Nevus Sebaceous

Nevus sebaceous is a congenital skin lesion, characterized by the presence of a hamartoma on the skin and surrounding tissue and abnormalities of the sebaceous, apocrine and follicular glands. It appears as a thin, hairless plaque with an orange to yellow color and the diagnosis is made clinically. Because malignant tumors can develop at the site of this lesion, complete excision is the recommended treatment.

  • Processes: congenital
  • Incidence: 4 / 100.000

Overview

Nevus sebaceous is a congenital skin lesion that most frequently occurs on the scalp and rarely on the face, and is characterized by the development of a skin hamartoma [1]. Several glands, including epidermal, sebaceous, follicular and apocrine, all have an impaired development. Nevus sebaceous can be observed in approximately 0.3% of all newborns [2] and both genders are equally affected. This congenital malformation of the skin is thought to occur due to postzygotic mutations in the HRAS and KHAS genes, which are involved in multiple pathways for cellular growth. Familial cases have been reported as well. Clinical presentation involves a well-demarcated solitary lesion which is usually elevated at birth, with a characteristic orange to yellow color. The area of nevus sebaceous is usually hairless, particularly if the lesion is located on the scalp. Fluctuations in its appearance may occur - it is usually flat or minimally raised at birth, while elevations, including verrucous and even nodular appearance may be observed in childhood and puberty, presumably because of hyperplasia of sebaceous and apocrine glands due to hormonal stimulation. The diagnosis of nevus sebaceous is made on clinical examination, while biopsy of this benign tumor may reveal underdeveloped or absent sebaceous glands, epidermal hyperplasia, enlarged sebaceous glands, as well as ectopic apocrine glands. Because this benign tumor may transform into a malignant lesion, primarily a basal cell carcinoma, full-thickness excision is performed to minimize chances of such a development.

Etiology

Nevus sebaceous is presumably caused by postzygotic mosaic mutations in KRAS and HRAS genes [3], which promote cell growth through signal-transduction pathways of mitogen-activating protein kinases (MAPK). It is thought that this benign skin tumor arises from pluripotent epithelial germ cells from which malignant neoplasms, such as basal cell carcinoma, may develop; this could explain the possible malignant transformation of nevus sebaceous. On the other hand, other factors have been proposed in the pathogenesis of nevus sebaceous, such as the maternal presence of human papillomavirus [4].

Mutations of HRAS and KHAS genes and the development of nevus sebaceous have been observed in several syndromes, such as Neurofibromatosis, Costello syndrome, as well as other genetic diseases, some of them with an increased risk of developing malignant neoplasms.

Epidemiology

It is established that the development of nevus sebaceous occurs in approximately 0.3% of newborns, with equal gender distribution [5]. The lesions are present from birth and have a characteristic appearance. 

Pathophysiology

Gene mutations that have been described, which occur during the postzygotic period, lead to the development of nevus sebaceous and eventually to the appearance of a benign hamartoma of the skin. The hamartoma denotes the presence of local disorganized tissue growth, which is demarcated by epidermal hyperplasia and an underdevelopment or absence of hair follicles. However, several changes are observed during puberty: androgens stimulate the tissue, a process which results in hyperplasia of apocrine glands, accompanied by a cyst.

Prognosis

Nevus sebaceous is classified as a benign tumor of the skin. However, malignant transformation of this tumor has been observed and up to 10-15% of all lesions have indeed transformed into malignant tumors in some studies. Such changes are rare in children and most commonly occur during adulthood. The most common malignant skin tumor arising from nevus sebaceous is the basal cell carcinoma (BCC) [6]. Other tumors, both benign and malignant, that may arise from nevus sebaceous include the keratoacanthoma, apocrine cystadenoma, leiomyoma, as well as the carcinoma of the apocrine glands which may rapidly metastasize [7]. For these reasons, a prompt diagnosis and proper treatment are absolutely mandatory.

Presentation

Nevus sebaceous is present from birth and usually appears as a solitary lesion, most commonly on the scalp, while the head, trunk and extremities are rather rare locations. Initial appearance includes a thin, hairless, smooth, oval or linear, yellow-to-orange colored plaque. It may be difficult to locate because of the surrounding dense hair covering the tumor and the lesion grows proportionally until puberty, when a significant progression in growth is observed. In these patients, nevus sebaceous may have a verrucous, or in rare cases, nodular appearance. In very rare cases, multiple and widespread lesions have been observed, while the oral cavity, as well as labia minora, have also been reported as sites of occurrence [8] [9].

Larger lesions have been associated with other abnormalities, such as seizures, mental retardation, skeletal abnormalities (rickets, spina bifida, bone hypertrophy and hyperplasia), ocular lesions (such as nystagmus, ptosis, hypoplasia of the optic nerve), and development of a hamartoma of the kidneys (Schimmelpenning syndrome) [10]. Schimmelpenning syndrome denotes the presence of multiple sebaceous nevi and symptoms related to the central nervous system, which may involve other organs as well.

Workup

The diagnosis of nevus sebaceous is made clinically, because of its characteristic features. If necessary, a biopsy of the lesion and a histological examination can confirm the diagnosis. Microscopy can reveal papillomatous hyperplasia, numerous apocrine glands, thin epidermis, absence of hair follicles and enlarged sebaceous glands. The diagnosis can be suspected during the fetal period and larger lesions can be observed with ultrasonographic techniques [11]. 

