Bilateral Pleural Effusion due to Mediastinal Fibrosis Induced by Radiotherapy
1993; Elsevier BV; Volume: 104; Issue: 4 Linguagem: Inglês
10.1378/chest.104.4.1276
ISSN1931-3543
AutoresNelson Morrone, Vera Lúcia Gama e Silva Volpe, Ada Maria Dourado, Fuad Mitre, Ester Nei Aparecida Martins Coletta,
Tópico(s)Polyomavirus and related diseases
ResumoA diagnosis of Hodgkin's disease was made 20 years ago in a 37-year-old woman; treatment included thoracic irradiation and chemotherapy. She was considered cured and remained well up to one year before, when she developed bilateral pleural effusion. No evidence of activity of Hodgkin's disease was detected. The pleural liquid was an exudate, with lymphocytic predominance. On thoracoscopy, enlarged lymphatic channels in the visceral pleura were noted, with tissue confirmation. To our knowledge, this report is the first to confirm by thoracoscopy and histologic study the proposed pathophysiologic condition of this uncommon entity. A diagnosis of Hodgkin's disease was made 20 years ago in a 37-year-old woman; treatment included thoracic irradiation and chemotherapy. She was considered cured and remained well up to one year before, when she developed bilateral pleural effusion. No evidence of activity of Hodgkin's disease was detected. The pleural liquid was an exudate, with lymphocytic predominance. On thoracoscopy, enlarged lymphatic channels in the visceral pleura were noted, with tissue confirmation. To our knowledge, this report is the first to confirm by thoracoscopy and histologic study the proposed pathophysiologic condition of this uncommon entity. Pleural effusion is associated with a number of pulmonary and extrapulmonary conditions; usually, it is not difficult to determine the cause, with cardiac failure, metastatic neoplasm, pneumonia, embolism with or without infarction, and tuberculosis being the most common.Biochemistry, bacteriology, cytology, and biopsy are useful to characterize the cause; however, the diagnostic criteria vary according to the cause and sometimes clinical aspects (for example, periodic familiar polyserosites and yellow nail syndrome) or unusual tests (for example, lupus erythematosus cells in pleural fluid in discoid lupus erythematosus and creatinine in urinothorax) are the key features.In up to 10 percent of the patients, it is not possible to establish the cause;1Morrone N. Derrames pleurais: Contribuição à determinação da causa. Paraná, 1974 (Tese-Doutoramento-Universidade Estadual de Londriná-PR.-Brasil)Google Scholar perhaps some of these cases are called idiopathic because the physician is unaware of a rare cause.This article presents a patient with pleural effusion due to a very uncommon condition.2Whitcomb ME Schwarz M Pleural effusion complicating intensive mediastinal radiation therapy.Am Rev Respir Dis. 1971; 103: 100-107PubMed Google Scholar3Rodrigues-Garcia JL Fraile G Moreno MA Sanchez-Corral SA Penalva R Recurrent massive pleural effusion as a late complication of radiotherapy in Hodgkin's disease.Chest. 1991; 100: 1165-1166Abstract Full Text Full Text PDF Scopus (29) Google ScholarCase ReportThe patient, a 37-year-old married white woman, presented to our service for the first time in October 1991; she reported that at the age of 17 years she had had a supraclavicular mass; a complete investigation was made in another service, including chest radiograph, biopsy of the mass, lymphography, bone marrow biopsy, and splenectomy. The final diagnosis was Hodgkin's disease, and treatment included radiotherapy to supraclavicular fossae, mediastinum, and abdomen, as well as chemotherapy in several cycles.Unfortunately, details of diagnosis (histologic type), stage, and treatment could not be obtained. The disease was considered controlled 1 year later and regular follow-up was interrupted in 1978.Between 1981 and 1988, she had lymph node biopsy in the chin and biopsy of a mass in the right breast, as well as resection of an ovarian cyst; malignancy was not present in any of the specimens.In December 1989, slowly progressive dyspnea appeared, with anorexia and weight loss of 1 kg in 1 year. The patient smoked 2 cigarettes a day 10 years ago and only occasionally drank a small amount of alcohol.Physical examination disclosed a well-nourished woman, without any acute distress. Pulse was 80 beats/min and blood pressure was 130/80 mm Hg; cyanosis, clubbing, and neck vein distention were not present. Besides signs of bilateral pleural effusion, no other abnormality was detected.Blood cell count, SGOT, SGPT, alkaline phosphatase, T3, T4, TSH, urea, creatinine, serum