Polarization Optical Studies of Hyperkeratosis, Parakeratosis and Dyskeratosis* Daphne Anderson Roe, M.D., M.R.C.P

Total Page:16

File Type:pdf, Size:1020Kb

Polarization Optical Studies of Hyperkeratosis, Parakeratosis and Dyskeratosis* Daphne Anderson Roe, M.D., M.R.C.P View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector POLARIZATION OPTICAL STUDIES OF HYPERKERATOSIS, PARAKERATOSIS AND DYSKERATOSIS* DAPHNE ANDERSON ROE, M.D., M.R.C.P. Previous polarization optical studies of adultlife, the epidermis reaches its final state; at this and embryonic human epidermis have beenstage the eornified layer shows intense double devoted to the elucidation of the morphology ofrefraction. It is of interest that in the chick its fibrous structure. In unstained verticalembryo, the long axis of the cells of the periderm sections of human abdominal skin, the mostand of the embryonic horny layer is parallel to intense double refraction occurs in the stratumthe skin surface and the early keratin fibres are corneum and stratum lucidum. In these layersalso oriented in the same plane. birefringent material is oriented parallel to the There is only one polarization optical study of surface plane; below this region the birefringentpathologic epidermis. Nieuwmeijer examined the fibres are oriented perpendicularly to the surfacetonofibrils in bullous dermatoses by this method (1). and found differences between the tonofibrillar Similar observations have been made by othersystems in pemphigus and dermatitis herpeti- authors (2, 3), among them Mercer, who hasformis (6). In pemphigus, in the areas of acan- compared the appearance of the epidermis undertholysis, the tonofibrils were greatly decreased, the polarization and electron microscopes. Hewhereas in dermatitis herpetiformis the tonofibrils noted that the fibrils (tonofibrils) in the lowerwere pushed aside by the fluid in the bullae. layers of the epidermis were weakly birefringent. Recently, I used polarization optical methods At the level of the appearance of keratohyalinto investigate the anomaly of keratin formation there was a sudden rise in birefringenee associatedin psoriasis (7). It was found that the birefringent with a change in orientation of the fibres from atonofibrillar system persisted throughout the vertical to a horizontal direction. psoriatic epidermis and in the parakeratotic scale, In tissue cultures of stripped epidermis,but the mature keratin fibres failed to develop Matoltsy has shown that in 3 to 5 days' oldinto a coherent horny layer. These changes were explants the originally vertically oriented bire-reflected in the psoriatic nail (8) where immature fringent material becomes reoriented in a planekeratinization was evident from the extensive parallel to the surface (4). On the 7th day, aparakeratosis combined with persistence of a low definite keratogenous zone became visible, whiledegree of double refraction in much of the fibrous all the birefringent epidermal fibres were stillstructure of the nail plate and in the adherent oriented parallel to the skin surface. The signifi-hyponychium. These abnormalities were as- cance of these findings will be discussed later. sociated with alterations in the non-fibrous com- Studies of the development of the birefringentponents of the nail and epidermis, manifested fibrillar system of the human epidermis have yethistochemically by cytoplasmie metachromasia to be carried out, but similar observations of thein the parakeratotie cells and by an increased chick embryo have been made (5) and it has beenuptake of the Gram stain in the affected areas. shown that around the 16th day of embryonic In the present work the defects in the fibrous life the periderm or epitrichium reveals a verystructure of the epidermis were investigated in weak birefringenee. However, moderate birefrin-conditions characterized by the formation of gence appears during the next 2 days of embry-anomalous horny layers. onic life when the true cornified layer is