"Less severe cases with a normal VEGF-D can be offered transbronchial biopsy, which has a diagnostic rate of < 50% 2,16. Transbronchial cryobiopsy offers higher diagnostic yield with intermediate morbidity between forceps biopsy and VATS, and VATS wedge resection has a higher diagnostic rate but greater morbidity and mortality 20."
"lung changes may pre-date typical serological abnormalities in Sjögren disease"
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"CLD may be detected through screening of known TSC cases, but in s-LAM the diagnosis is more likely to be delayed, and advanced cystic lung destruction may be mistaken for emphysema, which can lead to underdiagnosis."
"In s-LAM, the mutations are somatic and not heritable, whereas TSC germline mutations are transmissible to future generations in an autosomal dominant fashion. Even in TSC, sporadic mutations outnumber inherited disease 2:1, and these cases will have a negative family history. TSC affects about 1:6,000 live births. The true prevalence of s-LAM is lower, up to 8:1,000,000."
"In s-LAM, the mutations are somatic and not heritable, whereas TSC germline mutations are transmissible to future generations in an autosomal dominant fashion. Even in TSC, sporadic mutations outnumber inherited disease 2:1, and these cases will have a negative family history. TSC affects about 1:6,000 live births. The true prevalence of s-LAM is lower, up to 8:1,000,000."
"In s-LAM, the mutations are somatic and not heritable, whereas TSC germline mutations are transmissible to future generations in an autosomal dominant fashion. Even in TSC, sporadic mutations outnumber inherited disease 2:1, and these cases will have a negative family history. TSC affects about 1:6,000 live births. The true prevalence of s-LAM is lower, up to 8:1,000,000."
"In the absence of a TSC diagnosis, the guidelines recommend testing for vascular endothelial growth factor D (VEGF-D) before resorting to a lung biopsy, which must be stained appropriately, including for HMB-45 (other smooth muscle-predominant lesions in the lung do not react with this antibody). VEGF-D levels correlate with the severity of lymphatic involvement and higher levels predict more rapid disease progression and more robust responses to mTOR inhibitors. Serum VEGF-D >800 pg/mL is considered diagnostic."
"S-LAM affects women in their reproductive years and most commonly presents between the ages of 30 and 50. Oestrogen promotes LAM cell proliferation, survival, migration and invasiveness. Lung function worsens during pregnancy, exogenous oestrogen use and during the hormonal fluctuations of the menstrual cycle 14, while disease progression slows after menopause."
"TSC-LAM commonly presents during childhood with developmental delay, seizures, characteristic skin lesions or tumours. Cystic lung disease and renal angiomyolipoma (AML) are features of both conditions, and CLD can present in the following ways:"
"S-LAM arises due to biallelic somatic mutations in the TSC2 gene (rarely the TSC1 gene); loss of function of the TSC2 gene product, tuberin, leads to dysregulated mTOR signalling and abnormal proliferation of smooth muscle-like cells. Cystic disease, pneumothorax, and lymphatic abnormalities (chylous effusions and lymphangioleiomyomas predominate and renal angiomyolipomas have a lower incidence (30-40%) compared to TSC-LAM. The disease is almost exclusively seen in women in their reproductive years."
"S-LAM arises due to biallelic somatic mutations in the TSC2 gene (rarely the TSC1 gene); loss of function of the TSC2 gene product, tuberin, leads to dysregulated mTOR signalling and abnormal proliferation of smooth muscle-like cells. Cystic disease, pneumothorax, and lymphatic abnormalities (chylous effusions and lymphangioleiomyomas predominate and renal angiomyolipomas have a lower incidence (30-40%) compared to TSC-LAM. The disease is almost exclusively seen in women in their reproductive years."
"TSC-LAM occurs in individuals with tuberous sclerosis complex, a disorder caused by mutations in the TSC1 or TSC2 gene (which may be sporadic or, less commonly, germline), and is frequently accompanied by additional systemic manifestations of TSC. Renal angiomyolipomas occur in the majority. Cystic lung disease is milder in TSC-LAM women, and mild disease can occur in males (10-12%)."
"TSC-LAM occurs in individuals with tuberous sclerosis complex, a disorder caused by mutations in the TSC1 or TSC2 gene (which may be sporadic or, less commonly, germline), and is frequently accompanied by additional systemic manifestations of TSC. Renal angiomyolipomas occur in the majority. Cystic lung disease is milder in TSC-LAM women, and mild disease can occur in males (10-12%)."
"Lung disease, lymphatic disease and chylous leaks predominate in s-LAM, whereas widespread benign tumours and hamartomas are common in TSC. Epithelioid AML may have a relatively aggressive course and is normally rare, but occurs with greater frequency in s-LAM and TSC-LAM."
