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1
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Noble CA, Bhate C, Duong BT, Cruse AR, Brodell RT, Hanus RC. Clinical-pathologic correlation: The impact of grossing at the bedside. Semin Diagn Pathol 2025; 42:150836. [PMID: 38336505 DOI: 10.1053/j.semdp.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 01/02/2024] [Indexed: 02/12/2024]
Abstract
The unenlightened clinician may submit a skin specimen to the lab and expect an "answer." The experienced clinician knows that in performing skin biopsies, it is critical to select the most appropriate: 1) anatomic location for the biopsy1,2; 2) type of biopsy1,2; 3) depth and breadth of the biopsy; and 4) medium for hematoxylin and eosin staining (formalin) or direct immunofluorescence (Michel's Transport Medium or normal saline).2 Demographic information, anatomic location, clinical context, and differential diagnosis are all critical components of a properly completed requisition form.3-5 Proper biopsy design and appropriate grossing of the tissue at the bedside should be added to this list. In this article, we review the basics of gross pathologic examination and then provide four examples to demonstrate that optimal clinical-pathologic correlation requires the clinician consider the needs of the pathologist when tissue is presented to the lab.
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Affiliation(s)
- C Alexis Noble
- PGY-3, Department of Dermatology, University of Mississippi Medical Center, Jackson, MS, United States.
| | - Chinmoy Bhate
- Clinical Assistant Professor, Dermatology, Pathology & Laboratory Medicine Rutgers New Jersey Medical School Newark, New Jersey, United States
| | - Buu T Duong
- University of Mississippi Medical Center Jackson, Mississippi, United States
| | - Allison R Cruse
- Assistant Professor, Department of Dermatology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Robert T Brodell
- Professor and Chair, Department of Dermatology, Professor, Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Riley C Hanus
- Department of Mechanical Engineering, Georgia Institute of Technology Atlanta, GA, United States
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2
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Hamm C, Lipson J. Genital porokeratosis: A case report and review of pathogenesis and genitogluteal subtypes of porokeratosis. SAGE Open Med Case Rep 2025; 13:2050313X241311369. [PMID: 39781378 PMCID: PMC11707782 DOI: 10.1177/2050313x241311369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 11/19/2024] [Indexed: 01/12/2025] Open
Abstract
Porokeratosis is a condition characterized by abnormal epidermal keratinization with a unique morphology of papules or plaques surrounded by a thread-like border of scale corresponding to the cornoid lamella on histology. Many established subtypes have been described; however, genitogluteal porokeratosis is a rare entity. We present the case of a 58-year-old male with pruritic reddish lesions affecting the genitals and thighs, diagnosed with genital porokeratosis. This case highlights features of this rare and diagnostically challenging subtype of porokeratosis.
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Affiliation(s)
- Camille Hamm
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Jennifer Lipson
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- The Ottawa Hospital Division of Dermatology, Ottawa, ON, Canada
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3
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Zhao A, Wang X, Pan C, Wang Y, Cao Q, Li M, Li M. Epidermal second-hit mutation in MVK gene associated with linear porokeratosis. Genes Dis 2025; 12:101314. [PMID: 39386107 PMCID: PMC11462185 DOI: 10.1016/j.gendis.2024.101314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 03/16/2024] [Accepted: 04/21/2024] [Indexed: 10/12/2024] Open
Affiliation(s)
- Anqi Zhao
- Department of Dermatology, The Children's Hospital of Fudan University, Shanghai 201102, China
- Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
- Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Xinyi Wang
- Department of Dermatology, Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Chaolan Pan
- Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
- Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Yumeng Wang
- Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
- Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Qiaoyu Cao
- Department of Dermatology, The Children's Hospital of Fudan University, Shanghai 201102, China
| | - Min Li
- Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, Jiangsu 215000, China
| | - Ming Li
- Department of Dermatology, The Children's Hospital of Fudan University, Shanghai 201102, China
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4
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Tognetti L, Cappilli S, Falcinelli F, Soglia S, Lacarrubba F, Maione V, Ricci C, Suppa M, Venturini M, Cinotti E, Di Stefani A, Perrot JL, Rubegni P. Line-field confocal optical coherence tomography for the differential diagnosis of porokeratosis from clinical mimickers: a preliminary study. Clin Exp Dermatol 2024; 49:1641-1650. [PMID: 39056248 DOI: 10.1093/ced/llae285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 05/15/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Porokeratosis variants are relatively rare and can be clinically misdiagnosed with several common papulokeratotic mimickers. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to explore the skin in vivo up to a depth of 500 µm. OBJECTIVES To investigate the role of LC-OCT in the diagnosis of many porokeratosis variants in a preliminary study. METHOD In total, 130 LC-OCT images were obtained from 98 patients, 45 affected by a porokeratosis variant (69 images) and 53 with a mimicker condition (61 images). RESULTS We found almost perfect interobserver agreement for LC-OCT image interpretation and perfect correspondence with the findings from histological slides. In addition, a series of morphological in vivo and three-dimensional features related to the cornoid lamella were detected by LC-OCT that were not visible from the histology. CONCLUSIONS This device can be proposed to assist with rapid bedside noninvasive differentiation of porokeratosis variants from their mimickers, possibly sparing incisional biopsy in patients where the diagnosis is uncertain.
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Affiliation(s)
- Linda Tognetti
- Dermatology Unit and Skin Bank, Department of Medical, Surgical and Neurosciences, Siena University Hospital, Siena, Italy
| | - Simone Cappilli
- UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome,Italy
- Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Falcinelli
- Dermatology Unit and Skin Bank, Department of Medical, Surgical and Neurosciences, Siena University Hospital, Siena, Italy
| | - Simone Soglia
- Department of Dermatology, University of Brescia, Brescia, Italy
| | | | - Vincenzo Maione
- Department of Dermatology, University of Brescia, Brescia, Italy
| | - Costantino Ricci
- Unit of Pathology, Maggiore Hospital, AUSL Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Mariano Suppa
- Department of Dermatology, Hôpital Erasme, HUB, Université Libre de Bruxelles, Belgium
- Department of Dermatology, Institut Jules Bordet, HUB, Université Libre de Bruxelles, HUB, Brussels, Belgium
- Groupe d'imagerie cutanée noninvasive (GICNI) of the Société Française de Dermatologie (SFD), Paris, France
| | - Marina Venturini
- Department of Dermatology, University of Brescia, Brescia, Italy
| | - Elisa Cinotti
- Dermatology Unit and Skin Bank, Department of Medical, Surgical and Neurosciences, Siena University Hospital, Siena, Italy
- Groupe d'imagerie cutanée noninvasive (GICNI) of the Société Française de Dermatologie (SFD), Paris, France
| | - Alessandro Di Stefani
- UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome,Italy
- Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Jean Luc Perrot
- Groupe d'imagerie cutanée noninvasive (GICNI) of the Société Française de Dermatologie (SFD), Paris, France
- Department of Dermatology, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Pietro Rubegni
- Dermatology Unit and Skin Bank, Department of Medical, Surgical and Neurosciences, Siena University Hospital, Siena, Italy
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5
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Popa LG, Gradinaru TC, Giurcaneanu C, Tudose I, Vivisenco CI, Beiu C. Disseminated Superficial Non-actinic Porokeratosis: A Consequence of Post-traumatic Immunosuppression. Cureus 2024; 16:e73218. [PMID: 39650990 PMCID: PMC11624971 DOI: 10.7759/cureus.73218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2024] [Indexed: 12/11/2024] Open
Abstract
Disseminated superficial porokeratosis (DSP) is a very uncommon dermatologic condition of unknown etiology, characterized by the clonal proliferation of atypical keratinocytes associated with aberrant keratinocyte differentiation. These lead to the development of the specific cornoid lamella that separates atypical from normal keratinocytes. DSP is most frequently encountered in immunosuppressed patients. It has been described in patients receiving immunosuppressive treatments, organ transplantation and in patients diagnosed with human immunodeficiency virus, hepatitis B and hepatitis C virus infection. We present the case of a 78-year-old patient who developed disseminated non-actinic after multiple trauma and major orthopedic surgery. To our knowledge, this is the first case of DSP occurring as a consequence of post-traumatic immunosuppression reported in the medical literature. We discuss the pathogenic mechanisms, as well as the optimal diagnostic and therapeutic approach in such cases.
