Root Sheath Of Hair Follicles Research Articles

RECURRENCE OF TRICHILEMMAL CYSTS ON THE SCALP: A CASE REPORT

Background: Trichilemmal cysts, benign lesions originating from the outer root sheath of hair follicles, commonly present as asymptomatic nodules on the scalp. Despite their typically non-threatening nature, cases of recurrence and familial clustering underscore the need for a comprehensive understanding of their clinical course and potential genetic influences. Case Presentation: We present a 44-year-old male with a lifelong history of trichilemmal cysts who sought surgical intervention due to discomfort caused by cyst formation on the scalp. Over a 15-year period, three cysts were surgically removed, with one inadvertently missing, leading to its progressive enlargement and the emergence of new cysts over the subsequent eight years. Magnetic resonance imaging revealed multiple well-defined cystic lesions with distinct margins, consistent with trichilemmal cysts. A second surgical procedure successfully excised all cysts, confirming the diagnosis through histopathological examination. Conclusion: The presented case highlights the challenges in managing recurrent trichilemmal cysts and emphasizes the importance of comprehensive surgical intervention. The benign nature of the lesions was reaffirmed through negative histopathological findings for dysplasia or malignancy. The family history of similar cystic formations raises intriguing questions about potential genetic predispositions and shared environmental factors. This case contributes valuable insights into the clinical dynamics of trichilemmal cysts and prompts further exploration into their genetic underpinnings.

Malignant appearance of trichilemmal cyst: a case report with review of the literature

69 years old male presented with one month history of non-tender, nodular, pinkish left neck swelling, measuring 10×20 mm. CECT revealed left neck dermatofibrosarcoma protuberans with submandibular vascular malformation. Surgical wide local excision of the lesion and split skin graft was done. Histopathology confirmed trichilemmal cyst (TC). TC is adnexal lesions, found in hair bearing areas. Pinkus pointed out that TC are keratin-filled cysts with a wall resembling the external root sheath of hair follicle. 2% can develop into proliferating trichilemmal tumours (PTTs) and malignant proliferating trichilemmal tumours (MPTTs). PTTs were originally described by Jones as benign but locally aggressive skin neoplasms. Female to male preponderance of 6% to 1%, with average age of 65 years at presentation. 90% are located on the scalp, while the residual 10% occur mainly on the back but they can develop any part of the body such as submandibular region. Proliferating TCs present as lobulated masses, soft in consistency. The masses may become exophytic, ulceration and may show malignant transformation. On imaging, these lesions can be either cystic or solid mass. Histopathological, it is characterised by absence of intercellular bridges between epithelial cells lining the cyst wall. Cyst cavity contains amorphous eosinophilic keratin. Satyaprakash et al report, complete surgical excision is warranted for TCs as if there is proliferative or malignant potential, it would affect the postoperative management and overall prognosis. TC, locally aggressive skin neoplasms and rarely, occurrence at submandibular region or become malignant and appropriately managed to prevent recurrence.

FGF5

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies.

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.

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.

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.

Auricular Malignant Proliferating Trichilemmal Tumor: A Case Report.

Malignant proliferating trichilemmal tumor (MPTT) is a dermal adnexal tumor originated from the external root sheath of hair follicles. In this article, we reported a rare case of auricular MPTT in a 65-year-old male with gradually enlarging and bleeding mass on the right auricle measuring 30 × 20 × 12mm in size and detailed the surgical strategy for therapy. The diagnosis of MPTT was established primarily by histopathological observation with abrupt keratinization, cytological atypia, abnormal mitoses, and infiltrating margins. Following extensive excision, no recurrence was noted for 14months. We also discuss its clinicopathological features, differential diagnoses, and treatment methods and review the relevant literature in this regard.

