Type Of Cutaneous T-cell Lymphoma Research Articles

THE VALUE OF TOX AS A DIAGNOSTIC MARKER FOR MYCOSIS FUNGOIDES (MF)

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Differentiation of MF from its benign mimickers is important to ensure proper management. TOX is a critical regulator of early T-cell development that is considered as a useful marker for MF diagnosis and prognosis. The current study aimed to test the role of TOX immunohistochemistry (IHC) as a diagnostic marker of MF differentiating it from its benign mimickers. Materials and Methods: This work was carried out on 103 skin biopsies, 51 MF cases and 52 inflammatory mimickers. The diagnoses were established after clinicopathologic correlation. IHC was done in MF cases for TOX, CD4, CD8 and CD7 (in TOX negative cases), while the other mimickers stained only by TOX. Results: TOX expression showed a significant positive expression in MF cases compared to inflammatory dermatoses, with 62% sensitivity and 100% specificity. There was positive correlation between TOX staining and CD4/CD8 ratio in MF cases. In addition, TOX positivity in plaque MF was stronger than in patch MF. Also, TOX negative MF cases were negative for CD7. Conclusions: Positive TOX expression favors MF, but its negativity doesn't exclude the diagnosis of MF. Combining TOX with CD4/CD8 ratio and CD7 may be useful in diagnosis of MF beside the clinical and histopathological diagnosis. The stronger TOX positivity in plaque more than patch MF may correlate with the progression of the disease. Key Words: TOX, mycosis fungoides, cutaneous T cell lymphoma, marker.

Evidence of an oncogenic role of aberrant TOX activation in cutaneous T-cell lymphoma

AbstractTOX is a nuclear factor essential for the development of CD4+ T cells in the thymus. It is normally expressed in low amounts in mature CD4+ T cells of the skin and the peripheral blood. We have recently discovered that the transcript levels of TOX were significantly increased in mycosis fungoides, the most common type of cutaneous T-cell lymphoma (CTCL), as compared to normal skin or benign inflammatory dermatoses. However, its involvement in advanced CTCL and its biological effects on CTCL pathogenesis have not been explored. In this study, we demonstrate that TOX expression is also enhanced significantly in primary CD4+CD7− cells from patients with Sézary syndrome, a leukemic variant of CTCL, and that high TOX transcript levels correlate with increased disease-specific mortality. Stable knockdown of TOX in CTCL cells promoted apoptosis and reduced cell cycle progression, leading to less cell viability and colony-forming ability in vitro and to reduced tumor growth in vivo. Furthermore, TOX knockdown significantly increased 2 cyclin-dependent kinase (CDK) inhibitors, CDKN1B and CDKN1C. Lastly, blocking CDKN1B and CDKN1C reversed growth inhibition of TOX knockdown. Collectively, these findings provide strong evidence that aberrant TOX activation is a critical oncogenic event for CTCL.

Expression of T-follicular helper markers in sequential biopsies of progressive mycosis fungoides and other primary cutaneous T-cell lymphomas.

T-follicular helper (Tfh) lymphocytes represent the neoplastic cells of angioimmunoblastic T-cell lymphoma and have been observed also in several cutaneous T-cell lymphomas (CTCLs) and extracutaneous T-cell lymphomas, including peripheral T-cell lymphoma, not otherwise specified, mycosis fungoides (MF), cutaneous CD4 small/medium T-cell lymphoma (CD4SMTCL), and Sezary syndrome. We studied a large number of different types of primary CTCL for expression of Tfh markers, including 36 biopsies from 21 patients with MF (with sequential biopsies from patch stage and tumor stage of 15 patients), 13 patients with CD4SMTCL, 9 with lymphomatoid papulosis, 11 with cutaneous anaplastic large cell lymphoma (cALCL), 2 with cutaneous γ/δ T-cell lymphoma, 8 with subcutaneous panniculitis-like T-cell lymphoma, 3 with cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma, 6 with cutaneous peripheral T-cell lymphoma, not otherwise specified, and 1 with Sezary syndrome. Expression of at least 3 of 5 markers (PD-1, CXCL-13, ICOS, Bcl-6, and CD10) in >10% of tumor cells was observed in 33 biopsies (MF = 20; CD4SMTCL = 11; 1 each cutaneous anaplastic large cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma, respectively). Our study shows that a Tfh phenotype is very common in MF and CD4SMTCL but can be observed rarely also in other types of CTCL. Expression of Tfh markers should not be used for classification of any entity of CTCL and may only integrate other immunohistochemical stainings for a more accurate characterization of these disorders. Precise distinction of Tfh-positive CTCLs from secondary skin manifestations of angioimmunoblastic T-cell lymphoma cannot rest on demonstration of a Tfh phenotype alone and should be achieved by a synthesis of clinical, histological, and phenotypic features.