If there are other symptoms, such as mental retardation, appearance of multiple nevi, as well as skeletal and ocular lesions, a suspicion toward Schimmelpenning syndrome should be raised and careful evaluation must ensue.

Treatment

Treatment of nevus sebaceous is primarily surgical, and involves complete excision of the tumor.

Because of the risk for malignant transformation of the tumor at any age, complete surgical excision is recommended by the majority of guidelines, which suggest excision of the tumor before puberty.

Full-thickness skin excision is the method of choice. However, several factors play a role in timing, as well as choice of treatment, such as the location, the size of the tumor, and age. Anesthesia in early life has been discussed as an unnecessary exposure to children. Since general anesthesia is necessary for surgery in late childhood and local anesthesia is adequate in early adolescence [12], many clinicians discourage the patients from being operated on very early in life. Moreover, larger studies have concluded that the majority of tumors that arise from nevus sebaceous are of benign origin and because of the fact that virtually no malignant tumors develop in children, the assumption of delaying surgery until adolescence has been considered reasonable [13].

Prevention

Although the cause of nevus sebaceous is known, prevention strategies do not exist. In patients who have nevus sebaceous, however, prevention is oriented toward surgical removal of the tumor, to eliminate any chances of malignant transformation.

Patient Information

Nevus Sebaceous is a benign skin tumor that develops during the fetal period of life and occurs as a result of several mutations in genes that regulate cell growth. It is seen in less than 1% of individuals, making this skin lesion quite rare. However, because of its ability to cause other tumors on the site of the initial tumor, some of them malignant, prompt diagnosis is of vital importance.

Nevus Sebaceous typically presents as a single lesion on the scalp, while lesions on the head, trunk and extremities have been rarely reported. Features of the lesion include absence of hair, a yellow to orange appearance, linear or oval in shape and either mildly elevated or at the level of the skin. As patients grow, the lesion can grow as well and it rapidly proliferates in puberty, presumably because of hormonal influences. 

Because of its distinct and typical appearance, the diagnosis of Nevus Sebaceous is made clinically, while a biopsy of the tumor may be performed to confirm the diagnosis.

Treatment is recommended for all patients, because of the risk for the development of malignant tumors, principally basal cell carcinoma (BCC). Treatment is usually delayed until late childhood or early adolescence because it is considered uncertain for a child to undergo general anesthesia for minimal risks. This conclusion is based on the observation that malignant tumors do not develop until the age of adulthood.

References

  1. Terenzi V, Indrizzi E, Buonaccorsi S, et al. Nevus sebaceus of Jadassohn. J Craniofac Surg. 2006;17:1234-1239.
  2. Eisen DB, Michael DJ. Sebaceous lesions and their associated syndromes: part I. J Am Acad Dermatol. 2009;61(4):549-60;561-2.
  3. Happle R. Nevus sebaceus is a mosaic RASopathy. J Invest Dermatol. 2013;133:597-600.
  4. Moody MN, Landau JM, Goldberg LH. Nevus sebaceous revisited. Pediatr Dermatol. 2012;29:15-23.
  5. Paller A, Mancini A, eds. Tumors of epidermal appendages. Hurwitz Clinical Pediatric Dermatology. 3rd ed. Philadelphia, Pa: Elsevier Saunders. 2006;221-2.
  6. Altaykan A, Ersoy-Evans S, et al. Basal cell carcinoma arising in nevus sebaceous during childhood. Pediatr Dermatol. 2008;25:616-619.
  7. Jaqueti G, Requena L, Sanchez Yus E. Trichoblastoma is the most common neoplasm developed in nevus sebaceus of Jadassohn: a clinicopathologic study of a series of 155 cases. Am J Dermatopathol. 2000;22(2):108-18.
  8. Kavak A, Ozcelik D, Belenli O, et al. A unique location of naevus sebaceus: labia minora. J Eur Acad Dermatol Venereol. 2008;22(9):1136-8.
  9. Warnke PH, Russo PA, Schimmelpenning GW, et al. Linear intraoral lesions in the sebaceous nevus syndrome. J Am Acad Dermatol. 2005;52(2 Suppl 1):62-4.
  10. Ivker R, Resnick SD, Skidmore RA. Hypophosphatemic vitamin D-resistant rickets, precocious puberty, and the epidermal nevus syndrome. Arch Dermatol. 1997;133(12):1557-61.
  11. Dhombres F, Kolanska K, Garel C, et al. Prenatal diagnosis of exophytic nevus sebaceous of the scalp. Prenat Diagn. 2013;33:1305-1307.
  12. Barkham MC, White N, Brundler MA, et al. Should naevus sebaceus be excised prophylactically? A clinical audit. J Plast Reconstr Aesthet Surg. 2007;60(11):1269-70.
  13. Idriss MH, Elston DM. Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases. J Am Acad Dermatol. 2014;70(2):332-7.

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  • Alopecia: Syndromes of genetic significance - SA Muller - Journal of Investigative Dermatology, 1973 - nature.com