Explanation Benign metastasizing leiomyoma and lymphangioleiomyomatosis (LAM) are both characterized by abnormal proliferation of smooth muscle-like cells in the lung. A 32 year-old African woman was given a diagnosis of LAM based on a lung biopsy showing proliferation of smooth muscle cells with focal reactivity to HMB45, a monoclonal antibody that recognizes gp100, a melanoma antigen. She subsequently underwent myomectomy for uterine fibroids. The patients disease continued to progress, with an interstitial pattern seen on chest X-ray. Given the unusual course and presentation, a repeat lung biopsy was performed and an alternative diagnosis of benign metastasizing leiomyoma was made. Treatment with leuprolide acetate decreased pulmonary infiltrates and improved lung function and exercise tolerance. Accurately diagnosing benign metastasizing leiomyoma has important implications for clinical outcome. Since its clinical presentation may be misleading, immunohistochemistry techniques may assist in differentiating benign metastasizing leiomyoma from LAM. This is important because in BML, reduced tumor burden and improved pulmonary function may be achieved by suppressing gonadal steroids. This was found to be the case with the patient described here. Limited data are available regarding the role of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) as diagnostic tools in pulmonary Langerhans Cell Histiocytosis (LCH) and lymphangioleiomyomatosis (LAM).
The aim of this study was to assess the value of these two techniques in the diagnosis of these cystic lung diseases. Records of 452 patients with the presumptive diagnosis of interstitial lung disease were reviewed;67 had a clinical-radiological diagnosis of either LCH (n=27) or LAM (n= 40). Of 16 patients with LCH who underwent BAL, four specimens (25%) contained cells which had positive immunoreactivity for CD1a. Of three patients with negative BAL fluid who had TBB, one had a positive tissue diagnosis. Surgical lung biopsy was diagnostic in ten patients (5 with negative BAL fluid). Standard examination of BAL fluid was of no diagnostic value in LAM. TBB biopsies in six of seven LAM patients (85%) were diagnostic and did not result in complications. In thirteen LAM patients who underwent surgical lung biopsies, a histopathologic diagnosis was obtained. BAL may assist in the diagnosis of LCH whereas TBB has less value. TBB is useful in the diagnosis of LAM, thus avoiding the need for surgical biopsy.
The aim of this study was to determine whether a computed tomography (CT)-based method assessing tissue texture demonstrates lung lesions, grades their severity, and evaluates lung tissue in areas adjacent to or remote from cysts, in patients with lymphangioleiomyomatosis. 326 CT scans from 52 patients were studied. After segmenting the lungs and subdividing images into texture blocks, a multi-dimensional feature vector composed of 25 texture features was used to differentiate and group each texture block. Cysts were outlined, and texture around the cysts and in regions away from cysts, was analyzed. Longitudinal analysis was conducted on the sequential CT scans and the pulmonary function tests to assess the trend of change. Histopathological examination was performed on biopsies from 45 patients, 20 of whom were part of the radiologic cohort. Differences in texture features between areas adjacent to and remote from the cysts were observed. Cyst score and sum entropy in areas around the cysts correlated with lung function (p<0.0001). Emphysematous-like changes in non-cystic areas were identified in lung tissue from 31 of 45 patients. A computational method that uses texture analysis and feature correlation, can identify and quantify cystic areas where LAM exists, and detect abnormalities in areas near cysts. Pathological data also demonstrate lung damage in areas adjacent to cysts. Several texture features correlate with lung function. Decline in lung function paralled changes in texture features. In LAM, cystic changes alone may not define the extent of lung destruction. Normal-appearing areas of the chest CT scan correlate with pulmonary function and course of disease.

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Taveira-DaSilva, Angelo M; Jones, Amanda M; Julien-Williams, Patricia et al. (2017) Long-Term Effect of Sirolimus on Serum Vascular Endothelial Growth Factor D Levels in Patients With Lymphangioleiomyomatosis. Chest :
Cui, Ye; Steagall, Wendy K; Lamattina, Anthony M et al. (2017) Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation. Cancer Res 77:1492-1502
Nathan, Neera; Keppler-Noreuil, Kim M; Biesecker, Leslie G et al. (2017) Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway. Dermatol Clin 35:51-60
Nathan, N; Burke, K; Moss, J et al. (2017) A diagnostic and management algorithm for individuals with an isolated skin finding suggestive of tuberous sclerosis complex. Br J Dermatol 176:220-223
Reiss, Theodore F; Moss, Joel; Watkins, Timothy R et al. (2016) BEAR Cage: Mentoring through Engagement. Am J Respir Crit Care Med 193:714-6
Taveira-DaSilva, Angelo M; Moss, Joel (2016) EPIDEMIOLOGY, PATHOGENESIS and DIAGNOSIS of LYMPHANGIOLEIOMYOMATOSIS. Expert Opin Orphan Drugs 4:369-378
Nathan, Neera; Tyburczy, Magdalena E; Hamieh, Lana et al. (2016) Nipple Angiofibromas with Loss of TSC2 Are Associated with Tuberous Sclerosis Complex. J Invest Dermatol 136:535-8
Zhang, Li; Pacheco-Rodriguez, Gustavo; Steagall, Wendy K et al. (2015) Tuberous sclerosis complex 2 loss of heterozygosity in patients with lung disease and cancer. Am J Respir Crit Care Med 191:352-5
Barochia, Amisha V; Kaler, Maryann; Cuento, Rosemarie A et al. (2015) Serum apolipoprotein A-I and large high-density lipoprotein particles are positively correlated with FEV1 in atopic asthma. Am J Respir Crit Care Med 191:990-1000
Valencia, Julio C; Steagall, Wendy K; Zhang, Yi et al. (2015) Antibody ?PEP13h reacts with lymphangioleiomyomatosis cells in lung nodules. Chest 147:771-7

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