Root Sheath Research Articles

Trichilemmal carcinoma masquerading as a sebaceous cyst - A rare case report

ABSTRACT Trichilemmal carcinoma (TC) is a rare, malignant, cutaneous adnexal neoplasm derived from the external root sheath of hair follicle, commonly seen in elderly males in the seventh to ninth decade. It commonly affects the sun-exposed areas and has an indolent course. We report a case of TC in which a 67-year-old female presented with a swelling on the scalp, which was misdiagnosed as a case of sebaceous cyst. The patient underwent excision and based on histopathological examination and immunohistochemistry, the diagnosis of TC was obtained.

Mesenchymal Stem Cells Isolated from Equine Hair Follicles Using a Method of Air-Liquid Interface

Equine mesenchymal stem cells (MSC) of various origins have been identified in horses, including MSCs from the bone marrow and adipose tissue. However, these stem cell sources are highly invasive in sampling, which thereby limits their clinical application in equine veterinary medicine. This study presents a novel method using an air-liquid interface to isolate stem cells from the hair follicle outer root sheath of the equine forehead skin. These stem cells cultured herewith showed high proliferation and asumed MSC phenotype by expressing MSC positive biomarkers (CD29, CD44 CD90) while not expressing negative markers (CD14, CD34 and CD45). They were capable of differentiating towards chondrogenic, osteogenic and adipogenic lineages, which was comparable with MSCs from adipose tissue. Due to their proliferative phenotype in vitro, MSC-like profile and differentiation capacities, we named them equine mesenchymal stem cells from the hair follicle outer root sheath (eMSCORS). eMSCORS present a promising alternative stem cell source for the equine veterinary medicine.Graphical abstract

CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation

BackgroundCDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation.MethodsThe dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig’s epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket.ResultsCDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn’t disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs’ odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs.ConclusionsWe innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.

Identification of the Keratin-Associated Protein 22-2 Gene in the Capra hircus and Association of Its Variation with Cashmere Traits.

The Cashmere goat is an excellent local goat breed in Gansu Province of China, and it is expected to improve cashmere production and cashmere quality through selection and breeding to enhance its commercial value. Keratin-associated proteins (KAPs) play an important role in maintaining wool structure. The gene encoding the keratin-associated protein 22-2 (KAP22-2) gene has been identified in selected species other than goats, such as humans, mice, and sheep. In this study, the sequence of the sheep KAP22-2 gene (KRTAP22-2) was aligned into the goat genome, and the sequence with the highest homology was assumed to be the goat KRTAP22-2 sequence and used to design primers to amplify the goat gene sequence. A total of 356 Longdong Cashmere goats (Gansu Province, China) were used for screening of genetic variants. Four specific bands were detected by polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) analysis, and they formed a total of six band types individually or in combination. Four alleles were identified by DNA sequencing of PCR amplification products. A total of four single nucleotide polymorphic sites (SNPs) were detected in the four sequenced KRTAP22-2 alleles. Two of them are in the 5'UTR region and the other two are in the coding region, and the variants in the coding region are all non-synonymous mutations. In addition, there was a 6 bp length variation in allele C. The gene was expressed in the cortical layer of primary and secondary hair follicles, the inner root sheath, as well as hair papillae and hair maternal cells in goats. The results of the correlation analysis between genotypes and cashmere traits showed that after excluding genotypes with a gene frequency of less than 5%, the mean fiber diameter (MFD) of cashmere was significantly higher in the AB genotype than in the AA and AC genotypes. That is, the KRTAP22-2 gene variants are associated with mean fiber diameter in cashmere. The above results suggest that the goat KRTAP22-2 variant can be utilized as a molecular marker candidate gene for cashmere traits.

A loss-of-function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa.

Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.

Molar‐incisor‐malformation in a paediatric cancer patient: Case report

AbstractAimTo report a case of molar‐incisor‐malformation (MIM) in a 7‐year‐old boy with a history of congenital infantile fibrosarcoma of the upper chest, which was surgically treated, without adjuvant radio/chemotherapy.Material and MethodsThe boy presented with mobility and pain on percussion of the permanent mandibular first molars. The radiographic features were suggestive of MIM. Both teeth were extracted and processed for conventional light microscopic examination and non‐decalcified ground sections.ResultsThe microscopic features confirmed the diagnosis of MIM. Regular follow‐up was recommended.ConclusionsMedical interventions during hospitalization for cancer treatment, other than chemo/radiotherapy, may cause MIM by adversely affecting the function of Hertwig's epithelial root sheath. Regular dental screening in paediatric cancer patients may reveal more MIM cases and help in elucidating its pathogenesis.

