Materiały źródłowe

• #1 Seborrheic Keratosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545285/

  Seborrheic keratosis is caused by the benign clonal expansion of epidermal keratinocytes. […] The exact pathogenesis of this skin condition is also not known at this time, but there is a possible correlation with multiple abnormalities as follows: […] In cases of sporadic seborrheic keratosis, activating mutations in the tyrosine kinase receptor known as fibroblast growth factor receptor-3 (FGFR3) are common and are believed to be what drives the growth of this benign tumor. […] Seborrheic keratoses have been discovered to contain somatic activating mutations in the TERT and DHPH3 promoters, but with a lower frequency. […] UV radiation exposure increases the expression of amyloid precursor protein (APP) in skin locations, and this expression also rises with age. […] The expression of APP has been assessed in seborrheic keratoses compared to normal skin using immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction (qPCR).

• #1 Seborrheic Keratosis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1059477-overview

  Seborrheic keratoses are thought to result from a clonal expansion of a mutated epidermal keratinocyte. […] Seborrheic keratoses exhibit histologic evidence of proliferation. Increased cell replication has been demonstrated in seborrheic keratoses with bromodeoxyuridine incorporation studies and immunohistochemistry for proliferation-associated antigens. […] A high frequency of mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) has been found in certain types of seborrheic keratoses. This was the first clue into the genetic basis for the pathogenesis of seborrheic keratoses. […] More than 80% of seborrheic keratoses have at least one mutation, and 45% have more than one mutation in an oncogene such as FGFR3, PIK3CA, KRAS, and EGFR.

• #1 Seborrheic Keratosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28812

  Seborrheic keratosis is caused by the benign clonal expansion of epidermal keratinocytes. […] There is believed to be a genetic component to the development of a high number of seborrheic keratoses. […] The exact pathogenesis of this skin condition is also not known at this time, but there is a possible correlation with multiple abnormalities as follows: […] In cases of sporadic seborrheic keratosis, activating mutations in the tyrosine kinase receptor known as fibroblast growth factor receptor-3 (FGFR3) are common and are believed to be what drives the growth of this benign tumor. […] Seborrheic keratoses have been discovered to contain somatic activating mutations in the TERT and DHPH3 promoters, but with a lower frequency. […] UV radiation exposure increases the expression of amyloid precursor protein (APP) in skin locations, and this expression also rises with age.

• #1 Seborrheic Keratoses – The Most Common Benign Skin Tumor of Humans. Clinical presentation and an update on pathogenesis and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6290447/

  Seborrheic keratoses (SK) are the most common skin tumour of humanity. […] Recently, oncogenic mutations have been detected involved in the development of SK, which, however, do not bear the risk of malignant transformation. […] The etiopathology of SKs is not completely understood. They are considered a sign of ageing skin and UV-exposure may be associated with. […] Expression of the amyloid precursor protein (APP) has been evaluated in SKs versus normal skin by immunohistochemistry, Western blotting and quantitative real-time polymerase chain reaction (PCR). […] These findings suggest that overexpression of APP may promote the onset of SK and is a marker of skin ageing and UV damage. […] Exome sequencing of SKs indicated three mutations per megabase pairs of the targeted sequence.

• #1

  https://omim.org/entry/182000

  Logie et al. (2005) targeted an activated FGFR3 mutant, S249C (134934.0013), to basal cells of the epidermis of mice. FGFR3-mutant mice developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis.

• #1 Comparative study on the age-related incidence of seborrheic keratosis and verruca plana in patients with verruca plana-like lesions | Scientific Reports

  https://www.nature.com/articles/s41598-024-55617-1

  Seborrheic keratosis (SK) is a common skin disease in the elderly. […] SK had a higher prevalence among individuals older than 30 years, and relative frequency of SK should not be ignored in patients with a grouped distribution in their 20 s and 30 s. […] Therefore, our study suggests that multiple verrucous skin-colored to brownish plaques are also commonly diagnosed as SK in young people as well as VP, and the prevalence of SK and VP may not always depend solely on chronological aging, and the prevalence of SK among young people may be higher than commonly believed stereotypes suggest. […] SK mainly affects the elderly according to previous literature. […] However, in a previous study that investigated 170 Australian individuals aged 1530 years, the prevalence of SK was 32.3% in the 2530-year group.

