stratification will not only help differentiate the various clinical presentations of pigmented BCC but will provide incentive and opportunity to further investigate these potential differences in presentation, disease course, and therapeutics.
A study conducted by Scrivener et al highlights the remarkable variations between BCC subtypes in relation to patient demographics and its association with treatment.2 Scrivener et al, along with several others, discuss how BCC subtype, age, gender, and/or anatomic location may predict presentation, etiology, prognosis, and treatment.2-4 As an example, superficial BCCs are more prevalent on the trunk. When stratified by gender, however, Scrivener et al found that superficial BCCs may be more likely to affect the head and neck of women, but the trunk of men.2 Additionally, age of excision differed by location and gender, with head and neck lesions excised later in women and trunk lesions excised later in men, regardless of BCC subtype.2 It is possible the various morphologies of pigmented BCC have similar and other differences when subcategorized and stratified by age, gender, and/or anatomic location. Differences between BCC subtypes extend beyond patient age and gender, however, and exist within the context of race as well. A study by Lobl et al is the first study to compare mutational differences in BCC amongst individuals of color and suggests genetic variations between different races.5
Using targeted gene sequencing, Lobl et al found significant mutational differences in BCC between Asians, Caucasians, and Hispanics.5 The most common mutations reported for BCC throughout the literature are TP53 and KDR, however, a majority of previous studies and clinical trials pertaining to BCC were comprised of majority Caucasian participants.5 Lobl et al found the GATA3 mutation, which may serve as a predictor of metastasis, invasions, and high tumor grade for head and neck BCCs, to be the most common mutation amongst Hispanic participants and TP53 amongst Asian and Caucasian participants.5 Type of mutation also differed by race/ethnicity, with frameshift mutations more common amongst Hispanic patients and missense mutations amongst Asian and Caucasian patients.5 Although the clinical associations of these findings are unclear at this time, certain studies suggest frameshift mutations to be more immunogenic and thus more susceptible to immunotherapies.5 Lobl et al’s findings suggest that patient race/ethnicity may be associated with specific mutational differences that may ultimately translate into differences in prognosis and treatment. Larger, more racially and ethnically inclusive studies investigating potential mutational differences amongst the histological subtypes of BCC are needed, as there are currently no known specific mutations unique to any particular BCC subtype.
The classification of BCC subtypes along with additional subcategorizations for pigmented BCC, specifically, is critical to improved patient care. Implementation of this sub-classification system requires improved physician education and research pertaining to pigmented BCC. Educational resources, including textbooks, kodachromes, and lectures on pigmented BCC will aid diagnosis and evaluation as well as allow dermatologists to appreciate the nuances of these pigmented lesions, especially in darker skin types. Finally, larger investigational studies analyzing this classification system and how subcategorizations of pigmented BCC may vary by race, ethnicity, age, gender, and location in relation to genetics, clinical presentation, diagnosis, prognosis, and therapeutics are needed to continue to improve our understanding of conditions that disproportionately occur in SOC.
