Recurrent pneumothoraces with diffuse small ground-glass and solid nodules.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is the lesser known pulmonary manifestation of tuberous sclerosis. It manifests radiologically as diffuse small ground-glass and solid nodules. Accurate diagnosis is essential as it can be mistaken for miliary tuberculosis or malignant lesions which necessitates specific treatment.

Reduced risk of recurrent pneumothorax for sirolimus therapy after surgical pleural covering of entire lung in lymphangioleiomyomatosis.

Background: Patients with lymphangioleiomyomatosis (LAM) frequently experience pneumothorax. Although sirolimus is the standard therapy for LAM, its effect on pneumothorax is controversial. Recently, total pleural covering (TPC) and modified TPC (mTPC) were introduced as surgical treatment options for pneumothorax for patients with LAM.

Acute and repeated haemoperitoneum: a challenging case of lymphangioleiomyomatosis with uterine PEComa.

A 39-year-old woman presented in the emergency ward for abdominal pain and acute anemiation. Abdominal-thoracic CT scan showed haemoperitoneum, with a parauterine mass and a pathological pulmonary pattern suspicious for lymphangioleiomyomatosis (LAM), a systemic disease belonging to perivascular epithelioid cell tumours (PEComas). Gynaecological ultrasound showed a hypoechoic irregular solid mass of the uterine right wall.

The utility of gallium-68 DOTATOC PET/CT in lymphangioleiomyomatosis.

https://bit.ly/3l6BVZp.

The lung microbiome in end-stage Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease with mortality driven primarily by respiratory failure. Patients with LAM frequently have respiratory infections, suggestive of a dysregulated microbiome. Here we demonstrate that end-stage LAM patients have a distinct microbiome signature compared to patients with end-stage chronic obstructive pulmonary disease.

Assessment of Lung Structure and Regional Function Using 0.55 T MRI in Patients With Lymphangioleiomyomatosis.

Objectives: Contemporary lower-field magnetic resonance imaging (MRI) may offer advantages for lung imaging by virtue of the improved field homogeneity. The aim of this study was to evaluate the utility of lower-field MRI for combined morphologic imaging and regional lung function assessment. We evaluate low-field MRI in patients with lymphangioleiomyomatosis (LAM), a rare lung disease associated with parenchymal cysts and respiratory failure.

Protease activity sensors enable real-time treatment response monitoring in lymphangioleiomyomatosis.

Background: Biomarkers of disease progression and treatment response are urgently needed for patients with lymphangioleiomyomatosis (LAM). Activity-based nanosensors, an emerging biosensor class, detect dysregulated proteases and release a reporter to provide a urinary readout of disease. Because proteases are dysregulated in LAM and may directly contribute to lung function decline, activity-based nanosensors may enable quantitative, real-time monitoring of LAM progression and treatment response.

Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells.

Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either or Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking up-regulation of Interleukin-6 (IL-6). LAM patient plasma contained increased circulating IL-6 compared with healthy controls, and TSC2-deficient cells showed up-regulation of IL-6 transcription and secretion compared to wild-type cells. IL-6 blockade repressed the proliferation and migration of TSC2-deficient cells and reduced oxygen consumption and extracellular acidification.

Tuberous sclerosis complex-lymphangioleiomyomatosis involving several visceral organs: A case report.

Background: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease characterized by the proliferation, metastasis, and infiltration of smooth muscle cells in the lung and other tissues, which can be associated with tuberous sclerosis complex (TSC). The disorder of TSC has a variable expression, and there is great phenotypic variability.

Case Summary: A 32-year-old Chinese woman with a history of multiple renal angioleiomyolipoma presented with a productive cough persisting for over 2 wk.

Tuberous Sclerosis: Current Update.

Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant neurocutaneous disorder secondary to mutations in the or tumor suppressor genes. Although manifestation of the classic triad of seizures, intellectual disability, and facial angiofibromas may facilitate timely diagnosis of TSC, the multisystem features that may indicate TSC in the absence of these manifestations remain highly variable. In addition, patients with TSC are at risk of developing multiple benign and malignant tumors in various organ systems, resulting in increased morbidity and mortality.

COVID-19 in a patient with sporadic lymphangioleiomyomatosis awaiting lung transplantation.

Coronavirus disease 2019 (COVID-19) is an emerging viral disease with a mortality that depends on the individual's condition. Underlying comorbidities are major risk factors for COVID-19-related morbidity and mortality. However, information regarding the clinical course of COVID-19 in patients with rare respiratory system diseases is lacking.

A second hit somatic (p.R905W) and a novel germline intron-mutation of TSC2 gene is found in intestinal lymphangioleiomyomatosis: a case report with literature review.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs associated with germline mutations in TSC1 and TSC2, including exonic, intronic, or mosaic mutations. Gastrointestinal (GI) tract Lymphangioleiomyomatosis (LAM) is an extremely rare manifestation of TSC, with few reported cases. Herein, we aimed to determine the driver mutation, pathogenesis, and relationship of germline and somatic mutations of LAM through whole-genome sequencing (WGS) of the tumor and blood samples and whole transcriptome sequencing (WTS) analysis.

Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management.

