The Laryngoscope Lippincott Williams & Wilkins, Inc.

, Philadelphia 2003 The American Laryngological, Rhinological and Otological Society, Inc.

Tuberculosis of the Nasopharynx: A Rare Entity Revisited

Gary M. K. Tse, FRCPC; Tony K. F. Ma, FRCPA; Amy B. W. Chan, MBChB; Fiona N. Y. Ho, FRCS; Ann D. King, FRCR; Kitty S. C. Fung, FRCPA; Anil T. Ahuja, FRCR

Objectives: Tuberculosis of the nasopharynx is uncommon. A large series of 17 cases is reported, and the clinical and pathological features are discussed. Study Design: A retrospective review. Methods: Seventeen archived cases of biopsy-proven nasopharyngeal tuberculosis were reviewed for patient age and sex, presenting complaint and duration, systemic symptoms, cervical lymphadenopathy, and chest x-ray findings. These findings were compared with a compilation of 40 cases reported in the English literature. Results: There was a female predominance (13 women and 4 men), with age range of 20 to 74 years (mean age, 38 y). The most common presentation was enlargement of the cervical lymph nodes (53%), followed by hearing loss (12%), tinnitus, otalgia, nasal obstruction, and postnasal drip (6% each). The duration of the presenting symptoms ranged from 1 week to 1 year (mean duration, 16 wk). Ten patients (59%) had cervical lymphadenopathy, two (12%) had systemic symptoms (fever, weight loss, night sweats), and one patient (6%) had miliary pulmonary tuberculosis. Direct endoscopic examination showed nasopharyngeal mucosal irregularity or mass in the majority of patients (12 patients [70%]). These features were similar to those reported in the literature. Conclusions: Nasopharyngeal tuberculosis is uncommon, usually occurring without pulmonary or systemic involvement. Cervical lymphadenopathy occurs in more than half of the patients and is the most common presenting complaint; this, together with the nasopharyngeal findings of mass or mucosal irregularity, makes differentiation from carcinoma on clinical examination difficult, necessitating histological evaluation. Key Words: Nasopharynx, tuberculosis, undifferentiated carcinoma, granuloma, granulomatous inflammation. Laryngoscope, 113:737740, 2003

INTRODUCTION
Tuberculosis (TB) of the nasopharynx is rare. Although the upper respiratory tract is the usual portal of entry for pulmonary TB, involvement of the upper respiratory tract either in isolation or as part of systemic (or pulmonary) disease remains uncommon. In a large historical series of 843 cases of TB, only 1.8% of cases showed upper respiratory tract involvement, with one case of nasopharyngeal involvement.1 In the English literature, only three large series described nasopharyngeal TB in detail, and these series, respectively, reported 7 to 14 cases.2 4 The remainder of reports in the literature were single case reports, approximately 10 cases in all.514 In the present case series, the authors reviewed 17 cases, with emphasis on the disease features as compared with the previous series.

MATERIALS AND METHODS

Archived material from the Department of Pathology was searched for TB of nasopharynx from 1990 to 2002, yielding 20 cases in all. Three patients had a history of concurrent undifferentiated carcinoma (nasopharyngeal carcinoma [NPC]) and were excluded from the present review. All the medical records were retrieved. The information extracted, when available, included age, sex, presenting complaint and duration, systemic symptoms, clinical examination findings including appearance of the nasopharynx, and chest x-ray findings. The pathological materials of the nasopharyngeal biopsies were retrieved and reviewed, and the diagnosis confirmed. Ziehl Neelsen staining was performed on the biopsy material to detect acid-fast bacilli, and in some cases, multiple sections were examined.

RESULTS
Seventeen cases were reviewed, of which 13 were in women and four were in men. The patient age range was 20 to 74 years (mean age, 39 y). Ten patients (59%) presented with enlarged neck nodes, including eight (47%) with unilateral nodes and two (12%) with bilateral nodes. Two patients (12%) presented with hearing and one patient (6%) each presented with tinnitus, otalgia, nasal obstruction, and postnasal drip. One patient (6%) did not have any symptoms referable to the head and neck region. The duration of the presenting symptoms ranged from 1 week to 1 year (mean duration, 16 wk). Only two patients (12%) had fever, night sweats, Tse et al.: Nasopharyngeal Tuberculosis

From the Departments of Anatomical and Cellular Pathology (G.M.K.T., A.B.W.C.) and Surgery (F.N.Y.H.), Division of Otorhinolaryngology, and the Departments of Diagnostic Radiology and Organ Imaging (A.D.K., A.T.A.) and Microbiology (K.S.C.F.), Prince of Wales Hospital, Chinese University of Hong Kong; and the Department of Pathology (T.K.F.M.), Alice Ho Min Ling Nethersole Hospital, Republic of China. Editors Note: This Manuscript was accepted for publication November 26, 2002. Send Correspondence to Gary M. K. Tse, FRCPC, Department of Anatomical and Cellular Pathology, Ngan Shing Street, Shatin, NT, Hong Kong, Republic of China. E-mail: garytse@cuhk.edu.hk

