Hemorrhagic Bullous Lichen Sclerosus: A Case Report.

BACKGROUND Lichen sclerosus (LS) is a chronic autoimmune dermatosis characterized by white, sclerotic, atrophic plaques. Classic LS commonly occurs in the anogenital region, while extragenital lichen sclerosis typically occurs on the trunk and proximal extremities. Bullous lichen sclerosus is a rare variant that can occur in both genital and extragenital LS. Flaccid bullae can form, which may become hemorrhagic and produce a characteristic appearance clinically. CASE REPORT In this report, we describe the case of a 63-year-old female patient who presented for evaluation of a rapidly growing, erythematous, scaly growth on her back/shoulder that was biopsied and found to be hemorrhagic bullous LS. We will discuss the clinical and histologic features of this case as well as treatment of bullous LS, which in this case was a topical high-potency corticosteroid. CONCLUSIONS Bullous LS has been poorly studied due to the rarity of the condition, with limited investigation of the clinical and histopathologic characteristics of bullous LS and the available treatment options. Although rare, extragenital LS with hemorrhagic bullous features is an important variant of LS that should be considered to ensure appropriate diagnosis and treatment.

Mystery burns and nocturnal seizure safety.

Thermal burn injuries are common and are associated with physical and psychologic repercussions. For epileptic patients, the risk for environmental injuries is remarkably higher. We present 2 cases of thermal burn injuries following nocturnal seizures. Many epileptic patients are educated on ways to prevent injury; however, these safety precautions tend to focus primarily on daytime activities. We highlight the potential presentation and impacts of the thermal lesions. In addition, we offer suggestions for improvements in patient education and injury prevention.

Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin.

UVB wavelengths of light induce the formation of photoproducts in genomic DNA that are potentially mutagenic and detrimental to epidermal cell function. The mineralocorticoid and androgen receptor antagonist spironolactone (SP) was recently identified as an inhibitor of UV photoproduct removal in human cancer cells in vitro via its ability to promote the rapid proteolytic degradation of the DNA repair protein XPB. Using normal human keratinocytes in vitro and skin explants ex vivo, we found that SP rapidly depleted XPB protein in both systems and abrogated two major responses to UVB-induced DNA damage, including the removal of UV photoproducts from genomic DNA and the activation of ATR/ATM DNA damage kinase signaling. These effects were also correlated with both mutagenesis and a predisposition to UVB-induced cell death but were unique to SP, because neither the SP metabolites canrenone and 7α-thiomethylspironolactone nor the more specific mineralocorticoid receptor antagonist eplerenone affected XPB protein levels or the UVB response. Our findings provide an approach for studying XPB and its roles in the UVB DNA damage response in human skin ex vivo and indicate that SP may increase UVB mutagenesis and skin cancer risk in certain individuals.

Systemic Platelet-Activating Factor-Receptor Agonism Enhances Non-Melanoma Skin Cancer Growth.

Platelet-activating factor-receptor (PAF-R) agonists are pleiotropic lipid factors that influence multiple biological processes, including the induction and resolution of inflammation as well as immunosuppression. PAF-R agonists have been shown to modulate tumorigenesis and/or tumor growth in various skin cancer models by suppressing either cutaneous inflammation and/or anti-tumoral adaptive immunity. We have previously shown that a chronic systemic PAF-R agonist administration of mice enhances the growth of subcutaneously implanted melanoma tumors. Conversely, chronic topical applications of a PAF-R agonist suppressed non-melanoma skin cancer (NMSC) in a topical chemical carcinogenesis model (dimethylbenz[a]anthracene/phorbol 12-myristate 13-acetate (DMBA/PMA)) in-part via anti-inflammatory effects. These results indicate that the context of PAF-R agonist exposure via either chronic cutaneous or systemic administration, result in seemingly disparate effects on tumor promotion. To further dissect the contextual role of PAF-R agonism on tumorigenesis, we chronically administered systemic PAF-R agonist, carbamoyl-PAF (CPAF) to mice under a cutaneous chemical carcinogenesis protocol, recently characterized to initiate both NMSC and melanocytic nevus formation that can progress to malignant melanoma. Our results showed that while systemic CPAF did not modulate melanocytic nevus formation, it enhanced the growth of NMSC tumors.

Diagnostic Performance of Deep Learning Algorithms Applied to Three Common Diagnoses in Dermatopathology.

