Tuberculosis of the Thymus* J. Mark FitzGerald, M.B.;t John R. Mayo, M.D.;i Roberta R. MtUer, M.D., F.C .C.P.;§ W R. Eric jamieson, M.D.;II, and Fritz Baumgartner, M .D .t
Tuberculosis is increasing in prevalence in North America, mainly due to HIV infection. We describe an unusual case of TB of the thymus in a HIV sera-negative Filipino immigrant who preoperatively was thought to have a thymoma. We describe the clinical, radiologic and pathologic findings and review the literature on TB of the (Che'tl992;1~5) thymus.
A fter a steady decline in the number of cases of tubercu.l'. losis (TB) reported in North American over a number of years, this trend was reversed in the mid-80s. This change has been ascribed to the effects of human immunodeficiency virus (HIV) infection .' Although HIV-associated TB has been associated with a greater incidence of extrapulmonary disease , a review of the literature failed to identify any recent cases of thymic TB. In addition, to our knowledge, the CT findings in thymic TB have not been described . In this report , we describe a culture-proven case of TB of the thymus which was imaged with CT. CASE REPORT
A 20-yr-old Filipino woman presented in February 1991 with a first-trimester miscarriage . She admitted to a four-month history of cough and pos itional dyspnea , which had not responded to treatment with oral antibiotics or albuterol (salbutamol). A routine chest roentgenogram on admission showed a large anterior mediastinal mass (Fi~ 1). A contrast-enhanced scan of the chest revealed a 6 x 4 x 7-cm cyst ic and solid mass lying immediately anterior to the aortic arch in the anterior mediastinum (Fig 2). There was no associated mediastinal adenopathy or pericardial effusion . and the mass was separate from vascular structures. No abnormality was seen in the lung parenchyma. Normal th ymic tissue could not be identified . There was no evidence of continuity with the thyroid, which appeared normal. Due to the nonspecific findings, a differential diagnosis was provided which included thym ic lesions, germ cell tumor, and lymphoma. For further clarification, a Cf-gutded 18-~u~e needle aspirate was obtained, which showed lymphocytes, histiocytes, and clumps of bland thymic epithelial cells. These flndtngs were interpreted as consistent with a thymoma. The patient was then referred for an elective resection of the lesion at our institution. At the time of admission for resection, the patient had no new complaints. In particular, there was no history of night sweats , fever, weight loss, or risk factors for HIV infection. lIer history revealed that she had immigrated from the Philippines in 1987 and was uncertain as to her previous exposure to TB . She had received BCG as a child. The Bndings from clinical exam ination were unremarkable , and a repeat chest roentgenogram confirmed that the anterior mediastinal mass was unchanged . The results of spirometry and Row volume studies were norm al.
cr
*Frnm the Departments of Respiratory Medicine, Radiology, Pathology, and Cardiac Surgery, University of British Columbia, Vancouver Generaillospital, Vancouver, Canada. tDepartment of Respiratory Medicine. iDepartment of Radiolo!,'}'. §Department of Pathology, "Department of Cardiac Surgery,
Reprint requests: Dr. FitzGerald, 2iio5 Heather Street, Wmcouver General Hospital, Wmcouver, BC, Canada Vo5Z 3J5 1804
FIGURE 1. Ch est roentgenogram on admission shows mediastinal widening at the level of the aortopulmonary window. There are no associated lung parenchymal abnormalities. Surgical resection was performed through a median sternotomy. A large infiltrative anterior med iastinal mass was found , based in the inferior part of the thymus. Total thymectomy with complete resection of gross disease was accomplished, but required resection of a wedge of the left lung and mediastinal pleura. After surgery the patient was found to have a left recurrent laryngeal nerve palsy. Grossly, the thymic mass measured 11 x 7 cm . On section, there was a 3.5-cm central cavity with shaggy walls and thick yellow contents. In addition, multiple l -crn to 2-cm nodules were found throughout the gland . many of which were caseous . Histologically, there was extensive necrotizing granulomatous inRammation. Neerntizing granulomas were present in the left lung, which was adherent to the thymus. Ziehl-Neelsen stains were positive for acidfast bacilli (AFB), and th ymus tissue cultures were subsequently positive for Mycobacterium tuberculosis. Although there was an element of reactive thymic epithelial proliferation in the areas of inRammation, there was no evidence of a thymoma. Sputum smears after surgery were negative for AFB but grew M tuberculosis organisms. A skin test with 5 TV of purified protein derivative ~ave a 28-mm positive response . Serology for IIIV antibodies was negative, and both CD4 and CD8 helper cell counts were normal. The patient was started on and oral therapy with rifampin (600 rng), pyraz inamide (1.5 g), isoniazid (300 mg), and
