Tuberculosis of the Oral Cavity Misdiagnosed as Precancerous Lesion.

INTRODUCTION: The aim of this case report was to discuss an extremely rare oral lesion as a result of primary pulmonary tuberculosis. CASE REPORT: In this case report, the patient with refractory painless ulceration at ventral surface of the tongue was described. Detailed medical history was taken followed by clinical examination of the oral mucosa and palpation of regional lymph nodes. Clinical examination revealed ulceration on the patient's ventro-lateral surface of the tongue, approximately two centimeters in diameter. Palpation of regional lymph nodes has not revealed enlargement. The toluidine blue test of the suspected lesion was performed at each control examination. Biopsy samples for histopathologic diagnosis were taken three times. The analysis of the first biopsy sample for histopathology revealed a non-specific inflammation, the second biopsy revealed a caseous necrosis without positive Ziehl-Neelsen staining and the third biopsy revealed a granulomatous inflammation which was highly suspicious of sarcoidosis. During hospitalization, the patient underwent a complete physical examination, and laboratory and radiological diagnostics. Physical chest examination revealed bilaterally coarse crepitations and laboratory findings of his complete blood count revealed normocytic anemia of chronic disease. Radiographic examination of lungs showed multiple small nodules bilaterally and positive direct sputum smear.
CONCLUSION: Although oral tuberculosis is a rare condition, it must be taken into account in differential diagnosis of refractory painless oral ulcers.

Introduction

Despite advances in diagnostic and therapeutic opportunities, tuberculosis (TB) still remains one of the leading causes of death around the world. The World Health Organization (WHO) reported the incidence of 9.6 million global cases of TB in 2014, predominantly in South-East Asia and Western Pacific nations (). In the last ten years, the prevalence of TB has decreased. The incidence of TB in Croatia is lower than the average incidence in the European region of the WHO (12.4/100 000 in 2013), but it still falls short of morbidity in developed countries (). Risk factors for developing TB include medical conditions that reduce host immunity, such as diabetes or cancer, taking immunosuppressive drugs, HIV infection, elderly age (). TB is a chronic infectious, granulomatous disease caused by Mycobacterium tuberculosis which is usually confined to the lungs, albeit it may affect almost any organ in the body (skin, kidneys, pharynx, bones, gastrointestinal tract, central nervous system and lymphatic system) (). Tuberculosis usually occurs in its secondary form, as a result reactivation of a latent infection. It is estimated that one third of the world population, or about 2 billion people, have been affected with Mycobacterium tuberculosis, which are mainly asymptomatic infections (). Primary oral TB has rarely been described and usually oral TB is secondary manifestation of pulmonary TB through contaminated sputum or hematogenous spread. Oral lesions as initial manifestations of TB have also been described and are thought to be consequence of active pulmonary TB (). Oral TB is very rare in Croatia, as is the case in other countries such as Japan (). Oral TB lesions are found in 0.05%-5% of infected patients, mostly as chronic painless ulcers (, ). Secondary oral TB is usually seen on the tongue, lips, buccal mucosa, palate, gingiva and lingual frenulum (-). The preferred regimen for treating adults with TB consists of intensive phase of antituberculosis agents with isoniazid, rifampicin, ethambutol, pyrazinamide during two months followed by a continuous phase with isoniazid and rifampicin during four months ().

The aim of this case report was to describe an extremely rare oral lesion as a result of primary pulmonary tuberculosis, which was initially misdiagnosed as precancerous oral lesion.

Case report

The present case report describes a 68-year-old male patient who was referred to Department of Oral Medicine, School of Dental Medicine, University of Zagreb. He was complaining about painless tongue ulceration (Figure 1). A detailed medical history, clinical examination of the oral mucosa and palpation of regional lymph nodes were performed during the first examination. The toluidine test of suspected lesion was performed at each control examination. The first and second biopsy samples for histopathologic analysis were taken at the Department of Oral Surgery. The analysis of the first biopsy sample for histopathology revealed a non-specific inflammation, the second sample revealed caseous necrosis without positive Ziehl-Neelsen staining. The third biopsy was taken at the Department for Head and neck Surgery, Clinic for Tumors, Clinical Hospital Center “Sisters of Mercy”. After taking the third biopsy sample, histopathology revealed granulomatous inflammation, which was highly suspected to be sarcoidosis (Figure 2), and the patient was further referred to the Department of Clinical Immunology and Rheumatology, Clinical Hospital Centre Zagreb where active TB was suspected.

