TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

Sebaceous carcinoma with apocrine differentiation arising in a known case of basal cell carcinoma: A rare entity.

Sebaceous carcinoma is a ra malignant tumor of adnexal origin arising from sebaceous glands. It is most commonly seen arising from the eyelids and head and neck. It is predominantly seen in females with an average age of around 65 years. Apocrine differentiation in sebaceous carcinomas is rare but has been reported in the literature. Here, we present a case of sebaceous carcinoma with apocrine differentiation in a 62-year- old female who was a diagnosed case of basal cell carinoma.

Extra-ocular sebaceous carcinoma - A rare case report.

Sebaceous gland carcinoma is a rare and aggressive skin cancer derived from the sebaceous glands. Sebaceous carcinomas are divided into those occurring in ocular (75%) and extra-ocular locations. A 45-year-old female patient presented with rapidly growing swelling over the upper back region. It was provisionally diagnosed as an infected sebaceous cyst, and an excision biopsy was received in the pathology department. Histopathology was reported as sebaceous carcinoma, Grade II, Stage P T3 Nx. Immunohistochemistry was positive for epithelial membrane antigen. Sebaceous carcinoma accounts for 0.2-4.6% of all malignant cutaneous neoplasms, and the estimated rate of occurrence is only 1-2 per 1 million individuals per year. These tumors frequently present with a painless sub-cutaneous nodule, but they can also present as pedunculated lesions, irregular mass, or diffuse thickening of the skin. Hence, they are misinterpreted as other benign tumors or inflammatory conditions, thereby leading to delay in diagnosis, inappropriate treatment, increased morbidity, and mortality.

Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

Spindle Cell-Predominant Trichodiscoma With Palisading Arrangement: A Rare Variant.

ABSTRACT: Spindle cell-predominant trichodiscoma (SCPT) is a benign adnexal neoplasm, best categorized within the trichodiscoma-fibrofolliculoma continuum. SCPTs clinically present as dome-shaped papules usually on the face, particularly on the nose or the nasolabial fold. The SCPT variant has been described as a particularly cellular trichodiscoma composed of small interweaving fascicles and sheets of spindle cells. Identical lesions were previously referred to as neurofollicular hamartomas because of their predominantly fascicular stromal cellularity and focal S100 positivity. In this article, we report a rare variant of SCPT with a palisaded arrangement. The patient is a middle-aged man with no significant dermatologic history who presented with a skin-colored papule on the left nasal ala. It had been present for approximately 10 years with only minimal growth over that time. A biopsy was obtained. Histopathological analysis revealed a dermal papule composed of bland spindle cells arranged in a striking palisading pattern within a fibromyxoid stroma with associated peripheral hyperplasia of sebaceous glands. The palisaded pattern shared features reminiscent of Verocay bodies of a schwannoma. Immunohistochemical studies revealed stromal spindled cells with a strong and diffuse pattern of CD34 expression and absent S100 and SOX10 expressions. To our knowledge, only 2 cases of SCPT with a palisaded pattern have been presented. SCPT with a palisaded pattern is a rare histopathologic variant that may resemble a schwannoma but can be recognized by its strong epithelial components and immunohistochemical staining pattern.

Development and validation of a nomogram to predict the recurrence of eyelid sebaceous gland carcinoma.

