Sarcoidosis Resembling Angiokeratomas: A Case Report.

Sarcoidosis, a multifaceted systemic disorder characterized histologically by the presence of non-caseating granulomas, has a wide array of cutaneous manifestations. We describe a case of a 74-year-old woman with a complex medical history, who presented with asymptomatic hyperpigmented papules on her lower extremities. Histological examination of a punch biopsy specimen showed nodular and angiocentric patterns of granulomatous inflammation consistent with sarcoidosis, and chest radiography demonstrated bilateral hilar opacities, supporting the diagnosis. To our knowledge, this specific cutaneous presentation of sarcoidosis has not been described before, and it can easily be mistaken for other conditions. Therefore, this case underscores the importance of recognizing atypical cutaneous morphologies of sarcoidosis, particularly in patients with complex medical histories, to facilitate accurate diagnosis and timely intervention. We aim to increase awareness among clinicians regarding the diverse manifestations of sarcoidosis, thereby enhancing diagnostic acumen and patient care.

Iterative refinement of a histologic algorithm for burn depth categorization based on 798 consecutive burn wound biopsies.

INTRODUCTION: Our group previously reported a burn biopsy algorithm (BBA-V1) for categorizing burn wound depth. Here, we sought to promulgate a newer, simpler version of the BBA (BBA-V2). METHODS: Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn wounds assessed as likely to heal by 21 days were imaged within 72 h of injury and at 21 days. A sample of 798 burn wound biopsies were classified by both BBAV1 and BBAV2 algorithms. For nonoperative burn wounds, the proportion of healing versus nonhealing pixels at 21 days after injury were compared. RESULTS: The 798 biopsies were classified by BBAV1 as 24% SPT, 47% DPT, 28% FT and by BBAV2 as 3% SPT, 67% DPT, and 30% FT (p < 0.0001). Overall, the proportion of biopsies whose wound reclassification changed from a nonoperative to operative pathway was 21% (95% CI: 18-24%). Nonoperative wounds judged at injury as being SPT contained 12.8 million pixels. Repeat 21-day imaging revealed 11.3 million healed pixels (accuracy = 89.6% (95% CI: 89.59-89.62)). CONCLUSIONS: BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness.

A Physician's Guide to the Use of Gene Expression Profile Ancillary Diagnostic Testing for Cutaneous Melanocytic Neoplasms.

Objectives: Some melanocytic neoplasms suspicious for melanoma require additional workup to arrive at a final diagnosis. Within the last eight years, gene expression profiling (GEP) has become an important ancillary tool to aid in the diagnosis of melanocytic neoplasms with uncertain malignant potential. As the usage of two commercially available tests (23-GEP and 35-GEP) evolves, it is important to answer key questions about optimal utilization and their impact on patient care. Methods: Recent and relevant articles answering the following questions were included in the review. First, how do dermatopathologists synthesize the available literature, the latest guidelines, and their clinical experience to determine which cases would be most likely to benefit from GEP testing? Second, how best can a dermatologist convey to their dermatopathologist that the use of GEP in the diagnostic process could provide a more clearly defined result and thereby help empower the dermatologist to provide higher-quality patient care when making specific patient management decisions for otherwise pathologically ambiguous lesions? Results: When interpreted in the context of the clinical, pathologic, and laboratory information, GEP results can facilitate the rendering of timely, accurate, and definitive diagnoses for melanocytic lesions with otherwise uncertain malignant potential to inform personalized treatment and management plans. Limitations: This was a narrative review focused on clinical use of GEP compared to other ancillary diagnostic tests performed postbiopsy. Conclusion: Open communication between dermatopathologists and dermatologists, especially regarding GEP testing, can be a vital component to achieve appropriate clinicopathologic correlation for otherwise ambiguous melanocytic lesions.

Artificial intelligence in Dermatopathology.

INTRODUCTION: Ever evolving research in medical field has reached an exciting stage with advent of newer technologies. With the introduction of digital microscopy, pathology has transitioned to become more digitally oriented speciality. The potential of artificial intelligence (AI) in dermatopathology is to aid the diagnosis, and it requires dermatopathologists' guidance for efficient functioning of artificial intelligence. METHOD: Comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar." Articles published in English language were considered for the review. RESULTS: Convolutional neural network, a type of deep neural network, is considered as an ideal tool in image recognition, processing, classification, and segmentation. Implementation of AI in tumor pathology is involved in the diagnosis, grading, staging, and prognostic prediction as well as in identification of genetic or pathological features. In this review, we attempt to discuss the use of AI in dermatopathology, the attitude of patients and clinicians, its challenges, limitation, and potential opportunities in future implementation.

