Basal cell carcinoma (BCC) is the most common cutaneous malignancy treated by dermatologists [1]. Most BCCs are sporadic; however, certain genodermatoses may predispose patients to developing BCCs at an earlier age and in greater numbers [2]. Examples of such genodermatoses include nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome, Bazex-Dupré-Christol syndrome, xeroderma pigmentosum, and Rombo syndrome [2]. These diseases are typically associated with a constellation of extracutaneous symptoms that cue dermatologists to make the appropriate diagnosis. We define agminated BCC as the development of multiple, histologically confirmed basal cell carcinomas clustered within a discrete, localized region of skin. Unlike many previously reported agminated presentations, which describe a cluster of lesions arising over a short, discrete time interval, the two patients we present developed their clustered lesions progressively over more than a decade, raising the question of whether a temporal criterion should be incorporated into the definition. Most sporadic BCCs have a propensity for skin with a history of significant sun exposure/sunburns over the individual’s lifetime. Other factors, such as radiation, chemical exposure to carcinogens such as arsenic, and thermal burns, may increase the risk of BCCs in a specific area of the skin. Rarely do sporadic BCCs, in the absence of associated genetic mutations or injury/exposure of the affected skin, aggregate in a specific location, sparing other body parts.

Nonsyndromic development of numerous agminated BCCs is rarely reported and presents diagnostic and therapeutic challenges. Postzygotic somatic mutations affecting the sonic hedgehog (SHH) pathway, including protein patched homolog 1 (PTCH1), protein patched homolog 1 (PTCH2), suppressor of fused (SUFU), and smoothened (SMO), have been hypothesized in localized agminated BCCs, although this remains unconfirmed [3,4]. Patient 2 had prior full-face radiation for acne; however, this bilateral exposure does not fully explain the predominantly right-sided tumor burden, raising the possibility of additional localized susceptibility such as cutaneous mosaicism. Gene sequencing of affected skin was not performed, and mosaicism therefore remains a hypothesis. Although cutaneous mosaicism classically follows the lines of Blaschko, neither patient demonstrated a definitive distribution: patient 2’s lesions could span multiple right facial Blaschko lines, whereas patient 1’s horizontal distribution did not follow the longitudinal Blaschko lines of the forehead and frontal scalp. Systemic genetic testing was not pursued because neither patient exhibited other features of a BCC-associated genetic syndrome. Accordingly, both were diagnosed with nonsyndromic agminated BCC as a diagnosis of exclusion.

Previously reported cases identified through our narrative review are summarized in the table found in Multimedia Appendix 1. Because a systematic search was not performed, additional published, nonindexed, or unpublished cases may have been missed. Patient 2 represents, to our knowledge, the highest reported number of nonsyndromic agminated BCCs to date.

Treatment is challenging when numerous lesions involve a confined anatomic region. Although surgical excision and MMS offer high cure rates, repeated procedures may become impractical because of surgical burden and potential disfigurement [4]. Alternative approaches reported include topical 5-fluorouracil, imiquimod, carbon dioxide laser ablation, and photodynamic therapy [4]. In nevoid BCC syndrome, photodynamic therapy and SHH inhibitors have reduced development of new BCCs, suggesting potential relevance for patients with extensive nonsyndromic disease [5,6]. Topical sirolimus has also shown benefit in pediatric patients with NSBCC [7]. Acitretin and nicotinamide are guideline-supported chemopreventive options for patients at increased risk of nonmelanoma skin cancer, although their use in nonsyndromic agminated BCC remains largely unreported [8,9]. Ultimately, there is sufficient evidence that employing chemopreventive strategies and SHH inhibitors could greatly benefit patients with NSBCC experiencing surgical burnout [10].

We present two patients with nonsyndromic agminated BCCs successfully treated with surgical and destructive techniques. The focal clustering of numerous BCCs raises the possibility of underlying mosaicism or unrecognized environmental factors. Nonsyndromic agminated BCC may therefore represent a diagnosis of exclusion characterized by focal, nonlinear clustering. Further studies are needed to clarify its molecular basis and determine whether it represents a distinct disease entity.