Real-world study on the use of pegylated interferon alpha-2a for treatment of mycosis fungoides/Sézary syndrome using Time to Next Treatment as a measure of clinical benefit: An EORTC CLTG study.

INTRODUCTION: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon alpha (IFN-α, subtypes 2a and 2b) has been used for MF/SS since 1984, however its production was recently stopped and so the recombinant pegylated (PEG) form of IFN α-2a remains as single IFN alternative treatment, even though not approved for MF/SS. OBJECTIVE: To assess effectiveness and safety of PEG IFN α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in real world setting. METHODS: We conducted an international and multicenter retrospective study of patients with MF and SS at any stage, treated with PEG IFN α-2a, from July 2012 to February 2022. Patients were included across 11 centers in 10 countries. Primary endpoints were to determine TTNT of PEG IFN α-2a and the adverse events (AE) in MF/SS. RESULTS: In total 105 patients were included, mean age was 61 (22-86 years); 42 (40%) with disease stage IA-IIA, 63 (60%) with stage IIB-IVB. PEG IFN α-2a was combined with other therapies in 67 (64%) patients, usually with extracorporeal photopheresis (36%) and bexarotene (22%). Fifty-seven percent of stage I-IIA patients achieved ORR, whereas 51% of stage IIB-IVB. Combination therapy showed a TTNT of 10.4 months, while 7 months in monotherapy (p=0.0099). Overall, TTNT was 9.2 months, ORR was 53% (56/105), CR and PR were 13% and 40%, respectively.AE were described in 69% (72) of the patients. Flu-like symptoms (27%), lymphopenia (23%) and elevated liver function (10%) were the most frequently reported. Grade 3-4 adverse events were reported in 23 (21%) patients, which were mostly related to myelosuppression. LIMITATIONS: retrospective data analysis and unrestricted number of combination therapies. CONCLUSIONS: PEG IFN α-2a for MF/SS showed ORR of 53%, TTNT of 9.2 months, superiority of combination regimens in comparison to monotherapy and doses of 180 mcg/weekly related to higher ORR.

Cutaneous Reactions in Pediatric Patients Treated with MEK Inhibitors: A Retrospective Single-Center Study.

INTRODUCTION: Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency, and severity in a cohort of pediatric patients. METHODS: We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications. RESULTS: Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with a combination of trametinib and B-Raf proto-oncogene serine/threonine-protein kinase inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia, and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded. CONCLUSIONS: Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents.

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.

New Insights into Macular Type of Primary Cutaneous B-Cell Lymphoma: Extension of the Clinical and Histopathological Patterns.

BACKGROUND: Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, and nodules/tumors. Previous reports of PCBCL manifesting with macular lesions are scarce and focused on primary cutaneous follicle-center cell lymphoma (PCFCL). OBJECTIVES: The objective of this study was to report our experience with PCBCL presenting with erythematous macules. METHODS: Patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 through December 2019 at 2 tertiary cutaneous-lymphoma outpatient clinics, were included. Clinical data were retrospectively collected, and biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed. RESULTS: There were 14 patients, aged 16-67 years, 8 had PCFCL and 6 marginal zone lymphoma (PCMZL). All had 1-15 cm erythematous macules, mimicking: interstitial granuloma annulare/vascular tumors/early-stage folliculotropic mycosis fungoides, or presenting with figurate erythema or livedo reticularis-like/net-like pattern. In 3 patients, macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients, typical PCBCL lesions were observed during disease course. The macules showed in all, superficial and deep perivascular infiltrates, and in most, periadnexal infiltrates. Micronodules were observed in 11 specimens, with nodular infiltrates also observed in 4. B cells comprised the majority of the lymphocytes in only 4. Seven of 11 cases tested showed immunoglobulin heavy chain monoclonality. CONCLUSIONS: PCMZL and PCFCL may manifest with erythematous macules. Physicians should be aware of this unusual manifestation of low-grade PCBCL, which may represent a clinicopathological diagnostic pitfall.

The trichoscopic features of hair shaft anomalies induced by epidermal growth factor receptor inhibitors: A case series.

BACKGROUND: Although the clinical hair changes that occur under treatment with epidermal growth factor receptor inhibitors (EGFRIs) are documented, their trichoscopic features have not been reported. OBJECTIVE: To evaluate the trichoscopic findings in scalp and facial hair, induced by EGFRI treatment. METHODS: Patients treated with EGFRIs at a tertiary oncodermatology clinic in 2015 through 2017 were evaluated for macroscopic and trichoscopic changes. RESULTS: The cohort included 23 patients (13 women; median age, 68 years) treated with EGFRIs for an average of 13 months (range, 2-40 months). Macroscopically, 18 patients (78%) had dry, lusterless, coarse, kinky, brittle scalp hair, and 17 (74%) had trichomegaly of the eyebrows/eyelashes. Trichoscopic findings were of hair shaft anomalies including pili torti, affecting scalp hair in 20 patients (87%), eyebrows in 6 (26%), and eyelashes in 8 (50%), and asymmetric hyperpigmented fusiform widening of hair scalp in 3 (13%), eyebrows in 10 (43%), and eyelashes in 4 (25%). Dermoscopic findings of the peri- and interfollicular skin were scale, whitish erythematous structureless areas, and branching vessels. LIMITATIONS: Lack of trichoscopic-histologic correlation, lack of baseline examination. CONCLUSION: The trichoscopic correlates of the macroscopic hair changes under EFGRI treatment include pili torti, and asymmetric hyperpigmented fusiform widening, with dermoscopic cutaneous manifestations of scale, whitish erythematous structureless areas, and branching vessels.

