The clinical disease of primary tuberculosis is commonly found in the lungs and regional lymph nodes. Lymphohematogenous spreading of infection results in extrapulmonary disease, such as meningoencephalitis or disseminated or miliary tuberculosis. Tuberculosis of the thymus is very uncommon, even in adulthood. We report a case of thymic tuberculosis in a 6-month-old infant who presented with a mediastinal mass.
A 6-month-old infant presented with progressive dyspnea for a week. The initial physical examination revealed low-grade fever and fine crepitation in both lungs. His body weight was 6 kg, which was less than the third percentile curve for his age. His birth had been uneventful with a birth weight of 3 kg, and he had been healthy until a month previously, when he had been hospitalized for 1 week because of fever with dyspnea, which resolved with bronchodilator therapy. He had received Calmette-Guérin bacillus vaccine at birth, and his family was not aware of any contact with tuberculosis.
He was initially diagnosed with pneumonia and given parenteral antibiotics and a bronchodilator. After 2 weeks of treatment, fever had subsided, but he still had mild tachypnea with rhonchi in both lungs. Hydrocortisone was given to him, but his condition did not improve. A chest radiograph showed the right lung was hyperaerated and herniated into the left hemithorax, and a right paratracheal mass was detected (see Fig., Supplemental Digital Content 1, http://links.lww.com/INF/B692, which showed hyperaerated and herniated right lung). Congenital lobar emphysema with a mediastinal mass was suspected.
A computed tomography (CT) scan of his chest at the level of the aortic arch revealed a well-defined middle mediastinal mass with internal amorphous calcification. Contrast injection revealed minimal rim enhancement, which made us suspect necrosis. The mass was compressing the right main bronchus, which was causing hyperaeration in the right lung (see Fig., Supplemental Digital Content 2, http://links.lww.com/INF/B693, which illustrates a middle mediastinal mass with internal calcification and minimal rim enhancement). A small subcarinal node with the same calcification as the mediastinal mass was also detected on the CT scan. The presumptive diagnosis was a mediastinal tumor such as a germ cell tumor. Serum alpha-fetoprotein, beta-human chorionic gonadotropin, lactase dehydrogenase and urine vanillylmandelic acid were not elevated at 5 ng/mL, <1.0 mIU/mL, 537 U/L and 9.30 ug/mgCr, respectively. Because accessibility of the middle mediastinal area is quite restricted, a needle biopsy was not done before operating.
We performed a right thoracotomy and found a mass that seemed to originate at the thymus impacted within the tracheal wall and extending and adhering to the superior vena cava vein. This mass was removed successfully, with tracheal repair. Two small pneumatoceles were also detected at the right upper lobe and the superior segment of the right lower lobe and ligated.
On gross examination, the mass measured 4 × 3 × 3 cm and consisted of lobulated white solid tissue with some necrosis. Microscopically, the tissue was thymus gland tissue with massive caseous granulomas consistent with tuberculosis (see Fig., Supplemental Digital Content 3, http://links.lww.com/INF/B694, which demonstrates thymic tissue with Hassall corpuscles and area of granulomas with Langhans giant cells); however, no acid-fast bacilli could be detected with Ziehl-Neelsen staining. The mediastinal lymph node also had the same findings indicating tuberculosis. Unfortunately, tissue specimens were not preserved after the operation; thus, a mycobacterium culture could not be done.
His postoperative condition was satisfactory without serious complications. A tuberculin skin test resulted in a 20-mm induration. Neither a Ziehl-Neelsen stain nor culture demonstrated any acid-fast bacilli from 3 consecutive morning gastric aspirations. Detailed histories and chest radiographs were obtained from all household members, with none showing any evidence of existing tuberculosis. Based on the histopathologic findings that indicated tuberculosis, the standard antituberculosis drug regimen, including isoniazid, rifampicin, pyrazinamide and intramuscular streptomycin, was started as treatment. He showed good clinical response to this treatment with resolution of his shortness of breath and wheezing within the first 2 weeks of treatment.
After 2 months of therapy, a chest radiograph showed normal aeration in both lungs without any abnormalities (see Fig., Supplemental Digital Content 4, http://links.lww.com/INF/B695, which showed normoaeration equally in both lungs without lesions). The pyrazinamide and streptomycin were discontinued, but he was continued on the isoniazid and rifampicin for a total of 9 months. By the end of his treatment, his body weight had caught up to the normal range for his age, and he could tolerate exercise well and had no further episodes of wheezing.
Tuberculosis of the thymus is extremely rare, with only 14 cases reported in the English literature.1–13 The characteristics and diagnoses of these cases, including our latest one, are summarized in the Table (Supplemental Digital Content 5, http://links.lww.com/INF/B696, which summarized the characteristics of 15 reported cases of thymic tuberculosis). Almost all these cases involved adolescents and adults, with only 1 case diagnosed in a preschool girl.8 Our case was a 6-month-old infant, by far the youngest patient among all the reports.