proteins, blood glucose, and urinalysis were normal. There was no reaction to PPD (2 U). Chest radiograph disclosed bilateral pleural effusions. Spirometry results were as follows: FVC, 2.19 L (52 percent); FEV1, 1.78 IVs; FEF25-75 percent, 1.58 L/s; FEV1/FYC, 81.4 percent; and FEF25-75 percent/FVC, 71 percent. Cardiac echo Doppler showed slight mitral reflux; no other abnormalities were seen, including pericardial effusion. Thoracic computed tomography (slices with 10 mm) showed bilateral pleural effusion, larger in the right; no parenchymal or mediastinal abnormalities were detected.Several bilateral pleural biopsies with Cope needle were done; the fluid was clear yellow and the volume ranged between 400 and 1,200 ml in different times. Results of biochemical tests of pleural fluid were unchanged during the investigation and at the first examination, protein level was 3.3 g/dl, glucose was 91 mg/dl, DHL was 666 U/L, and amylase was 105 U/L; in other specimens, more tests were made; cholesterol, 37 mg/dl; triglycerides, 0 (two times); lupus erythematosus cells, absent; rheumatoid factor and antinuclear factor were negative. On three occasions, cytologic study showed only lymphocytes (100 percent). Three needle pleural biopsy specimens disclosed only nonspecific alterations.Fiberoptic bronchoscopy revealed only diminished lumen of the right middle lobe due to probable extrinsic compression. A transbronchial biopsy specimen showed alveolar septae edema, fibrin, and neutrophilic exudate in the alveolar lumen.At thoracoscopy, on the right, 4,000 ml of a clear fluid was drained; no nodules or masses were seen in parietal and visceral pleura. The parietal pleura was normal and through the visceral pleura a marked lymphatic engorgement in the whole lung was observed. Continuous formation of pleura fluid from the visceral pleura was noted, making complete drainage impossible. On the left, the aspect was identical but the fluid volume was less (800 ml); the rate of formation of pleural effusion was much less. Pleural adhesion with tetracycline was attempted.The left tube was removed on the second day because no more fluid was draining; on the right, the amount varied from 100 to 200 ml/d and the tube was removed on the 7th day; hydropneumothorax was still present.Right and left lung biopsy specimens obtained during thoracoscopy revealed marked lymphatic dilatation and slight lymphocytic infiltration (Fig 1).One month later, right hydropneumothorax was unchanged; on the left, a small pleural effusion was perceived. The patient felt well, w ith minimal dyspnea on exercise. New pleural puncture was not accepted by the patient.In the last visit (January 1992), the only complaint was dyspnea on great exertion; the chest radiograph showed small right pleural effusion, but without pneumothorax. On the left, a blunted costophrenie recess was noted.DiscussionPleural effusions are common in patients with Hodgkin's disease;4Harousseau JL Tricot G Gisselbrecht C Asselain B Flandrin G Les lymphomes mediastinaux de l'adulte: etude clinique et histologique de 30 cas.Nouv Presse Med. 1982; 11: 1393-1396PubMed Google Scholar pleural infiltration is detected through cytologic study and/or autopsy in half of the cases.5Billinghan ME Rawlinson DG Berry PF Kempson RL The cytodiagnosis of malignant lymphomas and Hodgkin's disease in cerebrospinal, pleural and ascitic fluids.Acta Cytol. 1975; 19: 547-556Google Scholar The other half is considered nonspecific, including drug toxicity.6Sostman HD Putman CE Gamsu G Diagnosis of chemotherapy lung.AJR. 1981; 136: 33-39Crossref PubMed Scopus (33) Google ScholarIn our case, bilateral pleural effusion appeared 17 years after initial diagnosis and successful treatment of Hodgkin's disease.No clinical or laboratory evidence of the disease was present, so it was mandatory to investigate other causes for the effusions. Common causes were not demonstrated. After irradiation, pericarditis and pericardial effusion were excluded by cardiac echo Doppler.We attributed the diagnosis of bilateral pleural effusion to lymphatic obstruction. Thoracoscopy revealed normal parietal pleura and marked lung lymphatic engorgement with biopsy specimen confirmation. The fluid was formed from visceral pleura and therefore its origin was not usual because normal pleural fluid is formed and reabsorbed by the parietal pleura.7Nakamura T Tanaka Y Fukabori T Ywasaki Y Nakawaga M Kira S The role of lymphatics in removing pleural liquid in discrete hydrothorax.Eur Respir J. 1988; 1: 826-831PubMed Google ScholarThe