An Atlas of Lumps and Bumps: Part 9
Alexander K. C. Leung, MD1,2 —Series Editor • Benjamin Barankin, MD3 • Joseph M. Lam, MD4 • Kin Fon Leong, MD5
1Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
2Alberta Children’s Hospital, Calgary, Alberta, Canada
3Toronto Dermatology Centre, Toronto, Ontario, Canada
4Department of Pediatrics and Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, British Columbia, Canada
5Pediatric Institute, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia
Leung AKC, Barankin B, Lam JM, Leong KF. An atlas of lumps and bumps, part 9. Consultant. 2021;61(10):e18-e20. doi:10.25270/con.2021.09.00003
Dr Leung is the series editor. He was not involved with the handling of this paper, which was sent out for independent external peer review.
Alexander K. C. Leung, MD, #200, 233 16th Ave NW, Calgary, AB T2M 0H5, Canada (firstname.lastname@example.org)
This article is part of a series describing and differentiating dermatologic lumps and bumps. To access previously published articles in the series, visit https://bit.ly/35J1I1v.
Tuberous sclerosis complex is an inherited neurocutaneous multisystem disorder characterized by the potential for the development of hamartomas in almost every organ, most notably in the skin, brain, kidneys, heart, and eyes.1,2 Facial angiofibromas are hamartomas composed of vascular and connective tissue elements and are found in approximately 75% of patients with tuberous sclerosis complex.1-6 Histologically, the lesion is characterized by dermal fibrosis and capillary dilatation.7 Sebaceous glands are often atrophic.1,2,7 As the lesion of angiofibroma is not related to sebaceous glands, the traditional term “adenoma sebaceum” is a misnomer and should be avoided.
Facial angiofibromas typically appear during preschool years in the malar area (“butterfly distribution”), nasolabial folds, and chin as small pink to red-brown dome-shaped papules with a smooth, glistening surface (Figures 1 and 2).1-3,6,8 The lesions gradually enlarge and become more numerous with age until adolescence, and they remain unchanged thereafter.3 Fibrous cephalic plaque, a variant of angiofibroma, is seen in approximately 20% of patients with tuberous sclerosis complex (Figure 3).5,9 The lesion may present at birth and commonly becomes more noticeable in early childhood, grows very slowly, and presents as a soft to firm, elevated plaque.10 The color varies from yellow, pink, tan, and brown.4,5,9 The lesion is usually on the forehead, but may occur on the scalp or any part of the face including the eyelid.10,11 A cephalic fibrous plaque may be the first and most readily recognized feature of tuberous sclerosis complex.
According to a National Institutes of Health consensus conference, a definitive diagnosis of tuberous sclerosis complex can be made when 2 major features or 1 major feature plus 2 minor features are demonstrated.12 In this regard, 3 or more facial angiofibromas or 1 or more cephalic plaques constitute a major feature of tuberous sclerosis complex.3,4
Multiple angiofibromas are found in approximately 88% of patients with multiple endocrine neoplasia type 1.13,14 The angiofibromas in patients with multiple endocrine neoplasia type 1 tend to be smaller and fewer than in patients with tuberous sclerosis complex.13,14 They also have a later age of onset. In addition, angiofibromas in patients with multiple endocrine neoplasia type 1 are often observed on the vermilion border of the upper lip—an area that tends to be spared in patients with tuberous sclerosis complex.13,14 Patients with multiple endocrine neoplasia type 1 do not have other features of tuberous sclerosis complex.
