Search

© 2018 The Authors Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C+CD301A+myeloid dendritic cell population in psoriatic epidermis, and IL1βhiCCL3hiCD14+monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation. Cheng et al. report single-cell RNA sequencing of normal and inflamed human epidermis, revealing a discrete set of specialized keratinocytes that exhibit a distinct composition at different anatomic sites. Myeloid dendritic cells and macrophages also vary sharply with epidermal anatomic site and inflammation, indicating dynamic programming of antigen-presenting cells.

Abstract: Silicone granulomas, or "siliconomas," are the common foreign-body inflammatory responses to injected silicone material. In rare cases, siliconomas develop remotely from the original site of injection, secondary to silicone migration. If a history of silicone injection is not noted, such lesions risk misdiagnosis (possibly as infection or malignancy). Intraocular silicone oil is commonly used in retinal detachment surgery, with occasional reports of granulomatous responses after its application in this context. Here, we report a 66-year-old man who developed a periocular silicone granuloma years after scleral buckle surgery for a detached retina and summarize the literature of similar reports of migratory siliconoma., Competing Interests: The authors declare no relevant conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas., Methods: We performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a fetal glial cell model following transduction with wildtype and tumor-derived mutant isoforms of SOX10., Results: We identified that nearly one-third of sporadic schwannomas lack alterations in known nerve sheath tumor genes and instead harbor novel recurrent in-frame insertion/deletion mutations in SOX10, which encodes a transcription factor responsible for controlling Schwann cell differentiation and myelination. SOX10 indel mutations were highly enriched in schwannomas arising from nonvestibular cranial nerves (eg facial, trigeminal, vagus) and were absent from vestibular nerve schwannomas driven by NF2 mutation. Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs., Conclusions: We thus speculate that SOX10 indel mutations drive a unique subtype of schwannomas by impeding proper differentiation of immature Schwann cells., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Genetic variation in the NF-κB inhibitors, ABIN1 and A20, increase risk for psoriasis. While critical for hematopoietic immune cell function, these genes are believed to additionally inhibit psoriasis by dampening inflammatory signaling in keratinocytes. We dissected ABIN1 and A20's regulatory role in human keratinocyte inflammation using an RNA sequencing-based comparative genomic approach. Here we show subsets of the IL-17 and tumor necrosis factor-α signaling pathways are robustly restricted by A20 overexpression. In contrast, ABIN1 overexpression inhibits these genes more modestly for IL-17, and weakly for tumor necrosis factor-α. Our genome-scale analysis also indicates that inflammatory program suppression appears to be the major transcriptional influence of A20/ABIN1 overexpression, without obvious influence on keratinocyte viability genes. Our findings thus enable dissection of the differing anti-inflammatory mechanisms of two distinct psoriasis modifiers, which may be directly exploited for therapeutic purposes. Importantly, we report that IL-17-induced targets of A20 show similar aberrant epidermal layer-specific transcriptional upregulation in keratinocytes from diseases as diverse as psoriasis, atopic dermatitis, and erythrokeratodermia variabilis, suggesting a contributory role for epidermal inflammation in a broad spectrum of rashes., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Undifferentiated pleomorphic sarcoma (UPS) encompasses rare neoplasms that can arise either in the dermis or in the subfascial soft tissue. The behavior of UPS ranges from indolent to aggressive, but data predicting outcomes are limited., Objective: Identify predictors of poor outcomes by analyzing a large collection of UPS cases., Methods: We evaluated all available cases of UPS (including those termed atypical fibroxanthoma, malignant fibrous histiocytoma, pleomorphic dermal sarcoma, and subfascial UPS) across 3 tertiary care centers., Results: Among the 319 patients, 45 experienced recurrence, 33 experienced metastasis, and 96 died of any cause. Risk factors for recurrence were clinical tumor size larger than 5 cm and invasion beyond subcutaneous fat. Risk factors for distant metastases were tumor site, tumor size larger than 2 cm, invasion beyond subcutaneous fat, and lymphovascular invasion. Risk factors for overall mortality were age, immunosuppression, tumor size larger than 2 cm, and lymphovascular invasion. History of skin cancer was associated with a lower risk of recurrence and metastasis., Limitations: This was a retrospective study., Conclusions: Using the unbiased approach of pooling all UPS cases regardless of terminology, we identified clinical and histologic factors predicting poor outcomes. We propose subcategorization of UPS (into superficial versus deep UPS), which is consistent with the American Joint Committee on Cancer staging of soft-tissue sarcoma., (Published by Elsevier Inc.)

Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C + CD301A + myeloid dendritic cell population in psoriatic epidermis, and IL1β hi CCL3 hi CD14 + monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Skin infections are not uncommon after cosmetic laser procedures. Infection rates following ablative laser resurfacing procedures are reported to be as high as 7.6%, compared to 1.9% for fractional ablation. An infrequent yet important infectious complication of ablative laser treatment is that caused by non-tuberculous mycobacteria (NTM).

