Diagnosis Of Lymphangioleiomyomatosis Research Articles

Lung Transplantation Outcomes and Peritransplant Sirolimus Use in Lymphangioleiomyomatosis

BackgroundWith the introduction of sirolimus as medical therapy for lymphangioleiomyomatosis (LAM), an updated evaluation of LAM lung transplant (LT) outcomes and characterization of peritransplant sirolimus use is needed. MethodsWe identified adult LT recipients from 2005-2021 using the Scientific Registry of Transplant Recipients database and stratified by diagnosis (LAM vs other). Multivariable Cox regression was performed to calculate the adjusted hazard ratio for LAM vs other diagnoses. A pharmacy claims database was linked to provide sirolimus prescription information, and a subgroup analysis comparing outcomes with pre- vs posttransplant sirolimus use was performed. ResultsOf 32,337 recipients identified, 156 (0.5%) were diagnosed with LAM. Operative complications, including airway dehiscence, did not significantly differ between groups. After adjusting for donor and recipient characteristics, LAM diagnosis was associated with 45% lower mortality than other diagnoses. Among recipients with pharmacy data, 32% were prescribed sirolimus at any point. Compared with only post-LT use only, recipients with pre-LT sirolimus use had increased mortality (log-rank P = .003). ConclusionsThis study supports lung transplant as a treatment for severe pulmonary LAM and identifies increased mortality associated with pre-LT sirolimus, though this may be due to uncharacterized baseline differences.

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

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. 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. 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. 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 32-Year-Old Female with Incidentally Detected Multifocal Cystic Pulmonary Lesions on Chest Computed Tomography

Lymphangioleiomyomatosis (LAM) is a rare condition that exclusively affects women and is characterized by lung parenchymal destruction and the formation of cysts due to infiltration by LAM cells. It can also impact the lymphatic system, leading to the development of fluid-filled cystic structures and abdominal involvement, including renal angiomyolipomas (AML) or lymphangioleiomyoma. LAM can occur sporadically or be associated with tuberous sclerosis complex. Common symptoms include respiratory issues such as dyspnea, pneumothorax, chylothorax, along with other manifestations like renal AML and lymphatic involvement. The diagnosis of LAM relies on a combination of clinical, radiological, and laboratory findings, and treatment options vary depending on symptoms and patient status, with mTOR inhibitors being considered as a treatment option. This case outlines the diagnostic journey and clinical course of a 32-year-old female patient with LAM.

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

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. To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients. A multicenter prospective cohort study. 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. 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%. Our results suggest that serum VEGF-D may be a useful biomarker for diagnosing LAM in Korean patients, similar to previous reports.

Safety and efficacy of cryobiopsy for the diagnosis of lymphangioleiomyomatosis compared with forceps biopsy and surgical lung biopsy

BackgroundTransbronchial lung forceps biopsy (TBFB) is recommended before a surgical lung biopsy (SLB) when a definitive diagnosis of lymphangioleiomyomatosis (LAM) is required for patients without any additional confirmatory features. Transbronchial lung cryobiopsy (TBCB) has been suggested as replacement test in patients considered eligible to undergo SLB for the diagnosis of interstitial lung diseases. The efficacy and safety of TBCB were compared with that of TBFB and SLB in the diagnosis of LAM.MethodsA retrospective analysis was conducted on 207 consecutive patients suspected with LAM in the First Affiliated Hospital of Guangzhou Medical University from 2005 to 2020.ResultsThe difference in diagnostic rate of patients suspected with LAM between TBCB (20/30, 66.7%) and TBFB (70/106, 66.0%) groups was not significant (p = 0.949). One patient performed TBCB with negative pathological results could be diagnosed exclusively after SLB. LAM diagnosis was confirmed by surgical pathological findings in 3 TBFB-negative patients. More patients with minimal cystic profusion were diagnosed with LAM by TBCB (5/19, 26.3%) and SLB (11/39, 28.2%) than by TBFB (3/61, 4.9%) (TBCB vs TBFB: p = 0.04, SLB vs TBFB, p < 0.001). The difference between the severity of cystic lung disease in patients diagnosed with LAM through TBCB and SLB was not significant (p > 0.05). One pneumothorax, 8 mild bleeding and 1 moderate bleeding were observed in TBCB. One pneumothorax, 15 mild bleeding and 1 moderate bleeding occurred after TBFB.ConclusionCompared to TBFB, TBCB is safe and effective in diagnosing LAM at a higher diagnostic rate in patients with minimal cystic profusion.