FIGURE 2. Computed tomographic scan lit the level of the pulmonary outflow tract , demonstrating a solid lind cystic mass Iying in the anterior mediastinum . Low-density cystic areas (arrows) represent necrotic areas within tuberculosis of thymus. TUberculosis of the Thymus (FitzGerald ellll)
ethambutol (800 mg) daily. Once the patient's organism was found to be fully sensitive, the ethambutol was discontinued. Following discharge the patient is tolerating her medication well and improving symptomatically. DISCUSSION
Although TB involvement of mediastinal nodes is common, TB of the thymus is extremely rare." It has been suggested that thymic tuberculosis represents remnants of postprimary localized mediastinal lymphadenitis," A review of the English literature uncovered only three other cases of thymic tuberculosis.v" of which only one was culturepositive." The management of anterior mediastinal masses varies according to the presumptive diagnosis.t" The most common lesions" include thymoma and benign germ cell tumors, for which primary surgical therapy is appropriate, and lymphoma and malignant germ cell tumors, for which primary nonsurgical therapy is appropriate. Although CT is useful in assessing the extent of these masses, all of these lesions may present as a cystic and solid mass. As this case demonstrates, thymic TB with central necrosis can also have this appearance. An IS-gauge needle aspiration biopsy under cr guidance was then performed to establish a histologic preoperative diagnosis; however, the role of needle aspiration biopsy of anterior mediastinal masses is controversial." The reason for the controversy is illustrated in this case, where there was an erroneous interpretation of thymoma due to the presence of clumps of thymic epithelial cells and lymphocytes in the aspirate. The source of these epithelial clusters appears to be reactive thymic epithelial proliferation at the edge of the granulomas. This type of reactive change is well known to be a source of diagnostic confusion" and led to surgical excision in this case. In summary, we present a case of thymic tuberculosis which simulated a low-grade thymic epithelial tumor both radiologically and on aspiration needle biopsy. This case demonstrates that thymic TB can appear as a cystic and solid mass on contrast-enhanced CT scan. In retrospect, the correct diagnosis could only have been established nonsurgically with a very high index of suspicion. REFERENCES
1 FitzGerald JM, Grzybowski S, Allen EA. The impact of human immunodeficiency virus infection on tuberculosis and its control. Chest 1991; 100:191-200 2 Peabody JW: Brown RB, Sullivan MB, Gannon A. Mediastinal gran ulomas: a revised concept of their incidence and etiology. J Thorac Surg 1958; 35:384-96 3 Karlson KE, Timmes JJ. Granulomata of the mediastinum surgically treated and followed up to nine years. J Thorne Surg 1958; 35:617-27 4 Duprez A, Cordier R, Schmitz ~ Tuberculoma of the thymus: first case of surgical excision. J Thorac Cardiovasc Surg 1962; 44:115-20 5 Silvola HJ, Lahdesmaki M. On tuberculosis of the thymus. Ann Chir Gynaecol Fenn 1966; 55:27-30 6 Peabody JW: Walkup HE, Murphy JD. Tuberculoma of the mediastinum: report of the first culturally proved case. J Thorac Surg 1958; 35:397-99 7 Ferguson MK, Lee E, Skinner DB, Little AG. Selective operative approach for diagnosis and treatment of anterior mediastinal masses. Ann Thorae Surg 1987; 44:583-86
8 Trastek VF. Management of mediastinal tumors. Ann Thome Surg 1987; 44:227-28 9 Fradet G, Evans KG, Nelems B, Miller RR, MUller NL. Primary anterior mediastinal tumours: an investigational algorithm. Can J Surg 1989; 32: 139-42 10 Davis RD jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thome Surg 1987; 44:229-37 11 Suster S, Rosa! J. Histology of the normal thymus. Am J Surg Patholl990; 14:284-303
Christmas Candy Maker's Asthma· IgG4-Medlated Pectin Allergy Allen Kraut, M.D.; Zhi1ceng ~ng, M.D.; Allan B. Becker, M.D.; and C. Peter W Warren, M.D.
