There are no established maintenance protocols for cutaneous lymphomas. We aim to determine patient treatments and outcomes during the COVID-19 pandemic in order to uncover the most effective maintenance protocols for cutaneous lymphomas and impact of treatment interruption. Data was collected retrospectively from nine international institutions, including 149 patients. Younger patients had earlier stages of disease and were most frequently treated with skin-directed therapies including topical steroids, mechlorethamine gel, and phototherapy. Treatment interruption varied by treatment type and stage, with patients on topical therapies and earlier stages of disease being least likely to experience interruption. Treatment interruption was significantly associated with progression of disease and worse outcomes, with twice as many patients progressing who had interruption compared to those without interruption. This study may demonstrate the significance of continuous maintenance therapies, even in younger patients with early stages of disease.

To the Editor: During the COVID-19 pandemic, health care facilities reduced or suspended their clinical services in an attempt to safeguard patients and providers from infection. These closures and scaled-back clinical hours resulted in considerable diagnostic delays for many malignancies typically detected by routine screening. Recent retrospective studies have demonstrated that COVID-19 had significant impacts on the absolute detection of melanomas at major referral centers.1-3 While absolute decreases were observed in these studies, it is unknown if the melanomas detected during COVID-19 represented proportionally more or less than would be expected when corrected for a decrease in total collections.

Supplementary Data from Single-Cell RNA Sequencing Unveils the Clonal and Transcriptional Landscape of Cutaneous T-Cell Lymphomas

Malignant T lymphocyte proliferation in mycosis fungoides (MF) is largely restricted to the skin, implying that malignant cells are dependent on their specific cutaneous tumor microenvironment (TME), including interactions with non-malignant immune and stromal cells, cytokines, and other immunomodulatory factors. To explore these interactions, we performed a comprehensive transcriptome analysis of the TME in advanced-stage MF skin tumors by single-cell RNA sequencing. Our analysis identified cell-type compositions, cellular functions, and cell-to-cell interactions in the MF TME that were distinct from those from healthy skin and benign dermatoses. While patterns of gene expression were common among patient samples, high transcriptional diversity was also observed in immune and stromal cells, with dynamic interactions and crosstalk between these cells and malignant T lymphocytes. This heterogeneity mapped to processes such as cell trafficking, matrix interactions, angiogenesis, immune functions, and metabolism that affect cancer cell growth, migration, and invasion, as well as antitumor immunity. By comprehensively characterizing the transcriptomes of immune and stromal cells within the cutaneous microenvironment of individual MF tumors, we have identified patterns of dysfunction common to all tumors that represent a resource for identifying candidates with therapeutic potential as well as patient-specific heterogeneity that has important implications for personalized disease management.