PURPOSE: Eyelid sebaceous gland carcinoma (SGC) is a malignancy with fatal risk, high recurrence rate, and pagetoid spread. Thus, recurrence risk prediction and prompt treatment are extremely important. This study aimed to develop a nomogram to predict SGC recurrence based on potential risk factors. METHODS: We conducted a retrospective study to train and test a nomogram based on the clinical data of 391 patients across our hospital (304) and other grass-roots hospitals (87). After Cox regression, predictors included in the nomogram were selected, and sensitivity, specificity, concordance index (C-index), etc., were calculated to test their discrimination ability. RESULTS: After a median follow-up period of 4.12 years, SGC recurred in 52 (17.11%) patients. The 1-, 2-, and 5-year recurrence-free survival rates were 88.3%, 85.4%, and 81.6%, respectively. We examined five risk factors, such as lymph node metastasis at initial diagnosis (hazard ratio [HR], 2.260; 95% confidence interval [CI], 1.021-5.007), Ki67 (HR, 1.036; 95% CI, 1.020-1.052), histology differentiation degree (HR, 2.274; 95% CI, 1.063-4.865), conjunctival pagetoid infiltration (HR, 2.100; 95% CI, 1.0058-4.167), and orbital involvement (HR, 4.764; 95% CI, 1.436-15.803). The model had good discrimination in both internal and external test sets. The model had good discrimination in both internal and external test sets. The sensitivity of the internal test and external test set were 0.722 and 0.806, respectively, and specificity of the internal test and external test set were 0.886 and 0.893, respectively. CONCLUSION: We examined the potential risk factors for eyelid SGC recurrence and constructed a nomogram, which complements the TNM system in terms of prediction, indicating that our nomogram has the potential to reach clinical significance. This nomogram has the potential to assist healthcare practitioners in promptly detecting patients who are at an elevated risk and in tailoring clinical interventions to meet their individualized needs.

SOAT1 missense variant in two cats with sebaceous gland dysplasia.

Spontaneously arisen hereditary diseases in domestic animals provide an excellent opportunity to study the physiological functions of the altered genes. We investigated two 4-month-old sibling domestic short haired kittens with dry dark debris around the eyes, nose, and ears, dark crusting on the legs and a thin poor hair coat. Skin biopsies revealed abnormal sebaceous gland morphology with lack of normal sebocyte arrangement and differentiation. Hair follicles had a distorted silhouette, interpreted as a change secondary to the observed sebaceous gland dysplasia. Whole genome sequencing on both affected kittens and 65 genetically diverse feline genomes was performed. Filtering for variants that were present in both kittens but absent from the control genomes revealed a homozygous missense variant in SOAT1, encoding sterol O-acyltransferase 1. The protein is localized in the endoplasmic reticulum and catalyzes the formation of cholesteryl esters, an essential component of sebum and meibum. The identified SOAT1:c.1531G > A variant is predicted to change a highly conserved glycine residue within the last transmembrane domain of SOAT1, p.Gly511Arg. In mice, variants in Soat1 or complete knockout of the gene lead to the "hair interior defect" (hid) or abnormal Meibomian glands, respectively. SOAT1:c.1531G > A represents a plausible candidate variant for the observed sebaceous gland dysplasia in both kittens of this study. The variant was not present in 10 additional cats with a similar clinical and histopathological phenotype suggesting genetic heterogeneity. SOAT1 variants should be considered as potential cause in hereditary sebaceous gland dysplasias of humans and domestic animals.

Blood group in relation to oral Fordyce's granules and serum cholesterol level.

BACKGROUND: The ABO and Rh systems are the most commonly used blood-group systems used to classify blood group globally. A number of studies have shown that ABO blood groups may be associated with an increased serum cholesterol levels which in turn may be related to the presence of oral Fordyce spots or granules. Oral Fordyce's granules are ectopic sebaceous glands within the oral cavity and are visible through epithelium. The aim of this study was to assess the relationship between ABO and Rhesus blood groups and the presence of oral Fordyce's granules and serum cholesterols level by gender. METHODS: Following ethical approval and informed consent, 124 subjects were recruited into this cross-sectional study. Clinical oral examination assessed the number of Fordyce's granules and blood samples were collected to determine the serum cholesterol and ABO/Rh blood-group systems of individual subjects. RESULTS: Blood group AB+ showed the highest mean of oral Fordyce's granules number and serum cholesterol level but this was not statistically significant compared to other blood groups. Female subjects in this study who were AB+ were had significantly higher serum cholesterol levels than males. CONCLUSION: This study indicates an association between ABO blood group, serum cholesterol level and mean number of oral Fordyce's granules. A larger sample size in a future study is required to ascertain whether number of Fordyce's granules is an important measure of serum cholesterol, but the study does show that for AB+ individuals, females may have higher serum cholesterol than males.