Mycosis Fungoides Diagnosed with an Initial Sign Resembling Benign Dermatosis on the Upper Eyelids.

Dear Editor: Mycosis fungoides (MF) is a mature T-cell non-Hodgkin's lymphoma that presents with persistent and slowly progressive skin lesions of varying size and shape1. As the skin lesions of MF are variable, MF can be misdiagnosed as a benign dermatological condition1,2. A 21-year-old man presented with a 4-month history of skin lesions on his eyelids. The skin lesions were diffuse erythematous to violet-colored patches on both upper eyelids with multiple 1~2-mm papules scattered on the patches. Both eyelids were edematous, making the patient look like he had swollen eyes (Fig. 1A). The patient did not complain of symptoms at the lesional area but did complain of feeling weak and lethargic over the last few months. We performed laboratory tests and skin biopsy of his right eyelid, and made a preliminary diagnosis of a heliotrope rash in dermatomyositis. We decided to withhold treatment until the diagnosis was confirmed. Laboratory tests including complete blood count, liver function test, fluorescent antinuclear antibody test (FANA), and creatinine kinase showed no abnormalities. Histopathological examination revealed epidermotropic and diffuse dermal infiltration of atypical lymphocytes with some eosinophils (Fig. 1B, C); the epidermotropic and dermal atypical lymphocytes were positive for CD3 and CD4, and some lymphocytes were positive for CD30 and negative for CD20 (Fig. 1D~F). Fig. 1 (A) Erythematous papules and patches with edematous swelling on the right eyelid. (B, C) Histological specimen showing diffuse dermal infiltration of atypical lymphocytes (HE B: ×40, C: ×400). Atypical lymphocytes infiltrating ... On the second visit, an erythematous papule 5 mm in diameter (Fig. 2A) had developed on the dorsum of the right hand, and there was no improvement in the skin lesions on the eyelids. Skin biopsy of the papule showed similar histopathological findings to those of the eyelids, i.e., epidermotropism and diffuse dermal infiltration of atypical lymphocytes with some eosinophils (Fig. 2B, C). Nested polymerase chain reaction for T-cell receptor-γ gene rearrangement showed monoclonality. Fig. 2 (A) Erythematous nodules on the dorsum of right hand at the second visit. (B, C) Epidermotropism and diffuse dermal infiltration of atypical lymphocytes stained with CD4 (B: CD4, ×40; C: H&E, ×40). Bone marrow biopsy, abdominal pelvic computed tomography-multiplanar reformation, and chest computed tomography showed no internal organ involvement. With this histological and immunophenotypic information, the patient was diagnosed with MF and was treated with chemotherapy and total skin electron beam therapy. MF is the most common type of cutaneous T-cell lymphoma and accounts for half of all primary cutaneous lymphomas1. Clinically, early in the course of MF, the skin lesions may be nonspecific and variable, making the diagnosis difficult even for dermatologists1,2. A new variant of MF was recently proposed, in which papular lesions are present in the absence of patches with the presence of histopathologic features of the classic patch/plaque stage2. Moreover, advanced MF can infiltrate or metastasiaze to the eye, causing blepharitis and cicatricial ectropion3. Eyelid lesions must be differentiated from many conditions that can produce redness of the eyelids. Eczematous dermatological conditions such as contact dermatitis, atopic dermatitis, and seborrheic dermatitis commonly involve the eyelids4,5. Allergic contact dermatitis often affects the upper eyelids, while atopic dermatitis causes dermatitis in both the upper and lower eyelids. Seborrheic dermatitis is accompanied by lesions at other sites. Because the present patient had erythema and edema only on the upper eyelids without any subjective symptoms, we made an initial diagnosis of heliotrope rash in dermatomyositis. The diagnosis of MF should be made carefully on the basis of detailed history taking and physical examination if the skin lesion is persistent without changes in the shape or symptoms after conventional dermatological treatment. The present case illustrates the diversity of the cutaneous manifestations of MF, such as mimicking the heliotrope rash of dermatomyositis or eyelid eczema, and highlights the importance of skin biopsy for correct diagnosis and treatment.