Clinical update on cutaneous and subcutaneous sarcomas.

BACKGROUND: Cutaneous sarcomas are uncommon cancers that can have a wide range of clinical symptoms and lead to considerable cutaneous as well as systemic morbidity. AIM: The objective of this review article is to discuss epidemiology, clinical features, diagnosis, and therapy of different types of cutaneous sarcomas. MATERIAL AND METHODS: Literature was screened to retrieve articles from PubMed/Medline and Google Scholar and related websites. Cross-references from the relevant articles were also considered for review. Review articles, clinical studies, systematic reviews, meta-analyses, and relevant information from selected websites were included. RESULTS AND DISCUSSION: Cutaneous sarcomas have a negative effect on the quality of life. In their diagnosis, clinical presentation and histological evaluation are crucial. Complete surgical removal is the solution for more or less all cutaneous and subcutaneous sarcomas. The prognosis for cutaneous sarcomas is generally favorable since they tend to recur locally with distant metastases only on rare occasions. Patients having advanced disease should be treated in the setting of clinical trials if possible; choices include radiation therapy and systemic medicines. The value of innovative immunotherapy cannot be determined decisively at this time due to a paucity of relevant trials. CONCLUSION: As cutaneous sarcomas are rarely diagnosed based on clinical findings, histology plays an important role in the diagnosis. They have a relatively favorable prognosis if treated properly. Patients should be treated at specialized centres.

Update of pathophysiology and treatment options of seborrheic keratosis.

Seborrheic keratosis (SK) is a common, benign tumor that can occur on everybody site and can be conservatively managed. Cosmetic concerns, especially when a lesion involves the facial area, are the most common reason for excision. SK shows male gender preponderance and increasing age is an independent association with the condition. Even though more prevalent in the elderly, it has also been reported in younger age groups like adolescents and young adults. Precise pathogenesis is still obscure, but ultra-violet exposure represents a predisposing factor to SK by altering the biochemical concentration and expression of factors like Glutamine deaminases, endothelin, and stem cell factor. Moreover, the accumulation of amyloid-associated protein has also been postulated. Involvement of genitalia has been associated with human papillomavirus infection. Recently, Merkel cell polyomavirus nucleic acid was also detected in SK. Several oncogenic mutations involving FGFR-3 and FOXN1 have been identified. SKs are usually classified clinically and histologically. Dermatoscopy is a noninvasive alternative diagnostic technique widely used in differentiating SK from other benign and malignant tumors. In terms of treatment, topical agents, shave dissection, cryosurgery, electrodesiccation, laser application and curettage under local anesthesia are safe methods for eradication of SKs, mostly for cosmetic purposes. Though generally safe, the latter techniques may occasionally cause post-procedure depigmentation, scarring, and recurrence. Nanosecond-pulsed electric field technology is a promising new technique with fewer side-effects.

Pathobiology of Cutaneous Manifestations Associated with COVID-19 and Their Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a rising concern since its declaration as a pandemic by the World Health Organization on 11 March 2020. Recently, its association with multiple underlying organs has been identified that includes cardiac, renal, gastrointestinal, nervous systems, and cutaneous manifestations. Cutaneous COVID-19 findings have been supposedly classified into the following categories: vesicular (varicella-like), papulo-vesiculsar, chilblains-like ("COVID toes") maculopapular, and urticarial morphologies. In this review, we aim to focus on the proposed pathophysiology behind the various dermatological manifestations associated with COVID-19 and their associated management. We also included prevalence and clinical features of the different COVID-19-related skin lesions in our review. A comprehensive narrative review of the literature was performed in PubMed databases. Data from case reports, observational studies, case series, and reviews till June 2022 were all screened and included in the review.

Androgens and COVID-19.

BACKGROUND: The humans have been disproportionately affected by the coronavirus disease (COVID-19) pandemic. The novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) causing coronavirus disease (COVID-19) has spread across the globe. Androgens have been suggested to have a role in COVID-19 pathogenesis. OBJECTIVE: The objective of this review article is to study the link between androgens and COVID-19. METHODOLOGY: PubMed and Google Scholar search was performed to retrieve literature related to the topic. Review articles, clinical trials, retrospective studies, observational studies, and case-control studies were considered for the review. RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected men are more inclined to be hospitalized for intensive care unit (ICU) as compared with women. This difference in the ICU admissions provides some clue for possible influence of androgens in the severity of COVID-19. The contribution of androgen and androgen receptor in COVID-19 disease and its severity, as well as the numerous medications targeting androgen and its receptor for lowering COVID-19 disease severity, are discussed in this review. Available literature suggests the role of androgen in the pathogenesis and severity of COVID-19. Sensitivity for androgen may be an important factor in regulating the severity of COVID-19 disease. CONCLUSION: There is a scope for the development of COVID-19 treatments based on androgen suppression. Clinical trials may furnish pivotal data and add more evidence-based options for the management of COVID-19.