Rinofima: reporte de un caso de Clínica Estrella / Rhinophyma: a case report of Clínica Estrella

La rinofima es una patología que se caracteriza por presentar hipertrofia de las glándulas sebáceas con proliferación de tejido fibroso, donde la nariz toma un aspecto lobulado dando como resultado la deformidad de la punta nasal; es una forma de rosácea. La prevalencia de esta variedad de rosácea es de aproximadamente un 5-7% en la población y con predominio en el sexo masculino de la quinta a séptima década de vida. Su etiología no se conoce con exactitud. Se presenta el caso de un paciente masculino de 84 años, con antecedentes patológicos de hipertensión arterial e hipotiroidismo; su lesión inició hace 10 años, como una lesión eritematosa con presencia de telangiectasia a nivel de alas y punta nasal, no dolorosa. Se realizó tratamiento con bisturí frío y radiofrecuencia, se realizaron cortes transversales hasta dejar el lecho desprovisto del tumor y finalmente se usó radiofrecuencia en toda la superficie de la lesión restante. Se realizó el procedimiento ambulatorio sin complicaciones inmediatas o tardías

Rhinophyma is a pathology characterized by hypertrophy of the sebaceous glands with proliferation of fibrous tissue, the nose has a lobed appearance, as a result there is a deformity of the nasal tip; rhinophyma is a form of rosacea. The prevalence of this variety of rosacea is approximately 5-7% in the population and predominantly in males from the fifth to seventh decade of life, the etiology is not well known, however there are several predisposing genetic and environmental factors. We present the case of an 84-year-old male patient with a pathological history of arterial hypertension and hypothyroidism; his lesion began 10 years ago, as an erythematous lesion with presence of telangiectasia in the wings and nasal tip, not painful. Treatment was performed with a cold scalpel and radiofrequency, transverse cuts were made until the tumor was gone, and finally radiofrequency was used on the entire surface of the remaining lesion. The outpatient procedure was performed without immediate or late complications.

Diagnostic Accuracy of GATA6 Immunostaining in Sebaceous Tumors of the Skin.

The accurate diagnosis of skin adnexal neoplasms is sometimes challenging but is necessary because medical management and follow-up may differ between tumors. GATA6 transcription factor has been identified as a new marker of the upper folliculosebaceous compartment (lower infundibulum, junctional zone and isthmus, and upper sebaceous gland) in the human skin. We aimed to determine the diagnostic accuracy of GATA6 immunostaining to diagnose sebaceous tumors compared with that to diagnose other adnexal and nonadnexal cutaneous neoplasms. We conducted a retrospective, evaluator-nonblinded study comparing the reference standard (diagnosis by an expert dermatopathologist) with GATA6 immunostaining to identify sebaceous tumors in a cohort containing 234 different tumors. The GATA6 expression score was significatively higher in sebaceous than that in nonsebaceous tumors. In addition, tumors originating from the upper hair follicle showed positive results for GATA6 staining; however, they showed lower GATA6 expression scores. Detection of sebaceous tumors using GATA6 positivity had a sensitivity of 95.7% (95% CI, 85.8-99.2), specificity of 80.8% (95% CI, 74.5-85.8), positive predictive value of 55.6% (95% CI, 44.7-65.9), and negative predictive value of 98.7% (95% CI, 95.4-99.8). GATA6 showed similar sensitivity to adipophilin, the reference marker; however, the specificity of GATA6 was higher, as observed in a cohort of 106 tumors enriched in squamous cell carcinomas with clear-cell histology. In addition, GATA6 positivity was assessed in 39 sebaceous carcinomas and compared with epithelial membrane antigen (EMA), CK7, and androgen receptor (AR) staining results. Although CK7 staining displayed lower diagnostic performances, GATA6 staining showed comparable results as EMA and AR. Finally, we found GATA6 expression in skin metastases of gastrointestinal origin, whereas GATA6 was absent in metastases originating from breast or lung cancers. Overall, our work identified GATA6 immunostaining as a new diagnostic tool for sebaceous tumors.

Integrated Whole-Exome and Transcriptome Sequencing Indicated Dysregulation of Cholesterol Metabolism in Eyelid Sebaceous Gland Carcinoma.

