Benign Mediastinal Lymphadenopathy in Congestive Heart Failure
2001; Elsevier BV; Volume: 119; Issue: 2 Linguagem: Inglês
10.1378/chest.119.2.653
ISSN1931-3543
AutoresAbdoukarim N’Gom, Pascal Dumont, P. Diot, Emeline Lemarié,
Tópico(s)Lymphadenopathy Diagnosis and Analysis
ResumoWe report threecases of benign mediastinal lymphadenopathy revealed by chestradiography in patients ranging in age from 61 to 75 years. All threepatients had severe coronary heart disease and a history of severalepisodes of acute cardiac decompensation. Chest CT scanning contributedto the diagnosis by revealing the existence of multiple enlarged lymphnodes, mostly 10 to 17 mm in short-axis diameter. CT scanning alsoconfirmed the disappearance of the mediastinal lymph nodes in onepatient on follow-up after treatment with diuretics and digitalis. Histopathology investigations of biopsy samples obtained bymediastinoscopy consistently revealed noninflammatory, benign lesionsthat did not affect the node structure. Our report draws attention tothe particular nosology of left heart disease represented by benignenlarged lymph nodes of the mediastinum and pulmonary edema. Thediagnostic approach to such lymphadenopathy should be guided by theradiologic regression seen on follow-up CT scanning while the patientwas undergoing appropriate therapy for congestive heart failure, whichconstitutes a decisive argument for the congestive heart failureorigin. We report threecases of benign mediastinal lymphadenopathy revealed by chestradiography in patients ranging in age from 61 to 75 years. All threepatients had severe coronary heart disease and a history of severalepisodes of acute cardiac decompensation. Chest CT scanning contributedto the diagnosis by revealing the existence of multiple enlarged lymphnodes, mostly 10 to 17 mm in short-axis diameter. CT scanning alsoconfirmed the disappearance of the mediastinal lymph nodes in onepatient on follow-up after treatment with diuretics and digitalis. Histopathology investigations of biopsy samples obtained bymediastinoscopy consistently revealed noninflammatory, benign lesionsthat did not affect the node structure. Our report draws attention tothe particular nosology of left heart disease represented by benignenlarged lymph nodes of the mediastinum and pulmonary edema. Thediagnostic approach to such lymphadenopathy should be guided by theradiologic regression seen on follow-up CT scanning while the patientwas undergoing appropriate therapy for congestive heart failure, whichconstitutes a decisive argument for the congestive heart failureorigin. Left-sided or complete congestive heart failure is a verycommon clinical situation. Although pulmonary or pleural edema is themost common radiologic and clinical finding, mediastinal edema andlymph node enlargement remain unrecognized in daily practice and havebeen little studied. However, according to Slanetz et al,1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholarat least 50% of patients with congestive heart failure are likely todevelop enlarged mediastinal lymph nodes without evidence of aninfectious, tumor-related, or specific inflammatory cause.Three patients with advanced cardiac insufficiency and benignmediastinal lymphadenopathy fell into this etiologic category afterroutine examinations. Their clinical features are described.Case ReportsCase 1A 73-year-old female nonsmoker was admitted in April 1994 forinvestigation of enlarged right mediastinal lymph nodes revealed bychest radiograph following a recent increase in exertional dyspnea. Herhistory included ischemic heart disease for which she had been treatedfor 5 years, with clear worsening of her condition in the previous 12months.On admission, the patient revealed she had had dyspnea with dry coughfor 3 weeks. On physical examination, she was apyretic and orthopneic. Pulmonary auscultation revealed crackles, mainly at the bases of bothlungs. Her arterial BP was 140/95 mm Hg. A mitral systolic murmur wasnoted along with irregular tachycardia. Hepatomegaly with hepatojugularreflux and malleolar edema were noted on palpation.ECG showed sinus rhythm and left-axis deviation with auricular andventricular extrasystoles. Measurements of arterial blood gas levelswhile the patient was breathing room air revealed the following: Pao2, 54 mm Hg; Paco2, 35 mm Hg; p, H, 7.35; andarterial oxygen saturation (Sao2),91%.A chest radiograph showed cardiomegaly, bilateralalveolointerstitial infiltrates predominating in lung bases and aright-sided homogenous suprahilar fullness with convex border, suggesting mediastinal lymphadenopathy (Fig 1). A CT scan of the chest subsequentlyrevealed several lymph nodes of varying size, between 10 and 17 mm inshort-axis diameter in the transverse plane (normal size, < 10 mm),located in two mediastinal compartments, the left anterior mediastinaland the right lower paratracheal compartments. An abdominal CT scandemonstrated no lymphadenopathy. The WBC count was normal, and the, C-reactive protein level was 3 mg/L. The results of tracheobronchialendoscopy were normal.Mediastinoscopy was performed for biopsy sampling of the lymph nodes. Macroscopically, the lymph nodes appeared to be benign. The pathologyexamination reported sinus histiocytosis without inflammatory ortumoral features. RBCs and a few anthracotic pigments were visible onthe sections. The results of microbiological studies (ie,for tuberculous bacilli, bacteria, parasites, and mycoticagents) were all negative on direct examination and on cultures oflymph node tissue.The immediate outcome was favorable within 24 h after treatmentwith digitalis and diuretics, leading to improvement in the clinicalpicture and in blood gas levels while breathing room air(Pao2, 72 mm Hg; Paco2, 41 mm Hg). A follow-up chestradiograph demonstrated the clearance of parenchymal and hilarinfiltrates (Fig 2). The morphologiccharacteristics of the mediastinal lymph nodes remained unchanged onfollow-up CT scans during 10 months of observation.Figure 2Chest radiograph taken after treatment (case 1). Improvement is marked by moderate clearance of parenchymal andperihilar infiltrates.View Large Image Figure ViewerDownload (PPT)Case 2This 75-year-old man was a smoker (18 pack-years) who hada history of chronic obstructive bronchitis, chronic arteritisobliterans of the lower limbs, and ischemic heart disease, which