The Clinical Spectrum of Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoproliferative Disorder: An Updated Systematic Literature Review and Case Series.

BACKGROUND: Primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoproliferative disorder (SMPLPD) is a provisional entity within the 2016 World Health Organization classification of primary cutaneous lymphomas. The condition is currently classified as a lymphoproliferative disorder to emphasize its benign course and discourage aggressive, systemic treatment modalities. OBJECTIVE: To provide a relevant synthesis for the dermatological practitioner on the prevalence, presentation, and treatment of SMPLPD. METHODS: We conducted an updated systematic literature review and a retrospective chart review of diagnosed cases of SMPLPD from 2 Canadian academic cutaneous lymphoma centers. RESULTS: A total of 23 studies with 136 cases were extracted from the systematic review and 24 patients from our retrospective chart review. SMPLPD proved relatively common accounting for 12.5% of all cutaneous T-cell lymphomas encountered in our cutaneous lymphoma clinics, second in frequency only to mycosis fungoides. The typical clinical presentation was that of an older individual (median age 59 years) with an asymptomatic solitary lesion on their upper extremity. The most common clinical differentials were cutaneous lymphoid hyperplasia, basal cell carcinoma, and lymphoma unspecified. T follicular helper markers were reliably detected. The main treatment modalities were surgical excision, local radiation therapy, and topical or intralesional steroids. Cure was achieved in the vast majority of cases. CONCLUSIONS: SMPLPD is an underdiagnosed T-cell lymphoma with an overtly benign clinical course. The condition has an excellent prognosis and responds well to skin-directed therapies. Practitioners should be aware of this condition to avoid aggressive systemic treatments.

The Neoantigen Landscape of Mycosis Fungoides.

Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens. Methods: Whole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality. Results: MF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity. Conclusions: The neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.

Muffin Technique Micrographic Surgery for Non-melanoma Skin Cancer.

Background: Mohs micrographic surgery (MMS) is the gold standard treatment for high-risk facial non-melanoma skin cancer. However, patients' access to MMS is limited by cost. The muffin technique micrographic surgery (MTMS) is an alternative micrographic technique wherein the entire excised margin is evaluated post-operatively by a pathologist using paraffin-embedded material. Herein, we describe the implementation and the preliminary results of MTMS in an academic dermatology center. Objective: To describe the MTMS and outline its efficacy and safety in a real-world clinical academic setting. Methods: A retrospective chart review was conducted of all patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) who underwent MTMS at the University of Alberta Dermatology Center from June 2016 until July 2019. Results: A total of 69 patients were included (64 BCCs and 5 SCCs). 68.1% of surgeries had clear margins following the first incision, 100% after second round re-excisions. There were no observed cases of tumor recurrence after a median 40 months of follow-up. There were no major adverse events or complications. Conclusions: MTMS is a superior alternative to simple excision of skin cancer by providing full margin control and residual tumor mapping.

Developing a Patient Charter for People Living With Conditions, Diseases, or Traumas Involving the Skin [Formula: see text].

BACKGROUND: Studies have shown disparities in the perception of skin disease burden between patients and physicians, with patients often feeling that the severity, emotional impact, and social repercussions of their skin condition are underestimated. Although physician's professional behavior is guided by documents such as the Hippocratic Oath, there are no patient-driven principles to guide healthcare interactions involving skin concerns. OBJECTIVE: To develop a concise and practical charter for patients based on their perceptions of unmet needs with the goals of helping patients express their needs and exercise their rights to accessing and utilizing the healthcare system for conditions, diseases, or traumas involving the skin. METHODS: An initial literature review examined healthcare delivery concerns of patients with skin conditions. Results were used to draft a charter that was reviewed by a Canadian patient focus group representing various skin condition advocacy groups. A revised charter was reviewed by Canadian dermatologists before being formally approved by the Canadian Skin Patient Alliance Board and endorsed by the Canadian Dermatology Association. RESULTS: The Patient Charter comprises 8 principles for providing and receiving professional services for the skin in the healthcare setting. CONCLUSIONS: This Patient Charter provides direct insights into patient priorities and will be used as an educational and advocacy tool in healthcare, occupational, and social settings. The intended goal is for the Patient Charter to empower patients and to educate health professions, government, industry, and society at large. Accordingly, the charter will be disseminated through print materials, informational videos, and social media campaigns.