lung has a great number of lymphatics with valves directed to the pleura; flow becomes retrograde with pleural collection when lymphatic pressure increases many times and the pouring is greater than the lymphatic clearance of parietal pleura. This seems to be the chief mechanism in the formation of pleural effusions associated with cardiac failure.8Broaddus VC Staub NC Pleural liquid and protein turnover in health and disease.Semin Respir Med. 1987; 9: 7-12Crossref Scopus (18) Google ScholarIn our patient, this mechanism has as an additional evidence of the presence of alveolar edema that was caused by impairment in lymphatic drainage. This was not recognized by us at first. Computed tomography with thin section would probably reveal the lymphatic engorgement and/or pulmonary edema.9Hansell DM Kerr IH The role of high resolution computed tomography in the diagnosis of interstitial lung disease.Thorax. 1991; 46: 77-84Crossref PubMed Scopus (59) Google ScholarAlveolar edema could play a role in the reduction in the terminal flows; however, the restriction is best explained by the pleural effusions.Some aspects of these pleural effusions deserve special considerations, such as the characteristics of exudate and the remarkable predominance of lymphocytes; the features are constant in cases of pleural effusion due to lymphatic obstruction.10Bashinsky RB Caldwell TO Kelly DR Lymphoid interstitial pneumonitis with dysproteinemia in a child.Ala J Med Sci. 1982; 19: 265-270Google Scholar It is also important to observe that although the effusions are related to lymphatic obstruction, they are not chylothorax, as demonstrated by the absence of triglycerides.11Light RW Chyiotorax and pseudo chylotorax in pleural diseases. 2nd ed. Lea & Febiger, Philadelphia1990: 269-282Google ScholarChylothorax is explained by the rupture or obstruction of thoracic duct and in our patient this structure was certainly normal; the level of obstruction should be placed in mediastinal lymph nodes.The almost complete resolution of the left pleural effusion is explained by the pleurodesis induced by tetracycline; the control of the right effusion is not easy to explain. Lewis et al12Lewis M Kallenbach J Zaltzman M Conlan A Zwis Abramowitz J Pleurectomy in the management of massive pleural effusion associated with primary lymphoedema: demonstration of abnormal pleural lymphatics.Thorax. 1983; 38: 637-639Crossref PubMed Scopus (12) Google Scholar described a patient with bilateral pleural effusion and generalized lymphedema, which in our opinion was due to yellow nail syndrome. The patient underwent left pleurectomy; marked fibrotic thickening and lymphangiectasis in the left parietal pleura were noted as well as lymphatic neogenesis. The right effusion was not treated, but fluid was not noted. The author did not find any explanation; the same was observed in our patient and we speculate about the role of lymphatic neogenesis.In animals, thoracic radiation causes, at an early stage, actinic pneumonia and a small pleural effusion; later on, lung changes regress completely and a large pleural effusion appears, probably due to lymphatic block.13Down JD Tarbell NJ Pitfalls in the assessment of late lung damage in irradiated mice: complications related to pleural effusion [letter].Int Radiat Biol. 1989; 55: 473-478Crossref PubMed Scopus (6) Google Scholar No histologic proof was presented, but we think our patient reproduced this experimental obstruction.In 1971, Whitcomb and Schwarz2Whitcomb ME Schwarz M Pleural effusion complicating intensive mediastinal radiation therapy.Am Rev Respir Dis. 1971; 103: 100-107PubMed Google Scholar described three patients with pleural effusion several months after thoracic radiation. Based on autopsy, a different mechanism was ascribed to each patient: constrictive pericarditis, caval obstruction, and mediastinal fibrosis, as in our patient.Recently Rodrigues-Garcia et al3Rodrigues-Garcia JL Fraile G Moreno MA Sanchez-Corral SA Penalva R Recurrent massive pleural effusion as a late complication of radiotherapy in Hodgkin's disease.Chest. 