Figure 1

Tongue ulceration of the patient with active lung tuberculosis

Figure 2

Microphotograph showing granuloma with central caseous necrosis

During hospitalization at the Department of Clinical Immunology and Rheumatology, Clinical Hospital Centre Zagreb the patient underwent a complete physical examination, and laboratory and radiological diagnostics. From a detailed medical history of the patient, we found out that he was healthy, was not taking any medication, and had no registered allergy. He was a cigarette smoker and alcohol consumer. He only reported a slight weight loss, but without signs of fever, cough or chest pain. Clinical examination revealed ulceration on his ventro-lateral surface of the tongue, approximately two centimeters in diameter. The remaining oral mucosa was without any clinical changes and symptoms. Palpation of regional lymph nodes has not revealed any enlargements. The toluidine test of the suspected lesion was performed at each control examination but it was always negative. During hospitalization at the Department of Clinical Immunology and Rheumatology, Clinical Hospital Centre Zagreb, physical chest examination revealed a bilaterally coarse crepitation and laboratory findings of his complete blood count revealed normocytic anemia of chronic disease. Radiographic examination of lungs showed multiple small nodules bilaterally and positive direct sputum smear confirmed the diagnosis of active primary lung TB (Figures 3-4).

Figure 3

Chest radiograph demonstrating multiple small nodules bilaterally

Figure 4

Antero-posterior (AP) view of chest radiograph

The patient was treated with four standard antituberculosis agents as following isoniazid (1x 400 mg), rifampicin (2x 300 mg), ethambutol (3x 400 mg) and pyrazinamide (3x 500 mg) and his ulcerated lesion of the tongue rapidly improved along with pulmonary status (Figure 5).

Figure 5

Lesion of the tongue rapidly improved along with pulmonary status after therapy with anti tuberculosis agents

Discussion

Although there has been an increase in the incidence of extrapulmonary TB due to rare clinical presentations, it is still an underdiagnosed entity (). This case report describes a painless oral ulcer as secondary lesion of active primary lung TB without other specific pulmonary symptoms. In the beginning, we thought that patient was unaware of the tongue thrusting either on remaining tooth 33 and/or inadequate denture and he was given a topical steroid (betamethasone) unguent in orabase to be applied four times a day and the lesion subsided. Moreover, the lesion subsided after two weeks of topical steroid treatment, only to reappear again after one month when the first biopsy was taken. The lesion subsided again on the same topical steroid treatment. After that, the lesion reappeared and the second biopsy was taken. It is interesting to mention that caseous necrosis was revealed only in the second biopsy sample, while Ziehl-Neelsen staining was negative and no acid-fast bacilli were identified. After taking the third biopsy of the sample, it was confirmed that a highly suspected granulomatous inflammation was sarcoidosis and the patient was further referred to hospital where active TB was suspected. During hospitalization the patient was treated by a combination of four standard antituberculosis agents: isoniazid, rifampicin, ethambutol and pyrazinamide. After the treatment, his ulcerated lesion of the tongue rapidly improved along with pulmonary status.

Oral TB is rarely seen and mostly recognized through case reports. This infection spreads via respiratory droplets. The mechanism of oral mucosa inoculation with TB is poorly understood (). Obviously, an intact mucosa together with saliva and its antimicrobial enzymes is known to inhibit many microbial agents such as HIV. Clinically, these changes are non-specific, such as ulcers or nodules, but can also manifest as lesions within the jaw, such as osteomyelitis or radiolucency (, ). A biopsy of oral lesion is often insufficient to establish a diagnosis because granulomatous changes may not be present in early stages of the disease and acid-fast bacilli are hard to prove in sample (). The literature data show that only a small number of histopathological specimens stain have been positive for acid-fast bacilli, hence a negative result should not be exclusive for a diagnosis of TB ().

Oral TB malignancy was highly suspected due to the chronic nature of non-healing ulcers in a large number of case reports on oral tuberculosis, a finding which was also seen in the present case. Furthermore, oral TB lesions were painful in most of the published case reports. However, in our case, there was no evidence of painful lesions.

Differential diagnosis regarding this case was as follows: oral cancer, traumatic lesion, major recurrent aphthous ulcer, orofacial granulomatosis, Wegener’s granulomatosis, self-inflicted lesions, sarcoidosis, foreign body reaction, tertiary syphilis, deep fungal infections (histoplasmosis), Behçetˈs disease, and oral manifestation of Crohnˈs disease (, ).

This case report highlights the necessity for physicians to remain cognizant of the rare manifestation of oral tuberculosis. As seen also in other case reports on oral TB, refractory ulcerative tongue lesions should be highly suspicious for oral TB. A detailed medical patient history, clinical and histopathological examination can be insufficient for establishing diagnosis. Radiological examination and laboratory confirmation are mandatory for establishing diagnosis ().

Conclusion

In conclusion, despite being a rare manifestation of tuberculosis, oral lesions should be included in differential diagnosis of lesions in the oral cavity in general, especially for lesions not responding to conventional antibiotic, anti-inflammatory treatment, or for lesions with biopsy negative for malignancy. Considering the possibility of tuberculosis as part of differential diagnosis for chronic oral lesions may lead to earlier diagnosis and treatment, thus preventing further dissemination of disease.