• #1 Clinicopathological Evaluation of Seborrheic Keratosis Lesions in Patients Referred to Afzalipour Hospital, Kerman, Iran

  https://brieflands.com/articles/jssc-122310

  Seborrheic keratosis is a benign epidermal proliferation, which is highly common in sun-exposed areas. […] Although the exact pathogenesis of the SK was not well-understood, factors such as sun exposure, genetic predisposition, and genetic mutation in FGFR3 due to ultraviolet (especially in adenoid type) were also considered. […] Most of the lesions were located in sun-exposed areas (65.6%) in the present study. […] Furthermore, there was no significant difference between pathological subtypes and sun-exposure in the present study. […] The most common pathological subtypes in the present study were acanthotic and hyperkeratotic types (47.5% 27.3%, respectively). […] In this study, the most common pathological features were horn cyst (75.8%), acanthosis (71.7%), and hyperkeratosis (60.6%), respectively.

• #1 FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization | Modern Pathology

  https://www.nature.com/articles/3800837

  Somatic activating fibroblast growth factor 3 (FGFR3) mutations in human skin can cause seborrheic keratoses, one of the most frequent skin tumors in man. […] We analyzed 65 acanthotic seborrheic keratoses with varying vertical diameters for FGFR3 mutations using a SNaPshot multiplex assay. […] FGFR3 mutations were detected in 37 of 65 seborrheic keratoses (57%). These mutations were found both in flat (initial) and thick seborrheic keratoses. […] Our results indicate that FGFR3 mutations can occur early in the pathogenesis of at least a subset of seborrheic keratoses. […] The thickness of acanthotic seborrheic keratoses varies considerably. […] We sought to investigate whether FGFR3 mutations are already present in flat (initial) seborrheic keratoses and therefore may represent early genetic alterations in the pathogenesis of seborrheic keratoses, or whether FGFR3 mutations are associated with more prominent acanthosis.

• #1 FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization | Modern Pathology

  https://www.nature.com/articles/3800837

  Our results show that FGFR3 mutations are already present in flat seborrheic keratoses. This finding indicates that the mutations may be early genetic events in the pathogenesis of at least a subset of seborrheic keratoses. […] Interestingly, we found that the frequency of FGFR3 mutations was significantly associated with an increased age. […] This result suggests that age is a major risk factor for the occurrence of somatic FGFR3 mutations in skin. […] The mechanisms leading to the development of acanthosis, papillomatosis, hyperkeratosis and hyperpigmentation in FGFR3 mutant skin and details of the involved signaling pathways downstream of the mutant FGFR3 protein in the epidermis are largely unknown. […] Expression of anti-apoptotic bcl-2 was significantly associated with FGFR3 mutations in acanthotic seborrheic keratoses, suggesting that the anti-apoptotic PI-3K/Akt-pathway upstream of bcl-2 may be involved in addition to an increased proliferation.

• #1 Seborrheic Keratosis – EyeWiki

  https://eyewiki.org/Seborrheic_Keratosis

  Seborrheic keratosis is a benign proliferation of immature keratinocytes between the basal layer and the keratinizing surface of the epidermis. […] The pathogenesis of seborrheic keratosis (SK) remains poorly understood. Immature epidermal keratinocytes slowly proliferate leading to macules, papules, and plaques known as seborrheic keratoses. […] Recent studies have proposed that increased expression of the transmembrane protein amyloid precursor protein (APP) may play an important role. APP is mainly expressed in keratinocytes and melanocytes in the epidermal basal layer with only a small amount in the dermal fibroblasts of the epidermal-dermal junction. […] The expression of APP is higher in UV-exposed skin and increases with age. APP was found to be present throughout all layers of SK tissue samples, and more extensively expressed when compared to adjacent normal skin tissue.

• #1 Seborrheic Keratosis – EyeWiki

  https://eyewiki.org/Seborrheic_Keratosis

  In epidermal keratinocytes, APP participates in protecting cells by inducing proliferation and migration while inhibiting apoptosis. […] APP is also believed to have a critical role in the regulation of epidermal growth factor receptor (EGFR). Different types of mutations and up-regulation of EGFR have been implicated in SK in addition to other tumors. […] Fibroblast growth factor receptor 3 (FGFR3, a tyrosine kinase) and /or PIK3CA oncogenes may also play a role in the development of SK. Activating mutations in the fibroblast growth factor receptor-3 (FGFR3), a tyrosine kinase receptor, are thought to drive the proliferation of epidermal keratinocytes. […] There is a genetic disposition for the development of these lesions, however the exact inheritance pattern is not clear. […] Pathology shows proliferation of keratinocytes with keratin-filled cysts. Hyperkeratosis, acanthosis, pseudocysts, hyperpigmentation, dyskeratosis, and lymphocytic infiltration (if inflamed) may also be seen. These lesions do not usually self resolve.