Spontaneous pneumothoraces during pregnancy in patients with lymphangioleiomyomatosis

Patients with lymphangioleiomyomatosis (LAM) are prone to developing spontaneous pneumothoraces (SPs). We aimed to characterize the burden of SPs during pregnancy in LAM, using a web-based survey. Among the 50 respondents, 12 (24%) had never been pregnant and 38 (76%) were pregnant at least once, resulting in a total of 80 pregnancies. Respiratory symptoms during pregnancy led to the diagnosis of LAM in 34% of (13/38) patients, with SPs being the presenting manifestation in most of these patients (10/13, 77%). Eleven of the 38 pregnant patients (29%) experienced at least one SP during pregnancy. The majority of the SPs (∼60%) occurred during the second trimester. Our study provides valuable insights regarding the risk, burden, and timing of pregnancy-related SPs in patients with LAM that would be useful for the LAM community.

Lymphangioleiomyomatosis: diagnosis of a rare cystic lung disease in a clinical case

Sporadic lymphangioleiomyomatosis (LAM) is an orphan disease that primarily affects women of childbearing age. Increasing awareness of this disease among physicians can contribute to its timely diagnosis and treatment.The aim of this work was to present a case of a young woman with a rare cystic lung disease. At the first visit to the clinic, the patient showed pronounced clinical, radiological and functional changes in the bronchopulmonary system, and a rare pathology was suspected. Establishing the definitive diagnosis in the shortest possible time was essential because pathogenetic therapy with an mTOR inhibitor had to be initiated as soon as the diagnosis of LAM had been clarified. Until 2010, a definitive diagnosis of LAM was made only by surgical lung biopsy. However, there is currently a shift in practice toward less invasive diagnostic methods that eliminate the need for surgical intervention in most patients.Conclusion. An algorithm for making a definitive diagnosis (sporadic LAM) without morphologic examination of the lung is demonstrated.

Systematic Review of Lymphangioleiomyomatosis Outcomes in Pregnancy and a Proposed Management Guideline.

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease that primarily affects women of reproductive age. Disease progression has been linked to estrogen exposure, and as such many patients are advised to avoid pregnancy. Data are limited regarding the interaction between LAM and pregnancy, and as such we performed a systematic review to summarize available literature reporting outcomes of pregnancies complicated by maternal LAM. This was a systematic review including randomized controlled trials, observational studies, systematic reviews, case reports, clinical practice guidelines, and quality improvement studies with full-text manuscripts or abstracts in the English language with primary data on pregnant or postpartum patients with LAM. The primary outcome was maternal outcomes during pregnancy as well as pregnancy outcomes. Secondary outcomes were neonatal outcomes and long-term maternal outcomes. This search occurred in July 2020 and included MEDLINE, Scopus, clinicaltrials.gov, Embase, and Cochrane Central. Risk of bias was ascertained using the Newcastle-Ottawa Scale. Our systematic review was registered with PROSPERO as protocol number CRD 42020191402. A total of 175 publications were identified in our initial search; ultimately 31 studies were included. Six (19%) studies were retrospective cohort studies and 25 (81%) studies were case reports. Patients diagnosed during pregnancy had worse pregnancy outcomes compared to those diagnosed with LAM prior to pregnancy. Multiple studies reported a significant risk of pneumothoraces during pregnancy. Other significant risks included preterm delivery, chylothoraces, and pulmonary function deterioration. A proposed strategy for preconception counseling and antenatal management is provided. Patients diagnosed with LAM during pregnancy generally experience worse outcomes including recurrent pneumothoraces and preterm delivery as compared to patients with a LAM diagnosis prior to pregnancy. Given that there are limited studies available, and that the majority are low-quality evidence and subject to bias, further investigation of the interaction between LAM and pregnancy is warranted to guide patient care and counseling. · Data are limited on the effects of lymphangioleiomyomatosis on pregnancy outcomes.. · We performed a systematic review to summarize pregnancy outcomes complicated by LAM.. · Patients diagnosed with LAM during pregnancy experience worse outcomes..