hadnecessitated a previous hospital admission for acute pulmonaryedema.In May 1997, the patient was admitted with dyspnea, exertion-relatedangina, and productive cough with hemoptysis. A clinical examinationrevealed a temperature of 38.4°C, an arterial BP of 100/60 mm Hg, apulse of 80 beats/min, orthopnea, and diffuse bilateral crackles onpulmonary auscultation. A murmur due to mitral insufficiency and agrade 3 systolic murmur were noted. Sensitive hepatomegaly waspalpable with hepatojugular reflux and edema of the lower limbs.An ECG revealed sinus rhythm and ventricular extrasystoles. Arterial blood gas values, measured while the patient was breathingroom air, were as follows: Pao2, 75mm Hg; Paco2, 38 mm Hg; p, H, 7.38; and, Sao2, 95%. A chest radiographrevealed right-sided pleural effusion with heterogeneous parenchymalinfiltrates of the right hemithorax, hypertrophic hila, andcardiomegaly. Chest CT scan showed lymphadenopathy (lymph node size, 10to 16 mm on short-axis diameter) in the right paratracheal compartmentand hila. The WBC count was 15,000/μL with 76% neutrophils, and the C-reactive protein level was 123 mg/L. The pleural effusion wasa transudate. The results of pleural cytology and biopsy specimentesting were both negative. Bronchial endoscopy demonstratedinflammatory features.Mediastinoscopy was performed. The lymph nodes were macroscopicallyenlarged. Pathology investigations concluded that there were lesions ofsinus histiocytosis, without changes in lymph node structure orsurrounding tissues. The results of microbiological examinations werenegative.Treatment with antibiotics, digitalis, and diuretics was followedby resolution of the patient's temperature 48 h later andby rapid improvement in blood gas values. Initial improvement in thepleural and parenchymal features was noted on follow-up radiograph, butthe mediastinal features persisted after 8 months.Case 3This 61-year-old male smoker (20 pack-years) was admittedin August 1998 for cough with hemoptysis and dyspnea. He had a historyof coronary artery disease that had necessitated hospital admission onthree occasions for acute congestive heart failure.On examination, auscultation indicated bilateral fine crepitant rales. Palpation revealed hepatomegaly, and there was edema of the lowerlimbs. Arterial blood gas values, measured while the patient wasbreathing room air, were as follows: Pao2, 82 mm Hg; Paco2, 35 mm Hg; p, H, 7.42; and, Sao2, 91%. An ECG showed signs ofventricular and auricular hypertrophy. Dilatation of the left ventriclewith hypokinesis of the posterior wall and a systolic ejection fractionof 52% were noted on echocardiographic examination.A chest radiograph revealed slight bilateral interstitial syndrome, predominating in the left base. A CT scan showed lymphadenopathy (lymphnode size, 10 to 15 mm on short-axis diameter) located in paratracheal, pretracheal, and subcarinal compartments. A slight pleural effusion wasvisualized in the right hemithorax (Fig 3). Biochemistry study of the pleural effusion indicated a transudate. Cytologic studies failed to reveal malignant pleural cells. Bronchialendoscopy demonstrated no abnormality.Figure 3Chest CT scan demonstrating right-sided lowerparatracheal lymph nodes and pleural effusion (case 3).View Large Image Figure ViewerDownload (PPT)Mediastinoscopy showed enlarged lymph nodes that were macroscopicallynormal. Microscopic examination revealed sinus histiocytosis associatedwith follicular hyperplasia of the cortex, and no inflammatory lesionsor capsular changes were seen (Fig 4). The results of microbiology studies were negative.Figure 4Photomicrograph of a histology slide from amediastinal lymph node (case 3) demonstrating sinus histiocytosis withslight follicular hyperplasia of the cortex (hematoxylin-eosin-saffron, original×100).View Large Image Figure ViewerDownload (PPT)Treatment was started with digitalis and diuretics, resulting inimmediate clinical and radiologic improvement. On follow-up 5 monthsafter the acute phase, a radiograph and CT scan showed that most of theenlarged mediastinal lymph nodes and the right-sided pleural effusionhad completely disappeared. The few remaining nodes measured < 6 mmin diameter (Fig 5).Figure 5Follow-up chest CT scan (case 3) showing thedisappearance of enlarged lymph nodes 5 months afterpresentation, after the patient had undergone treatment withdigitalis and diuretics.View Large Image Figure ViewerDownload (PPT)DiscussionIn contrast to alveolointerstitial edema, hypertrophy ofmediastinal lymph nodes is not a usual sign of congestive heartfailure. It is very probable that the frequency of lymphadenopathy incongestive heart failure is largely underestimated for various reasons, which can be explained mainly by the clinical presentation and thediagnostic circumstances.Slanetz et al1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar reported a study of 46 chest CT scanexaminations in patients with heart failure, which were performedduring periods of acute cardiac decompensation. Their retrospectiveanalysis identified 55% of patients with enlarged lymph nodes thatinitially were undiagnosed. The enlarged lymph node localizationsinvolved various mediastinal lymphatic chains but appeared to indicatehigher frequency in the subcarinal, paratracheal, and hilar nodes. Follow-up of 17 patients with elevated levels of pulmonary capillarywedge pressure detected 14 patients with enlarged mediastinal lymphnodes (size, 10 to 20 mm on short-axis diameter).The mechanisms underlying the pathogenesis of lymphadenopathy incardiogenic pulmonary edema are unclear. Lymphadenopathy in such casesis the expression of diffuse intrathoracic edema affecting thepulmonary parenchyma and neighboring structures, including themediastinum and associated lymph nodes.The lymphatic circulation has a primary role in the regulation ofpulmonary fluids. It ensures continuous low-pressure drainage of excessfluids from the interstitial space to the collecting ducts via thelymph nodes. These nodes are distributed along the lymph vessels andfilter the lymph during its circulation. The lymph flow rejoins thevenous blood circulation, thus enhancing interactions between the twocirculatory systems.2Wiener-Kronish JP Matthay MA Callen PW et al.Relationship of pleural effusion to pulmonary hemodynamics in patients with congestive heart failure.Am Rev Respir Dis. 1985; 132: 1253-1256PubMed Google Scholar Lymphadenopathy, therefore, mightresult from mediastinal edema, which itself is due to massive orrepeated pulmonary edema that is able to extend above the limits of thelungs and the pleura at a very developed stage of congestive cardiacfailure. Hypertrophy of the lymph nodes, thus, might be linked toedematous infiltration following lymphatic circulation overloading.Drake et al3Drake RE Dhother S Teague RA et al.Lymph flow in sheep with rapid cardiac ventricular pacing.Am J Physiol. 