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Affiliation(s)
- Liliana G Popa
- Dermatology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Teodora Cristiana Gradinaru
- Dermatology, Elias Emergency University Hospital, Bucharest, ROU
- Biochemistry, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Calin Giurcaneanu
- Dermatology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Irina Tudose
- Pathology, Elias Emergency University Hospital, Bucharest, ROU
| | | | - Cristina Beiu
- Oncologic Dermatology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
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6
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Agüero R, Navarrete-Dechent C, Akay BN. Scalp Porokeratosis: Dermoscopy Key Role in Unmasking a Hidden Condition. Dermatol Pract Concept 2024; 14:dpc.1404a248. [PMID: 39652907 PMCID: PMC11619971 DOI: 10.5826/dpc.1404a248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2024] [Indexed: 12/12/2024] Open
Affiliation(s)
- Rosario Agüero
- Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Cristián Navarrete-Dechent
- Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Melanoma and Skin Cancer Unit, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Bengu Nisa Akay
- Ankara University, Medicine Faculty, Department of Dermatology, Ankara, Turkey
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7
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Zhang X, Shi W, Wang J, Zhang R. A case of porokeratosis with a variety of morphological manifestations. Clin Case Rep 2024; 12:e9369. [PMID: 39206072 PMCID: PMC11348384 DOI: 10.1002/ccr3.9369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/02/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024] Open
Abstract
This case illustrates the clinical heterogeneity of porokeratosis (PK), with a patient presenting with both disseminated superficial actinic PK-like facial lesions and PK of Mibelli-like lesions on the buttocks and lower limbs. Ultraviolet exposure, infection, and immunosuppression may contribute to the manifestation of multiple clinical forms in a single patient. Close monitoring for potential malignant transformation is essential, particularly in elderly patients with long disease duration and a history of oncological conditions.
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Affiliation(s)
- Xiang Zhang
- Department of DermatologyThe Second Affiliated Hospital of Wannan Medical CollegeWuhuChina
| | - Weiwei Shi
- Department of DermatologyAffiliated Hospital 2 of Nantong UniversityNantongChina
- Department of DermatologyThe Third Affiliated Hospital of Soochow UniversityChangzhouChina
| | - Jun Wang
- Department of DermatologyThe Third Affiliated Hospital of Soochow UniversityChangzhouChina
| | - Ruzhi Zhang
- Department of DermatologyThe Second Affiliated Hospital of Wannan Medical CollegeWuhuChina
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8
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La Y, Zhu J, Mueller SM. Conventional and Novel Treatment Strategies for Porokeratoses: A Narrative Review. J Dtsch Dermatol Ges 2024; 22:1073-1077. [PMID: 38961534 DOI: 10.1111/ddg.15436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/25/2024] [Indexed: 07/05/2024]
Abstract
Porokeratoses are a heterogenous group of autoinflammatory keratinization disorders all characterized by the presence of a cornoid lamella. In addition to gene mutations affecting the mevalonate pathway, environmental factors such as UV radiation, immunosuppression, trauma, and infection are also thought to contribute to porokeratoses. To date, there are no management guidelines or levels of evidence for commonly used pharmacologic and non-pharmacologic treatment options for porokeratoses. Conventional treatment strategies encompass topical and systemic drugs (e.g., salicylic acid, topical glucocorticoids, and retinoids), phototherapy, laser, and surgical interventions. Better insights into the pathogenesis of porokeratoses have paved the way for the development of novel therapeutic approaches, such as topical statins or the use of monoclonal antibodies. This narrative review aims to summarize both conventional and novel treatment options, including their level of evidence, advantages, and disadvantages.
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Affiliation(s)
- Yumeng La
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, China
| | - Jie Zhu
- Department of Dermatology, University Hospital Basel, Basel, Switzerland
| | - Simon M Mueller
- Department of Dermatology, University Hospital Basel, Basel, Switzerland
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9
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La Y, Zhu J, Mueller SM. Konventionelle und neue Behandlungsstrategien bei Porokeratosen: Eine narrative Übersicht. J Dtsch Dermatol Ges 2024; 22:1073-1078. [PMID: 39105229 DOI: 10.1111/ddg.15436_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/25/2024] [Indexed: 08/07/2024]
Abstract
ZusammenfassungPorokeratosen sind eine heterogene Gruppe autoinflammatorischer Keratinisierungsstörungen, die durch kornoide Lamellen gekennzeichnet sind. Neben Genmutationen, die sich auf den Mevalonat‐Stoffwechselweg auswirken, werden auch Umweltfaktoren wie UV‐Strahlung, Immunsuppression, Traumata und Infektionen für die Entstehung von Porokeratosen verantwortlich gemacht. Bislang gibt es keine Behandlungsrichtlinien oder Evidenzgrade für die gängigen pharmakologischen und nicht‐pharmakologischen Behandlungsoptionen bei Porokeratosen. Zu den konventionellen Behandlungen zählen topische und systemische Medikamente wie Salicylsäure, topische Glucocorticoide und Retinoide, Phototherapie, Laser und chirurgische Verfahren. Bessere Erkenntnisse über die Pathogenese von Porokeratosen haben die Entwicklung neuartiger therapeutischer Ansätze ermöglicht, etwa topische Statine oder monoklonale Antikörper. In dieser narrativen Übersichtsarbeit werden sowohl die herkömmlichen als auch neuen Behandlungsmöglichkeiten einschließlich ihres Evidenzgrads sowie ihrer Vor‐ und Nachteile zusammengefasst.
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Affiliation(s)
- Yumeng La
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, China
| | - Jie Zhu
- Department of Dermatology, University Hospital Basel, Basel, Switzerland
| | - Simon M Mueller
- Department of Dermatology, University Hospital Basel, Basel, Switzerland
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10
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Hanly A, Turner N, Ko CJ, Panse G. Spiny Keratoderma: Clinical and Histopathological Findings in a Series of 3 Cases. Am J Dermatopathol 2024; 46:439-442. [PMID: 38574081 DOI: 10.1097/dad.0000000000002705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
ABSTRACT Spiny keratoderma is a rare entity presenting with minute keratotic spines on the palms and soles. Spiny keratoderma can be inherited or acquired, and the acquired form may be associated with underlying malignancy or systemic disease. Clinically, the differential diagnosis includes other digitate keratoses on acral sites, most notably arsenical keratosis, filiform verruca, and punctate porokeratosis. Biopsy findings typically include a column of parakeratosis overlying a diminished granular cell layer. In this article, we present 3 cases of acquired spiny keratoderma in patients with various systemic diseases, but no underlying malignancy.
