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Patients with a history of or a predisposition to autoimmune or collagen vascular diseases are inclined to develop drug-induced subacute cutaneous lupus erythematosus (SCLE) due to terbinafine therapy. Here, we report a case of terbinafine-induced SCLE in a male patient, although classic SCLE most commonly affects females, and he did not have a diagnosis of or a history suggestive of a predisposition to autoimmune or collagen vascular diseases. Although the mechanism for terbinafine-induced SCLE has not been fully elucidated, we suggest that there may be distinctive mechanisms of terbinafine-induced SCLE of patients with and without a predisposition to or history of autoimmune or connective tissue diseases, which should be a focus of future research.

Malignant melanoma and particularly metastatic melanoma represent a diagnostic challenge due to the wide variety of histologic patterns, resemblance to benign entities, and extensive range of clinical presentations. A high index of suspicion for melanoma is important for accurate diagnosis, especially when there is a previous history of malignancy. Here, we present a patient with a history of melanoma and locally metastatic melanoma, who subsequently developed a nodule on his right forearm near the site of his previous melanoma excision. Histologically, the melanoma appeared as granuloma annulare (GA) with benign cytologic features, but was identified as metastatic melanoma using SOX-10 immunohistochemical staining. Other malignancies, including lymphomas, leukemias, sarcomas, and cutaneous metastases of internal malignancies, have mimicked GA and interstitial granulomatous processes. Therefore, further immunohistochemical staining should be performed to assess for metastatic disease in the setting of a histological pattern that resembles a benign granulomatous process in a patient with a history of malignancy, including malignant melanoma.

Importance: Melanoma is diagnosed in approximately 200,000 people within the US each year and is responsible for more than 6,850 deaths. Currently, clinical suspicion guides biopsy decisions and melanoma is confirmed in approximately 4% of biopsied lesions. A non-invasive two-gene expression test (2-GEP) was shown to enhance the physical exam by evaluating genomic atypia to guide biopsy decisions. This study examines the corresponding histopathology of real-world 2-GEP-positive cases. Methods: Cutaneous lesions suspicious for melanoma (n=3,418) were 2-GEP tested by 90 licensed clinicians in real-world practice. 2-GEP-positive lesions (genomically atypical as indicated by the detection of LINC and/or PRAME) were biopsied in 316 out of 324 (97.5%) cases and 313 pathology reports were available for analysis. Results: Biopsied 2-GEP-positive lesions were separated into diagnostic subgroups based on corresponding pathology reports. The prevalence of melanoma in biopsies of 2-GEP-positive lesions was 18.7%. Gene expression of both LINC and PRAME was present in ever-increasing percentages of melanocytic lesions as pathology reports demonstrated increasing levels of atypia. Notably, 47.5% of the histopathologically-confirmed melanomas demonstrated this double positive genomic signature while 23.7% were single-positive for LINC and 28.8% were single-positive for PRAME. Discussion: These data show that biopsied 2-GEP-positive lesions are enriched almost five-fold for advanced histopathologic features compared to those biopsied based solely on visual assessment criteria. The close correlation between genomic atypia and atypical pathology should be considered when planning treatment of a 2-GEP-positive lesion. Consideration of genomic atypia may be a superior approach to guide biopsy decisions and manage pigmented lesions.

Purpose: A clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. While histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. The development and validation of a 35-gene expression profile (35-GEP) test that accurately differentiates benign and malignant pigmented lesions is described. Methods: Lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. Diagnostic utility of 76 genes was assessed with quantitative RT-PCR; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. To reflect the complex biology of melanocytic neoplasia, the 35-GEP test was developed to include an intermediate-risk zone. Results: Validation of the 35-GEP was performed in an independent set of 273 benign and 230 malignant lesions. The test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk. Conclusions: The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. A test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients.

Isotopic response refers to the occurrence of a new, unrelated cutaneous disease occurring at the same location of a previous healed disease. The etiology of isotopic responses is still not completely understood. Theories have included that viral particles may lead to the development of the second disease, the destruction of nerve fibers by herpes zoster may lead to an indirect influence on the immune system, an alteration of microcirculation from inflammation that causes future insults to localize to the same site, and an exaggerated and atypical hypersensitivity reaction to tissue antigens, viral antigens, or immune complex deposition. A wide variety of disease processes have been reported as the second disease in an isotopic response.Here, we discuss a case of an isotopic response following herpes zoster in which the second disease involved a granuloma annulare (GA)-like inflammatory reaction that resolved and recurred. These findings support the theory that the skin affected by herpes zoster is affected in a way that makes it a focus for the manifestation of further skin diseases.

