Poikilodermatous mycosis fungoides with a CD8+ CD56+ immunophenotype: a case report and literature review

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. MF shows varieties in both its clinical presentation and immunophenotype. We herein report one case of poikilodermatous MF with a CD8+ CD56+ immunophenotype and present a literature review. A 20‐year‐old Japanese woman presented with a 10‐year history of multiple poikilodermatous and reddish or brownish patches with mild pruritus on the chest, abdomen, back, buttock and thighs. Histopathologically, small‐ to medium‐sized atypical lymphocytes infiltrated into the epidermis, indicating epidermotropism, along the basal layer, and distributed in band‐like appearance in the papillary dermis. Immunohistochemically, atypical lymphocytes expressed CD3, CD8, CD56, T‐cell intracellular antigen (TIA)‐1, granzyme B and beta F1 but lacked expression of CD4, CD20, CD30 and Epstein‐Barr virus (EBV) latent membrane protein 1. An EBV‐encoded small non‐polyadenylated RNA‐1 (EBER‐1) signal was not detected. On the basis of these findings, the diagnosis of CD8+ CD56+ MF was established. Poikilodermatous MF with a CD8+ CD56+ immunophenotype, as presented herein, is extremely rare. Although further investigation is needed to fully clarify the nature of this aberrant phenotype of MF, we stress that it is important to recognize this rare immunophenotype of MF to distinguish it from aggressive cytotoxic cutaneous lymphomas.     

Pediatric CD8+/CD56+ mycosis fungoides with cytotoxic marker expression: A variant with indolent course

Mycosis fungoides is predominantly a disease of older patients, but occasionally occurs in children. We report a rare case of CD8+/CD56+ mycosis fungoides with cytotoxic marker (perforin, TIA‐1, and granzyme B) expression in a 10‐year‐old boy. Disease presented with three asymptomatic, slowly progressive erythematous and scaling plaques, surrounded by hypochromic alone in the left tight and lower trunk. UVB narrow band associated with topical corticosteroids resulted in complete remission in about 2 months, and no recurrence at 2‐year follow‐up. Three similar cases have been retrieved in children through PubMed search, showing similar clinical presentation with erythematous scaling lesions, good response to skin‐directed treatments and a favorable prognosis.     

Folliculotropic mycosis fungoides driven by DOCK8 immunodeficiency syndrome

DOCK8 immunodeficiency syndrome (DIDS) represents a rare primary immunodeficiency associated with cutaneous viral infections, allergy, and increased risk of malignancy. We report a case of folliculotropic mycosis fungoides with spontaneous resolution occurring in a patient with DIDS.     

Dyshidrotic mycosis fungoides

Mycosis fungoides (MF) represents the most common type of cutaneous T-cell lymphoma (CTCL). CTCL often progresses through patch, plaque and tumor stages but can also manifest with varied clinical presentations. MF rarely presents in vesiculobullous fashion, in which vesicles or bullae develop in pre-existing plaques or on the trunk or proximal extremities. We report a patient who presented with a vesiculobullous eruption on the palms and soles, resembling dyshidrotic dermatitis, which we believe represents dyshidrotic MF.     

Unilesional mycosis fungoides mimicking Bowen's disease

Cutaneous T-cell lymphoma includes a heterogeneous group of lymphomas that share the unique feature of T lymphocytes which are tropic to the skin. Clinically, the presentation of this disease is protean and can range from a single lesion to generalized erythroderma. Unilesional mycosis fungoides, a rare variant, is presented here. Its morphology mimicked squamous cell carcinoma in situ, and was refractory to conventional therapies. A review of the treatment of this subset is also presented.     