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Fig. 1. Nasopharyngeal biopsy specimen with surface respiratory epithelium (short arrow) and multiple granulomas composed of epithelioid histiocytes (long arrow) in the submucosa (H&E stain, original magnification 00). Inset: Acid-fast bacilli, consistent with Mycobacteria tuberculosis is seen (inset, Ziehl Neelsen, original magnification 400).

and weight loss. Endoscopic examination of the nasopharynx showed mucosal irregularity, resembling lymphoid hyperplasia in six (35%) patients, a nasopharyngeal mass in six patients (35%), mucosal swelling in one patient (6%), white patch on mucosa in one patient (6%), and ulceration in one patient (6%). In one patient (6%)

the nasopharynx appeared normal. In one case, the finding was not recorded. Chest x-ray examination showed miliary TB in one patient (6%) and features of old lesions in four patients (24%). For the remaining 12 patients, 4 (24%) had normal chest x-ray findings and the results were not recorded in 8 patients.

TABLE I. Clinical Features of All Patients.

Case No. Sex Age (y) Duration (wk) Presenting Symptoms Systemic Symptoms Nasopharyngeal Appearance Chest X-ray

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

F M F F F F F M F F F F F F M F M

24 20 30 69 74 28 19 23 22 64 29 49 29 31 22 61 63

8 Unknown 4 8 16 12 52 1 24 8 Unknown Unknown 16 Unknown 8 8 52

Otalgia Unknown Neck node Right ear tinnitus Neck node Neck node Nasal obstruction Neck node Neck node Neck node Hearing loss Left hearing loss Neck node (bilat) Neck node Neck node (bilat) Neck node Nasal obstruction

Yes Unknown Yes No No No No No No No No No No No No No No

Granular Unknown Lymphoid hyperplasia Roof mass Normal Rough right wall Large exophytic mass at all wall Irregular Central lymphoid hyperplasia Bulging mass Lymphoid Right whitish patch Central swelling Mass Irregular ulcer at right central NP Mass Mass

Not available Not available Normal Pleural thickening Apical pleural thickening Normal Not available Miliary TB Normal Right upper lobe old granuloma Not available Not available Not available Not available Normal Right upper zone fibrocalcified change Not available

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TABLE II. Clinical Features of All Patients Reported in the Literature.

Patient No. Year 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 1992 1992 1992 1992 1992 1992 1992 1992 1992 1972 1972 1972 1972 1972 1972 1972 1999 1984 1986 Reference 2* 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 5 6 7 Sex/Age (y) M/37 M/35 F/26 F/38 F/25 F/76 M/48 M/41 F/27 M/18 M/26 F/59 F/22 F/36 F/57 F/47 F/20 M/35 F/54 Complaint Neck node Neck node Decrease hearing Unknown Nasal obstruction Nasal obstruction Neck node Neck node Neck node Neck node Headache Neck node Neck node Neck node Neck node Sore throat Chronic otitis media Neck node Facial pain Duration (wk) 12 16 12 12 4 20 4 12 8 25 4 16 25 16 12 25 52 4 1 NP Appearance Irregularity Mass Irregularity Mass Mass Mass Irregularity Irregularity Mass Mass Mass White discoloration Mass Mass Irregularity Mass Unknown Irregular, right Mass Yes Yes No No Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Unknown Yes Unknown LN NP Biopsy Neg Pos Pos Pos Pos Pos Neg Neg Neg Pos Pos Pos Neg Pos Neg Pos Pos Pos Pos No No No Active TB No No No Old TB No No No No No No No No Old TB No Active TB on drug for 1 year No Micronodules, nodes pos No No Old TB No No 14 Active TB No 7 7 Lung

20 21 22 23 24 25 26

1992 1999 1994 2002 1997 1985 1981

8 9 10 11 12 13 14 4

F/58 F/64 F/42 F/58 F/70 F/18 M/62 M F Range Mean 12 2 1761 34

Otalgia Pharyngeal pain Nasal obstruction Snoring Altered taste/smell Neck LN Nasal obstruction Neck node 11 2 2

12 8 Unknown Unknown 16 3 Unknown 16 wk or 12 2

Slough Swelling Mass, midline Swelling Unknown Unknown Mass Mass Normal 11 2

No No Unknown No Unknown Yes Unknown Yes No 12 2

Neg Neg Neg Neg Neg Neg Pos Pos

2740 1996

Post nasal drip Brisk epistasis

16 wk

*This series reported 10 cases, but one patient had NPC and TB and was thus excluded from this review. This series reported 14 cases, but individual patients data were not reported or tabulated separately. LN cervical lymphadenopathy; NP biopsy nasopharyngeal biopsy; neg granulomatous inflammation but direct stain for acid fast bacilli negative; pos granulomatous inflammation and positive direct Ziehl Neelsen stain for acid fast bacilli.