We believed that thymic tuberculosis in our patient was most likely primary tuberculosis because this disease occurs in infancy, unlike the other reports in adults, which suggested that tuberculosis of the thymus was postprimary tuberculosis resulting from localized mediastinal lymphadenitis.4 The case of the preschool girl8 also indicated primary tuberculosis, as the thymic lesion occurred simultaneously with the pulmonary lesion and featured enlarged hilar and mediastinal lymph nodes, which are typical feature of primary tuberculosis. Our patient had isolated thymic involvement without pulmonary lesions of primary tuberculosis. Animal studies have found that following aerogenic infection, the thymus gland is as likely to be infected with Mycobacterium tuberculosis as lung tissue.14 The same study also found that growth of mycobacteria in thymus gland persisted longer than that in the lungs. It is possible that primary pulmonary focus of our patient had resolved before the infection in the thymus gland became symptomatic.
The presenting symptoms in previously reported case of tuberculosis of the thymus included retrosternal chest pain, cough and progressive dyspnea. Three of the cases had an asymptomatic mediastinal mass (see Table, Supplemental Digital Content 5, http://links.lww.com/INF/B696, which summarizes the characteristics of 15 reported cases of thymic tuberculosis). Although 4 of 11 symptomatic patients had evidence of a coexisting pulmonary lesion, their presenting symptoms such as cough, dyspnea and chest pain were more indicative of a mediastinal mass. The symptoms of these patients were not usually acute, but slowly progressive, with a few months to a year between onset of symptoms and their first seeking medical care, which is the most common course of this disease in other organs. The symptoms of our case, however, showed relatively rapid progress, becoming severe enough to cause the infant’s parents to seek medical care within a week of onset. An infant’s airway, unlike an adult’s airway, is easily compressible so complications resulting from airway obstruction, such as obstructive pneumonitis, occur more rapidly and prominently.
The CT scan of our patient showed a middle mediastinal mass, which was different from all previously reported cases whose lesions were located in the anterosuperior mediastinum, the usual site of the thymus gland. However, both operative findings and histology confirmed that the resected mass of our patient from the middle mediastinum was composed of thymic tissue. This unusual location may have resulted from overdistension of the right lung in our patient, which then distorted adjacent organs, including the mediastinal structure. The CT characteristics of thymic tuberculosis in reported cases have been heterogenous, as in our patient, or indicating a cystic-solid mass, and such findings are often interpreted as thymoma, which is less common in children.15,16 Therefore, secondary investigations in young children who present with a mass of thymic origin should emphasize excluding germ cell tumor rather than thymoma or thymic tumor, as although the radiological features are similar, this is a more common etiology of a mediastinal mass in childhood.
Among the earlier reports, there were 4 cases who underwent CT-guided fine needle aspiration preoperatively. We did not perform a fine needle biopsy or aspiration in our patient, as access to the middle mediastinum is difficult and risky in infants. Even when performed, however, the cytology is usually nonspecific and potentially misleading to an incorrect diagnosis.4,9,13 Performing a Ziehl-Neelsen stain and/or cultures for M. tuberculosis on an aspirated specimen may be useful in diagnosis, but such tests are not usually done unless the physician already strongly suspects tuberculosis may be involved. The diagnosis of tuberculosis of thymus in our patient, like many reported cases, was based on typical granulomatous inflammation in the thymic tissue without microbiologic confirmation. Only 5 of the 14 cases had M. tuberculosis documented by tissue culture, and in all these patients, the tissue specimens were obtained from surgical excision of the mediastinal mass via either a thoracotomy or a median sternotomy.
Children who acquire tuberculosis are usually infected by aerogenous spreading from an adult with active pulmonary tuberculosis, especially in a family member. However, in our case, there was no apparent history, so no reason for us to perform tuberculosis-specific investigations or initially consider this in the differential diagnosis.
Our patient received 4 first-line antituberculosis drugs, including isoniazid, rifampicin, pyrazinamide and intramuscular streptomycin, to which he responded quite well. Although the tuberculosis therapy and clinical response were not reported clearly in many of the tuberculosis of the thymus cases, it appears that most of them received first-line antituberculosis drugs in various regimens. Only the case reported by Kpodonu et al9 did not receive any antituberculosis drugs, and the symptoms of this patient resolved fully after surgery and she remained asymptomatic during the 18-month postoperation during which she was followed up. Hence, because the thymic lesions were totally removed by surgical procedure before starting antituberculosis drugs in all reported cases, the response rate of thymic tuberculosis to antituberculosis treatment alone cannot be established, and the role of surgery in thymic tuberculosis remains inconclusive.
The authors acknowledge the invulnerable assistance of Supika Kritsaneepaiboon, MD, for advising on reports of radiography and computed tomography and Anupong Nitiruangjaras, MD, for providing the histopathological asisstance.
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