OBJECTIVE: Interferon (IFN)-a is often used in combination with psoralen plus ultraviolet A (PUVA) in patients with mycosis fungoides (MF) refractory to skin-targeted therapies in early or advanced stages. The main objective is to evaluate the effectiveness of combined PUVA and low-dose IFN-α-2a therapy in patients with early- and advanced-stage MF.
METHODS: Sixty-eight patients who received a combination of PUVA twice or thrice a week and INF-a 3 MU thrice a week for at least 3 months were reviewed retrospectively. The treatment response was evaluated as complete remission (CR), partial remission, stable disease, or progression.
RESULTS: At the initiation, the majority of patients (66.2%) had early-stage disease. In 27.9% of cases, this was the initial treatment administered following the diagnosis of MF. The median duration of combination therapy was 11 months. Complete remission was achieved in 45.6% of the patients with an overall response rate of 60.3%. The mean duration of response was 5 months. Complete remission was statistically significantly higher in early-stage patients (p < .05). No statistically significant correlation was observed between CR and gender, histopathological features, or laboratory parameters. In patients with CR, 80% experienced relapse, significantly higher in early-stage patients (p < .05). However, there was no significant difference in disease-free survival between early and advanced stages (p > .05).
CONCLUSIONS: The study results indicated that PUVA + low-dose INF-a combination therapy was more effective in the early stage than in the advanced stage. Additionally, there was a high relapse rate after the cessation of treatment in patients who achieved CR.

The diagnosis of cutaneous T-cell lymphoma (CTCL) remains challenging. Demonstration of a clonal T-cell population using T-cell receptor (TCR) gene rearrangement studies by next-generation sequencing (NGS) has been explored in several studies. This review summarizes the current literature on NGS-based sequencing methods for the assessment of TCR clonality in the evaluation of atypical cutaneous lymphoid infiltrates and CTCL on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (lymphoproliferative subgroup). PubMed was searched for relevant articles, including CTCL and NGS, for clonality from 1967 to 2022. Thirteen studies were included in the analysis. The skin was the most commonly assayed compartment with TCR NGS. Sensitivity for TCR NGS in the skin ranged between 69% and 100%, compared to 44%-72% for polymerase chain reaction (PCR)-capillary electrophoresis. Specificity for TCR NGS in the skin ranged from 86% to 100%, compared to 77%-88% for PCR capillary electrophoresis. TCR NGS was also reported to have potential prognostic value in CTCL and can also be used to detect relapse and/or minimal residual disease after treatment.

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas.

UNASSIGNED: Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients.
UNASSIGNED: A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months.
UNASSIGNED: The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months (N = 22), 75.0% at 9 months (N = 24), and 60.0% at 12 months (N = 15) after ECP initiation.
UNASSIGNED: Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.

Sezary syndrome (SS) is a rare but aggressive type of cutaneous T-cell lymphoma (CTCL). Patients with SS have characteristic skin lesions (erythroderma) and a leukemic phase. The rash associated with CTCLs can often mimic common benign skin conditions such as psoriasis, atopic dermatitis, etc. and therefore can go undiagnosed until later stages. We present a case of a patient with SS who managed eczema for over one year with topical steroids before receiving a skin biopsy. Workup confirmed leukemic involvement, and the patient was started on systemic therapy with bexarotene. The patient continues to have a good response to systemic therapy. When treating patients with persistent rash of uncertain etiology and/or unresponsive to treatment, primary care physicians and internists need to consider SS/Mycosis fungoides as a possible differential and should have a low threshold to initiate early referral to dermatology for definitive diagnosis.

While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical picture is attributed to the complex interplay of host characteristics (hygiene and aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance and species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions. Thus, a literature examination was performed to provide a comprehensive analysis on rare and atypical superficial mycosis as well as an update on certain fungal clinical manifestations and their significance. The research and standard data extraction were performed using PubMed, Medline, Scopus, and EMBASE databases, and a total of 222 articles were identified. This review covers published research findings for the past six months.

Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.

Mycosis fungoides (MF) is the most prevalent type of cutaneous T-cell lymphoma and is generally characterized by multiple patches or plaques with fine scales. One of its variants manifests with multiple purpuric eruptions, mimicking benign pigmented purpuric dermatosis (PPD). To investigate clinicopathological features of PPD-like MF patients. We report four PPD-like MF cases and summarize the clinicopathological features described in reports of nine PPD-like MF cases published in the past 20 years. Compared with benign PPD, petechial lesions in PPD-like MF are more generalized, persistent, and resistant to conventional steroid treatment. Histologically, a superficial dermal band-like infiltrate of atypical lymphocytes with epidermotropism seems to be the most common feature of PPD-like MF. A lymphoid phenotype of CD4+ CD7- T cells and a monoclonal T-cell profile, demonstrated by T-cell receptor gene arrangement analysis, favour a diagnosis of PPD-like MF. Although the exact relationship between PPD and PPD-like MF remains unclear, our study has attached importance to the differential diagnosis of the two diseases in cases of overlooked MF variants. If persistent or generalized purpuric lesions are present, PPD-like MF should be taken into consideration. A thorough physical examination combined with pathological findings may lead to a correct diagnosis.

BACKGROUND: Granulomatous mycosis fungoides (GMF) is a rare form of cutaneous T-cell lymphoma characterized by a granulomatous inflammatory infiltrate.
OBJECTIVE: The impact of granulomatous inflammation on the prognosis of the disease remains controversial as there have been both favorable and unfavorable outcomes documented.
METHODS: We performed a systematic review of 116 GMF cases previously described in the literature.
RESULTS: In contrast to the classic Alibert-Bazin type of mycosis fungoides (MF), cutaneous lesions in GMF tend to involve distal extremities (lower legs, feet, hands) early in the disease course. In the literature, 30% of GMF patients developed organ metastasis, most frequently to the lung. The median time to stage progression was 25 months.
CONCLUSIONS: GMF is an aggressive form of MF. Therefore, screening for distant metastases should be considered at presentation and repeated during follow-up.

Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.