CD8+ mycosis fungoides clinically masquerading as alopecia areata

A 33‐year‐old female with a 7‐year history of CD8‐positive hypopigmented mycosis fungoides (MF) involving the trunk and extremities presented with a large well‐defined alopecic patch on her frontal scalp. Clinically, this area resembled alopecia areata (AA) and was without hypopigmentation or erythema. A scalp biopsy revealed a non‐scarring inflammatory alopecia and a superficial band‐like atypical lymphoid infiltrate with prominent epidermotropism. Atypical, predominately CD8‐positive lymphocytes were seen surrounding and infiltrating the bulb portion of several hair follicles. Treatments for her MF lesions have included topical bexarotene, topical corticosteroids and phototherapy. Her alopecia has been treated with high potency topical corticosteroids and multiple intralesional triamcinolone injections with very minimal hair regrowth to date. Alopecia due to cutaneous lymphoma is an uncommon phenomenon but can occur in erythrodermic MF or Sezary syndrome. AA‐like changes have most often been reported in conventional patch/plaque stage MF and folliculotropic MF. In these cases, the atypical lymphoid infiltrate is comprised predominately of CD4‐positive lymphocytes. This is a rare report of a CD8‐positive MF causing AA‐like changes. This case highlights the importance of a scalp biopsy in patients with a history of cutaneous lymphoma presenting with alopecia in order to evaluate the nature of their hair loss.     

Folliculotropic mycosis fungoides in a psoriatic patient under methotrexate treatment

Folliculotropic mycosis fungoides is a variant of mycosis fungoides with a worse prognosis than the classic form. It can be associated with follicular mucinosis. We report a case of folliculotropic mycosis fungoides developing in the months following methotrexate therapy in a psoriatic patient. This lymphoma did not regress after stopping the antipsoriatic treatment. There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies. However these lymphomas are mainly B‐cell non‐Hodgkin lymphomas associated with Epstein‐Barr virus. In our patient the short period of time from the beginning of the immunosuppressive treatment to the occurrence of the T‐cell lymphoma does not support a strong causal relationship between the drug intake and the development of mycosis fungoides. To the best of our knowledge, this is the first case of folliculotropic mycosis fungoides in a patient treated with methotrexate for psoriasis.     

Annular hypopigmented mycosis fungoides: a novel ringed variant

Hypopigmented mycosis fungoides (MF) is a relatively uncommon variant of cutaneous lymphoma that is mostly seen in darker skin types. We present a novel and unique clinical presentation in an African-American female patient, consisting of regular hypopigmented annular rings in areas of normal skin and in more typical hypopigmented patches of MF. The lesions appeared diffusely on all extremities, anterior chest and back. Histopathologic examination showed an atypical lymphocytic infiltrate at the dermal-epidermal junction with epidermotropism and few Pautrier's collections. The patient was otherwise healthy and improved with narrowband ultraviolet (UV)-B. This case represents a presentation of a most unusual variant of hypopigmented MF, for which we propose the name 'annular hypopigmented MF'.     

Circulating CD8+ lymphocytes, white blood cells, and survival in patients with mycosis fungoides

BACKGROUND: There is a need for reliable, easily measurable laboratory markers that may help dermatologists to predict the course of mycosis fungoides (MF) when they first evaluate their patients. OBJECTIVES: Our objective was to identify clinical, haematological or immunological parameters as predictors of mortality in patients with MF. METHODS: We conducted a retrospective study on a prevalent cohort of 124 patients with MF hospitalized at IDI-IRCCS, Rome, Italy, from 1983 to 2001. We calculated the proportion of patients surviving (Kaplan-Meier product-limit estimates) 5 and 10 years after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. RESULTS: Patients' survival was linked to age and staging (lower survival in older patients and in patients with staging IIB-IV). Higher numbers of white blood cells (WBC) and neutrophils, lower numbers of CD8+ lymphocytes, low haematocrit and lower levels of albumin were significantly associated with a lower survival probability. When simultaneously accounting for age and staging, CD8+ [HR = 3.02, 95% confidence interval (CI) 1.01-9.07 for CD8+ < 250 vs. > or = 600 cells microL(-1)] and WBC (HR = 2.59, 95% CI 0.96-6.96 for WBC > or = 9000 vs. < 6000 cells microL(-1)) were associated with survival. In addition, we observed an exceedingly high risk of death (HR = 12.40, 95% CI 3.11-49.43) for patients with a combination of WBC > or = 9000 and CD8+ < 600 cells microL(-1) vs. WBC < 9000 and CD8+ > or = 600 cells microL(-1)). CONCLUSIONS: The measurement of CD8+ cells and WBC in MF seems to be a promising criterion to predict survival, and possibly to support treatment decisions and inclusion of patients in randomized controlled trials.     

