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Tuberous Sclerosis Complex: State-of-the-Art Review with a Focus on Pulmonary Involvement

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Abstract

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disease with high phenotypic variability. The incidence is approximately one in 5000–10,000 births. TSC is characterized by widespread hamartomas and benign or rarely malignant neoplasms affecting various organs, most commonly the brain, skin, retinas, kidneys, heart, and lungs. The wide range of organs affected reflects the roles of TSC1 and TSC2 genes in the regulation of cell proliferation and differentiation. Clinical diagnostic criteria are important because genetic testing does not identify the mutation in up to 25 % of patients. Imaging is pivotal, as it allows a presumptive diagnosis of TSC and definition of the extent of the disease. Common manifestations of TSC include cortical tubers, subependymal nodules, white matter abnormalities, retinal abnormalities, cardiac rhabdomyoma, lymphangioleiomyomatosis (LAM), renal angiomyolipoma, and skin lesions. Pulmonary involvement consists of LAM and, less commonly, multifocal micronodular pneumocyte hyperplasia (MMPH), which causes cystic and nodular diseases, respectively. Recent reports indicate that pulmonary LAM is found by computed tomography in up to 35 % of the female patients with TSC. MMPH is rare and may be associated with LAM or, less frequently, occurs as an isolated pulmonary manifestation in women with TSC. Dyspnea and pneumothorax are common clinical presentations of LAM, whereas MMPH is usually asymptomatic. The aim of this review is to describe the main clinical, imaging, and pathological aspects of TSC, with a focus on pulmonary involvement.

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Authors and Affiliations

  1. Federal University of Rio de Janeiro, Rua Thomaz Cameron, 438. Valparaiso, Petrópolis, Rio de Janeiro, CEP 25685.120, Brazil

    Felipe Mussi von Ranke, Gláucia Zanetti & Edson Marchiori

  2. Federal University of Bahia, Salvador, Brazil

    Jorge Luiz Pereira e Silva & Cesar Augusto Araujo Neto

  3. M. D. Anderson Cancer Center, University of Texas, Houston, TX, USA

    Myrna C. B. Godoy

  4. Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada

    Carolina A. Souza

  5. Radiologia Anchieta, Anchieta Hospital, Taguatinga, DF, Brazil

    Alexandre Dias Mançano

  6. Medical School of Rio Preto and Ultra X, São José do Rio Preto, SP, Brazil

    Arthur Soares Souza Jr.

  7. Federal University of Parana, Curitiba, Brazil

    Dante Luiz Escuissato

  8. Santa Casa de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

    Bruno Hochhegger

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  1. Felipe Mussi von Ranke
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von Ranke, F.M., Zanetti, G., e Silva, J.L.P. et al. Tuberous Sclerosis Complex: State-of-the-Art Review with a Focus on Pulmonary Involvement. Lung 193, 619–627 (2015). https://doi.org/10.1007/s00408-015-9750-6

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