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.

Ixekizumab Survival in Heavily Pretreated Patients with Psoriasis: A Two-year Single-centre Retrospective Study.

The long-term effect of intra-anti-interleukin-17-class switch on drug survival is unclear. The aim of this study was to evaluate the efficacy and long-term survival of ixekizumab in bio-experienced psoriatic patients with and without previous exposure to anti-interleukin-17 treatment. Retrospective search of a tertiary medical centre database for 2017 to 2019 yielded 73 patients treated with ixekizumab: 50 previously exposed to secukinumab and 23 anti-interleukin-17-naïve. Median baseline Psoriasis Area Severity Index (PASI) was 23.0. Median number of received biologics was 4. Mean drug survival was 16.4 and 16.8 months in the anti-interleukin-17-exposed and naïve groups, respectively (p = 0.878). There was no between-group difference in proportion of patients achieving ≥ 75 PASI response. At study end, 25 anti-interleukin-17-exposed patients (50.0%) and 17 anti-interleukin-17-naïve patients (73.9%) were still on ixekizumab. The use of multiple previous biologic treatments was associated with substantially reduced ixekizumab survival. In conclusion, previous anti-interleukin-17-exposure was associated with an initially favourable response and did not further reduce ixekizumab survival.

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.

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.

The Course of Mycosis Fungoides under Cytokine Pathway Blockers: A Multicentre Analysis of Real-life Clinical Data.

Literature regarding the effect of biologics on the course of mycosis fungoides (MF) is scarce. This multicentre study analysed retrospective data on 19 patients with MF, who were treated with biologics; 12 for inflammatory conditions coexisting with MF, and 7 for MF misdiagnosed as an inflammatory skin disease. Eight patients were treated with anti-tumour necrosis factor-α-monotherapy; 6 had early-stage MF, in 3 patients MF preceded and in 3 MF was diagnosed after initiation of biologics, with no stage-progression or with stable disease, respectively (median treatment time concurrent with MF 57 months). Two patients had advanced stage MF: IIB, treated for 15 months with no stage-progression, and IVA1, treated for 8 months, died of disease 10 months later. The other 11/19 patients received anti-interleukin-17A and/or anti-interleukin-12/23 or anti-interleukin-23 (with/without anti-tumour necrosis factor-α/anti-interleukin-4/13), with stage-progression in 8 patients after a median of 8 months' treatment. Although, in general, biologics should be avoided in patients with MF, these results indicate that anti-tumour necrosis factor-α-monotherapy might not aggravate the disease course in early-stage patients. Interleukin-17A, interleukin-12/23 and interleukin-23 pathway-blockers may prompt progression of MF.

IL-17A Inhibitor Switching - Efficacy of Ixekizumab Following Secukinumab Failure. A Single-center Experience.

Interleukin-17A inhibitors are a promising alternative to tumor necrosis factor-α inhibitors for the treatment of psoriasis. In-class switch has been hardly investigated for interleukin-17A inhibitors. We report the experience (2017-2018) of a tertiary medical center with interleukin-17A-inhibitor switch in patients with moderate-to-severe psoriasis. Patient-, disease- and outcome-related data were retrospectively collected from the electronic files of 25 patients switched to ixekizumab following secukinumab failure. Mean ± standard deviation patient age was 56.7 ± 12.2 years. Mean baseline Psoriasis Area and Severity Index was 25. Secukinumab was discontinued due to primary failure in 7 patients and secondary failure in 18. Ixekizumab was administered for 7.3 ± 2.8 months; 22 patients were still on ixekizumab at the end of the study. Mean ± standard deviation Psoriasis Area and Severity Index reduction from baseline at study end was 75.5±20.0%. Patients with moderate-to-severe psoriasis seem to be amenable to treatment with ixekizumab following secukinumab failure. Further large multicenter studies are needed.

The Utility of 18F-fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Cutaneous B-Cell Lymphoma.

BACKGROUND: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated. OBJECTIVES: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL. METHODS: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment. RESULTS: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4-22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001). CONCLUSIONS: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

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.

Early clinical manifestations of Sézary syndrome: A multicenter retrospective cohort study.

