Cystic Lung Disease. Cristopher A. Meyer, MD
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1 Cystic Lung Disease Cristopher A. Meyer, MD Air filled structure with definable wall typically less than 1 mm thick Cris A. Meyer, M.D. Professor of Radiology University of Wisconsin School of Medicine and Public Health Langerhans Cell Histiocytosis Thin section CT 56 asymptomatic patients: older than 75 Younger than 55 Cysts in 10/40 older subjects and none of younger subjects (p=.02) Uniform distribution Copley SJ et al. Radiology 2009; 251: Langerhans Cell Histiocytosis (LCH) Lymphangioleiomyomatosis (LAM) Chronic Hypersensitivity Pneumonitis Lymphocytic Interstitial Pneumonia/Follicular Bronchiolitis (LIP/FB) Light Chain Deposition Disease Birt-Hogg-Dube Syndrome Cystic Metastases 60 LCH - mixed inflammatory nodule LAM smooth muscle proliferation Subacute/Chronic HP - peribronchial lymphoplasmacytoid infiltrate and OB LIP/FB lymphocytic inflammatory proliferation along BALT Amyloid/LCDD peribronchiolar extracellular protein deposition
2 2nd-4th decade, smokers >90% Sx: cough, dyspnea, PTX up to 20%. Bronchiolocentric mixed inflammatory lesions result in perifibrotic airspace enlargement, bronchiolar mural destruction and luminal dilation Pulmonary artery involvement may lead to intimal fibrosis and pulmonary HTN (LCH vasculopathy) Air cysts, <1cm, bizarre (late) Air trapping CP angles, anterior tips of RML and lingula spared* Adenopathy (rare) Pleural effusions (rare) Abbot GF et al. From the Archives of the AFIP: Pulmonary Langerhans Cell Histiocytosis. Radiographics 2004; 24: 827. Illustration courtesy of Dr. A. Frazier 61
3 25 y.o. heavy smoker with recurrent pneumothoraces 50 y.o. >20 pk-yr smoker with night sweats and dyspnea X 6 months. Air cysts Adenopathy Patchy ground glass No large nodules Diffuse fine nodules of MMPH in 28-43% (TSC > S-LAM) Chylous pleural effusion Air trapping 62 Proliferation of smooth muscle-like spindle cells along axial lymphatics of the chest and abdomen Sporadic LAM (S-LAM) and Tuberous Sclerosis Complex TSC-LAM is up to 10x more common than S-LAM (30% of women with TSC vs 1:1,000,000 S-LAM) Genetic dysregulation of mtor signaling results in perivascular epithelioid cell tumors (PEComas: AML, LAM and clear-cell tumor of lung) Serum VEGF-D biomarker
4 Spontaneous Pneumothorax Chylous Effusion Serum VEGF-D-1885 pg/ml! Angiomyolipomas Retroperitoneal LAM Immune mediated (type 3 and 4) inflammatory response to a variety of inhaled antigens Labs: serum precipitating Ab, BAL lymphocyte predominant (>50%) with CD4/CD8 >1. Pathology: Subacute bronchiolocentric lymphocyte predominant interstitial infiltrate with poorly formed noncaseating granulomas. Areas of NSIP, organizing pneumonia and obliterative bronchiolitis may be present. Chronic findings of subacute HP + fibrosis 63
5 Mosaic ground glass and/or centrilobular nodules Irregular linear opacities patchy or peribronchovascular distribution Air trapping (key feature) Emphysema Lung cysts (13-30%)* Honeycombing (16-69%), mild Franquet T et al. JCAT 2003; 27: Case courtesy of Dr. J Kanne, University of Wisconsin Spectrum of benign lymphoproliferative disorders Diffuse interstitial infiltrate of small lymphocytes and plasma cells along airways and interstitium (BALT) Associations: Sjogren s Disease (most commonly) risk of NHL (44x) Chronic infection Collagen vascular disease (RA) Familial immunodeficiency, AIDS Hypersensitivity reaction. Poorly defined centrilobular or peribronchial nodules (3-12 mm). Ground glass opacities Septal thickening* Thickened peribronchovascular interstitium Perivascular cysts* usually involving <10% of lung parenchyma Mosaic air trapping * Cysts non-reversible 64