Introduction: Cutaneous T-cell lymphomas (CTCL) are heterogeneous lymphoproliferative disorders on a spectrum of disease presentation and severity. Around two-thirds of cutaneous T-cell lymphomas can be classified as mycosis fungoides (MF) or Sézary syndrome (SS). While advanced stages of MF and SS are associated with decreased survival and worse outcomes, even early-stage patients can possess a variable course. Numerous deep sequencing studies have fallen short in identifying genetic abnormalities that drive disease pathogenesis and predict prognosis. Large-cell transformation and elevated lactate dehydrogenase levels are associated with worse prognosis in SS; however, such features cannot accurately prognosticate patient survival. There is a need for investigation that may assist in the prognostication of survival in patients with CTCL. Machine learning methods may help to elucidate correlations between clinical and genetic factors to predict disease progression and outcomes. Objective: Using integrated clinical and genomic data from six international sequencing studies, this investigation aimed to perform survival analysis to identify both clinical and genetic features of survival outcomes using artificial intelligence/machine learning methods. Methods: A total of 126 eligible patients were identified, of which 99 had sufficient clinical data and 88 had sufficient clinical and genetic data. Poisson distribution was used to assess genomic data and significant genetic abnormalities for each individual patient were linked with their corresponding clinical outcomes. Genetic inputs included mutational data at a frequency of greater than or equal to four dataset occurrences. Multiple imputation using a random forest model was applied to all included variables (rate of missingness <10%). Overall survival was assessed using three separate cox models fit with patient clinical, laboratory, or treatment covariates. Ten-fold cross validated Least Absolute Shrinkage and Selection Operator (LASSO) was applied using adaptive regularization, and an iterated approach using 100 ten-fold cross validation repeats (resampling validation) to select the lambda value with the highest average C-index. The one-standard-error rule was used for the adaptive LASSO, while the iterated LASSO penalty was relaxed by 0.1. Prior to adjusting the lambdas, the best performing C-index was 0.73 and 0.64 for the adaptive LASSO and iterated LASSO, respectively. Following adjustment, the C-indexes were 0.71 and 0.60. To elucidate genetic candidates, we performed genome-wide association studies (GWAS) which used the false discovery rate (FDR) multiple comparisons correction and adjusted for the first three principal components in a principal component analysis (PCA) that included the imputed non-mutational covariates. Results: We have used standard statistical and machine learning methodologies to elucidate prognostic factors in MF and SS. Using standard cox regression analysis and in agreement with prior investigations, our investigation showed significant associations for age at diagnosis (hazard ratio = 1.06, P<0.001), stage at sampling (hazard ratio =1.99, P=0.007), and lymph node involvement at diagnosis (hazard ratio = 4.59, P<0.001). For the first time, using PCA-adjusted GWAS and iterated and adaptive LASSO, we demonstrate the association of mutated genes with survival in patients with MF and SS (e.g. most significant GWAS hazard ratio of 0.17, P=0.007, FDR=0.35). Moreover, several mutated genes were associated with particularly poor outcomes and high mortality (e.g. most significant GWAS hazard ratio of 5.26, P=0.003, FDR=0.63). Mutated genes with the highest or lowest magnitude using LASSO effect estimates in GWAS (lowest P values) were highly associated with survival outcomes. When present, the mutated genes carried significant prognostic implications for these patients. Conclusions: Taken together, we demonstrate the potential of machine learning and artificial intelligence methodologies for investigation of novel genetic associations with survival prognostication. Future investigations are needed to validate our findings in prospective studies.

Pseudallescheria boydii is increasingly recognized as a source of infection in the immunocompromised. It has rarely been reported as a pathogen in immunocompetent patients, especially as a single cutaneous abscess. We present the case of a solitary P boydii abscess presenting in an immunocompetent man.

Combined BET inhibitor/histone deacetylase inhibitor treatment induces marked apoptosis of cutaneous T-cell lymphoma (CTCL) with minimal normal T-cell toxicity. At 96 hours when apoptosis was extensive, a majority of CTCL lines showed ≥2-fold suppression of T-cell survival factors (e.g., AKT1, BCL2 antiapoptotic factors, BIRC5, CD40, CD70, GADD45A, PRKCA, TNFRSF1B, ΔNp73) and ≥2-fold upregulation of proapoptotic factors and tumor suppressors (e.g., ATM, BAK, BIM, multiple caspases, FHIT, HIC1, MGMT, NOD1) (P < 0.05). The largest alterations were in TP73 isoform expression, resulting in increased TAp73/ΔNp73 ratios in CTCL lines and leukemic Sézary cells. Targeted ΔNp73 inhibition by small interfering RNA knockdown resulted in robust CTCL apoptosis comparable with that induced by BET inhibitor/histone deacetylase inhibitor with minimal normal T-cell toxicity. Chromatin immunoprecipitation analysis showed that BET inhibitor/histone deacetylase inhibitor treatment reduced RNA polymerase II binding to ΔNp73, MYC, and AKT1 while increasing its binding to TAp73. CTCL skin lesions expressed both TAp73 and ΔNp73 isoforms in situ. In aggregate, these findings implicate TAp73/ΔNp73 balance as a major factor governing CTCL survival, show that the expression of p73 isoforms can be altered by molecular biological and pharmaceutical means, show that p73 isoforms are expressed across the entire CTCL clinical spectrum, and identify the p73 pathway as a potential target for therapeutics.