Lymphangioleiomyomatosis (LAM) is a slowly progressive, low-grade, metastasising neoplasm of women, characterised by infiltration of the lung parenchyma with abnormal smooth muscle-like cells, resulting in cystic lung destruction. The invading cell in LAM arises from an unknown source and harbours mutations in tuberous sclerosis complex (TSC) genes that result in constitutive activation of the mechanistic target of rapamycin (mTOR) pathway, dysregulated cellular proliferation, and a programme of frustrated lymphangiogenesis, culminating in disordered lung remodelling and respiratory failure. Over the past two decades, all facets of LAM basic and clinical science have seen important advances, including improved understanding of molecular mechanisms, novel diagnostic and prognostic biomarkers, effective treatment strategies, and comprehensive clinical practice guidelines.

Sirolimus Suppresses Phosphorylation of Cofilin and Reduces Interstitial Septal Thickness in Sporadic Lymphangioleiomyomatosis.

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare lung disease characterized by the proliferation of smooth muscle-like LAM cells and progressive cystic destruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. However, the therapeutic mechanisms of sirolimus in LAM remain unclear.

Efficacy of Sirolimus Treatment in PEComa-10 Years of Practice Perspective.

Perivascular epithelioid cell tumors (PEComa) represent a family of rare mesenchymal tumors resultant from deregulation in mTOR pathway activity. The aim of this study is to evaluate the long-term efficacy of targeted PEComa treatment. We reviewed all consecutive patients with PEComa who started systemic treatment with sirolimus in our reference sarcoma center between January 2011 and August 2020.

Cathepsin K is Superior to HMB45 for the Diagnosis of Pulmonary Lymphangioleiomyomatosis.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare cystic lung disease affecting predominantly young women. Classified as a low-grade malignant soft tissue neoplasm from the family of perivascular epithelioid cell (PEC) tumors or PEComas, it is characterized by a proliferation of abnormal smooth muscle-like cells (LAM cells), coexpressing myogenic and melanocytic markers, with HMB45 as the gold-standard immunohistochemical diagnostic marker. Cathepsin K, a papain-like cysteine protease with high matrix degrading activity, is commonly used in the pathologic diagnosis of other PEComa tumors, but there are few data regarding its expression in pulmonary LAM.

Quantitative Assessment of Macropinocytosis in mTORC1-Hyperactive Cells using Flow Cytometry.

Macropinocytosis is a highly conserved, actin-dependent endocytic process that allows the uptake of extracellular material, including proteins and lipids. In proliferating cells, macropinocytosis can deliver extracellular nutrients to the lysosome, processed into critical macromolecule building blocks. Recent studies have highlighted the dependence of multiple cancers on macropinocytosis, including breast, colorectal and pancreatic cancer.

Desaturation-Distance Ratio During Submaximal and Maximal Exercise Tests and Its Association With Lung Function Parameters in Patients With Lymphangioleiomyomatosis.

The desaturation-distance ratio (DDR), the ratio of the desaturation area to the distance walked, is a promising, reliable, and simple physiologic tool for functional evaluation in subjects with interstitial lung diseases. Lymphangioleiomyomatosis (LAM) is a rare neoplastic condition frequently associated with exercise impairment. However, DDR has rarely been evaluated in patients with LAM.

Hyperpolarized Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases.

Rationale: There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding.

Multidisciplinary team approach to diagnosing lymphangioleiomyomatosis.

A 42-year-old woman with chronic obstructive pulmonary disease was referred to the respiratory team due to shortness of breath on exertion and significant deterioration in pulmonary function tests. Her symptoms were progressively getting worse. This prompted a referral to the specialist team where further investigations were undertaken including a high-resolution CT scan followed by lung biopsy, which eventually revealed a diagnosis of lymphangioleiomyomatosis (LAM).

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.

Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests.

Tuberous sclerosis complex for the pulmonologist.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder affecting almost all organs with no sex predominance. TSC has an autosomal-dominant inheritance and is caused by a heterozygous mutation in either the or gene leading to hyperactivation of the mammalian target of rapamycin (mTOR). TSC is associated with several pulmonary manifestations including lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and chylous effusions.

A 34-Year-Old Woman from Brazil with Pulmonary Lymphangioleiomyomatosis Diagnosed by Raised Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels and Lung Cysts on Computed Tomography Imaging Presenting with COVID-19 Pneumonia.

BACKGROUND There is growing concern about the clinical course of certain diseases in patients who are simultaneously infected by SARS-CoV-2. This report is of a 34-year-old woman from Brazil with a recent diagnosis of pulmonary lymphangioleiomyomatosis (LAM) diagnosed by raised serum VEGF-D levels and the finding of lung cysts on computed tomography (CT) imaging, who presented with COVID-19 pneumonia. CASE REPORT Five months after the diagnosis of pulmonary LAM, which was based on the presence of diffuse and bilateral cystic lesions on CT scan associated with high serum VEGF-D levels, the patient presented with worsening dyspnea, drop in peripheral oxygen oxygenation, fever, and diffuse myalgia.

Pleurography (thoracography) for pleural fistulas: A case series.

Background: Pleurography (PG) has been described previously but has not gained popularity. PG can determine the exact air leak points in the lung, which is important for treating pneumothorax and pleural fistulas. We believe that the usefulness of PG should be reassessed, and here we describe the method, air leak detection rate, and common complications.