An Evidence-Based Update on the Potential Association between Rheumatoid Arthritis and Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) represents an uncommon disorder characterized by cystic lung destruction and chronic respiratory failure. Lung damage caused by various mechanisms may represent a hypothesis for studying the association between LAM and rheumatoid arthritis (RA), which is the most prevalent autoinflammatory rheumatic disease and may affect the lungs as an extra-articular manifestation. Despite their distinct clinical presentations, the pathophysiology of both disorders includes dysregulated immunological function, abnormal cellular development, and inflammation. Current research suggests a potential relationship between RA and LAM, as some RA patients have been reported to develop LAM. However, the association of RA and LAM raises important therapeutic dilemmas. For this reason, the trajectory of a patient who was identified in our medical records as suffering from both LAM and RA, treated with many novel molecules and biological therapy, but with a negative outcome due to respiratory and multiorgan failure, has been exemplified. The delay in the diagnosis of LAM is due to a correlation between RA and LAM, worsening the vital prognosis and also hindering pulmonary transplantation. In addition, extensive research is essential for understanding the potential connection between these two disorders and discovering any similar mechanisms involved that may underlie their occurrence. This may contribute to the development of new therapeutic options that target shared pathways implicated in the pathogenesis of RA and LAM.

Chylopericardium causing cardiac tamponade in a patient with lymphangioleiomyomatosis

Background: Chylopericardium is a rare entity characterized by the accumulation of chylous fluid in the pericardial cavity. Lymphangioleiomyomatosis (LAM) is a rare, progressive systemic disease with prominent features of lung cysts, abdominal tumors, and the development of chylous effusions, usually in the thorax and/or abdomen. Chylopericardium in association with LAM is exceedingly rare, with only a few cases reported in the literature. Case Presentation: We report a case of a 61-year-old woman with chronic dyspnea and bilateral cystic lung disease who presented with a 1-week history of acutely worsening dyspnea. At presentation, she was tachycardiac and hypoxemic, an electrocardiogram detected sinus tachycardia, and a chest radiograph was indeterminate for a small right apical pneumothorax or an apical bulla. An urgent echocardiogram revealed a large pericardial effusion with features of cardiac tamponade, necessitating urgent pericardiocentesis. Analysis of the pericardial fluid confirmed the presence of chylopericardium and a diagnosis of LAM was made. Oral Sirolimus was started and at 1 year of follow-up, the patient has successfully avoided repeat pericardiocentesis. Conclusion: This case describes a rare presentation of a rare disease and suggests that treatment with sirolimus may potentially be effective in reducing the accumulation of chylopericardium in LAM.

A NOVEL CASE OF LYMPHANGIOLEIOMYOMATOSIS AND PULMONARY LIGHT CHAIN DEPOSITION DISEASE

A NOVEL CASE OF LYMPHANGIOLEIOMYOMATOSIS AND PULMONARY LIGHT CHAIN DEPOSITION DISEASE

A pulmonary lymphangioleiomyomatosis with multi-site angiomyolipoma: a case report