Epithelial-specific deletion of FAM20A leads to short root defects

Short Root Defects defined by a reduced ratio of root to crown, may culminate in root resorption and subsequent tooth loss, in spite of the absence of apparent symptoms. Such defects present considerable impediments to orthodontic treatment and restoration. Recent identification of Fam20a, an emergent pseudokinase, has been associated with enamel development and tooth eruption, yet its definitive role in root formation and eruption remains ambiguous. In this research, we initially ascertained that the targeted knockout of Fam20a within the epithelium led to truncated tooth roots, irregular breaks in the epithelial root sheath initiation of the WNT signaling pathway, and decreased expression of the cell polarity-related transcription factor Cdc42 in murine models. This was concomitant with the participation of the associated epithelial root sheath developmental pathways BMP2, Gli1, and Nfic. Furthermore, we observed that Fam20a predominantly affects the intraosseous eruption phase of tooth emergence. During this phase, the osteoclast peak around the mandibular first molar in cKO mice is delayed, leading to a slower formation of the eruption pathway, ultimately resulting in delayed tooth eruption in mice. The findings of this study enrich the extant knowledge regarding the role of Fam20a, suggesting its potential regulatory function in tooth root development through the WNT/β-catenin/Cdc42 pathway.

Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i−/−) arrested tooth root formation, indicated by truncated Hertwig’s epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i−/− mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i−/− mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i−/− odontoblasts. Through treating pulp precursor cells with Atp6i−/− or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i−/− OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i−/− mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.

LB1780 Transcriptomic profiling of laser captured suprabulbar outer root sheath reveals genes involved in immune privilege and inflammatory response by dandruff hair follicles

LB1780 Transcriptomic profiling of laser captured suprabulbar outer root sheath reveals genes involved in immune privilege and inflammatory response by dandruff hair follicles

The Defeathering Effect by Scalding in Chickens Follows Their Intrinsic Dermal Histologies.

This study aimed to delineate the fundamental skin histology and its association with feathers in broilers and native Red-Feather (RF) chickens and further elucidate their thermal alterations in respect to the defeathering effect by scalding. Comparisons of skin thickness between fresh samples and those after dehydration and fixation, as well as their collagen contents and histological differences, suggested that RF chickens had a thicker dermal layer with more collagen deposition and compact architecture, particularly in the neck and abdominal skin, but a thinner hypodermal layer in the back, chest, and abdomen skin. Despite an adolescent age, RF chickens showed a shorter calamus depth of tail feathers but a larger calamus diameter of wing feathers. Within the feather follicle punch, a very intense follicle sheath layer with compact collagenous matrixes to fulfill the space next to the inner feather root sheath was observed in RF chickens. Under both soft and hard scalding, RF chickens showed a lower degree of denaturation on hip skins and were more resistant to structural disintegration, primarily within the epidermal and dermal layer. Accordingly, a much narrower gap space between the feather sheath and surrounding follicle sheath was observed, and the gap expansion was also resistant to thermal changes. These results suggest that the defeathering effect by scalding follows the intrinsic skin histologies in chickens of various breeds and ages, primarily depending on the interaction of the feather calamus with the surrounding follicle sheath and neighboring cutaneous tissues, reflecting their resistance to thermal denaturation, but is irrelevant to the feathers per se.

