Early-stage Mycosis Fungoides Research Articles

Dermatoscopic Characteristics, Lesional Capillaroscopic Features, and Histopathological Correlation of Small Plaque Parapsoriasis and Mycosis Fungoides.

Dermatoscopy is a frequently used non-invasive diagnostic procedure. Considering that mycosis fungoides (MF) mimics parapsoriasis clinically in early stages, we aim to determine the dermatoscopic criteria and the histopathological correlations in patients with MF and small plaque parapsoriasis (SPP). This prospective study involved 28 patients with clinical and histopathological diagnoses of MF and 31 patients with SPP. Videodermoscopy and USB capillaroscope were used to evaluate the patients vessels at ×200 magnification. Vascularity was evaluated through microvascular density (MVD) scoring involving CD34 antibody staining. Fifty-nine patients were included in this study. The scores corresponding to the presence of short linear vessels, linear-curved vessels, branching linear vessels, and non- structured orange-colored areas were significantly higher in the MF patients than in the SPP patients (P < 0.05). The highest MVD (P = 0.01) scores were also higher in the MF patients than in the SPP patients. The SPP and early-stage MF patients differed in their MVD scores, and the findings correlated with the dermatoscopy and lesional capillaroscopy findings. Differentiating features between SPP and MF were thus identified.

Effectiveness and tolerability of chlormethine gel for the management of mycosis fungoides: a multicenter real-life evaluation.

Topical chlormethine (CL) is recommended as a first-line treatment for early-stage mycosis fungoides (MF) and in 2017, the European Medicines Agency approved the CL gel formulation to treat adult patients. More recently, to increase patient compliance and adherence, clinicians have developed flexible protocols that allow the concomitant use of CL gel with topical corticosteroids in daily practice regimens. Therefore, sharing real-life data on CL gel use and side effects management may help improve the use of this agent. To expand knowledge about the actual use of CL gel in patients with MF, the present study assessed the improvement of MF skin lesions after CL gel treatment and provided information on the management of cutaneous adverse events (AEs) in a real-life setting. This was an Italian retrospective study conducted among six dermatology referral centers. Patients ≥18 years affected by MF and in treatment with CL gel (160 µ/g), alone or in combination according to routine clinical practice, between December 2019 and December 2021 were considered. The study's primary aim was to evaluate the effectiveness of CL gel in terms of overall response rate (ORR) after 3 months of treatment. A total of 79 patients (61% male) with different stages of MF (84% early stage) were included. CL gel was prescribed mainly in association with topical corticosteroids (66% of patients). ORR after 3 months of treatment was 42%, with no differences between early- and advanced-stage MF. Response rates improved over time up to 97% after 18 months of treatment. Overall, 66 AEs were reported in 67% of patients; most were hyperpigmentation (45%) and irritant contact dermatitis (37%). Six AEs led to treatment discontinuation, and five out of six (83%) patients who reported these events resumed treatment after interruption. No AEs were classified as severe. Our observations support the use of CL gel in patients with early- and advanced-stage MF, making it a valuable treatment option.

Psychological Distress and Treatment Outcome in Patients With Early-Stage Mycosis Fungoides.

Skin diseases have been shown to worsen psychological distress, which, in turn, may be detrimental to treatment outcomes. Both the impact of psychological distress on response to treatment in mycosis fungoides (MF) and the effect of treatments on psychological well-being are unclear. To evaluate (1) the association between pretreatment psychological morbidity and treatment outcome in early-stage MF and (2) the impact of response to treatment on psychological well-being. This was a prospective cohort study of patients with early-stage MF who started a new stage-directed treatment for their disease. The response was determined using the modified severity-weighted assessment tool, and psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12) and Penn State Worry Questionnaire (PSWQ). Participants were followed for 1 year. In all, 24 consecutive patients were recruited. Objective response rate was 71% (17/24), consistent with existing literature. Prior to treatment, 9 patients (38%) had clinically significant psychological distress on the GHQ-12, while 8 (33%) demonstrated high-level worry on the PSWQ. Of these patients, 6 had pathologic scores on both instruments. Patients with significantly less baseline anxiety/depression on the GHQ-12 responded better to treatment than patients with higher levels (P = .004). In addition, responders' mean GHQ-12 scores decreased by 39% and their PSWQ scores by 17%, whereas nonresponders' GHQ-12 scores increased by 93% (P = .042) and their PSWQ scores by 11% (P = .019). These findings suggest that (1) baseline psychological distress is associated with worse outcomes in patients with early-stage MF and that (2) effective treatment improves psychological morbidity.

