Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

Schmitz, Lutz; Gambichler, Thilo; Kost, C; Gupta, Girish; Stücker, Markus; Stockfleth, Eggert; Dirschka, Thomas

doi:10.1111/bjd.16536

Cited by 54 publications

(85 citation statements)

References 16 publications

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“…). These findings are in line with a previously demonstrated histomorphological relationship between proliferative AK lesions and invasive SCCs . Hence, underlying histomorphological patterns of basal growth and subsequently invasive carcinoma (PRO I < PRO II < PRO III < SCC) seem to correlate consistently with the frequency of mutated KNSTRN gene.…”

Section: Discussionsupporting

confidence: 91%

“…It is therefore evident that a classification which is based only on the extent of atypical keratinocytes throughout the epidermis will lack predictive value in relation to development into or de novo generation of a SCC. In contrast, a recently proposed and evaluated classification scheme focusing on the basal proliferation pattern of AKs has shown a strong association between higher grades and invasive SCCs . The main difference to the classical histological grading system is the evaluation of the basal growth pattern at the basement membrane which resembles a key structure in terms of differentiation between in situ SCC and invasive SCC.…”

Section: Introductionmentioning

confidence: 95%

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Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma

Schmitz

Grinblat

Novak

et al. 2019

Acad Dermatol Venereol

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Background Mutations in kinetochore gene KNSTRN accelerate the development of cutaneous squamous cell carcinoma (SCC) and may correlate with different histological classifications of actinic keratosis (AKs). Objective To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings and invasive SCCs. Methods All samples were histologically evaluated. AK lesions were additionally classified according to their upwards (AK I–III) and downwards (PRO I–III) directed growth pattern. Mutation analyses of all samples were performed using the Sanger method. Results With one exception, all detected mutations in KNSTRN gene showed an alanine‐to‐glutamate substitution at codon 40 (p.Ala40Glu). p.Ala40Glu mutation was found in 6.9% (2/29) of HS, in 16.1% (5/31) of ADS, in 18.3% (20/109) of AKs and in 30.0% (9/30) of invasive SCCs. Further stratification of AKs using the common AK classification of Röwert‐Huber revealed the p.Ala40Glu mutation in 14.7% (5/43), 13.3% (4/30) and 24.4% (11/45) (AK I, II and III). In contrast, the new PRO classification showed a distribution of 3.6% (1/28) in PRO I, 21.7% (13/60) in PRO II and 28.6% (6/21) in PRO III. Mutation frequency in HS showed significant differences compared to AKs classified as PRO III and invasive SCCs (P < 0.05). In contrast, there were no statistically significant differences between HS and AKs when classified according to Röwert‐Huber. Conclusions Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating AKs in accordance with invasive SCCs. This supports the impact of basal proliferative pattern in terms of progression.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 95%

Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma

Schmitz

Grinblat

Novak

et al. 2019

Acad Dermatol Venereol

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“…It is, however, open to bias without a prospective approach as it is difficult to conclude whether the AK progressed to invasive SCC or what happened to skin adjacent to excised tissue. Moreover, this study was carried out prior to another recently published study which showed a significant association between basal proliferating AKs and invasive SCCs . Thus, the dermatopathologists were not aware of these results and subsequently not influenced by them, so that their conclusions were purely based on their dermatohistological experience.…”

Section: Discussionmentioning

confidence: 99%

“…Until now, there is no uniform consensus of what histological information on AK lesions should be provided by dermatopathologists to clinicians, particularly features which may give prognostic value as this is what clinicians require to decide on further management. With current evidence this prognostic information should focus on atypical keratinocytes along the basement membrane and their associated basal proliferation . Thus, a histological report should answer two main questions: (i) Invasive or in‐situ ?…”

Section: Discussionmentioning

confidence: 99%

“…AK III lesions representing full thickness atypia of the epidermis were not associated with the highest risk for invasion . On the contrary, AKs with atypical keratinocytes restricted to the lower third (AK I) of the epidermis as well as AKs with an advanced basal proliferation (PRO III) were more commonly associated with invasive SCCs in their direct vicinity . Thus, the assessment of basal growth pattern is important to evaluate progression risk and should be applied to histologically classify all AKs.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of two histological classifications for actinic keratoses – PRO classification scored highest inter‐rater reliability

Schmitz

Gupta

Stücker

et al. 2019

Acad Dermatol Venereol

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Background Actinic keratoses (AKs) can histologically be classified by the extent of atypical keratinocytes throughout the epidermis or their pattern of basal proliferation. Currently, no data on the inter‐rater reliability of both scores is available. Objective To evaluate the inter‐rater reliability of the two classification schemes; histological grade (AK I–III) and basal proliferation (PRO I–III). Methods Histological images of 54 AKs were classified by 21 independent dermatopathologists with regard to basal proliferation (PRO I–III), histological grade (AK I–III) and assumed risk of progression into invasive carcinoma. Results Overall, of the 54 AKs 16.7% (9/54) were classified as AK I, 66.7% (36/54) as AK II, and 16.7% (9/54) as AK III. With regards to basal growth pattern, 25.9% (14/54) were classified as PRO I, 42.6% (23/54) as PRO II, and 31.5% (17/54) as PRO III. We observed a highly significant inter‐rater reliability for PRO‐grading (P < 0.001) which was higher than for AK‐grading (Kendall's W coefficient: AK = 0.488 vs. PRO = 0.793). We found substantial agreement for assumed progression risk for AKs with worsening basal proliferation (k = 0.759) compared to moderate agreement (k = 0.563) for different AK‐gradings. Conclusions Histological classification of basal growth pattern (PRO) showed higher inter‐rater reliability compared to the established classification of atypical keratinocytes throughout epidermal layers. Moreover, experienced dermatopathologists considered basal proliferation to be more important in terms of progression risk than upwards directed growth patterns. It should be considered to classify AKs according to their basal proliferation pattern (PRO I–III).

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Squamous Cell Carcinoma and its Precursors

Gupta,

Dirschka

2024

Rook's Textbook of Dermatology

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Squamous cell carcinoma (SCC) is the second commonest skin cancer and arises from epidermal keratinocytes or its appendages. The incidence of SCC has increased over the last five decades and is predicted to rise significantly over the next decade. SCC is predominantly a disease of white populations and is especially prevalent in this group in areas of high ambient sun exposure. Predisposing factors include male sex, immune suppression (particularly in those who are organ transplant recipients), sun exposure and advanced age. Precursor lesions such as actinic keratosis and Bowen disease may often be present and patients are more susceptible to developing other UV radiation‐induced skin cancers. SCC has a low rate of metastasis but this increases with SCCs displaying high‐risk features. All SCCs should undergo full clinicopathological correlation and high‐risk SCCs should be managed within a multidisciplinary setting with adequate tumour clearance as the main outcome.

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Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

Cited by 54 publications

References 16 publications

Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma

Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma

Evaluation of two histological classifications for actinic keratoses – PRO classification scored highest inter‐rater reliability

Squamous Cell Carcinoma and its Precursors

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