Social distancing has played an important role in reducing the transmission of COVID-19, and, if the general public uniformly followed social distancing guidelines, we would theoretically expect no new diagnoses of sexually transmitted diseases (STDs) during this time period. However, during the COVID-19 era, we have diagnosed multiple cases of syphilis and molluscum contagiosum histopathologically with an increased incidence in our practice from the dates of March 1 to August 28, 2020, compared with these dates in 2019. The vast majority of these cases were not suspected by referring clinicians. Dermatologists are experts in the recognition of the cutaneous manifestations of venereal diseases which is critical to appropriate diagnosis and management, and they should continue to provide care during this pandemic. Individuals who acquire STDs during this time may increase the strain on already limited health care resources by disregarding social distancing recommendations. All medical providers must consider how we can better encourage individuals to abide by social distancing recommendations, optimize care for patients during the pandemic, and prevent the misallocation of valued health care resources.

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 (g7/10). 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.

Merkel cell carcinoma is a rare cutaneous carcinoma from the tactile Merkel cells. With fewer than half the patients surviving more than one year and fewer than 20% surviving beyond five years. These tumors are rarely suspected until the biopsy results return. Polyoma virus is associated with up to 80% of the tumors. 53% present on the head and neck and 35% present on the extremities while larger lesions are exceedingly rare in either location. Recently, A newly approved drug, Avelumab, has shown tumor response in patients with some patients experiencing complete remission.

Background: Despite the clinical availability and widespread usage of diagnostic and prognostic gene expression profiles (GEP) for the management of melanoma, no recommendations for Appropriate Use Criteria (AUC) exist to guide their integration into clinical practice.Objective: To develop a set of consensus-based AUC recommendations for the use of GEP profiling technology in the diagnosis and management of melanoma in specifically-defined situations commonly encountered by the practicing dermatologist.Methods: A systematic Medline literature search was performed to identify all existing evidence pertinent to the clinical efficacy and utility of three melanoma GEP tests that met the inclusion criteria (validated in peer-reviewed literature, US governmentally approved, and currently widely used) for review. A modified Delphi technique was used to achieve consensus and standard SORT criteria were applied. An expert panel of nine dermatologists/dermatologic surgeons/dermatopathologists developed a set of 29 clinical scenarios for the appropriate use of GEP assays and reviewed the available literature to make evidence-based recommendations for each indication.Results: The 2-GEP assay for melanoma diagnosis received 1 B-strength and 6 C-strength recommendations. The 23-GEP diagnostic test received 1 A-strength, 3 B-strength, and 4 C-strength recommendations. The 31-GEP prognostic assay received 1 A-strength, 7 B-strength, and 6 C-strength recommendations.Conclusions: These AUC recommendations provide an evidence-based framework for the integration of melanoma GEP tests into clinical practice.

Treatment plans for cutaneous melanoma are based upon individual risk of recurrence. Decisions made post-diagnosis include recommendation for a sentinel lymph node biopsy (SLNB), followed by management decisions such as surveillance, frequency of follow-up, and interdisciplinary consultations including possible adjuvant therapy use. These have traditionally been guided by clinicopathologic factors, but discordance exists, as a substantial number of melanoma deaths occur in patients diagnosed with disease considered to be early stage by such factors, including a negative SLNB. Molecular testing can be used to apply an objective approach that optimizes individualized patient care. The 31-gene expression profile (31-GEP) test has been validated in nearly 1600 patients as an independent predictor of risk of recurrence, distant metastasis and death in Stage I-III melanoma and can guide SLNB decisions in patient subgroups, as demonstrated in 1421 patients. While clinical use of the 31-GEP test has been adopted into routine practice, an evidence-based analysis of a decision point for use in thin, T1 tumors would be clinically useful. To help define an appropriate population for 31-GEP testing, we evaluated changes in patient management, cumulative differential risk across Breslow thicknesses based on a large dataset, and 31-GEP subclass distribution in a clinically tested cohort. Based on this, appropriate use of the 31-GEP test for management decisions was found to be in cutaneous melanoma tumors ≥0.3 mm thick.

Tools that help reduce the number of surgical biopsies performed on benign lesions have the potential to improve patient care. The pigmented lesion assay (PLA) is a noninvasive tool validated against histopathology that helps rule out melanoma and the need for surgical biopsies of atypical pigmented skin lesions. Genetic information is collected using adhesive patches and the expression of two genes, LINC and PRAME, is measured. By using genetic material collected noninvasively and to further validate the PLA, somatic hotspot mutations in genes known to be drivers of early melanoma development (BRAF other than V600E, NRAS, and the TERT promoter) can also be identified. The frequency of these hotspot mutations in samples of early melanoma was 77%, which is higher than the 14% found in nonmelanoma samples (P0.0001). TERT promoter mutations were the most prevalent mutation type in PLA-positive melanomas; 82% of PLA-negative lesions had no mutations, and 97% of histopathologically confirmed melanomas were PLA and/or mutation positive (cohort 1, n = 103). Mutation frequencies were similar in prospectively collected real-world PLA samples (cohort 2, n = 519), in which 88% of PLA-negative samples had no mutations. Combining gene expression and mutation analyses enhances the ability to noninvasively detect early cutaneous melanoma.