Purpose: To identify the molecular background of eyelid sebaceous gland carcinomas (SCs), we conducted the integrated whole-exome sequencing and transcriptome sequencing for eyelid SCs in this study. Methods: The genetic alterations were studied by whole-exome sequencing, and the messenger RNA expression was studied using Oxford Nanopore Technologies (ONT) in five paired fresh eyelid SC tissues and adjacent normal tissues. Integrated analysis of exome and transcriptomic information was conducted for filtering candidate driver genes. Protein-protein interaction (PPI) network of filtered candidate genes was analyzed by STRING. The protein expression was verified by immunohistochemistry in 29 eyelid SCs and 17 compared normal sebaceous gland tissues. Results: The average numbers of pathogenic somatic single-nucleotide variants (SNVs) and indels in eyelid SCs were 75 and 28, respectively. Tumor protein p53 (TP53), zinc finger protein 750 (ZNF750), filaggrin 2 (FLG2), valosin-containing protein (VCP), and zinc finger protein 717 (ZNF717) were recurrent mutated genes. A mean of 844 differentially expressed genes (DEGs) were upregulated, and 1401 DEGs were downregulated in SC samples. The intersection of DEG-based pathways and mutation-based pathways was mainly involved in microbial infection and inflammation, immunodeficiency, cancer, lipid metabolism, and the other pathways. The intersection of DEGs and mutated genes consisted of 55 genes, of which 15 genes formed a PPI network with 4 clusters. The PPI cluster composed of scavenger receptor class B member 1 (SCARB1), peroxisome proliferator-activated receptor γ (PPARG), peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) was involved in cholesterol metabolism. The expression of SCARB1 protein was found to be increased, whereas that of PPARG protein was decreased in eyelid SCs compared to that in the normal sebaceous glands. Conclusions: Increased SCARB1 and decreased PPARG indicated that dysregulation of cholesterol metabolism might be involved in carcinogenesis of eyelid SCs. Translational Relevance: The malfunction in cholesterol metabolism might advance our knowledge of the carcinogenesis of eyelid SCs.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

PURPOSE: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. METHODS: A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. RESULTS: Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. CONCLUSION: Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Sebaceous gland atrophy in seborrheic dermatitis of the scalp; a pilot study.

BACKGROUND: Sebaceous gland (SG) atrophy is well-documented in scalp lesions of psoriasis and has been considered as an important clue to psoriatic alopecia. However, its specificity for psoriasis has been questioned over the years. We hypothesize that SG atrophy is not specific for psoriasis and looked for its presence in biopsies of seborrheic dermatitis of the scalp. METHODS: We conducted a retrospective study of biopsy specimens of clinically suspected and histopathologically proven seborrheic dermatitis of the scalp for changes in SGs between January 1, 2014 and August 6, 2021. RESULTS: SGs lobules were smaller and narrower in five of the six cases of seborrheic dermatitis, and SG atrophy was present in four out of six cases. CONCLUSIONS: SG atrophy is observed in seborrheic dermatitis and is not specific for psoriasis or psoriatic alopecia.

A novel 1726-nm laser system for safe and effective treatment of acne vulgaris.

Selective photothermolysis of the sebaceous glands has the potential to be an effective alternative for treating acne vulgaris. However, the translation of this technique to clinical settings has been hindered by a lack of appropriate energy sources to target sebaceous glands, concerns surrounding safety, and treatment-related discomfort and downtime. In this work, we introduce the first FDA-approved system that combines a 1726-nm laser and efficient contact cooling to treat mild, moderate, and severe acne effectively while ensuring safety and minimal patient discomfort without adjunct pain mitigation techniques. Light transport and bioheat transfer simulations were performed to demonstrate the system's efficacy and selectivity. The resulting thermal damage to the skin and sebaceous glands was modeled using the Arrhenius kinetic model. Numerical simulations demonstrated that combining laser energy and optimal contact cooling could induce a significant temperature increase spatially limited to the sebaceous gland; this results in highly selective targeting and maximum damage to the sebaceous gland while preserving other skin structures. In vivo human facial skin histology results corroborated the simulation results. The studies reported here demonstrate that the presented 1726-nm laser system induces selective photothermolysis of the sebaceous gland, providing a safe and effective method for the treatment of acne vulgaris.

Sebaceous Gland Ectopia of the Esophagus: A Challenging Clinical Diagnosis.

