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Inflammatory Pseudotumor of the Thymus
Inflammatory Pseudohunor of the Thymus Noam Harpaz, Ph.D., M.D., Allen R. Gribetz, M.D., Daniel J. Krellenstein, M.D., Ph.D., and Albert0 M. Marchevsky, M.D.
ABSTRACT A 44-year-old man with inflammatory pseudotumor of the thymus is reported. The patient was seen with fever, myalgia, and dyspnea and was found to have an anterior mediastinal mass and bilateral pleural effusions. The resected lesion consisted of a wellcircumscribed mass of chronic inflammatory and fibrous tissue that virtually replaced the thymus. There was no morphological evidence of neoplasia. The patient's symptoms and roentgenographic abnormalities resolved with excision of most of the mass. To our knowledge, this report is the first instance of inflammatory pseudotumor of the thymus.
The term inflammatory pseudotumor has been applied to a group of unusual, slow-growing mass lesions that simulates neoplasms but consists of inflammatory and mesenchymal tissue elements that most authorities regard as reactive rather than neoplastic in nature. The etiology and pathogenesis of inflammatory pseudotumors are unclear. They have been described most frequently in the lung [l-31, but sporadic cases have also been reported in other sites, including the thyroid, pleura, liver, kidney, common bile duct, spinal cord, testis, scrotum, and soft tissues. We describe a patient with an inflammatory pseudotumor of the thymus. To our knowledge, a pseudotumor in this location has not been previously reported. A 44-year-old man with no previous illness or operations was admitted to this hospital with a three-week history of temperature to 102°F(38.8"C),night sweats, myalgias, and dyspnea. Physical examination results were notable only for decreased breath sounds and dullness at both lung bases. Chest roentgenograms showed an anterior mediastinal mass and bilateral pleural effusions. Computed tomography demonstrated a 7.0-cm nonhomogeneous anterior mediastinal mass located to the left of the midline, extending posteriorly toward the left side of the pulmonary artery and left pulmonary hilum, with apparent involvement of the adjacent pleura and posterior displacement of the aortic arch and trachea (Fig 1).Results of complete blood count were normal except for 11,000 white blood cells/mm3with a normal differential count. Values for other laboratory studies were norFrom the Departments of Pathology, Medicine, and Surgery, the Mount Sinai Medical Center. New York, NY. Accepted for publication Nov 29, 1985. Address reprint requests to Dr.Harpaz, Department of Pathology, The Mount Sinai Medical Center, 1 Gustave L. Levy PI, New York, NY 10029.
331
Ann Thorac Surg 42:331-333, Sep 1986
ma1 except for an alkaline phosphatase level of 525 mu/ ml (normal, 30-95 mU/ml). Reaction to purified intermediate protein derivative of tuberculin was negative, and VDRL antigen was nonreactive. Results of a liver scan and liver biopsy were normal. A left-sided thoracoscopy revealed dense fibrous and fibrinous pleural adhesions, and 500 ml of clear yellow exudate was removed. Pleural biopsy specimens showed chronic, nonspecific inflammation. A left-sided anterior parasternal mediastinotomy revealed a firm, well-circumscribed thymic mass that was not attached to the chest wall. A biopsy specimen showed thymic tissue with chronic inflammation and fibrosis. A median sternotomy was performed, and a 10-cm hard, well-circumscribed mass was found replacing the left lobe of the thymus, extending cephalad to the thyroid and posteriorly to the aorticopulmonary window. It was adherent to the parietal pleura, pericardium, and roots of the aorta and pulmonary artery. The right thymic lobe was also enlarged and indurated. Frozen-section biopsy specimens again showed thymic tissue with chronic inflammation and fibrosis. The mass was dissected from the pericardium and resected along with the attached mediastinal fat, leaving small amounts of tumor tissue on the aorta and main pulmonary artery in the aorticopulmonary window. Postoperatively, the patient did well and the alkaline phosphatase level returned to normal. Three weeks later, he became febrile and complained of chest pain. Multiple blood cultures were negative, and the electrocardiogram was unremarkable. Roentgenogram showed an enlarged cardiac