Recommended guidelines for sentinel lymph node biopsy, follow-up, and surveillance for cutaneous melanoma are based upon clinicopathologic staging. In effect, the accuracy of melanoma staging to estimate metastatic risk is critical to subsequent care, neither under-treating or over-treating the patient based on their tumor. Traditional staging continues to evolve based on additional data regarding clinicopathologic features and clinical outcomes. However, such features are subject to inter-observer variability, which puts a limit on their ability to improve prognostication. Reported discordance rates between initial and subsequent pathology review consistently impact both staging and disease management. Newer molecular techniques, such as gene expression profiling, can be used to help define the biology of the primary melanoma tumor and the best course of action after definitive surgical treatment.

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.

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., Author summary Human polyomaviruses (HPyV) have been linked to diseases including Merkel cell carcinoma (MCC), a skin cancer caused by Merkel cell polyomavirus (MCPyV), and skin and hair eruptions caused by trichodysplasia spinulosa polyomavirus (TSPyV). We discover that HPyVs generate single-stranded, circular RNAs (circRNAs) in affected tissues. Both MCPyV and TSPyV generate circRNAs encompassing part of the early region (circALTOs) that can be translated to the alternative large T antigen open reading frame (ALTO) protein in cultured cells. Previously described microRNAs (miRNAs) generated by MCPyV have the ability to inhibit the expression of ALTO. MCPyV circALTOs are enriched in extracellular vesicles produced by MCC cell lines and cells that express circALTO. Finally, we discover that MCPyV ALTO protein enhances transcription from some recombinant promoters and promotes the expression of multiple host cell genes previously implicated in MCPyV pathogenesis. Thus, HPyVs generate circRNAs, including circALTOs that are translated to ALTO protein, and MCPyV ALTO has the ability to regulate transcription.

As a result of increasing melanoma incidence and challenges with clinical and histopathologic evaluation of pigmented lesions, noninvasive techniques to assist in the assessment of skin lesions are highly sought after. This review discusses the methods, benefits, and limitations of adhesive patch biopsy, electrical impedance spectroscopy (EIS), multispectral imaging, high-frequency ultrasonography (HFUS), optical coherence tomography (OCT), and reflectance confocal microscopy (RCM) in the detection of skin cancer. Adhesive patch biopsy provides improved sensitivity and specificity for the detection of melanoma without a trade-off of higher sensitivity for lower specificity seen in other diagnostic tools to aid in skin cancer detection, including EIS and multispectral imaging. EIS and multispectral imaging provide objective information based on computer-assisted diagnosis to assist in the decision to biopsy and/or excise an atypical melanocytic lesion. HFUS may be useful for the determination of skin tumor depth and identification of surgical borders, although further studies are necessary to determine its accuracy in the detection of skin cancer. OCT and RCM provide enhanced resolution of skin tissue and have been applied for improved accuracy in skin cancer diagnosis, as well as monitoring the response of nonsurgical treatments of skin cancers and the determination of tumor margins and recurrences. These novel approaches to skin cancer assessment offer opportunities to dermatologists, but are dependent on the individual dermatologist's comfort, knowledge, and desire to invest in training and implementation of noninvasive techniques. These noninvasive modalities may have a role in the complementary assessment of skin cancers, although histopathologic diagnosis remains the gold standard for the evaluation of skin cancer.

Low-grade neuroendocrine tumors (NETs), also known as carcinoid tumor, commonly arise from the gastrointestinal (GI) and pulmonary tracts, but rarely occur in the skin. Cutaneous NET typically occurs as metastases or high-grade primary lesions, called Merkel cell carcinoma. In the few cases described in literature, primary low-grade neuroendocrine carcinomas of the skin (LGNECS) are usually indolent cutaneous nodules, presenting on the head and trunk of elderly patients. LGNECS tumors are histologically similar to its counterparts arising in other anatomic locations. As there is no NET cut-off for the skin due to their rarity, the GI scale was used instead; low-grade NETs have a Ki-67 proliferative index of less than 3%. The distinction between primary and metastatic NET, however, is not absolute and can be difficult. A primary vs metastatic NET diagnosis relies on clinical exclusion of a NET in other, more common, anatomic locations. Here, we present a case of an LGNECS on the scalp of a 72-year-old female patient. Whole body imaging failed to identify any octreotide-avid lesions elsewhere in the patient, aside from 2 positive cervical lymph nodes, which were confirmed with a node dissection and histologic evaluation. This is the 19th reported case of LGNECS and the 2nd reported case of LGNECS with nodal metastasis.