Co-existence of various clinical and histopathological features of mycosis fungoides in a young female.

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL) and a rare disorder that typically affects older adults with erythematous scaling patches and plaques. Hypopigmented patches are a rare clinical variant of the disease. Granulomatous mycosis fungoides (GMF) is also a rare type of CTCL. No particular clinical criteria are available for the diagnosis of GMF, because of its variable presentations, and so the detection of GMF is primarily considered as a histopathological diagnosis. Rarely, a co-existence of more than one clinical or histopathological feature of mycosis fungoides may be present. To the best of our knowledge this is the first report of MF that shows the simultaneous co-existence of more than one clinical and histopathological variant of MF. We present a 29-year-old female with clinical presentations of both classic and hypopigmented mycosis fungoides (MF), and also the histopathological features of the classic and granulomatous types of the disease.

Juvenile Onset Hypopigmented Mycosis Fungoides: A Case Series Of 3 Patients

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Primary cutaneous lymphomas (PCLs) are exceedingly rare in children and adolescents, with mycosis fungoides (MF) being the most frequent PCL diagnosed in childhood. The incidence of MF is 6.4 per 1, 000, 000 per year in adults, but the occurrence in children and young adults is rare and has not been well established yet. Hypopigmented mycosis fungoides (HMF) is an atypical and rare subtype of MF characterized by solely hypopigmented patches or in combination with erythematous patches or plaques. There are no criteria that define a typical case of HMF. We present three cases of juvenileonset HMF at Department of Dermatology and Venereology, University Hospital Center Zagreb between November 2014 and January 2015. Patients were between 9 and 12 years old at the time of diagnosis. The diagnosis was reached based on clinical, histopathological and immunohistochemical correlation. All patients were investigated at the time of diagnosis with complete blood count, peripheral smear, ultrasonography of abdomen and pelvis, and chest X-ray. They were all without extracutaneous progression of disease. Narrowband UVB (311nm) phototherapy and/or potent topical steroids were used as a first- line treatment. HMF is rare in Caucasians and with only few cases described in children. Juvenile-onset MF is often misdiagnosed at early stages as benign condition. HMF may simulate atopic dermatitis, pityriasis alba, pityriasis lichenoides, tinea versicolor, vitiligo, postinflammatory hyperpigmentation or leprosy (Hansen? disease). Although HMF has good prognosis, it is a malignant skin lymphoma and should always be treated as such. Treatment modalities for juvenile MF are based on general strategies for adults according to disease stage.

T Cells in CTCL Have an Exhausted Phenotype While Cutaneous Dendritic Cells Display a Normally Activated Mature Phenotype

