This study, which may have direct implications for treatment, explains why some actinic keratoses recur and progress after superficial destructive treatments - like cryotherapy.
The depth of follicular extension of atypical squamocytes in actinic keratosis correlates directly with the depth of invasion of an associated invasive squamous cell carcinoma, according to a recently published study in the Journal of the European Academy of Dermatology and Venereology.
This finding, the authors write, has direct implications for clinical treatment and offers an explanation of why some actinic keratoses recur and progress following superficial destructive treatments, like cryotherapy.
Researchers based in Spain and the U.S. retrospectively performed a histologic review of 193 invasive squamous cell carcinoma biopsy specimens, which had associated actinic keratosis, and studied the existence and depth of follicular extension of atypical keratinocytes in actinic keratosis.
More than a quarter of cases had follicular extension, which often extended into the lower follicular segment. In 58 percent of those cases, the invasive squamous cell carcinoma was directly adjacent to the follicular basalis and correlated strongly with follicular extension depth. The correlation exists regardless of the pathway of origin, they conclude.
Invasive squamous cell carcinomas arising from the follicular basalis had a median tumor thickness of 1.75 mm, compared to 0.9 mm for those skin cancers developing in the epidermis.
“It is therefore important to note the presence and the depth of follicular extension when diagnosing an [actinic keratosis], since follicular extension likely accounts for a significant proportion of recurrent [actinic keratosis] and the development of [invasive squamous cell carcinoma] following superficial treatment modalities,” they write.
Invasive squamous cell carcinoma of the skin usually starts as an actinic keratosis, but most actinic keratoses spare the follicular and adnexal epithelium, as they are confined to the interfollicular epidermis, according to the study.
Still, there are cases in which actinic keratoses have atypical squamocyte extensions down follicular and adnexal epithelium, which could be the precursor of many squamous cell carcinomas, the authors write. Researchers focusing on follicular involvement in invasive squamous cell carcinoma have reported, among other things, that “follicular” invasive squamous cell carcinoma selectively develops in the wall of the hair follicle, although this finding is not always in the setting of actinic keratosis.
The strong suggestion that deeply invasive squamous cell carcinoma often develops from the follicular basalis and direct implications for treatment.
“If the histopathological assessment carefully notes the presence and the depth of follicular extension of an [actinic keratosis], then more aggressive treatment modalities, such as curettage, excision or the use of photosensitizers, may be employed,” they write. “Such treatment would likely limit the incidence of recurrence and the development of [invasive squamous cell carcinoma].”
The study suggests hair follicles might contribute greatly to deeply invasive squamous cell carcinoma development - a relationship which has played out in animal studies. Another important take-away from the story for dermatologists: sweat glands, were rarely involved in this study and do not appear to play a major role in invasive squamous cell carcinoma in the presence of an actinic keratosis. While sweat glands might have been involved in their most superficial portion, the skin cancer never was identified nearby.
Together, the findings support the thinking that only the hair follicle, among adnexal structures, plays a key role in invasive squamous cell carcinoma genesis.
The study has no funding sources. Some of its authors are consultants to and speakers for Almirall, Novartis and Leo Pharma.
M.T. FernÃ¡ndezÃ¢€ÂFigueras X. SaenzÃ¢€ÂSardÃ P. Vargas, et al. "The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment," Journal of European Academy of Dermatology and Venereology (JEADV), March 23, 2018. https://doi.org/10.1111/jdv.14901