Utility of Low-Dose Duvelisib for Advanced Mycosis Fungoides: A Single-Institution Study.

Duvelisib, a small-molecule phosphatidylinositol 3-kinase-δ,γ inhibitor, has shown efficacy for mycosis fungoides (MF) at dosage ranges of 25-100 mg twice daily (BID), but with significant toxicity. We conducted a retrospective cohort study of patients with advanced MF treated with low-dose duvelisib (15 mg every other day to BID), in an effort to minimize toxicity. A total of 7 patients were included. The overall response rate on duvelisib was 71%, with the remaining patients maintaining stable disease. Mean modified Severity Weighted Assessment Tool score improved by 57.4% and mean percent body surface area involved improved by 52%. Median progression-free survival was 10.3 months. Adverse events occurred in 4 of 7 patients, the most common being fatigue (2/7; grades 1-2), nausea (2/7; grades 1-2), and transaminitis (2/7; grade 3). Overall, low-dose duvelisib showed efficacy for advanced MF with less toxicity, providing a rationale for its use as monotherapy and potentially combinatorial therapy.

Clinical Response in Heavily Pretreated Mycosis Fungoides with Pembrolizumab: A Case Report.

Mycosis fungoides (MF) is a disease almost impossible to cure. In the context of heavily pretreated patients, the anti-programmed cell death protein 1 (anti-PD-1) pembrolizumab is a valid therapeutic option. The alteration of the PD-1-PD ligand 1 (PD-L1) axis is often present in MF, and this aspect explains the feasibility of this therapy. We report the case of a 60-year-old woman diagnosed with MF in 2003, Olsen stage IA (T1M0NXBO). Since the moment of the diagnosis, she received 10 lines of therapy, with a short duration of response after each one of them. In April 2020, our patient started pembrolizumab 2 mg/kg every 3 weeks, and she achieved a partial response after the 4th cycle, consistent with the modified severity assessment tool (mSWAT) 1, which she is still maintaining after 10 cycles. No grade ≥3 adverse events were recorded. We conclude that pembrolizumab can induce extremely rapid responses in MF, with very low toxicity.

Evolution of Dupilumab-Associated Cutaneous Atypical Lymphoid Infiltrates.

BACKGROUND: Observations highlighting the "unmasking" of cutaneous T-cell lymphoma after treatment with dupilumab for atopic dermatitis (AD) have been recently reported. However, there remains a paucity of literature describing the evolution of clinical and histopathological features that characterizes this phenomenon. OBJECTIVE: To define the clinical and histopathologic evolution of atypical lymphoid infiltrates after the administration of dupilumab for AD. METHODS: A cross-sectional study of clinical and histopathologic features in 7 consecutive patients with a diagnosis of "atypical lymphoid infiltrate" or mycosis fungoides (MF) on dupilumab for AD was performed. RESULTS: Seven patients with atypical lymphoid infiltrates or MF in evolution after dupilumab therapy (age range 27-74 years) were reviewed. Average duration of AD before MF diagnosis was 5.7 years, and the average duration on dupilumab treatment was 9.8 months. Notable histopathologic features across predupilumab and postdupilumab biopsies included progressive increase in the densities of the atypical lymphoid infiltrates (7/7), presence of atypical epidermotropic lymphocytes (6/7), and papillary dermal fibrosis (6/7). LIMITATIONS: Small retrospective cohort study. CONCLUSION: These cases highlight the transformation of lymphoid infiltrates after dupilumab treatment for AD and emphasize the importance of clinical and histopathologic evaluation before and during treatment with dupilumab for treatment-refractory presumed AD.

[Reactivation of patch-stage mycosis fungoides caused by oral administration of dialyzable leukocyte extract. Case report]. / Reactivación de micosis fungoide en estadio de placa por administración de extracto dializado de leucocitos vía oral. Reporte de caso.

