Spontaneous Hydropneumothorax After Pleurodesis in a Patient With Pulmonary Lymphangioleiomyomatosis With Associated Endometrial Cancer.

Lymphangioleiomyomatosis (LAM) is a rare cystic disease that occurs due to the abnormal proliferation of smooth muscle-like cells. It primarily affects the lungs but can also have extrapulmonary manifestations such as lymphangioleiomyoma and angiomyolipomas. It is more common in young women of childbearing age, with female sex hormones contributing to the disease course. LAM can develop either through sporadic mutations or through genetic inheritance of the tuberous sclerosis complex (TSC) genes. TSC, LAM, and endometrial cancer are associated with mTOR pathway activation, which can explain why these diseases can co-exist, although the co-existence of LAM and endometrial cancer in the same patient is very rare. Due to the cystic nature of LAM, pneumothorax most often occurs at least once during the course of the disease, and most times, it is the first manifestation observed in LAM. These patients are also at high risk for recurrent pneumothorax, and when that occurs, pleurodesis is indicated. Unfortunately, pleurodesis still does not preclude a pneumothorax from occurring. We present the case of a female patient with LAM and endometrial cancer who was found to have an incidental spontaneous hydropneumothorax after pleurodesis. Patients with LAM should be closely monitored for the possible development of other mTOR-associated diseases. Moreover, when performing pleurodesis for recurrent pneumothorax in very high-risk patients, the procedure with the lowest recurrence rate should be utilized.

Diagnostic value of serum vascular endothelial growth factor-D in Korean patients with lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder characterized by the proliferation of abnormal smooth muscle-like cells. Although serum vascular endothelial growth factor-D (VEGF-D) is currently used as a diagnostic biomarker for LAM, its diagnostic value in Korean patients is unclear. OBJECTIVES: To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients. DESIGN: A multicenter prospective cohort study. METHODS: Serum samples were prospectively collected from five medical institutions, from patients with LAM (n = 40) and controls (n = 24; healthy participants = 3, other cystic lung diseases = 13, idiopathic pulmonary fibrosis = 4, idiopathic nonspecific interstitial pneumonia = 4). Serum VEGF-D levels were measured using the enzyme-linked immunosorbent assay, and the diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The mean age of patients with LAM was 44.5 years, and all were female (controls: 47.8 years; female: 70.8%, p < 0.001). The serum VEGF-D levels were significantly higher in patients with LAM than those in the control group (median: 708.9 pg/mL vs 325.3 pg/mL, p < 0.001). In the ROC curve analysis, serum VEGF-D levels showed good predicting performance for LAM diagnosis (area under the curve = 0.918) with an optimal cut-off value of 432.7 pg/mL (sensitivity = 85.0%, specificity = 87.5%). When 800 pg/mL was used as the cut-off value, the specificity of serum VEGF-D for LAM diagnosis increased to 100.0%. CONCLUSION: Our results suggest that serum VEGF-D may be a useful biomarker for diagnosing LAM in Korean patients, similar to previous reports.

Blood test for diagnosis of lymphangioleiomyomatosis in Korea: role of vascular endothelial growth factor-DIn this study, we discuss a blood test to diagnose a rare lung disease, called lymphangioleiomyomatosis (LAM). LAM primarily affects women, especially during their childbearing years, and can cause serious lung problems such as damage and cyst (air-filled sac) formation. The blood test looks for a special protein in the blood, called vascular endothelial growth factor-D (VEGF-D). If someone has a lot of this protein, it usually means that they have LAM. We have found that when VEGF-D levels are high, the test can effectively separate LAM from other lung diseases. We also found that raising this threshold to higher levels made it much more likely to correctly distinguish a group of people who do not have the disease from patients with LAM. Our study is important because it's the first to show the usefulness of blood VEGF-D testing in Korean LAM patients, and because it suggests an easier and less inconvenient way for physicians to diagnose LAM in Koreans. Our findings are an important step in improving the management of Korean patients with LAM.