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Affiliation(s)
- Ailish Hanly
- Department of Dermatology, Yale School of Medicine, New Haven, CT
| | - Noel Turner
- Integrated Dermatology of Clinton, Madison, CT; and
- Departments of Pathology, Yale School of Medicine, New Haven, CT
| | - Christine J Ko
- Department of Dermatology, Yale School of Medicine, New Haven, CT
- Departments of Pathology, Yale School of Medicine, New Haven, CT
| | - Gauri Panse
- Department of Dermatology, Yale School of Medicine, New Haven, CT
- Departments of Pathology, Yale School of Medicine, New Haven, CT
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11
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D'Agostino F, Gasparini G, Riva SF, Guadagno A, Parodi A. Annular Pigmented Macules on the Upper Trunk: A Quiz. Acta Derm Venereol 2024; 104:adv35278. [PMID: 38470166 PMCID: PMC10949078 DOI: 10.2340/actadv.v104.35278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 01/30/2024] [Indexed: 03/13/2024] Open
Abstract
Abstract is missing (Quiz)
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Affiliation(s)
- Federica D'Agostino
- Department of Health Sciences (DISSAL), Section of Dermatology, University of Genoa, Genoa, Italy; Department of Dermatology, Ospedale Policlinico San Martino IRCCS, Genoa, Italy.
| | - Giulia Gasparini
- Department of Health Sciences (DISSAL), Section of Dermatology, University of Genoa, Genoa, Italy; Department of Dermatology, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Silvia Francesca Riva
- Department of Health Sciences (DISSAL), Section of Dermatology, University of Genoa, Genoa, Italy; Department of Dermatology, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Antonio Guadagno
- Department of Health Sciences (DISSAL), Section of Dermatology, University of Genoa, Genoa, Italy; Department of Dermatology, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Aurora Parodi
- Department of Health Sciences (DISSAL), Section of Dermatology, University of Genoa, Genoa, Italy; Department of Dermatology, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
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12
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Portelli MG, Bălăceanu-Gurău B, Orzan OA, Zurac SA, Tudose I. Challenges in the Diagnosis and Management of Giant Porokeratosis: A Case Report. Cureus 2024; 16:e55155. [PMID: 38558715 PMCID: PMC10980269 DOI: 10.7759/cureus.55155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2024] [Indexed: 04/04/2024] Open
Abstract
Porokeratosis encompasses a diverse group of dermatoses, both acquired and genetic, marked by a keratinization disorder. Porokeratosis of Mibelli (PKM) presents as solitary plaques or multiple papules/macules with central atrophy and raised hyperkeratotic borders. Here, we present a case of giant porokeratosis (GPK), a rare form often considered a morphological variant of PKM, with unique clinical and histopathological aspects. Our case involves a 29-year-old patient with a 15 × 10 cm irregular plaque on the dorsal aspect of the right hand. The patient was previously prescribed various topical treatments (retinoids, calcineurin inhibitors, and combinations of corticosteroids with vitamin D3 analogs) and systemic retinoids without improvement before presenting to our department. Due to the high risk of neoplastic transformation and the unavailability of imiquimod, the patient was recommended topical 5-fluorouracil treatment. The trajectory of the lesion under treatment revealed a favorable evolution, and the patient was subjected to regular monitoring every three months to assess the ongoing progress. Recognizing GPK as a high-risk variant is crucial for dermatologists, and it requires a personalized approach. Regular monitoring is advised to detect potential malignant transformations promptly. Future research holds promise for diagnostic advancements, refined treatment modalities, and a deeper understanding of the molecular mechanisms underlying malignancy in porokeratosis.
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Affiliation(s)
| | | | - Olguta Anca Orzan
- Department of Dermatology, Elias Emergency University Hospital, Bucharest, ROU
- Department of Dermatology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Sabina Andrada Zurac
- Department of Pathology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Irina Tudose
- Department of Pathology, Elias Emergency University Hospital, Bucharest, ROU
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13
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Pietkiewicz P, Korecka K, Salwowska N, Kohut I, Adhikari A, Bowszyc-Dmochowska M, Pogorzelska-Antkowiak A, Navarrete-Dechent C. Porokeratoses-A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants. Metabolites 2023; 13:1176. [PMID: 38132857 PMCID: PMC10744643 DOI: 10.3390/metabo13121176] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/17/2023] [Accepted: 11/24/2023] [Indexed: 12/23/2023] Open
Abstract
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.
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Affiliation(s)
- Paweł Pietkiewicz
- Dermatology Private Practice, 61-683 Poznan, Poland
- Polish Dermatoscopy Group, 61-683 Poznan, Poland; (K.K.); (N.S.)
| | - Katarzyna Korecka
- Polish Dermatoscopy Group, 61-683 Poznan, Poland; (K.K.); (N.S.)
- Department of Dermatology and Venereology, Poznan University of Medical Sciences, 60-356 Poznan, Poland
| | - Natalia Salwowska
- Polish Dermatoscopy Group, 61-683 Poznan, Poland; (K.K.); (N.S.)
- Department of Dermatology, School of Medicine, Medical University of Silesia, 40-027 Katowice, Poland
| | - Ihor Kohut
- Skin Health Center, 46027 Ternopil, Ukraine;
| | | | - Monika Bowszyc-Dmochowska
- Cutaneous Histopathology and Immunopathology Section, Department of Dermatology, Poznan University of Medical Sciences, 60-356 Poznan, Poland;
| | | | - Cristian Navarrete-Dechent
- Melanoma and Skin Cancer Unit, Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile;
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14
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Diep D, Pyatetsky IA, Barrett KL, Kannan KS, Wright K, Baker W. Bilateral Linear Porokeratosis Treated With Topical Lovastatin 2% Monotherapy. Cureus 2023; 15:e43657. [PMID: 37719543 PMCID: PMC10505042 DOI: 10.7759/cureus.43657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 09/19/2023] Open
Abstract
Linear porokeratosis is a rare skin disorder that presents along dermatomal or Blashko lines. While the mechanism of linear porokeratosis formation is unknown, both disrupted cholesterol synthesis and mevalonate accumulation have been proposed as possible theories. There is a small chance of transforming into cutaneous malignancies, most commonly squamous cell carcinomas. The patient is a 61-year-old male with an unusual presentation of bilateral linear porokeratosis. His condition provided a unique opportunity to compare the efficacy of topical treatments in a single individual. A previous trial had successfully cleared the porokeratosis plaques with topical cholesterol 2%/lovastatin 2% on the patient's right arm. After a 12-week trial of topical lovastatin 2% monotherapy on the left arm, our current study demonstrated a comparable reduction of porokeratosis lesions. In our PubMed search, there has been a single reported case of disseminated superficial actinic porokeratosis successfully treated with topical lovastatin 2% monotherapy, but there have not been any reported cases of linear porokeratosis treated with this therapy. While topical lovastatin monotherapy for porokeratosis subvariants requires further studies, this case demonstrates similar efficacy of treating linear porokeratosis with topical lovastatin compared to cholesterol/lovastatin dual therapy. These findings support the theory of mevalonate accumulation as a more likely cause of linear porokeratosis compared to disruption of cholesterol synthesis.
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Affiliation(s)
- Darlene Diep
- Family Medicine, University of California San Francisco Fresno, Fresno, USA
| | - Ilana A Pyatetsky
- Family Medicine, Burrell College of Osteopathic Medicine, Las Cruces, USA
| | | | | | | | - William Baker
- Family Medicine, Burrell College of Osteopathic Medicine, Las Cruces, USA
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15
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Inci R, Zagoras T, Kantere D, Holmström P, Gillstedt M, Polesie S, Peltonen S. Porokeratosis is one of the most common genodermatoses and is associated with an increased risk of keratinocyte cancer and melanoma. J Eur Acad Dermatol Venereol 2023; 37:420-427. [PMID: 36152004 PMCID: PMC10092613 DOI: 10.1111/jdv.18587] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/17/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND Porokeratosis is a clinically heterogeneous group of keratinization disorders with a genetic background mainly affecting the mevalonate pathway, which is involved in the synthesis of cholesterol, an essential component for the formation of the extracellular lipid lamellae in the stratum corneum. Porokeratosis is reportedly associated with an increased risk of keratinocyte cancer, but to date, no large epidemiological studies have been conducted to further address this association. OBJECTIVES The first objective was to characterize a cohort of patients diagnosed with porokeratosis at the Department of Dermatology and Venereology, Sahlgrenska University Hospital (SU), Gothenburg, Sweden. The second objective was to conduct a nationwide registry-based cohort study to investigate the association, if any, between porokeratosis and the cutaneous malignancies squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. METHODS For the SU cohort, the hospital registry was searched for patients with a diagnosis of porokeratosis recorded between 2016 and 2020. Clinical data were extracted from the records of the identified patients. For the nationwide cohort, national registries were searched to identify patients with a diagnosis of porokeratosis between 2001 and 2020. A tenfold control cohort was formed by Statistics Sweden. The data was cross-referenced with the Swedish Cancer Register to study the associations between porokeratosis and SCC, BCC and melanoma. RESULTS Disseminated superficial actinic porokeratosis was the most common clinical type among the 108 patients in the SU cohort. In the nationwide search, 2277 patients with porokeratosis were identified (prevalence 1/4132). Porokeratosis was associated with an increased risk for SCC, BCC and melanoma with hazard ratios (95% CI) of 4.3 (3.4-5.4), 2.42 (1.97-2.98) and 1.83 (1.18-2.82), respectively, in the patient cohort, compared to the matched control group. CONCLUSION Porokeratosis is a common genodermatosis, and it is associated with an enhanced risk of skin cancer.