We report the unprecedented case of reactive eccrine syringofibroadenoma (ESFA) secondary to primary cutaneous amyloidosis. A 62-year-old woman of Asian ethnicity presented with a pruritic rash on the back of long-standing duration. Physical examination revealed diffuse hyperpigmentation localized to the interscapular region; there were a multitude of hyperpigmented macules merged in a rippled pattern intermixed with scattered papules and cobblestone-like areas. A punch biopsy from a papule was taken. Histopathological examination revealed a network of epithelial strands and cords hanging from the epidermis and harboring foci of ductal differentiation. Eosinophilic collections of amorphous material were found between the epithelial strands, obscuring the superficial dermis. The microscopic picture was consistent with primary cutaneous amyloidosis associated with reactive ESFA. Results of histochemical and immunohistochemical staining confirmed the diagnosis. We speculate that pathogenetic mechanisms intrinsic to primary cutaneous amyloidosis, in addition to unknown genetic factors, resulted in clinical changes of lichen amyloidosus associated with an abnormal hyperplastic epithelial response with histopathological features of ESFA rather than the common epidermal change of acanthosis and hyperkeratosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy after solid organ transplantation, with an increased risk of recurrence and metastasis over the general population. The newly updated 7th edition American Joint Committee on Cancer (AJCC) staging system for cSCC is based on consensus expert opinion and requires validation in large cohort studies and in specific patient subpopulations., Objective: Our objective was to evaluate the risk of cSCC recurrence in a high-risk population of heart and lung transplant recipients, based on the 7th edition AJCC staging system., Methods: We performed a 10-year retrospective cohort study of all primary cSCC diagnosed in heart and lung transplant recipients at a tertiary care academic dermatology center., Results: The cumulative incidence of local recurrence was 4% for cSCC in situ and 19% for stage I cSCC at 5 years, and 54% for stage II cSCC at 3 years. Stage II tumors had a 10-fold greater risk of recurrence than stage I, and a 43-fold greater risk of recurrence than in situ tumors., Limitations: This study is limited to a specific patient subgroup at a tertiary care center, and may not be generalizable to all populations., Conclusions: Heart and lung transplant recipients are at high risk for local recurrence of cSCC. These data substantiate the prognostic accuracy of the newly updated 7th edition AJCC staging system for stage 0, I, and II cSCC in this population and demonstrate the aggressive behavior of this cancer in immunosuppressed patients., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Despite its modest potential benefit, alpha-interferon is one of the most frequently employed therapies for melanoma. With the increasing incidence of melanoma, a parallel increase in interferon use and the associated adverse reactions that accompany interferon therapy should be expected. We present a case of an interferon-induced sarcoidosis-like reaction in a melanoma patient that was initially misinterpreted clinically and radiographically as metastatic melanoma. The etiology of sarcoidosis remains a mystery, but appears to involve Th-1 cytokines such as interferon and interleukin-2. Observance of a sarcoidosis-like reaction induced by interferon therapy lends additional support to the importance of this cytokine in the pathogenesis of sarcoidosis. It is important for pathologists to be aware of this entity when interpreting biopsies from melanoma patients treated with interferon., (Copyright © 2011 John Wiley & Sons A/S.)

Objective and Importance: The goal of this report was to describe the successful percutaneous endovascular use of a Gianturco-Roubin-2 coronary stent in the treatment of an acute atherothrombotic occlusion of the basilar artery. To our knowledge, the percutaneous endovascular deployment of an intra-arterial stent for the treatment of an acute atherothrombotic occlusion of the basilar artery and the percutaneous endovascular placement of a Gianturco-Roubin-2 stent in the basilar artery have not been previously reported., Clinical Presentation: An 83-year-old man presented with a recurrent, transient, locked-in syndrome resulting from a lower basilar artery occlusion caused by vertebrobasilar thrombosis superimposed on severe proximal basilar artery atheromatous stenosis., Intervention: After successful superselective intra-arterial thrombolysis of the vertebrobasilar clot, balloon angioplasty of the underlying basilar artery stenosis was performed, without significant angiographic improvement. Percutaneous endovascular deployment of a Gianturco-Roubin-2 coronary stent of 4-mm diameter was subsequently performed, with excellent angiographic results., Conclusion: The patient made a very good neurological recovery but unfortunately died as a result of cardiogenic shock and sepsis. Detailed neuropathological follow-up results are presented; stent patency was revealed in the postmortem examination. The anatomic and pathophysiological considerations of basilar artery stent placement for the treatment of acute basilar artery occlusion related to atherosclerotic stenosis are discussed.