin lesions versus blood. Blood values were relatively uniform; most patients had 50% or greater of CD3+, Leu-8+ T cells and CD3+, CD7+ T cells. In contrast, skin values were highly heterogeneous; most patients lacked expression of Leu-8 or CD7 by the majority of lesional CD3+ T cells. Furthermore, Leu-8/CD7 antigen deficiency was present in lesional skin in one patient with mycosis fungoides but not in her concurrently sampled pityriasis lichenoides chronica or blood. These findings suggest that Leu-8/CD7 antigen deficiencies in skin lesions of mycosis fungoides/Sézary syndrome do not represent generalized antigenic abnormalities of CD3+ T cells in other body compartments and that within the skin, these deficiencies are disease specific within individual patients with more than one dermatosis. Comparative peripheral blood immunophenotyping of the patients with mycosis fungoides/Sézary syndrome and of the control subjects indicated that the control ranges of CD3+/Leu-8+ and CD3+/CD7+ T cells (33% or greater) extend lower than reported previously (60% or greater) and suggested that leukemic involvement in patients with mycosis fungoides/Sézary syndrome may correlate with percentages of CD3+, Leu8+ and/or CD3+, CD7+ T cells that fall below the revised control range.     

A subpopulation of Langerhans cells (CD1a+Lag-) increased in the dermis of plaque lesions of mycosis fungoides.

The population of CD1a+ cells and the quantity of Birbeck granules were evaluated in comparison with the population of T lymphocytes in a variety of clinical lesions of mycosis fungoides. Anti-CD1a and Lag antibodies that specifically react with Birbeck granules and related structures of human Langerhans cells were used immunohistochemically. CD1a+ cells in the dermis of lesions of mycosis fungoides significantly increased in plaques of the plaque stage and in plaques of the tumor stage. They were most frequent in lesions with CD4+ cells ranging in number from 100 to 150/mm2. These lesions were suspected to be progressing from the plaque to the tumor stage. During the course of the disease, most of the dermal CD1a+ cells had few Lag antigens. These results suggest that dermal CD1a+Lag- cells may promote the progression of mycosis fungoides from the plaque to the tumor stage.     

儿童色素减退型蕈样肉芽肿1例

报告色素减退型蕈样肉芽肿1例.患儿男,4岁.全身散发绿豆大小色素减退斑半年余,加重1个月.皮肤科检查:颈部、胸、背及四肢可见多发类圆形或圆形色素减退斑,境界清楚,未见融合,部分白斑中央见暗红色丘疹及斑片,表面干燥,覆盖白色鳞屑.左手背有两颗高于皮面黑色斑丘疹.皮损组织病理:表皮灶性角化不全,基底细胞液化变性,淋巴样细胞...     

Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas

We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes.     

T-cell subsets with a naive phenotype are selectively decreased in the peripheral blood of patients with mycosis fungoides

Peripheral blood lymphocytes of 33 patients with histopathologic confirmation of mycosis fungoides and 27 healthy controls matched for age and sex were analyzed with a panel of monoclonal antibodies using both single and dual color immunofluorescence. Patients with mycosis fungoides had a significant reduction in the percentage of circulating T cells with a naive phenotype (i.e., CD4+2H4+ and CD4+Leu8+), as well as a significant reduction in the absolute numbers of circulating lymphocytes with the phenotype CD8+Leu8+ compared to the control cohort. The reduction in circulating naive T cells was found to occur irrespective of stage of disease, duration of disease, or mode of treatment. The depletion of circulating naive T cells may reflect increased conversion to memory T cells in the peripheral blood or skin.     