A Review of the Dermatologic Clinical Applications of Topical Photodynamic Therapy.

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.

The Battle of Cutaneous T Cell Lymphomas: Mycosis Fungoides Vs. Sezary Syndrome

Introduction: Mycosis Fungoides (MF) &amp; Sezary Syndrome (SS) are two distinct extra-nodal Cutaneous T Cell Lymphomas (CTCL), which are a subtype of Non-Hodgkin's Lymphoma (NHL). Although belonging to the same entity, its presentation varies drastically. Early stage of MF is limited to the skin and whereas advanced-stage disease can involve lymph nodes, blood, &amp; visceral organs, whereas SS involves the blood, lymph nodes, and skin. The aim of this retrospective analysis is to study the variance in the epidemiology and prognosis of MF and SS. Method: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted Mycosis Fungoides and Sezary Syndrome cases diagnosed after 20 years of age, with Lymphoid neoplasm recode 2(b)2.1.1 and 2(b)2.1.2. The analysis was stratified based on age, sex, racial incidence rates, &amp; survival curves based were compared, using the Log-rank test (GraphPad Prism). Results: 8853 cases of MF were identified between 2000-2020. The median age of diagnosis was 60 years. Of the affected individuals, 57.59% were males and 42.40% were females. The incidence of MF, per 1,000,000 population, in 2000 was 6.1 &amp; 6.05 in 2020. 62.45% were whites, 13.75% were blacks, 6.98% were Asians/Pacific Islanders, 0.42% were American Indians/Alaskan Natives, &amp; 11.64% were Hispanics. 5.2% of patients had localized disease, 8.38% patients had regionall disease, &amp; 1.34% had the evidence of distant metastasis. vs. 307 cases of SS were identified between 2000-2020. The median age of diagnosis was 71 years. Of the affected individuals, 56.35% were males and 43.64 were females. The incidence rate of SS, per 1,000,000 population, in 2000 was 0.17 &amp; 0.28 in 2020. 69.70% were whites, 14.00% were blacks, 2.28% were Asians/Pacific Islanders, 0.65% were American Indians/Alaskan Natives, &amp; 12.70% were Hispanics. 46.24% of patients had localized disease, 38.11% patients had regional disease, &amp; 16.61% had the evidence of distant metastasis. Survival analyses were compared for the general population &amp; further stratified based on races, between MF &amp; SS. The median of survival (mOS) was 238 months for MF &amp; 39 months for SS ( p&amp;lt;0.0001, Hazard Ratio (HR) 0.2215, Confidence Interval (CI) 0.1649 to 0.2975.) Conclusion: When the subtypes of CTCLs, MF &amp; SS, were compared, prevalence of MF was significantly more than SS. Incidence of MF somewhat stayed the same in 20 years vs SS showed an uptrend. Median age for diagnosis was higher SS (71 years) vs. SS(60 years). Both showed a strong predilection towards males. The most commonly affected race for both, was seen in Whites &amp; the least was for American Indians/Alaskan Natives. Survival for MF(238 months) was significantly higher than SS (39 months). Although rarer of the two CTCL, SS has a poorer prognosis. With this retrospective study, our aim was to understand the epidemiology of the two CTCLs, as with the newer treatment options for these diseases like Romidepsin and Brentuximab Vedotin, it would be interesting to do a follow-up study on the epidemiological variability &amp; survival, for these rare hematological malignancies.