silhouette, and echocardiogram showed a pericardial effusion. The patient was treated with aspirin for presumed postpericardiotomy syndrome, with remission of the fever, chest pain, and effusion. He has been well for the past year, and the chest roentgenogram has remained normal. The resected specimen consisted of a 10 x 7 x 2.2-cm well-circumscribed mass of firm, white fibrous tissue with scattered islands of softer tan-yellow tissue (Fig 2). Histologically, it consisted of a thymus almost completely effaced by chronic inflammatory and fibrous tissue. Most of the mass consisted of fibrous tissue composed of thin collagen bundles with numerous fibroblasts and a mixed inflammatory infiltrate of mature plasma cells, lymphocytes, occasional eosinophils, and a few neutrophils. The fibroblasts did not exhibit cytological atypia or mitotic activity. Numerous residual foci of predominantly medullary-type thymic tissue were present and contained Hassall's corpuscles, moderately sized lymphoid follicles with germinal centers, and scattered plasmacytic infiltrates. Many foci of epithelial hy-
332 The Annals of Thoracic Surgery
Vol 42 No 3 September 1986
Fig 3. Photomicrographs of inflammatory pseudotumor showing thymic tissue surrounded by inflammatory fibrous tissue. ( A ) Note irregular proliferation of thymic epithelium and lymphoid follicle with germinal center. ( H B E ; x 40.) (B) Residual thymic tissue surrounded by fibrous tissue with numerous plasma cells and lymphocytes. (HBE; ~ 1 0 0 . )
333 Case Report: Harpaz, Gribetz, Krellenstein, Marchevsky: Inflammatory Thymic Pseudotumor
perplasia were present (Fig 3). Occasional calcospherites were seen within the thymic and fibrous tissue. The surface of the mass consisted of a thin layer of fibrosing granulation tissue. No granulomatous inflammation was seen on multiple section. Cultures and special stains for bacteria, fungi, and acid-fast organisms were negative.
Comment The differential diagnosis of mass lesions of the thymus includes primary thymic neoplasms, metastatic tumors, and complicated intrathymic cysts [4, 51. To our knowledge, the present report is the first description of an inflammatory pseudotumor in the thymus. Its histological features are those of an exuberant fibrosing inflammatory process arising within and virtually replacing the thymus, similar to those of inflammatory pseudotumors located elsewhere. The principal differential diagnostic consideration, sclerosing mediastinitis, may be excluded on several grounds, including the circumscription of the mass, the cellularity of the fibroblastic and inflammatory cell components, the absence of keloidlike collagen bundles, and the absence of granulomatous inflammation or other evidence of microorganisms [6]. Rare instances of inflammatory pseudotumors have been reported in the anterior [7] as well as the posterior mediastinum [8]. The precise anatomical location and morphology of the single reported anterior mediastinal mass were not described, and there was no mention of thymic involvement. As is generally the case with inflammatory pseudotumors, the etiological basis for the present lesion is obscure. Systemic symptoms, which were prominent in our patient, frequently accompany inflammatory pseudotumors, particularly those that occur outside the lung, and usually resolve when the mass is excised [9]. Although some authors have interpreted this phenomenon as evidence for an infectious etiology (91, laboratory or histological evidence of infectious agents has been consistently lacking, as was true in the present case. Instances of thymitis associated with infectious diseases are infrequent and usually represent incidental thymic involvement in cases of blood-borne infections [lo]. Thymitis has been described in the course of influenza, measles, infectious mononucleosis, miliary tuberculosis, syphilis, brucellosis, and Kawasaki disease [4, 10-121,
none of which affected our patient. To the limited extent to which specific histological changes in these conditions have been documented, they are similar to the changes produced in other reticuloendothelial organs and quite different from those of our patient’s lesion [lo, 111. Thymitis can also occur in relation to thymic cysts complicated by rupture or hemorrhage [4,5]; however, there was no evidence of a preexisting cyst in our patient.
