mAb14, a Monoclonal Antibody against Cell Surface PCNA: A Potential Tool for Sezary Syndrome Diagnosis and Targeted Immunotherapy.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants.

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.

Real-life experience with chlormethine gel for early-stage mycosis fungoides with emphasis on types and management of cutaneous side-effects.

BACKGROUND: Real-life efficacy data on the recently approved once daily application of chlormethine gel (CG) for mycosis fungoides (MF) is limited, and detailed characterization of the side effects and their management are strikingly sparse. OBJECTIVE: To evaluate the efficacy and particularly the side effect profile of CG in early-stage MF patients in a real-life setting. METHODS: We performed a single-center retrospective analysis of 66 early-stage MF adult patients treated with CG in 2016-2019. RESULTS: Treatment with a once-daily application (52%), or at lower frequencies (48%), in some with topical corticosteroids (TCS) (40%), resulted in an overall response rate of 50%, with no significant difference between stage IA and IB. Cutaneous side effects (56%) included irritant or allergic contact dermatitis (36%, mostly mild/moderate and manageable by reducing application frequency and/or adding TCS or interrupting treatment), unmasking effect (9%), hyperpigmentation (14%), and pruritus (9%). Withdrawal due to side effects occurred in 19.6% of patients (15% for contact dermatitis). CONCLUSION: In real-life management, flexible regimens of CG sometimes with TCS, show efficacy in early-stage MF and may reduce the rate of contact dermatitis, the main treatment-limiting side effect. Practical recommendations with emphasis of the types, time of appearance, and management of side effects are provided.

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Melanoma Risk is Increased in Patients with Mycosis Fungoides Compared with Patients with Psoriasis and the General Population.

Patients with mycosis fungoides (MF) are thought to be at increased risk of melanoma. However, studies addressing surveillance-bias and treatments as a possible confounder are lacking. This retrospective study compared the prevalence and risk of melanoma between 982 patients with MF, and 3,165 patients with psoriasis attending tertiary cutaneous-lymphoma/psoriasis clinics during 2009 to 2018. Melanoma was diagnosed in 47 patients with MF (4.8%; 43 early-stage) and in 23 patients with psoriasis (0.7%) (odds ratio 6.6, p < 0.0001). In 60% of patients, MF/psoriasis preceded melanoma diagnosis. Hazard ratio (HR) for a subsequent melanoma in MF vs psoriasis was 6.3 (95% confidence interval (95% CI) 3.4-11.7, p < 0.0001). Compared with the general population, melanoma standardized incidence ratios were 17.5 in patients with MF (95% CI 11.0-23.9, p < 0.0001), and 2.2 (95% CI 0.6-3.8, p = 0.148) in patients with psoriasis. Narrow-band ultraviolet B was not a contributory factor (HR 1.15, 95% CI 0.62-2.14, p = 0.66). These findings add evidence that patients with MF have a significantly higher risk of melanoma, not only compared with the general population, but also compared with patients with psoriasis. This comorbidity may be inherent to MF.

Stage-dependent Increase in Expression of miR-155 and Ki-67 and Number of Tumour-associated Inflammatory Cells in Folliculotropic Mycosis Fungoides.

Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF. Immunohistochemical analysis revealed a significantly increased number of dermal Ki-67+ proliferating lymphocytes in tumour-stage FMF, together with an increased number of CD20+ B cells and CD68+ macrophages compared with early-stage FMF. Thus, similar to classic MF, miR-155, Ki-67 tumour cell immunoreactivity, and certain tumour-infiltrating inflammatory cells are differentially expressed in early- vs tumour-stage FMF. The results of this study corroborate the notion that FMF presents with 2 distinct stages.

Treatment of injection-induced ecchymoses with light/laser-assisted technology.

An increasing number of minimally invasive cosmetic procedures, such as filler or botulinum toxin injections, are performed annually. These procedures are associated with a high risk of post-procedure bruising or ecchymosis. Ecchymoses arise following hemorrhage and extravasation of red blood cells into the subcutaneous tissue, leading to local skin discoloration. Although ecchymoses generally resolve within 14 days, their appearance is cosmetically bothersome, and they may be painful and cause major distress to patients. Recent clinical evidence suggests that light/laser technology with pulsed dye laser (PDL) or intense pulsed light (IPL) can dramatically alleviate and minimize bruising when delivered within 24-72 hr of the injection. This article, will review reports of treatment of ecchymosis by lasers and IPL.