1997; 272: 1595-1598PubMed Google Scholar used an experimental approach in sheep todemonstrate that sudden induced cardiac insufficiency was associatedwith an increase in lymphatic flow measured in the efferent vessel of apreviously cannulated mediastinal lymph node, when venous pressure was< 15 cm H2O. This process was followedby a significant slowing of lymphatic flow for a venous pressure level>15 cm H2O. Leeds et al4Leeds SE Uhley HN Telesky LB Direct cannulation and injection lymphangiography of the canine cardiac and pulmonary efferent mediastinal lymphatics in congestive heart failure.Invest Radiol. 1981; 16: 193-200Crossref PubMed Scopus (11) Google Scholarshowed that experimental congestive heart failure in dogs caused thedilatation of lymphatic vessels, which was provoked by excessiveinterstitial fluid. Slanetz et al1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar reported aparticular hazy and heterogeneous appearance of mediastinal fat, whichwas consistently observed around enlarged lymph nodes that werevisualized on CT scans. It was attributed to local effects of edema. These studies support the hypothesis of hemodynamic mechanisms in lymphnode enlargement that are related to severe cardiac decompensation.Our report draws attention to the particular nosology of late heartdisease represented by benign enlarged lymph nodes of themediastinum and pulmonary edema. The circumstances revealing theenlarged mediastinal nodes in the three patients reported were almostidentical. All had known coronary heart disease and had experiencedseveral episodes of acute congestive heart failure with recentlyworsened symptoms. A suspicion of lymphadenopathy was based onradiographs that were taken to investigate dyspnea and heart failure. The identification of suspicious features is theoretically easier onfollow-up radiographic examinations, which provide better visibility ofhilar and mediastinal areas, after treatment to reduce pulmonary edema. Although CT scanning is much more effective for the identification andfollow-up of enlarged mediastinal lymph nodes,5Glazer G Gross BG Quint LE et al.Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping.AJR Am J Roentgenol. 1985; 144: 261-265Crossref PubMed Scopus (362) Google Scholar suchexaminations usually are not necessary in the clinical context ofcongestive heart failure. However, certain intrathoracic localizationsof Hodgkin's and non-Hodgkin's lymphomas, involving the heart andattributable to metastatic infiltration, may cause congestive heartfailure and, therefore, may present similar clinicalpictures.6Lynch M Cobbs Jr, W Miller RL et al.Massive cardiac involvement by malignant lymphoma.Cardiology. 1996; 87: 566-568Crossref PubMed Scopus (8) Google Scholar The results of lymph node biopsies in all threepatients showed similar histologic abnormalities (ie, sinushistiocytosis with slight follicular hyperplasia of the cortex in onepatient).The spectacular regression or disappearance of the nodes in one of thethree patients, who underwent therapy exclusively for heart disease, isevidence of the likelihood of cardiac origin. A similar outcomehas been reported in the literature after an acute episode ofcongestive heart failure lasting for a month.1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar Thediagnostic approach to such lymphadenopathy should be guided by theradiologic regression seen on follow-up chest radiographs or CT scansperformed while the patient is undergoing appropriate therapy forcongestive heart failure, which constitutes a decisive argument for thecongestive heart failure origin. Left-sided or complete congestive heart failure is a verycommon clinical situation. Although pulmonary or pleural edema is themost common radiologic and clinical finding, mediastinal edema andlymph node enlargement remain unrecognized in daily practice and havebeen little studied. However, according to Slanetz et al,1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholarat least 50% of patients with congestive heart failure are likely todevelop enlarged mediastinal lymph nodes without evidence of aninfectious, tumor-related, or specific inflammatory cause. Three patients with advanced cardiac insufficiency and benignmediastinal lymphadenopathy fell into this etiologic category afterroutine examinations. Their clinical features are described. Case ReportsCase 1A 73-year-old female nonsmoker was admitted in April 1994 forinvestigation of enlarged right mediastinal lymph nodes revealed bychest radiograph following a recent increase in exertional dyspnea. Herhistory included ischemic heart disease for which she had been treatedfor 5 years, with clear worsening of her condition in the previous 12months.On admission, the patient revealed she had had dyspnea with dry coughfor 3 weeks. On physical examination, she was apyretic and orthopneic. Pulmonary auscultation revealed crackles, mainly at the bases of bothlungs. Her arterial BP was 140/95 mm Hg. A mitral systolic murmur wasnoted along with irregular tachycardia. Hepatomegaly with hepatojugularreflux and malleolar edema were noted on palpation.ECG showed sinus rhythm and left-axis deviation with auricular andventricular extrasystoles. Measurements of arterial blood gas levelswhile the patient was breathing room air revealed the following: Pao2, 54 mm Hg; Paco2, 35 mm Hg; p, H, 7.35; andarterial oxygen saturation (Sao2),91%.A chest radiograph showed cardiomegaly, bilateralalveolointerstitial infiltrates predominating in lung bases and aright-sided homogenous suprahilar fullness with convex border, suggesting mediastinal lymphadenopathy (Fig 1). A CT scan of the chest subsequentlyrevealed several lymph nodes of varying size, between 10 and 17 mm inshort-axis diameter in the transverse plane (normal size, < 10 mm),located in two mediastinal compartments, the left