Mycosis fungoides with a CD56+ immunophenotype

We report 3 cases of mycosis fungoides (MF) with a CD56+ cytotoxic immunophenotype. Each patient presented with a different clinical phenotype: one exhibited limited poikilodermatous patches (skin stage T1); one, widespread hypopigmented lesions (skin stage T2); and one, poikiloderma with a single cutaneous tumor (skin stage T3). MF was confirmed both histologically and by the presence of a T-cell receptor clone in lesional skin in all cases. CD56 and T-cell intracellular antigen-1 were expressed by the malignant lymphocytes in all patients and two expressed CD8. No sample demonstrated loss of the pan T-cell markers CD2 or CD3. None of the 3 developed systemic disease and T-cell receptor gene analysis of peripheral blood was polyclonal in all cases. Only 3 cases of CD56+ MF have been reported previously, none of which exhibited tumor-stage disease. Currently, the disease in our patients appears to be behaving in a manner similar to that predicted for MF with a normal immunophenotype but the prognosis has to be guarded in view of the rarity of this subtype.     

Ultraviolet-B phototherapy is successful in Japanese patients with early-stage mycosis fungoides

UVB phototherapy is widely used for the treatment of psoriasis and atopic dermatitis, however, only limited reports evaluate its usefulness in the treatment of mycosis fungoides. We introduced UVB phototherapy to five patients with early-stage mycosis fungoides. All of them were classified as stage IB (erythematous stage), and none had obtained a satisfactory response to other therapies. After initial treatment with UVB phototherapy, all the patients obtained significant improvement in their skin lesions leaving pigmentary changes. After this satisfactory response was achieved, the same dose of UVB was administrated as a maintenance therapy with longer intervals between exposures. Histopathological examination of three patients revealed decreased numbers of inflammatory cells in both the epidermis and the dermis after the treatment. Immunohistochemical study showed that CD1a+/HLA-DR+ dendritic cells were present throughout the lesional epidermis before the treatment. In contrast, after the treatment, the dendritic cells in the epidermis were CD1a+/HLA-DR-. Although it remains unclear why only the expression of HLA-DR antigen was eliminated after treatment, we presume that this loss of HLA-DR antigen expression by epidermal Langerhans cells was, in part, responsible for the improvement of skin lesions. This preliminary study suggests that UVB phototherapy is an effective treatment for patients with early-stage mycosis fungoides.     

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.     

Granulomatous mycosis fungoides with small intestinal involvement and a fatal outcome

We report a case of granulomatous mycosis fungoides that progressed into fatal gastrointestinal involvement 4 years after the onset of skin lesions, despite improvement of the skin lesions in response to a combination of PUVA and systemic interferon-gamma therapy. Histological examination showed Pautrier's microabscesses with granuloma annulare-like features and sarcoidal granuloma formation in the plaque stage, proliferation of blast-transformed atypical lymphocytes with persistent granuloma formation in the tumour stage, and metastatic lesions. A literature review of granulomatous mycosis fungoides revealed that 11 of the 24 reported cases died of the disease, and like our case, seven died within 5 years. We suggest that mycosis fungoides with granulomatous reactions does not indicate a favourable prognosis.     

A Case of Hypopigmented Mycosis Fungoides in a Young Caucasian Boy

Abstract: Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described aimost always in young black or dark-skinned patients. The only white patient described was a 64-year-oid woman who not oniy had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunoiogic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder, Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.     

Unilesional mycosis fungoides: a study of seven cases

BACKGROUND: Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized by a solitary lesion clinically and by histopathological features indistinguishable from those of MF, and typically having a benign course. OBJECTIVE: To describe the clinicopathological features of a series of patients with unilesional MF. METHODS: The records of cases of unilesional MF identified during a 10-year period in two medical departments were reviewed. RESULTS: There were 7 patients: 6 males, 1 female; mean age at the time of diagnosis: 32 years; age range: 12-58 years; 3 were below the age of 18 years. The mean pretherapy follow-up period was 9 years (range: 2-20 years). In 5 patients, the eruption consisted of a characteristic patch or plaque of MF located on the trunk or upper extremity; in 2 it was atypical - in 1, a hypopigmented patch, and in 1, a plaque indistinguishable from MF-associated follicular mucinosis. Histopathologically all the lesions exhibited features characteristic of MF, with CD3+ lymphoid cells. In 6 cases (with available fresh frozen tissue) there was a predominance of CD3+ CD4+ cells; in 1 of 5 there was deletion of CD7, and in 3 of 5 there was an overexpression of IL-2 receptor. T-cell receptor gamma gene rearrangement was found in 1 of 4 cutaneous lesions tested; in 2 cases it was found in the blood but not in the skin. Treatment modalities included localized electron beam, excision, topical nitrogen mustard or topical steroids and sunbathing, resulting in all cases in a sustained complete clinical response. In 1 patient, however, there were 2 local recurrences and in yet another patient there was distant cutaneous spread 3.5 years after therapy. CONCLUSIONS: Unilesional MF is a rare variant of CTCL, has heterogeneous clinical manifestations and can affect any age group, including children. The histopathological and immunophenotypical features are in general indistinguishable from those observed in multilesional MF. Although it is a unifocal event, there may occasionally be cutaneous spread with the appearance of noncontiguous lesions, even a long time after therapy. Whether all cases represent minimal-stage IA MF or whether some are actually T-cell pseudolymphoma remains to be clarified.     