The COVID-19 pandemic has led to numerous challenges in dermatology. Here, we discuss our experience of diagnosing multiple metastatic cutaneous cancers during the COVID-19 era and consider how perceived and existing barriers for patients receiving dermatologic care in the pandemic may have led to the progression of cancer. In Texas, the attorney general issued a statement that dermatologists could not perform “routine” procedures. Unfortunately, many dermatologists delayed biopsies and surgeries for skin cancer due to misinterpreting the ambiguous nature of the term “routine.” Dermatologists provide valuable expertise and crucial services to society at all times, including during life-threatening pandemics, and this should be emphasized to the public and governmental agencies.

No Abstract Available

The Pigmented Lesion Assay (PLA, sensitivity 91-95%, specificity 69-91%, negative predictive value ?99%) is a commercially available, non-invasive gene expression test that helps dermatologists guide pigmented lesion management decisions and rule out melanoma. Earlier studies have demonstrated high clinical utility and no missed melanomas in a 3-6-month follow-up period. We undertook the current investigations to provide 12-month follow-up data on PLA(-) tests, and to further confirm utility. A 12-month chart review follow-up of 734 pigmented lesions that had negative PLA results from 5 US dermatology centers was performed. Thirteen of these lesions (1.8%) were biopsied in the follow-up period and submitted for histopathologic review. None of the lesions biopsied had a histopathologic diagnosis of melanoma. The test's utility was studied further in a registry (N=1575, 40 US dermatology offices, 62 participating providers), which demonstrated that 99.9% of PLA(-) lesions were clinically monitored, thereby avoiding a surgical procedure, and 96.5% of all PLA(+) lesions were appropriately biopsied, most commonly with a tangential shave. This long-term follow-up study confirms the PLA's high negative predictive value and high utility in helping guide the management of pigmented lesions to avoid unnecessary surgical procedures.

Early diagnosis and treatment of melanoma improve survival. New technologies are emerging that may augment the diagnosis, assessment, and management of melanoma but penetrance into everyday practice is low. In the current health care climate, greater emphasis will be placed on the incorporation of technology for clinically suspicious pigmented lesions to facilitate better, more cost-effective management.

Actinic (solar) keratoses (AK) have the potential for malignant transformation and are the second most common diagnosis in dermatologic practices. No well-established clinical criteria are available to determine which AK are more likely to undergo malignant transformation; therefore, many dermatologists utilize field-directed approaches to treat all visible and subclinical AK on an affected skin surface. Current topical therapeutic agents require lengthy treatment regimens and are less well tolerated than many newer and investigational agents. We review and compare the efficacy and tolerability of well-established topical agents for the management of AK in the United States including 5-fluorouracil, imiquimod 5 % cream as well as the newer 2.5 and 3.75 % formulations, diclofenac 3 % gel, photodynamic therapy, and the recently approved ingenol mebutate gel and discuss the therapeutic potential of investigational agents. Cryotherapy and 5-fluorouracil are efficacious at treating AK but less tolerable than imiquimod cream, particularly at its lower concentrations. The newer agents, diclofenac gel and ingenol mebutate, appear to be more tolerable than cryotherapy and 5- fluorouracil; however, comparative studies regarding efficacy are not available.

Background Human polyomavirus (HPyV)6 and HPyV7 are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective We determined whether biopsy specimens showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods We screened biopsy specimens showing "peacock plumage" histology by polymerase chain reaction for HPyVs. Cases positive for HPyV6 or HPyV7 were then analyzed by immunohistochemistry, electron microscopy, immunofluorescence, quantitative polymerase chain reaction, and complete sequencing, including unbiased, next-generation sequencing. Results We identified 3 additional cases of HPyV6 or HPyV7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared with normal-appearing skin and the identification of intact virions by both electron microscopy and next-generation sequencing support a role for active viral infections in these skin diseases. Limitation This was a small case series of archived materials. Conclusion We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a distinctive histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses."