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Affiliation(s)
- Rahime Inci
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Theofanis Zagoras
- Department of Clinical Genetics and Genomics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Despoina Kantere
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Peter Holmström
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Martin Gillstedt
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Sam Polesie
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Sirkku Peltonen
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
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16
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Shrestha S, Aryal R, Homagain S, Tiwari SB, Rayamajhi B, Parajuli S, Paudel U. Porokeratosis of gluteal region: A case report. SAGE Open Med Case Rep 2022; 10:2050313X221139559. [PMID: 36467011 PMCID: PMC9709175 DOI: 10.1177/2050313x221139559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 10/31/2022] [Indexed: 11/29/2022] Open
Abstract
Genitogluteal porokeratosis is a rare localized disorder of keratinization. Due to the rarity of the case and non-specific keratotic lesion, it is often misdiagnosed until a histological examination is performed. Treatment of this condition can be challenging, which comprises various topical and systemic drugs, lasers, cryotherapy, phototherapy, and also surgical intervention. Regular follow-up is necessary in the view of this disorder being a premalignant condition.
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Affiliation(s)
- Suraj Shrestha
- Maharajgunj Medical Campus, Institute of Medicine, Kathmandu, Nepal
| | - Roshan Aryal
- Maharajgunj Medical Campus, Institute of Medicine, Kathmandu, Nepal
| | - Sushan Homagain
- Maharajgunj Medical Campus, Institute of Medicine, Kathmandu, Nepal
| | - Sansar Babu Tiwari
- Department of Pathology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
| | - Buddha Rayamajhi
- Department of Dermatology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
| | - Sudip Parajuli
- Department of Dermatology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
| | - Upama Paudel
- Department of Dermatology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
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17
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MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway. Sci Rep 2022; 12:18443. [PMID: 36323841 PMCID: PMC9630378 DOI: 10.1038/s41598-022-23205-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 10/26/2022] [Indexed: 11/06/2022] Open
Abstract
The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR‑874 targets. Next-generation sequencing analysis revealed a significant miR-874-mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874-induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.
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18
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Abstract
Annular lichenoid diseases encompass a diverse range of pathologies that present as circular, raised, or flat lesions that may vary in size and number. Examples include annular lichenoid dermatitis of youth, annular lichen planus, erythema dyschromicum perstans, erythema multiforme, fixed drug eruption, lichen sclerosus, neonatal lupus, porokeratosis, subacute cutaneous lupus erythematosus, and lichenoid syphilis. Clinical morphology and histopathology can differentiate these entities.
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19
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Twists and turns of the genetic story of mevalonate kinase-associated diseases: A review. Genes Dis 2022; 9:1000-1007. [PMID: 35685471 PMCID: PMC9170606 DOI: 10.1016/j.gendis.2021.05.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/19/2021] [Accepted: 05/12/2021] [Indexed: 11/26/2022] Open
Abstract
Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate kinase gene (MVK). Their clinical manifestations are highly variable, ranging from more or less serious systemic disorders, such as hereditary recurrent fevers, to purely localized pathologies such as porokeratosis. The oldest condition identified as linked to this gene is a metabolic disease called mevalonic aciduria, and the most recent is disseminated superficial actinic porokeratosis, a disease limited to the skin. The modes of inheritance of MK-associated diseases also diverge among the different subtypes: recessive for the systemic subtypes and dominant with a post-zygotic somatic genetic alteration for MVK-associated porokeratosis. This review quickly retraces the historical steps that led to the description of the various MK-associated disease phenotypes and to a better understanding of their pathophysiology, then summarizes and compares the different genetic mechanisms involved in this group of disorders, and finally discusses the diverse causes that could underlie this phenotypic heterogeneity.
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20
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Xu HJ, Wen GD. Mixed porokeratosis with a novel mevalonate kinase gene mutation: A case report. World J Clin Cases 2022; 10:4528-4534. [PMID: 35663074 PMCID: PMC9125269 DOI: 10.12998/wjcc.v10.i14.4528] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/11/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Porokeratosis is a rare, acquired, or inherited disorder of keratinization. There are numerous clinical types of porokeratosis and they can coexist in one patient and multiple members of an affected family. However, coexistence of disseminated superficial actinic porokeratosis (DSAP) and porokeratosis ptychotropica (Ppt) is rare.
CASE SUMMARY A 45-year-old man presented with long-standing skin lesions. Physical examination identified numerous small, brown 2-mm to 4-mm patches on his face and several hyperkeratotic, verrucous plaques on his trunk and extremities. His father and one of his brothers also had similar lesions for years. Skin biopsies indicated a cornoid lamella in the epidermis. We identified c.155G>A mutation in the mevalonate kinase (MVK) gene, which converted a serine residue to asparagine (p.Ser52Asn) and was causative for porokeratosis in this family. A clinicopathologic diagnosis of DSAP and Ppt with a novel MVK gene mutation was made. The hyperkeratotic plaques on the patient’s scrotum were completely removed more than 10 times using a microwave knife.
CONCLUSION An unusual case of DSAP coexisting with Ppt harbored a novel MVK gene mutation also present in the patient’s family.
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Affiliation(s)
- Hong-Jun Xu
- Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Guang-Dong Wen
- Department of Dermatology, Peking University People's Hospital, Peking University, Beijing 100044, China
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21
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Akiyama M. Autoinflammatory keratinization diseases: The concept, diseases involved, and pathogeneses. DERMATOL SIN 2022. [DOI: 10.4103/1027-8117.365590] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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22
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Klager S, Khalil M, Shulman K, Sami N. Abatacept-Induced Disseminated Superficial Porokeratosis. J Clin Rheumatol 2021; 27:S634-S635. [PMID: 33337807 DOI: 10.1097/rhu.0000000000001691] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Skylar Klager
- From the University of Central Florida College of Medicine
| | | | - Kenneth Shulman
- Department of Dermatology; New York Medical College, Valhalla, New York
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23
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Huber F, Lautenschlager S. [CME Dermatology 24: Porokeratosis]. PRAXIS 2021; 110:709-716. [PMID: 34583541 DOI: 10.1024/1661-8157/a003756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
CME Dermatology 24: Porokeratosis Abstract. Porokeratoses are a heterogeneous group of cornification disorders with the characteristic histological feature of the cornoid lamellae in the area of the marginal ridge. It is a rare but characteristic disease that occurs primarily in adulthood. Men are slightly more likely to be affected. The etiopathogenesis that leads to the transformation of the keratinocytes remains unclear; associations with genetic mutations and trigger factors such as UV rays and immunosuppression were observed. Due to the risk of malignant degeneration, consistent sun protection and regular clinical controls should take place. Cryotherapy, ablative laser therapy, curettage, photodynamic therapy or topical application of fluorouracil (5-FU), imiquimod and retinoids can be used to treat itchy, painful or cosmetically disturbing porokeratoses, depending on the location and severity.