anterior mediastinaland the right lower paratracheal compartments. An abdominal CT scandemonstrated no lymphadenopathy. The WBC count was normal, and the, C-reactive protein level was 3 mg/L. The results of tracheobronchialendoscopy were normal.Mediastinoscopy was performed for biopsy sampling of the lymph nodes. Macroscopically, the lymph nodes appeared to be benign. The pathologyexamination reported sinus histiocytosis without inflammatory ortumoral features. RBCs and a few anthracotic pigments were visible onthe sections. The results of microbiological studies (ie,for tuberculous bacilli, bacteria, parasites, and mycoticagents) were all negative on direct examination and on cultures oflymph node tissue.The immediate outcome was favorable within 24 h after treatmentwith digitalis and diuretics, leading to improvement in the clinicalpicture and in blood gas levels while breathing room air(Pao2, 72 mm Hg; Paco2, 41 mm Hg). A follow-up chestradiograph demonstrated the clearance of parenchymal and hilarinfiltrates (Fig 2). The morphologiccharacteristics of the mediastinal lymph nodes remained unchanged onfollow-up CT scans during 10 months of observation.Case 2This 75-year-old man was a smoker (18 pack-years) who hada history of chronic obstructive bronchitis, chronic arteritisobliterans of the lower limbs, and ischemic heart disease, which hadnecessitated a previous hospital admission for acute pulmonaryedema.In May 1997, the patient was admitted with dyspnea, exertion-relatedangina, and productive cough with hemoptysis. A clinical examinationrevealed a temperature of 38.4°C, an arterial BP of 100/60 mm Hg, apulse of 80 beats/min, orthopnea, and diffuse bilateral crackles onpulmonary auscultation. A murmur due to mitral insufficiency and agrade 3 systolic murmur were noted. Sensitive hepatomegaly waspalpable with hepatojugular reflux and edema of the lower limbs.An ECG revealed sinus rhythm and ventricular extrasystoles. Arterial blood gas values, measured while the patient was breathingroom air, were as follows: Pao2, 75mm Hg; Paco2, 38 mm Hg; p, H, 7.38; and, Sao2, 95%. A chest radiographrevealed right-sided pleural effusion with heterogeneous parenchymalinfiltrates of the right hemithorax, hypertrophic hila, andcardiomegaly. Chest CT scan showed lymphadenopathy (lymph node size, 10to 16 mm on short-axis diameter) in the right paratracheal compartmentand hila. The WBC count was 15,000/μL with 76% neutrophils, and the C-reactive protein level was 123 mg/L. The pleural effusion wasa transudate. The results of pleural cytology and biopsy specimentesting were both negative. Bronchial endoscopy demonstratedinflammatory features.Mediastinoscopy was performed. The lymph nodes were macroscopicallyenlarged. Pathology investigations concluded that there were lesions ofsinus histiocytosis, without changes in lymph node structure orsurrounding tissues. The results of microbiological examinations werenegative.Treatment with antibiotics, digitalis, and diuretics was followedby resolution of the patient's temperature 48 h later andby rapid improvement in blood gas values. Initial improvement in thepleural and parenchymal features was noted on follow-up radiograph, butthe mediastinal features persisted after 8 months.Case 3This 61-year-old male smoker (20 pack-years) was admittedin August 1998 for cough with hemoptysis and dyspnea. He had a historyof coronary artery disease that had necessitated hospital admission onthree occasions for acute congestive heart failure.On examination, auscultation indicated bilateral fine crepitant rales. Palpation revealed hepatomegaly, and there was edema of the lowerlimbs. Arterial blood gas values, measured while the patient wasbreathing room air, were as follows: Pao2, 82 mm Hg; Paco2, 35 mm Hg; p, H, 7.42; and, Sao2, 91%. An ECG showed signs ofventricular and auricular hypertrophy. Dilatation of the left ventriclewith hypokinesis of the posterior wall and a systolic ejection fractionof 52% were noted on echocardiographic examination.A chest radiograph revealed slight bilateral interstitial syndrome, predominating in the left base. A CT scan showed lymphadenopathy (lymphnode size, 10 to 15 mm on short-axis diameter) located in paratracheal, pretracheal, and subcarinal compartments. A slight pleural effusion wasvisualized in the right hemithorax (Fig 3). Biochemistry study of the pleural effusion indicated a transudate. Cytologic studies failed to reveal malignant pleural cells. Bronchialendoscopy demonstrated no abnormality.Figure 3Chest CT scan demonstrating right-sided lowerparatracheal lymph nodes and pleural effusion (case 3).View Large Image Figure ViewerDownload (PPT)Mediastinoscopy showed enlarged lymph nodes that were macroscopicallynormal. Microscopic examination revealed sinus histiocytosis associatedwith follicular hyperplasia of the cortex, and no inflammatory lesionsor capsular changes were seen (Fig 4). The results of microbiology studies were negative.Figure 4Photomicrograph of a histology slide from amediastinal lymph node (case 3) demonstrating sinus histiocytosis withslight follicular hyperplasia of the cortex (hematoxylin-eosin-saffron, original×100).View Large Image Figure ViewerDownload (PPT)Treatment was started with digitalis and diuretics, resulting inimmediate clinical and radiologic improvement. On follow-up 5 monthsafter the acute phase, a radiograph and CT scan showed that most of theenlarged mediastinal lymph nodes and the right-sided pleural effusionhad completely disappeared. The few remaining nodes measured < 6 mmin diameter (Fig 5).Figure 5Follow-up chest CT scan (case 3) showing thedisappearance of enlarged lymph nodes 5 months afterpresentation, after the patient had undergone treatment withdigitalis and diuretics.View Large Image Figure ViewerDownload (PPT) Case 1A 73-year-old female nonsmoker was admitted in April 1994 forinvestigation of enlarged right mediastinal lymph nodes revealed bychest radiograph following a recent increase in exertional dyspnea. Herhistory included ischemic heart disease for which she had been treatedfor 5 years, with clear worsening of her condition in the previous 12months.On admission, the patient revealed she had had dyspnea with dry coughfor 3 weeks. On physical examination, she was apyretic and orthopneic. Pulmonary auscultation revealed crackles, mainly at the bases of bothlungs. Her arterial