Previously, we showed that deficiencies in apoptotic factors occur in cutaneous T-cell lymphoma (CTCL) and can be enhanced through epigenetic mechanisms (Stutz et al., 2012; Wu and Wood, 2011; Wu et al., 2009). Now, we have further explored the epigenetic regulation of apoptosis in CTCL with special attention to the DNA methyltransferase (DNMT)/signal transducer and activator of transcription (STAT) 3 promoter methylation complex responsible for silencing several tumor suppressor genes, including those involved in apoptosis.

Abstract Purpose: Clonal malignant T lymphocytes constitute only a fraction of T cells in mycosis fungoides skin tumors and in the leukemic blood of Sézary syndrome, the classic types of cutaneous T-cell lymphomas. However, lack of markers specific for malignant lymphocytes prevents distinguishing them from benign T cells, thus delaying diagnosis and the development of targeted treatments. Here we applied single-cell methods to assess the transcriptional profiles of both malignant T-cell clones and reactive T lymphocytes directly in mycosis fungoides/Sézary syndrome patient samples. Experimental Design: Single-cell RNA sequencing was used to profile the T-cell immune repertoire simultaneously with gene expression in CD3+ lymphocytes from mycosis fungoides and healthy skin biopsies as well as from Sézary syndrome and control blood samples. Transcriptional data were validated in additional advanced-stage mycosis fungoides/Sézary syndrome skin and blood samples by immunofluorescence microscopy. Results: Several nonoverlapping clonotypes are expanded in the skin and blood of individual advanced-stage mycosis fungoides/Sézary syndrome patient samples, including a dominant malignant clone as well as additional minor malignant and reactive clones. While we detected upregulation of patient-specific as well as mycosis fungoides– and Sézary syndrome–specific oncogenic pathways within individual malignant clones, we also detected upregulation of several common pathways that included genes associated with cancer cell metabolism, cell-cycle regulation, de novo nucleotide biosynthesis, and invasion. Conclusions: Our analysis unveils new insights into mycosis fungoides/Sézary syndrome pathogenesis by providing an unprecedented report of the transcriptional profile of malignant T-cell clones in the skin and blood of individual patients and offers novel prospective targets for personalized therapy.

Mycosis fungoides (MF), the most common form of cutaneous T cell lymphoma (CTCL), is primarily an indolent disease [1,2]. However, advanced stages of MF and Sezary syndrome (SS) may involve the blood or visceral organs, carrying a poor prognosis [1,2]. Peripheral T-cell lymphoma (PTCL) is a form of non-Hodgkin’s lymphoma distinct from CTCL that is also known for its aggressive clinical course [3,4]. Accordingly, PTCL and advanced stage CTCL are malignancies requiring intensive treatment with systemic therapies to induce and maintain remissions [5]. Histone deacetylase inhibitors (HDACis) are a novel class of drugs first approved for the treatment of CTCL in 2006 [6,7]. Romidepsin was first approved by the U.S. Food and Drug Administration (USFDA) in 2009 for use