Diagnosis
Pathology did not find any evidence for lymphoma, other neoplastic process, rheumatologic, or infectious disease; there was evidence for a chronic inflammatory reactive process. Specifically, increased connective tissue substrate was noted, with areas of intense hyalinization, a mild to moderate chronic inflammatory infiltration with deposits of hemosiderin, and hyperplasia of the mesothelial cells. These lesions were suggestive of a chronic fibroplastic pericarditis with elements of an old hemorrhage, more likely due to effects of radiation.

Differential diagnosis
Many neoplastic conditions, among of which are thoracic, pulmonary and ovarian cancer and, lymphomas can cause accumulation of fluid in the pleura. In view of the patient's history, the possibility of persistent pleural effusion related to recurrence of Hodgkin lymphoma or a new neoplastic process should have been strongly considered. However, the absence of convincing laboratory or imaging evidence for such a diagnosis and the fact that the process did not advance during the last seven years make this possibility less likely.

Teaching points

1. Mediastinal radiotherapy can cause acute lung injury such as radiation pneumonitis, which typically occurs 2 weeks to 4 months after treatment and is usually limited to the irradiated field. Late post-radiation complications from the organs of the neck and chest include pericarditis, myocardial fibrosis, coronary artery disease, valvular abnormalities, conduction disturbances, pulmonary fibrosis, benign cysts of the thymus, esophageal carcinoma, recurrent laryngeal nerve paralysis, and thyroid dysfunction. In addition, fatigue seems to be one of the most frequently reported symptoms among long-term Hodgkin's disease survivors.
2. The most likely cause for the pericardial and pleural effusions of this patient is late effect of radiation. Pericarditis may occur in an acute, subacute, and chronic form after mediastinal radiation therapy. In a study of 499 patients with all stages of Hodgkin's disease who received mediastinal irradiation, 9.5% had developed pericarditis after a period of ten years. Post-radiation pericarditis and pleuritis may occasionally appear very late after treatment for Hodgkin lymphoma. Pericarditis is frequently self-limiting and can occur acutely in 1% of patients given radiation treatment. The use of new imaging methods facilitates the accurate detection and management of complications such as pericardial effusion.
3. The management of pleural effusion after radiation treatment is unclear. A possible therapy is pleurodesis (fusion of the visceral and parietal pleura) with a sclerosing agent. The substances preferably used for pleurodesis are, in the order of decreasing frequency of use, tetracycline, bleomycin, talc, doxycycline or minocycline. Doxycycline can be injected in the pleural cavity (500 mg in a total volume of 50 ml), through a chest tube.

References

1. Abid SH, Malhorta V, Perry MC. Radiation-induced and chemotherapy-induced pulmonary injury. Cur Opin Oncol. 2001;13:242-248.
2. Adams MJ, Lipsitz SR, Colan SD, Tarbell NJ, Treves ST, Diller L, et all. Cardiovascular status in long-term survivors of Hodkin's disease treated with chest chemotherapy. J Clin Oncol. 2004;22:3139-3148.
3. Kim HC, Nosher J, Haas A, Sweeney W, Lewis R. Cystic degeneration of thymic Hodgkin's disease following radiation therapy. Cancer. 1985;55:354-56.
4. Micke O, Schafer U, Glashorster M, Prott FJ, Willich N. Radiation-induced esophageal carcinoma 30 years after mediastinal irradiation: case report and review of the literature. Jpn J Clin Oncol. 1999;29:164-70.
5. Rosanowski F, Tigges M, Eysholdt U. Esophagomediastinal fistula and recurrent laryngeal nerve paralysis after radiotherapy of Hodgkin's disease. Laryngorhinootologie. 1995;74:516-7.
6. Knobel H, Lage JH, Lund MB, Forfang K, Nome O, Kaasa S. Late medical complications and fatigue in Hodgkin's disease survivors. J Clin Oncol 2001;Vol 19:3226-3233.
7. Cosset JM, Henry-Amar M, Pellae-Cosset B, Carde P, Girinski T, Tubiana M, et all. Pericarditis and myocardial infarction after Hodgkin's disease therapy. Int J Radiat Oncol Biol Phys. 1991;21:447-9.
8. Troughton RW, Asher CR, Klein AL. Pericarditis. Lancet. 2004;363:717-27.
9. Bronner GM, Baas P, Beijnen JH. Pleurodesis in malignant pleural effusion. Ned Tijdschr Geneeskd. 1997;141:1810-4.
10. Antony VB, Rothfuss KJ, Godbey SW, Sparks JA, Hott JW. Mechanism of tetracycline-hydrochloride-induced pleurodesis. Tetracycline-hydrochloride stimulated mesothelial cells produce a growth-factor-like activity for fibroblasts. Am Rev Respir Dis. 1992;146:1009-13.
11. Sassoon CS, Light RW, Vargas FS, Gruer SE, Wang NS. Temporal evolution of pleural fibrosis induced by intrapleural minocycline injection. Am J Respir Crit Care Med. 1995;151:731-4.
12. Chen JS, Hsu HH, Kuo SW, Tsai PR, Chen RJ, Lee JM, et all. Effects of additional minocycline pleurodesis after thoracoscopic procedures for primary spontaneous pneumothorax. Chest. 2004;125:50-5.
13. Putnam JB Jr, Light RW, Rodriguez RM, Ponn R, Olak J, Pollak JS, et all. A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer. 1999;86:1992-9.

Acknowledgments

1. The case was prepared for our website by Konstantinos N. Fragoulis, M.D.
2. We thank Eleni Handrinou, M.D., Vasilis Papadopoulos, M.D., Konstantinos Dardoufas, M.D. and Tamamidou Maria, Ph.D. for their contribution in the care of the patient.