It is well documented that histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature has been clinically validated as an adjunctive diagnostic test to differentiate benign nevi from malignant melanomas. This study aimed to quantify the impact of this test on diagnosis and treatment recommendations made by dermatopathologists. Diagnostically challenging melanocytic lesions encountered during routine dermatopathology practice were submitted for gene expression testing and received a melanoma diagnostic score (MDS). Submitting dermatopathologists completed a survey documenting pre-test diagnosis, level of diagnostic confidence, and recommendations for treatment. The survey was repeated after receiving the MDS. Changes between the pre- and post-test surveys were analyzed retrospectively. When the MDS was available as part of a comprehensive case evaluation in diagnostically challenging cases, definitive diagnoses were increased by 56.6% for cases that were initially indeterminate and changes in treatment recommendations occurred in 49.1% of cases. Treatment recommendations were changed to align with the test result in 76.6% of diagnostically challenging cases. The MDS impacts diagnosis and treatment recommendations by dermatopathologists confronted with diagnostically challenging melanocytic lesions. Increased data are needed in order to completely understand how use of the MDS will translate from dermatopathology to clinical practice.

Pleuroparenchymal fibroelastosis (PPFE) is a rare progressive disease that manifests as parenchymal fibrosis of the upper lobe and pleura. Approximately 100 cases have been reported. Cutaneous manifestations of PPFE have not previously been described. Diagnosis is dependent on histologic identification of fibrosis with atypical elastic fibers, necessitating an invasive peripheral lung wedge biopsy.A 68-year-old male with a history of pleuroparenchymal fibroelastosis presented with an asymptomatic, telangiectatic erythematous eruption on bilateral lower extremities. Biopsies demonstrated a subtle perivascular infiltrate with marked increase in atypical elastic fibers, similar to the elastosis in the patient's lungs.This is the first documented case of cutaneous manifestations in PPFE. Clinicians need to be aware that cutaneous eruptions clinically simulating telangiectasia macularis eruptiva perstans but lacking a mast cell infiltrate histologically, may have increased abnormal elastic fibers. Thus, early recognition of these lesions in patients with an undefined restrictive lung disorder, may facilitate the diagnosis of PPFE in some patients.

BACKGROUND Recently, a 23‐gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. METHODS A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. RESULTS The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. CONCLUSIONS These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617–628. © 2016 American Cancer Society., A 23‐gene signature has recently been developed to differentiate malignant and benign melanocytic lesions. This study shows that the gene expression signature differentiates benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5% in comparison with a triple‐concordant histopathologic review.

The mitotic rate (MR) of malignant melanoma (MM) refers to the number of mitoses per square millimeter. Studies have suggested that it is an independent prognostic variable predicting survival in patients with MM, and it was recently included in the American Joint Committee on Cancer (AJCC) recommendations for diagnosis and treatment of MM. The AJCC melanoma staging committee recommends using the "hot-spot" approach to determine the MR, whereby it is reported as the maximum dermal mitotic figures identified in a 1-mm area of the melanoma. The AJCC has recommended that the MR be determined in all melanomas, irrespective of Breslow depth or other features. We aimed to quantify the MR in MM ≤1 mm in thickness and to identify statistical associations between the MR, Breslow depth, and Clark level. In addition, we hoped to identify practical issues in determining the MR via the hot-spot technique. We conducted a prospective study to determine the MR, Breslow depth, and Clark level in MM ≤1 mm in thickness. Seven melanomas were identified with epidermal mitoses only (7.4%). Sixteen melanomas had dermal mitoses (16.8%); of these, the majority (75.0%) contained only one mitotic figure. Seventy-nine melanomas had no dermal mitoses (83.2%). Seven lesions (7.4%) demonstrated multiple mitoses; 4 with ≥2 dermal mitoses/mm and 3 with multiple epidermal mitoses. We conclude that thin MM with >1 mitosis/mm is rare and discuss practical and theoretical issues with determining the MR using the hot-spot approach.

Most actinic keratoses (AKs) respond to standard treatments, but a subset persist and require further intervention. We report a series of 10 patients with AKs that failed to respond to conventional treatment with cryotherapy and topical monotherapy but responded completely to simultaneous therapy with topical 5-fluorouracil (5-FU) and imiquimod creams.To report the success of this combination therapy in refractory AKs and to determine whether any clinical or histologic features predict for treatment resistance.Case-control study with two control groups matched to each patient according to lesion location and sex.Mean lesion diameter (p.001), lesion diameter greater than 1 cm (p.001), and the presence of pain (p = .01) were statistically associated with failure of cryotherapy and topical monotherapy. None of the histologic features evaluated were found to be statistically significant, although thicker epidermis was nearly so (p = .054).In patients who have failed standard therapy for AKs, combination treatment using topical 5-FU and imiquimod cream may be an effective alternative therapeutic strategy. Larger lesion diameter, specifically greater than 1 cm, and the presence of pain predict conventional treatment resistance.