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Affiliation(s)
- Fabienne Huber
- Institut für Dermatologie und Venerologie, Stadtspital Zürich
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24
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Farinazzo E, Zelin E, Conforti C, Ramella V, Bussani R, Zalaudek I, Di Meo N. Small annular lesions on the nose of a young Caucasian woman. Int J Dermatol 2021; 61:164-166. [PMID: 34152616 PMCID: PMC9291466 DOI: 10.1111/ijd.15709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 05/24/2021] [Indexed: 12/01/2022]
Affiliation(s)
- Eleonora Farinazzo
- Dermatology Clinic, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Enrico Zelin
- Dermatology Clinic, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Claudio Conforti
- Dermatology Clinic, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Vittorio Ramella
- Department of Plastic and Reconstructive Surgery, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Rossana Bussani
- Department of Pathological Anatomy and Histology, Cattinara Hospital, University of Trieste, Trieste, Italy
| | - Iris Zalaudek
- Dermatology Clinic, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Nicola Di Meo
- Dermatology Clinic, Maggiore Hospital, University of Trieste, Trieste, Italy
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25
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Byth LA, Byth J. Topical simvastatin-cholesterol for disseminated superficial actinic porokeratosis: An open-label, split-body clinical trial. Australas J Dermatol 2021; 62:310-313. [PMID: 34028808 DOI: 10.1111/ajd.13601] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 02/22/2021] [Accepted: 03/10/2021] [Indexed: 01/20/2023]
Abstract
BACKGROUND/OBJECTIVES Disseminated superficial actinic porokeratosis (DSAP) is a porokeratosis variant that is cosmetically disfiguring and may be associated with squamous cell carcinoma. It is an autosomal dominant condition caused by germline mutations in mevalonate pathway genes involved in cholesterol synthesis. Lesions are precipitated by ultraviolet radiation-induced second-hit mutations. Modulation of this pathway by topical simvastatin-cholesterol may lead to improvement. METHODS This open-label, split-body clinical trial was carried out in 2020 at a metropolitan dermatology clinic. Eight patients contributing 13 limb pairs were recruited. Limbs within each pair were randomly allocated to 2% simvastatin/2% cholesterol cream applied twice daily or bland emollients. Lesion number, erythema, scale and patient-reported disease activity were measured at baseline and 6 weeks. Data were analysed using Bayesian ordinal logistic regression. Odds ratios compare the odds of a higher score at 6 weeks in treated limbs with the odds in controls. Values less than one indicate improvement. RESULTS Patients had a median age of 65 years (interquartile range [IQR] 58 to 69 years). The median baseline DLQI was 5 (range 2-21). Odds ratios were 0.12 (95% credible interval [CI] 0.01 to 0.72) for lesion number, 0.25 (95% CI 0.05 to 0.79) for erythema score, 0.18 (95% CI 0.03 to 0.64) for scale score and 0.33 (95% CI 0.09 to 0.89) for patient-reported disease activity. CONCLUSIONS Topical simvastatin-cholesterol cream improved lesion number, erythema and scale on treated limbs compared with controls. Patient-reported disease activity also improved. These findings warrant confirmation in blinded, vehicle-controlled trials.
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Affiliation(s)
- Lachlan A Byth
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Griffith University School of Medicine, Southport, Queensland, Australia
| | - Jenny Byth
- Byth Medical Pty. Ltd., Wesley Hospital, Auchenflower, Queensland, Australia
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26
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Shiiya C, Aoki S, Nakabayashi K, Hata K, Amagai M, Kubo A. Linear and disseminated porokeratosis in one family showing identical and independent second hits in MVD among skin lesions, respectively: a proof-of-concept study. Br J Dermatol 2021; 184:1209-1212. [PMID: 33481264 DOI: 10.1111/bjd.19824] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/17/2021] [Accepted: 01/18/2021] [Indexed: 12/24/2022]
Affiliation(s)
- C Shiiya
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan
| | - S Aoki
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan
| | - K Nakabayashi
- Department of Maternal-Fetal Biology, National Centre for Child Health and Development, Tokyo, Japan
| | - K Hata
- Department of Maternal-Fetal Biology, National Centre for Child Health and Development, Tokyo, Japan
| | - M Amagai
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan
| | - A Kubo
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan
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27
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Boursier G, Rittore C, Milhavet F, Cuisset L, Touitou I. Mevalonate Kinase-Associated Diseases: Hunting for Phenotype-Genotype Correlation. J Clin Med 2021; 10:jcm10081552. [PMID: 33917151 PMCID: PMC8067830 DOI: 10.3390/jcm10081552] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/30/2021] [Accepted: 04/01/2021] [Indexed: 12/11/2022] Open
Abstract
Mevalonate kinase-associated diseases (MKAD) are caused by pathogenic mutations in the mevalonate kinase gene (MVK) and encompass several phenotypically different rare and hereditary autoinflammatory conditions. The most serious is a recessive systemic metabolic disease called mevalonic aciduria, and the most recently recognized is disseminated superficial actinic porokeratosis, a dominant disease limited to the skin. To evaluate a possible correlation between genotypes and (1) the different MKAD clinical subtypes or (2) the occurrence of severe manifestations, data were reviewed for all patients with MVK variants described in the literature (N = 346), as well as those referred to our center (N = 51). The genotypes including p.(Val377Ile) (homozygous or compound heterozygous) were more frequent in mild systemic forms but were also sometimes encountered with severe disease. We confirmed that amyloidosis was more prevalent in patients compound heterozygous for p.(Ile268Thr) and p.(Val377Ile) than in others and revealed new associations. Patients homozygous for p.(Leu264Phe), p.(Ala334Thr) or compound heterozygous for p.(His20Pro) and p.(Ala334Thr) had increased risk of severe neurological or ocular symptoms. All patients homozygous for p.(Leu264Phe) had a cataract. The variants associated with porokeratosis were relatively specific and more frequently caused a frameshift than in patients with other clinical forms (26% vs. 6%). We provide practical recommendations focusing on phenotype-genotype correlation in MKAD that could be helpful for prophylactic management.
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Affiliation(s)
- Guilaine Boursier
- Department of Medical Genetics, Rare Diseases and Personalized Medicine, Rare and Autoinflammatory Diseases Unit, CHU, 34295 Montpellier, France; (G.B.); (C.R.); (F.M.)
| | - Cécile Rittore
- Department of Medical Genetics, Rare Diseases and Personalized Medicine, Rare and Autoinflammatory Diseases Unit, CHU, 34295 Montpellier, France; (G.B.); (C.R.); (F.M.)
| | - Florian Milhavet
- Department of Medical Genetics, Rare Diseases and Personalized Medicine, Rare and Autoinflammatory Diseases Unit, CHU, 34295 Montpellier, France; (G.B.); (C.R.); (F.M.)
- IRMB, University of Montpellier, INSERM, 34295 Montpellier, France
| | - Laurence Cuisset
- Genetic and Molecular Biology Laboratory, Cochin Hospital, 75014 Paris, France;
| | - Isabelle Touitou
- Department of Medical Genetics, Rare Diseases and Personalized Medicine, Rare and Autoinflammatory Diseases Unit, CHU, 34295 Montpellier, France; (G.B.); (C.R.); (F.M.)
- IRMB, University of Montpellier, INSERM, 34295 Montpellier, France
- Correspondence:
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28
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Novice T, Nakamura M, Helfrich Y. The Malignancy Potential of Porokeratosis: A Single-Center Retrospective Study. Cureus 2021; 13:e13083. [PMID: 33680623 PMCID: PMC7932828 DOI: 10.7759/cureus.13083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background Porokeratosis (PK) is a rare group of keratinization disorders. While the overall prognosis of PK is favorable, malignant transformation of PK to skin cancer has been reported in 6.9% to 11.6% of the cases. Prior estimates of malignant transformation of PK have been based on reviews of published cases, which introduces possible publication bias. We aim to eliminate this potential bias and quantify the characteristics, risk factors, and malignancy potential of PK. Methodology A single-center retrospective chart review of patients with a diagnosis of PK was conducted. Results In this study, 6.4% to 16.4% of histologically confirmed PK lesions demonstrated malignant transformation. A higher proportion of disseminated superficial actinic porokeratosis (DSAP) cases (as high as 29.3%) showed malignant transformation compared to PK of Mibelli (as high as 6.0%). Out of the two cases of linear PK, both demonstrated malignant transformation. Conclusions In summary, PKs are at risk for malignant transformation, and patients with DSAP and linear PK, in particular, should receive more long-term surveillance. Limitations of this study include the inability to control for confounding factors due to the retrospective nature and the small size of our cohort.