Safety and efficacy of COVID-19 vaccination in the Chinese population with pulmonary lymphangioleiomyomatosis: a single-center retrospective study.

BACKGROUND: The safety and efficacy of vaccination against coronavirus disease 2019 (COVID-19) in patients with lymphangioleiomyomatosis (LAM) is still unclear. This study investigates COVID-19 vaccine hesitancy, vaccine safety and efficacy, and COVID-19 symptoms in LAM patients. RESULTS: In total, 181 LAM patients and 143 healthy individuals responded to the questionnaire. The vaccination rate of LAM patients was 77.34%, and 15.7% of vaccinated LAM patients experienced adverse events. Vaccination decreased the risk of LAM patients developing anorexia [OR: 0.17, 95% CI: (0.07, 0.43)], myalgia [OR: 0.34, 95% CI: (0.13, 0.84)], and ageusia [OR: 0.34, 95% CI: (0.14, 0.84)]. In LAM patients, a use of mTOR inhibitors reduced the risk of developing symptoms during COVID-19, including fatigue [OR: 0.18, 95% CI: (0.03, 0.95)], anorexia [OR: 0.30, 95% CI: (0.09, 0.96)], and ageusia [OR: 0.20, 95% CI: (0.06, 0.67)]. CONCLUSIONS: Vaccination rates in the LAM population were lower than those in the general population, as 22.7% (41/181) of LAM patients had hesitations regarding the COVID-19 vaccine. However, the safety of COVID-19 vaccination in the LAM cohort was comparable to the healthy population, and COVID-19 vaccination decreased the incidence of COVID-19 symptoms in LAM patients. In addition, mTOR inhibitors seem not to determine a greater risk of complications in patients with LAM during COVID-19.

Unsupervised Exercise in Interstitial Lung Disease: A Delphi Study to Develop a Consensus Preparticipation Screening Tool for Lymphangioleiomyomatosis.

BACKGROUND: Little research is available to provide practical guidance to health-care providers for exercise preparticipation screening and referral of patients with interstitial lung diseases (ILDs), including lymphangioleiomyomatosis (LAM), to participate in remote, unsupervised exercise programs. RESEARCH QUESTION: What exercise preparticipation screening steps are essential to determine whether a patient with LAM is medically appropriate to participate in a remote, unsupervised exercise program? STUDY DESIGN AND METHODS: Sixteen experts in LAM and ILD participated in a two-round modified Delphi study, ranking their level of agreement for 10 statements related to unsupervised exercise training in LAM, with an apriori definition of consensus. Additionally, 60 patients with LAM completed a survey of the perceived risks and benefits of remote exercise training in LAM. RESULTS: Seven of the 10 statements reached consensus among experts. Experts agreed that an in-person clinical exercise test is indicated to screen for exercise-induced hypoxemia and prescribe supplemental oxygen therapy as indicated prior to initiating a remote exercise program. Patients with recent pneumothorax should wait to start an exercise program for at least 4 weeks until after resolution of pneumothorax and clearance by a physician. Patients with high cardiovascular risk for event during exercise, severe resting pulmonary hypertension, or risk for falls may be more appropriate for referral to a rehabilitation center. A LAM-specific remote exercise preparticipation screening tool was developed from the consensus statements and agreed upon by the panelists. INTERPRETATION: A modified Delphi study approach was useful to develop disease-specific recommendations for safety and preparticipation screening prior to unsupervised, remotely administered exercise in LAM. The primary product of this study is a clinical decision aid for providers to use when medically screening patients prior to participation in the newly launched LAMFit remote exercise program.

A 20-year-old woman with chronic cough and dyspnea.

Lymphangioleiomyomatosis is a rare progressive disease characterized by abnormal smooth muscle cell proliferation leading to a diffuse cystic lung disease and extrapulmonary manifestations. Most cases are caused by mutations in the TSC1 and/or TSC2 genes, which are also associated with tuberous sclerosis complex. We describe a case of sporadic lymphangioleiomyomatosis with autosomal dominant polycystic kidney disease and renal angiolipomas in a patient who tested negative for gene mutations on the TSC1 and TSC2 gene panel.

Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study.

BACKGROUND: Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist. METHODS: We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors. RESULTS: Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose. CONCLUSIONS: Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible.

A Study on the Psychological Profile and Coping With the Disease in Patients With Lymphangioleiomyomatosis.

Introduction: Lymphangioleiomyomatosis (LAM) is a rare disease that affects women almost exclusively. We aimed to determine the psychological profile in patients with LAM, and their potential association with sociodemographic and clinical features, and to know their role in coping with the disease. Material and methods: Cross-sectional and descriptive study in collaboration with the Spanish Association of LAM (AELAM). The variables measured were: socio-demographic, psychological (anxiety, depression, demoralization, spirituality, resilience, social support), clinical (treatment) and health-related quality of life. Results: We studied 87 LAM patients, with a mean (SD) age of 47.7 (7.7) years, and time since diagnose was 10.1 (5.4) years. 75.9% of patients were receiving sirolimus or everolimus, and oxygen therapy was required in 34.5% of patients. Anxiety was found in 46% of patients, depression in 55%, while only 2% presented demoralization and 14% deficit in spirituality. Social support and resilience were adequate. The "non-severe" group (without oxygen therapy) presented worse results in anxiety. A structural equation model to explore association between variables, showed very adequate fit indices: χ2(14) = 29.743 (p = .074); CFI = .983; TLI = .967; SRMR = .058; RMSEA = .075[.000-.128]. The model identifies resilience, spirituality and social support as "protective factors" from anxiety, depression, and demoralization. Conclusions: This study performed on a large series of women with LAM describes their psychological profile, in addition to showing how they cope with the disease. We have found that other psychological constructs, such as perceived social support and resilience, are protective factors. Early psychological evaluation and intervention is necessary to reduce comorbidities and prevent mental health problems in women with LAM.

Introducción: La linfangioleiomiomatosis (LAM) es una enfermedad rara que afecta casi exclusivamente a las mujeres. Nuestro objetivo fue determinar el perfil psicológico en los pacientes con LAM, y su potencial asociación con características sociodemográficas y clínicas, y conocer su papel en el afrontamiento de la enfermedad. Material y métodos: Estudio transversal y descriptivo en colaboración con la Asociación Española de LAM (AELAM). Las variables medidas fueron: sociodemográficas, psicológicas (ansiedad, depresión, desmoralización, espiritualidad, resiliencia, apoyo social), clínicas (tratamiento) y calidad de vida relacionada con la salud. Resultados: Se estudiaron 87 pacientes con LAM, con una edad media (DE) de 47,7 ± 7,7 años y un tiempo desde el diagnóstico de 10,1 ± 5,4 años. El 75,9% de los pacientes estaban recibiendo sirolimus o everolimus, y el 34,5% de los pacientes requirió oxigenoterapia. La ansiedad se encontró en el 46% de los pacientes, la depresión en el 55%, mientras que solo el 2% presentó desmoralización y el 14% déficit en la espiritualidad. El apoyo social y la resiliencia fueron adecuados. El grupo «no grave¼ (sin oxigenoterapia) presentó peores resultados en ansiedad. Un modelo de ecuaciones estructurales para explorar asociación entre variables, mostró índices de ajuste muy adecuados: χ2(14) = 29,743 (p = 0,074); CFI = 0,983; TLI = 0,967; SRMR = 0,058; RMSEA = 0,075 (0,000-0,128). El modelo identifica la resiliencia, la espiritualidad y el apoyo social como «factores protectores¼ contra la ansiedad, la depresión y la desmoralización. Conclusiones: Este estudio realizado en una amplia serie de mujeres con LAM describe su perfil psicológico, además de mostrar cómo afrontan la enfermedad. Hemos descubierto que otros constructos psicológicos, como el apoyo social percibido y la resiliencia, son factores protectores. La evaluación e intervención psicológica temprana es necesaria para reducir las comorbilidades y prevenir problemas de salud mental en mujeres con LAM.

