BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. As the early clinical manifestations of MF are non-specific (e.g., erythema or plaques), it is often misdiagnosed as inflammatory skin conditions (e.g., atopic dermatitis, psoriasis, and pityriasis rosea), resulting in delayed treatment. As there are no effective biological markers for the early detection and management of MF, the aim of the present study was to perform a proteomic analysis of urine samples (as a non-invasive protein source) to identify reliable MF biomarkers.
METHODS: Thirteen patients with early-stage MF were administered a subcutaneous injection of interferon α-2a in combination with phototherapy for 6 months. The urine proteome of patients with early-stage MF before and after treatment was compared against that of healthy controls by liquid chromatography-tandem mass spectrometry. The differentially expressed proteins were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Clusters of Orthologous Groups analyses. For validation, the levels of the selected proteins were evaluated by enzyme-linked immunosorbent assay (ELISA).
RESULTS: We identified 41 differentially expressed proteins (11 overexpressed and 30 underexpressed) between untreated MF patients and healthy control subjects. The proteins were mainly enriched in focal adhesion, endocytosis, and the PI3K-Akt, phospholipase D, MAPK, and calcium signaling pathways. The ELISA results confirmed that the urine levels of Serpin B5, epidermal growth factor (EGF), and Ras homologous gene family member A (RhoA) of untreated MF patients were significantly lower than those of healthy controls. After 6 months of treatment, however, there was no significant difference in the urine levels of Serpin B5, EGF, and RhoA between MF patients and healthy control subjects. The area under the receiver operating characteristic curve values for Serpin B5, EGF, and RhoA were 0.817, 0.900, and 0.933, respectively.
CONCLUSIONS: This study showed that urine proteomics represents a valuable tool for the study of MF, as well as identified potential new biomarkers (Serpin B5, EGF, and RhoA), which could be used in its diagnosis and management.

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs.Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023.Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, β2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival.Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.

OBJECTIVE: Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects.
METHODS: This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model.
RESULTS: In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0% vs. 54.3%, p = 0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4 vs. 6 months, p = 0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients\' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed.
CONCLUSIONS: Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.

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UNASSIGNED: Unlike most cases, the lesions were localized to the dorsum of the hand, lacked pruritus (itching), and did not exhibit \"sperm-like blood vessels,\" which are typically pathognomonic to classical MF.
UNASSIGNED: The study presents a rare case involving a 44-year-old woman who developed a skin condition on the base of her left thumb. Initially misdiagnosed as pigmented purpura, the need for further investigation arose to determine the nature of the condition accurately. The medical evaluation encompassed a comprehensive analysis of the patient\'s skin ailment. A series of diagnostic examinations were conducted to ascertain the underlying cause. Although routine blood tests yielded unremarkable results, the distinct characteristics of the rash prompted a more thorough investigation. Subsequent assessment revealed that the skin condition was not pigmented purpura, as initially presumed, but rather a manifestation of cutaneous T-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF is an infrequent lymphoma predominantly affecting individuals aged 45-65, exhibiting a male-to-female sex ratio of 2:1. The annual incidence of MF ranges from 0.3 to 0.96 cases per 100,000 individuals. The woman\'s skin exhibited discrete patches adorned with colored dots, progressively thickening and pigmentation. Notably, the absence of pruritus did not dispel suspicion. This case underscores the significance of accurately diagnosing uncommon dermatological disorders to facilitate appropriate medical intervention. The unique appearance of the rash and its distinctive features, despite normal blood results, enabled the identification of MF. The patient\'s treatment encompassed a combination of steroids and narrowband UV therapy. Vigilance, continued research, and heightened awareness are paramount for early intervention and improved patient outcomes. Such efforts contribute to an enhanced understanding of the complexities of this condition.

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma.
Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF.
Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment.
Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001) and after 3 months (p < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred.
Conclusion: IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.

Mycosis fungoides (MF) is a low-grade malignant cutaneous T-cell lymphoma that originates from memory T cells. It typically follows a unique and relatively indolent disease course. MF is used to be characterized by a tissue-resident memory T cell (TRM) phenotype, although recent molecular research has revealed its complexity, casting doubt on the cell of origin and the TRM-MF paradigm. Recent clonal heterogeneity studies suggest that MF may originate from immature early precursor T cells. During development, the tumour microenvironment (TME) influences tumour cell phenotype. The exact origin and development trajectory of MF remains elusive. Clarifying the origin of MF cells is vital for accurate diagnosis and effective treatment.

Advanced-stage cutaneous T-cell lymphomas (CTCLs) are notorious for their highly aggressive behavior, resistance to conventional treatments, and poor prognosis, particularly when large-cell transformation occurs. PEG10 has been recently proposed as a potent driver for large-cell transformation in CTCL. However, the targeting of PEG10 continues to present a formidable clinical challenge that has yet to be addressed. In this study, we report an important post-translational regulatory mechanism of PEG10 in CTCL. USP9X, a deubiquitinase, interacted with and deubiquitinated PEG10, thereby stabilizing PEG10. Knockdown of USP9X or pharmacological targeting of USP9X resulted in a prominent downregulation of PEG10 and its downstream pathway in CTCL. Moreover, USP9X inhibition conferred tumor cell growth disadvantage and enhanced apoptosis in vitro, an effect that occurred in part through its regulation on PEG10. Furthermore, we demonstrated that inhibition of USP9X obviously restrained CTCL tumor growth in vivo and that high expression of USP9X is associated with poor survival in patients with CTCL. Collectively, our findings uncover USP9X as a key post-translational regulator in the stabilization of PEG10 and suggest that targeting PEG10 stabilization through USP9X inhibition may represent a promising therapeutic strategy for advanced-stage CTCL.

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UNASSIGNED: A 44-year-old woman presented with extensive skin patches and pruritus persisting for 3 years. Histopathological examination of the skin from the right abdomen confirmed mycosis fungoides-type cutaneous T-cell lymphoma. Staging PET with 18 F-FDG PET/CT) showed increased uptake in the skin on the right abdomen and left hip. Subsequently 18 F-FAPI-42 PET/CT revealed additional foci of abnormal uptake on the skin of the chest and back.