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Affiliation(s)
| | - Mio Nakamura
- Dermatology, University of Michigan, Ann Arbor, USA
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29
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Wu YH, Yao XF. Postirradiation multiple minute digitate porokeratosis: A case report. DERMATOL SIN 2021. [DOI: 10.4103/ds.ds_13_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Lu JD, Mufti A, Sachdeva M, Rahat S, Lansang RP, Yeung J. Drugs associated with development of porokeratosis: A systematic review. Dermatol Ther 2021; 34:e14560. [PMID: 33210788 DOI: 10.1111/dth.14560] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/01/2020] [Accepted: 11/14/2020] [Indexed: 01/07/2023]
Abstract
Porokeratosis is a rare disorder characterized by atrophic macules or patches, with a well-defined ridge-like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug-induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug-induced porokeratosis in MEDLINE and Embase in June 2020. After full-text review, 25 studies were included for analysis. We identified 26 patients with drug-induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large-scale studies are required to confirm our findings and further explore the pathogenesis for drug-induced porokeratosis.
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Affiliation(s)
- Justin D Lu
- Faculty of Medicine, Michael G. DeGroote School of Medicine, Hamilton, Ontario, Canada
| | - Asfandyar Mufti
- Department of Dermatology, University of Toronto, Toronto, Ontario, Canada
| | - Muskaan Sachdeva
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Shahmina Rahat
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | | | - Jensen Yeung
- Department of Dermatology, University of Toronto, Toronto, Ontario, Canada
- Division of Dermatology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Division of Dermatology, Women's College Hospital, Toronto, Ontario, Canada
- Probity Medical Research Inc., Waterloo, Ontario, Canada
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31
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Disseminated Superficial Actinic Porokeratosis in the Elderly: A Case Report. SERBIAN JOURNAL OF DERMATOLOGY AND VENEREOLOGY 2020. [DOI: 10.2478/sjdv-2020-0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Currently, most authors believe that disseminated superficial actinic porokeratosis (DSAP) is an inherited or acquired dermatologic disorder of keratinization that occurs in genetically predisposed individuals after adequate exposure to ultraviolet (UV) rays, or immunosuppression. Lesions in DSAP start in sun-exposed areas most commonly in the third or fourth decade of life. The lesions are pink to brownish papules and plaques with a raised scaling ridge, histologically seen as a column of parakeratotic keratinocytes, the cornoid lamella. DSAP is not only the most common, but also the most often overlooked form of porokeratosis (P). Here we present a 77-year-old male with DSAP, who sporadically developed initial skin lesions at the age of 67, at the time when his personal and medical history were significantly long for chronic intensive sun exposure and type 1 insulin dependent diabetes mellitus. We established the diagnosis of DSAP based on personal and medical history, clinical presentation, auxiliary methods such as dermoscopy, and confirmed with pathohistological findings. We advised the patient to avoid sun exposure and to apply photo-protective sunscreens, emollients and keratolytics. After five years of monitoring his changes, we continue to control his lesions for any possible alteration. Although mutations in several genes and data on sun exposure may be responsible for the onset of the disease, most cases of DSPA occur sporadically and without involving the facial skin, as in our case. Lesions usually begin in the third or fourth decade of life. In the elderly, an additional trigger may be present, such as e.g. age-related decreased immune competence. Diabetes mellitus may also be associated with immunodeficiency in the elderly. Recently, DSPA has been a special subtype of DSPA in the elderly. Malignant alteration can occur in DSPA, most commonly in lesions that are long lasting, large, in the elderly, or in lesions in immunocompromised individuals. In conclusion, this is the case of a 77-year-old male person, who sporadically developed the so-called subtype DSPA in the elderly. In addition to UV radiation, the relevant suggestive trigger factors were the immunosuppressive effects of diabetes mellitus and chronological aging.
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Vargas-Mora P, Morgado-Carrasco D, Fustà-Novell X. Porokeratosis: A Review of its Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment. ACTAS DERMO-SIFILIOGRAFICAS 2020. [DOI: 10.1016/j.adengl.2020.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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de Wet J, Swart M, Jordaan HF, Schneider JW, Mulder S, Visser WI. An unusual case of generalized hyperkeratotic and verrucous porokeratosis. JAAD Case Rep 2020; 6:925-930. [PMID: 32923569 PMCID: PMC7475069 DOI: 10.1016/j.jdcr.2020.07.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Johann de Wet
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Minette Swart
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - H Francois Jordaan
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Johann W Schneider
- Division of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Suzanne Mulder
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Willem I Visser
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
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Li Q, Wang W, Zhuang J, Zhang J, Liu J, Chen Y. Improvements in two subtypes of porokeratosis by superficial X-ray radiotherapy. Dermatol Ther 2020; 33:e13876. [PMID: 32558081 DOI: 10.1111/dth.13876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/09/2020] [Accepted: 06/17/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Qingwen Li
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Weijia Wang
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Jiayi Zhuang
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Jiao Zhang
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Jiarui Liu
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Yongfeng Chen
- Dermatology Hospital, Southern Medical University, Guangzhou, China
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35
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Xu X, Pradhan S, Wang D, Li W. Multiple porokeratomas (porokeratotic acanthoma) coexisting with disseminated superficial porokeratosis: Clinical, dermoscopic and pathological observations, and review of published work. J Dermatol 2020; 47:787-791. [PMID: 32415691 DOI: 10.1111/1346-8138.15376] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 04/06/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Xiaoxi Xu
- Department of Dermatology Rare Disease Center West China Hospital Sichuan University Chengdu China
| | - Sushmita Pradhan
- Department of Dermatology Rare Disease Center West China Hospital Sichuan University Chengdu China
| | - Dan Wang
- Department of Dermatology Rare Disease Center West China Hospital Sichuan University Chengdu China
| | - Wei Li
- Department of Dermatology Rare Disease Center West China Hospital Sichuan University Chengdu China
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Vargas-Mora P, Morgado-Carrasco D, Fustà-Novell X. Porokeratosis: A Review of Its Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment. ACTAS DERMO-SIFILIOGRAFICAS 2020; 111:545-560. [PMID: 32401728 DOI: 10.1016/j.ad.2020.03.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 03/14/2020] [Accepted: 03/30/2020] [Indexed: 12/17/2022] Open
Abstract
Porokeratosis comprises a group of heterogeneous and uncommon acquired or congenital skin diseases of unknown origin characterized by a keratinization disorder resulting from abnormal clonal expansion of keratinocytes. Numerous genetic mutations are thought to be involved. These conditions are characterized histologically by the presence of a cornoid lamella. Clinical manifestations are variable, with localized, disseminated, and even eruptive forms. Porokeratosis has been associated with immunosuppression, ultraviolet radiation, and systemic, infectious, and neoplastic diseases. Many authors consider it to be a premalignant condition because of the potential for malignant transformation to squamous cell or basal cell carcinoma. Therefore, long-term follow-up is a key component of treatment, which is usually complex and often unsatisfactory. We review the latest advances in our understanding of the pathogenesis, diagnosis, and treatment and propose a treatment algorithm.
