Isolated mediastinal tuberculous lymphadenitis is a rare disease in adults. It is usually found in older, immunocompromised patients, especially those with acquired immune deficiency syndrome; however, there have also been some reports of tuberculous lymphadenitis occurring in immunocompetent patients.1 Organisms, like Mycobacterium tuberculosis, enters to the lymphatics from the site of infection in the respiratory tract, often resulting in a greater lesion in the regional lymph nodes than the original site.2 When it progresses, it causes symptoms, including epigastric discomfort or dysphagia, resulting in external compression or complications like fistula.3

In the cases of a lesion protruding on the middle esophagus, we can consider it, not only, as a tumorous lesion of the intramural or external origin, but also extrinsic compression being caused by lymphadenopathy, lymphoma or metastasis from mediastinal lymph nodes and sarcoidosis.4, 5 It is difficult to confirm a diagnosis of the lesion simply by using endoscopic findings. Examinations, including computed tomography and endoscopic ultrasonography (EUS), can contribute in making a differential diagnosis.1, 6 Herein, we report a 26-year-old woman finally diagnosed as mediastinal tuberculous lymphadenitis, which was initially manifested as esophageal subepithelial tumor.

A 26-year-old woman was referred to our hospital for an esophageal subepithelial tumor. She did not complain of any signs and symptoms. She denied cigarette smoking and alcohol drinking, and had no medical history like infectious disease. There was no specific finding on physical exams, including palpable lymph nodes. Vital sign was stable without fever. According to the laboratory results, including antibody screening test for human immunodeficiency virus (HIV), there were no remarkable findings. Esophagogastroduodenoscopy revealed a subepithelial lesion, with a size of about 15×10 mm, approximately 30 cm from the upper incisor (Fig. 1). A chest computed tomography scan showed a 49×41 mm lobulated contoured mass with a heterogeneous enhancement and internal necrosis abutting the mid-to-distal esophagus (Fig. 2). EUS showed a hypoechoic heterogeneous lesion over the fourth layer, suggesting an extra-esophageal origin (Fig. 3). EUS-guided fine-needle aspiration (FNA) (19G Procore needle; Cook®, Bloomington, IN, USA) was performed for a pathological diagnosis, and pus-like material oozed from the lesion. The histological examination revealed many granulomas and lymphoid cells in a necrotic background, which was consistent with tuberculosis (Fig. 4). Although acid fast bacilli (AFB) stain of the aspirated specimen was negative, a real-time Tb PCR test (LG Life Sciences, Seoul, Korea) showed a positive result. The patient was treated with the standard four-drug, orally administered anti-tuberculous regimen (first two months, combination of isoniazid, rifampin, ethambutol, and pyrazinamide, additional four months of 3 drug regimen except pyrazinamide), and the esophageal lesion improved after the course of medication on subsequent esophagogastroduodenoscopy (Fig. 5) and chest computed tomography (Fig. 6).

Fig. 1 Esophagogastroduodenoscopy demonstrating 15×10 mm sized subepithelial lesion. Click for larger image

Fig. 2 Chest computed tomography presenting lobulated mass abutting the mid to distal esophagus. Click for larger image

Fig. 3 Enodoscopic ultrasonography demonstrating hypererchoic heterogeneous lesion over fourth layer. Fine needle aspiration was performed. Click for larger image

Fig. 4 Histological findings of aspirated specimens. Granulomas in a necrotic background consistent with tuberculosis (Papanicolaou stain, ×200). Click for larger image

Fig. 5 Consecutive esophagogastroduodenoscopy presented improved esophageal lesion six months after anti-tuberculous medication. Click for larger image

Fig. 6 Consecutive chest computed tomography demonstrated improved esophageal lesion six months after anti-tuberculous medication. Click for larger image

Herein, we reported a rare case of mediastinal lymphadenitis diagnosed by EUS-guided FNA. To the best of our knowledge, this is the first case reported in Korea of tuberculous mediastinal lymphadenitis initially presenting as a submucosal tumor diagnosed by EUS-FNA. Compared with previous reports,4, 7 it is remarkable that there was no mucosal abnormality, including ulceration, other than a mild yellow discoloration. The discoloration of the mucosa suggested the possibility of an additional diagnosis, such as infectious diseases rather than typical subepithelial tumor. In most previous cases, the final diagnosis was made based on surgical procedures8 or endoscopic biopsy.4, 5 However, in the present case, EUS was performed initially, revealing the origin of the lesion, which mimicked a submucosal lesion. The diagnosis based on FNA of coarse hypoechoic lesion over the fourth layer should be considered.

