Guidelines of care for the management of actinic keratosis Eisen, Daniel B.; Asgari, Maryam M.; Bennett, Daniel D. ...
Journal of the American Academy of Dermatology,
October 2021, 2021-10-00, Letnik:
85, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
This analysis examined the literature related to the ...management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed.
A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus.
Analysis of the evidence resulted in 18 recommendations.
This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data.
Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
There are too few board-certified dermatologists to treat all patients with skin disease. Primary care physicians often serve at the frontline of skin cancer screening.
To compare biopsy use among ...dermatologist physicians, dermatology advanced practice professionals (APPs), primary care physicians (PCPs), and other nondermatology clinicians.
Pathology reports, requisition forms, and clinical notes of skin biopsies submitted to our institution during the study period were reviewed. Skin biopsies for inflammatory conditions, cosmetic or functional purposes, and re-excisions were excluded. The number needed to biopsy (NNB) was calculated as the number of biopsied lesions divided by histologically proven skin cancers.
The NNB by clinician type was 2.82 for dermatology physicians, 4.69 for APPs, 4.55 for nondermatology PCPs, and 6.55 for other nondermatology clinicians (P < .001). The NNB was significant between clinician groups for nonmelanoma skin cancer (dermatology physicians, 2.00; APPs, 2.71; PCPs, 2.36; and other nondermatology clinicians, 3.47; P < .001) but not for melanoma (dermatology clinicians, 14.33; APPs, 20.78; PCPs, 27.80; and other nondermatology clinicians, 53.56; P = .061).
The NNB represents a measure of use but gives no insight into the number of malignant lesions that go unbiopsied and, therefore, undiagnosed. The prevalence of skin cancer varies among dermatology and nondermatology practices. The results are not generalizable to all practice settings.
Dermatology physicians had the lowest NNB of all clinician groups. PCPs performed similarly to dermatology APPs.
MAGE A3, which belongs to the family of cancer-testis antigens, is an attractive target for adoptive therapy given its reactivation in various tumors and limited expression in normal tissues. We ...developed an affinity-enhanced T cell receptor (TCR) directed to a human leukocyte antigen (HLA)-A*01-restricted MAGE A3 antigen (EVDPIGHLY) for use in adoptive therapy. Extensive preclinical investigations revealed no off-target antigen recognition concerns; nonetheless, administration to patients of T cells expressing the affinity-enhanced MAGE A3 TCR resulted in a serious adverse event (SAE) and fatal toxicity against cardiac tissue. We present a description of the preclinical in vitro functional analysis of the MAGE A3 TCR, which failed to reveal any evidence of off-target activity, and a full analysis of the post-SAE in vitro investigations, which reveal cross-recognition of an off-target peptide. Using an amino acid scanning approach, a peptide from the muscle protein Titin (ESDPIVAQY) was identified as an alternative target for the MAGE A3 TCR and the most likely cause of in vivo toxicity. These results demonstrate that affinity-enhanced TCRs have considerable effector functions in vivo and highlight the potential safety concerns for TCR-engineered T cells. Strategies such as peptide scanning and the use of more complex cell cultures are recommended in preclinical studies to mitigate the risk of off-target toxicity in future clinical investigations.
Abstract
Pilomatricomas (PMs) are common benign adnexal tumors that show a predilection for the head and neck region and are characterized at the molecular level by activating mutations in the ...beta‐catenin (
CTNNB1
) gene. Giant PMs are a rare histopathological variant, according to the World Health Organization, which are defined by a size greater than 4 cm and are reported to show upregulation of yes‐associated protein compared to PMs of typical 1–3 cm size. We describe the case of a 67‐year‐old man with an 8 cm giant PM involving his temporal scalp, whose PM we characterized by 10X spatial gene expression analysis. This revealed five total transcriptomic clusters, including four distinct clusters within the giant PM, each with a unique transcriptional pattern of hair follicle‐related factors, keratin gene expression, and beta‐catenin pathway activity.
Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, ...EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as “EMPSGC” in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.
Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is the most common lymphoid malignancy in the Western world and classically presents as a rapidly enlarging nodal or extranodal ...mass. Cutaneous involvement by systemic DLBCL NOS is an infrequent clinical presentation, encountered in only 1.5-3.5% of cases, while disseminated cutaneous disease with multiple subcutaneous nodules at the time of diagnosis is unusual and can present a diagnostic challenge. The differential diagnosis when encountering a high-grade B-cell malignancy at a cutaneous site is broad and includes primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-MYC/BCL2), and other potential entities which must all be carefully considered before rendering a final diagnosis. In this report, we describe the case of a 69-year-old man who was seen at our hospital due to generalized weakness and was found to have multiple subcutaneous nodules representing disseminated DLBCL NOS. The case was complicated by concurrent monoclonal B-cell lymphocytosis involving the bone marrow.
Clinical decision support (CDS) design best practices are intended to provide a narrative representation of factors that influence the success of CDS tools. However, they provide incomplete direction ...on evidence-based implementation principles.
This study aims to describe an integrated approach toward applying an existing implementation science (IS) framework with CDS design best practices to improve the effectiveness, sustainability, and reproducibility of CDS implementations.
We selected the Practical Robust Implementation and Sustainability Model (PRISM) IS framework. We identified areas where PRISM and CDS design best practices complemented each other and defined methods to address each. Lessons learned from applying these methods were then used to further refine the integrated approach.
Our integrated approach to applying PRISM with CDS design best practices consists of 5 key phases that iteratively interact and inform each other: multilevel stakeholder engagement, designing the CDS, design and usability testing, thoughtful deployment, and performance evaluation and maintenance. The approach is led by a dedicated implementation team that includes clinical informatics and analyst builder expertise.
Integrating PRISM with CDS design best practices extends user-centered design and accounts for the multilevel, interacting, and dynamic factors that influence CDS implementation in health care. Integrating PRISM with CDS design best practices synthesizes the many known contextual factors that can influence the success of CDS tools, thereby enhancing the reproducibility and sustainability of CDS implementations. Others can adapt this approach to their situation to maximize and sustain CDS implementation success.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Standard of care treatment for metastatic cutaneous adnexal carcinomas is not well established. In this case report, we highlight the successful use of anti-programmed cell death protein 1 ...(anti-PD-1) therapy in treating a patient with low tumor mutation burden, microsatellite stable, high programmed death-ligand 1 (PD-L1) gene expression, metastatic primary cutaneous adnexal carcinoma with significant radiographic, and circulating tumor DNA response with durable benefit. Immune checkpoint inhibitors hold promise as a future treatment option in rare instances of metastatic disease from primary skin adnexal carcinoma. Further studies are needed to identify better immune checkpoint inhibitor predictive biomarkers for rare, advanced-stage non-melanoma skin cancers.
Diagnosis and Management of Vulvovaginal Lichen Planus Jacques, Laura; Kornik, Rachel; Bennett, Daniel D ...
Obstetrical & gynecological survey,
2020-October, 2020-Oct, 2020-10-00, 20201001, Letnik:
75, Številka:
10
Journal Article
Recenzirano
IMPORTANCEGenital lichen planus is a debilitating disorder that lacks definitive recommendations regarding diagnosis and treatment.
OBJECTIVEThe aim of this study was to present best practices from ...available evidence for the diagnosis and treatment of genital lichen planus.
EVIDENCE ACQUISITIONWe conducted a narrative review of the literature on genital lichen planus by searching PubMed using the following search terms“vulvar lichen planus” OR (vulvar diseasesmesh OR vulvamesh) AND lichen planusmesh OR vulvarti AND “lichen planus”ti. We included all languages and years in the search.
RESULTSThe search resulted in 273 citations that we reviewed for relevancy and selected 60 as the foundation for this review that focuses on genital sites. Diagnosis can be made without biopsy, and when a biopsy is taken, the pathologic findings may be nonspecific. Topical ultrapotent corticosteroids are most commonly used as first-line treatment of genital lichen planus.
CONCLUSIONS AND RELEVANCEWhen patients present with genital lichen planus, a complete review of systems and a thorough physical examination should be performed because of the prevalence of extragenital sites. Treatment of genital disease should start with a topical, ultrapotent steroid, and follow-up visits should occur to ensure improvement and to monitor for adverse drug reactions and malignancy.
TARGET AUDIENCEObstetricians, gynecologists, and family physicians.
LEARNING OBJECTIVESAfter reading this article, readers should be able to differentiate between lichen planus and other common vulvar dermatoses on physical examination; evaluate a patient for nongenital manifestations of lichen planus; assess if a vulvar biopsy is necessary for diagnosis; and construct a management plan for patients affected by genital lichen planus.
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