When Bullous Pemphigoid Is Not Bullous Pemphigoid: The Importance of Going Beyond Direct Immunofluorescence.

Bullous pemphigoid (BP) is the most common autoimmune bullous disease, but rarer forms of pemphigoid may appear identical to BP on routine histopathology and direct immunofluorescence (DIF). Here, we present the case of a 60-year-old man, who was initially thought to have BP, with supportive findings on routine histopathology and DIF. However, prominent oral involvement and cutaneous lesions refractory to conventional treatment suggested an alternate diagnosis. Further workup was performed, including indirect immunofluorescence (IIF) on salt-split skin, which showed binding of antibodies to the dermal floor rather than to the blister roof, and enzyme-linked immunosorbent assay for pemphigus and pemphigoid antibodies. With these additional tests, we concluded that the patient does not have BP but rather anti-p200 pemphigoid, anti-p105 pemphigoid, or a yet undiscovered form of pemphigoid. We reached a presumptive diagnosis of anti-p200 pemphigoid, as it is the most common pemphigoid with serum antibodies to the dermal floor of human salt-split skin by IIF. This case demonstrates that suspicion for other autoimmune bullous diseases in cases of treatment-refractory and clinically aberrant BP is essential. A limited workup may lead to a missed diagnosis and ultimately less efficient disease management.

Merkel Cell Carcinoma: From Pathobiology to Clinical Management.

Merkel cell carcinoma (MCC) is an infrequent, rapidly growing skin neoplasm that carries a greater probability of regional lymph node involvement, and a grim prognosis in advanced cases. While it is seen predominantly in old age in sun-exposed body parts, the prevalence varies among different races and geographical regions. Merkel cell polyomavirus and UV radiation-induced mutations contribute to its etiopathogenesis. The clinical presentation of MCC lacks pathognomonic features and is rarely considered highly at the time of presentation. Histopathological examination frequently reveals hyperchromatic nuclei with high mitotic activity, but immunohistochemistry is required to confirm the diagnosis. Sentinel lymph node biopsy (SLNB) and imaging are advised for effective staging of the disease. Multimodal management including surgery, radiation therapy, and/or immunotherapy are deployed. Traditional cytotoxic chemotherapies may result in an initial response, but do not result in a significant survival benefit. Checkpoint inhibitors have dramatically improved the prognosis of patients with metastatic MCC, and are recommended first-line in advanced cases. There is a need for well-tolerated agents with good safety profiles in patients who have failed immunotherapies.

Machine Learning and Its Application in Skin Cancer.

Artificial intelligence (AI) has wide applications in healthcare, including dermatology. Machine learning (ML) is a subfield of AI involving statistical models and algorithms that can progressively learn from data to predict the characteristics of new samples and perform a desired task. Although it has a significant role in the detection of skin cancer, dermatology skill lags behind radiology in terms of AI acceptance. With continuous spread, use, and emerging technologies, AI is becoming more widely available even to the general population. AI can be of use for the early detection of skin cancer. For example, the use of deep convolutional neural networks can help to develop a system to evaluate images of the skin to diagnose skin cancer. Early detection is key for the effective treatment and better outcomes of skin cancer. Specialists can accurately diagnose the cancer, however, considering their limited numbers, there is a need to develop automated systems that can diagnose the disease efficiently to save lives and reduce health and financial burdens on the patients. ML can be of significant use in this regard. In this article, we discuss the fundamentals of ML and its potential in assisting the diagnosis of skin cancer.

Use of 816 Consecutive Burn Wound Biopsies to Inform a Histologic Algorithm for Burn Depth Categorization.