Retinoic acid receptor agonist as monotherapy for early-stage mycosis fungoides: does it work?

BACKGROUND: Retinoids exert their biologic effects by binding to intracellular retinoic-acid receptors (RARs) and/or retinoid X receptors (RXRs). Early-stage mycosis fungoides (MF) has been effectively treated with bexarotene, an RXR-agonist, with overall response (OR) rates 54-67% and complete response (CR) rates 7-27%. Data on RAR-agonist monotherapy are limited. OBJECTIVE: To analyze the effectiveness of RAR-agonist monotherapy for early-stage MF. METHODS: Data on patients with early-stage MF treated with acitretin/isotretinoin monotherapy at a tertiary cutaneous lymphoma clinic in 2010-2017 were collected retrospectively from the medical files. RESULTS: Thirty-five patients (26 males) of median age 50 years (range 8-83) with early-stage MF (IA 9, IB 26) underwent 37 treatment events: 25 acitretin and 12 isotretinoin at a median dosages of 0.3 mg/kg (range 0.2-0.9) and 0.2 mg/kg (range 0.1-0.7), respectively. Median time to maximal response was 6 months for both (range 1-10 for acitretin, 3-16 for isotretinoin); median treatment duration was 10 months (range 3-46) for acitretin, and 9 months (range 3-55) for isotretinoin. OR was 64% for acitretin and 80% for isotretinoin, and CR, 4% and 8%, respectively. Side-effect profiles were as previously reported for retinoids. CONCLUSIONS: Early-stage MF patients may benefit from low dose RAR-agonist monotherapy, although the CR rate is low.

Treatment of Early Folliculotropic Mycosis Fungoides with Special Focus on Psoralen plus Ultraviolet A.

Data on the treatment of early folliculotropic mycosis fungoides, a recently defined clinicopathological subgroup of folliculotropic mycosis fungoides with an indolent course, is limited. Treatment outcomes were studied in a retrospective cohort of 47 adults with early folliculotropic mycosis fungoides, with a focus on psoralen plus ultraviolet A (PUVA) monotherapy, including dosimetric data, and the findings were compared with data for PUVA in 18 adults with early-classic mycosis fungoides. PUVA was given to 27 patients with early folliculotropic mycosis fungoides: 70% achieved complete response and 26% partial response. Significantly more treatments were needed to achieve complete response in stage IB compared with stage IA. There was no significant difference in the complete response rate from classic plaque-stage disease, although the early folliculotropic mycosis fungoides group required more treatments to achieve complete response, and a higher cumulative dose of UVA. Thus, PUVA is an effective treatment for early folliculotropic mycosis fungoides. Its complete response rate might be equal to early-classic mycosis fungoides; however, a longer induction phase is needed to achieve complete response.

New insights into folliculotropic mycosis fungoides (FMF): A single-center experience.

BACKGROUND: It is generally accepted that folliculotropic mycosis fungoides (FMF) is usually typified by indurated plaques and tumors mainly on the head/neck and an aggressive course. However, its clinical manifestations have long been recognized to be quite variable, and some studies indicate a better prognosis for certain presentations. OBJECTIVE: We sought to summarize our experience with the clinicopathological presentations of FMF and impact on prognosis. METHODS: Data were collected retrospectively for adults with FMF followed up prospectively at a tertiary medical center in 1995 through 2014. RESULTS: In all, 34 patients presented with follicle-based patch/flat plaques, keratosis pilaris-like lesions, and/or acneiform lesions, defined clinically as early stage (IA, IB), and 15 presented with follicle-based infiltrated plaques and/or tumors, defined as advanced stage (IIB). The head/neck was involved in all tumor-stage cases, whereas early-stage lesions involved mainly the trunk/limbs. The tumor stage was characterized by more pruritus, heavier perifollicular infiltrates, greater vertical depth, and more frequent presence of eosinophils. On multivariate analysis, infiltrate density was the only significant histopathological discriminator between the stages. Estimated 5-year survival was 0.94 in the early-stage group and 0.69 in the tumor-stage group. LIMITATIONS: Lack of long-term follow-up and relatively small sample are limitations. CONCLUSION: FMF presents with 2 distinct patterns of clinicopathologic features, early stage and advanced stage, each with different prognostic implications.