References 1. Bahadori M, Liebow AA: Plasma cell granulomas of the lung. Cancer 31:191, 1973 2. Carter D, Eggleston JC: Inflammatory pseudotumors: tumors of the lower respiratory tract. Atlas of Tumor Pathology, series 2, fascicle 17. Washington DC, Armed Forces Institute of Pathology, 1979, pp 300-307 3. Berardi RS, Lee SS, Chen HP, et al: Inflammatory pseudotumors of the lung. Surg Gynecol Obstet 156:89, 1982 4. Rosai J, Levine GD: Tumors of the thymus. In Atlas of Tumor Pathology, series 2, fascicle 13. Washington DC, Armed Forces Institute of Pathology, 1976, pp 206-211 5. Marchevsky AM, Kaneko M: Surgical Pathology of the Mediastinum. New York, Raven Press, 1984, pp 51-159 6. Eggleston JC: Sclerosing mediastinitis. In Fenoglio CM, Wolff M (eds): Progress in Surgical Pathology. New York, Masson, 1980, vol 2, pp 1-177 7. Streltsov VP, Adamovich VN, Chefranov VS, et al: Plasmacellular granulomas of the lung and mediastinum. Grudn Khir 5:59, 1980 8. Childress WG, Adie GC: Plasma cell tumors of the mediastinum and lung: report of two cases. J Thorac Surg 19:794, 1950 9. Chen KTK: Inflammatory pseudotumor of the liver. Hum Pathol 15:694, 1984 10. Symmers WS: The thymus gland. In Wright GP, Symmers WS (eds): Systemic Pathology. First edition. London, Longmans, Green, vol 1. 1966, p 279 11. Henry K: The thymus gland. In Symmers WS (ed): Systemic Pathology. Second edition. Edinburgh, Churchill Livingstone, vol 2, 1978, p 907 12. Amano S, Hazama F, Kubagawa H, et al: General pathology of Kawasaki disease. On the morphological alterations corresponding to the clinical manifestations. Acta Pathol Jpn 30:681, 1980
Additional references are available upon request from the authors.
ABSTRACT A 44-year-old man with inflammatory pseudotumor of the thymus is reported. The patient was seen with fever, myalgia, and dyspnea and was found to have an anterior mediastinal mass and bilateral pleural effusions. The resected lesion consisted of a wellcircumscribed mass of chronic inflammatory and fibrous tissue that virtually replaced the thymus. There was no morphological evidence of neoplasia. The patient's symptoms and roentgenographic abnormalities resolved with excision of most of the mass. To our knowledge, this report is the first instance of inflammatory pseudotumor of the thymus.
The term inflammatory pseudotumor has been applied to a group of unusual, slow-growing mass lesions that simulates neoplasms but consists of inflammatory and mesenchymal tissue elements that most authorities regard as reactive rather than neoplastic in nature. The etiology and pathogenesis of inflammatory pseudotumors are unclear. They have been described most frequently in the lung [l-31, but sporadic cases have also been reported in other sites, including the thyroid, pleura, liver, kidney, common bile duct, spinal cord, testis, scrotum, and soft tissues. We describe a patient with an inflammatory pseudotumor of the thymus. To our knowledge, a pseudotumor in this location has not been previously reported. A 44-year-old man with no previous illness or operations was admitted to this hospital with a three-week history of temperature to 102°F(38.8"C),night sweats, myalgias, and dyspnea. Physical examination results were notable only for decreased breath sounds and dullness at both lung bases. Chest roentgenograms showed an anterior mediastinal mass and bilateral pleural effusions. Computed tomography demonstrated a 7.0-cm nonhomogeneous anterior mediastinal mass located to the left of the midline, extending posteriorly toward the left side of the pulmonary artery and left pulmonary hilum, with apparent involvement of the adjacent pleura and posterior displacement of the aortic arch and trachea (Fig 1).Results of complete blood count were normal except for 11,000 white blood cells/mm3with a normal differential count. Values for other laboratory studies were norFrom the Departments of Pathology, Medicine, and Surgery, the Mount Sinai Medical Center. New York, NY. Accepted for publication Nov 29, 1985. Address reprint requests to Dr.Harpaz, Department of Pathology, The Mount Sinai Medical Center, 1 Gustave L. Levy PI, New York, NY 10029.