BP was 140/95 mm Hg. A mitral systolic murmur wasnoted along with irregular tachycardia. Hepatomegaly with hepatojugularreflux and malleolar edema were noted on palpation.ECG showed sinus rhythm and left-axis deviation with auricular andventricular extrasystoles. Measurements of arterial blood gas levelswhile the patient was breathing room air revealed the following: Pao2, 54 mm Hg; Paco2, 35 mm Hg; p, H, 7.35; andarterial oxygen saturation (Sao2),91%.A chest radiograph showed cardiomegaly, bilateralalveolointerstitial infiltrates predominating in lung bases and aright-sided homogenous suprahilar fullness with convex border, suggesting mediastinal lymphadenopathy (Fig 1). A CT scan of the chest subsequentlyrevealed several lymph nodes of varying size, between 10 and 17 mm inshort-axis diameter in the transverse plane (normal size, < 10 mm),located in two mediastinal compartments, the left anterior mediastinaland the right lower paratracheal compartments. An abdominal CT scandemonstrated no lymphadenopathy. The WBC count was normal, and the, C-reactive protein level was 3 mg/L. The results of tracheobronchialendoscopy were normal.Mediastinoscopy was performed for biopsy sampling of the lymph nodes. Macroscopically, the lymph nodes appeared to be benign. The pathologyexamination reported sinus histiocytosis without inflammatory ortumoral features. RBCs and a few anthracotic pigments were visible onthe sections. The results of microbiological studies (ie,for tuberculous bacilli, bacteria, parasites, and mycoticagents) were all negative on direct examination and on cultures oflymph node tissue.The immediate outcome was favorable within 24 h after treatmentwith digitalis and diuretics, leading to improvement in the clinicalpicture and in blood gas levels while breathing room air(Pao2, 72 mm Hg; Paco2, 41 mm Hg). A follow-up chestradiograph demonstrated the clearance of parenchymal and hilarinfiltrates (Fig 2). The morphologiccharacteristics of the mediastinal lymph nodes remained unchanged onfollow-up CT scans during 10 months of observation. A 73-year-old female nonsmoker was admitted in April 1994 forinvestigation of enlarged right mediastinal lymph nodes revealed bychest radiograph following a recent increase in exertional dyspnea. Herhistory included ischemic heart disease for which she had been treatedfor 5 years, with clear worsening of her condition in the previous 12months. On admission, the patient revealed she had had dyspnea with dry coughfor 3 weeks. On physical examination, she was apyretic and orthopneic. Pulmonary auscultation revealed crackles, mainly at the bases of bothlungs. Her arterial BP was 140/95 mm Hg. A mitral systolic murmur wasnoted along with irregular tachycardia. Hepatomegaly with hepatojugularreflux and malleolar edema were noted on palpation. ECG showed sinus rhythm and left-axis deviation with auricular andventricular extrasystoles. Measurements of arterial blood gas levelswhile the patient was breathing room air revealed the following: Pao2, 54 mm Hg; Paco2, 35 mm Hg; p, H, 7.35; andarterial oxygen saturation (Sao2),91%. A chest radiograph showed cardiomegaly, bilateralalveolointerstitial infiltrates predominating in lung bases and aright-sided homogenous suprahilar fullness with convex border, suggesting mediastinal lymphadenopathy (Fig 1). A CT scan of the chest subsequentlyrevealed several lymph nodes of varying size, between 10 and 17 mm inshort-axis diameter in the transverse plane (normal size, < 10 mm),located in two mediastinal compartments, the left anterior mediastinaland the right lower paratracheal compartments. An abdominal CT scandemonstrated no lymphadenopathy. The WBC count was normal, and the, C-reactive protein level was 3 mg/L. The results of tracheobronchialendoscopy were normal. Mediastinoscopy was performed for biopsy sampling of the lymph nodes. Macroscopically, the lymph nodes appeared to be benign. The pathologyexamination reported sinus histiocytosis without inflammatory ortumoral features. RBCs and a few anthracotic pigments were visible onthe sections. The results of microbiological studies (ie,for tuberculous bacilli, bacteria, parasites, and mycoticagents) were all negative on direct examination and on cultures oflymph node tissue. The immediate outcome was favorable within 24 h after treatmentwith digitalis and diuretics, leading to improvement in the clinicalpicture and in blood gas levels while breathing room air(Pao2, 72 mm Hg; Paco2, 41 mm Hg). A follow-up chestradiograph demonstrated the clearance of parenchymal and hilarinfiltrates (Fig 2). The morphologiccharacteristics of the mediastinal lymph nodes remained unchanged onfollow-up CT scans during 10 months of observation. Case 2This 75-year-old man was a smoker (18 pack-years) who hada history of chronic obstructive bronchitis, chronic arteritisobliterans of the lower limbs, and ischemic heart disease, which hadnecessitated a previous hospital admission for acute pulmonaryedema.In May 1997, the patient was admitted with dyspnea, exertion-relatedangina, and productive cough with hemoptysis. A clinical examinationrevealed a temperature of 38.4°C, an arterial BP of 100/60 mm Hg, apulse of 80 beats/min, orthopnea, and diffuse bilateral crackles onpulmonary auscultation. A murmur due to mitral insufficiency and agrade 3 systolic murmur were noted. Sensitive hepatomegaly waspalpable with hepatojugular reflux and edema of the lower limbs.An ECG revealed sinus rhythm and ventricular extrasystoles. Arterial blood gas values, measured while the patient was breathingroom air, were as follows: Pao2, 75mm Hg; Paco2, 38 mm Hg; p, H, 7.38; and, Sao2, 95%. A chest radiographrevealed right-sided pleural effusion with heterogeneous parenchymalinfiltrates of the right hemithorax, hypertrophic hila, andcardiomegaly. Chest CT scan showed lymphadenopathy (lymph node size, 10to 16 mm on short-axis diameter) in the right paratracheal compartmentand hila. The WBC count was 15,000/μL with 76% neutrophils, and the C-reactive protein level was 123 mg/L. The pleural effusion wasa transudate. The results of pleural cytology and biopsy specimentesting were both negative. Bronchial endoscopy demonstratedinflammatory features.Mediastinoscopy was performed. The lymph nodes were macroscopicallyenlarged. Pathology investigations concluded that there were lesions ofsinus histiocytosis, without