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Clinical Reviews in Allergy & Immunology Dec 2023Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant... (Review)
Review
Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant keratosis. This led to introducing the term autoinflammatory keratinization diseases encompassing entities in which monogenic mutations cause spontaneous activation of the innate immunity and subsequent disruption of the keratinization process. Originally, autoinflammatory keratinization diseases were attributed to pathogenic variants of CARD14 (generalized pustular psoriasis with concomitant psoriasis vulgaris, palmoplantar pustulosis, type V pityriasis rubra pilaris), IL36RN (generalized pustular psoriasis without concomitant psoriasis vulgaris, impetigo herpetiformis, acrodermatitis continua of Hallopeau), NLRP1 (familial forms of keratosis lichenoides chronica), and genes of the mevalonate pathway, i.e., MVK, PMVK, MVD, and FDPS (porokeratosis). Since then, endotypes underlying novel entities matching the concept of autoinflammatory keratinization diseases have been discovered (mutations of JAK1, POMP, and EGFR). This review describes the concept and pathophysiology of autoinflammatory keratinization diseases and outlines the characteristic clinical features of the associated entities. Furthermore, a novel term for NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) describing the spectrum of autoinflammatory keratinization diseases secondary to NLRP1 mutations is proposed.
Topics: Humans; Psoriasis; Inflammation; Mutation; Immunity, Innate; Keratosis; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; Interleukins
PubMed: 38103162
DOI: 10.1007/s12016-023-08971-3 -
Frontiers in Oncology 2023Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we...
BACKGROUND
Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs.
METHODS
Immunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations.
RESULTS
In the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in , , , and genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in and genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis.
CONCLUSION
LS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.
PubMed: 37529690
DOI: 10.3389/fonc.2023.1194232 -
Journal of Yeungnam Medical Science Oct 2023Porokeratosis ptychotropica is an uncommon form of porokeratosis, which was initially described in 1995. It is clinically characterized by symmetrical reddish to...
Porokeratosis ptychotropica is an uncommon form of porokeratosis, which was initially described in 1995. It is clinically characterized by symmetrical reddish to brown-colored hyperkeratotic, verrucous, or psoriasiform plaques on the perianal and gluteal regions. The lesions tend to integrate and expand centrally, with small peripheral satellite lesions. Early skin biopsy and appropriate diagnosis are essential because malignant change occurs in 7.5% of porokeratotic lesions. Conventional treatment options include topical steroid, retinoid, imiquimod, 5-fluorouracil, isotretinoin, excimer laser, photodynamic therapy, intralesional steroid or bleomycin injection, cryotherapy, carbon dioxide (CO2) laser, and dermatome and excision, but none seem to achieve complete clearance. A 68-year-old woman presented with diffuse hyperkeratotic scaly lichenoid plaques on the buttocks that had persisted for several years. A skin biopsy of the buttocks revealed multiple cornoid lamellae and intense hyperkeratosis. There were some dyskeratotic cells beneath the cornoid lamellae and the granular layer was absent. Porokeratosis ptychotropica was diagnosed based on the characteristic clinical appearance and typical histopathological manifestations. She was treated with a CO2 laser in one session and topical application of urea and imiquimod cream for 1 month. The lesions slightly improved at the 1-month follow-up. We herein present a rare case of porokeratosis ptychotropica.
PubMed: 36464945
DOI: 10.12701/jyms.2022.00549 -
Metabolites Nov 2023Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the... (Review)
Review
Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porokeratosis (also known as genitogluteal porokeratosis), follicular porokeratosis and porokeratoma. Apart from the clinical presentation and epidemiology of each variant listed, this review aims at providing up-to-date information on the precise genetic background, introduces imaging methods facilitating the diagnosis (conventional and ultraviolet-induced fluorescence dermatoscopy, reflectance confocal microscopy and pathology), discusses their oncogenic potential and reviews the literature data on the efficacy of the treatment used, including the drugs directly targeting the isoprenoid-mevalonate pathway.
PubMed: 38132857
DOI: 10.3390/metabo13121176 -
Indian Dermatology Online Journal 2023
PubMed: 37521240
DOI: 10.4103/idoj.idoj_408_22 -
Case Reports in Dermatology 2023Porokeratosis is a group of well-known clinically distinct entities, characterised by different clinical aspects, but sharing a single common histological aspect, namely...
Porokeratosis is a group of well-known clinically distinct entities, characterised by different clinical aspects, but sharing a single common histological aspect, namely the cornoid lamella. Usually, porokeratosis occurs in the limbs and trunk, while it rarely involves the face, especially as an exclusive, single, and solitary lesion. We report the case of a 52-year-old Caucasian woman, with an 11-month history of a 2-cm slowly growing solitary, keratotic lesion on her left cheekbone. The patient did not present other cutaneous lesions on the face, as well as in other body sites. A cutaneous biopsy showed epidermal hyperplasia with multiple, sharply defined cornoid lamella, associated with an underlying attenuation of the granular layer and scattered dyskeratotic cells in the spinous layer. The superficial dermis underneath showed a mild lymphocytic infiltrate and fibrosis with remodelled collagen bundles. A final diagnosis of solitary facial porokeratosis was made.
PubMed: 37899946
DOI: 10.1159/000530936 -
Acta Dermato-venereologica Aug 2023This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated...
This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated healthcare usage. Patients diagnosed with genodermatoses were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) between 2016 and 2020. Clinical data from medical records were used to verify diagnoses recorded in the National Patient Registry (NPR). The NPR was then searched for International Classification of Diseases, Tenth Revision (ICD-10) codes Q80-82 and Q84 from 2001 to 2020. The local cohort included 298 patients with 36 unique genodermatosis diagnoses. Verification of these diagnoses in the NPR showed positive predictive values of over 90%. The NPR search yielded 13,318 patients with 73 unique diagnoses, including ichthyoses (n = 3,341; 25%), porokeratosis (n = 2,277; 17%), palmoplantar keratodermas (n = 1,754; 13%), the epidermolysis bullosa group (n = 1011; 7%); Darier disease (n = 770; 6%), Hailey-Hailey disease (n = 477; 4%) and Gorlin syndrome (n = 402; 3%). The incidence and prevalence of each diagnosis were calculated based on the nationwide cohort and are reported. A total of 149,538 outpatient visits were registered, a mean of 4.6 visits per patient. This study provides a valuable resource for the epidemiology of genodermatoses by reporting on the incidence and prevalence of 73 different genodermatoses.
Topics: Humans; Incidence; Prevalence; Sweden; Cohort Studies; Retrospective Studies
PubMed: 37615526
DOI: 10.2340/actadv.v103.12404