• #1 Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2911

  Seborrhoeic keratosis is an age-related skin disease. The aim of this study was to elucidate the expression characteristics of APP in seborrhoeic keratosis tissues (n=50), and explore whether the production of APP is related to the onset of seborrhoeic keratosis and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n=79). […] These findings suggest that overexpression of APP may promote the onset of seborrhoeic keratosis and is a marker of skin ageing and UV damage. […] The aim of this study was to examine the expression of APP, BACE1 and A42 in SK, and to elucidate the relationship between expression of APP and skin ageing. […] APP has been reported to be a marker for cellular senescence, and it is highly expressed or mutated in some age-related diseases, such as AD, atherosclerosis, Parkinsons disease and age-related macular degeneration.

• #1 Seborrheic Keratosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545285/

  Seborrheic keratoses have been shown to often develop oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signaling pathway, which leads to a heightened sensitivity to Akt inhibition. […] FoxN1 is a newly discovered biomarker that indicates the presence of an oncogenically active yet noncancerous phenotype in seborrheic keratoses.

• #1 Seborrheic Keratosis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1059477-overview

  Seborrheic keratoses have a higher proliferative rate than normal keratinocytes, and apoptosis is suppressed in seborrheic keratoses compared with healthy skin. […] Thus, the signaling kinase Akt is critical in preventing seborrheic keratosis cells from undergoing programmed cell death. […] In pigmented seborrheic keratoses, the proliferating keratinocytes trigger the activation of neighboring melanocytes by secreting melanocyte-stimulating cytokines. Endothelin-1 has dual stimulatory effects on DNA synthesis and melanization of human melanocytes and has been implicated as playing a part in the hyperpigmentation observed in seborrheic keratoses.

• #1 The Comparison of p16 Protein Expression between Single and Multiple Seborrheic Keratosis | Bioscientia Medicina : Journal of Biomedicine and Translational Research

  https://bioscmed.com/index.php/bsm/article/view/510

  Seborrheic keratosis (SK) is a benign epithelial tumor that attacks adults, the elderly, and an increasing number of age-related lesions. Various risk factors influence the pathogenesis of SK, including genetic predisposition and sun exposure. Recently, SK associated with a theory of keratinocytes aging. The aging prevents unlimited and uncontrolled growth of damaged cells, thereby preventing degeneration, but on the other hand, increases the resistance of the cells to apoptosis. From previous studies, the expression of p16 protein increased substantially with age, thus enabling it to be a biomarker of cellular aging at the molecular level. […] All single SK patients have a negative-weak expression of p16 protein (38.2%). Multiple SK patients have a moderate-strong expression of p16 protein (100%) and negative-weak expression of p16 protein (61.8%). Based on statistical analysis using Fisher Exact test has a statistically significant to p16 protein expression with number SK lesion (p-value 0,043). […] There is a significant correlation between p16 protein expression with single and multiple SK.

• #1 Internet Scientific Publications

  http://ispub.com/journal/the-internet-journal-of-dermatology/volume-6-number-2/acantholytic-seborrheic-keratosis.html

  Seborrheic keratosis with acantholysis is a rare variant. Acantholysis represents an epidermal cell separation as a result of breakdown of the intracellular connections, leading to the loss of cohesion between keratinocytes. […] The histogenesis of the acantholysis in the seborrheic keratosis is not clear. […] External trauma including sunlight, which causes dyskeratosis, may contribute to these changes. A moderate increase in the rate of apoptosis is observed in all varieties of seborrheic keratoses compared to normal skin. Alteration of epidermal growth factors or their receptors have been implicated in the development of seborrheic keratoses. The etiology and pathogenesis of seborrheic keratosis remain unknown.

• #1 Seborrheic Keratoses of the Penis: About a Rare Case

  https://clinmedjournals.org/articles/ijdrt/journal-of-dermatology-research-and-therapy-ijdrt-4-062.php

  Seborrheic keratoses (SK) are very common benign epidermal tumors. Their pathogenesis has been detected already in 2006 and includes several aetiological factors. The participation of human papilloma virus (HPV) is being discussed. […] The pathogenesis has been detected already in 2006 but is still not completely understood. Sun exposure, skin phenotype I and II, family predisposition and the activation of the FGFR3 (fibroblast growth factor receptor 3) signaling pathway would be the most likely aetiological factors. […] It has been suggested that HPV could play a role in the pathogenesis of SK, but the causal relationship is controversial. Tardío, et al. studied the relationship between genital and nongenital SK and HPVs. They confirmed HPVs in 70% of SK in the genital area, whereas in nongenital area, it was only in 5% of cases. Containing HPV 6 low-risk virus, they never lead to malignant transformation. […] The histopathological examination is used to confirm the diagnosis. The typical histopathological findings include acanthosis, papillomatosis, hyperkeratosis, horn cysts, and pseudocysts.