Ungual fibromas (Koenen tumors), a term for periungual fibromas and subungual fibroma, are hamartomatous fibromas. Generally, periungual fibromas are more common than subungual fibroma.4 Periungual and ungual fibromas are more commonly observed on toenails rather than fingernails.2,3 Typically, ungual fibromas present as smooth, firm, nodular, or fleshly lesions that are adjacent to the nails near the proximal nail fold (Figures 4 and 5).8,16 At times, they may appear underneath the nail plate or over the lateral nail groove (Figure 6).4 One of the initial features of ungual fibroma is a groove in the nail plate in the absence of an obvious tumor (Figure 7).8 Ungual fibromas are slow-growing.8,15 They are found in approximately 20% of unselected patients with tuberous sclerosis complex and are more commonly observed in adolescents and adults than in young children.3,16 These lesions occasionally develop subsequent to trauma.3,16 Two or more nontraumatic ungual fibromas constitute a major feature of tuberous sclerosis complex.3,16 Before correlating an ungual fibroma to tuberous sclerosis complex, one should explore the possibility whether the lesion is trauma-induced.16
The shagreen or “leather” patch is a connective tissue hamartoma made up of collagen and reduced elastic fibers.4 Typically, the patch is found in the lumbosacral region but can also be found on the neck, chest, abdomen, and thighs.4,8 Shagreen patches often occur in the first decade of life, although they might not be apparent in young children (Figures 8 and 9).8,16
Characteristically, the lesion presents as an irregularly shaped, unevenly thickened plaque with a cobblestone or orange-peel appearance with a texture of pigskin (Figure 10).2,16 The color ranges from pink, grayish green to light brown.4,8,16 Shagreen patches are observed in approximately 50% of patients with tuberous sclerosis complex and are a major feature of the disease.3,4,8
1. Leung AK, Robson WL. Tuberous sclerosis complex: a review. J Pediatr Health Care. 2007;21(2):108-114. https://doi.org/10.1016/j.pedhc.2006.05.004
2. Leung AKC, Kamat D. Tuberous sclerosis complex. In: Kimura R, ed. Genetic Inheritance Patterns. Nova Biomedical Books; 2008; 271-289.
3. Ebrahimi-Fakhari D, Meyer S, Vogt T, Pföhler C, Müller CSL. Dermatological manifestations of tuberous sclerosis complex (TSC). J Dtsch Dermatol Ges. 2017;15(7):695-700. https://doi.org/10.1111/ddg.13264
4. Nguyen QD, DarConte MD, Hebert AA. The cutaneous manifestations of tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018;178(3):321-325. https://doi.org/10.1002/ajmg.c.31649
5. Sweeney SM. Pediatric dermatologic surgery: a surgical approach to the cutaneous features of tuberous sclerosis complex. Adv Dermatol. 2004;20:117-135.
6. Zamora EA, Aeddula NR. Tuberous Sclerosis. In: StatPearls. StatPearls Publishing; July 20, 2021. http://www.ncbi.nlm.nih.gov/books/nbk538492/
7. Schwartz RA, Fernández G, Kotulska K, Jóźwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007;57(2):189-202. https://doi.org/10.1016/j.jaad.2007.05.004
8. Cardis MA, DeKlotz CMC. Cutaneous manifestations of tuberous sclerosis complex and the paediatrician's role. Arch Dis Child. 2017;102(9):858-863. https://doi.org/10.1136/archdischild-2016-312001
9. Singanamalla B, Bhagwat C, Madaan P, Saini L, De D. Forehead plaque in a child with epilepsy: A clue for tuberous sclerosis. Trop Doct. 2021;51(2):259-260. https://doi.org/10.1177/0049475520972523
10. Oyerinde O, Buccine D, Treichel A, et al. Fibrous cephalic plaques in tuberous sclerosis complex. J Am Acad Dermatol. 2018;78(4):717-724. https://doi.org/10.1016/j.jaad.2017.12.027
11. Park SM, Kim BS, Kim MB, Lee YJ, Ko HC. Fibrous plaque of the eyelid in a patient with tuberous sclerosis responding to everolimus. Ann Dermatol. 2018;30(2):247-249. https://doi.org/10.5021/ad.2018.30.2.247
12. Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000;57(5):662-665. https://doi.org/10.1001/archneur.57.5.662
13. Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol. 1997;133(7):853-857.
14. Zeller S, Marx SJ, Lungu AO, Cowen EW, Turner ML. Multiple angiofibromas and collagenomas in a 45-year-old man with recurrent nephrolithiasis, fatigue, and vision loss. J Am Acad Dermatol. 2009;61(2):319-322. https://doi.org/10.1016/j.jaad.2009.01.026
15. Ortega-Quijano D, Pérez-García B, Vañó-Galván S. Tuberous sclerosis complex presenting as periungual fibromas and seizures in a 52-year-old woman. CMAJ. 2020;192(26):E714. https://doi.org/10.1503/cmaj.190449
16. Roach ES, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol. 2004;19(9):643-649. https://doi.org/10.1177/08830738040190090301