Abstract
Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant disorder characterized by the presence of various adnexal tumors including multiple cylindromas, trichoepitheliomas and spiradenomas. A 35-year-old female presented with multiple asymptomatic nodular lesions over face and scalp since the age of 5 years. There were no complaints suggestive of systemic involvement. Her son, elder sister, younger sister, father, father's sister, and grandmother had history of similar lesions. On examination, there were multiple asymptomatic skin-colored firm papulonodular lesions measuring from 2 to 8 mm in diameter, with smooth surface mainly affecting central part of face. Scalp showed pinkish, firm, smooth-surfaced, dome-shaped nodules measuring about 1 to 3 cm in size. Histopathological examination was consistent with trichoepitheliomas for the facial lesions and cylindromas for the scalp lesions. The diagnosis of BSS was thus confirmed.
Keywords: Brooke-Spiegler, cylindromas, trichoepithelioma
INTRODUCTION
Brooke-Spiegler syndrome (BSS) known as familial autosomal dominant cylindromatosis is a rare disorder characterized by various adnexal tumors including cylindromas, trichoepitheliomas, and spiradenomas. Other associated tumors are trichoblastomas, basal-cell carcinomas, follicular cysts, and organoid nevi.[1,2] We are reporting the case due to its rarity.
CASE REPORT
A 35-year-old female presented with multiple asymptomatic nodules which started over face and gradually increased in size and number since age of 5 years [Figure 1a]. Few nodules appeared over scalp 5 years back and gradually increased in size [Figure 1b]. Her son, younger and elder sister, father, father's sister, and grandmother had history of similar lesions [Figure 1c & d and 2]. On examination, multiple, asymptomatic, skin-colored, firm, papulonodular lesions measuring from 2 to 8 mm with smooth surface were present on central part of face [Figure 1a]. Scalp showed pinkish, firm, dome-shaped nodules with smooth surface measuring about 1 to 3 cm [Figure 1b]. No abnormality was detected on systemic examination. Routine blood and urine examination were normal. Histopathological examination of punch biopsy sample from lesion over face showed basaloid inclusions with multiple immature hair follicles and abundant stroma, thus confirming the diagnosis of trichoepithelioma [Figure 3a]. The lesions over scalp showed well-circumscribed epithelial neoplasm in mid and deep dermis comprising of basaloid cells arranged in closely crowded reticulated pattern giving a jigsaw puzzle appearance. Within these nodules, several scattered ductal structures lined by eosinophilic cuticle and pink colloidal intracytoplasmic bodies were present. These findings were consistent with the diagnosis of cylindroma [Figure 3b]. Based on clinical and histopathological features, diagnosis of BSS was made. As the only concern of patient was regarding cosmetic appearance, she was referred to plastic surgeon for excision of nodular lesions.
Figure 1.
(a) Multiple skin-colored papulonodular lesions affecting forehead, upper lip, nasolabial folds (arrow). (b) Single, smooth surfaced, skin colored dome shaped nodule over scalp (arrow). (c) Similar lesions in elder sister (arrow). (d) Similar lesions in her son (arrow)
Figure 2.
Family pedigree showing seven members in four successive generations affected with the disease
Figure 3.