The Overlap of Skin and Blood T-Cell Clones in Early-Stage Mycosis Fungoides

Introduction: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma that initially starts in the skin but can progress to involve blood with significant mortality in late stages. Even in early stages and in the absence of blood involvement, changes in blood T-cell receptor (TCR) repertoire have been observed in MF patients. While prior work has explored the significance of dominant blood T-cell clones in the prognosis of early MF, the relationship between TCR sequences and T-cell repertoires of blood and skin in early-stage MF patients has not been characterized. Objectives: To determine the relationship of blood and skin T-cell repertories and to reassess the impact of dominant blood T-cell clones on selected outcome endpoints in early-stage MF. Materials and Methods: We used high-throughput sequencing to interrogate TCR sequences in blood and skin of MF patients without blood involvement at the Jefferson Cutaneous Lymphoma Clinic (Adaptive Biotechnologies). ImmunoSEQ Analyzer provided T-cell repertoire overlap metric (Morisita's index) and diversity measure (Simpson's clonality score). Time to systemic treatment (TTST) was calculated as the time from initial diagnosis to initiation of first systemic therapy. Results: 60 MF patients with no blood involvement were enrolled. 28% had a dominant clone in blood; of these, 18% were identical to dominant skin clones and 82% were distinct from the dominant clones identified in skin. We found that MF patients with discordant dominant T-cell clones in blood and skin had a longer TTST when compared to the identical clone cohort (P=0.0057) (Figure 1A). Furthermore, patients with discordant dominant clones had a lower degree of T-cell repertoire overlap between blood and skin (P&amp;lt;0.0001) and higher blood T-cell repertoire diversity scores (P=0.013) when compared to the identical clone group (Figure 1B). In all patients, the degree of T-cell overlap in blood and skin did not significantly change over a period of months to years or among skin biopsies obtained from different anatomical locations. Finally, in a subset of patients with discordant clones, the dominant skin clone did not appear to be detected in blood even at low frequencies. Conclusion: Our data highlight the importance of establishing clonal associations between dominant T-cell clones of the skin and blood in MF. We propose that early-stage MF patients with dominant clones in blood segregate into two cohorts with distinct prognoses and T-cell repertoires based on the identity of their peripheral T-cell clones. In addition, our findings suggest that not all MF patients have reservoirs of malignant T-cell clones readily available in peripheral circulation to seed new lesions in skin. Figure 1: A: Kaplan-Meier analyses of time to systemic treatment (TTST) in skin-limited mycosis fungoides (MF) patients with an identical dominant T-cell clone in blood and skin, a discordant dominant T-cell clone in blood and skin, and no dominant blood clones. NS- not significant (P =0.5274), ** (P =0.0057), *** (P &amp;lt;0.0003). B: Average Morisita's index for blood and skin overlap for patients in indicated groups of I: identical dominant clones in blood and skin, D: discordant dominant clones in blood and skin, and N: no dominant clone in blood. **** (P &amp;lt;0.0001).

The effect of phototherapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides

   Introduction. The role of the cytokine environment and immune deregulation in the pathogenesis of mycosis fungoides is unquestionable. Despite the fact that one of the methods of therapy for the early stages of mycosis fungoides is phototherapy (PUVA, UVB-311 nm), the effect of ultraviolet radiation on the lymphoproliferative substrate and pathogenetic links in mycosis fungoides has not been fully studied.   Aim: to evaluate the effect of NB-UVB and PUVA therapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides.   Material and Methods. A comparative non-randomized study of the cytokine mRNA expression dynamics in the affected skin and of the effectiveness of phototherapy was carried out in 28 patients with early stage of mycosis fungoides. The IL4, IL17A, IL17F, and IL22 mRNA expression was determined relative to the endogenous control GAPDH using the real-time reverse transcription PCR (RT-PCR). Evaluation of the effectiveness of NB-UVB and PUVA therapy was carried out using a BSA score (skin lesion area) and a modified severity-weighted assessment tool (mSWAT) score.   Results. The study included 28 patients with early stages (IA–IIA) of mycosis fungoides; 9 patients received NB-UVB and 19 received PUVA therapy. 3.71-fold decrease in mSWAT (p &lt; 0.008), and 3-fold decrease in BSA scores (p &lt; 0.013) were observed in the NB-UVB-treated group. In the PUVA-treated group 3.47- and 2.19-fold lower scores of mSWAT (p &lt; 0.001) and BSA (p &lt; 0.001) were found. There were no significant differences in the expression of the studied cytokines in the NB-UVB-treated group; however, a significant 19 and 72 % increase in IL17F (p = 0.003) and IL22 (p = 0.021) was revealed afterPUVA therapy. Correlation analysis has shown a weak correlation between IL4 and IL17A (r = 0.43, p &lt; 0.027), and IL17F (r = 0.43, p &lt; 0.028) before the treatment. Under the influence of phototherapy, the formation of a cytokine network in the affected skin was observed: there were positive associations between IL4 and IL17A (r = 0.73, p &lt; 0.001), IL17F (r = 0.7, p &lt; 0.001) and IL22 (r = 0.43, p &lt; 0.024); IL17A and IL17F (r = 0.78, p &lt; 0.001); IL22 and IL17A (r = 0.63, p &lt; 0.001) and IL17F (r = 0.66, p &lt; 0.001). In the PUVA-treated group a high negative correlation between IL17A and mSWAT (r = -0.79415, p =0.010586), BSA (r = -0.75432, p = 0.018849) were found.   Conclusion: The positive correlations between IL4, IL17A, IL17F and IL22 in the affected skin of patients with mycosis fungoides may underlie the positive effect of phototherapy.