• #1 Pityrosporum and seborrheic keratosis: An association

  https://escholarship.org/uc/item/1v6514zk

  Seborrheic keratoses (SK) are one of the most common benign tumors of the skin. Studies have suggested that human papillomavirus or a benign clonal proliferation of epidermal cells is involved in the pathogenesis of some SK’s, however, this issue remains to be resolved. […] Pityrosporum ovale has been implicated in the pathogenesis of seborrheic dermatitis, however, its potential role in association with SK’s has not been evaluated; there are no publications in the English literature regarding this issue. […] This study found that a majority of the SK’s evaluated had Pityrosporum organisms in the stratum corneum. This proportion was greater than expected. Although the current study demonstrates an association between SK and Pityrosporum, it does not establish cause and effect. […] It is possible, as postulated with seborrheic dermatitis, that SK’s form as the skin’s response to an irritant or as a reactive phenomenon to colonization with Pityrosporum. […] If this association proves to be significant and Pityrosporum is involved in the pathogenesis of SK, then it is possible that antifungal medications may be useful for the prevention or treatment of SK, as these agents are useful in seborrheic dermatitis.

• #1 Seborrhoeic keratoses (brown warts, basal cell papillomas, seborrheic keratosis)

  https://dermnetnz.org/topics/seborrhoeic-keratosis

  Seborrhoeic keratoses are considered degenerative in nature. […] Stable and clonal mutations or activation of FRFR3, PIK3CA, RAS, AKT1 and EGFR genes are found in seborrhoeic keratoses. […] FRFR3 mutations also arise in solar lentigines. These mutations are associated with increased age and location on the head and neck, suggesting a role of ultraviolet radiation in these lesions. […] Seborrhoeic keratoses do not harbour tumour suppressor gene mutations. […] Epidermal growth factor receptor inhibitors (used to treat cancer) often result in an increase in verrucal (warty) keratoses.

• #1 Seborrheic Keratosis | Ento Key

  https://entokey.com/seborrheic-keratosis/

  FGFR3 mutations are the most frequent, detected in 48% of SK lesions, followed by the PIK3CA (32%), TERT promoter (24%), and DPH3 promoter mutations (24%). […] SK and squamous cell carcinoma (SCC) are both clonal tumors derived from keratinocytes, and they both have similar and overlapping genomic alterations. […] Yet SK exhibits a benign clinical behavior and remains in situ, whereas cutaneous SCC is locally invasive and has a small but definite malignant potential. […] In SK there is a defect in the cornification process of epithelial differentiation, where some cells live longer than normal and undergo inappropriate intraepithelial cornification, forming so-called pseudocysts. […] The high levels of Akt activity seem to underlie this pathological condition.

• #1 Eruptive seborrheic keratosis: A perilous clue | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/88/8/428

  A 51-year-old man presented with a 1-month history of multiple eruptive seborrheic keratoses on his back and a single painless nodule on his chest. […] An abrupt increase in the size and number of seborrheic keratoses in patients with an underlying malignancy is called the Leser-Trlat sign. More than 50% of associated malignancies are adenocarcinomas, especially those of the stomach, colon, rectum, and breast, although this sign has also been reported in other malignancies, including lung cancer. […] The exact pathogenesis of the Leser-Trlat sign is unclear. One hypothesis attributes it to growth factors released by tumor cells, such as growth hormone, epidermal growth factor, and transforming growth factor alpha. Another suggests that extracellular matrix components, such as glycosaminoglycans released from stroma of the tumor, become incorporated in distant normal skin, causing epithelial alteration and eruption of seborrheic keratoses. […] Despite the nonspecific nature of the Leser-Trlat sign, our case exemplifies the importance of performing a thorough evaluation in patients presenting with sudden-onset eruptive seborrheic keratoses.

