it can affect the lung ( pulmonary tb ) and other sites ( extrapulmonary tb ) as well . according to the who 2014 , 6.1 million cases of tb were reported with 5.7 million newly diagnosed cases and 0.4 million previously diagnosed cases . in new cases ,
head and neck regions can be present in up to 10% of all tb cases with cervical lymph nodes
most commonly involved . in 1974 , rohwedder   reported 16 ( 1.8% ) upper respiratory tract tb cases among 843 tb patients .
nasopharyngeal tuberculosis ( nptb ) was identified less than 1% in the head and neck tb category [ 2 , 3 ] .
previous literatures usually presented single case reports of nptb ; however , recently more large case series have been observed .
this review summarized the epidemiology , mechanism of infection , clinical manifestations , diagnostic techniques , and management and also emphasized the association between nptb and pulmonary tb .
prior to the introduction of chemotherapy , 1.4% of adenoids   and 6.5% of tonsils   removed from asymptomatic patients were infected by tubercle bacillus .
mahindra et al .   found adenoid tb in 18 out of 67 patients with tb cervical adenitis who underwent adenotonsillectomy . with the advent of effective antituberculous
therapy and pasteurization of cow 's milk , worldwide prevalence of this phenomenon appears to be reduced [ 7 , 8 ] .
 between august , 1947 , and april , 2015 , case reports of nptb were noted in over 60 cases from both english and non - english articles .
large series studies were frequently reported from asia ( table 1 ) [ 918 ] .
there was a slight predominance of woman in all large series studies [ 10 , 11 , 1315 , 18 ] .
four large series studies indicated a mean age between 30 and 40 years [ 10 , 11 , 13 , 14 ] while two peaks of frequency were estimated , between 15 and 30 years and 50 and 60 years [ 19 , 20 ] .
markham , however , reported three of the youngest patients who were 11 , 13 , and 15 months old from their adenotonsillectomy specimens . according to the who global tb report , the most common coexisting condition for all tb patients was hiv infection which had an influence on treatment outcomes .
but in nptb , only some of articles mentioned this relationship with good treatment outcomes in all articles whether hiv - positive or hiv - negative [ 11 , 14 , 2224 ] . in addition , nptb may mimic nasopharyngeal carcinoma ( npc ) [ 17 , 25 ] or coexist with other conditions in the head and neck such as laryngeal tb , oropharyngeal tb , and postradiation of npc [ 22 , 23 , 25 , 26 ] .
in 1981 , innes   suggested six mechanisms whereby extrapulmonary tb might arise : ( 1 ) nonpulmonary primary infection , ( 2 ) lymphatic spread from a pulmonary primary complex , ( 3 ) haematogenous spread from a primary complex , ( 4 ) haematogenous spread from a postprimary lesion , ( 5 ) contiguous spread from organ to organ , and ( 6 ) epithelial implantation .
however , for nptb , both a primary nasopharyngeal infection which was defined as an isolated tuberculous infection of the nasopharynx in the absence of pulmonary or systemic diseases [ 11 , 24 ] and a secondary spread via haematogenous or lymphatic system were described [ 11 , 13 , 14 , 20 , 28 ] .
the rich lymphatic network of waldeyer 's ring explains lymphatic nasopharyngeal contamination [ 6 , 11 , 19 , 20 ] .
.   indicated primary nasopharyngeal infection as droplet transfer due to this area being an impact area for inhaled air which was similar to other published articles [ 10 , 13 , 17 ] .
while three large series studies supported theoretical secondary infection from the lymphatic system with a high percentage of pulmonary tb association [ 11 , 13 , 14 ] , the association of pulmonary tb was observed in a wide range between 8.3% and 55.6% [ 10 , 11 , 13 , 14 , 16 , 17 ] .
furthermore , graft   reported that the highest prevalence of pulmonary tb associated with nptb was 82% in his study . in summary ,
both mechanisms of infection were possible depending on the percentage of the association between nptb and pulmonary tb in each study .
in addition , chan et al .   described the mechanism of nptb developed in postradiotherapy of the npc .
this may be partially due to local damage to the nasopharynx which achieved a high dose of radiotherapy ( 60 to 74  gy ) , resulting in a breakdown of the mucosal barrier and a localized immunodeficiency or susceptibility .
nptb can develop in a healthy patient without underlying disease and no history of tuberculosis contact nor an immune - compromised host [ 6 , 24 ] .