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) represent the most common types of cutaneous T-cell lymphoma (CTCL). CTCL develops from clonally-expanded, effector/central memory CD4+ T cells in a background of chronic inflammation. The eliciting Ag(s) and how this inflammation contributes to the development and progression of CTCL remain important unknowns. Despite tumor-infiltrating CD8+ T cells in skin, the malignant CD4+ T-cell population persists, indicating that these CD8+ T cells cannot exert an effective anti-tumor response, potentially due to T-cell exhaustion, which has been observed in chronic viral infections and is associated with disease progression in hematologic malignancies like ATLL and CLL. Exhausted T-cells are characterized by immunoinhibitory molecules, like programmed death-1 (PD-1). Engagement of PD-1 by PD-Ligand (L)-1/L-2 transduces a signal that leads to inhibition of T-cell functions, but the cells are not deleted. PD-L1 is expressed on T cells, dendritic cells (DCs), and many tumor cells, whereas PD-L2 expression is limited to antigen-presenting cells. Although malignant CD4+ T cells in Sézary syndrome lesions express PD-1, the relevance of the PD-1/PD-L1/2 pathway in CTCL and the immune cells in CTCL that express PD-L1/L2 are not known.Methods: Epidermis and dermis of skin biopsies from consented CTCL pts (12) and healthy donors (3) were separated using dispase-II and incubated in RPMI-10% pooled human serum for 24 hrs. Migrated cutaneous T cells and DCs were phenotyped by flow cytometry for a variety of maturation markers and immune checkpoint molecules. In 3 pts skin findings were compared with matched PBMCs.Results: Freshly isolated cutaneous CD8+ T cells displayed distinct effector and memory subsets with a higher frequency of effector-memory (CD28-CD45RA-CCR7-) and terminally differentiated effector cells (CD28-CD45RA+CCR7-). In addition, CD8+ T-cells exhibited enhanced expression of PD-1, Lag-3, Tim-3, and ICOS. PD-1 was the receptor most overexpressed in CD8+ T cells compared with healthy controls. PD-1 expression on circulating CD8+ T cells was lower compared with skin-infiltrating CD8+ T-cells. In contrast, the malignant CD4+ T-cells expressed predominantly a central memory or transient memory subtype (CD28+CD45RA-CCR7+/-), with overexpression of PD-1, CTLA-4, Lag-3, and ICOS. Immune-suppressive CD3+CD4+FoxP3+CD127-Tregs were not increased in PBMCs of CTCL pts. Migrated DCs displayed an activated, mature phenotype expressing HLA-DR+, CD1a+/-, CD207 (Langerin)+/-, CD14+/-, CD11c+, CD83low/med, CD86low/med and PD-L1+/- phenotype.Conclusion: Both the malignant CD4+ T cells and tumor-infiltrating CD8+ T cells display an exhausted phenotype, while DC subsets display a normal activated phenotype. Our preliminary data imply a role for PD-1 and other checkpoint molecules like ICOS, Tim-3, Lag-3 in attenuating the anti-tumor response. Studies are underway in vitro to establish the function of PD-1, Lag-3, Tim-3, and ICOS on T cells in response to DC/LC stimulation to develop a rationale for therapeutic checkpoint blockade inhibitors to reverse the exhausted T cell phenotype and attendant lack of immune reactivity. DisclosuresNo relevant conflicts of interest to declare.

IL32 Is Progressively Expressed in Mycosis Fungoides Independent of Helper T-cell 2 and Helper T-cell 9 Polarization

Mycosis fungoides, the most common type of cutaneous T-cell lymphoma (CTCL), is characterized by a helper T-cell 2 (Th2) skewing with a mature CD4(+) memory T-cell phenotype. Using skin samples from patients with mycosis fungoides (n = 21), healthy volunteers (n = 17), and individuals with atopic dermatitis (n = 17) and psoriasis (n = 9), we found IL32 mRNA expression significantly higher in mycosis fungoides samples than in samples from benign inflammatory skin diseases, and its expression increases with disease progression. By IHC and immunofluorescence, we confirmed IL32 protein expression in many CD3(+)CD4(+) T cells and some epidermotropic T cells in mycosis fungoides lesions. MyLa cells (a mycosis fungoides cell line) express IL32, which, in turn, could promote cellular proliferation and viability in a dose-dependent fashion. IL32-treated MyLa and CTCL HH cells upregulated cell proliferation and survival genes. Of the major "polarizing" T-cell cytokines, only IFNγ mRNA increases with mycosis fungoides progression and positively correlates with IL32 mRNA expression. Th2 cytokines do not positively correlate with IL32 mRNA expression or mycosis fungoides progression. Furthermore, by flow cytometry, IL32 production by circulating activated T cells in healthy individuals was found in both IFNγ(+) and IFNγ(-) cells but not in IL4(+) or IL13(+) cells. In conclusion, we have identified IL32(+) cells as the likely tumor cells in mycosis fungoides, and demonstrated that IL32 mRNA expression increases with mycosis fungoides progression and is significantly higher than mRNA expression in other skin diseases, and that some IL32(+) T cells are independent from the defined Th subsets. Thus, IL32 may play a unique role in mycosis fungoides progression as an autocrine cytokine.

A specific DNA methylation profile correlates with a high risk of disease progression in stage I classical (Alibert-Bazin type) mycosis fungoides

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma; in its classical presentation it evolves slowly, but it can have an aggressive course in a subset of patients. To investigate the impact of epigenetic mechanisms on the progression of early stage MF. We analysed DNA methylation at 12 different loci and long interspersed nucleotide elements-1 (LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 patients with stage I MF followed up for at least 12years or until disease progression. The methylation profiles were also analysed in two T-cell lymphoma cell lines and correlated with gene expression. The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least four loci was more frequent in cases progressing within 1-3 and 3-6years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3years (61%, P<0·001) than in those at 12years (67%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6years, after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest. Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early-stage MF, providing insights into its pathogenesis, prognosis and therapy.