• #1 Seborrheic Keratoses – The Most Common Benign Skin Tumor of Humans. Clinical presentation and an update on pathogenesis and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6290447/

  The mutational pattern depicted typical UV signature with the majority of alterations being C T and CC TT base changes at dipyrimidinic sites. […] Neel et al., (2016) investigated SKs, which frequently have acquired oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signalling cascade. […] They demonstrated that SKs have a hypersensitivity to Akt inhibition.

• #1 Hydrogen Peroxide 40% (Eskata) for Seborrheic Keratosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2019/1115/p643.html

  Hydrogen peroxide 40% (Eskata) is a topical solution for the in-office treatment of raised seborrheic keratosis lesions. Although the mechanism of action is not fully understood, supraphysiologic concentrations of hydrogen peroxide may cause oxidative damage and death to seborrheic keratosis cells. […] Hydrogen peroxide 40% topical solution is not particularly effective for removing seborrheic keratosis lesions, and skin reactions are common. Long-term minor cosmetic changes may occur, including hyperpigmentation and hypopigmentation.

• #2 Seborrheic Keratosis | Ento Key

  https://entokey.com/seborrheic-keratosis/

  Seborrheic keratosis (SK) is the most common benign epithelial tumor and accounts for about 20% of benign epithelial neoplasms seen on the eyelid. […] The pathogenesis of SK is not completely understood, but they are considered to arise in aging skin associated with UV exposure. […] It does not represent reactive epidermal hyperplasia but more likely results from clonal expansion of a somatically mutated keratinocyte. […] Genetic mutations have been detected in SK, showing a typical UV signature. […] A viral etiology involving human papillomavirus has been proposed, but this has not been substantiated in recent studies. […] Amyloid precursor protein (APP) and its downstream products are expressed more strongly in SK than in adjacent normal skin tissues, and also more strongly in UV-exposed skin compared with nonexposed skin. This suggests that overexpression of APP may promote the initiation of SK in aging, UV-damaged skin.

• #2 Seborrheic Keratosis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1059477-overview

  Seborrheic keratoses are thought to result from a clonal expansion of a mutated epidermal keratinocyte. […] Seborrheic keratoses exhibit histologic evidence of proliferation. Increased cell replication has been demonstrated in seborrheic keratoses with bromodeoxyuridine incorporation studies and immunohistochemistry for proliferation-associated antigens. […] A high frequency of mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) has been found in certain types of seborrheic keratoses. This was the first clue into the genetic basis for the pathogenesis of seborrheic keratoses. […] More than 80% of seborrheic keratoses have at least one mutation, and 45% have more than one mutation in an oncogene such as FGFR3, PIK3CA, KRAS, and EGFR.

• #2 Seborrhoeic keratoses (brown warts, basal cell papillomas, seborrheic keratosis)

  https://dermnetnz.org/topics/seborrhoeic-keratosis

  Seborrhoeic keratoses are considered degenerative in nature. […] Stable and clonal mutations or activation of FRFR3, PIK3CA, RAS, AKT1 and EGFR genes are found in seborrhoeic keratoses. […] FRFR3 mutations also arise in solar lentigines. These mutations are associated with increased age and location on the head and neck, suggesting a role of ultraviolet radiation in these lesions. […] Seborrhoeic keratoses do not harbour tumour suppressor gene mutations. […] Epidermal growth factor receptor inhibitors (used to treat cancer) often result in an increase in verrucal (warty) keratoses.

• #2

  https://journals.lww.com/ijd/fulltext/2024/01000/is_seborrheic_keratosis_really_benign___a_case.16.aspx

  Seborrheic keratosis (SK) is the most common benign skin tumour seen in middle aged and elderly. […] While the exact pathogenesis is still unclear, increasing age, cumulative sun exposure, and genetic factors have been attributed. […] Various etiological factors like age, cumulative UV radiation exposure, genetic predisposition, and HPV infection have been proposed. […] Accumulation of p16 and somatic alteration in FGFR3, PIK3CA, HRAS, KRAS, AKT1, EGFR, CDKN2A, TERT and DHPH3 have been reported. […] Multiple SKs arising in response to internal malignancy termed as Lesser-Trelat sign is a well-known entity. […] Though SK is considered to be benign, the incidence of tumorigenesis is reported to be 1.4%7%. […] Malignant transformation is more commonly seen in the elderly and in the head area associated with symptoms like pruritus, ulceration and pain.

