Linear basal cell nevus.

To the Editor: We read with interest the article of Colvett et al (1) describing a patient with numerous basal cell carcinomas on the lower extremity occurring in a linear distribution. The authors concluded from the patient's presentation that this was a case of multiple metastases occurring in a linear distribution from a primary tumor on the foot. We are concerned that their diagnosis is incorrect, and that the patient rather has a linear basal cell nevus.

The authors are correct to point out the rarity of primary basal cell carcinomas on the distal lower extremity and of metastases arising from basal cell carcinomas. To date, there have been no reports of in-transit metastases from basal cell carcinomas. Moreover, the patient's "primary" tumor does not fit the profile of a metastasizing basal cell carcinoma in terms of size or invasion. Finally, the histology does not support a diagnosis of metastatic basal cell carcinoma, as one of the lesions they biopsied revealed fibroepithelioma of Pinkus, which is histologically characterized by basaloid strands of cells arising from the epidermis. A cutaneous metastasis, by definition, has to be a dermal tumor, not a de novo epidermal tumor with a histologic pattern distinct from the presumed primary.

Mutations in the patched gene have been found to underlie the basal cell nevus syndrome in which patients develop innumerable basal cell carcinomas, as well as odontogenic jar keratocysts, craniofacial and musculoskeletal abnormalities, palmar pits, and a variety of other tumors including medulloblastomas. (2) We have previously reported unilateral basal cell nevus syndrome affecting half the body with a sharp midline cutoff, presumably due to postzygotic mutations in the patched gene. (3) Moreover, several cases of linear basal cell nevi have been reported in the literature in which numerous basal cell carcinomas develop in a linear fashion following the lines of Blaschko, due to postzygotic mutations that affect only a small portion of the cutaneous surface. (4) The lines of Blaschko represent clonal postzygotic migration of epidermal and mesenchymal cells of the skin. As such, a postzygotic mutation would lead to cutaneous involvement of either half the body or involvement following the lines of Blaschko. That the reported patient's lesions follow the line of Blaschko is clear because the figures demonstrate that the lesions followed a thin, linear, vertical distribution on the thigh and leg, while respecting the junction between the plantar skin and hair-bearing skin, as is classically described for the lines of Blaschko on the foot. (4)

We believe that the patient described is a fascinating example of a rare genetic phenomenon. Further genetic studies comparing this patient's skin in the affected line of Blaschko to the patient's normal skin would reveal the underlying genetic basis of this condition, which is likely a mutation in the patched gene or a related member of the sonic hedgehog pathway.

References

1. Colvett KT, Wilson FC, Stanton RA. Atypical presentation of metastatic basal cell carcinoma. South Med J 2004;97:305-307.

2. Johnson RL, Rothman AL, Xie J, et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996;272:1668-1671.

3. Jih MH. Linear unilateral basal-cell nevus syndrome with comedones. Dermatol Online J 2002;8:12.

4. Bolognia JL, Orlow SJ, Glick SA. Lines of Blaschko. J Am Acad Dermatol 1994;31:157-190.

Arash Kimyai-Asadi, MD and Ming H. Jih, MD, PHD

DermSurgery Associates, Houston, TX