Dermatologic toxicities of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a new and emerging category of oncologic treatments that combine the target specificity of a monoclonal antibody with a cytotoxic payload. These drugs are associated with unique cutaneous toxicities that vary across agents. Currently, there are eleven ADCs with regulatory approval for solid and liquid tumors and over 80 ADCs currently in clinical development, it is critical for dermatologists to recognize and appropriately mitigate the cutaneous toxicities associated with these therapies. This clinical review will summarize the novel mechanisms and indications of approved ADCs, discuss dermatologic toxicities demonstrated in clinical trials and postmarketing studies, and impart recognition and management guidance when encountering these reactions to help maintain patients safely and comfortably on their medications.

Mohs micrographic surgery in the surgical treatment paradigm of melanoma in situ and invasive melanoma: A clinical review of treatment efficacy and ongoing controversies.

Mohs Micrographic Surgery (MMS) for treatment of melanoma offers several advantages over wide local excision (WLE), including complete histologic margin evaluation, same-day resection and closure, and sparing of healthy tissue in critical anatomic sites. Recently, a large volume of clinical data demonstrating efficacy in MMS treatment of melanoma was published, leading to emerging patient safety considerations of incurred treatment costs, risk of tumor upstaging, and failure of care coordination for sentinel lymph node biopsy (SLNB). MMS offers a safe, effective, and value-based treatment for both melanoma in situ (MIS) and invasive melanoma (IM), particularly with immunohistochemistry use on frozen sections. Compared to wide local excision, MMS treatment demonstrates similar or improved outcomes for local tumor recurrence, melanoma-specific survival, and overall survival at long-term follow-up. Tumor upstaging risk is low, and if present, alteration to clinical management is minimal. Discussion of SLNB for eligible head and neck IM cases should be done prior to MMS. Though challenging, successful multidisciplinary coordination of SLNB with MMS has been demonstrated. Herein, we provide a detailed clinical review of evidence for MMS treatment of cutaneous melanoma and offer recommendations to address current controversies surrounding the evolving paradigm of surgical management for both MIS and invasive melanoma (IM).

Safety of dermatologic medications in pregnancy and lactation: An update - Part I: Pregnancy.

The breadth of therapeutic options for the management of dermatologic skin conditions continues to expand rapidly as exemplified by biologics and small molecule drug development. While dermatologists and health care providers are aware of the underlying mechanisms and indications for these therapeutics, there is a recognized practice gap due to an incomplete understanding of the safety of these medications in women of childbearing age during the prepartum, antepartum, and postpartum phases. Although a two-part continuing medical education review was published regarding the prescribing practices and safety profiles of these new therapeutics in women of childbearing age while pregnant or lactating in 2014, many new medications have been approved since then. Herein, we will update the safety of dermatologic therapies during pregnancy and Part II will review the safety of medications during lactation.

Safety of dermatologic medications in pregnancy and lactation: An update-Part II: Lactation.

Multiple recently approved medications have been added to our treatment armamentarium for various dermatologic conditions. Herein, we have reviewed the literature, consolidated available safety data, and offered recommendations based upon available evidence as a reference guide for clinicians treating patients for dermatologic conditions during lactation.

Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

Declining invasive and rising in situ melanoma incidence trends in Iceland: A nationwide cohort study.

BACKGROUND: Melanoma is increasing worldwide, with incidence rates of invasive melanoma and melanoma in situ (MIS) varying by country. OBJECTIVE: To provide updated invasive melanoma and MIS incidence and mortality trends in Iceland and explore differences among sex and rurality. METHODS: In this whole-population study using the Icelandic Cancer Registry, patients diagnosed with invasive melanoma or MIS between 1957 and 2021 were included. Sex-specific world standardized incidence (WSR) and mortality rates were assessed by rurality. Joinpoint analysis was used to calculate trends using annual per cent change (APC). RESULTS: Invasive melanoma incidence rates increased from 0.66 to 7.0 (men) and 1.6 to 11.0 (women) per 100,000 person-years, and from 0.2 to 4.0 and 0.9 to 9.5 per 100,000 person-years for MIS in men and women, respectively, with a statistically significant linear trend (p = 0.001). WSR peaked in both men and women (10.7, 17.9 per 100,000 person-years) between 2002 and 2006 and has since been trending down. Between 1991 and 2005, the rise in invasive melanoma occurred more frequently in urban regions. Between 2003 and 2005, joinpoint analysis demonstrated a downtrend in invasive melanoma in men and women (-0.29, -0.73; p < 0.05). For MIS, the WSR peaked at 12.4 per 100,000 person-years in women between 1997 and 2001 before down-trending to 4.2. In recent years (2017-2021), the WSR has been steadily increasing in women with an APC of 1.43. Melanoma-specific mortality has decreased since 2012 (-0.07; p < 0.05). CONCLUSIONS: Declining invasive melanoma incidence and mortality rates in conjunction with the recent rise in MIS may reflect the impact of Iceland's sun safety and anti-sunbed educational campaigns, federal regulation of sunbeds and earlier melanoma detection in urban areas.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Dysplastic nevus part II: Dysplastic nevi: Molecular/genetic profiles and management.