We evaluated a 29-year-oldcandy maker with DO history of asthma who developed asthma after exposure to pectin, a compound manufactured from fruits and fruit rinds. Following eight years of employment during which he added pectin to a recipe Cor Christmas candies, the candymaker developed acute respiratory symptoms. Challenge testing with the pectin mixture caused a 40 percent decrease in FEV•. Skin prick testing was positive to the pectin extract. Total 19E was normal and pectin-specmc 19E antibodies were not detected. A strongly positive pectin-specmc 19G4 antibody response was present that was not detected in a control serum and could be inhibited by the addition of pectin. Antigen-speci8c 19G4 should be sought in 19E negative cases of occupational asthma. (CIIe., 1992; 1605-07) ELISA = enz~e-linked immunosorbent assay; PBS-TIO =
phosphate-bUffered saline with 0.05" Tween 10
O
ccupational asthma has been reported following exposure to a variety of organic compounds.':' Pectin, a product manufactured from fruits and fruit rinds, is a large molecular weight organic compound (lSO,OOO to SOO,OOO Daltons) made up of a mixture of methyl-esterified galacturonan, galactan, and araban." To our knowledge, there have been only two reports of occupational asthma following pectin exposure. 5,8 Cases of occupational asthma due to high molecular weight compounds are usually, but not always, mediated by IgE antibodies.! In recent years, the role of IgG4 in the etiology of a variety of allergic disorders in general':" and occupational allergic disorders in particular" has received increasing scrutiny Thus, IgG4 may play a role in some cases of occupational asthma that are not mediated by IgE. We wish to report a case of occupational asthma with increased pectin-specific IgG4. *From the MFL-Occupational Health Center (Dr. Kraut), and the Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada (Drs. Kraut, Peng, Becker, and Warren). Reprint requests: Dr. Kraut, NAt-6I8, 700 McDermot, Winnipeg, MN, Canada R3E OW3 CHEST I 102 I 5 I NOVEMBER, 1992
180&
Tuberculosis is increasing in prevalence in North America, mainly due to HIV infection. We describe an unusual case of TB of the thymus in a HIV sera-negative Filipino immigrant who preoperatively was thought to have a thymoma. We describe the clinical, radiologic and pathologic findings and review the literature on TB of the (Che'tl992;1~5) thymus.
A fter a steady decline in the number of cases of tubercu.l'. losis (TB) reported in North American over a number of years, this trend was reversed in the mid-80s. This change has been ascribed to the effects of human immunodeficiency virus (HIV) infection .' Although HIV-associated TB has been associated with a greater incidence of extrapulmonary disease , a review of the literature failed to identify any recent cases of thymic TB. In addition, to our knowledge, the CT findings in thymic TB have not been described . In this report , we describe a culture-proven case of TB of the thymus which was imaged with CT. CASE REPORT
A 20-yr-old Filipino woman presented in February 1991 with a first-trimester miscarriage . She admitted to a four-month history of cough and pos itional dyspnea , which had not responded to treatment with oral antibiotics or albuterol (salbutamol). A routine chest roentgenogram on admission showed a large anterior mediastinal mass (Fi~ 1). A contrast-enhanced scan of the chest revealed a 6 x 4 x 7-cm cyst ic and solid mass lying immediately anterior to the aortic arch in the anterior mediastinum (Fig 2). There was no associated mediastinal adenopathy or pericardial effusion . and the mass was separate from vascular structures. No abnormality was seen in the lung parenchyma. Normal th ymic tissue could not be identified . There was no evidence of continuity with the thyroid, which appeared normal. Due to the nonspecific findings, a differential diagnosis was provided which included thym ic lesions, germ cell tumor, and lymphoma. For further clarification, a Cf-gutded 18-~u~e needle aspirate was obtained, which showed lymphocytes, histiocytes, and clumps of bland thymic epithelial cells. These flndtngs were interpreted as consistent with a thymoma. The patient was then referred for an elective resection of the lesion at our institution. At the time of admission for resection, the patient had no new complaints. In particular, there was no history of night sweats , fever, weight loss, or risk factors for HIV infection. lIer history revealed that she had immigrated from the Philippines in 1987 and was uncertain as to her previous exposure to TB . She had received BCG as a child. The Bndings from clinical exam ination were unremarkable , and a repeat chest roentgenogram confirmed that the anterior mediastinal mass was unchanged . The results of spirometry and Row volume studies were norm al.
