Widespread presentation and spontaneous regression of porokeratotic eccrine ostial and dermal duct nevus

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon hamartomatous growth with disordered keratinization. The lesions typically appear on the limbs, often at birth or in early childhood, as linearly distributed papules and plaques. We report 4 cases of PEODDN, 2 of which showed significant spontaneous regression

IL-1 Generated Subsequent to Radiation-induced Tissue Injury Contributes to the Pathogenesis of Radiodermatitis

Radiation injury in the skin causes radiodermatitis, a condition in which the skin becomes inflamed and the epidermis can break down. This condition causes significant morbidity and if severe it can be an independent factor that contributes to radiation mortality. Radiodermatitis is seen in some settings of radiotherapy for cancer and is also of concern as a complication post-radiation exposure from accidents or weapons, such as a ‘‘dirty bomb’’. The pathogenesis of this condition is incompletely understood. Here we have developed a murine model of radiodermatitis wherein the skin is selectively injured by irradiation with high-energy electrons. Using this model we showed that the interleukin-1 (IL-1) pathway plays a significant role in the development of radiodermatitis. Mice that lack either IL-1 or the IL-1 receptor developed less inflammation and less severe pathological changes in their skin, especially at later time- points. These findings suggest that IL-1 pathway may be a potential therapeutic target for reducing the severity of radiodermatitis

Sentinel Lymph Node Biopsy Does Not Improve Disease-Specific Survival in Elderly Patients with Intermediate Thickness Melanoma

Objective: To determine whether sentinel lymph node biopsy (SLNB) is associated with improved disease-specific survival among elderly patients with intermediate-thickness melanoma Design: Retrospective cohort study of prospectively-maintained tumor registry Setting: Single institution tertiary care center. P atients: Adults ≥ 70 years of age, who underwent surgical intervention for melanoma from 2000-2013. Main Outcome Measures: The primary outcomes were overall survival (OS) and disease-free survival (DFS). Other clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, presence of adverse features, receipt and result of SLNB, and receipt of completion lymph node dissection (CLND). Results: Ninety-one patients (mean age 80 years, 54% male) underwent wide excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients (71%) went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (Fig. 1A). However, 5-year DFS was 79% in patients who did not receive SLNB and 77% in patients who did receive SLNB (Fig. 1B). Conclusions: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had higher 5-year OS than those who did not receive SLNB. However, the 5-year DFS is similar between the two groups, which suggests that the OS differences are related to non-melanoma factors. Routine SLNB for intermediate-thickness melanoma patients may not significantly change the outcome for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care

Sarcoid-like reaction in a patient recovering from coronavirus disease 19 pneumonia

As coronavirus disease 2019 (COVID-19) cases continue to increase, so do the reported extrapulmonary manifestations of this disease. To date, described dermatologic manifestations of COVID-19 include pernio-like acral nodules, dengue fever–like petechiae, vesiculobullous eruptions, pityriasis rosea and viral-like exanthems, retiform purpura, and livedo reticularis.1 We describe a patient with new-onset, biopsy confirmed sarcoid-like reaction in the setting of COVID-19 pneumonia and postulate a role for this immunologic reaction in hastening disease recovery

YAP/TAZ Activation Drives Uveal Melanoma Initiation and Progression

Uveal melanoma (UM), the most common ocular malignancy, is characterized by GNAQ/11 mutations. Hippo/YAP and Ras/mitogen-activated protein kinase (MAPK) emerge as two important signaling pathways downstream of G protein alpha subunits of the Q class (GalphaQ/11)-mediated transformation, although whether and how they contribute to UM genesis in vivo remain unclear. Here, we adapt an adeno-associated virus (AAV)-based ocular injection method to directly deliver Cre recombinase into the mouse uveal tract and demonstrate that Lats1/2 kinases suppress UM formation specifically in uveal melanocytes. We find that genetic activation of YAP, but not Kras, is sufficient to initiate UM. We show that YAP/TAZ activation induced by Lats1/2 deletion cooperates with Kras to promote UM progression via downstream transcriptional reinforcement. Furthermore, dual inhibition of YAP/TAZ and Ras/MAPK synergizes to suppress oncogenic growth of human UM cells. Our data highlight the functional significance of Lats-YAP/TAZ in UM initiation and progression in vivo and suggest combination inhibition of YAP/TAZ and Ras/MAPK as a new therapeutic strategy for UM

Apocrine-Eccrine Carcinomas: Molecular and Immunohistochemical Analyses

Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH) for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53), 27% (14/51), 16% (8/51), 85% (44/52) and 12% (6/52), respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46). Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%). Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest

Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma

Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver genes affected by CNV has been difficult, as these rearrangements are often contained in large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene by performing comparative oncogenomics of human and zebrafish melanomas. We determined that the gene encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP family, is recurrently amplified and transcriptionally upregulated in melanoma. GDF6-induced BMP signaling maintained a trunk neural crest gene signature in melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting cell death, and promoting tumor growth. GDF6 was specifically expressed in melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were inversely correlated with patient survival. Our study has identified a fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene signature to promote melanoma progression, thus providing potential opportunities for targeted therapy to treat GDF6-positive cancers

Niagara, County of and Niagara County White Collar Employee Unit, CSEA Local 1000, AFSCME, AFL-CIO, Local 832 (2012) (MOA)

Liquid chromatography–tandem mass spectrometry (LC–MS/MS) and multiple reaction monitoring mass spectrometry (MRM-MS) proteomics analyses were performed on eccrine sweat of healthy controls, and the results were compared with those from individuals diagnosed with schizophrenia (SZ). This is the first large scale study of the sweat proteome. First, we performed LC–MS/MS on pooled SZ samples and pooled control samples for global proteomics analysis. Results revealed a high abundance of diverse proteins and peptides in eccrine sweat. Most of the proteins identified from sweat samples were found to be different than the most abundant proteins from serum, which indicates that eccrine sweat is not simply a plasma transudate and may thereby be a source of unique disease-associated biomolecules. A second independent set of patient and control sweat samples were analyzed by LC–MS/MS and spectral counting to determine qualitative protein differential abundances between the control and disease groups. Differential abundances of selected proteins, initially determined by spectral counting, were verified by MRM-MS analyses. Seventeen proteins showed a differential abundance of approximately 2-fold or greater between the SZ pooled sample and the control pooled sample. This study demonstrates the utility of LC–MS/MS and MRM-MS as a viable strategy for the discovery and verification of potential sweat protein disease biomarkers

XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53

Additional file 1. Table S1: Clinicopathologic and molecular characteristics of DLBCL patients with high or low XPO1 expression. Table S2: Significantly differentially expressed genes between XPO1high and XPO1low DLBCL patients with concurrent TP53 mutation and high MYC expression. Figure S1: Biomarker study for XPO1 and selinexor. (A–B) XPO1high expression showed significant adverse prognostic impact in the ABC subtype but not the GCB subtype of DLBCL. (C) XPO1high expression showed a trend of unfavorable prognostic effect on PFS in MYC-rearranged (MYC-R+) DLBCL. (D) XPO1high expression was associated with significantly poorer survival in DLBCL patients with wild type (Wt) TP53. (E) ABC-DLBCL and GCB-DLBCL cells showed similar sensitivity to the cytotoxicity of selinexor. (F) TP53 mutation (Mut-TP53) significantly reduced the anti-lymphoma efficacy of selinexor in HGBCL-DH cells. IC50 values were calculated by GraphPad Prism 8 based on the cell viability data after 72-hour treatment