BACKGROUND/AIM: Sebaceous gland ectopia (SGE) defines the presence of normal sebaceous tissue in an unusual location. This condition is rare and was first described in ectodermal-derived organs, such as the oral cavities and palms, and later in endodermal-derived tissues including the esophagus. SGE of the esophagus is believed to represent a form of acquired metaplasia. SGE is asymptomatic and usually discovered during routine endoscopic examinations for other gastrointestinal complaints and symptoms. It is a benign entity and to date no cases of malignant transformation have been reported. Once diagnosed, SGE requires no further work up or follow up, and does not require treatment. CASE REPORT: We present two cases of SGE arising in the esophagi of two female patients who presented with complaints of gastro-esophageal reflux and underwent endoscopy. These lesions presented as patchy yellow-white nodules in the mid and upper esophagus and were endoscopically interpreted as suggestive of candidiasis or glycogen acanthosis. Biopsies showed foci of non-keratinizing squamous mucosa overlying the sebaceous glands. These glands exhibited a characteristic lobulated structure with germinative cells at the periphery and vacuolated, well-differentiated cells in the center of the lobules. After histologic examination, the endoscopic impressions of candidiasis and acanthosis were ruled out and the final diagnosis of SGE was made. There was no evidence of dysplasia or malignancy in our cases. CONCLUSION: Histopathology examination is important to differentiate SGE from malignant and infectious conditions that are more common, and which can be clinically and endoscopically similar to SGE.

Research on the effect of an androgenic hormone product on the functional status of common sebaceous glands in dogs.

Nowadays, a high incidence of cutaneous tumors is observed in domestic carnivorous in pet clinic, the sebaceous glands being the starting point for the development of these tumors. The hormonal imbalances are considered to be the most common etiology for these tumors, so the current research is based on the effects of an androgenic like hormonal drug on the functionality of the sebaceous glands in dogs. For this purpose, 32 dogs were distributed in 4 groups: control group 1 (8 dogs - females), control group 2 (8 dogs - males), experimental group 1 (8 dogs - females) and experimental group 2 (8 dogs - males). The investigation targeted the pH of skin and the rate of sebum's secretion. The animals from the experimental groups were treated with Anabolin forte for 2 days at a dose of 1 mg/kg body weight/day, intramuscular. The obtained results revealed that administration of Anabolin forte in males induced a significantly distinct intensification (with 10.66%) of sebum's secretion and a significant decrease of pH of the skin (with 17.1%) compared to the animals from the control group. The administration of Anabolin forte in females induced a significantly distinct intensification (with 17.47%) of sebum's secretion and a significant decrease of the pH of the skin (with 14.32%) compared to the animals from the control group.

PRAME immunostain expression in sebaceous lesions, cutaneous carcinomas and adnexal structures.

The use of immunostain for PRAME antigen is well established for cutaneous melanolocytic lesions. However, its staining in other cutaneous structures and lesions is under reported. This study assessed PRAME staining in a large cohort of normal skin tissue, sebaceous lesions, and cutaneous carcinomas to better delineate patterns of PRAME immunoreactivity. PRAME immunostaining was performed on sections of sebaceous lesions and tissue microarrays of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Normal cutaneous adnexal structures were assessed on the sections of sebaceous lesions. For sebaceous lesions and non-lesional sebaceous glands, PRAME immunostaining was assessed for mature, germinative and sebocytes independently. A total of 193 sebaceous lesions, 64 BCCs and 35 SCCs were stained for PRAME immunostain. Staining pattern was predominantly cytoplasmic in normal apocrine glands, germinative sebocytes of sebaceous glands, and hair germs (p<0.001). Lesional sebocytes did not show different staining compared to normal sebaceous glands (p>0.05). Rare nuclear staining was observed in the normal epidermis (0.6%) and junctional melanocytes (4.1%). BCC, SCC and sebaceous carcinoma all showed low levels of PRAME immunoreactivity with variable proportions of cases demonstrating nuclear staining (BCC 59.4%, SCC 37.1%, sebaceous carcinoma 5.3%). PRAME immunostaining is positive in germinative sebocytes, various cutaneous structures and carcinomas. Nuclear staining, identical to melanoma, was observed in normal epidermis, junctional melanocytes, BCCs, SCCs, and sebaceous carcinomas. The pattern of PRAME staining in the skin must be recognised to avoid pitfalls in interpretating PRAME immunostain.