in patients with CTCL or PTCL who have received at least one prior systemic therapy [7]. At the time of its approval, the USFDA issued a warning cautioning against the usage of romidepsin in patients with a history of significant cardiovascular disease, congenital long QT syndrome, or those receiving QTc-prolonging medications [8]. Preclinical studies of romidepsin reported increases in heart rate following infusions, suggesting potential cardiac toxicity and prompting the inclusion of extensive cardiac monitoring in Phase 1 studies, including serial echocardiograms, electrocardiograms (ECGs), and cardiac troponins [7,9–11]. Adverse ECG changes were reported in multiple Phase 1 studies, including ST/T wave flattening, ST depression, ST inversions, and QTc prolongation, as well as Grade 4 atrial fibrillation, transient left bundle branch block, and a clinically silent wall motion abnormality [7,9–11]. These data led to strict exclusion criteria for patients with preexisting cardiovascular disease in the pivotal trials that preceded FDA approval (See Table 1). However, phase 1 trials did not include stringent monitoring of blood magnesium and potassium levels, a critical safeguard instituted during phase 2 trials due to persistent drugrelated nausea and vomiting observed in the majority of patients [9]. In addition, two Phase 1 studies included dose-finding arms, which led to patients being exposed to treatment doses far higher than current prescribing recommendations, including maximum dosages of 24.9mg/m and 17.7mg/m, respectively [9,10]. Follow-up studies have demonstrated no clear association between romidepsin and cardiotoxicity. Analysis of routine cardiac evaluation in phase II studies, where potassium and magnesium were strictly monitored and repleted, found no evidence of romidepsin-associated structural heart damage [12,13]. Though ECG changes were observed, there was no clinically meaningful heart rate-corrected QT interval changes (QTc > 500ms) amongst study participants [13]. In the National Cancer Institute (NCI) 1312 phase II study of romidepsin in CTCL or PTCL, both Grade 1 T-wave flattening and Grade 2 STsegment depression were noted, but these were not associated with troponin elevations, structural changes, or arrhythmias [14]. Furthermore, a review of 110 patients across 3 clinical studies found no clinically meaningful ECG changes or functional abnormalities following romidepsin treatment [15]. Strikingly, this study noted that asymptomatic changes in ECG readings following romidepsin infusion, including ST depression and T wave flattening, occurred with the same frequency in patients prior to infusion, suggesting the ECG changes observed may simply represent baseline noise in the ECG data [15]. QTc changes observed following romidepsin infusion have also been attributed in multiple studies to the use of anti-emetics for the pretreatment of drug-related nausea [13,15]. The strict cardiac exclusion criteria instituted in Phase II trials and the USFDA’s label warning regarding a need for cardiovascular monitoring precautions in patients with significant cardiovascular disease have led to the exclusion of patients with advanced stage CTCL/PTCL