BACKGROUND: Mycosis fungoides is a cutaneous T-cell lymphoma. The patch stage is limited to the skin and may spontaneously involute or progress, spreading to peripheral blood, lymph nodes and viscera. CASE REPORT: 64 year-old female with a 6-year history of dermatosis with scaly, poorly delimited and pruritic plaques on the chest and extremities. She had received oral steroids and antihistamines, with transient partial remissions been experienced. Skin biopsy revealed Pautrier's microabscesses, which are pathognomonic of mycosis fungoides. Positron-emission tomography and peripheral blood smear ruled out dissemination and confirmed patch-stage mycosis fungoides. She received nitrogen mustard topical derivatives, psoralen plus UVA therapy, steroids and tacrolimus. She achieved complete remission at 6 months. Two years later, she was treated with dialyzable leukocyte extract, which reactivated the patch lesions with severe itching; the extract was discontinued. The lesions resolved two weeks after topical clobetasol was applied. CONCLUSIONS: Th2 predominates in mycosis fungoides. Given that dialyzable leukocyte extract reinforces the Th1 profile, it was unlikely for it to reactivate the disease, but the diversity of lymphocyte immunophenotypes in mycosis fungoides and the complex activation networks caused a paradoxical reactivation.

Antecedentes: La micosis fungoide es un linfoma cutáneo de células T. El estadio de placa se encuentra limitado a piel y puede involucionar o progresar, diseminándose a sangre periférica, ganglios y vísceras. Reporte de caso: Mujer de 64 años de edad con dermatosis de seis años de evolución con placas descamativas, mal delimitadas y pruriginosas en tórax y extremidades. Había recibido esteroides orales y antihistamínicos, con los que presentaba remisiones parciales transitorias. Mediante biopsia cutánea se encontraron microabscesos de Pautrier, patognomónicos de micosis fungoide. La tomografía por emisión de positrones y el frotis de sangre periférica descartaron diseminación y confirmaron micosis fungoide en estadio de placa. La paciente recibió derivados tópicos de mostaza nitrogenada, psoralenos con radiaciones ultravioleta A, esteroides y tacrolimus. Presentó remisión total a los seis meses. Dos años después recibió extracto dializado de leucocitos, con el que se reactivaron las lesiones con prurito intenso; suspendió el extracto. Las lesiones involucionaron dos semanas después de iniciar el clobetasol tópico. Conclusiones: En la micosis fungoide predomina Th2. Dado que el extracto dializado de leucocitos refuerza el perfil Th1 no se esperaba que reactivara la enfermedad, pero los diversos inmunofenotipos de los linfocitos en la micosis fungoide y las complejas redes de activación ocasionaron reactivación paradójica.

Mycosis fungoides two decades after exposure to sulphur mustard: a follow-up of 1100 victims.

BACKGROUND: Sulphur mustard (SM) is an alkylating chemical warfare agent which causes acute and chronic injuries to the eyes, skin, lung and respiratory tract. OBJECTIVE: We aimed to investigate the relationship between SM poisoning and Mycosis fungoides (MF) as a late consequence. MATERIAL AND METHODS: In this retrospective study, the medical files of 1100 Iranian veterans confirmed to have exposure to SM agent during the Iraq-Iran war of the 1980s were reviewed. RESULTS: All 10 cases with MF were confirmed by clinical and histopathological examinations. The mean age of the studied subjects was 43.3 ± 9.8 (years). In comparison to MF incidence rate in Iranian general population (0.39/100 000 person-years), we found an incidence rate of 0.799/100 000 person-years for MF among those who had short-term exposure to SM. The most common sites for SM lesions were flexural and thin skin areas. The main limitation was the retrospective design. CONCLUSION: This study indicates that the risk of MF in those exposed to SM may increase over time. Therefore, their follow-up is recommended.

Micosis fungoide e inhibidores del TNFα: ¿riesgo o beneficio?

The growing use of anti-TNF drugs during the last years has reopened the discussion about the possible increased risk of developing non-Hodgkin lymphoma in patients with such type of treatments. We present our clinical experience and critical opinion about the current situation of such issue regarding cutaneous T-cell lymphomas.El creciente uso de fármacos anti-TNF durante los últimos años ha reabierto el debate sobre el posible aumento de riesgo de linfomas no Hodgkin en los pacientes con este tipo de tratamientos. Presentamos nuestra experiencia clínica y opinión critica sobre la situación actual de este tema en relación a los linfomas cutáneos de células T.

Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis.

Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate. Since then, few cases of methotrexate-induced skin ulcers in patients with mycosis fungoides have been published. We report an additional patient with erythrodermic mycosis fungoides who developed cutaneous ulcerations as a sole manifestation of methotrexate toxicity.

Cutaneous lymphoproliferative disorders in organ transplant recipients: update 2014.

Post-transplant lymphoproliferative disorders (PTLD) are lymphoid or plasmacytic proliferations that develop after solid organ, bone marrow or stem cell transplantation. PTLD are the leading cause of cancer-related mortality and graft loss in both pediatric and adult solid organ transplant recipients (ORT). These disorders comprise a spectrum ranging from usually EBV-driven, mostly B-cell polyclonal proliferations to B- and T-cell lymphomas indistinguishable from their counterparts occurring in immunocompetent individuals. PTLD usually present in extranodal sites; isolated skin involvement of PTLD is rare. A recent multicenter European case series showed that primary cutaneous T-cell PTLD are more common than primary cutaneous B-cell PTLD, and along with its folliculotropic variant, mycosis fungoides (MF) is the most frequent form of posttransplant primary cutaneous T-cell lymphoma (CTCL). This case series also disclosed that primary cutaneous CD30+ lymphoproliferative disorders is the second most common posttransplant CTCL subtype, indicating that the spectrum of primary CTCL in OTR is similar to that in the general population. However, in contrast with the immunocompetent individuals, the prognosis of primary cutaneous CD30+ anaplastic large T-cell lymphoma is worse than posttransplant MF and than its counterpart in the general population which has an excellent prognosis. The recent case series indicated that the spectrum of primary cutaneous B-cell PTLD differs significantly from cutaneous B-cell lymphoma in the general population, with a predominance of EBV-associated forms. Currently, the best therapeutic intervention(s) for primary cutaneous PTLD remains unknown.

Occupational exposure to chlorinated and petroleum solvents and mycosis fungoides.

OBJECTIVE: To evaluate the potential association between occupational exposure to chlorinated and petroleum solvents and mycosis fungoides (MF). METHODS: A questionnaire on lifetime job history was administered to 100 patients diagnosed with MF and 2846 controls. Odds ratios (ORs) were calculated as the measure of the association between exposure to each specific solvent and MF. RESULTS: In the total sample and in men, cases and controls did not differ in relation to exposure to any of the solvents studied. In women, an association with MF was seen for the highest level of estimated exposure to perchloroethylene (OR = 11.38; 95% confidence interval: 1.04 to 124.85) and for exposure less than the median to kerosene/fuel/gasoil (OR = 8.53; 95% confidence interval: 1.11 to 65.62). CONCLUSIONS: These results do not provide conclusive evidence that exposure to solvents may increase risk of MF because they were not found in men.

Clinicopathological features of mycosis fungoides in patients exposed to Agent Orange during the Vietnam War.

There are no reports on the clinicopathological features of mycosis fungoides (MF) among veterans exposed to Agent Orange, one of the herbicides used during the Vietnam War. To evaluate the clinical, histopathological and genotypic findings of Vietnam War veterans with MF and a positive history of exposure to Agent Orange, we performed a comparative clinicopathological study between MF patients with a history of Agent Orange exposure and those without a history of Agent Orange exposure. Twelve Vietnam War veterans with MF were identified. The mean interval from Agent Orange exposure to diagnosis was 24.5 years (range, 9-35). Skin lesions were significantly present on exposed and unexposed areas. Most patients (75%) experienced pruritus (mean visual analog scale score of 6.7). MF was manifested by plaques in 10 patients and by lichenification in five. Histopathological features of most cases were consistent with MF. Biopsy specimens also demonstrated irregular acanthosis (66.7%). In the comparative study, MF patients with a history of Agent Orange exposure differed significantly from those without exposure to Agent Orange in demographic and clinical characteristics. In addition, patients with exposure had an increased tendency for lesions in the exposed area. Notably, our patients showed a higher frequency (33.3%) of mycosis fungoides palmaris et plantaris than in previous studies. Histologically, irregular acanthosis was more frequently observed than ordinary MF. Our results indicate that dermatologists should pay close attention to these clinicopathological differences. Careful assessment of history of exposure to defoliants is warranted in some cases suspicious for MF.

