A 56-year-old Caucasian male presented with an approximately 25-year history of gradually enlarging, asymptomatic scalp nodules. His father, unavailable for examination due to his death in an auto accident decades earlier, had a nearly lifelong history of many 2-mm to 3-mm flesh-colored papules both in his nasolabial folds and on his upper lip. The patient’s sister had similar scalp nodules. Results of a recent routine laboratory panel were entirely normal. One medium-sized nodule was removed by deep shave biopsy and submitted for histologic examination. It demonstrated large, lobulated nests of basaloid cells arranged in a jigsaw puzzle pattern.
D. Adenocarcinoma of the parotid gland
The skin biopsy results, along with the clinical picture shown, are absolutely classic for the diagnosis of cylindroma. The history strongly suggests a sister similarly affected, and a parent displaying trichoepithelioma. The familial cluster of these specific two benign dermal hamartomas (and also, when present, spiradenomas), characterize the rare autosomal dominant Brooke-Spiegler syndrome. In addition to the three signature dermal hamartomas, occasional patients will also develop less common benign cutaneous neoplasms (trichoblastomas, organoid nevi) as well as typical basal cell carcinomas (even in sun-protected areas). Of particular interest, aside from skin tumors, patients with this genodermatosis are also at high risk for developing major or minor salivary gland tumors, such as adenomas and adenocarcinomas.
This disorder is now known to be caused by mutations in the CYLD (cylindromatosis) gene, located on chromosome 16q12-13.[3,4] The CYLD gene is a tumor suppressor gene which represses the tumor necrosis-alfa pathway to activation of NF-κB. Mutations in the CYLD gene, therefore, result in increased expression of NF-κB, leading to apoptotic resistance.[1,5] This is especially manifested by proliferative phenomena associated with cells located in the folliculosebaceous-apocrine unit, the characteristic neoplasm being the cylindroma. However, due to variable penetrance and expressivity of the CYLD gene, members of any given affected family may vary in which hamartoma(s) they develop.
Cylindroma lesions may be solitary or may be so numerous as to cover the scalp (so-called “turban tumors”). Positive staining with p63 indicates cells of myoepithelial origin, suggesting a differentiation toward eccrine secretory cells. While the cylindroma gradually enlarges, it only rarely undergoes malignant degeneration; this phenomenon is more common when many lesions are present.[6,7] Treatments for cosmetically bothersome cylindroma tumors include: standard excision, dermabrasion, shave excision with electrodesiccation to the base, CO2 laser ablation, cryotherapy, and radiotherapy.[2,8] However, due to a high recurrence rate with other modalities, wide local excision remains the treatment of choice.
1. Doherty SD, Barrett TL, Joseph AK. Brooke-Spiegler syndrome: Report of a case of multiple cylindromas and trichoepitheliomas. Dermatol Online J. 2008;14: 8.
2. Rajan N, Langtry JAA, Ashworth A, et al. Tumor mapping in two large multigenerational families with CYLD mutations: Implications for patient management and tumor induction. Arch Dermatol. 2009;145:1277-84.
3. Biggs PJ, Wooster R, Ford D, et al. Familial cylindromatosis (turban tumour syndrome) gene localized to chromosome 16q12-q13: evidence for its role as a tumor suppressor gene. Nat Genet. 1995;11:441-43.
4. Bignell GR, Warren W, Seal S, et al. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet. 2000;25:160-65.
5. Brummelkamp TR, Nijman SM, Dirac AM, et al. Loss of cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature. 2003;424:797-801.
6. Gerretsen AL, van der Putte SCJ, Deenstra W, et al. Cutaneous cylindroma with malignant transformation. Cancer. 1993;72:1618-23.
7. Volter C, Baier G, Schwager K, et al. Cylindrocarcinoma in a patient with Brooke-Spiegler syndrome. Laryngorhinootologie. 2002;81:243-46.
8. Rallan D, Harland CC. Brooke-Spiegler syndrome: Treatment with laser ablation. Clin Exp Dermatol. 2005;30:355-57.