Burn experts are only 77% accurate when subjectively assessing burn depth, leaving almost a quarter of patients to undergo unnecessary surgery or conversely suffer a delay in treatment. To aid clinicians in burn depth assessment (BDA), new technologies are being studied with machine learning algorithms calibrated to histologic standards. Our group has iteratively created a theoretical burn biopsy algorithm (BBA) based on histologic analysis, and subsequently informed it with the largest burn wound biopsy repository in the literature. Here, we sought to report that process. This was an IRB-approved, prospective, multicenter study. A BBA was created a priori and refined in an iterative manner. Patients with burn wounds assessed by burn experts as requiring excision and autograft underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn biopsies were histologically assessed for presence/absence of epidermis, papillary dermis, reticular dermis, and proportion of necrotic adnexal structures by a dermatopathologist using H&E with whole slide scanning. First degree and superficial second degree were considered to be burn wounds likely to have healed without surgery, while deep second- and third-degree burns were considered unlikely to heal by 21 days. Biopsy pathology results were correlated with still photos by five burn experts for consensus of final burn depth diagnosis. Sixty-six subjects were enrolled with 117 wounds and 816 biopsies. The BBA was used to categorize subjects' wounds into four categories: 7% of burns were categorized as first degree, 13% as superficial second degree, 43% as deep second degree, and 37% as third degree. Therefore, 20% of burn wounds were incorrectly judged as needing excision and grafting by the clinical team as per the BBA. As H&E is unable to assess the viability of papillary and reticular dermis, with time our team came to appreciate the greater importance of adnexal structure necrosis over dermal appearance in assessing healing potential. Our study demonstrates that a BBA with objective histologic criteria can be used to categorize BDA with clinical misclassification rates consistent with past literature. This study serves as the largest analysis of burn biopsies by modern day burn experts and the first to define histologic parameters for BDA.

Advances and Considerations in the Management of Actinic Keratosis: An Expert Consensus Panel Report.

BACKGROUND: Actinic Keratosis (AK) is a potentially pre-malignant tumor with a poorly defined risk of progression to invasive squamous cell carcinoma (SCC). Because of the typical need for recurrent cycles of AK treatment, outcomes can be limited by both therapeutic efficacy and patient adherence. OBJECTIVE: To synthesize the available and most current literature into overarching principles to provide guidance on the management of AKs, improving patient experiences and treatment outcomes. METHODS: A systematic review querying epidemiology, natural history, prognosis, management of AKs as well as the mechanism of action of and adherence to current AK therapy was conducted. After reviewing the literature, an expert consensus panel consisting of 10 expert dermatologists and dermatopathologists used a modified Delphi process to develop statements regarding the pathogenesis and management of AKs. Final statements were only adopted with a supermajority vote (≥7/10). RESULTS: The panel developed 7 consensus statements regarding AKs pathogenesis and management. CONCLUSION: The poorly defined risk for AK progression into invasive SCC without universally accepted clinical-histopathological factors highlights the importance of long-term efficacious treatment. To effectively counsel and treat patients with actinic keratoses, dermatologists must understand how newer therapeutic approaches with mechanisms of action that have more rapid onset of action, shorter treatment courses, and less intense local skin reaction (LSRs) may promote adherence and improve long-term outcomes. J Drugs Dermatol. 2021;20(8):888-893. doi:10.36849/JDD.6078 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Scurvy and Tinea Corporis Simulating Leukocytoclastic Vasculitis.

ABSTRACT: Leukocytoclastic vasculitis (LCV) is a small vessel inflammatory condition considered to be caused by circulating immune complexes and often occurs after an acute infection or exposure to a new medication, although it may be associated with an underlying systemic disease or be idiopathic in nature. It is important to determine the etiology, identify the extent of the disease for early intervention and appropriate management, and treat and/or eliminate the underlying cause. Here, we report cases of scurvy and tinea corporis that presented with histopathologic features of LCV and had significant clinical improvement with treatment of the underlying etiologies. These cases emphasize that histopathologic features of early evolving LCV may be seen in other settings including scurvy and tinea corporis. Appropriate treatment of the underlying condition is important for optimized patient management.

Characterization of ALTO-encoding circular RNAs expressed by Merkel cell polyomavirus and trichodysplasia spinulosa polyomavirus.

Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions, including serving as messenger RNAs that are translated into peptides. Here we describe circular RNAs generated by human polyomaviruses (HPyVs), some of which encode variants of the previously described alternative large T antigen open reading frame (ALTO) protein. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N6-methyladenosine (m6A) modified. The translation of MCPyV circALTOs into ALTO protein is negatively regulated by MCPyV-generated miRNAs in cultured cells. MCPyV ALTO expression increases transcription from some recombinant promoters in vitro and upregulates the expression of multiple genes previously implicated in MCPyV pathogenesis. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation in MCPyV-negative cells. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and infected tissues and express proteins that have the potential to modulate the infectious and tumorigenic properties of these viruses.