A Combinatorial Approach to Regenerate the Periodontal Ligament and Cementum in a Nondental Microenvironment

While treated dentin matrix (TDM) has been used for regeneration of dental tissues, the quality and quantity of regenerated periodontal tissue structure are suboptimal. The present study was undertaken to test whether the combined use of the TDM with dental follicle cells (DFCs) and Hertwig’s epithelial root sheath (HERS) cells enhances the regeneration of periodontal structures in a nondental microenvironment. TDMs were fabricated from 3-month-old Sprague–Dawley (SD) rats. DFCs and HERS cells were isolated from postnatal 7-day SD rats. Purified DFCs and HERS cells, both in combination or alone, were seeded and cultured on TDM in vitro and characterized. The cell-seeded TDMs were subsequently implanted into a 3-month-old rat greater omentum for 6 weeks, and further histological evaluation was performed. The results showed that cells grew well on the surface of TDMs, and mineralized nodules could be seen, especially in the HERS + DFCs group. After transplantation in rat omentum, periodontal ligament-like fibers and cementum-like structures were observed around the TDM in 1/3 of the samples in both the HERS group and the DFCs group and in 2/3 of the samples in the HERS + DFCs group, while almost no attached tissue formation was found in the TDM only group. The formed cementum width and the periodontal ligament length were significantly larger in the HERS + DFCs group. The periodontal ligament-like fibers in the HERS + DFCs group were orderly arranged and attached to the cementum-like tissues, which resembled the cementum-periodontal structure. Therefore, the combined use of DFCs, TDM, and HERS cells may be a promising strategy for the regeneration of the periodontal structures, especially in the nondental microenvironment.

Proliferating Pilar Tumors in the Scalp Over a Period of 23 Years in a General Hospital in Mexico City.

Proliferating pilar tumors are an unusual skin tumor, and they have a cystic component with trichilemmal keratinization and epithelial proliferation. These arise from the outer root sheath of hair follicles. It mainly affects women. The scalp is the most affected area. Diagnosis can be made by biopsy. Surgical excision is the best treatment option. Report the frequency of proliferating pilar tumors in the scalp in general hospital in Mexico over a period of 23 years. The authors reviewed the database of the dermatopathology service of the General Hospital "Dr Manuel Gea González" from 1999 to August 2022, selecting diagnosticated cases of proliferating pilar tumor, pilar cyst, trichilemmal cyst, or proliferating trichilemmal cyst in the scalp. The authors discovered 17 cases, 13 were women, the average age was 54.9 years, all the tumors affecting the scalp, and just 3 cases were reported as malignant. In comparison with the existing data, the authors can observe that most of their patients were women and the scalp is the most affected area. Most did not present associated symptoms. As the authors can see, most are benign and long-lasting: however, the authors cannot ignore that a small percentage can be malignant.

Red Ginseng Water Extract Aggravates Inflammation in Sebocytes and Outer Root Sheath Cells after Treatment with Lipopolysaccharide and Mice with Cutibacterium acnesinduced Inflammatory Nodules

Background: Ginseng, a well-known health-supportive herbal medicine in Korea, has various forms, including red ginseng (RG) produced through steaming and drying white ginseng. RG has been associated with numerous protective functions in various diseases. Objective: The objective of this study was to investigate whether RG water extract exacerbates inflammation in human sebocytes and outer root sheath (ORS) cells following treatment with lipopolysaccharide (LPS) and Cutibacterium acnes strain (ATCC 1182)-induced inflammatory nodules in mice. Methods: Sebocytes and ORS cells were isolated and cultured from the human scalp. Reverse transcriptionpolymerase chain reaction and enzyme-linked immunosorbent assay were used to measure the expression of inflammatory cytokine and sebum-related genes after treatment with RG and LPS. Mice with Cutibacterium acnesinduced inflammatory nodules were orally administered RG in water for two weeks, and immunofluorescence staining was performed to assess the inflammatory nodules. Results: RG enhanced LPS-mediated inflammation by increasing the mRNA and protein expression of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α in sebocytes and ORS cells. RG also upregulated the expression of p-nuclear factor-kappa B (p-NFκB), p-c-Jun, and c-Jun N-terminal kinase (p-JNK) in LPS-treated sebocytes and ORS cells. Moreover, RG promoted LPS-induced sebum production in sebocytes. Additionally, RG hindered the improvement of inflammatory nodules in mice and increased the expression of inflammatory biomarkers, such as neutrophil, myeloperoxidase, and IL-1β, as well as tissue remodeling biomarkers, such as myeloperoxidase (MMP)-2, MMP-3, and MMP-9 in the inflammatory nodules. Conclusion: Our findings strongly suggest that RG exacerbates acne vulgaris. It is advisable to avoid using RG in patients with inflammatory acne.