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Affiliation(s)
- P Vargas-Mora
- Departamento de Dermatología, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - D Morgado-Carrasco
- Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, España.
| | - X Fustà-Novell
- Servicio de Dermatología, Althaia, Xarxa Assistencial Universitària de Manresa, España
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Atzmony L, Khan HM, Lim YH, Paller AS, Levinsohn JL, Holland KE, Mirza FN, Yin E, Ko CJ, Leventhal JS, Choate KA. Second-Hit, Postzygotic PMVK and MVD Mutations in Linear Porokeratosis. JAMA Dermatol 2020; 155:548-555. [PMID: 30942823 DOI: 10.1001/jamadermatol.2019.0016] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Importance Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because linear porokeratosis manifests in the lines of Blaschko representing the dorsoventral migration patterns of keratinocyte precursors, it has been suggested that postzygotic somatic mutation underlies the disease. However, no genetic evidence has supported this hypothesis to date. Objective To identify genetic mutations associated with linear porokeratosis. Design, Setting, and Participants Paired whole-exome sequencing of affected skin and blood/saliva samples from 3 participants from 3 academic medical centers with clinical and histologic diagnoses of linear porokeratosis. Interventions or Exposures Whole-exome sequencing of paired blood/saliva and affected tissue samples isolated from linear porokeratosis lesions. Main Outcomes and Measures Germline and somatic genomic characteristics of participants with linear porokeratosis. Results Of the 3 participants, 2 were male. Participant ages ranged from 5 to 20 years old. We found a combination of a novel germline mutation and a novel somatic mutation within affected tissue in all cases. One participant had a germline heterozygous PMVK c.329G>A mutation and a somatic copy-neutral loss of heterozygosity confined to the lesional skin, while a second had a germline heterozygous PMVK c.79G>T mutation and an additional PMVK c.379C>T mutation in the lesional skin. In a third participant, there was a germline splice-site mutation in MVD (c.70 + 5G>A) and a somatic deletion in MVD causing frameshift and premature codon termination within the lesional skin (c.811_815del, p.F271Afs*33 frameshift). Conclusions and Relevance Our findings suggest that linear porokeratosis is associated with the presence of second-hit postzygotic mutations in the genes that encode enzymes within the mevalonate biosynthesis pathway, and provide further evidence that the mevalonate pathway may be a potential target for therapeutic intervention in porokeratosis.
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Affiliation(s)
- Lihi Atzmony
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
| | - Habib M Khan
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
| | - Young H Lim
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.,Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.,Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
| | - Amy S Paller
- Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Jonathan L Levinsohn
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.,Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.,Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
| | | | - Fatima Nadeem Mirza
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
| | - Emily Yin
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
| | - Christine J Ko
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.,Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
| | - Jonathan S Leventhal
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
| | - Keith A Choate
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.,Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.,Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
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Zhang F, Bai W, Sun S, Li N, Zhang X. Squamous cell carcinoma arising from giant porokeratosis and rare postoperative recurrence and metastasis: A case report. Medicine (Baltimore) 2020; 99:e18697. [PMID: 31914072 PMCID: PMC6959887 DOI: 10.1097/md.0000000000018697] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Giant porokeratosis is considered to be a variant of porokeratosis of Mibelli (PM) by some medical scholars. Porokeratosis can develop into several epidermal malignant tumors, such as Bowen disease and basal cell carcinoma, among which squamous cell carcinoma (SCC) is the most common. PATIENT CONCERNS The patient was a 53-year-old man who was admitted to our hospital due to postoperative recurrence and metastasis as SCC arising from giant PM in his left leg and foot. DIAGNOSES The pathological results are porokeratosis and well-differentiated squamous cell carcinoma. Positron emission tomography and computed tomography results show the local recurrence of the tumor with multiple lymph node metastasis. INTERVENTIONS This patient was transferred to orthopedic surgery for amputation of the middle and lower left thigh. OUTCOMES Follow-up for 3 months has shown no recurrence after the surgery. LESSONS This report reminds us to pay close attention to the likelihood of giant porokeratosis. The physicians should explore all clinical possibilities to avoid misdiagnosis of this rare disease.Although the recurrence rate of SCC arising from giant PM is very low, the surgical resection region should be expanded appropriately such as the en-block resection.
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Affiliation(s)
- Fang Zhang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine
| | - Wenzhe Bai
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine
| | - Shuna Sun
- Department of Dermatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Na Li
- Department of Dermatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Xiaojie Zhang
- Department of Dermatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, Shandong, China
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Smirnov A, Anemona L, Novelli F, Piro CM, Annicchiarico-Petruzzelli M, Melino G, Candi E. p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer. Int J Mol Sci 2019; 20:E5781. [PMID: 31744230 PMCID: PMC6888618 DOI: 10.3390/ijms20225781] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 11/07/2019] [Accepted: 11/15/2019] [Indexed: 01/02/2023] Open
Abstract
Skin cancer is the most common type of cancer worldwide. Ozone depletion and climate changes might cause a further increase in the incidence rate in the future. Although the early detection of skin cancer enables it to be treated successfully, some tumours can evolve and become more aggressive, especially in the case of melanoma. Therefore, good diagnostic and prognostic markers are needed to ensure correct detection and treatment. Transcription factor p63, a member of the p53 family of proteins, plays an essential role in the development of stratified epithelia such as skin. In this paper, we conduct a comprehensive review of p63 expression in different types of skin cancer and discuss its possible use in the diagnosis and prognosis of cutaneous tumours.
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Affiliation(s)
- Artem Smirnov
- Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Lucia Anemona
- Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Flavia Novelli
- Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Cristina M. Piro
- Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | | | - Gerry Melino
- Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
- MRC-Toxicology Unit, University of Cambridge, Cambridge CB2 1QP, UK
| | - Eleonora Candi
- Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
- Istituto Dermopatico dell’Immacolata-IRCCS, 00163 Rome, Italy
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40
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Maredia H, Simkin D, Soni A, Loss MJ. Eruptive porokeratosis during pembrolizumab treatment of invasive cutaneous squamous cell carcinoma. Int J Dermatol 2019; 59:e141-e142. [DOI: 10.1111/ijd.14701] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 08/07/2019] [Accepted: 10/04/2019] [Indexed: 11/26/2022]
Affiliation(s)
- Hasina Maredia
- Department of Dermatology Johns Hopkins University School of Medicine Baltimore MD USA
| | - Daren Simkin
- Department of Dermatology Johns Hopkins University School of Medicine Baltimore MD USA
| | - Abha Soni
- Department of Dermatology Johns Hopkins University School of Medicine Baltimore MD USA
| | - Manisha J. Loss
- Department of Dermatology Johns Hopkins University School of Medicine Baltimore MD USA
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41
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Clonal Expansion of Second-Hit Cells with Somatic Recombinations or C>T Transitions Form Porokeratosis in MVD or MVK Mutant Heterozygotes. J Invest Dermatol 2019; 139:2458-2466.e9. [PMID: 31207227 DOI: 10.1016/j.jid.2019.05.020] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 05/21/2019] [Accepted: 05/28/2019] [Indexed: 12/13/2022]
Abstract
Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK. Here, we showed that each skin lesion of DSAP exhibited an individual second hit genetic change in the wild-type allele of the corresponding gene specifically in the epidermis, indicating that a postnatal second hit triggering biallelic deficiency of the gene is required for porokeratosis to develop. Most skin lesions exhibited one of two principal second hits, either somatic homologous recombinations rendering the monoallelic mutation biallelic or C>T transition mutations in the wild-type allele. The second hits differed among DSAP lesions but were identical in those of congenital LP, suggesting that DSAP is attributable to sporadic postnatal second hits and congenital LP to a single second hit in the embryonic period. In the characteristic annular skin lesions of DSAP, the central epidermis featured mostly second hit keratinocytes, and that of the annular ring featured a mixture of such cells and naïve keratinocytes, implying that each lesion reflects the clonal expansion of single second hit keratinocytes. DSAP is therefore a benign intraepidermal neoplasia, which can be included in the genetic tumor disorders explicable by Knudson's two-hit hypothesis.