changes in lymph node structure orsurrounding tissues. The results of microbiological examinations werenegative.Treatment with antibiotics, digitalis, and diuretics was followedby resolution of the patient's temperature 48 h later andby rapid improvement in blood gas values. Initial improvement in thepleural and parenchymal features was noted on follow-up radiograph, butthe mediastinal features persisted after 8 months. This 75-year-old man was a smoker (18 pack-years) who hada history of chronic obstructive bronchitis, chronic arteritisobliterans of the lower limbs, and ischemic heart disease, which hadnecessitated a previous hospital admission for acute pulmonaryedema. In May 1997, the patient was admitted with dyspnea, exertion-relatedangina, and productive cough with hemoptysis. A clinical examinationrevealed a temperature of 38.4°C, an arterial BP of 100/60 mm Hg, apulse of 80 beats/min, orthopnea, and diffuse bilateral crackles onpulmonary auscultation. A murmur due to mitral insufficiency and agrade 3 systolic murmur were noted. Sensitive hepatomegaly waspalpable with hepatojugular reflux and edema of the lower limbs. An ECG revealed sinus rhythm and ventricular extrasystoles. Arterial blood gas values, measured while the patient was breathingroom air, were as follows: Pao2, 75mm Hg; Paco2, 38 mm Hg; p, H, 7.38; and, Sao2, 95%. A chest radiographrevealed right-sided pleural effusion with heterogeneous parenchymalinfiltrates of the right hemithorax, hypertrophic hila, andcardiomegaly. Chest CT scan showed lymphadenopathy (lymph node size, 10to 16 mm on short-axis diameter) in the right paratracheal compartmentand hila. The WBC count was 15,000/μL with 76% neutrophils, and the C-reactive protein level was 123 mg/L. The pleural effusion wasa transudate. The results of pleural cytology and biopsy specimentesting were both negative. Bronchial endoscopy demonstratedinflammatory features. Mediastinoscopy was performed. The lymph nodes were macroscopicallyenlarged. Pathology investigations concluded that there were lesions ofsinus histiocytosis, without changes in lymph node structure orsurrounding tissues. The results of microbiological examinations werenegative. Treatment with antibiotics, digitalis, and diuretics was followedby resolution of the patient's temperature 48 h later andby rapid improvement in blood gas values. Initial improvement in thepleural and parenchymal features was noted on follow-up radiograph, butthe mediastinal features persisted after 8 months. Case 3This 61-year-old male smoker (20 pack-years) was admittedin August 1998 for cough with hemoptysis and dyspnea. He had a historyof coronary artery disease that had necessitated hospital admission onthree occasions for acute congestive heart failure.On examination, auscultation indicated bilateral fine crepitant rales. Palpation revealed hepatomegaly, and there was edema of the lowerlimbs. Arterial blood gas values, measured while the patient wasbreathing room air, were as follows: Pao2, 82 mm Hg; Paco2, 35 mm Hg; p, H, 7.42; and, Sao2, 91%. An ECG showed signs ofventricular and auricular hypertrophy. Dilatation of the left ventriclewith hypokinesis of the posterior wall and a systolic ejection fractionof 52% were noted on echocardiographic examination.A chest radiograph revealed slight bilateral interstitial syndrome, predominating in the left base. A CT scan showed lymphadenopathy (lymphnode size, 10 to 15 mm on short-axis diameter) located in paratracheal, pretracheal, and subcarinal compartments. A slight pleural effusion wasvisualized in the right hemithorax (Fig 3). Biochemistry study of the pleural effusion indicated a transudate. Cytologic studies failed to reveal malignant pleural cells. Bronchialendoscopy demonstrated no abnormality.Mediastinoscopy showed enlarged lymph nodes that were macroscopicallynormal. Microscopic examination revealed sinus histiocytosis associatedwith follicular hyperplasia of the cortex, and no inflammatory lesionsor capsular changes were seen (Fig 4). The results of microbiology studies were negative.Figure 4Photomicrograph of a histology slide from amediastinal lymph node (case 3) demonstrating sinus histiocytosis withslight follicular hyperplasia of the cortex (hematoxylin-eosin-saffron, original×100).View Large Image Figure ViewerDownload (PPT)Treatment was started with digitalis and diuretics, resulting inimmediate clinical and radiologic improvement. On follow-up 5 monthsafter the acute phase, a radiograph and CT scan showed that most of theenlarged mediastinal lymph nodes and the right-sided pleural effusionhad completely disappeared. The few remaining nodes measured < 6 mmin diameter (Fig 5).Figure 5Follow-up chest CT scan (case 3) showing thedisappearance of enlarged lymph nodes 5 months afterpresentation, after the patient had undergone treatment withdigitalis and diuretics.View Large Image Figure ViewerDownload (PPT) This 61-year-old male smoker (20 pack-years) was admittedin August 1998 for cough with hemoptysis and dyspnea. He had a historyof coronary artery disease that had necessitated hospital admission onthree occasions for acute congestive heart failure. On examination, auscultation indicated bilateral fine crepitant rales. Palpation revealed hepatomegaly, and there was edema of the lowerlimbs. Arterial blood gas values, measured while the patient wasbreathing room air, were as follows: Pao2, 82 mm Hg; Paco2, 35 mm Hg; p, H, 7.42; and, Sao2, 91%. An ECG showed signs ofventricular and auricular hypertrophy. Dilatation of the left ventriclewith hypokinesis of the posterior wall and a systolic ejection fractionof 52% were noted on echocardiographic examination. A chest radiograph revealed slight bilateral interstitial syndrome, predominating in the left base. A CT scan showed lymphadenopathy (lymphnode size, 10 to 15 mm on short-axis diameter) located in paratracheal, pretracheal, and subcarinal compartments. A slight pleural effusion wasvisualized in the right hemithorax (Fig 3). Biochemistry study of the pleural effusion indicated a transudate. Cytologic studies failed to reveal malignant pleural cells. Bronchialendoscopy demonstrated no abnormality. Mediastinoscopy showed enlarged lymph nodes that were macroscopicallynormal. Microscopic examination revealed sinus histiocytosis associatedwith follicular hyperplasia of the cortex, and no inflammatory