<unk>  occurs in two settings: in the disease tuberous sclerosis complex (TSC-LAM) and in a sporadic form, in women who do not have TSC (sporadic<unk> . In both settings, genetic evidence indicates that<unk>  is caused by inactivating or “loss of function” mutations in the TSC1 or TSC2 genes, which were cloned in 1997 and 1993 respectively. The TSC1 gene is located on the long arm of chromosome 9 (9q34) and the TSC2 gene is located on the short arm of chromosome 16 (16p13). TSC-LAM occurs in women who have germline mutations in either the TSC1 or the TSC2 gene. Sporadic<unk>  is primarily associated with somatic TSC2 gene mutations. Germline and somatic mutations in<unk>  include many types of mutations spread across the genes, with no clear “hot spots,” including missense changes, in-frame deletions and nonsense mutations. Because of the large size of the genes (together they have more than 60 exons) and because mutations can be located virtually anywhere within the genes, mutation detection is often challenging. On a cellular basis,<unk>  cells carry bi-allelic inactivation of the TSC2 genes, consistent with the “two-hit” tumor suppressor gene model. The second hit event in<unk>  cells is often loss of the chromosomal region containing the wild-type copy of the TSC2 gene; this is referred to as loss of heterozygosity or LOH. LOH can be detected in microdissected<unk>  cells, in angiomyolipomas and lymph nodes from women with<unk> , and in circulating<unk>  cells (cells in blood and urine). Angiomyolipomas and pulmonary<unk>  cells from women with the sporadic form of<unk>  carry identical mutations in TSC2. This, together with the fact that recurrent<unk>  after lung transplantation carries the same TSC2 mutations as the original<unk> , has led to the "benign metastasis" hypothesis that<unk>  cells can migrate or metastasize from one site to another.
Lymphangioleiomyomatosis
Intravenous leiomyomatosis
Lymphangiomatosis
Angiodysplasia
Adenomyomatosis
Papillomatosis
Bagassosis
Fibromuscular dysplasia