SU-E-T-68: Clinical Implementation of Total Skin Electron Beam Therapy: A New- York Presbyterian Hospital Experience

Purpose: Total skin electron beam therapy (TSET) is used in the treatment of rare skin diseases such as mycosis fungoides, the most common type of cutaneous T-cell lymphoma. We report our experience with clinical implementation of TSET. Methods: A modified six-dual-field irradiation technique was chosen to deliver TSET. A Varian Trilogy linear accelerator with a nominal 6 MeV beam using high dose rate total skin electron mode (HDTSe) was employed. The recommendations of AAPM task group report 23 were followed for the commissioning. An acrylic plate (energy degrader) of 3.2 mm depth was mounted on the HDTSe applicator. The nominal source to skin distance was set at 450 cm. The optimum tilt angle of the gantry was determined using NACP-02 ionization chamber embedded in certified therapy grade solid water. Percent depth dose measurements were performed using ionization chamber and radiochromic films embedded in solid water and anthropomorphic phantom. For absolute dose measurements, TG-51 formalism was employed. The dose distribution on the entire skin was measured by irradiating the anthropomorphic phantom, with TLDs attached, mimicking the real treatment. Results: The 3.2 mm acrylic plate mounted on the HDTSe applicator degraded the energy of the electron beam to 4.1 MeV in themore » treatment plane, located at an SSD of 450 cm. The optimum tilt angle was found to be ±20°. A single-dual field had a longitudinal uniformity, measured at a depth of dose maximum, of ±7% over a length of about 200 cm. For the entire treatment the multiplication factor was found to be 2.86. On the surface of the phantom, the dose varied from 108% to 93% of the prescription dose. Conclusion: We have successfully commissioned TSET meeting the guidelines of the TG report 23, and treated our first patient on February 25, 2014.« less

Excimer laser in the treatment of mycosis fungoides

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents as a patch or plaque in early-stage disease. Phototherapy including psoralen plus ultraviolet A and ultraviolet B are well-established treatment modalities in management of early-stage MF. Only a limited number of reports have evaluated the efficacy of 308-nm excimer laser in therapy of cutaneous T-cell lymphoma. We sought to evaluate the efficacy of 308-nm excimer laser (XTRAC, PhotoMedex, Montgomeryville, PA) in patients with stage IA to IIA MF. We reviewed the clinical and laboratory characteristics of 6 consecutive patients given the diagnosis of refractory MF who underwent treatment with excimer laser. We found that the 308-nm excimer laser is a safe and well-tolerated alternative therapy for early-stage MF. In addition, we were able to delineate criteria to help predict treatment response. Our data showed that 4 (66%) patients achieved clinical improvement (3 complete responses, 1 partial response), 1 had stable disease, and 1 had progressive disease. This was a retrospective study consisting of 6 patients. A prospective study with a larger sample size would be desirable for future studies. The use of 308-nm excimer laser in the treatment of stage IA to IIA MF showed clinical and pathological benefit for patients with isolated lesions or lesions in areas that may be difficult to treat because of anatomic location.

Hypopigmented mycosis fungoides in Saudi Arabia, epidemiological and pathological study

IntroductionMycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. Hypopigmented MF is one of the less common variants of MF. Although rare, the exact frequency of HMF is still unknown. Materials and methodsWe performed a retrospective review of 17 cases of hypopigmented mycosis fungoides at two major tertiary centers in Saudi Arabia from the period 2010–2013. We described the clinical and important histological features of these cases. CD3, CD4, CD8, and CD7 stains performed for these cases have also been reviewed. ResultsThere were 5 male and 11 female patients. The age of onset of disease ranged between 5 and 60 with a mean of 17years. All the patients presented with hypopigmented scaly patches. Most common sites of distribution of the lesions were upper and lower extremities (100%) then the trunk (76%). The presence of lymphocytes at the dermoepidermal junction was the most frequent finding seen in 100% cases. Basilar predilection of the lymphocytes was seen in 75.5%. CD8 positivity in epidermal and dermal lymphocytes was seen in 14/17 biopsies. Focal positivity CD4 of the dermal lymphocytes was evident in 5/17. Loss of CD7 is noted in 14/17 biopsies.