To the Editor: Outcomes of patients with cutaneous T-cell lymphoma (CTCL), a diverse group of non-Hodgkin lymphomas, during the COVID-19 pandemic are unknown. Patients with CTCL require active management and rely on various local and systemic therapies administered in-hospital or in-office, representing an increased risk for contracting COVID-19. There are no established maintenance protocols for cutaneous lymphomas. The COVID-19 pandemic served as an "experiment of nature" to understand the effects of reduced regimens and maintenance therapy. The professional societies developed emergency guidelines for the management of patients with cutaneous lymphomas during the pandemic to ensure patient safety.1Zic J.A. Ai W. Akilov O.E. et al.United States Cutaneous Lymphoma Consortium recommendations for treatment of cutaneous lymphomas during the COVID-19 pandemic.J Am Acad Dermatol. 2020; 83: 703-704Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar,2Papadavid E. Scarisbrick J. Ortiz Romero P. et al.Management of primary cutaneous lymphoma patients during COVID-19 pandemic: EORTC CLTF guidelines.J Eur Acad Dermatol Venereol. 2020; 34: 1633-1636Crossref PubMed Scopus (13) Google Scholar The International Society for Cutaneous Lymphomas created an International Cutaneous Lymphomas Pandemic Section to collect data to assess the impact of these guidelines. Using these data, we can determine if these measures were effective in preventing COVID-19 infection, what the impact was of maintenance therapy, and how delays in treatment affected disease outcomes in CTCL patients. We performed a retrospective analysis of data from the electronic medical records at 9 international academic medical centers in 7 countries from March to October 2020, including 149 patients, actively managed with an established diagnosis of cutaneous lymphoma. Patient demographics, date of diagnosis, staging details, treatment details, delays or changes to treatment regimens, disease outcomes, and COVID-19 disease history including the source of transmission were recorded (Fig 1). Treatment was delayed for 53.0% of patients for a mean of 3.2 months (range: 10 days-10 months). Adjusting for age, race, biological sex, COVID-19 status, and disease stage, treatment delay was associated with a significant risk of disease relapse or progression across all stages (odds ratio 5.00; 95% confidence interval [2.38, 11.0], P value < .001) and, for each additional month that a patient experienced treatment delay, the odds of disease progression increased by 37.0% (odds ratio 1.37; 95% confidence interval [1.14, 1.70], P value < .001) (Table I). A total of 28 (18.8%) patients with CTCL were diagnosed with COVID-19, none acquired from outpatient office visits. Patients who contracted COVID-19 did not have a statistically significant increase in odds of disease progression compared to COVID-19–negative patients (odds ratio 0.41; 95% confidence interval [0.15, 1.08], P value = .07).Table IDemographic and outcomes by treatment delay statusTreatment delay (n = 79) N (%)No treatment delay (n = 70) N (%)Total (N = 149) N (%)Age Mean6459 Median (IQR)65 (53, 78)62 (48, 72) Range28, 9522, 88Biological sex Male43 (54.4)40 (57.1)83 (55.7) Female36 (45.6)30 (42.9)66 (44.3)Race White60 (75.9)44 (62.9)104 (69.8) Black/African American8 (10.1)19 (27.1)27 (18.1) Other/unknown/declined11 (13.9)7 (10.0)18 (12.1)Stage IA-IIA40 (50.6)37 (52.9)77 (51.6) IIB11 (13.9)12 (17.1)23 (15.4) IIIA-IIIB4 (5.1)2 (2.8)6 (4.0) IVA1 (SS)19 (24.1)16 (22.9)35 (23.5) IVA2-IVB3 (3.8)3 (4.3)6 (4.0) PC CD30+ LPD2 (2.5)0 (0.0)2 (1.3)COVID-19 status Positive18 (22.8)10 (14.3)28 (18.8) Negative61 (77.2)60 (85.7)121 (81.2)Length of treatment delay (mo) Mean3.200.00 Median (IQR)3.00 [1.05, 4.00]0.00 [0.00, 0.00] Range0.30, 10.000.00, 0.00 Unknown20Outcomes Improvement of disease5 (6.3)10 (14.3)15 (10.1) Stable disease15 (19.0)36 (51.4)51 (34.2) Disease progression/relapse52 (65.8)22 (31.4)74 (49.7) Deceased7 (8.9)2 (2.9)9 (6.0) Open table in a new tab Based on the results of this study, we conclude the following:1.Adequate safety measures and protocols can prevent transmission of COVID-19 at physicians' offices as no outpatient office-acquired infections were reported.2.Patients with cutaneous lymphomas who develop COVID-19 do not have worse outcomes than expected according to their risk factors.3.As the pandemic continues, our data reveals the need to re-evaluate the initial recommendations made by the USCLC and EORTC-CLTG, and it provides reassurance that our current COVID-19–conscious management practices are safe and effective.4.Delays in therapy lead to adverse clinical outcomes and should be avoided, as the risk of contracting COVID-19 in the outpatient setting did not outweigh the risk of morbidity and mortality due to disease progression.5.Ensuring continuity of treatment and maintenance therapy appears critical to avoiding disease progression, underscoring the importance of maintenance therapy for CTCL. None disclosed.