BACKGROUND: Artificial intelligence is advancing at an accelerated pace into clinical applications, providing opportunities for increased efficiency, improved accuracy, and cost savings through computer-aided diagnostics. Dermatopathology, with emphasis on pattern recognition, offers a unique opportunity for testing deep learning algorithms. AIMS: This study aims to determine the accuracy of deep learning algorithms to diagnose three common dermatopathology diagnoses. METHODS: Whole slide images (WSI) of previously diagnosed nodular basal cell carcinomas (BCCs), dermal nevi, and seborrheic keratoses were annotated for areas of distinct morphology. Unannotated WSIs, consisting of five distractor diagnoses of common neoplastic and inflammatory diagnoses, were included in each training set. A proprietary fully convolutional neural network was developed to train algorithms to classify test images as positive or negative relative to ground truth diagnosis. RESULTS: Artificial intelligence system accurately classified 123/124 (99.45%) BCCs (nodular), 113/114 (99.4%) dermal nevi, and 123/123 (100%) seborrheic keratoses. CONCLUSIONS: Artificial intelligence using deep learning algorithms is a potential adjunct to diagnosis and may result in improved workflow efficiencies for dermatopathologists and laboratories.

Early assessment of burn severity in human tissue ex vivo with multi-wavelength spatial frequency domain imaging.

Early knowledge about burn severity and depth can lead to improved outcome for patients. In this study, we investigated the change in optical properties in ex vivo human skin following thermal burn injuries. Human skin removed during body contouring procedures was subjected to thermal burn injury for either 10 or 60 s. Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on each sample and the optical properties (absorption and scattering parameters) were obtained at each wavelength. Multi-wavelength fitting was used to quantify absorption and scattering parameters, and these parameters were compared to histologic assessments of burn depth related to burn severity. Our results indicated substantial changes in optical scattering parameters and these changes correlated well with the burn severity and depth, and fit closely with previously reported studies using porcine in vivo models. This study provides the characterization of thermal burn injury on human skin ex vivo by using the optical method of SFDI with high sensitivity and specificity. This preclinical human model system without live animals could have uses in testing the imaging parameters of other skin injuries, including from caustic agents.

Frequent expression of fibroblast growth factor-23 (FGF23) mRNA in aneurysmal bone cysts and chondromyxoid fibromas.

Osteomalacia has multiple aetiologies including the least common, tumour-induced osteomalacia (TIO). Recently, most cases of TIO have been confirmed to be due to phosphaturic mesenchymal tumour of mixed connective tissue type (PMTMCT). Most cases of TIO are the result of production of the fibroblast growth factor-23 (FGF-23) by the tumour. The authors recently showed reverse transcriptase PCR (RT-PCR) for FGF-23 to be valuable in the diagnosis of PMTMCT. However, the authors also noted FGF-23 expression in some cases of aneurysmal bone cyst (ABC) and chondromyxoid fibroma (CMF). For the present study, the authors studied FGF-23 expression by RT-PCR in 19 cases of ABC and eight cases of CMF, all with typical clinical and radiographic features and without evidence of TIO. Seven of 16 (44%) ABC and two of seven (29%) CMF were positive for FGF-23. These results confirm that ABC and CMF not uncommonly express FGF-23. These results strongly suggest caution and careful integration with all other clinical and radiographic data in the use of FGF-23 RT-PCR for the diagnosis of PMTMCT.

Pathologic and clinical features of Hodgkin lymphoma--like posttransplant lymphoproliferative disease.

Because of its rarity, pathologic and clinical features of Hodgkin lymphoma-like posttransplant lymphoproliferative disorder (HL-like PTLD) are not well understood, and it is unclear whether its biological behavior is more closely related to classical Hodgkin disease or to monomorphic B-cell PTLD. The authors compared 6 cases of HL-like PTLD with 5 cases of monomorphic B-cell PTLD for differences in histology, immunophenotype, and clinical behavior. Histologically, all cases of HL-like PTLD resembled classical HL with typical Reed-Sternberg (RS) cells and a cellular background mimicking mixed cellularity subtype. CD45 was absent on RS-like cells, but the expression pattern of B-cell-associated markers Oct-2 and BOB.1 resembled monomorphic B-cell PTLD. Whereas Epstein-Barr virus early RNA expression is normally restricted to RS cells of classical HL, it was expressed in both RS-like cells and background lymphocytes in HL-like PTLD. Although all patients diagnosed with monomorphic B-cell PTLD show no evidence of disease following treatment, half of the patients with HL-like PTLD relapsed or died, indicating a more aggressive clinical behavior. The findings suggest that HL-like PTLD represents a distinct clinicopathologic entity with an aggressive clinical course.

Frictional asymptomatic darkening of the extensor surfaces.

Frictional asymptomatic darkening of the extensor surfaces (FADES), also known as hyperkeratosis of the elbows and knees, is commonly seen by dermatologists but has never been well characterized. Patients present with uniform, asymptomatic, brown darkening over the extensor surfaces of the elbows and knees with minimal scaling. Both frictional stress and family history may play a role in the pathogenesis of this condition. The results of cutaneous biopsy specimens typically reveal hyperkeratosis, acanthosis, and mild papillomatosis with minimal inflammation. Keratolytic agents such as lactic acid and urea cream along with avoiding frictional stress can be effective in the management of this condition. We describe a series of cases of FADES and its etiology and management options.