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42
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Zhu PQ, Yan HM, Zhao HJ, Guo DY, Jiang W. A novel premature termination mutation in FDPS in a Chinese family with disseminated superficial actinic porokeratosis. Br J Dermatol 2019; 180:1545-1546. [PMID: 30561051 DOI: 10.1111/bjd.17531] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- P-Q Zhu
- Department of Dermatology, Peking University Third Hospital, Haidian District, Beijing, China
| | - H-M Yan
- Department of Dermatology, Peking University Third Hospital, Haidian District, Beijing, China
| | - H-J Zhao
- Department of Dermatology, Peking University Third Hospital, Haidian District, Beijing, China
| | - D-Y Guo
- Department of Dermatology, Peking University Third Hospital, Haidian District, Beijing, China
| | - W Jiang
- Department of Dermatology, Peking University Third Hospital, Haidian District, Beijing, China
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43
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Cho YR, Kim HJ, Seo JW, Kim TH, Song KH, Kim KH. Topical Methyl Aminolevulinate Photodynamic Therapy in Porokeratosis of Mibelli: An Alternative Treatment for a Refractory Disease. Ann Dermatol 2019; 31:341-343. [PMID: 33911603 PMCID: PMC7992740 DOI: 10.5021/ad.2019.31.3.341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 04/30/2018] [Accepted: 05/04/2018] [Indexed: 11/08/2022] Open
Affiliation(s)
- Yeo-Rye Cho
- Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea
| | - Ho-Jin Kim
- Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea
| | - Jeong-Wan Seo
- Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea
| | - Tae-Hoon Kim
- Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea
| | - Ki-Hoon Song
- Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea
| | - Ki-Ho Kim
- Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea
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44
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Radoš S, Milovanović M, Rajović M, Kostić K, Tufegdžić I, Kandolf Sekulović L. Squamous Cell Carcinoma Arising from Linear Porokeratosis - a case report and review of the literature. SERBIAN JOURNAL OF DERMATOLOGY AND VENEREOLOGY 2018. [DOI: 10.1515/sjdv-2017-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Porokeratosis belongs to a group of disorders of keratinization that are characterized by the histopathological feature of the cornoid lamella, a column of tightly fitted parakeratotic cells. The etiology of porokeratosis is still unclear. Different variants of porokeratosis (PK) have been subsequently recognized, each with its own specific properties in terms of morphology, distribution and clinical course. Linear porokeratosis is one of the variants of porokeratosis, a rare disorder of keratinization that may develop into several epidermal malignancies, squamous cell carcinoma being the most frequent among all of them. Thus, a clinical surveillance for malignancy is an imperative. We present a case of a 54-year-old man with non-healing ulcer of the lower leg caused by squamous cell carcinoma arising on long-standing linear porokeratosis. The treatment included wide excision of tumor with the reconstruction of the area. Acitretin was prescribed for linear porokeratosis treatment. The follow-up of our patient so far has shown that he does not have new malignant lesions after surgical excision.
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Affiliation(s)
- Snežana Radoš
- City Institute for Skin and Venereal Diseases, Džordža Vašingtona 17, 11000, Belgrade , Serbia
| | | | - Milica Rajović
- Deparment of Plastic and Reconstructive Surgery, Military Medical Academy, Belgrade , Serbia
| | - Kristina Kostić
- Department of Dermatology, School of Medicine, Military Medical Academy, Belgrade , Serbia
| | - Ivana Tufegdžić
- Institute of Pathology and Forensic Medicine, School of Medicine, Military Medical Academy, Belgrade , Serbia
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45
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Novel mevalonate kinase missense mutation in a patient with disseminated superficial actinic porokeratosis. JAAD Case Rep 2018; 4:340-343. [PMID: 29693064 PMCID: PMC5911812 DOI: 10.1016/j.jdcr.2017.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
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46
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Bari O, Calame A, Marietti-Shepherd S, Barrio VR. Pediatric penile porokeratosis: A case report. Pediatr Dermatol 2018; 35:e103-e104. [PMID: 29341221 DOI: 10.1111/pde.13378] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
We present what we believe to be the second case of pediatric penile porokeratosis and the youngest case reported. A 6-year-old boy presented with a pruritic, verrucous growth at the urethral meatus that recurred after two meatotomies. The diagnosis of porokeratosis was confirmed by biopsy. Porokeratosis should be added to the differential diagnosis of chronic hyperkeratotic penile lesions in children.
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Affiliation(s)
- Omar Bari
- School of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Antoanella Calame
- Compass Dermatopathology, San Diego, CA, USA.,Department of Dermatology, University of California, San Diego, La Jolla, CA, USA
| | - Sarah Marietti-Shepherd
- Rady Children's Hospital, San Diego, CA, USA.,Department of Urology, University of California, San Diego, La Jolla, CA, USA
| | - Victoria R Barrio
- Department of Dermatology, University of California, San Diego, La Jolla, CA, USA.,Rady Children's Hospital, San Diego, CA, USA
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47
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Rajesh G, Devan P, Keerthi S, Karthikeyan K. Acral porokeratosis associated with anonychia. Indian J Dermatol Venereol Leprol 2017; 84:81-82. [PMID: 29271370 DOI: 10.4103/ijdvl.ijdvl_940_16] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Gurumoorthy Rajesh
- Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
| | - Prakash Devan
- Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
| | - Subramaniam Keerthi
- Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
| | - Kaliaperumal Karthikeyan
- Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
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48
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Al-Haseni A, Chitgopeker P, Ho JD, Goldberg LJ, Sahni D. Amelanotic melanoma arising within a lesion of disseminated superficial actinic porokeratosis: An unusual presentation leading to a novel therapeutic approach. Dermatol Ther 2017; 31. [PMID: 28976625 DOI: 10.1111/dth.12552] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 08/07/2017] [Indexed: 11/28/2022]
Abstract
Disseminated superficial actinic porokeratosis (DSAP) is the most common variant of porokeratosis with a potential for malignant transformation. Its association with malignant melanoma, however, is exceedingly rare. Treatment of DSAP is often ineffective. We report a unique case of amelanotic melanoma arising within a lesion of DSAP. The melanoma was managed surgically, and her DSAP were treated successfully with a novel approach utilizing 5-fluorouracil chemowraps.
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Affiliation(s)
- Ali Al-Haseni
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts
| | - Pooja Chitgopeker
- Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Jonathan D Ho
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts.,Section of Dermatopathology, Boston University School of Medicine, Boston, Massachusetts
| | - Lynne J Goldberg
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts.,Section of Dermatopathology, Boston University School of Medicine, Boston, Massachusetts
| | - Debjani Sahni
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts
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49
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Enhanced dendritic cells and regulatory T cells in the dermis of porokeratosis. Arch Dermatol Res 2017; 309:749-756. [DOI: 10.1007/s00403-017-1779-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 08/13/2017] [Accepted: 09/05/2017] [Indexed: 12/13/2022]
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50
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Abstract
BACKGROUND Porokeratosis (PK) is a rare skin disease of unknown etiology. It consists of a keratinization disorder, which may appear in several clinical forms and can undergo malignant transformation. The histopathological hallmark of PK is the cornoid lamella. While many topical, systemic, and surgical treatment modalities for PK have been described, no randomized controlled trials have been performed yet. Because of a lack of treatment standards for PK, European and international guidelines cannot be created. OBJECTIVE The aim of this systematic review is to outline options for treating PK. METHODS We performed a systematic literature search in an electronic database for published literature. A total of 88 articles fulfilling our inclusion criteria were found. RESULTS There were no randomized controlled trials on the treatment of PK, but mainly case reports and case series. Porokeratosis of Mibelli showed the best outcomes after treatment with imiquimod cream and linear PK responded well to topical or systemic retinoids. Topical vitamin D acid derivatives may be the best therapeutic option for disseminated PK. Surgical interventions and cryotherapy may be preferred in areas where the use of topical agents is difficult or contraindicated. CONCLUSION To offer patients with PK an evidence-based high-quality standardized therapy, randomized controlled trials are needed.
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