lesionsor capsular changes were seen (Fig 4). The results of microbiology studies were negative. Treatment was started with digitalis and diuretics, resulting inimmediate clinical and radiologic improvement. On follow-up 5 monthsafter the acute phase, a radiograph and CT scan showed that most of theenlarged mediastinal lymph nodes and the right-sided pleural effusionhad completely disappeared. The few remaining nodes measured < 6 mmin diameter (Fig 5). DiscussionIn contrast to alveolointerstitial edema, hypertrophy ofmediastinal lymph nodes is not a usual sign of congestive heartfailure. It is very probable that the frequency of lymphadenopathy incongestive heart failure is largely underestimated for various reasons, which can be explained mainly by the clinical presentation and thediagnostic circumstances.Slanetz et al1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar reported a study of 46 chest CT scanexaminations in patients with heart failure, which were performedduring periods of acute cardiac decompensation. Their retrospectiveanalysis identified 55% of patients with enlarged lymph nodes thatinitially were undiagnosed. The enlarged lymph node localizationsinvolved various mediastinal lymphatic chains but appeared to indicatehigher frequency in the subcarinal, paratracheal, and hilar nodes. Follow-up of 17 patients with elevated levels of pulmonary capillarywedge pressure detected 14 patients with enlarged mediastinal lymphnodes (size, 10 to 20 mm on short-axis diameter).The mechanisms underlying the pathogenesis of lymphadenopathy incardiogenic pulmonary edema are unclear. Lymphadenopathy in such casesis the expression of diffuse intrathoracic edema affecting thepulmonary parenchyma and neighboring structures, including themediastinum and associated lymph nodes.The lymphatic circulation has a primary role in the regulation ofpulmonary fluids. It ensures continuous low-pressure drainage of excessfluids from the interstitial space to the collecting ducts via thelymph nodes. These nodes are distributed along the lymph vessels andfilter the lymph during its circulation. The lymph flow rejoins thevenous blood circulation, thus enhancing interactions between the twocirculatory systems.2Wiener-Kronish JP Matthay MA Callen PW et al.Relationship of pleural effusion to pulmonary hemodynamics in patients with congestive heart failure.Am Rev Respir Dis. 1985; 132: 1253-1256PubMed Google Scholar Lymphadenopathy, therefore, mightresult from mediastinal edema, which itself is due to massive orrepeated pulmonary edema that is able to extend above the limits of thelungs and the pleura at a very developed stage of congestive cardiacfailure. Hypertrophy of the lymph nodes, thus, might be linked toedematous infiltration following lymphatic circulation overloading.Drake et al3Drake RE Dhother S Teague RA et al.Lymph flow in sheep with rapid cardiac ventricular pacing.Am J Physiol. 1997; 272: 1595-1598PubMed Google Scholar used an experimental approach in sheep todemonstrate that sudden induced cardiac insufficiency was associatedwith an increase in lymphatic flow measured in the efferent vessel of apreviously cannulated mediastinal lymph node, when venous pressure was< 15 cm H2O. This process was followedby a significant slowing of lymphatic flow for a venous pressure level>15 cm H2O. Leeds et al4Leeds SE Uhley HN Telesky LB Direct cannulation and injection lymphangiography of the canine cardiac and pulmonary efferent mediastinal lymphatics in congestive heart failure.Invest Radiol. 1981; 16: 193-200Crossref PubMed Scopus (11) Google Scholarshowed that experimental congestive heart failure in dogs caused thedilatation of lymphatic vessels, which was provoked by excessiveinterstitial fluid. Slanetz et al1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar reported aparticular hazy and heterogeneous appearance of mediastinal fat, whichwas consistently observed around enlarged lymph nodes that werevisualized on CT scans. It was attributed to local effects of edema. These studies support the hypothesis of hemodynamic mechanisms in lymphnode enlargement that are related to severe cardiac decompensation.Our report draws attention to the particular nosology of late heartdisease represented by benign enlarged lymph nodes of themediastinum and pulmonary edema. The circumstances revealing theenlarged mediastinal nodes in the three patients reported were almostidentical. All had known coronary heart disease and had experiencedseveral episodes of acute congestive heart failure with recentlyworsened symptoms. A suspicion of lymphadenopathy was based onradiographs that were taken to investigate dyspnea and heart failure. The identification of suspicious features is theoretically easier onfollow-up radiographic examinations, which provide better visibility ofhilar and mediastinal areas, after treatment to reduce pulmonary edema. Although CT scanning is much more effective for the identification andfollow-up of enlarged mediastinal lymph nodes,5Glazer G Gross BG Quint LE et al.Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping.AJR Am J Roentgenol. 1985; 144: 261-265Crossref PubMed Scopus (362) Google Scholar suchexaminations usually are not necessary in the clinical context ofcongestive heart failure. However, certain intrathoracic localizationsof Hodgkin's and non-Hodgkin's lymphomas, involving the heart andattributable to metastatic infiltration, may cause congestive heartfailure and, therefore, may present similar clinicalpictures.6Lynch M Cobbs Jr, W Miller RL et al.Massive cardiac involvement by malignant lymphoma.Cardiology. 