• #2 Seborrheic Keratoses – The Most Common Benign Skin Tumor of Humans. Clinical presentation and an update on pathogenesis and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6290447/

  The mutational pattern depicted typical UV signature with the majority of alterations being C T and CC TT base changes at dipyrimidinic sites. […] Neel et al., (2016) investigated SKs, which frequently have acquired oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signalling cascade. […] They demonstrated that SKs have a hypersensitivity to Akt inhibition.

• #2 Seborrheic Keratoses – The Most Common Benign Skin Tumor of Humans. Clinical presentation and an update on pathogenesis and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6290447/

  Seborrheic keratoses (SK) are the most common skin tumour of humanity. […] Recently, oncogenic mutations have been detected involved in the development of SK, which, however, do not bear the risk of malignant transformation. […] The etiopathology of SKs is not completely understood. They are considered a sign of ageing skin and UV-exposure may be associated with. […] Expression of the amyloid precursor protein (APP) has been evaluated in SKs versus normal skin by immunohistochemistry, Western blotting and quantitative real-time polymerase chain reaction (PCR). […] These findings suggest that overexpression of APP may promote the onset of SK and is a marker of skin ageing and UV damage. […] Exome sequencing of SKs indicated three mutations per megabase pairs of the targeted sequence.

• #2 Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2911

  Seborrhoeic keratosis is an age-related skin disease. The aim of this study was to elucidate the expression characteristics of APP in seborrhoeic keratosis tissues (n=50), and explore whether the production of APP is related to the onset of seborrhoeic keratosis and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n=79). […] These findings suggest that overexpression of APP may promote the onset of seborrhoeic keratosis and is a marker of skin ageing and UV damage. […] The aim of this study was to examine the expression of APP, BACE1 and A42 in SK, and to elucidate the relationship between expression of APP and skin ageing. […] APP has been reported to be a marker for cellular senescence, and it is highly expressed or mutated in some age-related diseases, such as AD, atherosclerosis, Parkinsons disease and age-related macular degeneration.

• #2 Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2911

  Therefore, the activation of APP is correlated with UV exposure and age. […] Taken together, APP is an age-dependent protein and can be considered as a marker of skin ageing. […] We herein found that APP was highly expressed in the whole epithelial SK tissue. […] In summary, this study demonstrates, for the first time, that APP is highly expressed in SK tissues. APP expression in the epidermis of normal skin tissues increased with age. APP may be a biomarker of skin ageing, but whether this is a primary event, or is secondary to other processes involved in skin ageing and SK pathogenesis, needs further research.

• #2 Seborrheic Keratosis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1059477-overview

  Seborrheic keratoses have a higher proliferative rate than normal keratinocytes, and apoptosis is suppressed in seborrheic keratoses compared with healthy skin. […] Thus, the signaling kinase Akt is critical in preventing seborrheic keratosis cells from undergoing programmed cell death. […] In pigmented seborrheic keratoses, the proliferating keratinocytes trigger the activation of neighboring melanocytes by secreting melanocyte-stimulating cytokines. Endothelin-1 has dual stimulatory effects on DNA synthesis and melanization of human melanocytes and has been implicated as playing a part in the hyperpigmentation observed in seborrheic keratoses.

• #2 FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization | Modern Pathology

  https://www.nature.com/articles/3800837

  Our results show that FGFR3 mutations are already present in flat seborrheic keratoses. This finding indicates that the mutations may be early genetic events in the pathogenesis of at least a subset of seborrheic keratoses. […] Interestingly, we found that the frequency of FGFR3 mutations was significantly associated with an increased age. […] This result suggests that age is a major risk factor for the occurrence of somatic FGFR3 mutations in skin. […] The mechanisms leading to the development of acanthosis, papillomatosis, hyperkeratosis and hyperpigmentation in FGFR3 mutant skin and details of the involved signaling pathways downstream of the mutant FGFR3 protein in the epidermis are largely unknown. […] Expression of anti-apoptotic bcl-2 was significantly associated with FGFR3 mutations in acanthotic seborrheic keratoses, suggesting that the anti-apoptotic PI-3K/Akt-pathway upstream of bcl-2 may be involved in addition to an increased proliferation.

• #2 Seborrheic Keratosis | Concise Medical Knowledge

  https://www.lecturio.com/concepts/seborrheic-keratosis/

  Clonal expansion of somatically mutated cells (not epidermal hyperplasia): Growth is driven by mutations in oncogenes, most commonly FGFR3 and PIK3CA. […] Lack malignant potential, possibly owing to: Lack of tumor suppressor gene mutations, FGFR3 stimulation of the differentiation transcription factor FOXN1.