Tuberculosis lymphadenitis is reported in 4-7% of all tuberculosis cases, and mediastinal lymphadenopathy accounts for 10% of tuberculosis cases with lymph node involvement.6, 9 Lymphadenitis is the major extrapulmonary manifestation of tuberculosis. Its incidence is higher in children and young females, and its peak age of onset is 20-40 years. The cervical nodes are the most common sites of tuberculous lymphadenopathy, and the mediastinal, axillary, and inguinal lymph nodes may also be involved.10 Mediastinal lymphadenitis results in dysphagia due to extrinsic compression, vocal cord palsy that causes recurrent laryngeal nerve palsy, or fistulation that extends to the esophageal wall.3, 5, 11, 12 Isolated lymphadenopathy is rare, and it usually occurs in HIV-positive patients.11 Tuberculous lymphadenitis in adults without lung involvement typically occurs in patients with acquired immune-deficiency syndrome and is rare in immunocompetent patients.1

The majority of previous cases have been associated with disseminated diseases or reactivation of latent tuberculosis13; however, the present case did not show an association with either, and it did not manifest any symptoms.

The endoscopic findings of mediastinal tuberculous lymphadenitis have varied among previous reports. The observed endoscopic presentations include extrinsic compression of the esophagus without mucosal changes,14 mucosal ulceration resulting in secondary tuberculosis,4, 7 and a normal presentation.12

Because differentiating tuberculous lymphadenitis from other medical conditions is problematic, a computed tomography imaging is used to evaluate the cause of extrinsic compression. A central low density and surrounding peripheral enhancement have been reported as typical characteristics of tuberculous lymphadenitis.15

In the present case, EUS and EUS-guided FNA facilitated the evaluation of lymph nodes and obtainment of tissue specimens. On EUS, tuberculous lymphadenitis is predominantly coarse and hypoechoic, with the anechoic areas suggesting necrosis.16 Hyperechoic foci suggesting patchy fibrosis or speckled calcification can also be described.6 Histologically, tuberculous lymph nodes show epithelioid cell granulomas, multinucleated giant cells, and caseous necrosis. According to Puri et al.,16 when a diagnosis was made based on cytomorphologic findings, EUS-FNA had an overall diagnostic yield of 93%, sensitivity of 71%, specificity of 100%, and positive predictive value of 100%. In this case, granuloma with necrotic background, which suggested tuberculosis, was found on a histological examination of the aspirated specimens. AFB staining of an aspirated specimen was negative, and the real-time PCR detection of M. tuberculosis (Tb) was positive. Typical caseous necrosis is present in approximately 77% of fine-needle-aspirated specimens.17 Necrotic findings are 47% of positivity.17 Real-time PCR detection of Tb is reported to have a 90.3% sensitivity, 81.8% specificity, 91.5% positive predictive value, and 79.4% negative predictive value.18 AFB staining may be positive in 25-50% of smears, with a 22.9% sensitivity and 92.4% specificity.17, 19 In the absence of definite symptoms, isolation of the tubercular bacillus or histologic evidence of caseating granulomas is required, but is often difficult to achieve.6 Although the histological diagnosis was possible in the present case, a real-time PCR detection of Tb in FNA specimens allows for the diagnosis of tuberculous lymphadenitis in cases with negative AFB staining and non-specific cytological findings. Therefore, EUS-FNA in combination with cytology and PCR analysis of Tb facilitates a higher accuracy of the diagnosis of mediastinal tuberculous lymphadenitis.

The mainstay for the treatment of Tb mediastinal lymphadenitis is medical chemotherapy. The chemotherapy regimens used to treat pulmonary tuberculosis should be considered.4, 5, 11 Both six and nine months of anti-tuberculous chemotherapy are effective.20 However, if complications—such as fistulation, bleeding, or stricture formation— are observed, surgical treatment may be considered as an adjunct to medical treatment.4, 7, 12, 15

Here, we presented our experience of a rare case of esophageal lymphadenitis presenting as an esophageal subepithelial tumor. In the absence of definite diagnostic symptoms and accompanying pulmonary involvement, the diagnosis of tuberculous mediastinal lymphadenitis can be difficult. Moreover, this condition can present as a lesion in the digestive tract. Consensus opinion supports conservative management and regular surveillance of esophageal submucosal lesions of less than 2 cm.21 However, in the case of unusual findings, such as discoloration of mucosa, EUS and FNA facilitated early diagnosis and guided treatment planning, preventing possible complications.