as a common head and neck cancer , nasopharyngeal carcinomas are generally either keratinizing or nonkeratinizing squamous cell carcinomas .
primary nasopharyngeal adenocarcinomas ( npacs ) are rare neoplasms , constituting only 0.38% to 0.48% of all malignant nasopharyngeal neoplasms .
thyroid - like low - grade nasopharyngeal papillary adenocarcinoma ( tl - lgnppa ) is a small minority of conventional nasopharyngeal adenocarcinoma that exhibits papillary growth and abnormal expression of thyroid transcription factor 1 ( ttf-1 ) . to the best of our knowledge ,
only thirteen cases have been reported in the english - language literature and eleven in the chinese - language literature to date ( table 1 ) . in this article , we present a case of primary tl - lgnppa and an analysis of its clinicopathological features .
a 15-year - old chinese girl presented with a complaint of rhinorrhoea and nasal congestion with a duration of 1 month . on clinical examination , no thyroid tumor or other physical abnormalities were found .
nasal endoscopy identified a pedunculated polypoid mass with smooth surface that measured approximately 2.52 cm arising from the posterior nasal septum ( fig .
follow - up data showed no signs of local recurrence at up to 2 years after complete surgical removal .
the tissue was fixed in formalin and embedded in paraffin , after which 4-m thin sections were cut and stained with hematoxylin and eosin .
immunohistochemical staining was performed using commercially available antibodies to the following antigens : pan - cytokeratin ( ckpan ) , epithelial membrane antigen ( ema ) , vimentin , cytokeratin ( ck ) 7 , cd15 , thyroid transcription factor 1 ( ttf-1 ) , ki-67 , p40 , s100 , glial fibrillary acidic protein ( gfap ) , ck20 , cdx-2 , and thyroglobulin . at the same time , in situ hybridization for the presence of small epstein - barr virus ( ebv)encoded rna was performed to identify the association between this tumor and ebv .
histological examination of the biopsy specimen revealed a tumor that showed papillary configuration with hyalinized fibrovascular cores , similar to thyroid papillary carcinoma ( fig .
the papillae were complex and tightly packed , and most were lined with cuboidal or columnar epithelia containing overlapping round to ovoid nuclei that displayed fine chromatin and mildly eosinophilic cytoplasm ( fig . 2c ) .
small intra - nuclear cytoplasmic inclusions were present focally , although neither nuclear grooving nor ground glass nuclei were found . in small parts of the tumor ,
no necrosis or mitotic activity was discerned and no continuity between the tumor epithelia and normal nasopharyngeal mucosa or mucous glands was identified .
immunoperoxidase studies showed that neoplastic cells were positive for ck7 , vimentin , ttf-1 , ckpan , and ema ( fig .
there was no immunoreactivity for thyroglobulin , cd15 , s100 , p40 , ck20 , cdx-2 , and gfap . in the most concentrated spot ,
npac contains two subtypes : conventional / surface origin - type and salivary gland - type .
the latter includes polymorphous low - grade adenocarcinoma , mucoepidermoid adenocarcinoma , and adenoid cystic carcinoma . in 1988 , wenig et al .  
first described thyroid - like papillary adenocarcinoma of the nasopharynx and proposed that these papillary adenocarcinomas should been regarded as a distinct entity from conventional adenocarcinomas in this region based on their indolent clinical behavior and low - grade histological features .
nasopharyngeal papillary adenocarcinoma ( nppa ) was enrolled in the world health organization classification system of malignant epithelial tumors of the nasopharynx in 2005 .
papillary configuration and aberrant ttf-1 expression are the distinguishing features of tl - lgnppa , mimicking papillary thyroid carcinoma ( ptc ) .
tl - lgnppa is an extremely rare neoplasm . to the best of our knowledge ,
the median age is 35 years in patients , ranging from 9 to 68 years .
instances of tl - lgnppa were usually localized in the roof of the nasopharynx and posterior edge of the nasal septum .
the excellent prognosis was obvious , with local excision being performed in all reported cases , and no local recurrence or metastasis reported .
histologically , these neoplasms frequently exhibit papillary architecture lined by moderately pleomorphic columnar epithelial cells with fibrovascular cores , overlapping nuclei with clear optically chromatin , and psammoma bodies .
however , the biphasic pattern of low - grade nppa with a spindle cell component has been described in three case reports . in this case , no obvious spindle cell component was observed .
the biphasic pattern of tl - lgnppa should be further investigated if a large number of cases can be collected .