1991; 100: 1165-1166Abstract Full Text Full Text PDF Scopus (29) Google Scholar described a similar patient, with bilateral serohemorrhagic pleural effusion detected 8 years after thoracic irradiation. The authors considered presumptive the diagnosis and ascribed it to impaired lymphatic drainage; no histologic proof was presented.However, we believe that a lung biopsy specimen demonstrating enlarged lymphatic vessels is a strong suggestion to this diagnosis and should be seen as diagnostic in a compatible clinical set. Pleural effusion is associated with a number of pulmonary and extrapulmonary conditions; usually, it is not difficult to determine the cause, with cardiac failure, metastatic neoplasm, pneumonia, embolism with or without infarction, and tuberculosis being the most common. Biochemistry, bacteriology, cytology, and biopsy are useful to characterize the cause; however, the diagnostic criteria vary according to the cause and sometimes clinical aspects (for example, periodic familiar polyserosites and yellow nail syndrome) or unusual tests (for example, lupus erythematosus cells in pleural fluid in discoid lupus erythematosus and creatinine in urinothorax) are the key features. In up to 10 percent of the patients, it is not possible to establish the cause;1Morrone N. Derrames pleurais: Contribuição à determinação da causa. Paraná, 1974 (Tese-Doutoramento-Universidade Estadual de Londriná-PR.-Brasil)Google Scholar perhaps some of these cases are called idiopathic because the physician is unaware of a rare cause. This article presents a patient with pleural effusion due to a very uncommon condition.2Whitcomb ME Schwarz M Pleural effusion complicating intensive mediastinal radiation therapy.Am Rev Respir Dis. 1971; 103: 100-107PubMed Google Scholar3Rodrigues-Garcia JL Fraile G Moreno MA Sanchez-Corral SA Penalva R Recurrent massive pleural effusion as a late complication of radiotherapy in Hodgkin's disease.Chest. 1991; 100: 1165-1166Abstract Full Text Full Text PDF Scopus (29) Google Scholar Case ReportThe patient, a 37-year-old married white woman, presented to our service for the first time in October 1991; she reported that at the age of 17 years she had had a supraclavicular mass; a complete investigation was made in another service, including chest radiograph, biopsy of the mass, lymphography, bone marrow biopsy, and splenectomy. The final diagnosis was Hodgkin's disease, and treatment included radiotherapy to supraclavicular fossae, mediastinum, and abdomen, as well as chemotherapy in several cycles.Unfortunately, details of diagnosis (histologic type), stage, and treatment could not be obtained. The disease was considered controlled 1 year later and regular follow-up was interrupted in 1978.Between 1981 and 1988, she had lymph node biopsy in the chin and biopsy of a mass in the right breast, as well as resection of an ovarian cyst; malignancy was not present in any of the specimens.In December 1989, slowly progressive dyspnea appeared, with anorexia and weight loss of 1 kg in 1 year. The patient smoked 2 cigarettes a day 10 years ago and only occasionally drank a small amount of alcohol.Physical examination disclosed a well-nourished woman, without any acute distress. Pulse was 80 beats/min and blood pressure was 130/80 mm Hg; cyanosis, clubbing, and neck vein distention were not present. Besides signs of bilateral pleural effusion, no other abnormality was detected.Blood cell count, SGOT, SGPT, alkaline phosphatase, T3, T4, TSH, urea, creatinine, serum proteins, blood glucose, and urinalysis were normal. There was no reaction to PPD (2 U). Chest radiograph disclosed bilateral pleural effusions. Spirometry results were as follows: FVC, 2.19 L (52 percent); FEV1, 1.78 IVs; FEF25-75 percent, 1.58 L/s; FEV1/FYC, 81.4 percent; and FEF25-75 percent/FVC, 71 percent. Cardiac echo Doppler showed slight mitral reflux; no other abnormalities were seen, including pericardial effusion. Thoracic computed tomography (slices with 10 mm) showed bilateral pleural effusion, larger in the right; no parenchymal or mediastinal abnormalities were detected.Several bilateral pleural biopsies with Cope needle were done; the fluid was clear yellow and the volume ranged between 400 and 1,200 ml in different times. Results of biochemical tests of pleural fluid were unchanged during the investigation and at the first examination, protein level was 3.3 g/dl, glucose was 91 mg/dl, DHL was 666 U/L, and amylase was 105 U/L; in other specimens, more tests were made; cholesterol, 37 mg/dl; triglycerides, 0 (two times); lupus erythematosus cells, absent; rheumatoid factor and antinuclear factor were negative. On three occasions, cytologic study showed only lymphocytes (100 percent). Three needle pleural biopsy specimens disclosed only nonspecific alterations.Fiberoptic bronchoscopy revealed only diminished lumen of the right middle lobe due to probable extrinsic compression. A transbronchial biopsy specimen showed alveolar septae edema, fibrin, and neutrophilic exudate in the alveolar lumen.At thoracoscopy, on the right, 4,000 