Follicular mucinosis and mycosis-fungoides-like drug eruption due to leuprolide acetate: a case report and review.

Leuprolide acetate represents a gonadotropin-releasing hormone agonist, used as part of the treatment of prostate cancer. We report an unusual case of disseminated urticarial rash following leuprolide injection in a 67-year-old man that histopathologically and immunohistochemically resembled mycosis-fungoides, including the presence of follicular mucinosis and eosinophils in the follicles. This histopathologic pattern has not been previously described as a drug reaction pattern due to leuprolide, and it underscores the importance of correlation with the clinical impression to arrive at a correct diagnosis.

[Syringotropic cutaneous T-cell lymphoma mimicking dermatomycosis]. / Lymphome cutané T syringotrope simulant une dermatomycose.

INTRODUCTION: Cutaneous syringotropic T-cell lymphoma is a rare form of lymphoma. We report a case involving a misleading cutaneous presentation on the sole of the foot. PATIENTS AND METHODS: A 55-year-old woman presented discrete coalescent papules on her left foot, having an anhidrotic appearance, for which a number of antifungal treatments had been given without success. The skin biopsy revealed CD4+ T lymphocytic dermal infiltrate, mainly near the sweat glands, with syringotropism. The diagnosis of syringotropic T-cell lymphoma was reinforced by the presence of dominant cutaneous T-lymphocyte clone in the skin biopsy. Staging tests were negative. Treatment was initiated with an extremely potent (class IV) dermal corticosteroid. DISCUSSION: Syringotropic T-cell lymphoma is an extremely rare form of cutaneous lymphoma similar in presentation to mycosis fungoides, characterised by the mainly perisudoral and syringotropic nature of the lymphocytic infiltrate. The value of this case report lies in the extremely mild nature of the misleading skin lesions, which could only be diagnosed through biopsy. Treatment for this condition is not as yet codified due to the extremely low number of cases reported in the literature.

Mycosis fungoides in a patient with ankylosing spondylitis during infliximab therapy.

Immunosuppressive therapies, in particular cyclosporine, are known to induce the development of lymphoproliferative malignancies. In general, the lymphomas that occur in the setting of impaired immune function are B cell non-Hodgkin's lymphomas, often large cell lymphomas. Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphomas, which can require persistent antigen and superantigen stimulation by way of chronic immunosuppression and HIV. Tumor necrosis factor antagonists, which are novel immunomodulatory agents, might produce significant adverse effects, including an increased risk of malignancy. Currently available data do not show whether these agents were the proximate cause of the reported lymphomas. We present a 32-year-old male with ankylosing spondylitis treated with infliximab who developed MF during the second year of therapy.

Mycosis fungoides progression and chronic solvent exposure.

The effect of repeated exposure to specific chemicals on the initiation or progression of mycosis fungoides (MF) remains unsettled. A patient with low-grade patch stage MF progressively developed MF plaques restricted to his arms, and a tumour on his right thigh. These areas were subject to repeated exposure to solvents. His thigh was indeed in close contact with his trousers pocket where he used to store a wiping rag drenched into white spirit and cellulosic thinner. Immunophenotyping these lesions revealed a dense LCA+, CD2+, CD3+, CD4+, CD5+, CD7+, CD45+, CD45RO+ T-cell infiltrate admixed with many factor XIIIa+ dendrocytes. T-cell receptor rearrangement analysis identified a monoclonal T-cell infiltrate. An internal work-up remained negative. Stopping further solvent exposure failed to improve his condition. Oral corticotherapy combined with low-dose interferon-alpha2a halted disease progression. This observation suggests that long-term solvent exposure may trigger MF and hasten its progression from the patch stage to the plaque and tumour stages.