Cutaneous atrophic conditions are typically caused by changes in the dermis or subcutaneous tissue, sometimes consisting of the loss of a single fiber type. Since a significant decrease of subepidermal tissue is necessary for these lesions to be macroscopically atrophic, many conditions may not be appreciated as atrophy in the clinical setting. Clinicians should be familiar with the common or classic disorders causing cutaneous atrophy; however, there are a few new or rarely described atrophic conditions which are more difficult to identify and may not be atrophic clinically. This paper serves to describe the salient clinical and histological features of these new or rare disorders.

The 7th edition of the AJCC Cancer Staging Manual represents a dramatic shift in the way that cutaneous squamous cell carcinoma (cSCC) is staged, in that it is first attempt to incorporate evidence-based medicine into the staging guidelines for cSCC. In our opinion, the changes made to the seventh edition represent a significant improvement over previous editions and will ultimately lead to improved patient stratification, more accurate prognostic data, and a better framework to guide clinical decision making. However, there are a number of issues within the latest guidelines that require clarification or are impractical for clinical practice. The purpose of this paper is to highlight the key changes to the 6th edition staging manual as they pertain to cSCC, to point out impractical component of the 7th edition and/or aspects that require further clarification, and to make recommendations that address any current shortcomings to improve subsequent editions. Specific focus will be given to the inclusion of separate guidelines for cSCC and Merkel cell carcinoma (MCC), the incorporation of high-risk factors as modifiers of T stage, the addition of new guidelines for advanced T stage, and the changes in stratification of lymph node status. This paper is modified from a more comprehensive treatment of the staging of nonmelanoma skin cancer by Warner and Cockerell entitled“The new 7th edition American joint committee on cancer staging of cutaneous nonmelanoma skin cancer: a critical review,”in the American Journal of Clinical Dermatology (paper accepted, pending publication).

not available. Disclosures: Study sponsored by Dermtech. Copyright 2018 SKIN

Skin cancers may be derived from any part of the skin, and the classification of all variants is extensive. Overall they are the most common cancers of the body, and include those that are highly mortal and those that are associated with an increased morbidity. In this review the most common skin cancers confronted by the clinician and their management are discussed. New associations are highlighted, as well as new information that can help the clinician to better understand the pathogenesis of many of these entities.

Dermatofibrosarcoma protuberans is a rare, malignant, slow-growing, locally invasive tumor of the skin. Although most cases are acquired and diagnosed in adulthood, there have been an increasing number of congenital dermatofibrosarcoma protuberans mimicking benign birthmarks described in the literature. The clinical presentation of this tumor is often one of an indurated exophytic plaque or nodule; however, a rare variant can present as atrophic or sclerotic in nature. We report a case of congenital atrophic dermatofibrosarcoma protuberans of the groin in a 7-month-old boy, successfully treated with Mohs micrographic surgery.

The development of pityriasis rubra pilaris (PRP) in three patients with human immunodeficiency virus (HIV) infection is described. Two of the patients had onset of severe generalized cystic acne concomitant with their development of PRP. PRP and acne conglobata should be added to the group of cutaneous disorders that can present in a more virulent manner in the setting of HIV infection. The association of cystic acne with PRP and their response to treatment are discussed.

Bacillary angiomatosis is a recently recognized bacterial infectious disease that is seen mainly in patients with the acquired immunodeficiency syndrome. Including this publication, 45 patients have been described in the medical literature. In this report we describe examples of the clinical presentations of bacillary angiomatosis and review therapeutic strategies.

Dermatoses associated with cutaneous photosensitivity are a group of photodistributed skin eruptions caused or exacerbated by light. Multiple clinical variants of photosensitive dermatoses have been characterized including polymorphous light eruption, chronic actinic dermatitis, solar urticaria, phototoxic and photoallergic dermatitis, reticular erythematous mucinosis, acute cutaneous lupus erythematosus, and dermatomyositis. As there may be significant overlap among the clinical presentation of these conditions, the specific diagnosis of individual photodermatosis relies heavily on characteristic histopathologic features. We present here 5 cases of photodistributed eruptions with virtual absence of histologic epidermal changes and dermal inflammation, yet all were described clinically as being "inflammatory" and erythematous. All cases of this "pauci-inflammatory photodermatitis" presented with photodistributed bright red macular erythema or slightly indurated plaques that developed over a period of weeks to months and clinically resembled photoallergic or phototoxic drug reactions or polymorphous light eruption. Microscopically, however, only very sparse dermal lymphocytic infiltrate was noted with no or minimal epidermal changes. To our knowledge, the observation of clinically evident photodistributed dermatoses that demonstrate such minimal histopathologic findings has not been reported. Clinicians and histologists should be aware of the disparity that may be encountered in this setting, as the clinical features are usually far more impressive than those seen histologically.