formed. Between the 18th and 21st days of embryonic METHOD AND MATERIALS *Fromthe Department of Pathology, Memorial For the polarization optical investigations we Hospital, Wilmington, Delaware. used a Reichert monocular microscope fitted with This study was supported by a grant from thepolaroid discs as substage polarizer and tube Permanent Science Fund of the Americananalyzer. Photographic records were made with a Academy of Arts and Sciences. Presented at the Twentieth Annual Meeting ofRetina IIC camera, used in conjunction with a The Society for Investigative Dermatology, Inc.,Kodak photomicrographic unit. The sign of bire- Atlantic City, N. J., June 6, 1959. fringence was determined by means of a Zeiss first 257 258 THEJOURNAL OF INVESTIGATIVE DERMATOLOGY order red retardation plate, together with a capalso stained with hematoxylin and eosin, buffered analyzer (9). As in our previous studies (7, 8),thionin (10) and by a modified Gram-Weigert birefringenee referred to the optic axis of themethod (11). keratin and pre-keratin fibres (tonofibrils) in the Previous routine staining technics had estab- histologic material under examination. With thislished in the specimens histologic characteristics equipment, unstained skin sections were ex-associated with hyperkeratosis, parakeratosis or amined. Biopsy specimens were fixed in 10 perdyskeratosis. The sections were classified as fol- cent formalin, embedded in paraffin and sectionedlows: to 3 m thickness. The sections were then depar- 1. Simple hyperkeratosis: callus. affinized, cleared in xylene and mounted in syn- 2. Hyperkeratosis with acanthosis: lichen thetic resin. From each specimen sections weresimplex chronicus. FIG. 1. Pseudo-epitheliomatous hyperplasia associated with stasis dermatitis. The normal pattern of epidermal birefringenee is exaggerated with a widened keratogenous zone and increased tonofibrils. Magnification X400. FIG. 2. Chronic radiation dermatitis showing moderate hypcrkeratosis and orientation of birefringent tonofibrils parallel to the surface. Magnification X400. HYPERKERATOSIS, PARAKERATOSIS AND DYSKERATOSIS 259 FIG.3 FIG. 4 Fias. 3 and 4. Keratotie basal celled carcinoma showing horn cyst and orientation of tonofibrils paral- lel to the surface. Magnification X200, X400. 3. Hyperkeratosis with epidermal hyperplasia: 8. Parakeratosis, hyperkeratosis and dyskera- a) Pseudo-epitheliomatous hyperplasia in stasistosis: senile keratosis. dermatitis b) Verrucous nevus pigmentosus. 0. Dyskeratosis: Darier's disease. 4. Hyperkeratosis with epidermal atrophy: 10.Dyskeratosisand hyperkeratosis involv- chronic radiation dermatitis. ing epidermal and mucosal surfaces: leukoplakia. 5. Hyperkeratosis, parakeratosis and aean- thosis: Verruca plantaris. RESULTS 6. Hyperkeratosis with dyskeratosis: cornu cutaneum. In simple hyperkeratosis, the normal pattern of 7. Parakeratosis: a) psoriasis, h) seborrheic der-epidermal birefringence was observed, though matitis, c) keratotic basal cell carcinoma. the stratum corneum containing highly hire- 260 THEJOURNAL OF INVESTTGATIVE DERMATOLOGY I - a. a I' h Fro. 5. Early leukoplakia showing orientation of cells and doubly refractile fibres parallel to the sur- face. Section stained buffered thionin and viewed under polarized light. Magnification X400. .1 7-4 t*t_t4 1 • Ad5 Fio. 6. Plantar wart with a central area occupied by compressed cornifled cells displaying intense birefringence. Magnification X300. fringent mature keratin fibres was increased in In chronic radiation dermatitis, when hy- thickness. perkeratosis was associated with epidermal Where the hyper/ceratosis was associated withatrophy, there was a paucity of tonofibrils and acanthosis, especially in lesions with pseudo-these were oriented parallel to the skin sur- epitheliomatous hyperplasia, as in a case offace (Fig. 2). A similar orientation of the tono- chronic stasis dermatitis, this normal patternfibrils was seen in an example of keratotic basal was exaggerated. In particular, the keratogenouscell carcinoma with epidermal atrophy and in zone was broadened and very sharply defined;leukoplakia involving the muco-cutaneous junc- the hirefringent tonofibrils were increased intion of the lip (Figs. 3, 4, 5)* number, hut their orientation was identical with *Ithas been shown that in sections of the those in the normal epidermis (Fig. 1). huceal mucosa and in sections of the cow's nose HYPERKERATOSTS, PARAKERATOSIS AND DYSKERATOSIS 261 Inpsoriasis, as previously described (7), the prekeratin fibrils persisted throughout the epi- dermis and in the parakeratotie scale. The birefringent fibres were oriented perpendicularly or at an angle to the surface plane. Mature kera- tin fibres occurred in isolated groups, oriented parallel to the surface. This pattern is appar- ently specific for psoriasis; in other pathologic material no comparable distribution was found. Thus in seborrheic dermatitis, with marked parakeratosis, the normal orientation of the doubly refractilc epidermal fibres was retained, though in parakeratotic areas the bircfringcnce was less intense than in the normal horny layer. Dyskeratosis, defined as a faulty keratinization of individual cpidermal cells (12), is reflected £ under the polarization microscope. In Darier's disease, the villous epidermal projections showed normal tonofibrils. The corps ronds contained bircfringent fibres of low intensity, oriented parallel to the long axis of the cells. In the ab- normal horny layer, the grains appeared to be FIG. 7. Plantar wart showing peripheral area with alternating columns of highly bircfringent and poorly birefringcnt fibres, following the areas of fully cornified and parakeratotic cells and ori- ented in the long axis of these cells. A well-defined keratogenous zone can be
Recommended publications
  • Paraneoplastic Syndrome Presenting As Giant Porokeratosis in a Patient with Nasopharyngeal Cancer
    Paraneoplastic Syndrome Presenting As Giant Porokeratosis in A Patient with Nasopharyngeal Cancer Fitri Azizah, Sonia Hanifati, Sri Adi Sularsito, Lili Legiawati, Shannaz Nadia Yusharyahya, Rahadi Rihatmadja Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia / Dr. Cipto Mangunkusumo National General Hospital Keywords: porokeratosis, giant porokeratosis, paraneoplastic syndrome, nasopharyngeal Abstract: Giant porokeratosis is a rare condition in which the hyperkeratotic plaques of porokeratosis reach up to 20 cm in diameter. Porokeratosis is characterized clinically by hyperkeratotic papules or plaques with a thread-like elevated border. Although rare, porokeratosis has been reported in conjunction with malignancies suggesting a paraneoplastic nature. Associated malignancies reported were hematopoietic, hepatocellular, and cholangiocarcinoma. We report a case of giant porokeratosis in a patient with nasopharyngeal cancer responding to removal of the primary cancer by chemoradiotherapy. 1 INTRODUCTION regress completely after the treatment of malignancy, suggestive of paraneoplastic syndrome. Porokeratosis is a chronic progressive disorder of keratinization, characterized by hyperkeratotic papules or plaques surrounded by a thread-like 2 CASE elevated border corresponds to a typical histologic hallmark, the cornoid lamella . O regan, 2012) There Mr. SS, 68-year-old, was referred for evaluation of are at least six clinical variants of porokeratosis pruritic, slightly erythematous plaques with raised, recognized with known genetic disorder.1 Some hyperpigmented border of one and a half year clinical variant of porokeratosis has been reported in duration on the extensor surface of both legs. The the setting of immunosuppressive conditions, organ lesions shown minimal response to potent topical transplantation, use of systemic corticosteroids, and corticosteroids and phototherapy given during the infections, suggesting that impaired immunity may last 8 months in another hospital.
    [Show full text]
  • Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R.
    [Show full text]
  • Loss-Of-Function Mutations in the Gene Encoding Filaggrin Cause Ichthyosis
    LETTERS Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris Frances J D Smith1, Alan D Irvine2, Ana Terron-Kwiatkowski1, Aileen Sandilands1, Linda E Campbell1, Yiwei Zhao1, Haihui Liao1, Alan T Evans3, David R Goudie4, Sue Lewis-Jones5, Gehan Arseculeratne5, Colin S Munro6, Ann Sergeant6, Gra´inne O’Regan2, Sherri J Bale7, John G Compton7, John J DiGiovanna8,9, Richard B Presland10,11, Philip Fleckman11 & W H Irwin McLean1 Ichthyosis vulgaris (OMIM 146700) is the most common composed of the 400-kDa protein profilaggrin. Following a short, inherited disorder of keratinization and one of the most unique N-terminal domain, most of the profilaggrin molecule consists frequent single-gene disorders in humans. The most widely of 10–12 repeats of the 324-residue filaggrin sequence6. Upon terminal cited incidence figure is 1 in 250 based on a survey of differentiation of granular cells, profilaggrin is proteolytically cleaved 1 B http://www.nature.com/naturegenetics 6,051 healthy English schoolchildren . We have identified into 37-kDa filaggrin peptides and the N-terminal domain contain- homozygous or compound heterozygous mutations R501X and ing an S100-like calcium binding domain. Filaggrin rapidly aggregates 2282del4 in the gene encoding filaggrin (FLG) as the cause of the keratin cytoskeleton, causing collapse of the granular cells into moderate or severe ichthyosis vulgaris in 15 kindreds. In flattened anuclear squames. This condensed cytoskeleton is cross- addition, these mutations are semidominant; heterozygotes linked by transglutaminases during formation of the cornified cell show a very mild phenotype with incomplete penetrance. envelope (CCE). The CCE is the outermost barrier layer of the skin The mutations show a combined allele frequency of B4% which not only prevents water loss but also impedes the entry of in populations of European ancestry, explaining the high allergens and infectious agents7.
    [Show full text]
  • An Abridged Compendium of Words. a Discussion of Them and Opinions About Them
    DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Dermatopathology: An abridged compendium of words. A discussion of them and opinions about them. Part 6 (I-L) Bruce J. Hookerman1 1 Dermatology Specialists, Bridgeton, Missouri, USA Citation: Hookerman BJ. Dermatopathology: An abridged compendium of words. A discussion of them and opinions about them. Part 6 (I-L). Dermatol Pract Concept. 2014;4(4):1. http://dx.doi.org/10.5826/dpc.0404a01 Copyright: ©2014 Hookerman. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Corresponding author: Bruce J. Hookerman, M.D., 12105 Bridgeton Square Drive, St. Louis, MO 63044, USA. Email: [email protected] – I – term “id reaction” only for a spongiotic dermatitis manifested by tiny vesicles on the hands of patients with florid dermato- ICHTHYOSIS: a generic term for skin conditions character- phytosis at another site, usually the feet, or for an analogue ized by what are said to be fishlike scales, i.e., scales that are of that phenomenon such as widespread vesicles that appear broad and polygonal with free edges, as are seen in ichthyosis subsequent to injudicious treatment, i.e., with Gentian violet vulgaris (and its look-alike, acquired ichthyosis), X-linked (known sardonically in times past as “Gentian violent”) of ichthyosis, and lamellar ichthyosis. Conditions reputed to be an exuberant spongiotic dermatitis, usually on the feet, such ichthyosis, such as ichthyosis hystrix and ichthyosis linearis as an allergic contact dermatitis. A time-honored explana- circumflexa, do not qualify because they are not associated tion for an “id” reaction is hematogenous dissemination of with broad polygonal scales.
    [Show full text]
  • Features of Reactive White Lesions of the Oral Mucosa
    Head and Neck Pathology (2019) 13:16–24 https://doi.org/10.1007/s12105-018-0986-3 SPECIAL ISSUE: COLORS AND TEXTURES, A REVIEW OF ORAL MUCOSAL ENTITIES Frictional Keratosis, Contact Keratosis and Smokeless Tobacco Keratosis: Features of Reactive White Lesions of the Oral Mucosa Susan Müller1 Received: 21 September 2018 / Accepted: 2 November 2018 / Published online: 22 January 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract White lesions of the oral cavity are quite common and can have a variety of etiologies, both benign and malignant. Although the vast majority of publications focus on leukoplakia and other potentially malignant lesions, most oral lesions that appear white are benign. This review will focus exclusively on reactive white oral lesions. Included in the discussion are frictional keratoses, irritant contact stomatitis, and smokeless tobacco keratoses. Leukoedema and hereditary genodermatoses that may enter in the clinical differential diagnoses of frictional keratoses including white sponge nevus and hereditary benign intraepithelial dyskeratosis will be reviewed. Many products can result in contact stomatitis. Dentrifice-related stomatitis, contact reactions to amalgam and cinnamon can cause keratotic lesions. Each of these lesions have microscopic findings that can assist in patient management. Keywords Leukoplakia · Frictional keratosis · Smokeless tobacco keratosis · Stomatitis · Leukoedema · Cinnamon Introduction white lesions including infective and non-infective causes will be discussed
    [Show full text]
  • Deimination, Intermediate Filaments and Associated Proteins
    International Journal of Molecular Sciences Review Deimination, Intermediate Filaments and Associated Proteins Julie Briot, Michel Simon and Marie-Claire Méchin * UDEAR, Institut National de la Santé Et de la Recherche Médicale, Université Toulouse III Paul Sabatier, Université Fédérale de Toulouse Midi-Pyrénées, U1056, 31059 Toulouse, France; [email protected] (J.B.); [email protected] (M.S.) * Correspondence: [email protected]; Tel.: +33-5-6115-8425 Received: 27 October 2020; Accepted: 16 November 2020; Published: 19 November 2020 Abstract: Deimination (or citrullination) is a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs). Deimination is involved in physiological processes (cell differentiation, embryogenesis, innate and adaptive immunity, etc.) and in autoimmune diseases (rheumatoid arthritis, multiple sclerosis and lupus), cancers and neurodegenerative diseases. Intermediate filaments (IF) and associated proteins (IFAP) are major substrates of PADs. Here, we focus on the effects of deimination on the polymerization and solubility properties of IF proteins and on the proteolysis and cross-linking of IFAP, to finally expose some features of interest and some limitations of citrullinomes. Keywords: citrullination; post-translational modification; cytoskeleton; keratin; filaggrin; peptidylarginine deiminase 1. Introduction Intermediate filaments (IF) constitute a unique macromolecular structure with a diameter (10 nm) intermediate between those of actin microfilaments (6 nm) and microtubules (25 nm). In humans, IF are found in all cell types and organize themselves into a complex network. They play an important role in the morphology of a cell (including the nucleus), are essential to its plasticity, its mobility, its adhesion and thus to its function.
    [Show full text]
  • Identification of Trichoplein, a Novel Keratin Filament- Binding Protein
    Research Article 1081 Identification of trichoplein, a novel keratin filament- binding protein Miwako Nishizawa1,*, Ichiro Izawa1,*, Akihito Inoko1,*, Yuko Hayashi1, Koh-ichi Nagata1, Tomoya Yokoyama1,2, Jiro Usukura3 and Masaki Inagaki1,‡ 1Division of Biochemistry, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan 2Department of Dermatology, Mie University Faculty of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan 3Department of Anatomy and Cell Biology, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan *These authors contributed equally to this work ‡Author for correspondence (e-mail: [email protected]) Accepted 29 November 2004 Journal of Cell Science 118, 1081-1090 Published by The Company of Biologists 2005 doi:10.1242/jcs.01667 Summary Keratins 8 and 18 (K8/18) are major components of the antibody in a complex with K8/18 and immunostaining intermediate filaments (IFs) of simple epithelia. We report revealed that trichoplein colocalized with K8/18 filaments here the identification of a novel protein termed in HeLa cells. In polarized Caco-2 cells, trichoplein trichoplein. This protein shows a low degree of sequence colocalized not only with K8/18 filaments in the apical similarity to trichohyalin, plectin and myosin heavy chain, region but also with desmoplakin, a constituent of and is a K8/18-binding protein. Among interactions desmosomes. In the absorptive cells of the small intestine, between trichoplein and various IF proteins that we trichoplein colocalized with K8/18 filaments at the apical tested using two-hybrid methods, trichoplein interacted cortical region, and was also concentrated at desmosomes.
    [Show full text]
  • Review an Overview of the Pale and Clear Cells of the Nipple Epidermis
    Histol Histopathol (2009) 24: 367-376 Histology and http://www.hh.um.es Histopathology Cellular and Molecular Biology Review An overview of the pale and clear cells of the nipple epidermis M.F. Garijo, D. Val and J.F. Val-Bernal Department of Anatomical Pathology, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain Summary. The stratified squamous epithelium of the exterior. In the non-lactating breast these duct openings nipple-areola complex may contain pale or clear cells are usually filled with plugs of keratin. The nipple and including: Paget’s disease cells (PDCs), Toker cells areola are covered by keratinizing stratified squamous (TCs), and so-called clear cells (CCs). Paget’s disease is epithelium similar to that seen in the epidermis an uncommon presentation of breast carcinoma. PDCs elsewhere in the body. The collecting ducts show a are large, atypical, have abundant, pale-staining double epithelial and myoepithelial lining. The cytoplasm that may contain mucin secretion vacuoles epithelium is columnar and the myoepithelial cells lie and bulky heterochromatic nuclei. They are commonly between the epithelial layer and the basal lamina. A concentrated along the basal layer and stain for EMA, cross section of the major ducts shows an irregular, CAM5.2, cytokeratin 7, and HER2/neu oncoprotein. TCs pleated or serrated outline and an investment with are bland cells with roundish and scant chromatin nuclei. muscular tissue. The areola dermis contains numerous They are found incidentally and are reactive for EMA, sebaceous glands. Some of them open directly onto the CAM5.2, and cytokeratin 7, but show negativity for surface, whereas others drain into a collecting duct or HER2/neu oncoprotein.
    [Show full text]
  • Keratinization and Its Disorders
    Oman Medical Journal (2012) Vol. 27, No. 5: 348-357 DOI 10. 5001/omj.2012.90 Review Article Keratinization and its Disorders Shibani Shetty, Gokul S. Received: 03 May 2012 / Accepted: 08 July 2012 © OMSB, 2012 Abstract Keratins are a diverse group of structural proteins that form the epithelium (buccal mucosa, labial mucosa) and specialized intermediate filament network responsible for maintaining the mucosa (dorsal surface of the tongue).2 An important aspect structural integrity of keratinocytes. In humans, there are around of stratified squamous epithelia is that the cells undergo a 30 keratin families divided into two groups, namely, acidic and terminal differentiation program that results in the formation basic keratins, which are arranged in pairs. They are expressed in of a mechanically resistant and toughened surface composed of a highly specific pattern related to the epithelial type and stage of cornified cells that are filled with keratin filaments and lack nuclei cellular differentiation. A total of 54 functional genes exist which and cytoplasmic organelles. In these squames, the cell membrane codes for these keratin families. The expression of specific keratin is replaced by a proteinaceous cornified envelope that is covalently genes is regulated by the differentiation of epithelial cells within cross linked to the keratin filaments, providing a highly insoluble the stratifying squamous epithelium. Mutations in most of these yet flexible structure that protects the underlying epithelial cells.1 genes are now associated with specific tissue fragility disorders Keratinization, also termed as cornification, is a process which may manifest both in skin and mucosa depending on the of cytodifferentiation which the keratinocytes undergo when expression pattern.
    [Show full text]
  • An Update on the Biology and Management of Dyskeratosis Congenita and Related Telomere Biology Disorders
    Expert Review of Hematology ISSN: 1747-4086 (Print) 1747-4094 (Online) Journal homepage: https://www.tandfonline.com/loi/ierr20 An update on the biology and management of dyskeratosis congenita and related telomere biology disorders Marena R. Niewisch & Sharon A. Savage To cite this article: Marena R. Niewisch & Sharon A. Savage (2019) An update on the biology and management of dyskeratosis congenita and related telomere biology disorders, Expert Review of Hematology, 12:12, 1037-1052, DOI: 10.1080/17474086.2019.1662720 To link to this article: https://doi.org/10.1080/17474086.2019.1662720 Accepted author version posted online: 03 Sep 2019. Published online: 10 Sep 2019. Submit your article to this journal Article views: 146 View related articles View Crossmark data Citing articles: 1 View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ierr20 EXPERT REVIEW OF HEMATOLOGY 2019, VOL. 12, NO. 12, 1037–1052 https://doi.org/10.1080/17474086.2019.1662720 REVIEW An update on the biology and management of dyskeratosis congenita and related telomere biology disorders Marena R. Niewisch and Sharon A. Savage Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA ABSTRACT ARTICLE HISTORY Introduction: Telomere biology disorders (TBDs) encompass a group of illnesses caused by germline Received 14 June 2019 mutations in genes regulating telomere maintenance, resulting in very short telomeres. Possible TBD Accepted 29 August 2019 manifestations range from complex multisystem disorders with onset in childhood such as dyskeratosis KEYWORDS congenita (DC), Hoyeraal-Hreidarsson syndrome, Revesz syndrome and Coats plus to adults presenting Telomere; dyskeratosis with one or two DC-related features.
    [Show full text]
  • Progressive Widespread Warty Skin Growths
    DERMATOPATHOLOGY DIAGNOSIS Progressive Widespread Warty Skin Growths Patrick M. Kupiec, BS; Eric W. Hossler, MD Eligible for 1 MOC SA Credit From the ABD This Dermatopathology Diagnosis article in our print edition is eligible for 1 self-assessment credit for Maintenance of Certification from the American Board of Dermatology (ABD). After completing this activity, diplomates can visit the ABD website (http://www.abderm.org) to self-report the credits under the activity title “Cutis Dermatopathology Diagnosis.” You may report the credit after each activity is completed or after accumu- lating multiple credits. A 33-year-old man presented with progres- sive widespread warty skin growths that had been present copysince 6 years of age. Physical examination revealed numerous verrucous papules on the face and neck along with Figure 1. H&E, original magnification ×40. Figure 2. H&E, original magnification ×40. verrucous, tan-pink papules and plaques diffuselynot scattered on the trunk, arms, and legs. A biopsy of a lesion on the neck Dowas performed. H&E, original magnification ×200. The best diagnosisCUTIS is: a. condyloma acuminatum b. epidermodysplasia verruciformis c. herpesvirus infection d. molluscum contagiosum e. verruca vulgaris PLEASE TURN TO PAGE 99 FOR DERMATOPATHOLOGY DIAGNOSIS DISCUSSION Mr. Kupiec is from the State University of New York (SUNY) Upstate Medical University, Syracuse. Dr. Hossler is from the Departments of Dermatology and Pathology, Geisinger Medical Center, Danville, Pennsylvania. The authors report no conflict of interest. Correspondence: Patrick M. Kupiec, BS, 50 Presidential Plaza, Syracuse, NY 13202 ([email protected]). 82 CUTIS® WWW.CUTIS.COM Copyright Cutis 2017. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher.
    [Show full text]
  • Trichohyalin-Like 1 Protein Plays a Crucial Role in Proliferation and Anti
    Makino et al. Cell Death Discovery (2020) 6:109 https://doi.org/10.1038/s41420-020-00344-5 Cell Death Discovery ARTICLE Open Access Trichohyalin-like 1 protein plays a crucial role in proliferation and anti-apoptosis of normal human keratinocytes and squamous cell carcinoma cells Teruhiko Makino 1,MegumiMizawa1, Yoko Yoshihisa1, Seiji Yamamoto2, Yoshiaki Tabuchi 3, Masashi Miyai4, Toshihiko Hibino4, Masakiyo Sasahara2 and Tadamichi Shimizu1 Abstract Epidermal differentiation is a complex process that requires the regulated and sequential expression of various genes. Most fused-type S100 proteins are expressed in the granular layer and it is hypothesized that these proteins may be associated with cornification and barrier formation. We previously identified a member of the fused-type S100 proteins, Trichohyalin-like 1 (TCHHL1) protein. TCHHL1 is distributed in the basal layer of the normal epidermis. Furthermore, the expression is markedly increased in cancerous/non-cancerous skin samples with the hyperproliferation of keratinocytes. We herein examined the role of TCHHL1 in normal human keratinocytes (NHKs) and squamous cell carcinoma (SCC). The knockdown of TCHHL1 by transfection with TCHHL1 siRNA significantly inhibited proliferation and induced the early apoptosis of NHKs. In TCHHL1-knockdown NHKs, the level of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was markedly decreased. In addition, the slight inhibition of v-akt murine thymoma viral oncogene homolog (AKT) phosphorylation and upregulation of forkhead box-containing protein O1(FOXO1), B-cell lymphoma2 (BCL2) and Bcl2-like protein 11 (BCL2L11) was observed. Skin-equivalent models fi 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; built by TCHHL1-knockdown NHKs showed a markedly hypoplastic epidermis.
    [Show full text]