1996; 87: 566-568Crossref PubMed Scopus (8) Google Scholar The results of lymph node biopsies in all threepatients showed similar histologic abnormalities (ie, sinushistiocytosis with slight follicular hyperplasia of the cortex in onepatient).The spectacular regression or disappearance of the nodes in one of thethree patients, who underwent therapy exclusively for heart disease, isevidence of the likelihood of cardiac origin. A similar outcomehas been reported in the literature after an acute episode ofcongestive heart failure lasting for a month.1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar Thediagnostic approach to such lymphadenopathy should be guided by theradiologic regression seen on follow-up chest radiographs or CT scansperformed while the patient is undergoing appropriate therapy forcongestive heart failure, which constitutes a decisive argument for thecongestive heart failure origin. In contrast to alveolointerstitial edema, hypertrophy ofmediastinal lymph nodes is not a usual sign of congestive heartfailure. It is very probable that the frequency of lymphadenopathy incongestive heart failure is largely underestimated for various reasons, which can be explained mainly by the clinical presentation and thediagnostic circumstances. Slanetz et al1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar reported a study of 46 chest CT scanexaminations in patients with heart failure, which were performedduring periods of acute cardiac decompensation. Their retrospectiveanalysis identified 55% of patients with enlarged lymph nodes thatinitially were undiagnosed. The enlarged lymph node localizationsinvolved various mediastinal lymphatic chains but appeared to indicatehigher frequency in the subcarinal, paratracheal, and hilar nodes. Follow-up of 17 patients with elevated levels of pulmonary capillarywedge pressure detected 14 patients with enlarged mediastinal lymphnodes (size, 10 to 20 mm on short-axis diameter). The mechanisms underlying the pathogenesis of lymphadenopathy incardiogenic pulmonary edema are unclear. Lymphadenopathy in such casesis the expression of diffuse intrathoracic edema affecting thepulmonary parenchyma and neighboring structures, including themediastinum and associated lymph nodes. The lymphatic circulation has a primary role in the regulation ofpulmonary fluids. It ensures continuous low-pressure drainage of excessfluids from the interstitial space to the collecting ducts via thelymph nodes. These nodes are distributed along the lymph vessels andfilter the lymph during its circulation. The lymph flow rejoins thevenous blood circulation, thus enhancing interactions between the twocirculatory systems.2Wiener-Kronish JP Matthay MA Callen PW et al.Relationship of pleural effusion to pulmonary hemodynamics in patients with congestive heart failure.Am Rev Respir Dis. 1985; 132: 1253-1256PubMed Google Scholar Lymphadenopathy, therefore, mightresult from mediastinal edema, which itself is due to massive orrepeated pulmonary edema that is able to extend above the limits of thelungs and the pleura at a very developed stage of congestive cardiacfailure. Hypertrophy of the lymph nodes, thus, might be linked toedematous infiltration following lymphatic circulation overloading. Drake et al3Drake RE Dhother S Teague RA et al.Lymph flow in sheep with rapid cardiac ventricular pacing.Am J Physiol. 1997; 272: 1595-1598PubMed Google Scholar used an experimental approach in sheep todemonstrate that sudden induced cardiac insufficiency was associatedwith an increase in lymphatic flow measured in the efferent vessel of apreviously cannulated mediastinal lymph node, when venous pressure was< 15 cm H2O. This process was followedby a significant slowing of lymphatic flow for a venous pressure level>15 cm H2O. Leeds et al4Leeds SE Uhley HN Telesky LB Direct cannulation and injection lymphangiography of the canine cardiac and pulmonary efferent mediastinal lymphatics in congestive heart failure.Invest Radiol. 1981; 16: 193-200Crossref PubMed Scopus (11) Google Scholarshowed that experimental congestive heart failure in dogs caused thedilatation of lymphatic vessels, which was provoked by excessiveinterstitial fluid. Slanetz et al1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar reported aparticular hazy and heterogeneous appearance of mediastinal fat, whichwas consistently observed around enlarged lymph nodes that werevisualized on CT scans. It was attributed to local effects of edema. These studies support the hypothesis of hemodynamic mechanisms in lymphnode enlargement that are related to severe cardiac decompensation. Our report draws attention to the particular nosology of late heartdisease represented by benign enlarged lymph nodes of themediastinum and pulmonary edema. The circumstances revealing theenlarged mediastinal nodes in the three patients reported were almostidentical. All had known coronary heart disease and had experiencedseveral episodes of acute congestive heart failure with recentlyworsened symptoms. A suspicion of lymphadenopathy was based onradiographs that were taken to investigate dyspnea and heart failure. The identification of suspicious features is theoretically easier onfollow-up radiographic examinations, which provide better visibility ofhilar and mediastinal areas, after treatment to reduce pulmonary edema. Although CT scanning is much more effective for the identification andfollow-up of enlarged mediastinal lymph nodes,5Glazer G Gross BG Quint LE et al.Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping.AJR Am J Roentgenol. 1985; 144: 261-265Crossref PubMed Scopus (362) Google Scholar suchexaminations usually are not necessary in the clinical context ofcongestive heart failure. However, certain intrathoracic localizationsof Hodgkin's and non-Hodgkin's lymphomas, involving the heart andattributable to metastatic infiltration, may cause congestive heartfailure and, therefore, may present similar clinicalpictures.6Lynch M Cobbs Jr, W Miller RL et al.Massive cardiac involvement by malignant lymphoma.Cardiology. 1996; 87: 566-568Crossref PubMed Scopus (8) Google Scholar The results of lymph node biopsies in all threepatients showed similar histologic abnormalities (ie, sinushistiocytosis with slight follicular hyperplasia of the cortex in onepatient). The spectacular regression or disappearance of the nodes in one of thethree patients, who underwent therapy exclusively for heart disease, isevidence of the likelihood of cardiac origin. A similar outcomehas been reported in the literature after an acute episode ofcongestive heart failure lasting for a month.1Slanetz PJ Truong M Shepard JA et al.Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.AJR Am J Roentgenol. 1998; 171: 1307-1309Crossref PubMed Scopus (38) Google Scholar Thediagnostic approach to such lymphadenopathy should be guided by theradiologic regression seen on follow-up chest radiographs or CT scansperformed while the patient is undergoing appropriate therapy forcongestive heart failure, which constitutes a decisive argument for thecongestive heart failure origin.
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