Laryngeal Tuberculosis and Laryngeal Cancer: Two Similar Diagnoses in an Elderly Person in Tuberculosis-Endemic Area ()
1. Introduction
Tuberculosis is a chronic bacterial infection caused by Mycobacterium tuberculosis. Pulmonary tuberculosis is the most common manifestation, but it can occur in any other organ such as larynx [1] . Pulmonary tuberculosis and laryngeal tuberculosis are the two contagious forms of tuberculosis. Laryngeal tuberculosis remains the most common granulomatous disease of the larynx. It is a rare form of extrapulmonary tuberculosis, accounting for less than 1% of all tuberculosis cases [1] [2] . It classically develops due to direct spread of Mycobacterium tuberculosis to the larynx from contaminated sputum but can also occur due to hematogenous spread [3] . Rarely isolated, it often reveals an associated lung involvement that may be clinically unrecognized [1] [2] . Its diagnosis can be challenging, as the clinical symptoms and the macroscopic lesions sometimes mimic a laryngeal cancer [2] [3] [4] .
We report a case of laryngeal tuberculosis discovered following chronic dysphonia. Through a review of the literature, we outline the epidemiological, clinical and diagnostic aspects of this pathology.
2. Case Report
A 77-year-old female Senegalese patient living in a rural area, with no particular pathological history, nor alcohol or tobacco intoxication, presented with a 2-month history of dysphonia. She reported symptoms such as dry cough and right-sided chest pain, which had been evolving for over a year. Those symptoms were associated with fever, chills, and night sweats, and she also experienced a deterioration in her performance status with physical asthenia, anorexia and weight loss. There was no personal history of tuberculosis or any tuberculosis contact. The patient was also complaining of selective dysphagia to solid food, which had been evolving for several weeks. Clinical examination revealed dysphonia with a weak, puffy voice, right pulmonary condensation syndrome rising to mid lung zone, and inflammatory suboccipital, cervical and axillary lymphadenopathies. Her standard blood test results (CBC, renal and liver functions) were unremarkable. The chest X-ray revealed a right apical excavation associated with a bilateral interstitial infiltrate (Figure 1). Direct laryngoscopy showed a budding tumoral lesion in the right ventricular band (Figure 2(a)), decreased mobility of the left vocal cord and an ulcerated epiglottis (Figure 2(b)). Pathological examination of biopsies revealed an epithelio-gigantocelullary granuloma with many lymphocytes, plasma cells, epithelioid cells and Langhans-type giant cells, associated with necrosis infiltrated by inflammatory cells. Tuberculosis diagnosis was retained. The intradermal tuberculin test was phlyctenular and sputum examination revealed acid-fast bacilli (AFB). Fasting blood glucose was normal and HIV serology was negative.
Antituberculosis treatment was started with a standard regimen of Rifampicin (R), Isoniazid (H), Ethambutol (E) and Pyrazinamide (Z). The patient clinically improved with partial recovery of the voice noticed on day 20. At day 40 of treatment, voice recovery was complete, and the patient reported significantly reduced coughing, no more dysphagia and regained appetite. The regimen was continued until M2 and follow-up laboratory tests (transaminases and uricemia) were unremarkable. Treatment will be continued according to the RH regimen for 4 months, and a follow-up chest X-ray and endoscopy are scheduled at M6 of treatment.
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Figure 1. Front chest X-ray: right apical excavation associated with bilateral interstitial infiltrate.
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Figure 2. (a) Tumoral lesion of the right ventricular band; (b) ulcerated epiglottis.
3. Discussion
Tuberculosis remains a public health concern, especially in endemic countries. Pulmonary involvement is the usual localization but it can affect any other organ, due to hematogenous dissemination. Laryngeal involvement is exceedingly rare, accounting for less than 1% of all tuberculosis cases [2] [4] . It is exceptionally primary and is usually diagnosed in patients with advanced lesions of active pulmonary tuberculosis, whether symptomatic or not [3] [5] [6] . It appears to affect both men and women, with no age predilection. The risk factors of the disease are mainly the endemic area, alcohol and/or tobacco intoxication, and immunodepression especially HIV [1] [2] . These risk factors seem to be the same for laryngeal cancer. This situation can lead to misdiagnosis in elderly persons where laryngeal cancer is the first diagnosis the diagnosis to be made in cases of chronic dysphonia. Our patient was 77 years old, living in an endemic zone, and had no particular risk factors.