Trichoscopy of pemphigus vulgaris in remission. A tool for treatment-cessation decision making. Preliminary results

Background: One of the controversies in the treatment of Pemphigus Vulgaris (PV), is the time of treatment cessation. Scalp involvement is often the most stubborn to treatment human area and may reflect disease activity. Trichoscopy (Dermoscopy of hair and scalp) features have not been studied in clinically “healthy-looking” skin of PV patients in full remission. Aims and Objectives:To find out if there are any trichoscopy features in PV patients in clinical and immunologic remission, and accommodate treatment decision. Methods: The age and disease duration of 3 women with PV were correspondingly 62, 63, 55 and 5, 6, 15 years. Treatment at examination was 2,5 mg prednisone(Pr), for the last 22, 5 and 7 months. The 2nd patient was also taking 1 mg/kg/d of Azathioprine. Anti Desmoglein antibodies turned to negative since Oct/2017, Feb/2017, Sept/2015. Contact dermoscopy and hand lens X10 magnifier for clinical evaluation, were used. Results: A red hue background, peripillar scales and tubular casts were observed by trichoscopy in the first 2 patients. Only peripilar scales on a small brown round area were the features in the 3rd patient. Treatment cessation was decided only in this patient, since casts observed in the other two patients, were considered as a consequence of outer root sheath acantholysis and a sign of disease activity. Patients’ follow up justified the aforementioned treatment decisions. Conclusions: Areas of red hue skin background and movable cylindical scales (casts) around hair shafts may be observed, even in the absence of apparent scalp clinical involvement, in PV patients in remission. Since these features may drive physicians to treatment continuation, dermoscopy of the scalp is required in clinically “healthy-looking” PV patients, before a decision of treatment cessation is made. Future studies with greater number of patients, furtherly validated by long term disease course outcome, are needed.

Expression and tissue distribution analysis of vimentin and transthyretin proteins associated with coat colors in sheep (Ovis aries).

Pigment production and distribution are controlled through multiple proteins, resulting in different coat color phenotypes of sheep. The expression distribution of vimentin (VIM) and transthyretin (TTR) in white and black sheep skins was detected by liquid chromatography-electrospray ionization tandem MS (LC-ESI-MS/MS), gene ontology (GO) statistics, immunohistochemistry, Western blot, and quantitative real time polymerase chain reaction (qRT-PCR) to evaluate their role in the coat color formation of sheep. LC-ESI-MS/MS results showed VIM and TTR proteins in white and black skin tissues of sheep. Meanwhile, GO functional annotation analysis suggested that VIM and TTR proteins were mainly concentrated in cellular components and biological process, respectively. Further research confirmed that VIM and TTR proteins were expressed at significantly higher levels in black sheep skins than in white sheep skins by Western blot, respectively. Immunohistochemistry notably detected VIM and TTR in hair follicle, dermal papilla, and outer root sheath of white and black sheep skins. qRT-PCR results also revealed that the expression of VIM and TTR mRNAs was higher in black sheep skins than in white sheep skins. The expression of VIM and TTR were higher in black sheep skins than in white sheep skins and the transcription and translation were unanimous in this study. VIM and TTR proteins were expressed in hair follicles of white and black sheep skins. These results suggested that VIM and TTR were involved in the coat color formation of sheep.

Cholesterol homeostasis in hair follicle keratinocytes is disrupted by impaired ABCA5 activity

The importance of cholesterol in hair follicle biology is underscored by its links to the pathogenesis of alopecias and hair growth disorders. Reports have associated defects in ABCA5, a membrane transporter, with altered keratinocyte cholesterol distribution in individuals with a form of congenital hypertrichosis, yet the biological basis for this defect in hair growth remains unknown. This study aimed to determine the impact of altered ABCA5 activity on hair follicle keratinocyte behaviour. Primary keratinocytes isolated from the outer root sheath of plucked human hair follicles were utilised as a relevant cell model. Following exogenous cholesterol loading, an increase in ABCA5 co-localisation to intracellular organelles was seen. Knockdown of ABCA5 revealed a dysregulation in cholesterol homeostasis, with LXR agonism leading to partial restoration of the homeostatic response. Filipin staining and live BODIPY cholesterol immunofluorescence microscopy revealed a reduction in endo-lysosomal cholesterol following ABCA5 knockdown. Analysis of oxysterols showed a significant increase in the fold change of 25-hydroxycholesterol and 7-β-hydroxycholesterol following cholesterol loading in ORS keratinocytes, after ABCA5 knockdown. These data suggest a role for ABCA5 in the intracellular compartmentalisation of free cholesterol in primary hair follicle keratinocytes. The loss of normal homeostatic response, following the delivery of excess cholesterol after ABCA5 knockdown, suggests an impact on LXR-mediated transcriptional activity. The loss of ABCA5 in the hair follicle could lead to impaired endo-lysosomal cholesterol transport, impacting pathways known to influence hair growth. This avenue warrants further investigation.