In all cases, nasopharyngeal biopsies were performed to rule out NPC, which has a similar presentation and a high incidence in this locality. The biopsy specimens showed granulomatous inflammation with epithelioid histiocytes and multinucleated giant cells of Langerhans type. Ziehl Neelsen staining for acid-fast bacilli was positive in all cases (Fig. 1). All the patients responded to treatment for TB.

DISCUSSION
Nasopharyngeal TB represents an uncommon and unique form of TB infection. This disease is rare, and the number of reported cases in the English literature is low. The current report represents the largest series. Before the present report, there were three large series reported in the English literature, being written 6, 10, and 30 years Laryngoscope 113: April 2003

ago, respectively.13 Hence, it is of great interest to compare the clinical features of the current cases (Table I) in the present series with the historical compilation (Table II). In our series, neck lymph node enlargement as a presenting symptom accounted for 53% of cases, whereas symptoms referable to the ear and nose area in terms of tinnitus, nasal obstruction, hearing loss, and otalgia accounted for most of the remainder. These findings were similar to those in the literature, in which enlarged lymph nodes was the most common (58%) presenting symptom followed by nasal obstruction (10%) and pain around the head and neck region, tinnitus, and hearing loss. Direct examination of the nasopharynx revealed a combination of mass and irregularity, which, together, accounted for a major proportion (70%) in our series and 75% of cases in the literature. More important, findings on direct examiTse et al.: Nasopharyngeal Tuberculosis

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nation may be normal, as was shown in one case (6%) in our series and two cases (5%) in the literature. The relation among TB of the nasopharynx, cervical lymph nodes, and pulmonary infection merits further discussion. In primary nasopharyngeal TB, involvement of the cervical nodes is common, occurring in more than 50% of cases. Co-existing active or old pulmonary involvement or systemic disease is less common, with 30% (five cases) occurring in our series and 25% in the literature. Conversely, nasopharyngeal involvement in TB cervical lymphadenopathy and pulmonary TB is exceeding rare. In an elegant study of 75 patients with excision-proven TB of cervical nodes, the nasopharynx was shown to be the only primary focus of infection in one patient (1%), without pulmonary or systemic involvement.15 The same was true for pulmonary TB, with a reported incidence of nasopharyngeal involvement in 1.8% of cases only.1 The inference is that TB of the nasopharyngeal is usually primary and isolated; the chance of co-existing lung infection is low. The mechanism for such a phenomenon remains unclear. Involvement of TB of the upper airways was by contiguous spread from the active lung lesion through infected sputum or other secretion. In a large series of cases of laryngeal TB, abnormal findings on chest x-ray examination were noted in 95% of patients.16 However, the rate of lung involvement in nasopharyngeal TB is low, suggesting that contiguous spread would have to occur from ongoing or reactivation of subclinical pulmonary TB, or the nasopharynx truly represents the primary portal of transmission from inhalation of TB in airborne droplets. Cervical lymphadenopathy in nasopharyngeal TB is common and does not imply systemic spread of the disease. The common scenario of enlarged cervical lymph nodes with a nasopharyngeal mass or irregularity, but without systemic symptoms, makes the disease virtually indistinguishable from NPC, making histological evaluation imperative in endemic areas such as southern China. The contribution of TB in the causation of granulomatous diseases in the head and neck region remains difficult to estimate. Other causes of granulomas include sarcoidosis, vasculitic diseases such as Wegeners granulomatosis, fungal infections or reactive changes in response to carcinoma or lymphoma (particularly Hodgkins disease), and radiotherapy. Because positive identification of the acid-fast bacilli in smears or cultures is a prerequisite for diagnosis of TB, its incidence is likely to be underestimated. In a study of 22 cases of tonsillar granulomas,17 no underlying cause was identified in one-third of the cases, and the possibility of undiagnosed TB has to be considered. With the improvement of techniques for detecting TB, including polymerase chain reaction for the bacterial DNA, and increased awareness, particularly in view of the resurgence of TB, the incidence of TB of the upper aerodigestive tract is likely to increase.

The authors have reported a large series of cases of nasopharyngeal TB, which showed a female predominance, as well as neck node enlargement as the most common presentation. In the majority of cases, examination showed a mass lesion or mucosal irregularity in the nasopharynx, making differentiation from carcinoma difficult. This poses a particular diagnostic problem in some regions of the world such as Southeast Asia and Africa, where NPC and TB are endemic, particularly because enlarged cervical lymph nodes are a common presenting symptom in both diseases. Furthermore, nasopharynx TB is usually isolated, without pulmonary or systemic symptoms. The similar clinical features of patients included in the current series and those reported 10 to 30 years ago has suggested that little progress has been made in the early detection of the disease. With the recent resurgence of TB, it is imperative to be aware of the rare cases of nasopharyngeal TB.

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