(a) Basaloid inclusions with immature hair follicles and abundant stroma which is consistent with trichoepithelioma (hematoxylin and eosin, original magnification ×100). (b) Wellcircumscribed epithelial neoplasm in mid to deep dermis with basaloid inclusions, giving a jigsaw puzzle appearance which is diagnostic of cylindromas (hematoxylin and eosin, original magnification ×100)
DISCUSSION
BSS is an autosomal dominant disease characterized by multiple adnexal neoplasia particularly cylindromas, trichoepitheliomas, spiradenomas located on head and neck. Women are commonly affected, usually in third or fourth decade of life.[1,2] They are occasionally present in association with basal cell adenomas of the parotid glands, milia, organoid nevi, and basal cell carcinomas. A defect in the differentiation of folliculo-sebaceous-apocrine unit is considered in the pathogenesis.[3] The susceptibility locus has been mapped to chromosome 16q12-q13 and mutations in the cylindromatosis tumor - suppressor gene have been implicated in the phenotype diversity.[4,5] Cylindromas occur as numerous papules, nodules, or tumors distributed over scalp and sometimes on face and trunk.[2] Malignant transformation to cylindrocarcinomas is rare.[6] Trichoepitheliomas are skin-colored papules distributed on face with a predilection for nasolabial folds, forehead, chin, and preauricular area.[2] Histopathology of various adnexal tumors is characteristic and diagnostic. Cylindromas show a well-circumscribed lesion composed of tumor islands and cords of basaloid cells arranged in a jigsaw puzzle like pattern.[7] Histopathologically, trichoepithelioma is aggregations of relatively monomorphic basaloid (germinative) cells in dermis surrounded by fibrous stroma.[7]
Treatment modalities for cylindromas include excision, dermabrasion, electrodessication, Carbon dioxide (CO2) laser, cryotherapy, and radiotherapy. Considering the high recurrence and risk of malignant transformation, wide local excision is the preferred treatment.[8] Medical treatments like sodium salicylate and prostaglandin A1, which restore growth control by inhibiting NF-kB activity, are being tried in few cases.[9]
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
REFERENCES
- 1.Layegh P, Sharifi-Sistani N, Abadian M, Moghiman T. Brooke-Spiegler syndrome. Indian J Dermatol Venereol Leprol. 2008;74:632–4. doi: 10.4103/0378-6323.45109. [DOI] [PubMed] [Google Scholar]
- 2.Taylor RS, Perone BJ, Kaddu S, Kerl H. Appendage Tumors and Hamartomas of the Skin. In: Fitzpatrick TB, Wolff K, Goldsmith AL, Gilchrest AB, Paller SA, Leffell JD, editors. Dermtology in General Medicine. 7th ed. New York, NY: Mc-Graw-Hill; 2008. pp. 1068–87. [Google Scholar]
- 3.Szepietowski JC, Wasik F, Szybejko-Machaj G, Bieniek A, Schwartz RA. Brooke-Spiegler syndrome. J Eur Acad Dermatol Venereol. 2001;15:346–9. [PubMed] [Google Scholar]
- 4.Hu G, Onder M, Gill M, Aksakal B, Oztas M, Gürer MA, et al. A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome. J Invest Dermatol. 2003;121:732. doi: 10.1046/j.1523-1747.2003.12514.x. [DOI] [PubMed] [Google Scholar]
- 5.Sima R, Vanecek T, Kacerovska D, Trubac P, Cribier B, Rutten A, et al. Brooke-Spiegler syndrome: report of 10 patients from 8 families with novel germline mutations: Evidence of diverse somatic mutations in the same patient regardless of tumor type. Diagn Mol Pathol. 2010;19:83–91. doi: 10.1097/PDM.0b013e3181ba2d96. [DOI] [PubMed] [Google Scholar]
- 6.De Francesco V, Frattasio A, Pillon B, Stinco G, Scott CA, Trotter D, et al. Carcinosarcoma arising in a patient with multiple cylindromas. Am J Dermatopathol. 2005;27:21–6. doi: 10.1097/01.dad.0000141548.69423.c7. [DOI] [PubMed] [Google Scholar]
- 7.Ahmed SS, Priore DJ, Seykora TJ. Tumors of the epidermal appendages. In: Elder DE, Elenitsas R, Johnson BL, Murphy GF, editors. Lever's Histopathology of the skin. 10th ed. Philadelphia: Lippincott Williams and Williams; 2009. pp. 851–909. [Google Scholar]
- 8.Rajan N, Trainer AH, Burn J, Langtry JA. Familial cylindromatosis and brooke-spiegler syndrome: A review of current therapeutic approaches and the surgical challenges posed by two affected families. Dermatol Surg. 2009;35:845–52. doi: 10.1111/j.1524-4725.2009.01142.x. [DOI] [PubMed] [Google Scholar]
- 9.Brummelkamp TR, Nijman SM, Dirac AM, Bernards R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature. 2003;424:797–801. doi: 10.1038/nature01811. [DOI] [PubMed] [Google Scholar]