Dermatologists frequently see patients with clinically atypical nevi and dermatopathologists interpret histologically dysplastic nevi on a near-daily basis, but there is great variability in the definition and management of such lesions. This part of the CME review focuses on information published since the previous comprehensive review (2012), with emphasis on molecular and genetic attributes of histologically dysplastic nevi and clinical management.

Dysplastic nevus part I: Historical perspective, classification, and epidemiology.

Since the late 1970s, the diagnosis and management of dysplastic nevi have been areas fraught with controversy in the fields of dermatology and dermatopathology. Diagnostic uncertainty and lack of standardized nomenclature continue to propagate confusion among clinicians, dermatopathologists, and patients. In part I of this CME review article, we summarize the historical context that gave rise to the debate surrounding dysplastic nevi and review key features for diagnosis, classification, and management, as well as epidemiology. We discuss essentials of clinical criteria, dermoscopic features, histopathologic features, and the diagnostic utility of total body photography and reflectance confocal microscopy in evaluating dysplastic nevi, with emphasis on information available since the last comprehensive review a decade ago.

Surface anatomy in dermatology: Part I - Clinical importance, diagnostic utility, and impact on medical management.

This continuing medical education (CME) series reviews updated Delphi consensus surface anatomy terminology through the lens of common medical and procedural dermatology scenarios, helping to underscore high-yield points that can be readily integrated into clinical practice to support patient care. Part I of this series will discuss the current state of surface anatomy terminology in dermatology, outline implications of precise and consistent terminology, provide an illustrative overview of high-yield consensus terminology, highlight prominent landmarks that can aid in critical diagnoses, and relate the importance of precise terminology to medical management. Part II will draw upon consensus terminology to inform management of cutaneous malignancies and support optimal outcomes in dermatologic procedures.

Dermatology workforce in the United States - Part I: Overview, transformations, and implications.

The dermatology workforce continues to evolve to meet the growing and diversified demands of the US population. Part 1 of this continuing medical education series is designed to provide an overview of the dermatology workforce as well as delineate the motivators and socioeconomic implications of significant workforce transformations which are impacting dermatologic health care. Part 2 of the series will consider the impact of workforce challenges on patient outcomes and discuss potential actions that may help to optimize workforce organization and care delivery.

Dermatology workforce in the United States - Part II: Patient outcomes, challenges, and potential solutions.

This continuing medical education (CME) series assesses key features and ongoing transformations within the dermatology workforce. Part 1 of this series described precipitants and implications of recent workforce changes. Part 2 reviews the influence that these workforce dynamics have had on patient access, outcomes, and satisfaction. Additionally, it assesses potential solutions for optimizing care for underserved groups and the broader dermatologic patient population.

Surface anatomy in dermatology: Part II - Impact on perioperative management, procedural technique, and cosmesis.

This continuing medical education (CME) series reviews updated Delphi consensus surface anatomy terminology through the lens of common medical and procedural dermatology scenarios, helping to underscore high-yield points that can be readily integrated into clinical practice to support patient care. Part I of the series reviewed the current state of standardized surface anatomy, provided an illustrative review of consensus terminology, highlighted prominent landmarks that can aid in critical diagnoses, and related the importance of precise terminology to principles of medical management. Part II will utilize consensus terminology to heighten recognition of key landmarks in procedural dermatology to support optimal functional and aesthetic outcomes.

Concordance of reflectance confocal microscopy and gene expression profiling for melanocytic lesions with uncertain malignant potential: A case series.

For a small yet significant proportion of melanocytic lesions, histopathologic analysis may be unable to definitively evaluate malignant potential. These cases may signify a specific need for newer ancillary diagnostic technologies, including in vivo reflectance confocal microscopy (RCM) and gene expression profiling (GEP), both of which are highly sensitive in the diagnosis of melanoma. We report four cases of clinically suspicious melanocytic lesions that lacked definitive malignant features on histopathology and that were aided by use of RCM and GEP. Three of the four cases showed concordance between RCM and GEP in the diagnosis of melanoma. In one case, RCM was suggestive of melanoma; on the other hand, GEP and histopathology supported a final diagnosis of compound Spitz nevus. These cases support the role of RCM as a novel, non-invasive diagnostic tool to aid in the diagnosis of clinically suspicious melanocytic lesions with uncertain malignant potential, although RCM may have relatively lower accuracy for some atypical spitzoid lesions.