• #2 Hydrogen Peroxide Use for Chemical Destruction in Seborrheic Keratosis: A Review

  https://opendermatologyjournal.com/VOLUME/13/PAGE/68/FULLTEXT/

  Seborrheic Keratoses (SK) are common, benign tumors of the epidermis that first appear most often in middle-aged men and women. […] They are benign neoplasms characterized by the accumulation of epidermal keratinocytes arrested in the G1 phase of the cell cycle, in cellular senescence. Expression of a cyclin-dependent kinase inhibitor, p16 is implicated in its pathogenesis. […] Somatic mutations have also been implicated in SK pathogenesis, such as FGFR3, in which increasing age and ultraviolet light exposure increase the risk for development. […] The exact mechanism by which hydrogen peroxide treats seborrheic keratoses is unknown. However, topical treatment is thought to result in dissociation of the chemical into water and Reactive Oxygen Species (ROS), which results in skin cell death.

• #2 Seborrheic keratosis – Wikipedia

  https://en.wikipedia.org/wiki/Seborrheic_keratosis

  A seborrheic keratosis is a non-cancerous (benign) skin tumour that originates from cells, namely keratinocytes, in the outer layer of the skin called the epidermis. […] The cause of seborrheic keratosis is not known. The only definitive association is that its prevalence increases with age. […] Melanoacanthoma (pigmented seborrheic keratosis) involves a proliferation of keratinocytes and melanocytes.

• #2 Seborrheic keratosis: current concepts of pathogenesis – Aleksandrova – Vestnik dermatologii i venerologii

  http://vestnikdv.ru/jour/article/view/48

  The article covers problems of seborrheic keratosis. The authors discuss current concepts of the etiology and pathogenesis of the disease paying special attention to the histology and immunohistochemistry of different forms and diverse clinical presentations. […] The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1. […] Paracrine cytokine mechanisms underlying the hyperpigmentation of seborrheic keratosis in covered skin areas.

• #2 Clinicopathological Evaluation of Seborrheic Keratosis Lesions in Patients Referred to Afzalipour Hospital, Kerman, Iran

  https://brieflands.com/articles/jssc-122310

  Seborrheic keratosis is a benign epidermal proliferation, which is highly common in sun-exposed areas. […] Although the exact pathogenesis of the SK was not well-understood, factors such as sun exposure, genetic predisposition, and genetic mutation in FGFR3 due to ultraviolet (especially in adenoid type) were also considered. […] Most of the lesions were located in sun-exposed areas (65.6%) in the present study. […] Furthermore, there was no significant difference between pathological subtypes and sun-exposure in the present study. […] The most common pathological subtypes in the present study were acanthotic and hyperkeratotic types (47.5% 27.3%, respectively). […] In this study, the most common pathological features were horn cyst (75.8%), acanthosis (71.7%), and hyperkeratosis (60.6%), respectively.

• #2 Hydrogen Peroxide Use for Chemical Destruction in Seborrheic Keratosis: A Review

  https://opendermatologyjournal.com/VOLUME/13/PAGE/68/FULLTEXT/

  Possible methods to increase the efficiency of hydrogen peroxide as a topical treatment include creating a solution with an activator such as a tertiary amine in which the chemical release of ROS is maximized, agitating the solution before application, priming the skin surface, and managing the timing and location of the H202 reaction with the skin such that maximal ROS release is achieved.

• #2 Seborrheic Keratosis | Ento Key

  https://entokey.com/seborrheic-keratosis/

  FGFR3 mutations are the most frequent, detected in 48% of SK lesions, followed by the PIK3CA (32%), TERT promoter (24%), and DPH3 promoter mutations (24%). […] SK and squamous cell carcinoma (SCC) are both clonal tumors derived from keratinocytes, and they both have similar and overlapping genomic alterations. […] Yet SK exhibits a benign clinical behavior and remains in situ, whereas cutaneous SCC is locally invasive and has a small but definite malignant potential. […] In SK there is a defect in the cornification process of epithelial differentiation, where some cells live longer than normal and undergo inappropriate intraepithelial cornification, forming so-called pseudocysts. […] The high levels of Akt activity seem to underlie this pathological condition.

• #3 Seborrheic Keratosis | Concise Medical Knowledge

  https://www.lecturio.com/concepts/seborrheic-keratosis/

  Clonal expansion of somatically mutated cells (not epidermal hyperplasia): Growth is driven by mutations in oncogenes, most commonly FGFR3 and PIK3CA. […] Lack malignant potential, possibly owing to: Lack of tumor suppressor gene mutations, FGFR3 stimulation of the differentiation transcription factor FOXN1.