A 52-year-old man with a history of renal transplantation 2 years prior presented with a 4-month history of brown-to-pink papules on the forehead, nose, and ears as well as follicular hyperkeratotic papules on the arms, legs, and trunk (Fig 1, A to C). He reported that his eyebrows and eyelashes began to thin when the papules first appeared. Dermatoscopy revealed perifollicular hyperpigmentation with central white circles and bright white spicules (Fig 2, A and B). Histopathologic examination demonstrated a dilated hair follicle with keratin plugging and a marked increase in trichohyalin granules. There was a sparse superficial perivascular mononuclear cell infiltrate. A diagnosis of trichodysplasia spinulosa was made (Fig 3, A and B).Key messageTrichodysplasia spinulosa (TS) is a rare cutaneous eruption in immunosuppressed patients caused by TS-associated polyomavirus, which presents as folliculocentric papules with protruding keratin spicules, most frequently on the face and ears. Associated alopecia affecting the eyebrows is common.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,2Narayanan D. Rady P.L. Tyring S.K. Recent developments in trichodysplasia spinulosa disease.Transpl Infect Dis. 2020; 22: e13434Crossref PubMed Scopus (3) Google Scholar Histologically, TS is characterized by dilated hair follicles with enlarged, eosinophilic trichohyalin granules and dystrophy of the inner root sheath epithelium with apoptotic follicular keratinocytes.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,2Narayanan D. Rady P.L. Tyring S.K. Recent developments in trichodysplasia spinulosa disease.Transpl Infect Dis. 2020; 22: e13434Crossref PubMed Scopus (3) Google ScholarTimely diagnosis of TS is crucial as it may progress to leonine facies if left untreated.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,2Narayanan D. Rady P.L. Tyring S.K. Recent developments in trichodysplasia spinulosa disease.Transpl Infect Dis. 2020; 22: e13434Crossref PubMed Scopus (3) Google Scholar Dermatoscopic evaluation can aid in rendering a timely diagnosis. The most specific dermatoscopic clue for distinguishing TS from other hyperkeratotic follicular disorders is the presence of bright white spicules that protrude peripherally from follicular openings.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,3Liew Y.C.C. Kee T.Y.S. Kwek J.L. Tang P.Y. Oh C.C. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: A case report and review of literature.JAAD Case Rep. 2021; 7: 74-83Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In contrast to the dark, confined keratin plugging seen in other hyperkeratotic disorders, it is both the stark whiteness of the spicules and their considerable length that are characteristic of TS.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,3Liew Y.C.C. Kee T.Y.S. Kwek J.L. Tang P.Y. Oh C.C. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: A case report and review of literature.JAAD Case Rep. 2021; 7: 74-83Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar TS in patients with skin of color may also present with perifollicular hyperpigmentation with a central white or pink circle. Treatment options include reduction of immunosuppression, topical cidofovir, or systemic valganciclovir, among other regimens. Trichodysplasia spinulosa (TS) is a rare cutaneous eruption in immunosuppressed patients caused by TS-associated polyomavirus, which presents as folliculocentric papules with protruding keratin spicules, most frequently on the face and ears. Associated alopecia affecting the eyebrows is common.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,2Narayanan D. Rady P.L. Tyring S.K. Recent developments in trichodysplasia spinulosa disease.Transpl Infect Dis. 2020; 22: e13434Crossref PubMed Scopus (3) Google Scholar Histologically, TS is characterized by dilated hair follicles with enlarged, eosinophilic trichohyalin granules and dystrophy of the inner root sheath epithelium with apoptotic follicular keratinocytes.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,2Narayanan D. Rady P.L. Tyring S.K. Recent developments in trichodysplasia spinulosa disease.Transpl Infect Dis. 2020; 22: e13434Crossref PubMed Scopus (3) Google Scholar Timely diagnosis of TS is crucial as it may progress to leonine facies if left untreated.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,2Narayanan D. Rady P.L. Tyring S.K. Recent developments in trichodysplasia spinulosa disease.Transpl Infect Dis. 2020; 22: e13434Crossref PubMed Scopus (3) Google Scholar Dermatoscopic evaluation can aid in rendering a timely diagnosis. The most specific dermatoscopic clue for distinguishing TS from other hyperkeratotic follicular disorders is the presence of bright white spicules that protrude peripherally from follicular openings.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,3Liew Y.C.C. Kee T.Y.S. Kwek J.L. Tang P.Y. Oh C.C. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: A case report and review of literature.JAAD Case Rep. 2021; 7: 74-83Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In contrast to the dark, confined keratin plugging seen in other hyperkeratotic disorders, it is both the stark whiteness of the spicules and their considerable length that are characteristic of TS.1Curman P. Näsman A. Brauner H. Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.J Eur Acad Dermatol Venereol. 2021; 35: 1067-1076Crossref PubMed Scopus (1) Google Scholar,3Liew Y.C.C. Kee T.Y.S. Kwek J.L. Tang P.Y. Oh C.C. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: A case report and review of literature.JAAD Case Rep. 2021; 7: 74-83Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar TS in patients with skin of color may also present with perifollicular hyperpigmentation with a central white or pink circle. Treatment options include reduction of immunosuppression, topical cidofovir, or systemic valganciclovir, among other regimens. None disclosed.