BackgroundLymphangioleiomyomatosis (LAM) is a rare low-grade malignant tumor featured with diffuse cystic changes due to the destructive proliferation of LAM cells, closely related to angiomyolipoma (AML). Here, we reported a rare case of pulmonary LAM coexisting with AMLs in multiple sites of the lung, liver, kidney, and retroperitoneum. We aimed to contribute to the body of knowledge regarding the diagnosis, identification and treatment of such cases.Case DescriptionA 48-year-old female with no symptoms underwent a chest computed tomography (CT) scan that showed diffuse thin-walled cysts and multiple solid nodules in the lungs. She received a right nephrectomy due to right kidney AML 30 years previously. The pathological manifestations of the right lower lung mass removed by thoracoscopic surgery was a multifocal AML with mutations in the tuberous sclerosis complex gene. Abdominal magnetic resonance imaging (MRI) reveals a vast area of fat signal shadow behind the peritoneum and multiple scattered fatty signal nodules in the liver parenchyma. No other treatment was given due to personal factors of the patient, and there was no significant change at the 1-year follow-up.ConclusionsLAM and AML are two different but substantively related rare neoplastic diseases. When typical LAM imaging features are found on chest CT or in pathological specimens collected from patients diagnosed with AML, multisystem screening should be performed for the early detection and diagnosis of LAM.

Tuberous sclerosis complex: a complex case.

Tuberous sclerosis complex (TSC) is an inheritable disorder characterized by the formation of benign yet disorganized tumors in multiple organ systems. Germline mutations in the TSC1 (hamartin) or more frequently TSC2 (tuberin) genes are causative for TSC. The malignant manifestations of TSC, pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML), may also occur as independent sporadic perivascular epithelial cell tumor (PEComa) characterized by somatic TSC2 mutations. Thus, discerning TSC from the copresentation of sporadic LAM and sporadic AML may be obscured in TSC patients lacking additional features. In this report, we present a case study on a single patient initially reported to have sporadic LAM and a mucinous duodenal adenocarcinoma deficient in DNA mismatch repair proteins. Moreover, the patient had a history of Wilms’ tumor, which was reclassified as AML following the LAM diagnosis. Therefore, we investigated the origins and relatedness of these tumors. Using germline whole-genome sequencing, we identified a premature truncation in one of the patient's TSC2 alleles. Using immunohistochemistry, loss of tuberin expression was observed in AML and LAM tissue. However, no evidence of a somatic loss of heterozygosity or DNA methylation epimutations was observed at the TSC2 locus, suggesting alternate mechanisms may contribute to loss of the tumor suppressor protein. In the mucinous duodenal adenocarcinoma, no causative mutations were found in the DNA mismatch repair genes MLH1, MSH2, MSH6, or PMS2. Rather, clonal deconvolution analyses were used to identify mutations contributing to pathogenesis. This report highlights both the utility of using multiple sequencing techniques and the complexity of interpreting the data in a clinical context.

X-ray Dark-field Chest Radiography of Lymphangioleiomyomatosis.