immunohistochemically , the positive expression of ttf-1 was the most characteristic feature of tl - lgnppa .
as a homeodomain containing transcription factor coded by nkx2 - 1 , ttf-1 is usually found in lung , thyroid , and central nervous system tissue .
nevertheless , the positive expression of ttf-1 was also observed in other organs , including endometrium , colon , and breast .
although the etiology of ttf-1 positive staining in tl - lgnppa is still not clear , three mechanisms to explain this phenomenon were proposed in a recent case report .
second , a gene rearrangement that affects ttf-1/nkx2 - 1 may result in abnormal expression of ttf-1 . finally , genetic instability and reprogramming of the cancer cells can cause dis - differentiation and lead to deregulation of ttf-1/nkx2 - 1 . however , these presumptions are poorly evidenced owing to the extreme rarity of this tumor at the present time .
there are limited options available for differential diagnosis of papillary lesions in the nasopharynx . because tl - lgnppa display a striking resemblance to ptc , it is important to exclude nasopharyngeal metastasis from papillary adenocarcinoma of the thyroid gland for accurate diagnosis , treatment , and prognosis of the patient .
immunostaining for thyroglobulin and cd15 are critical and highly recommended to distinguish these two entities .
however , a case of tl - lgnppa with focal expression of thyroglobulin was recently reported .
polymorphous low - grade papillary adenocarcinoma ( plga ) is more aggressive and positive for vimentin and s100-protein . to date , positivity for ttf-1 has never been reported in plga .
papillary variants of the intestinal type of adenocarcinoma ( itac ) show more nuclear atypia and commonly display mucinous differentiation .
acinic cell carcinomas ( acc ) with a papillary component are frequently cystic and variably positive for s100-protein and vimentin according to the range of differentiation ( acinar to intercalated ducts ) .
extraventricular choroid plexus papillomas ( cpp ) at unusual localization must be taken into consideration , most of them was positive for s100 and negative for ema , part of them was positive for gfap .
in our report , negative staining for thyroglobulin , cd15 , s100 , gfap , ck20 , and cdx-2 was revealed ; therefore , ptc , plga , itac , acc , and cpp should not be considered for accurate diagnosis .
it has been well documented that tumors originating from the nasopharyngeal epithelium were associated with the ebv
. investigation of in situ hybridization for ebv revealed negative results , which is concordant with reports by wu et al .  
a close relationship between tl - lgnppa and ebv was not confirmed ; however , further investigation is needed because of the rarity of this neoplasm . to date ,
no case of lymphatic metastasis or recurrence has been reported , indicating excellent prognosis for patients with thyroid - like papillary adenocarcinoma .
generally , surgical excision is adequate for the treatment of tl - lgnppa . when surgical excision is not feasible or positive surgical margins have been observed , radiotherapy can be employed as an adjuvant treatment .
in conclusion , we present here a novel case of tl - lgnppa with a review of its main clinicopathological features . due to the rarity of this neoplasm and favorable clinical outcome
, clinicians should pay more attention to accurate diagnosis of this entity , as well as its treatment and clinical prognosis .
 purposeprimary low - grade thyroid - like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx . here 
 , we describe a novel case of a 15-year - old chinese girl who was diagnosed with low - grade thyroid - like papillary adenocarcinoma , including a brief review of the literature to reveal the clinicopathological features of low - grade thyroid - like nasopharyngeal papillary adenocarcinoma.materials and methodsimmunohistochemistry was used to evaluate the expression of pan - cytokeratin ( ckpan ) , cytokeratin ( ck ) 7 , thyroid transcription factor 1 ( ttf-1 ) , vimentin , epithelial membrane antigen ( ema ) , thyroglobulin , cd15 , s100 , p40 , ck20 , cdx-2 , glial fibrillary acidic protein ( gfap ) , and ki-67 . 
 additionally , in situ hybridization investigation was utilized to identify the presence of small epstein - barr virus ( ebv)encoded rna.resultshistopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores . 
 immunohistochemically , the neoplastic cells were positive for ckpan , ck7 , ttf-1 , vimentin , and ema , but negative for thyroglobulin , cd15 , s100 , p40 , ck20 , cdx-2 , and gfap . 
 the ki-67labeling index reached 5% in the most concentrated spot . 
 in situ hybridization for ebv was negative.conclusiondue to the distinct rarity of low - grade thyroid - like papillary adenocarcinomaswith a favorable clinical outcome , a nationwide effort to raise public awareness of this neoplasm is required . 
Introduction
Materials and Methods
Results
Discussion
Conclusion