• #3 Seborrheic Keratosis | Ento Key

  https://entokey.com/seborrheic-keratosis/

  FGFR3 mutations are the most frequent, detected in 48% of SK lesions, followed by the PIK3CA (32%), TERT promoter (24%), and DPH3 promoter mutations (24%). […] SK and squamous cell carcinoma (SCC) are both clonal tumors derived from keratinocytes, and they both have similar and overlapping genomic alterations. […] Yet SK exhibits a benign clinical behavior and remains in situ, whereas cutaneous SCC is locally invasive and has a small but definite malignant potential. […] In SK there is a defect in the cornification process of epithelial differentiation, where some cells live longer than normal and undergo inappropriate intraepithelial cornification, forming so-called pseudocysts. […] The high levels of Akt activity seem to underlie this pathological condition.

• #3 Seborrheic Keratosis – EyeWiki

  https://eyewiki.org/Seborrheic_Keratosis

  Seborrheic keratosis is a benign proliferation of immature keratinocytes between the basal layer and the keratinizing surface of the epidermis. […] The pathogenesis of seborrheic keratosis (SK) remains poorly understood. Immature epidermal keratinocytes slowly proliferate leading to macules, papules, and plaques known as seborrheic keratoses. […] Recent studies have proposed that increased expression of the transmembrane protein amyloid precursor protein (APP) may play an important role. APP is mainly expressed in keratinocytes and melanocytes in the epidermal basal layer with only a small amount in the dermal fibroblasts of the epidermal-dermal junction. […] The expression of APP is higher in UV-exposed skin and increases with age. APP was found to be present throughout all layers of SK tissue samples, and more extensively expressed when compared to adjacent normal skin tissue.

• #3 Seborrheic Keratosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28812

  Seborrheic keratoses have been shown to often develop oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signaling pathway, which leads to a heightened sensitivity to Akt inhibition. […] FoxN1 is a newly discovered biomarker that indicates the presence of an oncogenically active yet noncancerous phenotype in seborrheic keratoses.

• #3 Seborrheic Keratoses of the Penis: About a Rare Case

  https://clinmedjournals.org/articles/ijdrt/journal-of-dermatology-research-and-therapy-ijdrt-4-062.php

  Seborrheic keratoses (SK) are very common benign epidermal tumors. Their pathogenesis has been detected already in 2006 and includes several aetiological factors. The participation of human papilloma virus (HPV) is being discussed. […] The pathogenesis has been detected already in 2006 but is still not completely understood. Sun exposure, skin phenotype I and II, family predisposition and the activation of the FGFR3 (fibroblast growth factor receptor 3) signaling pathway would be the most likely aetiological factors. […] It has been suggested that HPV could play a role in the pathogenesis of SK, but the causal relationship is controversial. Tardío, et al. studied the relationship between genital and nongenital SK and HPVs. They confirmed HPVs in 70% of SK in the genital area, whereas in nongenital area, it was only in 5% of cases. Containing HPV 6 low-risk virus, they never lead to malignant transformation. […] The histopathological examination is used to confirm the diagnosis. The typical histopathological findings include acanthosis, papillomatosis, hyperkeratosis, horn cysts, and pseudocysts.

• #3 The Comparison of p16 Protein Expression between Single and Multiple Seborrheic Keratosis | Bioscientia Medicina : Journal of Biomedicine and Translational Research

  https://bioscmed.com/index.php/bsm/article/view/510

  Seborrheic keratosis (SK) is a benign epithelial tumor that attacks adults, the elderly, and an increasing number of age-related lesions. Various risk factors influence the pathogenesis of SK, including genetic predisposition and sun exposure. Recently, SK associated with a theory of keratinocytes aging. The aging prevents unlimited and uncontrolled growth of damaged cells, thereby preventing degeneration, but on the other hand, increases the resistance of the cells to apoptosis. From previous studies, the expression of p16 protein increased substantially with age, thus enabling it to be a biomarker of cellular aging at the molecular level. […] All single SK patients have a negative-weak expression of p16 protein (38.2%). Multiple SK patients have a moderate-strong expression of p16 protein (100%) and negative-weak expression of p16 protein (61.8%). Based on statistical analysis using Fisher Exact test has a statistically significant to p16 protein expression with number SK lesion (p-value 0,043). […] There is a significant correlation between p16 protein expression with single and multiple SK.

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