Lymphangioleiomyomatosis and pregnancy: a mini-review.

Lymphangioleiomyomatosis(LAM) is a slow progressive, rare cystic lung disease in women of reproductive age, associated with infiltration of the lung by atypical smooth muscle like cells, leading to the cystic destruction of the lung parenchyma. As LAM exclusively affects women of childbearing age, it can arise or exacerbate during pregnancy. Many patients with LAM are discouraged from pregnancy, although there is not much objective evidence effect on fertility. Patients diagnosed with LAM during pregnancy experience worse outcomes, so the safety of pregnancy is a vexing problem. What was worse, treatment strategies are limited on the effects of LAM on pregnancy outcomes. Pregnancy could be considered in LAM patients. Successful delivery in women with LAM depends on the condition of the LAM, which is in turn dependent on obstetricians and respiratory physicians. In this review, we describe the epidemiology, pathogenesis, diagnosis, clinical features and the treatment strategies of LAM during pregnancy.

Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB's unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here, we establish that GPNMB expression is dependent on mTORC1 signaling, and that GPNMB regulates TSC2-null tumor cell invasion in vitro. Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth in vivo, and that ectodomain release is required for this xenograft growth. We also show that GPNMB's ectodomain is released from the cell surface of TSC2-null cells by proteases ADAM10 and 17, and we identify the protease target sequence on GPNMB. Finally, we demonstrate that GPNMB's ectodomain is present at higher levels in LAM patient serum compared to healthy controls and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker.

Epidemiology of patients with lymphangioleiomyomatosis: A descriptive study using the national database of health insurance claims and specific health checkups of Japan.

BACKGROUND: Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality. METHODS: We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients. RESULTS: In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%. CONCLUSIONS: The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%.

Lymphangioleiomyomatosis as a potent lung cancer risk factor: Insights from a Japanese large cohort study.

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available. RESULTS: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS. CONCLUSION: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.

A 24-year-Old woman with recurrent pneumothoraces.

Lymphangioleiomyomatosis (LAM) is an abnormal proliferation of smooth muscle-like cells and may occur sporadically or in association with tuberous sclerosis complex. Patients are typically female, nonsmoking and may have cystic lung disease with pneumothorax. Diagnosis can be made by compatible imaging findings with a history of tuberous sclerosis complex, or in conjunction with vascular endothelial growth factor-D 800 pg/ml or greater, a highly specific finding. Sirolimus is first line treatment for LAM.

Intraoperative mechanical ventilation and incidence of pneumothorax in lymphangioleiomyomatosis.

Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.

Lymphangioleiomyomatosis in patients with tuberous sclerosis: a national centre audit.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is common in tuberous sclerosis complex (TSC) yet under recognised with management mostly based upon evidence obtained from patients with sporadic LAM. We performed a prospective audit of patients with TSC-LAM attending a national referral centre to inform management guidelines. METHODS: The UK LAM Centre was established in 2011 and conducts a prospective audit of pre-defined quality outcomes for all subjects. Audit data are reported on all patients with TSC-LAM and a comparator population of patients with sporadic LAM. RESULTS: Between 2011 and 2022, 73 patients were seen with TSC-LAM. All were women with a mean (SD) age of 39 (12) years. Referral rates were similar over the study period including after the introduction of CT screening. Median age of diagnosis with TSC was 11 years (range 0-70) with one third diagnosed with TSC as adults. Compared with all TSC patients in the 'TOSCA' registry, TSC-LAM patients tended to have been diagnosed with TSC at an older age, had fewer neuro-cognitive manifestations and were more likely to have angiomyolipoma. The most common presentations of TSC-LAM were following workup for angiomyolipoma, pneumothorax or dyspnoea with only one fifth detected after CT screening. Baseline FEV1 and DLCO at first assessment were reduced to 77 and 63% predicted respectively and were similar to patients with sporadic LAM. During follow-up, FEV1 fell by a mean of 81 ml/year and DLCO fell by 0.309 mmol/ml/kPa/year in patients not being treated with an mTOR inhibitor. 55% required treatment with either sirolimus or Everolimus for LAM or angiomyolipoma respectively. For those treated with an mTOR inhibitor, mean FEV1 fell by 3 ml/year and DLCO increased by 0.032 mmol/ml/kPa/year and was similar to sporadic LAM. Risk of death due to LAM or need for lung transplant in patients with TSC-LAM was 0.67%/year. CONCLUSIONS: Despite screening recommendations, LAM is often diagnosed in TSC after symptoms develop which may delay treatment. Complications including pneumothorax and loss of lung function are significant and similar to sporadic LAM. Work is needed to implement the recommended CT screening for LAM and improve respiratory care for TSC-LAM.