Identification of a peptide ligand facilitating percutaneous delivery of macromolecular cargo via inner root sheath in hair follicles by phage display combined with quantitative real-time PCR as a validation tool

To identify transdermal peptide ligands, an in vivo phage display was conducted by percutaneous administration of a phage-peptide library through the abdominal skin of rats, and the skin-traversing phages were recovered from the systemic circulation after three round of biopannings. Among total 182 peptide sequences consisting of seven amino acids which were identified from the third round phages, four peptide sequences (ST1-ST4) showing high rank in abundance were selected as transdermal peptide candidates, then their transdermal abilities were further validated simultaneously by phage quantification from blood using quantitative real-time PCR (qRT-PCR). While ST1 showed the highest appearance frequency after the third round of biopanning, the most efficient transdermal activity was observed with ST3 (AFTPAKT) by qRT-PCR. The ST3-encoding phage delivered across intact epidermis was detected in blood during test period up to 240 min. Fluorescent microscopy analysis further revealed specific localization of the ST3-encoding phage on the inner root sheath surrounding the hair follicles after its percutaneous administration. Thus, it is inferred that the hair follicles would be the transdermal route for ST3 which enables its access into systemic circulation. The overall results suggest that the ST3 peptide could be potentially utilized as an efficient transdermal carrier to deliver macromolecular therapeutics into body. It is also expected that qRT-PCR could be adopted as a reliable validation tool after phage display screening in the aspects of its accuracy, promptness and economic feasibility.

Extension of separation along the follicular epithelium and follicular basement membrane in pemphigus and bullous pemphigoid.

The outer root sheath of hair follicle and the interfollicular epidermis are continuous and basically similar in many aspects. The expression of various basement membrane (BM) components in the upper portion of the hair follicle is similar to that of the interfollicular BM. The extension of acantholysis into the adnexal structures was highlighted in the pemphigus group of diseases. On the other hand, extension of separation down the hair follicle BM has not been studied in subepidermal autoimmune bullous dermatoses. The aim of the present work was to study the extension of separation along follicular epithelium and follicular BM in pemphigus and bullous pemphigoid. This retrospective study was conducted on pemphigus and bullous pemphigoid cases. For each case, 4-μm-thick sections stained with hematoxylin and eosin were examined for the presence of hair follicles and the extension of separation down follicular epithelium and follicular BM. Positive extension of acantholysis down the follicular epithelium was seen in 23/27 (85.2%) of pemphigus vulgaris (PV) and 7/9 (77.8%) of pemphigus foliaceus (PF) cases with hair follicles. Follicular extension was limited to the infundibulum in PF but down the entire follicular length in PV. As for bullous pemphigoid (BP) cases, 20/26 cases (76.9%) that had hair follicles showed positive extension of the separation down the follicular BM. The cellular infiltrate detected was identical in its nature and density to that of subepidermal blister in all cases. Extension of the separation along follicular epithelium and follicular basement membrane was observed in PV, PF, and BP without significant difference.

Generation of Pigmented Skin Grafts from Human Hair Follicles and Dermal Fibroblasts.

Skin equivalents are able to mimic key features of human skin and they can be used for a very broad range of applications, such as fundamental studies of skin biology, disease, and toxicological models, as well as an alternative for animal testing. The high end of their use is in therapy of wound healing and repigmentation and disorders that massively affect individual health as well as quality of life and pose considerable burden to health care systems worldwide. Tissue-engineered skin grafts often originate from invasively obtained cell material (i.e., biopsy). Hereby, an unmet need for noninvasively gained autologous biological starting material has been created. The hair follicle, entirely noninvasively available by plucking, harbors a heterogeneous cell pool, including stem cells with an immense differentiation capacity, hereby representing an attractive source of cells, especially for purposes of regenerative medicine. In this study, we engineered three-dimensional pigmented epidermal and dermoepidermal grafts using human keratinocytes and melanocytes from the outer root sheath of hair follicles combined with dermal fibroblasts. The grafts were generally anatomically correct and functional regarding stratification and formation of epidermal melanin units, as well as extracellular matrix deposition, exhibiting moderate differences to the skin anatomy and function, typical for the in vitro culture. Impact statement The study focuses on generation of tissue-engineered skin equivalents, in particular, as a possible treatment for nonhealing wounds and depigmentation disorders. We developed an in vitro-generated three-dimensional pigmented epidermal and dermoepidermal graft using keratinocytes and melanocytes from the outer root sheath of human hair follicle combined with dermal fibroblasts. The anatomically and functionally correct grafts showed stratification, epidermal melanin units, and extracellular matrix deposition. They present an in vitro base for an autologous, pigmented graft as well as for further personalized in vitro experimental models generated from a noninvasively obtained cell source, addressing the unmet needs of the currently available clinical treatments.