TRPS1: A Marker of Follicular Differentiation.

The trichorhinophalangeal syndrome type 1 (TRPS1) immunohistochemical (IHC) stain has increased in use in recent years as a marker for breast carcinomas. The TRPS1 gene is involved in various tissues, including the growth and differentiation of hair follicles. This article seeks to evaluate the IHC expression of TRPS1 in cutaneous neoplasms with follicular differentiation, such as trichoblastoma (TB), trichoepithelioma (TE), and basal cell carcinoma (BCC). IHC studies were performed on 13 TBs, 15 TEs, and 15 BCCs with an antibody against TRPS1. The study found a variable staining expression of TRPS1 in the tumor nests of TB, TE, and BCC. BCCs were distinct in that none of the BCCs demonstrated intermediate or high positivity, while TBs and TEs showed intermediate-to-high positivity in 5/13 (38%) and 3/15 (20%) of cases, respectively. We observed a distinct staining pattern among the mesenchymal cells of TB and TE. We found that TRPS1 highlighted perifollicular mesenchymal cells adjacent to the nests of TB and TE tumor cells. This staining pattern was absent in BCCs, where only scattered stromal cells were positive for TRPS1. Papillary mesenchymal bodies were also highlighted by TRPS1 in TB and TE. TRPS1 stained various parts of the normal hair follicle, including the nuclei of cells in the germinal matrix, outer root sheaths, and hair papillae. TRPS1 may be a useful IHC marker for follicular differentiation.

The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata.

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Proliferating Trichilemmal Tumor of Scalp—An Eye Opener for a Pathologist

Proliferating trichilemmal tumor is a rare tumor of external root sheath of hair follicles, originating mainly from the scalp of middle-aged females. Grossly and microscopically, it mimics squamous cell carcinoma; hence, it is important to understand the cytological as well as histological features of this tumor diligently. In addition, there are no standard guidelines present for the treatment of these tumors and recurrence is not uncommon which make its management a challenge. Here we are reporting a case of a 65-year-old woman with proliferating trichilemmal tumor in a form of an ulcerated lobulated mass on her occipital area of the scalp.

SIRT1 downregulation provokes immune-inflammatory responses in hair follicle outer root sheath cells and may contribute to development of alopecia areata

BackgroundSilent information regulator 1 (SIRT1), a type III histone deacetylase, is involved in various cutaneous and systemic autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. However, little is known about the role of SIRT1 in the development of alopecia areata (AA). ObjectivesThis study investigated whether SIRT1 regulates the hair follicle immune system and is involved in AA pathogenesis. MethodsSIRT1 expression in human scalp tissue was analyzed using immunohistochemical staining, qPCR, and western blotting. The regulatory effect of SIRT1 was evaluated after stimulation with the double-stranded RNA mimic polyinosinic:polycytidylic acid (poly I:C) in hair follicle outer root sheath (ORS) cells and C3H/HeJ mice. ResultsSIRT1 expression was significantly reduced in the AA scalp compared to the normal scalp. SIRT1 inhibition upregulated MHC class I polypeptide-related sequence A and UL16 binding protein 3 in hair follicle ORS cells. SIRT1 inhibition also promoted the production of Th1 cytokines (IFN-γ and TNF-α), IFN-inducible chemokines (CXCL9 and CXCL10), and T cell migration in ORS cells. Conversely, SIRT1 activation suppressed the autoreactive inflammatory responses. The counteractive effect of the immune response by SIRT1 was mediated through the deacetylation of NF-κB and phosphorylation of STAT3. ConclusionSIRT1 downregulation induces immune-inflammatory responses in hair follicle ORS cells and may contribute to AA development.