Bacteria have long been considered drivers in the development of cutaneous lymphoma, as bacterial antigens may encourage reactive, dysregulated lymphocytic proliferation.1,2 For example, Staphylococcus aureus infection has been implicated in the pathogenesis of mycosis fungoides and Sézary syndrome, whereas Borrelia burgdorferi is clinically associated with primary cutaneous B-cell lymphoma.3-7 Stenotrophomonas maltophilia is an opportunist gram-negative bacterium, primarily recognized as a cause of nosocomial infection among immunocompromised individuals.

Mycosis fungoides is a type of cutaneous T-cell lymphoma, which accounts for the majority of cases of cutaneous T-cell lymphoma. Mycosis fungoides can be classified as early-stage (IA-IIA) or late-stage (IIB or greater) disease. In early-stage mycosis fungoides, skin-directed therapies are commonly used to manage the disease. Chlormethine, or mechlorethamine, is a topical chemotherapeutic, which has been in use for over 60 years. In 2013, the US Food and Drug Administration approved chlormethine/mechlorethamine gel (Valchlor®) for treatment of stage IA and IB mycosis fungoides. Chlormethine/mechlorethamine gel is an effective therapy; however, its use may be limited by the development of adverse cutaneous reactions. Off-label dosing modifications, as well as co-administration of topical steroids and an aggressive moisturization regimen, can be used to reduce these side-effects. We report here 4 cases of mycosis fungoides treated with chlormethine/mechlorethamine gel at the Comprehensive Skin Cancer Center at Columbia University Irving Medical Center, which provide insights into the use of this therapy in clinical practice.

INTRODUCTION Preoperative visits are an exceptional opportunity to encourage smoking cessation, as studies demonstrate the experience of scheduling elective surgery produces an actionable incentive to quit. However, studies suggest surgeons do not regularly assess smoking behavior or offer cessation therapies. Clinical decision support (CDS) is a system in which providers are presented with clinically integrated tools to enhance decision-making. METHODS A CDS tool was designed to facilitate treatment referrals for smoking cessation services among patients seeking elective surgery. Two clinics were selected: the plastic and vascular surgeries. The study objectives were to assess the utilization rate and effectiveness of this system. RESULTS No smoking cessation referrals had been submitted by the plastic surgery or vascular surgery clinics in the year before CDS tool implementation. Providers at the plastic surgery clinic utilized the CDS tool in 95.0% (191 of 201) eligible patient encounters. Of these patients, 16.3% were identified as active smokers, and 16.1% of these smokers accepted treatment referrals. Providers at the vascular surgery clinic utilized the CDS tool in 50.3% (98 of 195) eligible patient encounters. Of these patients, 10.2% were identified as active smokers, and 30.0% of these smokers accepted treatment referrals. CONCLUSIONS The CDS tool improved the incidence of smoking cessation referrals in two surgical clinics from pretest baselines and achieved satisfactory utilization rates. This report demonstrates the feasibility of CDS tools to actualize the preoperative visit as an opportunity to promote smoking cessation.