Immunohistochemical Expression of Keratins in Normal Ovine Skin and in Chronic Dermatitis due to Sarcoptes scabiei

Hyperproliferation of epidermal keratinocytes is a major histopathological feature of chronic Sarcoptes scabiei dermatitis. We investigated the immunohistochemical expression of several keratins in scabietic dermatitis in sheep and in the skin of healthy sheep, using a panel of commercially available anti-human antibodies for keratins. Keratins AE1/AE3 and 34BE12 were expressed in all epithelial structures in healthy skin. Keratin MNF116 was expressed in the stratum basale and in the three lowest layers of the stratum spinosum, in follicular epithelium and in apocrine glands. Keratin K5/6 expression was seen in the stratum basale, in the two lowest cell layers of the stratum spinosum, in the outer root sheath of hair follicles and in myoepithelial cells of apocrine glands. K14 expression was observed in the stratum basale, in locally extensive regions of the two lowest cell layers of the stratum spinosum, in the outer root sheath of hair follicles and in sebaceous glands. Immunolabelling of K19 antigen was confined to apocrine glands. In scabietic skin, immunolabelling of keratin 34BE12 was seen in all layers of hyperplastic stratum spinosum and stratum granulosum but was restricted to some locally extensive regions in hyperkeratotic and parakeratotic stratum corneum. Keratin MNF116 was widely labelled in all layers of hyperplastic stratum spinosum and stratum granulosum. There was expansive labelling of K5/6 keratin in all layers of hyperplastic stratum spinosum and in locally extensive regions of stratum granulosum, as well as in hyperkeratotic or parakeratotic stratum corneum. Expansive labelling of K14 keratin was detected in all layers of hyperplastic stratum spinosum and in the layers of the hyperplastic stratum granulosum. K5/6 and K14 keratins were also labelled in the inner root sheath of occasional hair follicles.

Autologous, Non-Invasively Available Mesenchymal Stem Cells from the Outer Root Sheath of Hair Follicle Are Obtainable by Migration from Plucked Hair Follicles and Expandable in Scalable Amounts.

Background: Regenerative therapies based on autologous mesenchymal stem cells (MSC) as well as stem cells in general are still facing an unmet need for non-invasive sampling, availability, and scalability. The only known adult source of autologous MSCs permanently available with no pain, discomfort, or infection risk is the outer root sheath of the hair follicle (ORS). Methods: This study presents a non-invasively-based method for isolating and expanding MSCs from the ORS (MSCORS) by means of cell migration and expansion in air–liquid culture. Results: The method yielded 5 million cells of pure MSCORS cultured in 35 days, thereby superseding prior art methods of culturing MSCs from hair follicles. MSCORS features corresponded to the International Society for Cell Therapy characterization panel for MSCs: adherence to plastic, proliferation, colony forming, expression of MSC-markers, and adipo-, osteo-, and chondro-differentiation capacity. Additionally, MSCORS displayed facilitated random-oriented migration and high proliferation, pronounced marker expression, extended endothelial and smooth muscle differentiation capacity, as well as a paracrine immunomodulatory effect on monocytes. MSCORS matched or even exceeded control adipose-derived MSCs in most of the assessed qualities. Conclusions: MSCORS qualify for a variety of autologous regenerative treatments of chronic disorders and prophylactic cryopreservation for purposes of acute treatments in personalized medicine.

Spray-Dried Rosuvastatin Nanoparticles for Promoting Hair Growth.