331
Ann Thorac Surg 42:331-333, Sep 1986
ma1 except for an alkaline phosphatase level of 525 mu/ ml (normal, 30-95 mU/ml). Reaction to purified intermediate protein derivative of tuberculin was negative, and VDRL antigen was nonreactive. Results of a liver scan and liver biopsy were normal. A left-sided thoracoscopy revealed dense fibrous and fibrinous pleural adhesions, and 500 ml of clear yellow exudate was removed. Pleural biopsy specimens showed chronic, nonspecific inflammation. A left-sided anterior parasternal mediastinotomy revealed a firm, well-circumscribed thymic mass that was not attached to the chest wall. A biopsy specimen showed thymic tissue with chronic inflammation and fibrosis. A median sternotomy was performed, and a 10-cm hard, well-circumscribed mass was found replacing the left lobe of the thymus, extending cephalad to the thyroid and posteriorly to the aorticopulmonary window. It was adherent to the parietal pleura, pericardium, and roots of the aorta and pulmonary artery. The right thymic lobe was also enlarged and indurated. Frozen-section biopsy specimens again showed thymic tissue with chronic inflammation and fibrosis. The mass was dissected from the pericardium and resected along with the attached mediastinal fat, leaving small amounts of tumor tissue on the aorta and main pulmonary artery in the aorticopulmonary window. Postoperatively, the patient did well and the alkaline phosphatase level returned to normal. Three weeks later, he became febrile and complained of chest pain. Multiple blood cultures were negative, and the electrocardiogram was unremarkable. Roentgenogram showed an enlarged cardiac silhouette, and echocardiogram showed a pericardial effusion. The patient was treated with aspirin for presumed postpericardiotomy syndrome, with remission of the fever, chest pain, and effusion. He has been well for the past year, and the chest roentgenogram has remained normal. The resected specimen consisted of a 10 x 7 x 2.2-cm well-circumscribed mass of firm, white fibrous tissue with scattered islands of softer tan-yellow tissue (Fig 2). Histologically, it consisted of a thymus almost completely effaced by chronic inflammatory and fibrous tissue. Most of the mass consisted of fibrous tissue composed of thin collagen bundles with numerous fibroblasts and a mixed inflammatory infiltrate of mature plasma cells, lymphocytes, occasional eosinophils, and a few neutrophils. The fibroblasts did not exhibit cytological atypia or mitotic activity. Numerous residual foci of predominantly medullary-type thymic tissue were present and contained Hassall's corpuscles, moderately sized lymphoid follicles with germinal centers, and scattered plasmacytic infiltrates. Many foci of epithelial hy-
332 The Annals of Thoracic Surgery
Vol 42 No 3 September 1986
Fig 3. Photomicrographs of inflammatory pseudotumor showing thymic tissue surrounded by inflammatory fibrous tissue. ( A ) Note irregular proliferation of thymic epithelium and lymphoid follicle with germinal center. ( H B E ; x 40.) (B) Residual thymic tissue surrounded by fibrous tissue with numerous plasma cells and lymphocytes. (HBE; ~ 1 0 0 . )
333 Case Report: Harpaz, Gribetz, Krellenstein, Marchevsky: Inflammatory Thymic Pseudotumor
perplasia were present (Fig 3). Occasional calcospherites were seen within the thymic and fibrous tissue. The surface of the mass consisted of a thin layer of fibrosing granulation tissue. No granulomatous inflammation was seen on multiple section. Cultures and special stains for bacteria, fungi, and acid-fast organisms were negative.