The vocal cords and ventricular bands are the most frequently affected sites, accounting for around 90% of laryngeal tubercular localizations. More rarely, tuberculous granulomas occur in the arytenoids, posterior commissure, and epiglottis [7] . The routes of laryngeal contamination include aerial dissemination of the germ from a pulmonary focus (retrograde airborne route), and this contamination mode prevails in glottic localizations. In other cases, contamination may occur via hematogenous or lymphatic dissemination [5] [8] [9] [10] . The contamination mode may be difficult to identify in our case, as the airborne route remains probable due to the pulmonary focus. Lymphatic contamination is also a possibility, considering the homolateral laryngeal and lung localizations, and the existence of lymphadenopathies.
Symptoms of laryngeal tuberculosis are non-specific and clinically, it is difficult to distinguish it from a malignant tumor of the larynx. Dysphonia, however, is a constant symptom, progressing rapidly from hoarseness of voice to voice loss. It usually has a chronic course, lasting from 1 to 6 months in 85% to 100% of cases [5] [11] [12] . Other non-specific signs may also be present. Dysphagia and odynophagia are often reported, while dyspnea is much rarer and indicates advanced involvement [5] [11] . Furthermore, signs such as dry or productive cough, chest pain, fever, etc… should be systematically sought, as they may indicate associated pulmonary involvement. Soda et al., [7] and Galietti et al., [12] found associated pulmonary symptoms in all their patients diagnosed with laryngeal tuberculosis. Chest X-ray must be performed, as well as a sputum examination, which can be positive in about 20% of patients [13] . This was the case in our patient, in whom an apical excavated lesion on chest X-ray and the acid-fast bacillus found on sputum examination revealed a pulmonary localization of the infection.
Examination of the larynx relies essentially on direct laryngoscopy, which can pinpoint the location and characteristics of tuberculous lesions. They mostly appear as pseudotumoral or tumoral lesions, as reported by El Ayoubi et al. who found 90% pseudotumoral forms in their study [1] . Less often, they can be ulcerated or, when minimal, present as edema, hyperemia, or laryngeal immobility [1] [5] . The lesions are therefore not specific to tuberculosis, and this makes diagnosis difficult, particularly in elderly persons where tumor cause is the first to be suggested. This was the case in our patient, whose age and the tumoral lesion further supported the suspicion of neoplasia. Moreover, laryngeal endoscopy enables biopsies to be taken, which remain the key to diagnosis. Anatomopathological examination reveals the classic tubercular follicle, consisting of a central zone of caseation surrounded by epithelioid cells with lymphocytes, and especially the giganto-cellular aspects of Langhans cells [1] [14] [15] . Thus, the discovery of lymphocytic laryngitis in a suggestive context of tuberculosis should lead to the performance of a special Ziehl-Nielsen stain, and/or culture of the biopsy fragments on the Lowenstein-Jensen medium, allowing the identification of Mycobacterium tuberculosis. It is therefore recommended to carry out at least two biopsy fragments during endoscopy, one for the pathologist and one for the bacteriologist [10] [16] .
The curative treatment for laryngeal tuberculosis is the same as for classic tuberculosis, based on a six-month course of anti-tuberculosis chemotherapy: 02 months of rifampicin, isoniazid, ethambutol, and pyrazinamide (RHZE) in combination, followed by 04 months of dual therapy combining isoniazid and rifampicin (RH). Corticosteroids may be added in some situations such as severe airway edema. Surgery is exceptional but may be necessary in some dyspneic forms requiring tracheotomy, or in cases of laryngeal fibrosis. Response to treatment is generally great, usually leading to regression of symptoms and laryngeal lesions, as observed by Ayoubi et al., who had noted a recovery in all their patients [1] [17] . If there is no improvement after a few weeks, non-compliance with treatment should be suspected [1] . In our case, voice recovery was noted after 20 days of anti-tuberculosis treatment, along with a significant improvement in performance status. Regular monitoring is essential to watch out for the undesirable effects inherent to anti-tuberculosis treatment, such as hepatic cytolysis, allergic reactions, or symptomatic hyperuricemia.
4. Conclusion
Laryngeal tuberculosis is a rare localization of extrapulmonary tuberculosis. Clinical and endoscopic signs are not specific, therefore it should be suspected in patients living in endemic areas and suffering from chronic dysphonia, even if they are not alcoholics or smokers. Pulmonary involvement must be systematically sought. Treatment is essentially based on the classic anti-tuberculosis regimen, with a good prognosis and usually favorable response to therapy.
Consent
Consent was obtained from the patient for the publication of this case report, which is available.
Authors’ Contributions
The original manuscript was written by NAS and DT. NN contributed to patient management. NAS collected and prepared the figures. LATD and SAD drafted and approved the final version to be published.