In this research, we examined the effect of rosuvastatin calcium-loaded nanoparticles on the hair growth-promoting activity on Albino rats. Nanoparticles were prepared using 2:1 weight ratio of drug to methyl-β-cyclodextrin with 10, 20, and 30% stabilizers (phospholipid, polyvinyl pyrrolidone K30, and Compritol 888 ATO) using nanospray dryer. Subsequently, the prepared nanoparticles were evaluated for their process yield, particle size, polydispersity index, zeta potential, and in vitro drug release as well as in vivo studies. The dried nanoparticles showed process yield values up to 84% with particle size values ranging from 218 to 6258nm, polydispersity index values ranging from 0.32 to 0.99, and zeta potential values ranging from - 6.1 to - 11.9mV. Combination of methyl-β-cyclodextrin with 10% polyvinyl pyrrolidone K30 accomplished nanoparticles with the lowest particle size (218nm) and polydispersity index (0.32) values. These nanoparticles had suitable process yield value (70.5%) and were able to retard drug release. The hair growth-promoting activity for the selected nanoparticles revealed the highest hair length values in Albino rats after 14days of the hair growth study compared with non-medicated nanoparticles, nanoparticles' physical mixture, rosuvastatin solution, and marketed minoxidil preparation groups as well as the control group. The immunohistochemistry images for both selected nanoparticles and marketed minoxidil groups showed a significant increase in the diameter of hair follicle and percent area fraction of cytokeratin 19 in the outer root sheath of hair follicle compared with other tested groups. Rosuvastatin nanoparticles prepared by nanospray drying technique could be a good competitor to minoxidil for hair growth-promoting activity. Graphical abstract.

Mutations in SREBF1, Encoding Sterol Regulatory Element Binding Transcription Factor 1, Cause Autosomal-Dominant IFAP Syndrome

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2, encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. Invitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function.

Eyelid skin trichilemmoma and underlying local malignancy: is an aggressive treatment necessary?

ObjectiveTrichilemmoma is a benign tumour derived from the outer root sheath of hair follicles. Trichilemmoma can be associated with basal cell carcinoma (BCC), either as a collision lesion or from malignant transformation. This study evaluates malignancy associated with eyelid trichilemmoma and principles of treatment.Methods and analysisRetrospective study involving biopsy-proven eyelid trichilemmoma cases over 14 years encountered at a tertiary referral centre. Presenting features, differential diagnosis, type and number of operations required and histopathological features including coexisting BCC were analysed.ResultsWe identified 36 cases with an average age of 66 years. The clinical differential diagnoses were mainly BCC (44%), papilloma (36%) and squamous cell carcinoma (SCC) (3%). Three patients (8%) had trichilemmoma with associated BCC. Of the 19 cases (53%) of trichilemmomas without BCC with equivocal surgical margins, seven patients (19%) opted for further excision while 12 patients (33%) opted for observation and were discharged. A patient re-presented two years later with invasive BCC. Overall, 11% of our biopsy-proven eyelid trichilemmoma cases were associated with BCC.ConclusionPatients should be informed that a proportion of incompletely excised eyelid trichilemmomas may conceal underlying BCC. Therefore, further surgery to achieve clear surgical margins should be offered. Patients who opt for observation should be offered 6-monthly follow-up for three to five years. Alternatively, they can be discharged with advice to report any recurrence of lumps, skin changes or loss of lashes at the site of previous lesion.

Giant aggressive forehead tumor: A 15-year follow-up.

Proliferating trichilemmal tumors are rare tumors that originate from adnexal structures – specifically from the outer root sheaths of hair follicles. These tumors can be benign or malignant. We report a rare case of a giant aggressive forehead trichilemmal tumor that was paradoxically benign on pathology. It was surgically excised and followed-up for 15 years.

Pulling force deforms hair follicle root sheath nuclei and surrounding dermal collagen matrix differently at infundibulum, isthmus and suprabulbar regions.

The biomechanical properties of the collagenous dermal matrix are well described but responses to mechanical force by the hair follicles have not been characterised so far. We applied a pulling force on hair follicles to visualise and quantify changes in the keratin-14 and involucrin-positive cell layers of the follicles using nuclear dimensions as an indicator of tissue deformation. Moreover, we used second-harmonic generation imaging to visualise changes in the dermal collagen. We report how the anatomical regions of the follicle respond to the force. Nuclei of the isthmus region were most affected. The nuclei in both K14-positive outer root sheath cells and in involucrin-positive cells were significantly compressed, whereas the response in the infundibulum and suprabulbar regions was more variable. The deformation of the nuclei did not correlate with lamin A/C expression. The changes in the collagenous matrix were distinct at different depths of the dermis as collagen fibrils were compressed closer to each other in the region adjacent to upper suprabulbar follicle and pulled apart near the infundibulum. Thus, the responses to the force are locally defined and the cells in the permanent and cycling parts of the follicle behave differently.

Sulfated hyaluronan-containing artificial extracellular matrices promote proliferation of keratinocytes and melanotic phenotype of melanocytes from the outer root sheath of hair follicles.

The aim of this work was to establish improved cultivation conditions for human keratinocytes (HUKORS) and melanocytes (HUMORS) from the outer root sheath (ORS) of human hair follicles for purposes of generating an epidermal graft. To this end, the cells were cultivated on artificial extracellular matrix coatings composed of collagen (COLL) and hyaluronan (HA) with varying sulfation degrees. HUKORS and HUMORS were characterized based on their morphology and proliferation, marker gene expression, protein expression and melanin content in melanocytes. Depending on the sulfation degree, the matrices provided a favorable proliferation environment for HUKORS and improved the balance between proliferation and the exertion of melanotic phenotype (gene expression and melanin content) in HUMORS. Based on the increased gene expression of microphthalmia-associated transcription factor, as well as the downstream-affected melanotic genes premelanosome protein and tyrosinase in HUMORS cultivated on collagen matrices with high-sulfated HA, we assume that sulfated HA enhanced melanotic phenotype either by directly binding the CD44 receptor or by concentrating signaling mediators on site. Being a promising cultivation environment for both HUKORS and HUMORS, collagen matrices with sulfated HA have a potential of significantly improving the development of ORS-based epidermal grafts. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1640-1653, 2019.

Expression analysis of proteasome maturation protein (POMP) gene in Liaoning Cashmere goat

Liaoning Cashmere goat is a precious genetic resource of China. To explore the relationship between POMP and cashmere growth, we analyzed the expression of POMP. POMP encodes a hudrophilic protein which is most closely related to bos. RT-PCR showed that POMP was expressed in skin, heart, liver, spleen, lung, and kidney tissues. Real-time PCR showed that the expression of POMP was more active in the secondary hair follicles than the primary hair follicles in anagen. In situ hybridization showed that POMP was obviously expressed in the Inner Root Sheath (IRS) but no expression in Outer Root. The treatment of fibroblasts with melatonin (MT), fibroblast growth factors 5 (FGF5) and insulin-like growth factors 1 (IGF-1) showed that MT/FGF5/IGF-1 much performance for inhibiting the expression of POMP; MT + FGF5 inhibited the expression of POMP; MT + IGF-1 promoted the expression of POMP. When Noggin expression is decreased by siRNA, the expression of POMP is inhibited. To sum up, POMP strongly expressed in the root sheath of hair follicles, related to the development of the primary and secondary hair follicle; In addition, by adding MT/FGF5/IGF-1 or interfering with the Noggin expression to regulate the expression of POMP, to control the growth of Liaoning Cashmere goat cashmere.

Expression and tissue distribution analysis of Angiotensin II in sheep (Ovis aries) skins associated with white and black coat colors

Angiotensin II (AngII) regulates pigment synthesis by tyrosinase in melanocytes. To evaluate the association between AngII and coat color formation, we detected the expression distribution of AngII in white and black sheep skins by LC-ESI-MS/MS, western blot, quantitative real-time-PCR (qPCR) and distribution of AngII by immunohistochemistry.Liquid chromatography-electrospray ionization tandem MS (LC-ESI-MS/MS) results showed that AngII was found in white and black skin tissues of sheep. Western blot results verified the LC-ESI-MS/MS results and suggested that AngII was expressed at significantly higher levels in black sheep skins compared with the white sheep skins. Quantitative real time PCR (qRT-PCR) results also revealed that the expression level of AngII mRNA was higher in black sheep skins than that in white sheep skins. Immunohistochemical analysis further demonstrated that AngII protein was localized in the hair bulb and outer root sheath of hair follicle in sheep. In summary, protein and transcripts exhibited the same expression pattern in white and black sheep skins. Furthermore, the expressions of AngII in the hair bulb and outer root sheath of black sheep were stronger than those in white sheep. These results suggested that AngII functions in sheep coat color regulation and offer a novel insight for further investigation on the role of AngII in the coat color formation in sheep.