common complaints are malaise , low grade fever , elevated temperature in the evening , repeated cold , night sweat , weight loss , and productive cough [ 6 , 13 , 14 , 17 , 19 , 20 ] .
the most common symptom is cervical lymph node enlargement which was observed more than 70% in many studies [ 10 , 11 , 13 , 14 , 17 , 25 ] .
the pattern of nodal enlargement in nptb was different from primary cervical tuberculous lymphadenitis ; the latter usually involved supraclavicular and posterior group also presented in unilaterally , multiple , or matted lymphadenopathy [ 3033 ] , while the former was affected along nasopharyngeal lymphatic drainage [ 10 , 11 , 14 ] .
a retropharyngeal lymph node is a first echelon node and most commonly affected firstly and was identified from imaging .
however the upper jugular , middle jugular , and posterior group of cervical lymph nodes were more commonly found on physical examination , respectively [ 10 , 11 , 14 ] .
nodal features usually manifested as multiple and bilateral involvement ( table 2 ) [ 10 , 11 , 13 , 14 , 17 ] . the nasopharyngeal symptoms which could be presented alone or associated with nodal enlargement included ( 1 ) ear problems : aural fullness , hearing loss , otorrhea , otalgia , tinnitus , and middle ear effusion [ 3436 ] , ( 2 ) nose problems : running nose , postnasal drip , nasal obstruction , and epistaxis [ 25 , 37 , 38 ] , ( 3 ) others : snoring , headache , and diplopia [ 10 , 24 , 3941 ] . on nasopharyngoscopic examination ,
different appearances on nasopharyngeal findings can be detected consisting of normal appearance , irregular mucosa , ulcerative lesion , mass , bulging or swelling , white patch cover the nasopharyngeal area ( figure 1 ) , and lymphoid hyperplasia ( table 3 ) [ 11 , 13 , 14 , 17 ] .
treatment outcomes were worse for hiv - positive tb patients ( 74% ) compared with hiv - negative patients ( 88% ) and mortality was more than three times higher among hiv - positive tb patients . although the relationship between nptb and hiv infection has not been clarified yet , few articles mentioned good treatment outcomes in both hiv - positive and hiv - negative nptb patients [ 11 , 14 , 2224 ] .
however , hiv testing should be performed in every tb cases for reducing the burden of hiv - associated tb patients .
computed tomography ( ct ) and magnetic resonance imaging ( mri ) were reported as valuable tools in head and neck tb , demonstrating the sites , pattern , and extension of the disease [ 42 , 43 ] .
in addition , finer details of lesion detected from mri imaging were helpful in distinguishing nasopharyngeal diseases .
both nasopharynx and lymph nodes reveal their own suspected characteristics ( table 4 ) [ 10 , 44 ] .
nasopharyngeal polypoid mass was the common finding on ct / mri followed by diffuse mucosal thickening [ 10 , 44 ] .
the lesion was usually confined in the nasopharyngeal area without invasion into the surrounding structures such as skull base , prevertebral muscle , nasal cavity , and oropharyngeal area ( figure 2 ) .
.   suggested that a small necrosis in a nasopharyngeal lesion which was caseous necrosis on pathology might be a valuable clue to diagnose nptb ( figure 3 ) , although the area of necrosis might have a similar appearance on npc but was seen more often in a large tumor or after treatment .
king et al .   mentioned that tb which involved lymphoid tissue sometimes causes destruction of the normal lymphoid architecture .
thus a striped feature which is a recognized feature of benign enlargement of the nasopharyngeal adenoid can cause destruction .
these points might be helpful in distinguishing between nptb and adenoids [ 10 , 44 ] .
cervical lymphadenopathy also detected from imaging had their own different features according to the stage of nodal disease ( table 4 ) [ 10 , 44 ] .
recently , 18f - fdg pet / ct has become an established imaging tool in oncology and is now being applied to the field of infection and inflammatory diseases [ 42 , 45 , 46 ] .
the advantages for nptb include ( 1 ) clearly indicated locations of tb lesions ; ( 2 ) identification of extrapulmonary tb [ 42 , 45 ] ; ( 3 ) a metabolic abnormality which guided biopsy sites ; ( 4 ) assessment of treatment response [ 45 , 46 ] .