6 Amyloidosis Light Chain Deposition Disease Pulmonary nodules (SPN 60%, Ca++ 29%) Interlobular septal thickening Honeycombing Ground glass opacity Lymphadenopathy Lung cysts (rare and often in association with LIP and Sjogren s disease*) *Jeong YJ et al. JCAT 2004; 28:
7 Rare (report of 3 cases) Young women without renal involvement Progressive obstructive respiratory failure Dominant B cell clone restricted to the lung May be an antigen driven primary pulmonary lymphoproliferative process Colombat M et al. Blood 2008; 112: AD mutation at gene locus 17p11.2 encodes for folliculin, a tumor suppressor protein Clinical manifestations: Fibrofolliculomas over the face, neck, upper trunk Multiple lung cysts Renal tumors benign oncocytomas to renal cell carcinomas (multifocal or bilateral) colonic polyposis chorioretinal disease Lung cysts reported in > 80% Pathologically the cysts are associated with the peripheral interlobular septa, visceral pleura or septo-pleural junction HRCT findings: Cysts (often large) with normal intervening lung parenchyma Basilar* subpleural predominance Cysts abutting or including the proximal portions of the lower PA or PV Cysts involve less than 30% of lung 66
8 32x increased risk of PTX! Reported in leiomyosarcoma, synovial cell sarcoma, and endometrial stromal cell sarcoma (ESS), angiosarcoma. Patients may present acutely with spontaneous pneumothorax. Metastatic sarcomas tend to be located focally in the lung periphery not associated with the lymphatics (HMB45 and CD34 immunostains typically negative) Excavation of a centrally necrotic tumor nodule Infiltration of the walls of a pre-existing bulla Ball valve effect of tumor on bronchi with distension of alveoli and small airways Tumor cell proliferation to form vascular cystic spaces (angiosarcoma) 67
9 Diagnosis % Cysts Clinical Distinct HRCT Features Associations Langerhans Cell Histiocytosis S LAM TSC-LAM 100 Smoker Early centrilobular nodules, CP angle sparing 100 Pre menopausal women Seizures, skin lesions Diffuse uniform cysts, chylous effusions, Chronic HP Nonsmoker,exposure Cysts with GGO FB/LIP Sjogren s syndrome, CVD, AIDS Amyloidosis LCDD Birt-Hogg-Dube Syndrome Cystic Metastases Rare Often in Sjogren s Young women Perivascular cysts Rare nodules (Ca+ +) and cysts >80 Skin lesions Basilar, subpleural lentiform cysts Rare Hx of malignancy CA 125+ Peripheral, hematogenous Pulmonary hypertension Serum VEGF- D, AML Lymphoproliferative disorders Renal failure Renal neoplasms LCH is a cystic lung disease in smokers at end stage may mimic emphysema TSC-LAM and B-H-D syndrome are both associated with skin, lung and renal lesions LIP cysts are perivascular Amyloidosis/LCDD consider in a patient with renal failure with calcified and noncalcified nodules and cystic lung disease. Copley SJ et al. Lung morphology in the elderly: comparative CT study of subjects over 75 years old versus those under 55 years old. Radiology 2009; 251: Abbott GF et al. From the archives of the AFIP: pulmonary Langerhans cell histiocytosis. Radiographics 2004; 24: Abbott GF et al. From the archives of the AFIP: lumphangioleiomyomatasis: radiologic-pathologic correlation. Radiographics 2005; 25: Franquet T et al. Lung cysts in subacute hypersensitivity pneumonitis. J Comput Assist Tomogr 2003; 27: Jeong YJ et al. Amylooidosis and Lymphoproliferative Disease in Sjogren syndrome. J Comput Assist Tomogr 2004; 28: Colombat M et al. Pathomechanisms of cyst formation in pulmonary light chain deposition disease. Eur Respir J 2008; 32: Tobino K et al. Characteristics of pulmonary cysts in Birt Hogg Dube syndrome: Thin-section CT findings of the chest in 12 patients. Eur J Radiol
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