皮肤色素减退性淋巴增殖性疾病41例临床病理分析

目的:探讨色素减退性蕈样肉芽肿（HMF）与色素减退性界面T细胞异常增生（HITCD）的临床与病理特征。方法:收集2015年1月至2020年9月在杭州市第三人民医院皮肤科就诊、具有完整临床病理资料的皮肤色素减退性淋巴增殖性疾病患者41例,分析临床病理及免疫表型特征。符合正态分布的定量数据使用 t检验,分类数据...     

Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides

Background It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders. Objectives In this study, we immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs in the lesional skin of psoriasis vulgaris, mycosis fungoides and eczematous dermatitis. Methods We used immunohistochemistry to examine the presence of Foxp3+ Tregs in fixed sections of the lesional skin from 16 patients with psoriasis vulgaris, 17 patients with mycosis fungides and 18 patients with eczematous dermatitis in addition to 10 normal skin samples. Results In normal skin, epidermal and dermal Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and eczematous dermatitis samples contained substantial numbers of epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+ cells was significantly lower in eczematous dermatitis than in psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+ cells was significantly lower in psoriasis vulgaris than in eczematous dermatitis or mycosis fungoides. Conclusions The lower percentage of epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis vulgaris, respectively, might contribute to their pathogenesis.     

Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides

Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma. Several rare clinicopathological variants of mycosis fungoides have been described. Patients with these variants often also have classic mycosis fungoides at other sites of the body. Anetoderma is a cutaneous disorder in which multiple, oval lesions or atrophic plaques with wrinkled surface develop progressively due to loss of the dermal elastic tissue. Primary anetoderma occurs when there is no underlying associated disease and it arises on clinically normal skin, whereas secondary anetoderma appears in the same site as a previous specific skin lesion. There is a large list of heterogeneous dermatoses associated with secondary anetoderma. Two patients developed areas of secondary anetoderma on plaque stage lesions of mycosis fungoides. The lesions consisted of exophytic nodular lesions, with very soft consistency on palpation, scattered over the hyperpigmented plaques in one patient and violaceous indurated plaques with overlying epidermal atrophy and mild scale in the other. Histopathological study demonstrated that the cells involving the dermis were mainly T-helper lymphocytes, with few histiocytes and some multinucleate giant cells engulfing distorted elastic fibres. Elastic tissue stain demonstrated that elastic fibres were almost completely absent in the dermis of the anetodermic lesions. Anetodermic mycosis fungoides should be added to the list of clinicopathological variants of mycosis fungoides and mycosis fungoides should also be considered as a possible disease causing secondary anetoderma. Anetodermic mycosis fungoides shows clinical and histopathological features different from those of granulomatous slack skin.     