ml of a clear fluid was drained; no nodules or masses were seen in parietal and visceral pleura. The parietal pleura was normal and through the visceral pleura a marked lymphatic engorgement in the whole lung was observed. Continuous formation of pleura fluid from the visceral pleura was noted, making complete drainage impossible. On the left, the aspect was identical but the fluid volume was less (800 ml); the rate of formation of pleural effusion was much less. Pleural adhesion with tetracycline was attempted.The left tube was removed on the second day because no more fluid was draining; on the right, the amount varied from 100 to 200 ml/d and the tube was removed on the 7th day; hydropneumothorax was still present.Right and left lung biopsy specimens obtained during thoracoscopy revealed marked lymphatic dilatation and slight lymphocytic infiltration (Fig 1).One month later, right hydropneumothorax was unchanged; on the left, a small pleural effusion was perceived. The patient felt well, w ith minimal dyspnea on exercise. New pleural puncture was not accepted by the patient.In the last visit (January 1992), the only complaint was dyspnea on great exertion; the chest radiograph showed small right pleural effusion, but without pneumothorax. On the left, a blunted costophrenie recess was noted. The patient, a 37-year-old married white woman, presented to our service for the first time in October 1991; she reported that at the age of 17 years she had had a supraclavicular mass; a complete investigation was made in another service, including chest radiograph, biopsy of the mass, lymphography, bone marrow biopsy, and splenectomy. The final diagnosis was Hodgkin's disease, and treatment included radiotherapy to supraclavicular fossae, mediastinum, and abdomen, as well as chemotherapy in several cycles. Unfortunately, details of diagnosis (histologic type), stage, and treatment could not be obtained. The disease was considered controlled 1 year later and regular follow-up was interrupted in 1978. Between 1981 and 1988, she had lymph node biopsy in the chin and biopsy of a mass in the right breast, as well as resection of an ovarian cyst; malignancy was not present in any of the specimens. In December 1989, slowly progressive dyspnea appeared, with anorexia and weight loss of 1 kg in 1 year. The patient smoked 2 cigarettes a day 10 years ago and only occasionally drank a small amount of alcohol. Physical examination disclosed a well-nourished woman, without any acute distress. Pulse was 80 beats/min and blood pressure was 130/80 mm Hg; cyanosis, clubbing, and neck vein distention were not present. Besides signs of bilateral pleural effusion, no other abnormality was detected. Blood cell count, SGOT, SGPT, alkaline phosphatase, T3, T4, TSH, urea, creatinine, serum proteins, blood glucose, and urinalysis were normal. There was no reaction to PPD (2 U). Chest radiograph disclosed bilateral pleural effusions. Spirometry results were as follows: FVC, 2.19 L (52 percent); FEV1, 1.78 IVs; FEF25-75 percent, 1.58 L/s; FEV1/FYC, 81.4 percent; and FEF25-75 percent/FVC, 71 percent. Cardiac echo Doppler showed slight mitral reflux; no other abnormalities were seen, including pericardial effusion. Thoracic computed tomography (slices with 10 mm) showed bilateral pleural effusion, larger in the right; no parenchymal or mediastinal abnormalities were detected. Several bilateral pleural biopsies with Cope needle were done; the fluid was clear yellow and the volume ranged between 400 and 1,200 ml in different times. Results of biochemical tests of pleural fluid were unchanged during the investigation and at the first examination, protein level was 3.3 g/dl, glucose was 91 mg/dl, DHL was 666 U/L, and amylase was 105 U/L; in other specimens, more tests were made; cholesterol, 37 mg/dl; triglycerides, 0 (two times); lupus erythematosus cells, absent; rheumatoid factor and antinuclear factor were negative. On three occasions, cytologic study showed only lymphocytes (100 percent). Three needle pleural biopsy specimens disclosed only nonspecific alterations. Fiberoptic bronchoscopy revealed only diminished lumen of the right middle lobe due to probable extrinsic compression. A transbronchial biopsy specimen showed alveolar septae edema, fibrin, and neutrophilic exudate in the alveolar lumen. At thoracoscopy, on the right, 4,000 ml of a clear fluid was drained; no nodules or masses were seen in parietal and visceral pleura. The parietal pleura was normal and through the visceral pleura a marked lymphatic engorgement in the whole lung was observed. Continuous