BACKGROUND The ability to clinically diagnose actinic keratoses (AKs) lesions has been taken for granted for some time. The importance of the malignant potential of these lesions is well known. However, a recent Phase IV, multicenter study assessing the long-term benefit of aminolevulinic acid-based photodynamic therapy provided a unique opportunity to prospectively examine the clinical histopathologic correlation of AKs. OBJECTIVE The objective was to characterize the histopathology of clinically diagnosed AK lesions in the study population. METHODS Punch biopsies of 220 clinically diagnosed untreated AKs were performed at baseline plus 51 lesions unresponsive to treatment (total, 271). RESULTS Clinical diagnosis and histopathologic findings agreed in 91% (246/271) of the lesions biopsied. The balance of the biopsied lesions were: (1) benign changes 4% (11/271) and (2) occult cutaneous malignancy in 5% (14/271) of the cases, 12 squamous cell carcinomas and 2 basal cell carcinomas. CONCLUSIONS In this study, about 1 in 25 clinically diagnosed AK lesions identified by board-certified dermatologist investigator(s) were occult early-stage squamous cell carcinomas on histologic assessment, a fact surmised by the medical community that until now had not been well quantified. These findings should be considered when clinicians decide how to treat and manage AK patients.

Introduction. Recent advances in molecular biology have helped establish differences between psoriasis and a group of inflammatory skin disorders commonly referred to as eczema. The authors have observed significant overlap between these two conditions such that a distinction between them may not always be made, even with histologic examination of skin biopsy specimens. Objective. To determine how frequently psoriasis patients present features of both psoriasis and eczema. Methods. The authors conducted a prospective analysis of 100 consecutive psoriasis patients in their clinic. Results. The authors found that 20% could be diagnosed as “intermediate,” having lesions with characteristics of both psoriasis and eczema, or a personal history of both. The authors suggest naming this category of inflammatory dermatosis “PsEma”—an overlap condition in which the clinical, histologic, molecular, biologic, and therapeutic responses show characteristics of both psoriasis and eczema.

Decubitus ulcers are a worldwide health care concern affecting tens of thousands of patients and costing over a billion dollars a year. Susceptibility to pressure ulcers comes from a combination of external factors (pressure, friction, shear force, and moisture), and internal factors (e.g. fever, malnutrition, anaemia, and endothelial dysfunction). Often, enough damage is done to create the basis for a decubitus ulcer after as little as 2 h of immobility, a situation which may be difficult to avoid if the patient must undergo prolonged surgery or remain bedridden. Damage owing to pressure may also occur hours before the patient receives medical attention, especially if the patient falls or becomes immobilized owing to a vascular event. Several classification systems for decubitus ulcers have been described, based on where injury first occurs. The histologic progression of decubitus ulcers is a dynamic process involving several stages, each having characteristic histologic features. A team-focused approach integrating all aspects of care, including pressure relief, infection control, nutrition, and surgery, may improve healing rates. With accurate risk assessment and preventative care, we can hope to minimize complications and mortality owing to decubitus ulcers.

Background Partial regression of primary cutaneous malignant melanoma is not uncommon and may predict a higher likelihood of metastasis and decreased survival. Complete histologic regression of a primary cutaneous melanoma is a rarer occurrence, with only 34 cases reported in the English-language or English language–summarized literature. Observation We detail 4 cases of complete histologic regression of primary cutaneous melanoma, discovered at presentation with metastatic disease. A pigmented lesion or its remnant, coupled with historical information, was strongly suggestive of cutaneous melanoma. Histologic examination of the lesions, using multiple levels and immunohistochemical stains, failed to reveal residual melanoma. Our cases are typified by the presence of metastasis of melanoma to regional lymph nodes, with the absence of other suspect skin lesions or malignancies. In addition, we present a fifth case involving a completely regressed lesion on the scalp in a patient with cerebral melanoma metastasis and comment on the implications of this case to accepted diagnostic criteria, proposing that consideration of modification to the criteria be entertained. Conclusion The concept of completely regressed primary cutaneous melanoma is reviewed and the literature critically appraised. When one considers a diagnosis of completely regressed primary cutaneous melanoma, cases must be well documented and biopsy proven. Patients with metastatic melanoma and an occult primary lesion require a thorough skin examination, with serious consideration given to the possibility of completely regressed cutaneous melanoma.

