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

• Published in: Lung Vol. 193; no. 5; pp. 619 - 627
• Main Authors: von Ranke, Felipe Mussi, Zanetti, Gláucia, e Silva, Jorge Luiz Pereira, Neto, Cesar Augusto Araujo, Godoy, Myrna C. B., Souza, Carolina A., Mançano, Alexandre Dias, Souza, Arthur Soares, Escuissato, Dante Luiz, Hochhegger, Bruno, Marchiori, Edson
• Format: Journal Article Book Review
• Language: English
• Published: New York Springer US 01-10-2015; Springer; Springer Nature B.V
• Subjects: Angiomyolipoma - etiology; Carcinoma, Renal Cell - etiology; Care and treatment; Cell differentiation; Cysts - etiology; Development and progression; Genotype & phenotype; Humans; Hyperplasia - epidemiology; Hyperplasia - pathology; Kidney Neoplasms - etiology; Lung - pathology; Lung diseases; Lung Neoplasms - etiology; Lung Neoplasms - pathology; Lymphangioleiomyomatosis - etiology; Lymphangioleiomyomatosis - pathology; Medicine; Medicine & Public Health; Nervous System Diseases - etiology; Neurofibromatosis; Patient outcomes; Pneumology/Respiratory System; Pulmonary arteries; Retinal diseases; Risk factors; Skin Diseases - etiology; Tuberous sclerosis; Tuberous Sclerosis - complications; Tumors; United States; Computed tomography; Imaging; Lung diseases; Tuberous sclerosis complex; Lymphangioleiomyomatosis
• ISSN: 0341-2040; 1432-1750
• DOI: 10.1007/s00408-015-9750-6

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.