Abstract
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disease characterized by cutaneous and extracutaneous hamartomas. The diagnosis is based on the association of major and minor criteria, defined by a consensus conference updated in 2012. The clinical examination of the skin is crucial because seven diagnostic criteria are dermatological: four major (hypomelanotic macules, angiofibroma or fibrous cephalic plaques, ungual fibromas, shagreen patches) and three minor criteria (confetti skin lesions, dental enamel pits, intraoral fibromas). Skin biopsy is commonly performed to assert the diagnosis of TSC when the clinical aspect is atypical. Histopathology of TSC cutaneous lesions have been poorly reported until now. In this article, we review the histologic features described in the literature and share our experience of TSC skin biopsies in our pediatric hospital specialized in genetic disorders. Both hypomelanotic lesions and cutaneous hamartomas (angiofibroma/fibrous cephalic plaques, ungual fibromas, shagreen patches) are discussed, including the recent entity called folliculocystic and collagen hamartoma, with a special emphasis on helpful clues for TSC in such lesions.
Highlights
Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by cutaneous and extracutaneous hamartomas
The TSC1/TSC2 mutations lead to increased protein synthesis and cell growth [3]
Mutations are not identified by conventional genetic testing in 10 to 25% of TSC patients, possibly be due to mosaicism: TSC1/TSC2 mutation would be present in only some organs and only some cells within those organs, a “second-hit” mutation inactivates the remaining wild-type copy of
Summary
Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by cutaneous and extracutaneous hamartomas (kidney, eyes, heart, brain, lungs). Skin manifestations are present in almost 100% of the patients affected by TSC [2]. TSC results from an inactivating mutation in TSC1 or TSC2, two genes encoding tumor suppressor proteins: hamartin and tuberin, respectively. These proteins belong to the m-TOR pathway. The dermatologist has a central role in the diagnosis of TSC because cutaneous manifestations account for 4 (hypomelanotic macules, angiofibromas or fibrous cephalic plaques, ungual fibromas, shagreen patches) of 11 major and 3 (confetti skin lesions, dental enamel pits, intraoral fibromas) of 6 minor diagnostic criteria.
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