Clinical characteristics and course of CD8+ cytotoxic variant of mycosis fungoides: a case series of seven patients

Background  Fewer than 5% of cases of mycosis fungoides (MF) present with a cytotoxic/suppressor CD8+ phenotype which, despite immunophenotypic similarities with CD8+ aggressive lymphomas, is regarded as a phenotypic variant of MF. Poikilodermatous MF showing a CD8+ phenotype has been reported to have a nonaggressive clinical behaviour and a good response to psoralen plus ultraviolet A treatment.
Objectives  To perform a retrospective study of CD8+ MF cases diagnosed in the skin lymphoma clinic of Andreas Sygros Hospital.
Methods  We analysed the clinical characteristics, the immunophenotypic and molecular indices, as well as the clinical course of these patients.
Results  Seven cases of CD8+ MF (6·5% of all cases of cutaneous T-cell lymphoma) were diagnosed during 2002–2007. One of seven patients had stage IA, five stage IB and one stage IIB disease. Clinical characteristics were variable: four of seven patients presented with poikilodermatous plaques (in one of them lesions of lymphomatoid papulosis with CD8+ phenotype coexisted), one patient with classic MF, one with plantar MF and one with follicular MF. The time period between disease onset and diagnosis was long for most patients (up to 33 years). All patients received the recommended treatment according to TNM staging. Five of seven patients had complete remission, one partial response and one stable disease.
Conclusions  Special clinical characteristics, such as hyperpigmentation and poikiloderma, are often noted in CD8+ MF cases. In our series CD8+ MF presented with a long-standing disease and indolent course suggesting that CD8+ cytotoxic immunophenotype may represent a marker of mild biological behaviour.     

Etoposide as a single agent in the treatment of mycosis fungoides: A retrospective analysis

Several chemotherapy agents have shown efficacy in the treatment of mycosis fungoides (MF). In the literature, there is limited data on the use of single agent etoposide for MF. We aimed to retrospectively review our experience with single agent etoposide in the treatment of advanced‐stage or refractory early‐stage MF with focus on analyzing its efficacy and safety. We included 13 MF patients who were treated with single agent etoposide. Patients were identified through the Cutaneous T Cell Lymphoma Database of Indiana University that involves patients treated from 2006 to 2016. Overall nine patients (69%) responded to treatment. No complete response was identified. Median time to response was 12.5 weeks (range: 6–25.4). Median duration of response was 43 weeks (range: 5–60) and median time to treatment failure was 31.3 weeks (range: 12.4–230). Hematological toxicity was observed in eight patients including two patients with grade 4 neutropenia and/or lymphopenia leading to sepsis. Higher doses of etoposide were significantly correlated with higher grades of anemia, neutropenia or lymphopenia (p < .05). Our study demonstrates that etoposide is an effective treatment for MF and may be considered in selected patients with progressive MF who have failed other treatments.     

Cutis laxa-like mycosis fungoides

Mycosis fungoides is the most common form of primary cutaneous T-cell lymphoma. Several clinical and clinicopathological variants of mycosis fungoides have been reported. A 75-year-old woman presenting with multiple ill-defined areas of marked cutaneous wrinkling on the trunk and extremities is reported. Histopathological examination showed characteristic features of mycosis fungoides along with an interstitial dermal infiltrate composed predominantly of atypical lymphocytes with histiocytes intermingled within the collagen bundles. A focal reduction and fragmentation of elastic fibers was demonstrated. This observation illustrates a peculiar and previously unreported clinicopathological presentation of mycosis fungoides: cutis laxa-like mycosis fungoides, expanding the spectrum of mycosis fungoides variants associated with abnormalities of the dermal elastic fibers.     