A study conducted by Scrivener et al highlights the remarkable variations between BCC subtypes in relation to patient demographics and its association with treatment.2 Scrivener et al, along with several others, discuss how BCC subtype, age, gender, and/or anatomic location may predict presentation, etiology, prognosis, and treatment.2-4 As an example, superficial BCCs are more prevalent on the trunk. When stratified by gender, however, Scrivener et al found that superficial BCCs may be more likely to affect the head and neck of women, but the trunk of men.2 Additionally, age of excision differed by location and gender, with head and neck lesions excised later in women and trunk lesions excised later in men, regardless of BCC subtype.2 It is possible the various morphologies of pigmented BCC have similar and other differences when subcategorized and stratified by age, gender, and/or anatomic location. Differences between BCC subtypes extend beyond patient age and gender, however, and exist within the context of race as well. A study by Lobl et al is the first study to compare mutational differences in BCC amongst individuals of color and suggests genetic variations between different races.5
Using targeted gene sequencing, Lobl et al found significant mutational differences in BCC between Asians, Caucasians, and Hispanics.5 The most common mutations reported for BCC throughout the literature are TP53 and KDR, however, a majority of previous studies and clinical trials pertaining to BCC were comprised of majority Caucasian participants.5 Lobl et al found the GATA3 mutation, which may serve as a predictor of metastasis, invasions, and high tumor grade for head and neck BCCs, to be the most common mutation amongst Hispanic participants and TP53 amongst Asian and Caucasian participants.5 Type of mutation also differed by race/ethnicity, with frameshift mutations more common amongst Hispanic patients and missense mutations amongst Asian and Caucasian patients.5 Although the clinical associations of these findings are unclear at this time, certain studies suggest frameshift mutations to be more immunogenic and thus more susceptible to immunotherapies.5 Lobl et al’s findings suggest that patient race/ethnicity may be associated with specific mutational differences that may ultimately translate into differences in prognosis and treatment. Larger, more racially and ethnically inclusive studies investigating potential mutational differences amongst the histological subtypes of BCC are needed, as there are currently no known specific mutations unique to any particular BCC subtype.
The classification of BCC subtypes along with additional subcategorizations for pigmented BCC, specifically, is critical to improved patient care. Implementation of this sub-classification system requires improved physician education and research pertaining to pigmented BCC. Educational resources, including textbooks, kodachromes, and lectures on pigmented BCC will aid diagnosis and evaluation as well as allow dermatologists to appreciate the nuances of these pigmented lesions, especially in darker skin types. Finally, larger investigational studies analyzing this classification system and how subcategorizations of pigmented BCC may vary by race, ethnicity, age, gender, and location in relation to genetics, clinical presentation, diagnosis, prognosis, and therapeutics are needed to continue to improve our understanding of conditions that disproportionately occur in SOC.
DISCLOSURES
The authors have no conflicts of interest to disclose. All
manuscripts contributed substantially to this manuscript and
have been listed accordingly.
REFERENCES
1. Higgins S, Nazemi A, Chow M, et al. Review of Nonmelanoma Skin Cancer in African Americans, Hispanics, and Asians. Dermatol Surg. 2018;44(7):903- 910.
2. Scrivener Y, Grosshans E, Cribier B. Variations of Basal Cell Carcinomas According to Gender, Age, Location and Histopathological Subtype. British Journal of Dermatology. 2002;147(1):41-47.
3. Raasch BA, Buettner PG, Garbe C. Basal Cell Carcinoma: Histological Classification and Body-Site Distribution. Br J Dermatol. 2006;155(2):401- 407.
4. McCormack CJ. Differences in Age And Body Site Distribution of the Histological Subtypes of Basal Cell Carcinoma. Arch Dermatol. 1997;133(5).
5. Lobl M, Hass B, Clarey D, et al. Basal Cell Carcinoma Gene Mutations Differ Between Asian, Hispanic, and Caucasian Patients: A Pilot Study. J Drugs Dermatol. 2021;20(5):504-510.
2. Scrivener Y, Grosshans E, Cribier B. Variations of Basal Cell Carcinomas According to Gender, Age, Location and Histopathological Subtype. British Journal of Dermatology. 2002;147(1):41-47.
3. Raasch BA, Buettner PG, Garbe C. Basal Cell Carcinoma: Histological Classification and Body-Site Distribution. Br J Dermatol. 2006;155(2):401- 407.
4. McCormack CJ. Differences in Age And Body Site Distribution of the Histological Subtypes of Basal Cell Carcinoma. Arch Dermatol. 1997;133(5).
5. Lobl M, Hass B, Clarey D, et al. Basal Cell Carcinoma Gene Mutations Differ Between Asian, Hispanic, and Caucasian Patients: A Pilot Study. J Drugs Dermatol. 2021;20(5):504-510.
AUTHOR CORRESPONDENCE
Nada Elbuluk MD MSc nada.elbuluk@med.usc.edu