BACKGROUND: Classic Sézary syndrome (SS) is defined by erythroderma, generalized lymphadenopathy, and leukemic blood involvement. Clinical observations suggest that SS begins as a nonerythrodermic disease. OBJECTIVE: To describe the early clinical characteristics of patients with SS. METHODS: A retrospective, multicenter chart review was performed for 263 confirmed cases of SS diagnosed during 1976-2015. RESULTS: Erythroderma was the earliest recorded skin sign of SS in only 25.5% of cases, although most patients (86.3%) eventually developed erythroderma. In patients without erythroderma during their initial visit, the first cutaneous signs of SS were nonspecific dermatitis (49%), atopic dermatitis-like eruption (4.9%), or patches and plaques of mycosis fungoides (10.6%). The mean diagnostic delay was 4.2 years overall, 2.2 years for cases involving erythroderma at the initial presentation, and 5.0 years for cases not involving erythroderma at the initial presentation. LIMITATIONS: This study is retrospective. CONCLUSION: Erythroderma is uncommon as an initial sign of SS. Early SS should be considered in cases of nonerythrodermic dermatitis that is refractory to conventional treatments. In these cases, examination of the blood by PCR for monoclonal T-cell receptor rearrangement and by flow cytometry to identify an expanded or aberrant T-cell population should be considered.

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.

Juvenile mycosis fungoides: cutaneous T-cell lymphoma with frequent follicular involvement.

BACKGROUND: The literature on mycosis fungoides (MF) in children/adolescents is sparse. OBJECTIVE: We sought to evaluate the characteristics of juvenile MF in a large cohort. METHODS: Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively. RESULTS: There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA. LIMITATIONS: Relatively short follow-up is a limitation. CONCLUSIONS: This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear.

Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization.

OBJECTIVES: Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors approved for the treatment of chronic myeloid leukemia (CML). In clinical trials, they have both been reported to cause rash in a significant number of patients, but its incidence varies significantly and has not been characterized clinically or histologically. The aim of this study was to determine the incidence of rash with nilotinib and dasatinib, and to provide a clinical and histopathological description of the rash. METHODS: We conducted a meta-analysis of clinical trials evaluating nilotinib and dasatinib to determine and compare the incidence of rash with these medications. Additionally, we performed a retrospective chart review to analyze the clinical presentation and histology of patients presenting with rash. RESULTS: The incidence of all-grade (grade 1-4) rash with nilotinib was 34.3% (95% CI, 27.9-41.3), higher (P = 0.017) than with dasatinib (23.3%; 95% CI, 18.8-28.6). Similarly, the incidence of high-grade rash with nilotinib (2.6%; 95% CI, 2.1-3.4) was higher (P = 0.002) than with dasatinib (1.1%; 95% CI, 0.8-1.6). The clinical presentation often consisted of a pruritic, perifollicular hyperkeratotic, occasionally erythematous papular rash affecting most areas of the body, depending on the severity. CONCLUSIONS: Both nilotinib and dasatinib are associated with rash in a significant number of patients. Further studies to prevent and treat rash with nilotinib and dasatinib are required to improve patient quality of life, adherence with therapy and oncologic outcome.

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.

Hyperpigmented mycosis fungoides: an unusual variant of cutaneous T-cell lymphoma with a frequent CD8+ phenotype.

BACKGROUND: Hyperpigmented skin lesions rarely appear as a specific manifestation of mycosis fungoides (MF). OBJECTIVE: To study the clinical, histopathological, and immunohistochemical features of hyperpigmented MF. METHODS: Patients with hyperpigmented MF were identified by a file search of all patients with MF who had attended a cutaneous lymphoma outpatient clinic in the last 15 years, and the relevant data were collected. RESULTS: Eight patients had early-stage MF manifested by hyperpigmented patches and/or flat plaques. All but one had a dark complexion. Mean age at diagnosis was 43 years (range, 19-69), and mean interval from disease onset to diagnosis was 6.25 years (range, 1-14). In 5 patients, the hyperpigmented lesions were the sole manifestation of the disease; in the remainder, they appeared in conjunction with other unusual lesions of MF. Histologically, all our patients had interface changes with melanophages in addition to the classical findings of early MF. Only one patient had a CD4(+) epidermotropic T-cell phenotype; 5 patients had a CD8(+) phenotype, and 2 had a CD4(-)CD8(-) phenotype. Patients received skin-targeted therapies, and all had indolent course without evidence of disease progression after a mean follow-up of 3.8 years. LIMITATIONS: This was a case series descriptive study. CONCLUSION: Hyperpigmented MF is an atypical clinical variant of cutaneous T-cell lymphoma, with a predilection for patients with a dark complexion. It is characterized by a predominantly CD8(+) phenotype. Hyperpigmented lesions may be the sole manifestation or it may coexist with other unusual MF variants typified mostly by pigmentary changes.