Papular mycosis fungoides: report of two patients,literature review,and conceptual re‐appraisal

Recent reports of 10 patients have proposed a papular variant of mycosis fungoides (MF), characterized by the appearance of papules in the absence of patches and the presence of histopathologic features of classic patch/plaque stage MF. Given the overlapping clinical and pathologic features between this proposed entity and lymphomatoid papulosis (LyP)‐type B, however, the optimal classification for such cases remains somewhat unclear. Herein, two patients are described who presented to the dermatology clinic with persistent erythematous papular eruptions on the trunk, upper and lower extremities and histopathology compatible with MF. Of note, these patients represent the oldest reported cases of papular MF, and one patient had documented peripheral blood involvement by atypical CD4+ cells. The clinicopathologic characteristics of this purported entity suggest that it may occupy the intersection between MF and CD30+ lymphoproliferative disorders. These two cases expand the clinicopathologic spectrum of papular MF to include older individuals, and further emphasize the importance of recognition of this morphology as a possible MF manifestation. Furthermore, consideration of our cases in conjunction with the previously documented 10 other patients in the literature, offers potential insight into the relationship between MF and CD30+ lymphoproliferative disorders.     

Phototherapy of mycosis fungoides

Background/purpose: Among the primary cutaneous T‐cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow‐ and broadband UVB and 8‐methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance.     

miR‐155 is involved in tumor progression of mycosis fungoides

Biopsy specimens from 23 early stage and 19 tumor‐stage mycosis fungoides (MF) patients were evaluated for miR‐155 expression by real‐time qualitative PCR and compared with 15 biopsy specimens from patients with T‐cell‐rich inflammatory skin diseases. Significant upregulation of miR‐155 was found in MF tumors compared with both early‐stage MF lesions and controls. There was no difference in miR‐155 expression between early‐stage and inflammatory dermatoses. Using laser capture microdissection, it was found that miR‐155 was significantly higher in the lymphoma cells in tumor stage compared with the intraepidermal lymphocytes in early stage. In contrast, there was no difference in miR‐155 expression between the intraepidermal lymphocytes and the dermal lymphocytes in early‐stage MF. These findings suggest that although miR‐155 expression cannot serve to discriminate early‐stage MF from inflammatory dermatoses; however, it is involved in the switch from the indolent early stage into the aggressive tumor stage of the disease.     

Clinicopathological spectrum of mycosis fungoides

Cutaneous lymphomas represent a heterogeneous group of T-, NK- and B-cell neoplasms, with mycosis fungoides (MF) being the most common subtype. MF has a plethora of clinicopathological manifestations. Many variants of this lymphoma differ substantially from the 'classical' Alibert-Bazin disease and are therefore sometimes referred to as 'atypical' forms of the disease. This review addresses the whole clinicopathological spectrum of mycosis fungoides with respect to epidemiology, clinical, histopathological, immunophenotypic and genotypic features and the clinical course and prognosis of its variants: classical, erythrodermic, follicular, syringotropic, bullous/vesicular, granulomatous, poikilodermic, hypo- and hyperpigmented, unilesional, palmoplantar, hyperkeratotic/verrucous, vegetating/papillomatous, ichthyosiform, pigmented purpura-like, pustular and mucosal involvement in MF.     

Hypopigmented mycosis fungoides in childhood and adolescence: a long‐term retrospective study

Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long‐term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty‐five patients had clinical follow‐up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T‐lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1–12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow‐up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing‐and‐waning course and relapse after discontinuation of therapy, requiring repetitive treatment.     

Double‐positive CD4/CD8 mycosis fungoides: a rarely reported immunohistochemical profile

Mycosis fungoides (MF) represents the most common epidermotropic cutaneous T‐cell lymphoma (CTCL), and tumor cells typically express a mature T‐helper memory phenotype. A minority of MF patients display an unusual phenotype, which may be either CD4(?)/CD8(+) or double negative. Herein, we report a case of biopsy‐proven MF in a 31‐year‐old woman who presented with infiltrated plaques involving photoprotected areas of the skin. Immunohistochemical study combined with confocal microscopy revealed co‐expression of CD4 and CD8 in a subset of atypical T lymphocytes. To our knowledge, this is the second report of a CD4/CD8 dual‐positive MF.