儿童色素减退型蕈样肉芽肿一例并文献复习

报告儿童色素减退型蕈样肉芽肿一例并对相关文献进行复习。患儿,男,7岁。周身皮肤出现色素减退斑、红斑结痂1年,无明显瘙痒。组织病理检查：角层轻度角化,表皮轻度增生,可见淋巴样细胞亲表皮现象,真皮内可见团块状样细胞浸润。免疫组化示：CD3(+);CD20(个别+);CD21（-）;Ki-67（+10%）;CD2（+）;CD5（+）;CD7（+）;CD8（少许+）;CD4（+）。诊断：色素减退型蕈样肉芽肿。给予患儿NB-UVB治疗3个月皮损基本消退,目前维持治疗中。     

Expression of T-cell receptor antigens in mycosis fungoides and inflammatory skin lesions

Using immunohistologic methods, we studied the expression of the T-cell receptor (TCR)-associated antigens CD3, TCR-beta, and TCR-delta by cutaneous T cells in mycosis fungoides (MF) (36 patients) and a variety of inflammatory diseases (16 patients). Most T cells in the inflammatory diseases and patch/plaque mycosis fungoides expressed the immunophenotype characteristic of the vast majority of mature peripheral T cells: CD3+ TCR-beta+ TCR-delta-. In contrast, abnormal CD3/TCR-beta antigen expression was seen in 3 of 6 cases (50%) of tumor stage mycosis fungoides. Furthermore, we were able to document its evolution from the normal pattern present in earlier patch/plaque lesions of the two cases in which serial biopsies were available for study. Divergence of epidermal versus dermal CD3/TCR-beta antigen expression was seen in 2 of 34 (6%) of biopsies of patch/plaque mycosis fungoides but not in inflammatory controls. The TCR-delta+ cells were generally rare regardless of diagnosis. We conclude that inflammatory skin diseases and most patch/plaque mycosis fungoides are typically composed of T lymphocytes that resemble mature peripheral T cells in regard to their expression of TCR-associated antigens. In contrast, aberrant patterns of TCR-associated antigen expression can be seen in tumor stage MF, and, more rarely in patch/plaque MF.     

Langzeitergebnisse der Ganzhautelektronenbestrahlung (GET) in der Therapie der Mycosis fungoides

BACKGROUND AND OBJECTIVE: Total skin electron beam therapy (TSEBT) is an important therapeutic option for the treatment of mycosis fungoides. The aim of this study was to find out long term results in 10 patients with the clinical and histological diagnosis of mycosis fungoides. PATIENTS AND METHODS: Between 1982 and 1997 we performed a total skin electron beam therapy in 10 patients. One patient was in stage I A; 5, in stage I B; 3, in stage II B; and one, in stage IV A. The indication for TSEBT was disease progression in spite of PUVA therapy. The doses of electron beam therapy were 30- 36 Gy at 5-6 MeV. In 7 of 10 cases additional local electron beam therapy was given, because individual lesions persisted or recurred after a short time. RESULTS: Complete remission was achieved in 5 patients. The follow- up has been up to 10 years. One patient died of systemic lymphoma 10 years after electron beam therapy. Three patients died of illnesses unrelated to mycosis fungoides. One patient developed a high grade T-cell lymphoma. CONCLUSIONS: Total skin electron beam therapy is a very effective, but technically difficult therapy for mycosis fungoides, especially in stage I B and II B. Particularly interesting has been the long duration of complete response of three patients, who had follicular mucinosis preceding their mycosis fungoides.     

UNILESIONAL MYCOSIS FUNGOIDES: CLINICAL, MICROSCOPIC AND IMMUNOPHENOTYPIC FEATURES

Seven cases are reviewed in which the histologic and immunohistologic features were those of mycosis fungoides, although the patients presented with solitary lesions which did not recur after local therapy (excision in six, radiotherapy in one), with follow-up of 10 months to 18 years. Immunophenotypic staining of paraffin-embedded tissue revealed a predominant T-lymphocyte proliferation in all cases, None of the four cases studied for BER-H2(Ki-1) were positive, in contrast to the "activated" types of spontaneously regressing lymphoid lesion, lymphomatoid papulosis and "Ki-1" lymphoma. Electron microscopy in one case demonstrated the highly convoluted nuclei of the T cells within the infiltrate. These seven cases represent examples of unilesional mycosis fungoides in which the disease has not recurred after therapy, despite features indistinguishable from those of typical generalised mycosis fungoides-type of cutaneous T-cell lymphoma.