An elderly woman with Birt-Hogg-Dubé syndrome having multiple pulmonary cysts mimicking lymphangioleiomyomatosis.

The characteristics of the pulmonary cysts on the high-resolution computed tomography (HRCT) chest images are an important diagnostic clue to distinguish among cystic lung diseases. The diagnostic accuracy of HRCT was reported to be as high as 90% by experienced pulmonologists and radiologists. Herein, we report the case of an elderly woman with Birt-Hogg-Dubé syndrome (BHDS) whose HRCT images displayed lymphangioleiomyomatosis-like features of the pulmonary cysts, rendering it difficult for us to diagnose BHDS. This case illustrates the significance of a thorough anamnesis, physical examination, and skin biopsy of facial papules to establish an accurate diganosis.

Case report: If it is not asthma-think of lymphangioleiomyomatosis in younger female patients.

Lymphangioleiomyomatosis (LAM) is a rare lung disease predominantly affecting women, and it is characterized by the proliferation of smooth muscle cells and cystic lung destruction. LAM diagnosis is challenging due to varied clinical presentations and resemblance to common conditions such as asthma. We present two female cases where LAM was initially misdiagnosed. Case 1 describes a woman treated for asthma-chronic obstruction pulmonary disease overlap syndrome, while also undergoing treatment with vascular endothelial growth factor (VEGF) inhibitor pazopanib for a retroperitoneal leiomyoma, the latter responding well to treatment. Due to progressive dyspnea, pazopanib-induced pneumonitis was suspected. High-resolution computed tomography (HRCT) showed changes compatible with LAM. A revision of biopsies showed that the leiomyoma was in fact a lymphangioleiomyoma, and VEGF-D was increased. Both supported the LAM diagnosis. Treatment with mTORC1 inhibitor sirolimus was initiated. Case 2 describes a woman, who in resemblance with the woman from case 2 was also suspected of asthma and did not respond clinically to treatment. After several years, HRCT was performed and suspicion of LAM was raised. Transbronchial biopsy and later, an increased VEGF-D supported the LAM diagnosis. As in case 1, treatment with sirolimus was initiated. These cases underscore the importance of reevaluating diagnoses when treatments fail to yield expected results. Improved awareness and early detection of LAM can enhance patient outcomes and life quality. Early LAM diagnosis is vital as mTORC1 inhibitors such as sirolimus can prevent further decline in lung function. Notably, the response of case 2 to pazopanib treatment supports suggestions of its potential as a second-line therapy for perivascular epithelioid cell tumors (PEComas), including LAM.

A chylothorax in a young woman: The difficulties of medical management.

Lymphangioleiomyomatosis is a rare pulmonary disease affecting women of childbearing age. Whilst chylothorax is a well-recognized complication of the condition, management strategies aren't well-defined, have low success rates and are often only available at tertiary or specialist centres. We describe a case of a young woman referred to pleural clinic with a chylous effusion found to be secondary to lymphangioleiomyomatosis. Initial medical management was unsuccessful and recurrent drainages caused significant complications. Remission was ultimately achieved with a combination of mTOR inhibitors and interventional radiology techniques.