Gene Expression Differences Identified in Skin Samples of Early-Stage Mycosis Fungoides, Atopic Dermatitis, and Psoriasis

Gene Expression Differences Identified in Skin Samples of Early-Stage Mycosis Fungoides, Atopic Dermatitis, and Psoriasis

74 Interstitial fluid immunophenotyping characterizes topical chlormethine-induced changes in the tumor micro-environment in early-stage mycosis fungoides

74 Interstitial fluid immunophenotyping characterizes topical chlormethine-induced changes in the tumor micro-environment in early-stage mycosis fungoides

235 Cellular and molecular profiling of early-stage mycosis fungoides in comparison to parapsoriasis and atopic dermatitis reveals disease-specific markers

235 Cellular and molecular profiling of early-stage mycosis fungoides in comparison to parapsoriasis and atopic dermatitis reveals disease-specific markers

Brentuximab vedotin treatment for mycosis fungoides with CD30+ large‐cell transformation in the early stage

In this paper, we bring hope to patients with mycosis fungoides (MF) with CD30+ large‐cell transformation (LCT), which is often a histological marker of poor prognosis and is associated with a mean 5‐year survival of &lt;20%. Although skin biopsy is a painful procedure, it is the only test for early diagnosis of LCT. Stage IIB has a significantly worse 5‐year survival rate compared with stage IB/IIA, which often plagues clinicians regarding appropriate treatment selection. In this case, the discovery of LCT by skin biopsy prompted treatment with BV. Thus, proactive rebiopsy is important so that CD30+ LCT is not overlooked in the early stage of MF.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study

Background: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. Objective: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. Methods: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. Results: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5–22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA – 4, IB – 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1–8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB – 4, III – 1). Conclusions: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

P-168 - Blood tumour burden does not correlate with skin tumour burden in early-stage mycosis fungoides (MF): PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) registry analysis

P-168 - Blood tumour burden does not correlate with skin tumour burden in early-stage mycosis fungoides (MF): PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) registry analysis

P-171 - Non-invasive digital disease severity scoring compared to CAILS in early-stage mycosis fungoides

P-171 - Non-invasive digital disease severity scoring compared to CAILS in early-stage mycosis fungoides

O-136 - The overlap of skin and blood T-cell clones in early-stage mycosis fungoides

O-136 - The overlap of skin and blood T-cell clones in early-stage mycosis fungoides

O-106 - Interstitial fluid immunophenotyping of early-stage mycosis fungoides patients after chlormethine treatment

O-106 - Interstitial fluid immunophenotyping of early-stage mycosis fungoides patients after chlormethine treatment

The overlap of skin and blood T-cell clones in early-stage mycosis fungoides

The overlap of skin and blood T-cell clones in early-stage mycosis fungoides

Socs1-knockout in skin-resident CD4+ T cells in a protracted contact-allergic reaction results in an autonomous skin inflammation with features of early-stage mycosis fungoides