cr
*Frnm the Departments of Respiratory Medicine, Radiology, Pathology, and Cardiac Surgery, University of British Columbia, Vancouver Generaillospital, Vancouver, Canada. tDepartment of Respiratory Medicine. iDepartment of Radiolo!,'}'. §Department of Pathology, "Department of Cardiac Surgery,
Reprint requests: Dr. FitzGerald, 2iio5 Heather Street, Wmcouver General Hospital, Wmcouver, BC, Canada Vo5Z 3J5 1804
FIGURE 1. Ch est roentgenogram on admission shows mediastinal widening at the level of the aortopulmonary window. There are no associated lung parenchymal abnormalities. Surgical resection was performed through a median sternotomy. A large infiltrative anterior med iastinal mass was found , based in the inferior part of the thymus. Total thymectomy with complete resection of gross disease was accomplished, but required resection of a wedge of the left lung and mediastinal pleura. After surgery the patient was found to have a left recurrent laryngeal nerve palsy. Grossly, the thymic mass measured 11 x 7 cm . On section, there was a 3.5-cm central cavity with shaggy walls and thick yellow contents. In addition, multiple l -crn to 2-cm nodules were found throughout the gland . many of which were caseous . Histologically, there was extensive necrotizing granulomatous inRammation. Neerntizing granulomas were present in the left lung, which was adherent to the thymus. Ziehl-Neelsen stains were positive for acidfast bacilli (AFB), and th ymus tissue cultures were subsequently positive for Mycobacterium tuberculosis. Although there was an element of reactive thymic epithelial proliferation in the areas of inRammation, there was no evidence of a thymoma. Sputum smears after surgery were negative for AFB but grew M tuberculosis organisms. A skin test with 5 TV of purified protein derivative ~ave a 28-mm positive response . Serology for IIIV antibodies was negative, and both CD4 and CD8 helper cell counts were normal. The patient was started on and oral therapy with rifampin (600 rng), pyraz inamide (1.5 g), isoniazid (300 mg), and
FIGURE 2. Computed tomographic scan lit the level of the pulmonary outflow tract , demonstrating a solid lind cystic mass Iying in the anterior mediastinum . Low-density cystic areas (arrows) represent necrotic areas within tuberculosis of thymus. TUberculosis of the Thymus (FitzGerald ellll)
ethambutol (800 mg) daily. Once the patient's organism was found to be fully sensitive, the ethambutol was discontinued. Following discharge the patient is tolerating her medication well and improving symptomatically. DISCUSSION
Although TB involvement of mediastinal nodes is common, TB of the thymus is extremely rare." It has been suggested that thymic tuberculosis represents remnants of postprimary localized mediastinal lymphadenitis," A review of the English literature uncovered only three other cases of thymic tuberculosis.v" of which only one was culturepositive." The management of anterior mediastinal masses varies according to the presumptive diagnosis.t" The most common lesions" include thymoma and benign germ cell tumors, for which primary surgical therapy is appropriate, and lymphoma and malignant germ cell tumors, for which primary nonsurgical therapy is appropriate. Although CT is useful in assessing the extent of these masses, all of these lesions may present as a cystic and solid mass. As this case demonstrates, thymic TB with central necrosis can also have this appearance. An IS-gauge needle aspiration biopsy under cr guidance was then performed to establish a histologic preoperative diagnosis; however, the role of needle aspiration biopsy of anterior mediastinal masses is controversial." The reason for the controversy is illustrated in this case, where there was an erroneous interpretation of thymoma due to the presence of clumps of thymic epithelial cells and lymphocytes in the aspirate. The source of these epithelial clusters appears to be reactive thymic epithelial proliferation at the edge of the granulomas. This type of reactive change is well known to be a source of diagnostic confusion" and led to surgical excision in this case. In summary, we present a case of thymic tuberculosis which simulated a low-grade thymic epithelial tumor both radiologically and on aspiration needle biopsy. This case demonstrates that thymic TB can appear as a cystic and solid mass on contrast-enhanced CT scan. In retrospect, the correct diagnosis could only have been established nonsurgically with a very high index of suspicion. REFERENCES