in addition , 18f - fdg pet had its own ability to distinguish active from inactive disease in pulmonary tb by dual time point imaging
. however , standardized uptake value measurements are high in both tb and malignant lesions , with significant overlap that limits their usefulness [ 42 , 45 ] .
bacterial culture either from tissue or from sputum that also achieves drug sensitivity [ 2 , 32 , 33 , 44 ] . but this test required a waiting period from four to six weeks [ 20 , 32 , 33 ] .
nptb gross lesions can mimic other nasopharyngeal treatable diseases including npc , lymphoma , minor salivary gland carcinoma , wegener 's granulomatosis , angiofibroma , fungal infection , sarcoidosis , periarteritis nodosa , leprosy , syphilis , and castleman 's disease [ 22 , 25 , 26 , 34 , 38 , 44 , 47 ] .
a typical pathological report for diagnosing nptb is caseating granulomatous inflammation with multinucleated giant cells of langhans ' type and foreign body giant cells , with or without necrosis [ 25 , 32 , 33 ] , although npc itself can develop a granulomatous reaction , similar to tb , in peritumoral tissue [ 25 , 44 ] .
furthermore chronic granulomatous inflammation with positive ziehl - neelsen staining for acid - fast bacilli or bacterial culture can also be demonstrated [ 11 , 14 , 33 , 44 ] .
in addition , the case which is strongly suspicious for tb but negative for bacterial culture , bacterial stain , and polymerase chain reaction ( pcr ) analysis for m. tuberculosis dna is helpful [ 2 , 22 , 24 , 25 , 32 ] .
many authors suggested that ziehl - neelsen staining for acid - fast bacilli in a histologic section is reliable and sensitive and is faster and less costly than bacterial culture and pcr analysis .
the latter method should be reserved for the stain negative cases to avoid missing a treatable , potentially lethal infection [ 13 , 20 , 22 , 24 , 25 ] .
the minimal duration of extrapulmonary tb treatment is six months [ 11 , 14 , 19 , 20 ] .
treatment regimen is either a triple combination including isoniazid ( inh ) , rifampicin ( rfp ) , and ethambutol ( eb ) for 918 months or a quadritherapy which add pyrazinamide ( pza ) for nine months [ 19 , 20 ] . in addition , waldron et al .   preferred a standard regimen of inh , rfp , and pza for a minimum period of six months and added streptomycin during the first two to three months .
some authors preferred two months of inh , rfp , eb , and pza followed by inh and rfp for four to seven months [ 11 , 14 , 22 , 40 ] .
with adequate medical treatment , nasopharyngeal tuberculosis carries a good prognosis and no cases of resistance to antituberculous drugs or therapeutic failure had been noticed [ 9 , 11 , 14 , 1720 , 22 , 40 ] .
although nptb is uncommon in previous literature , recently an increased number of large case series have been reported .
the suspected reasons include ( 1 ) awareness of the disease ; ( 2 ) improvement of knowledge regarding clinical manifestation ; ( 3 ) improvement of diagnostic techniques ; and ( 4 ) increased incidence of the disease . according to the variability of clinical manifestations , awareness of this disease and precise evaluation of the patient
the former has similar clinical presentations which include cervical lymph node enlargement and lesions in nasopharynx .
 nasopharyngeal tuberculosis ( nptb ) is a noteworthy disease especially in its worldwide spread of the mycobacterium infection . 
 although nptb has been identified in less than one percent of tb cases , recent multiple case reports indicate an either increased awareness or incidence of this disease . the most helpful diagnostic tool is an uncomplicated nasopharyngeal biopsy . however , nptb is usually ignored because it has varied clinical manifestations and similar presentations with other more common head and neck diseases . 
 furthermore , the most common presenting symptom is cervical lymphadenopathy mimicking nasopharyngeal carcinoma , a more common and serious disease . 
 treatment outcomes of nptb are good in both hiv - positive or hiv - negative patients . 
 in addition , pulmonary tuberculosis association was reported in wide range between 8.3% and 82% which should be considered in a treatment program . in conclusion 
 , early diagnosis and management in nptb can be achieved by ( 1 ) increased awareness of this disease , ( 2 ) improvement in knowledge regarding clinical manifestations , and ( 3 ) improvement of diagnostic techniques . 
1. Introduction
2. Epidemiology
3. Mechanism of Infection
4. Clinical Manifestations
5. NPTB Associated with HIV Infection
6. Diagnostic Techniques
7. Management
8. Conclusion