Recent detailed genomic analysis of mycosis fungoides (MF) identified suppressor of cytokine signaling 1 (SOCS1), an inhibitor of JAK/STAT signaling, as one of the frequently deleted tumor suppressors in MF, and one-copy deletion of SOCS1 was confirmed in early-stage MF lesions. To better understand the functional role of SOCS1 in the genesis of MF, we used a genetically engineered mouse model emulating heterozygous SOCS1 loss in skin resident CD4+ T cells. In these mice an experimentally induced contact-allergic reaction was maintained for 20 weeks. Ten weeks after discontinuing contact-allergic challenges, only the skin with locally one-copy deletion of Socs1 in CD4+ T cells still showed high numbers of CD3+/CD4+ Socs1 k.o. cells in the dermis (p ＜ 0.0001) with prevalent Stat3 activation (p ＜0.001). And in one out of 9 mice, this had progressed to far more dramatic increases, including the thickened epidermis, and with an explosive growth of Socs1 k.o. T cells in circulation; indicative of cutaneous lymphoma. Hence, we show that Socs1 mono-allelic loss in CD4+ T cells locally in protractedly inflamed skin results in autonomous skin inflammation with features of early-stage MF.

Successful Treatment of Early-Stage Mycosis Fungoides With Topical PUVA in Adult Patient: Case Report

Mycosis fungoides is fairly common type of cutaneous T-cell lymphoma with prolonged indolent course. Early-stage MF patch/plaque stage disease (T1/T2) can be treated safely and effectively by Phototherapy. Systemic PUVA and Narrowband UVB widely used with considerable result in MF. Topical PUVA is rarely considered as a phototherapy line in MF. We represent in our patient complete clearance of MF plaque after topical PUVA phototherapy without relapse.

P54 Blood tumour burden does not correlate with skin tumour burden in early-stage mycosis fungoides: analysis of the PROspective Cutaneous Lymphoma International Prognostic Index international registry

Abstract Blood involvement B1, defined as absolute counts 250–1000 IU of an aberrant CD4+CD7– or CD4+CD26– phenotype, may be found in early-stage mycosis fungoides (MF). There is a suggestion that B1 blood involvement is a poor prognostic marker, but there is limited evidence investigating the prognostic significance of B0 or B1 blood involvement in early-stage MF. Loss of CD26 and/or CD7 expression on CD4 cells may occur in MF; however, it is unclear whether loss of either one of these immunophenotypic markers bears more significance on prognosis. For B2 blood involvement (&amp;gt; 1000 IU), the International Society for Cutaneous Lymphomas (ISCL) criteria define Sézary syndrome as CD26 loss of &amp;gt; 30% or CD7 loss of &amp;gt; 40%. Understanding the impact of B1 and comparative loss of CD26 and/or CD7 in early-stage MF may allow patients at higher risk of stage progression to be identified and selected for better therapeutic options. The aims of this study were to analyse B0 vs. B1 blood involvement at diagnosis in patients with early-stage MF (IA–IIA) and evaluate the relative CD4+CD7– and CD4+CD26– absolute cell counts. Prospective data from the PROCLIPI registry were analysed. Ninety-four patients with early-stage MF were identified from our database, 67 (71%) of whom were B0 [stage IA, n = 23 (34%); stage IB, n = 24 (36%); stage IIA, n = 20 (30%)] and 27 (29%) were B1 [stage IA, n = 12 (44%); stage IB, n = 10 (37%); stage IIA, n = 5 (18%)]. Median age at diagnosis in B0 patients was 59 years (range 20–91) vs. 61 years (range 21–81) in B1 patients. Median CD4+CD7– cell count was 16.4% (range 0–41%) in patients with B0 involvement and 28.1% (range12–45%) in B1 patients. Median CD4+CD26– cell count was 16% (range 0–39.1%) in B0 and 28% (range 0–44%) in B1 patients. The Median Modified Severity-Weighted Assessment Tool score in B1 patients was 11 (range 1–73) vs. 20 (range 0.5–100) in B0 patients. There was no significant difference in progression to the advanced stage between B0 and B1 (P = 0.112) patients or overall survival between B0 and B1 patients during median follow-ups of 49 months and 45 months, respectively. These results suggest that blood tumour burden in early-stage MF, measured by the percentage aberrancy in CD4+CD7– and CD4+CD26– cell counts, does not correlate with clinical stage, skin tumour burden or stage progression. This suggests that in B1 involvement, atypical lymphocytes may lose their skin-homing properties. Interestingly, levels of CD4+7– and CD26– are similar in B1 involvement, despite the ISCL criteria defining B2 involvement as a lower relative loss of CD26–. Identifying B1 patients is important as certain therapeutic options such as extracorporeal photopheresis and mogamulizumab may be indicated in patients with early-stage MF, refractory to skin-directed therapies.