formation of pleura fluid from the visceral pleura was noted, making complete drainage impossible. On the left, the aspect was identical but the fluid volume was less (800 ml); the rate of formation of pleural effusion was much less. Pleural adhesion with tetracycline was attempted. The left tube was removed on the second day because no more fluid was draining; on the right, the amount varied from 100 to 200 ml/d and the tube was removed on the 7th day; hydropneumothorax was still present. Right and left lung biopsy specimens obtained during thoracoscopy revealed marked lymphatic dilatation and slight lymphocytic infiltration (Fig 1). One month later, right hydropneumothorax was unchanged; on the left, a small pleural effusion was perceived. The patient felt well, w ith minimal dyspnea on exercise. New pleural puncture was not accepted by the patient. In the last visit (January 1992), the only complaint was dyspnea on great exertion; the chest radiograph showed small right pleural effusion, but without pneumothorax. On the left, a blunted costophrenie recess was noted. DiscussionPleural effusions are common in patients with Hodgkin's disease;4Harousseau JL Tricot G Gisselbrecht C Asselain B Flandrin G Les lymphomes mediastinaux de l'adulte: etude clinique et histologique de 30 cas.Nouv Presse Med. 1982; 11: 1393-1396PubMed Google Scholar pleural infiltration is detected through cytologic study and/or autopsy in half of the cases.5Billinghan ME Rawlinson DG Berry PF Kempson RL The cytodiagnosis of malignant lymphomas and Hodgkin's disease in cerebrospinal, pleural and ascitic fluids.Acta Cytol. 1975; 19: 547-556Google Scholar The other half is considered nonspecific, including drug toxicity.6Sostman HD Putman CE Gamsu G Diagnosis of chemotherapy lung.AJR. 1981; 136: 33-39Crossref PubMed Scopus (33) Google ScholarIn our case, bilateral pleural effusion appeared 17 years after initial diagnosis and successful treatment of Hodgkin's disease.No clinical or laboratory evidence of the disease was present, so it was mandatory to investigate other causes for the effusions. Common causes were not demonstrated. After irradiation, pericarditis and pericardial effusion were excluded by cardiac echo Doppler.We attributed the diagnosis of bilateral pleural effusion to lymphatic obstruction. Thoracoscopy revealed normal parietal pleura and marked lung lymphatic engorgement with biopsy specimen confirmation. The fluid was formed from visceral pleura and therefore its origin was not usual because normal pleural fluid is formed and reabsorbed by the parietal pleura.7Nakamura T Tanaka Y Fukabori T Ywasaki Y Nakawaga M Kira S The role of lymphatics in removing pleural liquid in discrete hydrothorax.Eur Respir J. 1988; 1: 826-831PubMed Google ScholarThe lung has a great number of lymphatics with valves directed to the pleura; flow becomes retrograde with pleural collection when lymphatic pressure increases many times and the pouring is greater than the lymphatic clearance of parietal pleura. This seems to be the chief mechanism in the formation of pleural effusions associated with cardiac failure.8Broaddus VC Staub NC Pleural liquid and protein turnover in health and disease.Semin Respir Med. 1987; 9: 7-12Crossref Scopus (18) Google ScholarIn our patient, this mechanism has as an additional evidence of the presence of alveolar edema that was caused by impairment in lymphatic drainage. This was not recognized by us at first. Computed tomography with thin section would probably reveal the lymphatic engorgement and/or pulmonary edema.9Hansell DM Kerr IH The role of high resolution computed tomography in the diagnosis of interstitial lung disease.Thorax. 1991; 46: 77-84Crossref PubMed Scopus (59) Google ScholarAlveolar edema could play a role in the reduction in the terminal flows; however, the restriction is best explained by the pleural effusions.Some aspects of these pleural effusions deserve special considerations, such as the characteristics of exudate and the remarkable predominance of lymphocytes; the features are constant in cases of pleural effusion due to lymphatic obstruction.10Bashinsky RB Caldwell TO Kelly DR Lymphoid interstitial pneumonitis with dysproteinemia in a child.Ala J Med Sci. 1982; 19: 265-270Google Scholar It is also important to observe that although the effusions are related to lymphatic obstruction, they are not chylothorax, as demonstrated by the absence of triglycerides.11Light RW Chyiotorax and pseudo chylotorax in pleural diseases. 