HomeRadiologyVol. 303, No. 3 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyX-ray Dark-field Chest Radiography of LymphangioleiomyomatosisFlorian T. Gassert , Franz PfeifferFlorian T. Gassert , Franz PfeifferAuthor AffiliationsFrom the Department of Diagnostic and Interventional Radiology, School of Medicine & Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str 22, 81675 Munich, Germany (F.T.G., F.P.); and Department of Physics, School of Natural Sciences (F.P.), and Institute for Advanced Study (F.P.), Technical University of Munich, Garching, Germany.Address correspondence to F.T.G. (e-mail: [email protected]).Florian T. Gassert Franz PfeifferPublished Online:Mar 29 2022https://doi.org/10.1148/radiol.212490MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 31-year-old woman presented to our emergency department with persistent pain following epigastric herniotomy. Abdominal CT showed no evidence of recurrent hernia or incarceration. However, the partially imaged lung bases showed cystic changes in the parenchyma and multiple small nodules. A dedicated chest CT scan confirmed these findings throughout both lungs, consistent with lymphangioleiomyomatosis (LAM) (Fig 1). Transbronchial biopsy revealed cystically dilated alveolar spaces, confirming the diagnosis of LAM. LAM is a rare, idiopathic disease resulting from the proliferation of abnormal smooth muscle LAM cells in the lungs and other organs. It almost exclusively affects women of childbearing age. It is a slowly progressive disease that can lead to chronic respiratory insufficiency, and lung transplant is currently the only effective treatment available.Figure 1: (A) Coronal and (B) axial reformatted chest CT images in a 31-year-old woman show thin-walled cysts of variable sizes (arrowheads) surrounded by normal lung parenchyma as well as interlobular septal thickening in all lobes and multiple vessel-associated round foci, most likely corresponding to pulmonary arteriovenous malformations (arrows in A). The yellow line in A indicates the position of the axial reformation.Figure 1:Download as PowerPointOpen in Image Viewer X-ray dark-field chest radiography is a novel imaging technique that exploits the wave character of x-rays by measuring the amount of refraction occurring at air-tissue interfaces such as in the alveoli. Therefore, it enables assessment of the alveolar integrity and provides additional information complementing conventional, attenuation-based radiography (1,2). In animal models (3–5), dark-field imaging has previously been shown to be beneficial for the assessment of various pulmonary pathologic conditions, including lung cancer, pulmonary fibrosis, pneumonia, pneumothorax, and emphysema. In the presented case, additional x-ray dark-field chest radiography was performed, yielding both a conventional, attenuation-based radiograph and an x-ray dark-field chest radiograph (6) (Fig 2). The x-ray dark-field chest radiograph in the patient with LAM exhibited an overall low and inhomogeneous signal with focal areas of signal loss, predominantly in the right inferior lung field, corresponding well to the most affected lower lobe on the respective CT scan.Figure 2: (A, D) Conventional attenuation-based chest radiographs, (B, E) x-ray dark-field chest radiographs, and (C, F) color-coded dark-field images laid over inverted conventional radiographs in a 31-year-old woman diagnosed with lymphangioleiomyomatosis (LAM) (top row) and a healthy 33-year-old man (bottom row). The same window and level settings were applied within the respective modality. For the color-coded overlays in C and F, the dark-field signal (blue) was laid over the inverted chest radiograph. While the dark-field chest radiograph of the healthy man (E) exhibits a high, homogeneous signal, the dark-field chest radiograph of the patient with LAM (B) exhibits an overall low and inhomogeneous signal with focal areas of signal loss, predominantly in the right inferior lung field (arrowheads), corresponding well to the multiple cysts, in particular those present in the right lower lobe in the respective CT scan (Fig 1, arrowheads). The color-coded overlays combine information on both attenuating tissues and alveolar structure.Figure 2:Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: F.T.G. No relevant relationships. F.P. No relevant relationships.Supported by the European Research Council (AdG 695045) and the Deutsche Forschungsmeinschaft (GRK 2274). This work was carried out with the support of the Karlsruhe Nano Micro Facility, a Helmholtz Research Infrastructure at Karlsruhe Institute of Technology.

Soluble Immune-Related Proteins as New Candidate Serum Biomarkers for the Diagnosis and Progression of Lymphangioleiomyomatosis.

BackgroundThe goal of this study was to analyze serum from lymphangioleiomyomatosis (LAM) patients and healthy controls to identify novel biomarkers that could shed light on disease diagnosis and pathogenesis.MethodsFrom April 2017 to October 2019, qualified serum samples were obtained to explore differences in 59 immune proteins between 67 LAM patients and 49 healthy controls by the Luminex method.ResultsWe characterized 22 serum immune proteins that were differentially expressed in LAM patients compared with healthy people. Fifty-nine proteins were then classified into eight categories according to their biological function, and the results showed that LAM patients displayed significantly higher levels of growth factors (p = 0.006) and lower levels of costimulatory molecules (p = 0.008). LAG-3 was not only likely to have better predictive value than VEGF-D but also showed a significant difference between patients without elevated VEGF-D and healthy people. IL-18 was positively correlated with lung function and six-minute walk test (6MWT) distance and negatively correlated with St. George’s Respiratory Questionnaire (SGRQ) score and pulmonary artery systolic pressure (PASP), which suggested that IL-18 was related to disease severity. PD-1 was significantly different between patients with pneumothorax and/or chylothorax and those without complications.ConclusionWe performed a large-scale serum immune factor analysis of LAM. Our study provides evidence that LAG-3 may be a novel candidate serum biomarker for the diagnosis of LAM. Future independent validation in prospective studies is warranted.

Diagnostic performance of VEGF-D for lymphangioleiomyomatosis: a meta-analysis.