The gross and microscopic analysis of skin lesions at autopsy can help the pathologist understand diseases and injuries inflicted premortem, perimortem, or postmortem. From January 2003 to January 2004, skin findings at autopsy were closely examined by a dermatologist and sampled for microscopic analysis at the Southwestern Institute of Forensic Sciences. Dermatologic abnormalities in some of these cases led to the discovery of internal disease and allowed for a more complete understanding of the pathologic disease processes affecting the individual. We present four autopsy cases with skin manifestations of internal disease, including pseudoxanthoma elasticum, calciphylaxis, the sign of Leser Trelat, and papular mucinosis, and demonstrate the usefulness of the dermatological assessment at autopsy. In all cases, discovery of these skin lesions and internal disease manifestations allowed contributing factors to the death of the individual to be uncovered.

Background: Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm that has the potential for aggressive local growth and destruction if not treated appropriately. Although the storiform arrangement of spindle cells in DFSP is relatively characteristic, histologic patterns simulating other benign as well as malignant neoplasms such as dermatofibroma, neurofibroma, malignant fibrous histiocytoma, and atypical fibroxanthoma have been described. Methods: We collected and analyzed six cases of probable DFSP in which a specific diagnosis could not be rendered due to the predominant neurofibromatous changes in the histologic sections. In an attempt to reach a definitive diagnosis, the clinical history and physical characteristics of the lesions were taken into account, and all cases were further evaluated using immunostaining for CD34 and S-100 protein. Results: The average age of the patient was 56 years (range 21–80), and the male to female ratio was 1 : 1. The location of lesions included the scalp, neck, back, and abdomen. All cases displayed two distinct histological patterns: (i) a proliferation of spindle cells with wavy nuclei in a loose mucinous stroma suggesting neural differentiation and (ii) a proliferation of spindle cells which interweaved and filled the reticular dermis extending into the subcutis. The wide variety of clinical impressions and descriptions indicated that the diagnoses were not always straightforward, and clinical information did not always assist in the clinicopathologic correlation. All lesions stained positively for CD34; however, three of six cases also stained positively for S-100. The three cases which were CD34 positive and S-100 negative were likely DFSP, and this was the final diagnosis given. The three cases that were CD34 and S-100 positive did not allow for a straightforward diagnosis. Conclusions: DFSP may demonstrate areas with features more characteristic of a benign neural lesion, such as a neurofibroma, which can lead to underdiagnosis and subsequent failure to treat. Clinicians and pathologists should recognize this potential diagnostic pitfall and understand that equivocal clinical information, combined with non-specific immunohistochemical staining patterns, can further complicate the dilemma. In these situations, where DFSP is the likely diagnosis but definitive evidence cannot be obtained, full excision of the lesion should be recommended to avoid mistreatment of a potentially malignant lesion.

Degos' disease is described as a rare disorder, with approximately 100 cases detailed in the literature. Nearly all are characterized by the near "pathognomonic" appearance of porcelain-white, atrophic papules with peripheral erythema and telangiectases. Many Degos' disease variants have been described including benign cutaneous Degos' disease, familial Degos' disease, atrophie blanche with Degos'-like features, and connective tissue diseases with similar findings. The course, prognosis, and treatment have substantially varied. We present four patients: the first carries a diagnosis compatible with classic Degos' disease, the second and third demonstrate cutaneous and histological findings of Degos' disease but laboratory evidence suggestive of lupus erythematosus, while the fourth has dermatomyositis with Degos'-like lesions. Because of broad overlap in clinical and histological findings, we contend that Degos' disease may not be a specific entity, but rather, may represent a common end point to a variety of vascular insults, many of which have not been fully elucidated.

Sclerotic fibroma was first described in association with Cowden's disease by Weary et al. in 1972. In 1989, Rapini and Golitz detailed 11 cases of solitary sclerotic fibroma (SFS) in the absence of Cowden's disease, suggesting the term SFS of the skin. Classic histological features include hypocellular, hyalinized bands of collagen sharply demarcated from the surrounding skin. Numerous authors have described sclerotic fibroma-like changes in other entities including melanocytic nevi, dermatofibromas, lipomas, tendon sheath fibromas, giant cell collagenomas, neurofibromas, angiofibromas, erythema elevatum diutinum, and folliculitis. Dissension has arisen, with some dermatopathologists asserting that sclerotic fibroma is just an evolutionary end-point of a previous lesion. Others contend that SFS is a distinct lesion and cite recurrent cases and/or proliferation marker studies to corroborate this view. We detail the histopathological findings of lesions consistent with the classic description of SFS and compare these to sclerotic changes observed in an intradermal nevus, blue nevus, erythema elevatum diutinum, neurofollicular hamartoma, angiofibroma, neurofibroma, accessory nipple, and dermatofibromas. Sclerotic fibroma-like change may be seen in a variety of lesions and may represent a common reaction pattern in the skin.