Mycosis Fungoides With Large Cell Transformation and T Follicular Helper Phenotype

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and is usually characterized by a T-helper phenotype of neoplastic cells. Several clinical, histopathologic, and phenotypic variants of the disease have been described. We report on a case of MF in tumor stage with neoplastic cells expressing a T-follicular helper phenotype, characterized by positivity for PD-1, Bcl-6, and CXCL-13. Retrospective analysis of the first diagnostic biopsy of patch stage MF revealed a similar phenotype. This review addresses the clinical, histopathologic, phenotypic, differential diagnostic, and prognostic features of typical and of less conventional cases of MF.

Mycosis Fungoides Misdiagnosed As Squamous Cell Carcinoma

Mycosis Fungoides Misdiagnosed As Squamous Cell Carcinoma

Primary Cutaneous CD4+ Small to Medium‐Size Pleomorphic T‐Cell Lymphoma in a 12‐Year‐Old Girl

Primary cutaneous CD4+ small to medium-size pleomorphic T-cell lymphoma (PCSM-TCL) is a rare disease that has been added as a provisional entity to the World Health Organization European Organization for Research and Treatment of Cancer (WHO-EORTC) classification of lymphomas with primary cutaneous manifestations. Patients commonly present with a solitary nodule or plaque on the head or upper trunk, but are usually otherwise in good health. The prognosis is favorable, but the optimal treatment has not been defined. Recent publications have described the expression of programmed death-1 in PCSM-TCL and T-cell pseudolymphoma, suggesting a diagnostic value of this marker in the differential diagnosis of PCSM-TCL in contrast to other types of cutaneous T-cell lymphoma. We present the case of a 12-year-old girl with a tumor of the right supraorbital area. She was treated as an outpatient four times with intralesional triamcinolone acetonide at intervals of 3 to 4 weeks. In addition to the case history, this report includes the clinical and histologic findings and a review of the current literature.

Mycosis fongoïde papuleux

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. A new form of incipient MF has recently been described: papular MF. Herein, we report a case and propose a literature review. A 63-year-old man presented with erythematous and non-pruritic papular lesions of the trunk. The general examination was unremarkable. A skin biopsy showed moderately dense epidermotropic lymphocytic infiltration consistent with MF. Screening for CD30 was negative. Treatment with an extremely potent corticosteroid (clobetasol, one application per day) seemed effective, with almost complete disappearance of the lesions. Many clinical variants of the initial stages of MF have been described, one of the most recent of which is papular mycosis fungoides (PMF), of which 10 cases are reported in the literature. PMF begins clinically with an erythematous, non-pruritic and chronic papular rash that is not associated with the classic erythematous-squamous lesions of incipient MF. There appears to be no predominance of gender, and the age of onset ranges from 31 to 63 years. Histological examination of the PMF lesions revealed an epidermotropic subepidermal infiltrate composed predominantly of CD4+T-cells. The prognosis appeared good with the treatments conventionally used for incipient MF. PMF is likened to a form of incipient MF with a good prognosis. Associated classic MF lesions comprising erythematous-squamous plaques have been described as the condition progresses. Differential diagnoses include pilotropic MF, pityriasis lichenoides chronica, pityriasis lichenoides varioliformis acuta, and especially type B lymphomatoid papulosis, the histopathological findings of which may be close to PMF. Papular MF would appear to be a papular variant of incipient MF with a good prognosis. However, it is necessary to obtain clinical and disease progression data for a greater number of patients in order to better characterize this entity.

Hyperpigmented mycosis fungoides: a rare variant

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. The diagnosis of classic MF is based on a combination of clinical presentation, histopathology, immunohistochemistry, and T-cell monoclonality detected by molecular studies. However, the diagnosis can be difficult in some cases. We report a case of hyperpigmented mycosis fungoides. A 60-year-old woman, phototype IV, presented for more than 4 years a history of asymptomatic hyperpigmented non- infiltrated plaques on the face. Cutaneous lupus was diagnosed based on a skin biopsy. Hydroxychloroquine and photoprotection was started. Considering non improvement, another biopsy was done, in favor of a mycosis fungoides CD3+, CD4+, CD8-. The diagnostic of hyper pigmented mycosis fungoides stage I was retained and topical steroid was introduced. Mycosis fungoides can appear in various clinical forms, the hyperpigmented form is rare but this diagnosis should be evoked.