New York-Presbyterian Hospital and Columbia University Irving Medical Center were heavily impacted by the COVID-19 pandemic. Various measures were taken in an effort to ensure patient and staff safety. The management of patients with complex dermatological oncologic conditions, such as cutaneous T-cell lymphoma (CTCL) was especially challenging. We present a case review of patients diagnosed with CTCL who also had confirmed or suspected COVID-19 infection (n = 6). Diagnoses included were mycosis fungoides (n = 2), Sézary syndrome (n = 2), and primary cutaneous CD30+ lymphoproliferative disorder (n = 2). Treatment regimens included oral medications (methotrexate), infusions (eg, brentuximab vedotin, romidepsin), extracorporeal photopheresis or phototherapy. Due to safety reasons, patients who contracted COVID-19 and had stable CTCL, (3/6 or 50%) experienced an interruption in treatment. Three patients had no interruption in treatment because the timing of their COVID-related illness and scheduled treatments did not overlap. Treatments were delayed for approximately 2 weeks to 4 months. Of those patients with treatment interruptions (n = 3), two out of three experienced disease relapse. We also provide a review of outcomes and changes in management during the height of the pandemic and discuss how it affected patients with CTCL who did not have COVID-19. We have learned that with effective safety measures, we can provide continued care to patients effectively and safely, limiting interruptions in necessary therapies.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas that diff er greatly in clinical presentation and prognosis.Mycosis fungoides (MF) is the most frequent subtype.Sézary syndrome (SS) is less prevalent but has a much more unfavourable prognosis.Previous studies have shown that the incidence of CTCL has tripled between 1970 and 2000 but since then has stabilized.However, data on the incidence of MF and SS in the Netherlands have never been published.The aim of the present study was to estimate the changes in incidence of newly diagnosed MF and SS in the Netherlands over the last 20 years.Annual incidence rates were retrieved from the Dutch Cutaneous Lymphoma Registry (DCLR) between January 2000 and December 2019.In all cases, the diagnosis was based on the clinicopathological criteria of the World Health Organization European Organisation for Research and Treatment of Cancer classification and confirmed by an expert panel of dermatologists and pathologists at a periodical meeting of the Dutch Cutaneous Lymphoma Working Group.We calculated the number of registered patients with MF and SS per 100 000 persons, corrected for the size of the Dutch population.1044 patients with MF, including 238 patients with folliculotropic MF (FMF), and 93 patients with SS were included.In 2000, the corrected number of cases of MF was 0.19 per 100 000 persons, while this was 0.35 per 100 000 in 2010 and 0.46 per 100 000 persons in 2019.This means that a 2.42-fold increase, corrected for Dutch population growth, was seen between 2000 and 2019 for the incidence of MF in the Netherlands.In 2000, 2010 and 2019 the corrected incidences for SS were 0.013, 0.018 and 0.075 per 100 000 persons, respectively.The overall increase for SS was 6.0-fold corrected for the Dutch population between 2000 and 2019.In summary, a significant increase of patients with classical MF, FMF and SS included in the DCLR was seen over the past 20 years.In contrast to previous studies that suggest a stabilization since 2000, this study shows that the incidence of patients with MF and SS in the Netherlands increased 2.42-fold over the past two decades.

Primary cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. CTCL subtypes demonstrate a variety of clinical, histological, and molecular features, and can follow an indolent or a very aggressive course. The underlying pathogenetic mechanisms are not yet entirely understood. The pathophysiology of CTCL is complex and a single initiating factor has not yet been identified. Diagnosis is based on clinicopathological correlation and requires an interdisciplinary team. Treatment decision is made based on short-term and long-term goals. Therapy options comprise skin-directed therapies, such as topical steroids or phototherapy, and systemic therapies, such as monoclonal antibodies or chemotherapy. So far, the only curative treatment approach is allogeneic haematopoietic stem cell transplantation. Novel therapies, such as chimeric antigen receptor T cells, monoclonal antibodies or small molecules, are being investigated in clinical trials. Patients with CTCL have reduced quality of life and a lack of effective treatment options. Further research is needed to better identify the underlying mechanisms of CTCL development and course as well as to better tailor treatment strategies to individual patients.

Kaposi sarcoma (KS) is an angioproliferative malignancy with five clinical subtypes: classic, African endemic, iatrogenic, AIDs-associated, and a nonepidemic variant. Classic KS has been traditionally defined as violaceous patches, plaques, and tumors occurring on the lower extremities of elderly men of Mediterranean or Eastern European descent. We present a case series of 17 patients from Latin America diagnosed at our institution from 1999-2020 with presentations similar to classic KS. All of the patients were immunocompetent, HHV-8+/HIV-, were not men who have sex with men (MSM), had no history of intravenous drug use, and had biopsy-proven KS. The majority of patients were male (12 males; 5 females). The average age of diagnosis was 69.5 years (SD 14.2 years). Seven had lower extremity involvement alone (41%). Four had upper and lower extremity involvement (24%). Other locations included the nose (n = 1), penis (n = 2), hands/upper arms alone (n = 1), cervical lymph node (n = 1), and unknown sites (n = 1). The majority of patients in both groups responded well to therapy and had no progression of disease or complete response. A comprehensive literature review revealed a significant number of classic KS cases have been reported in Venezuela, Ecuador, Colombia, Brazil, Argentina, Chile, French Guiana, and Peru. In fact, a survey of biopsy samples from a national pathology registry demonstrated 18% of classic KS diagnoses in the United States were in those of non-European Hispanic origin. Therefore, we propose that the patients observed in this case series may represent an unrecognized Latin American KS variant.