Reflectance confocal microscopy of facial neoplasms: Follicular involvement as a clue to diagnosis.

BACKGROUND: Facial skin is characterized by high density of follicles. Facial neoplasms may present overlapping clinical and dermoscopic findings. Our goal was to evaluate and compare, via reflectance confocal microscopy (RCM), follicular involvement in facial neoplasms. METHODS: We retrospectively searched our image database, between January 2008 and December 2020, for all facial lesions with (1) a standardized set of clinical, dermoscopic, and RCM images, and (2) a biopsy-proven diagnosis of lentigo maligna/lentigo maligna melanoma (LM/LMM, n = 39), basal cell carcinoma (BCC, n = 51), squamous cell carcinoma in situ (SCCIS, n = 5), actinic keratosis (AK, n = 11), and lichen-planus-like keratosis (LPLK, n = 18). Two readers jointly evaluated the RCM images for a set of predefined features of follicular involvement. RESULTS: Diffuse obliteration of follicles was frequent in BCC (88%), while follicular infiltration by refractile dendritic cells and/or by bright round nucleated cells was common in melanoma (90% and 44%, respectively). Extension of atypical keratinocytes down follicles was more prominent among SCCIS than AK (80% vs. 45%, p = 0.01). In most LPLK (89%), there was follicular sparing. CONCLUSIONS: Evaluation of RCM criteria centering on the follicles can be useful in the differential diagnosis between common facial neoplasms.

"Pediatric" Drug Studies Might Be the Largest Abuse in Medical Research in History. It Is Time for Lawyers to Step In.

A new type of research has emerged with United States and European Union pediatric laws that request/demand separate clinical studies for vaccines and drugs in minors less than 18 years of age. Physiologically, minors mature before their 18th birthday. Medicine treats the body, not the administrative status. Many "pediatric" studies are performed in minors that bodily are no longer children, which makes them pointless. Traditional malpractice litigation in clinical research involves patients that were harmed in clinical studies. In the new type of "pediatric" studies, drugs known to work in humans are retested, pretending that "children" are uniquely different, which is incorrect. Minors are not another species. Patients are not treated at all (placebo group) or below standard-of-care (comparison to outdated treatment). Pediatric laws are the law, but not a free pass for harming patients. Where "pediatric" studies violate accepted norms of medical practice, lawyers should be aware of this challenge at the interface of medicine and law.

Cutaneous manifestations of child abuse and neglect: Part I.

Child abuse and neglect remains a significant cause of morbidity and mortality in children. Dermatologists may not fully conceptualize their crucial role in the evaluation of child abuse and neglect as both mandated reporters and experts in skin pathology. This CME article summarizes the current information on cutaneous signs and clinical signs of abuse for dermatologists so that they gain more insight into the skin examination for child abuse and neglect, develop confidence in their ability to distinguish dermatologic signs of accidental versus inflicted trauma, and more frequently consider abuse and neglect in their differential diagnosis.

Cutaneous mimics of child abuse and neglect: Part II.

Given that some cutaneous mimics of child abuse result from a rare disease, they may be more prone to misdiagnosis. For possible child abuse cases in which diagnosis remains uncertain at the time of initial dermatologic evaluation, it is important that dermatologists are prepared to distinguish actual dermatologic conditions in cases of ambiguous skin findings. Additionally, this review will aid clinicians in recognizing the possibility of concurrent actual dermatologic disease and skin findings related to abuse with the acknowledgment that they are not mutually exclusive. A proper recognition of mimics of abuse may prevent unnecessary stress and child protective service investigation.

Melanoma: An update on systemic therapies.

Despite advances in early detection as described in part 1 of this continuing medical education series, melanoma continues to be a large contributor to cutaneous cancer-related mortality. In a subset of patients with unresectable or metastatic disease, surgical clearance is often not possible; therefore, systemic and local therapies are considered. The second article in this series provides dermatologists with an up-to-date working knowledge of the treatment options that may be prescribed by oncologists for patients with unresectable stage III, stage IV, and recurrent melanoma.

Melanoma: How and when to consider clinical diagnostic technologies.

In response to rising rates of melanoma worldwide, novel noninvasive melanoma detection techniques are emerging to facilitate the early detection of melanoma and decrease unnecessary biopsies of benign pigmented lesions. Because they often report similar study findings, it may be difficult to determine how best to incorporate these technologies into clinical practice based on their supporting studies alone. The first article in this continuing medical education series provides practical advice on how and when to use various noninvasive melanoma detection techniques in clinical practice.