2nd ed. Lea & Febiger, Philadelphia1990: 269-282Google ScholarChylothorax is explained by the rupture or obstruction of thoracic duct and in our patient this structure was certainly normal; the level of obstruction should be placed in mediastinal lymph nodes.The almost complete resolution of the left pleural effusion is explained by the pleurodesis induced by tetracycline; the control of the right effusion is not easy to explain. Lewis et al12Lewis M Kallenbach J Zaltzman M Conlan A Zwis Abramowitz J Pleurectomy in the management of massive pleural effusion associated with primary lymphoedema: demonstration of abnormal pleural lymphatics.Thorax. 1983; 38: 637-639Crossref PubMed Scopus (12) Google Scholar described a patient with bilateral pleural effusion and generalized lymphedema, which in our opinion was due to yellow nail syndrome. The patient underwent left pleurectomy; marked fibrotic thickening and lymphangiectasis in the left parietal pleura were noted as well as lymphatic neogenesis. The right effusion was not treated, but fluid was not noted. The author did not find any explanation; the same was observed in our patient and we speculate about the role of lymphatic neogenesis.In animals, thoracic radiation causes, at an early stage, actinic pneumonia and a small pleural effusion; later on, lung changes regress completely and a large pleural effusion appears, probably due to lymphatic block.13Down JD Tarbell NJ Pitfalls in the assessment of late lung damage in irradiated mice: complications related to pleural effusion [letter].Int Radiat Biol. 1989; 55: 473-478Crossref PubMed Scopus (6) Google Scholar No histologic proof was presented, but we think our patient reproduced this experimental obstruction.In 1971, Whitcomb and Schwarz2Whitcomb ME Schwarz M Pleural effusion complicating intensive mediastinal radiation therapy.Am Rev Respir Dis. 1971; 103: 100-107PubMed Google Scholar described three patients with pleural effusion several months after thoracic radiation. Based on autopsy, a different mechanism was ascribed to each patient: constrictive pericarditis, caval obstruction, and mediastinal fibrosis, as in our patient.Recently Rodrigues-Garcia et al3Rodrigues-Garcia JL Fraile G Moreno MA Sanchez-Corral SA Penalva R Recurrent massive pleural effusion as a late complication of radiotherapy in Hodgkin's disease.Chest. 1991; 100: 1165-1166Abstract Full Text Full Text PDF Scopus (29) Google Scholar described a similar patient, with bilateral serohemorrhagic pleural effusion detected 8 years after thoracic irradiation. The authors considered presumptive the diagnosis and ascribed it to impaired lymphatic drainage; no histologic proof was presented.However, we believe that a lung biopsy specimen demonstrating enlarged lymphatic vessels is a strong suggestion to this diagnosis and should be seen as diagnostic in a compatible clinical set. Pleural effusions are common in patients with Hodgkin's disease;4Harousseau JL Tricot G Gisselbrecht C Asselain B Flandrin G Les lymphomes mediastinaux de l'adulte: etude clinique et histologique de 30 cas.Nouv Presse Med. 1982; 11: 1393-1396PubMed Google Scholar pleural infiltration is detected through cytologic study and/or autopsy in half of the cases.5Billinghan ME Rawlinson DG Berry PF Kempson RL The cytodiagnosis of malignant lymphomas and Hodgkin's disease in cerebrospinal, pleural and ascitic fluids.Acta Cytol. 1975; 19: 547-556Google Scholar The other half is considered nonspecific, including drug toxicity.6Sostman HD Putman CE Gamsu G Diagnosis of chemotherapy lung.AJR. 1981; 136: 33-39Crossref PubMed Scopus (33) Google Scholar In our case, bilateral pleural effusion appeared 17 years after initial diagnosis and successful treatment of Hodgkin's disease. No clinical or laboratory evidence of the disease was present, so it was mandatory to investigate other causes for the effusions. Common causes were not demonstrated. After irradiation, pericarditis and pericardial effusion were excluded by cardiac echo Doppler. We attributed the diagnosis of bilateral pleural effusion to lymphatic obstruction. Thoracoscopy revealed normal parietal pleura and marked lung lymphatic engorgement with biopsy specimen confirmation. The fluid was formed from visceral pleura and therefore its origin was not usual because normal pleural fluid is formed and reabsorbed by the parietal pleura.7Nakamura T Tanaka Y Fukabori T Ywasaki Y Nakawaga M Kira S The role of lymphatics in removing pleural liquid in discrete hydrothorax.Eur Respir J. 1988; 1: 826-831PubMed Google Scholar The lung has a great number of lymphatics with valves directed to the pleura; flow becomes