Comment The differential diagnosis of mass lesions of the thymus includes primary thymic neoplasms, metastatic tumors, and complicated intrathymic cysts [4, 51. To our knowledge, the present report is the first description of an inflammatory pseudotumor in the thymus. Its histological features are those of an exuberant fibrosing inflammatory process arising within and virtually replacing the thymus, similar to those of inflammatory pseudotumors located elsewhere. The principal differential diagnostic consideration, sclerosing mediastinitis, may be excluded on several grounds, including the circumscription of the mass, the cellularity of the fibroblastic and inflammatory cell components, the absence of keloidlike collagen bundles, and the absence of granulomatous inflammation or other evidence of microorganisms [6]. Rare instances of inflammatory pseudotumors have been reported in the anterior [7] as well as the posterior mediastinum [8]. The precise anatomical location and morphology of the single reported anterior mediastinal mass were not described, and there was no mention of thymic involvement. As is generally the case with inflammatory pseudotumors, the etiological basis for the present lesion is obscure. Systemic symptoms, which were prominent in our patient, frequently accompany inflammatory pseudotumors, particularly those that occur outside the lung, and usually resolve when the mass is excised [9]. Although some authors have interpreted this phenomenon as evidence for an infectious etiology (91, laboratory or histological evidence of infectious agents has been consistently lacking, as was true in the present case. Instances of thymitis associated with infectious diseases are infrequent and usually represent incidental thymic involvement in cases of blood-borne infections [lo]. Thymitis has been described in the course of influenza, measles, infectious mononucleosis, miliary tuberculosis, syphilis, brucellosis, and Kawasaki disease [4, 10-121,
none of which affected our patient. To the limited extent to which specific histological changes in these conditions have been documented, they are similar to the changes produced in other reticuloendothelial organs and quite different from those of our patient’s lesion [lo, 111. Thymitis can also occur in relation to thymic cysts complicated by rupture or hemorrhage [4,5]; however, there was no evidence of a preexisting cyst in our patient.
References 1. Bahadori M, Liebow AA: Plasma cell granulomas of the lung. Cancer 31:191, 1973 2. Carter D, Eggleston JC: Inflammatory pseudotumors: tumors of the lower respiratory tract. Atlas of Tumor Pathology, series 2, fascicle 17. Washington DC, Armed Forces Institute of Pathology, 1979, pp 300-307 3. Berardi RS, Lee SS, Chen HP, et al: Inflammatory pseudotumors of the lung. Surg Gynecol Obstet 156:89, 1982 4. Rosai J, Levine GD: Tumors of the thymus. In Atlas of Tumor Pathology, series 2, fascicle 13. Washington DC, Armed Forces Institute of Pathology, 1976, pp 206-211 5. Marchevsky AM, Kaneko M: Surgical Pathology of the Mediastinum. New York, Raven Press, 1984, pp 51-159 6. Eggleston JC: Sclerosing mediastinitis. In Fenoglio CM, Wolff M (eds): Progress in Surgical Pathology. New York, Masson, 1980, vol 2, pp 1-177 7. Streltsov VP, Adamovich VN, Chefranov VS, et al: Plasmacellular granulomas of the lung and mediastinum. Grudn Khir 5:59, 1980 8. Childress WG, Adie GC: Plasma cell tumors of the mediastinum and lung: report of two cases. J Thorac Surg 19:794, 1950 9. Chen KTK: Inflammatory pseudotumor of the liver. Hum Pathol 15:694, 1984 10. Symmers WS: The thymus gland. In Wright GP, Symmers WS (eds): Systemic Pathology. First edition. London, Longmans, Green, vol 1. 1966, p 279 11. Henry K: The thymus gland. In Symmers WS (ed): Systemic Pathology. Second edition. Edinburgh, Churchill Livingstone, vol 2, 1978, p 907 12. Amano S, Hazama F, Kubagawa H, et al: General pathology of Kawasaki disease. On the morphological alterations corresponding to the clinical manifestations. Acta Pathol Jpn 30:681, 1980
Additional references are available upon request from the authors.