CD8+ mycosis fungoides with esophageal involvement: A case report

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and is characterized clinically by an indolent course with slow progression. MF is limited to the skin with widespread distribution, however, extracutaneous involvement of MF occurs during the advanced stages of the disease. Esophageal involvement of MF is a rare event. In the present study, we describe the first documented case of CD8(+) MF with esophageal involvement that was endoscopically diagnosed antemortem. A 70-year-old male with a 15-year history of MF presented with difficulty in swallowing. Endoscopic examination revealed a tumorous lesion with ulceration in all regions of the esophagus. Esophagus biopsy demonstrated atypical lymphocytic infiltrates with ulceration. Immunohistochemically, these atypical lymphocytes were positive for CD3, CD8 and cytotoxic granules. Therefore, a diagnosis of CD8(+) MF involving the esophagus was made. Extracutaneous involvement of the esophagus in MF is extremely rare and the majority of previously reported cases have been diagnosed postmortem. Only two cases of MF with esophageal involvement endoscopically diagnosed antemortem have been previously reported and this is the first documented case of CD8(+) MF with esophageal involvement diagnosed by this method. Early detection of extracutaneous involvement of MF is important for accurate treatment and endoscopic examination is a useful tool for detection of this pathology.

Vascular endothelial growth factor receptor-3 expression in mycosis fungoides

Here, we have studied vascular endothelial growth factor receptor-3 (VEGFR-3) expression in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). Immunohistochemistry revealed that in two-thirds of 34 patients, VEGFR-3 was expressed in situ by both tumor and stromal cells irrespective of the disease stage. The natural VEGFR-3 ligand, VEGF-C, partially protected malignant T-cell lines from growth inhibition by the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA). Whereas the malignant T cells did not produce VEGF-C in vitro, its expression was induced during tumor formation in vivo in a xenograft mouse model of MF. In conclusion, malignant and stromal cells express high levels of VEGFR-3 in all stages of MF. Moreover, malignant T cells trigger enhanced VEGF-C expression in fibroblasts, suggesting that cross-talk between tumor and stromal cells plays a role in lymphangiogenesis and possibly disease progression.

Interventions for mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. To assess the effects of interventions for mycosis fungoides in all stages of the disease. We searched the following databases up to January 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also checked reference lists of included studies for further references to relevant RCTs. We searched online trials registries for further references to unpublished trials and undertook a separate search for adverse effects of interventions for mycosis fungoides in non-RCTs in MEDLINE in May 2011. Randomised controlled trials (RCTs) of interventions for mycosis fungoides in people with any stage of the disease. At least 90% of participants in the trials must have been diagnosed with mycosis fungoides (Alibert-Bazin-type). Two authors independently assessed eligibility and methodological quality for each study and carried out data extraction. We resolved any disagreement by discussion. Primary outcomes were the impact on quality of life and the safety of interventions. When available, we reported on our secondary outcomes, which were the improvement or clearance of skin lesions, disease-free intervals, survival rates, relapse rates, and rare adverse effects. When possible, we combined homogeneous studies for meta-analysis. We used The Cochrane Collaboration's 'Risk of bias' tool to assess the internal validity of all included studies in six different domains. The review included 14 RCTs involving 675 participants, covering a wide range of interventions. Eleven of the included trials assessed participants in clinical stages IA to IIB only (please see Table 1 for definitions of these stages).Internal validity was considerably low in studies with a high or unclear risk of bias. The main reasons for this were low methodological quality or missing data, even after we contacted the study authors, and a mean dropout rate of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a maximum of 103 participants. Only one study provided a long enough follow-up for reliable survival analysis.Included studies assessed topical treatments, such as imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional injections of interferon-α (IFN-α). The light therapies investigated included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis (photochemotherapy), and visible light. Oral treatments included acitretin, bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted of denileukin diftitox; a combination of chemotherapy and electron beam radiation; and intramuscular injections of active transfer factor. Nine studies evaluated therapies by using an active comparator; five were placebo-controlled RCTs.Twelve studies reported on common adverse effects, while only two assessed quality of life. None of these studies compared the health-related quality of life of participants undergoing different treatments. Most of the reported adverse effects were attributed to the interventions. Systemic treatments, and here in particular a combined therapeutic regimen of chemotherapy and electron beam, bexarotene, or denileukin diftitox, showed more adverse effects than topical or skin-directed treatments.In the included studies, clearance rates ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis combining the results of 2 trials comparing the effect of IFN-α and PUVA versus PUVA alone showed no significant difference in the relative risk of clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included studies demonstrated a significant increase in disease-free intervals, relapse, or overall survival. This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary.