{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T19:16:40Z","timestamp":1788376600200,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of M\u00fcnster Medical School","award":["S\u00dc212007"],"award-info":[{"award-number":["S\u00dc212007"]}]},{"award":["S\u00dc212007"],"award-info":[{"award-number":["S\u00dc212007"]}],"id":[{"id":"https:\/\/ror.org\/00pd74e08","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Deutsche Dermatologische Gesellschaft"},{"DOI":"10.13039\/501100006693","name":"Arbeitsgemeinschaft Dermatologische Forschung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006693","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/010k7sz25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatopathology"],"abstract":"<jats:p>Desmosomes are specialized cell\u2013cell junctions that play a crucial role in maintaining the structural integrity of both cornifying and non-cornifying epithelium. Disruption of desmosomal cohesion in autoimmune, infectious, and other diseases is typically associated with acantholysis, often leading to intraepidermal blisters and erosions. In recent decades, genetic mutations have been identified that impair desmosomal integrity to varying degrees, giving rise to a spectrum of genodermatoses. These conditions, which include palmoplantar keratoderma, epidermolysis bullosa, and ichthyoses, can range from mild to severe, with some forms being syndromic and life-threatening. We investigated dermatopathologic changes in patients with mutations in genes encoding desmosomal proteins seen in consultations at our genodermatoses unit. A series of cases, including keratosis palmoplantaris areata et striata (striated palmoplantar keratoderma type 1), Carvajal\u2013Huerta syndrome, severe dermatitis\u2013multiple allergies\u2013metabolic wasting (SAM) syndrome, ectodermal dysplasia\u2013skin fragility syndrome, and inflammatory peeling skin disease, was examined histologically and, when necessary, immunohistochemically. Findings from our cohort were compared with histopathological consultation cases from our dermatopathology laboratory and previously published cases in the literature. Through these observations, we defined a distinct form of acantholysis associated with desmosomal protein mutations, which we term \u201cdesmosomal-type acantholysis.\u201d We outline the spectrum of this newly characterized pattern and highlight its differences from conventional forms of acantholysis. Furthermore, for the first time, we describe incidental cases where \u201cdesmosomal-type acantholysis\u201d appears sporadically in solitary acanthoma and in association with a melanocytic nevus.<\/jats:p>","DOI":"10.3390\/dermatopathology13020017","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T01:12:33Z","timestamp":1775437953000},"page":"17","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Desmosomal-Type Acantholysis\u2014A New Histologic Pattern Related to Mutations of Genes for Desmosomal Proteins"],"prefix":"10.3390","volume":"13","author":[{"given":"Dieter","family":"Metze","sequence":"first","affiliation":[{"name":"International Training Centre for Dermatopathology of the ICDP\/UEMS, Dermatopathology Unit, Department of Dermatology, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Dermatology, University Hospital Muenster, Von-Esmarch-Str. 56, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"S\u00fc\u00dfmuth","sequence":"additional","affiliation":[{"name":"Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Metze","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Cologne, Kerpener Stra\u00dfe 62, 50937 K\u00f6ln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinzenz","family":"Oji","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Muenster, Von-Esmarch-Str. 56, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Traupe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Muenster, Von-Esmarch-Str. 56, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Griffiths, C.E.M., Barker, J., Bleiker, T.O., Hussain, W., and Simpson, R.C. (2024). Inherited Disorders of Cornification. Rook\u2019s Textbook of Dermatology, John Wiley & Sons. [10th ed.]. Chapter 65.","DOI":"10.1002\/9781119709268"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"S\u00fc\u00dfmuth, K., Oji, V., Bodes, J., Jochum, I., Muhs, F., Komlosi, K., Hausser, I., Schmuth, M., Traupe, H., and Fischer, J. (2026). Defining Histological Patterns in Inherited Ichthyoses: Toward a Diagnostic Algorithm Based on 66 Confirmed Cases. Dermatopathology, 13.","DOI":"10.3390\/dermatopathology13010009"},{"key":"ref_3","first-page":"1","article-title":"The structure and function of skin","volume":"Volume 1","author":"Calonje","year":"2020","journal-title":"McKee\u2019s Pathology of the Skin"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1111\/bjd.19342","article-title":"Mutations in genes encoding desmosomal proteins: Spectrum of cutaneous and extracutaneous abnormalities","volume":"184","author":"Lee","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bariani, R., Rigato, I., Cason, M., Marinas, M.B., Celeghin, R., Pilichou, K., and Bauce, B. (2022). Genetic Background and Clinical Features in Arrhythmogenic Left Ventricular Cardiomyopathy: A Systematic review. J. Clin. Med., 11.","DOI":"10.3390\/jcm11154313"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijcard.2020.06.005","article-title":"Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria","volume":"319","author":"Corrado","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Hatzfeld, M., and Keil, R. (2021). Desmosomes as Signaling Hubs in the Regulation of Cell Behavior. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.745670"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jdermsci.2014.02.005","article-title":"Genetic skin diseases related to desmosomes and corneodesmosomes","volume":"74","author":"Igawa","year":"2014","journal-title":"J. Dermatol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s40257-022-00700-4","article-title":"Biologic Therapies for the Management of Cutaneous Findings in Genodermatoses: A Review","volume":"23","author":"Joshi","year":"2022","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/bjd\/ljae420","article-title":"Biologics in congenital ichthyosis: Are they effective?","volume":"192","author":"Milesi","year":"2025","journal-title":"Br. J. Dermatol."},{"key":"ref_11","unstructured":"Patterson, J.W. (2025). The vesiculobullous reaction patterns. Weedons\u2019s Skin Pathology, Elsevier. [6th ed.]. Chapter 7."},{"key":"ref_12","first-page":"405","article-title":"Autoimmune bullous dermatoses","volume":"21","author":"Holtsche","year":"2023","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/1346-8138.13769","article-title":"Mimickers of classic acantholytic diseases","volume":"44","author":"Ho","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1001\/archderm.1970.04000090015003","article-title":"Histopathologic concept of epidermolytic hyperkeratosis","volume":"102","author":"Ackerman","year":"1970","journal-title":"Arch. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1001\/archderm.1972.01620140050014","article-title":"Focal acantholytic dyskeratosis","volume":"106","author":"Ackerman","year":"1972","journal-title":"Arch. Dermatol."},{"key":"ref_16","unstructured":"Patterson, J.W. (2025). Disorders of epidermal maturation and keratinization. Weedons\u2019s Skin Pathology, Elsevier. [6th ed.]. Chapter 10."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/ng1097-240","article-title":"Mutations in the plakophilin 1 gene result in ectodermal dysplasia\/skin fragility syndrome","volume":"17","author":"McGrath","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jaad.2009.05.016","article-title":"Disadhesion of epidermal keratinocytes: A histologic clue to palmoplantar keratodermas caused by DSG1 mutations","volume":"62","author":"Bergman","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/j.1365-2133.2004.05996.x","article-title":"Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1 mutations is associated with contrasting perturbations of desmosomes and the keratin filament network","volume":"150","author":"Wan","year":"2004","journal-title":"Br. J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1001\/archderm.141.5.625","article-title":"Diffuse nonepidermolytic palmoplantar keratoderma caused by a recurrent nonsense mutation in DSG1","volume":"141","author":"Keren","year":"2005","journal-title":"Arch. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/bjd.13247","article-title":"Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies","volume":"172","author":"Has","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S0190-9622(98)70317-2","article-title":"Epidermolytic palmoplantar keratoderma with woolly hair and dilated cardiomyopathy","volume":"39","year":"1998","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1093\/hmg\/9.18.2761","article-title":"Recessive mutation in desmoplakin disrupts desmoplakin\u2013intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma","volume":"9","author":"Norgett","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1086\/496901","article-title":"Loss of desmoplakin tail causes lethal acantholytic epidermolysis","volume":"77","author":"Jonkman","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/ng.2739","article-title":"Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting","volume":"45","author":"Samuelov","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.jaci.2015.05.002","article-title":"Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin","volume":"136","author":"McAleer","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/exd.13551","article-title":"SAM syndrome is characterized by extensive phenotypic heterogeneity","volume":"27","author":"Taiber","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.jaci.2018.04.007","article-title":"Epithelial barrier dysfunction in desmoglein-1 deficiency","volume":"142","author":"Polivka","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1172\/JCI65220","article-title":"Desmoglein-1\/Erbin interaction suppresses ERK activation to support epidermal differentiation","volume":"123","author":"Harmon","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/exd.14096","article-title":"Ectodermal dysplasia-skin fragility syndrome: Two new cases and review of this desmosomal genodermatosis","volume":"29","author":"Doolan","year":"2020","journal-title":"Exp. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1083\/jcb.149.1.209","article-title":"The function of plakophilin 1 in desmosome assembly and actin filament organization","volume":"149","author":"Hatzfeld","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1046\/j.1365-2133.1999.02667.x","article-title":"Skin fragility and hypohidrotic ectodermal dysplasia resulting from ablation of plakophilin 1","volume":"140","author":"McGrath","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.det.2009.10.014","article-title":"Ectodermal dysplasia-skin fragility syndrome","volume":"28","author":"McGrath","year":"2010","journal-title":"Dermatol. Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/01.dad.0000157451.46657.a6","article-title":"Histopathologic and ultrastructural study of Ectodermal dysplasia\/skin fragility syndrome","volume":"27","author":"Bergman","year":"2005","journal-title":"Am. J. Dermatopathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/jid.2010.434","article-title":"Peeling skin syndrome: Genetic defects in late terminal differentiation of the epidermis","volume":"131","author":"Bowden","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ygeno.2012.01.005","article-title":"Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome","volume":"99","author":"Cabral","year":"2012","journal-title":"Genomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ajhg.2010.07.005","article-title":"Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: Unraveling the peeling skin disease","volume":"87","author":"Oji","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/sj.ejhg.5200605","article-title":"Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma","volume":"9","author":"Hunt","year":"2001","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/j.1365-2133.2008.08946.x","article-title":"Acantholytic ectodermal dysplasia: Clinicopathological study of a new desmosomal disorder","volume":"160","author":"Winik","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1038\/jid.2010.7","article-title":"Homozygous mutations in the 5\u2032 region of the JUP gene result in cutaneous disease but normal heart development in children","volume":"130","author":"Cabral","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1111\/j.1365-2133.2010.09668.x","article-title":"Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: Expanding the phenotype and implications for desmoplakin function in skin and heart","volume":"162","author":"Bolling","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/hmg\/ddr064","article-title":"Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: A novel clinico-genetic entity","volume":"20","author":"Pigors","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/bjd.18921","article-title":"Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility","volume":"183","author":"Has","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/hmg\/ddv481","article-title":"Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome","volume":"25","author":"Boyden","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/DAD.0000000000000425","article-title":"Skin Biopsy in Netherton Syndrome: A Histological Review of a Large Series and New Findings","volume":"38","author":"Bodemer","year":"2016","journal-title":"Am. J. Dermatopathol."},{"key":"ref_46","first-page":"53","article-title":"Disorders of Keratinization","volume":"Volume 1","author":"Calonje","year":"2020","journal-title":"McKee\u2019s Pathology of the Skin"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/DAD.0000000000001927","article-title":"Hyaline Inclusion Acanthoma","volume":"43","author":"Tran","year":"2021","journal-title":"Am. J. Dermatopathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1600-0560.1996.tb01469.x","article-title":"Involvement of the adherens junction-actin filament system in acantholytic dyskeratosis of Hailey-Hailey disease. A histological, ultrastructural, and histochemical study of lesional and non-lesional skin","volume":"23","author":"Metze","year":"1996","journal-title":"J. Cutan. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1001\/archderm.1986.01660130075029","article-title":"Continual skin peeling syndrome. An electron microscopic study","volume":"122","author":"Silverman","year":"1986","journal-title":"Arch. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/bjd\/ljac026","article-title":"Biallelic TUFT1 variants cause woolly hair, superficial skin fragility and desmosomal defects","volume":"188","author":"Jackson","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jid.2023.02.044","article-title":"Disruption of TUFT1, a desmosome-associated protein, causes skin fragility, woolly hair, and palmoplantar keratoderma","volume":"144","author":"Verkerk","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/00000372-199502000-00005","article-title":"Incidental epidermolytic hyperkeratosis","volume":"17","author":"Mahaisavariya","year":"1995","journal-title":"Am. J. Dermatopathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0190-9622(98)70599-7","article-title":"Incidental focal acantholytic dyskeratosis","volume":"38","author":"DiMaio","year":"1998","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/cup.12165","article-title":"Solitary epidermolytic acanthoma","volume":"40","author":"Kazlouskaya","year":"2013","journal-title":"J. Cutan. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/1346-8138.13323","article-title":"Case of isolated epidermolytic acanthoma: Genetic and immunohistochemical analysis","volume":"43","author":"Adachi","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/00000372-200110000-00020","article-title":"Incidental histolopathologic patterns: Possible evicence of \u2018field cancerization\u2019 surrounding skin tumors","volume":"23","author":"Carlson","year":"2001","journal-title":"Am. J. Dermatopathol."}],"container-title":["Dermatopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2296-3529\/13\/2\/17\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:53:30Z","timestamp":1788170010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2296-3529\/13\/2\/17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["dermatopathology13020017"],"URL":"https:\/\/doi.org\/10.3390\/dermatopathology13020017","relation":{},"ISSN":["2296-3529"],"issn-type":[{"value":"2296-3529","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]}}}