Weight Loss and Dietary Interventions for Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a common inflammatory disorder characterized by recurrent, painful, and malodorous abscesses and nodules predominantly in skin folds. HS is associated with substantial morbidity and poor quality of life. There are no curative therapies, and the only approved biologic drug has variable efficacy and requires high doses, making adjunct treatments crucial. An important risk factor for disease severity is obesity. Our primary objective was to conduct a systematic review examining weight loss and dietary interventions, in HS. Our secondary objective was to examine nutritional supplements in HS.A systematic literature search was conducted using Medline, EMBASE, and the Cochrane Database. We included all study types in adults (>18 years), with a minimum sample size of 5, examining the effects of any dietary or weight loss intervention on HS severity. Two authors screened n = 1279 articles of which 9 met inclusion criteria. All included studies were observational and all interventions were associated with various measures of decreased HS severity. Patient-controlled weight loss and bariatric surgery were associated with HS regression, though a subset of patients with significant increase in panniculi experienced exacerbations and required excision of excess skin. Diets demonstrating benefit eliminated dairy and brewer's yeast. Nutritional supplements including zinc gluconate, vitamin D, and riboflavin had a suppressive, rather than curative, effect on HS lesions in single studies. Overall, the reviewed interventions show promise as potential adjunct treatments in a HS management plan. Prospective randomized controlled trials should validate these findings.

Immunotherapy for Cutaneous T-Cell Lymphoma: Current Landscape and Future Developments.

Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic, progressive primary cutaneous T-cell lymphomas (CTCLs) for which there are no curative treatments. Skin-directed therapies, such as phototherapy, radiation therapy, or topical nitrogen mustard, provide only short-term remissions. Numerous attempts with different chemotherapeutic regimes failed to achieve meaningful clinical responses. Immunotherapy seems to be a promising avenue to achieve long-term disease control in CTCL. There is compelling evidence indicating that MF and SS are immunogenic lymphomas, which can be recognized by the patient's immune system. However, CTCL uses different strategies to impair host's immunity, eg, via repolarizing the T-cell differentiation from type I to type II, recruiting immunosuppressive regulatory T-cells, and limiting the repertoire of lymphocytes in the circulation. Many currently used therapies, such as interferon-α, imiquimod, extracorporeal phototherapy, and allogeneic bone marrow transplant, seem to exert their therapeutic effect via activation of the antitumor cytotoxic response and reconstitution of the host's immune system. It is likely that novel immunotherapies such as immune checkpoint inhibitors, cancer vaccines, and chimeric antigen receptor-T cells will help to manage CTCL more efficiently. We also discuss how current genomic techniques, such as estimating the mutational load by whole genome sequencing and neoantigen calling, are likely to provide clinically useful information facilitating personalized immunotherapy of CTCL.

Minimally Important Differences in Patient or Proxy-Reported Outcome Studies Relevant to Children: A Systematic Review.

CONTEXT: No study has characterized and appraised all anchor-based minimally important differences (MIDs) associated with patient-reported outcome (PRO) instruments in pediatric studies. OBJECTIVE: To complete a comprehensive systematic survey and appraisal of published anchor-based MIDs associated with PRO instruments used in children. DATA SOURCES: Medline, Embase, and PsycINFO (1989 to February 11, 2015). STUDY SELECTION: Studies reporting empirical ascertainment of anchor-based MIDs among PROs used in pediatric care. DATA EXTRACTION: All pertinent data items related to the characteristics of PRO instruments, anchors, and MIDs. RESULTS: Of 4179 unique citations, 30 studies (including 32 cohorts) proved eligible and reported on 28 unique PROs (8 generic, 13 disease-specific, 5 symptoms-specific, 2 function-specific), with 9 (32%) classified as patient-reported, 11 (39%) proxy-reported, and 8 (29%) both patient- and proxy-reported. Of the 30 studies, we rated 14 (44%) as providing highly credible estimates of the MID. Most cohorts (n = 20, 62%) recorded patients' direct response to the target PRO and the use of an independent standard of comparison (n = 25, 78%). Most, however, failed to effectively report measurement properties of the anchor (n = 24, 75%). LIMITATIONS: We have not yet addressed the measurement properties of instrument to measure credibility; our search was restricted to 3 electronic sources, and we used a single data abstractor. CONCLUSIONS: Our study found 28 PROs that have been developed for children, with fewer than half providing credible estimates. Clinicians, clinical trialists, systematic reviewers, and guideline developers seeking to effectively summarize and interpret results of studies addressing PROs in child health are likely to find our comprehensive compendium of MIDs of use, both in providing best estimates of MIDs and identifying credible estimates.