1 FitzGerald JM, Grzybowski S, Allen EA. The impact of human immunodeficiency virus infection on tuberculosis and its control. Chest 1991; 100:191-200 2 Peabody JW: Brown RB, Sullivan MB, Gannon A. Mediastinal gran ulomas: a revised concept of their incidence and etiology. J Thorac Surg 1958; 35:384-96 3 Karlson KE, Timmes JJ. Granulomata of the mediastinum surgically treated and followed up to nine years. J Thorne Surg 1958; 35:617-27 4 Duprez A, Cordier R, Schmitz ~ Tuberculoma of the thymus: first case of surgical excision. J Thorac Cardiovasc Surg 1962; 44:115-20 5 Silvola HJ, Lahdesmaki M. On tuberculosis of the thymus. Ann Chir Gynaecol Fenn 1966; 55:27-30 6 Peabody JW: Walkup HE, Murphy JD. Tuberculoma of the mediastinum: report of the first culturally proved case. J Thorac Surg 1958; 35:397-99 7 Ferguson MK, Lee E, Skinner DB, Little AG. Selective operative approach for diagnosis and treatment of anterior mediastinal masses. Ann Thorae Surg 1987; 44:583-86
8 Trastek VF. Management of mediastinal tumors. Ann Thome Surg 1987; 44:227-28 9 Fradet G, Evans KG, Nelems B, Miller RR, MUller NL. Primary anterior mediastinal tumours: an investigational algorithm. Can J Surg 1989; 32: 139-42 10 Davis RD jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thome Surg 1987; 44:229-37 11 Suster S, Rosa! J. Histology of the normal thymus. Am J Surg Patholl990; 14:284-303
Christmas Candy Maker's Asthma· IgG4-Medlated Pectin Allergy Allen Kraut, M.D.; Zhi1ceng ~ng, M.D.; Allan B. Becker, M.D.; and C. Peter W Warren, M.D.
We evaluated a 29-year-oldcandy maker with DO history of asthma who developed asthma after exposure to pectin, a compound manufactured from fruits and fruit rinds. Following eight years of employment during which he added pectin to a recipe Cor Christmas candies, the candymaker developed acute respiratory symptoms. Challenge testing with the pectin mixture caused a 40 percent decrease in FEV•. Skin prick testing was positive to the pectin extract. Total 19E was normal and pectin-specmc 19E antibodies were not detected. A strongly positive pectin-specmc 19G4 antibody response was present that was not detected in a control serum and could be inhibited by the addition of pectin. Antigen-speci8c 19G4 should be sought in 19E negative cases of occupational asthma. (CIIe., 1992; 1605-07) ELISA = enz~e-linked immunosorbent assay; PBS-TIO =
phosphate-bUffered saline with 0.05" Tween 10
O
ccupational asthma has been reported following exposure to a variety of organic compounds.':' Pectin, a product manufactured from fruits and fruit rinds, is a large molecular weight organic compound (lSO,OOO to SOO,OOO Daltons) made up of a mixture of methyl-esterified galacturonan, galactan, and araban." To our knowledge, there have been only two reports of occupational asthma following pectin exposure. 5,8 Cases of occupational asthma due to high molecular weight compounds are usually, but not always, mediated by IgE antibodies.! In recent years, the role of IgG4 in the etiology of a variety of allergic disorders in general':" and occupational allergic disorders in particular" has received increasing scrutiny Thus, IgG4 may play a role in some cases of occupational asthma that are not mediated by IgE. We wish to report a case of occupational asthma with increased pectin-specific IgG4. *From the MFL-Occupational Health Center (Dr. Kraut), and the Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada (Drs. Kraut, Peng, Becker, and Warren). Reprint requests: Dr. Kraut, NAt-6I8, 700 McDermot, Winnipeg, MN, Canada R3E OW3 CHEST I 102 I 5 I NOVEMBER, 1992
180&