ABSTRACTObjective:VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods:We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results:Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions:VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

Pulmonary lymphangioleiomyomatosis with an associated giant renal angiomyolipoma.

Pulmonary lymphangioleiomyomatosis (LAM), a rare, progressive disease predominantly affecting the lungs of women of reproductive age, is often associated with renal angiomyolipoma (AML). We report the case of a 29-year-old female patient who presented to our obstetrics department at 37 weeks’ gestation, complaining of abdominal pain, and constipation. Ultrasound noted a viable singleton with a large left-sided abdominal mass. After undergoing a caesarean section, she was referred to our urology department to assess her flank mass further. Computed tomography demonstrated a large, exophytic left renal mass measuring 22 cm x 16 cm x 13 cm, suggestive of an AML and numerous bilateral pulmonary cysts. A diagnosis of LAM and associated unilateral giant renal AML was made. As soon as she had fully recovered from her caesarean section, we removed the huge AML via a standard left-sided open nephrectomy without incident. We report this rare case of giant AML associated with LAM and review the literature about the association of these two conditions.

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. Here, we propose monoamine‐derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine‐derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF‐D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L‐histidine analog, or a low L‐histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.

The value of transbronchial lung biopsy in the diagnosis of lymphangioleiomyomatosis

BackgroundTransbronchial lung biopsy (TBLB) in the diagnosis of lymphangioleiomyomatosis (LAM) is not a common approach, although TBLB is often performed in diffuse lung diseases. We aimed to examine the diagnostic value and safety of TBLB in LAM patients based on the data collected in our center.MethodsWe reviewed LAM patients registered in our LAM Clinic from December 8, 2006, to December 31, 2019. All patients with definite or probable diagnosis of LAM who had been examined using TBLB were included. All available pathology slides were reviewed by an experienced LAM pathologist. All complications were reviewed by the medical records and confirmed using telephone interviews.ResultsThe pathology results of 86 patients (including 74 definite LAM and 12 probable LAM) were available. The positive rate of TBLB in LAM patients was 49/86 (57.0%). The positive rates of SMA, HMB-45, ER, and PR in LAM patients were 97.6%, 93%, 84.6%, and 78.4% respectively. The positive rate of TBLB was 40%, 60% and 60.8% in patients with CT Grade I, Grade II, and Grade III respectively, and the difference was not significant. Patients who had 3–4 or 5–6 biopsied specimens had a higher rate of diagnosis than those with 1–2 biopsied specimens. Four patients (5.6%) reported pneumothorax. No major hemoptysis was reported.ConclusionsTBLB is a feasible and safe procedure for obtaining a pathological diagnosis of LAM. Taking more than 2 samples during the biopsy procedure increased the rate of diagnosis.

Uncommon radiologic computed tomography appearances of the chest in patients with lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by multiple thin-walled pulmonary cysts. The currently proposed diagnostic algorithm emphasizes the characteristic cystic appearance on high-resolution computed tomography (HRCT) so uncommon HRCT appearances present challenges to establishing the proper LAM diagnosis. The objective of this study is to accrue uncommon chest HRCT appearances, determine frequencies in both tuberous sclerosis complex (TSC)-associated LAM (TSC-LAM) and sporadic LAM (S-LAM) patients. 311 females referred to our hospital, including 272 S-LAM patients (mean age 39.2 years) and 39 TSC-LAM patients (mean age 38.3 years), were retrospectively evaluated. We found 2 types of radiologic findings likely to make HRCT cyst appearance atypical: characteristics of the cyst itself and uncommon findings in addition to cysts. We found that approximately 80% of LAM patients, whether TSC-associated or sporadic, showed typical HRCT appearance with mild to severe cystic destruction. The remaining 20% displayed unusual profiles in cyst appearance as well as additional findings aside from cyst: the former includes large cyst, thickened walls, and irregularly shaped whereas the latter includes ground glass attenuation and diffuse noncalcified nodules. It is important to be aware of various radiologic findings that make HRCT cystic appearance atypical of LAM.