"LAM cells in women with s-LAM share features with uterine smooth muscle cells such as HMB-45 and Melan-A. It seems likely that these LAMCORE cells acquire somatic TSC2 mutations and subsequently disseminate to the lung via lymphatic or haematogenous routes 16. The origin in males is less clear, possibly from angiomyolipomas carrying bi-allelic mutations."
"TSC is characterised by benign tumours in almost any organ which are frequently detected in childhood or, in the case of cardiac rhabdomyomas, in utero. Children often have developmental delay, seizures and characteristic skin lesions. TSC2 on chromosome 16 codes for tuberin and is more commonly implicated and more severe than TSC1 on chromosome 9, which codes for hamartin. Pathological TSC gene mutations are detected in 75-90% of TSC cases 3."
"LAM is a low-grade destructive metastasising PEComatous tumour 1 resulting from the proliferation of LAM cells in the lung, kidney and axial lymphatics. The disease is caused by somatic mutations of the TSC2 or TSC1 genes with a ratio approximately 8:2. Cystic lung disease (CLD) is the most frequent manifestation."
"Smooth muscle-like LAM cells contain inactivating mutations of TSC2 or TSC1 tumour suppressor genes with consequent activation of the mechanistic target of rapamycin (mTOR) signalling pathway. This results in proliferation of LAM cells, which migrate through lymphatic vessels and infiltrate airways and blood vessels. Lymphatic and vascular obstruction and rupture may result, causing haemorrhage, chylous effusions, etc. The mechanism of cystic lung destruction is uncertain and could involve check-valve obstruction and/or metalloproteinases. LAM cells express oestrogen receptors and functional decline accelerates during pregnancy. Oestrogen is a driver of LAM cell proliferation and lymphatic dissemination."
Expected headings
"Chest"
"Plain radiograph"
"CT"
"Abdomen and pelvis"
"Skeletal"
"Complications"
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"Cystic lung disease (CLD) is associated with both sporadic lymphangioleiomyomatosis (s-LAM) and tuberous sclerosis complex (TSC-LAM). S-LAM is currently thought to be restricted to women 16; rare reports of s-LAM in males are widely considered to be linked with TSC or TSC mosaicism rather than true sporadic LAM. LAM cells uniformly express oestrogen and progesterone receptors, which explains the female susceptibility. Even in TSC, symptomatic CLD is rare in males 16."
"S-LAM arises due to biallelic somatic mutations in the TSC2 gene (rarely the TSC1 gene); loss of function of the TSC2 gene product, tuberin, leads to dysregulated mTOR signalling and abnormal proliferation of smooth muscle-like cells. Cystic disease, pneumothorax, and lymphatic abnormalities (chylous effusions and lymphangioleiomyomas predominate and renal angiomyolipomas have a lower incidence (30-40%) compared to TSC-LAM. The disease is almost exclusively seen in women in their reproductive years."
"VATS pleurodesis for recurrent pneumothorax; the method affects perioperative haemorrhage at transplantation"
"osteoporosis may result from immobility, mTOR inhibitor use, and oestrogen-related factors; thus, bone density monitoring is advisable"
"TSC is characterised by benign tumours in almost any organ which are frequently detected in childhood or, in the case of cardiac rhabdomyomas, in utero. Children often have developmental delay, seizures and characteristic skin lesions. TSC2 on chromosome 16 codes for tuberin and is more commonly implicated and more severe than TSC1 on chromosome 9, which codes for hamartin. Pathological TSC gene mutations are detected in 75-90% of TSC cases 3."
"S-LAM affects women in their reproductive years and most commonly presents between the ages of 30 and 50. Oestrogen promotes LAM cell proliferation, survival, migration and invasiveness. Lung function worsens during pregnancy, exogenous oestrogen use and during the hormonal fluctuations of the menstrual cycle 14, while disease progression slows after menopause."
"LAM is a low-grade destructive metastasising PEComatous tumour 1 resulting from the proliferation of LAM cells in the lung, kidney and axial lymphatics. The disease is caused by somatic mutations of the TSC2 or TSC1 genes with a ratio approximately 8:2. Cystic lung disease (CLD) is the most frequent manifestation."
"hepatic, adrenal or retroperitoneal AMLs"
"lymphangioleiomyomas: soft cystic/solid masses which can insinuate between normal structures without compressing them. These may be hormone-responsive, waxing and waning through the menstrual cycle 14"
"upper zone predominant and bronchocentric cavitating nodules, branching or irregular cysts"
"sirolimus or everolimus toxicity, including organising pneumonia, cryptogenic organising pneumonia, interstitial pneumonitis, focal fibrosis or alveolar haemorrhage, Pneumocystis jirovecii pneumonia, cardiac failure"