retrograde with pleural collection when lymphatic pressure increases many times and the pouring is greater than the lymphatic clearance of parietal pleura. This seems to be the chief mechanism in the formation of pleural effusions associated with cardiac failure.8Broaddus VC Staub NC Pleural liquid and protein turnover in health and disease.Semin Respir Med. 1987; 9: 7-12Crossref Scopus (18) Google Scholar In our patient, this mechanism has as an additional evidence of the presence of alveolar edema that was caused by impairment in lymphatic drainage. This was not recognized by us at first. Computed tomography with thin section would probably reveal the lymphatic engorgement and/or pulmonary edema.9Hansell DM Kerr IH The role of high resolution computed tomography in the diagnosis of interstitial lung disease.Thorax. 1991; 46: 77-84Crossref PubMed Scopus (59) Google Scholar Alveolar edema could play a role in the reduction in the terminal flows; however, the restriction is best explained by the pleural effusions. Some aspects of these pleural effusions deserve special considerations, such as the characteristics of exudate and the remarkable predominance of lymphocytes; the features are constant in cases of pleural effusion due to lymphatic obstruction.10Bashinsky RB Caldwell TO Kelly DR Lymphoid interstitial pneumonitis with dysproteinemia in a child.Ala J Med Sci. 1982; 19: 265-270Google Scholar It is also important to observe that although the effusions are related to lymphatic obstruction, they are not chylothorax, as demonstrated by the absence of triglycerides.11Light RW Chyiotorax and pseudo chylotorax in pleural diseases. 2nd ed. Lea & Febiger, Philadelphia1990: 269-282Google Scholar Chylothorax is explained by the rupture or obstruction of thoracic duct and in our patient this structure was certainly normal; the level of obstruction should be placed in mediastinal lymph nodes. The almost complete resolution of the left pleural effusion is explained by the pleurodesis induced by tetracycline; the control of the right effusion is not easy to explain. Lewis et al12Lewis M Kallenbach J Zaltzman M Conlan A Zwis Abramowitz J Pleurectomy in the management of massive pleural effusion associated with primary lymphoedema: demonstration of abnormal pleural lymphatics.Thorax. 1983; 38: 637-639Crossref PubMed Scopus (12) Google Scholar described a patient with bilateral pleural effusion and generalized lymphedema, which in our opinion was due to yellow nail syndrome. The patient underwent left pleurectomy; marked fibrotic thickening and lymphangiectasis in the left parietal pleura were noted as well as lymphatic neogenesis. The right effusion was not treated, but fluid was not noted. The author did not find any explanation; the same was observed in our patient and we speculate about the role of lymphatic neogenesis. In animals, thoracic radiation causes, at an early stage, actinic pneumonia and a small pleural effusion; later on, lung changes regress completely and a large pleural effusion appears, probably due to lymphatic block.13Down JD Tarbell NJ Pitfalls in the assessment of late lung damage in irradiated mice: complications related to pleural effusion [letter].Int Radiat Biol. 1989; 55: 473-478Crossref PubMed Scopus (6) Google Scholar No histologic proof was presented, but we think our patient reproduced this experimental obstruction. In 1971, Whitcomb and Schwarz2Whitcomb ME Schwarz M Pleural effusion complicating intensive mediastinal radiation therapy.Am Rev Respir Dis. 1971; 103: 100-107PubMed Google Scholar described three patients with pleural effusion several months after thoracic radiation. Based on autopsy, a different mechanism was ascribed to each patient: constrictive pericarditis, caval obstruction, and mediastinal fibrosis, as in our patient. Recently Rodrigues-Garcia et al3Rodrigues-Garcia JL Fraile G Moreno MA Sanchez-Corral SA Penalva R Recurrent massive pleural effusion as a late complication of radiotherapy in Hodgkin's disease.Chest. 1991; 100: 1165-1166Abstract Full Text Full Text PDF Scopus (29) Google Scholar described a similar patient, with bilateral serohemorrhagic pleural effusion detected 8 years after thoracic irradiation. The authors considered presumptive the diagnosis and ascribed it to impaired lymphatic drainage; no histologic proof was presented. However, we believe that a lung biopsy specimen demonstrating enlarged lymphatic vessels is a strong suggestion to this diagnosis and should be seen as diagnostic in a compatible clinical set.
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