mammary analogue secretory carcinoma ( masc ) is a recently described pathological entity arising in the salivary glands . in 2010 , skalova et al . reported a case series comprising 16 cases of this salivary gland tumor showing identical histological as well as molecular features to breast secretory carcinoma . the fusion gene encodes a chimeric tyrosine kinase , which has potential transformation activity and plays a major role in carcinogenesis [ 2 , 3 ] . histopathologically , masc is a distinctive entity , and histology in combination with appropriate immunohistochemical analysis is sufficient for a diagnosis in most cases . however , several histopathological features of masc overlap with those of other salivary gland tumors , such as acinic cell carcinoma ( acicc ) , adenocarcinoma not otherwise specified ( adc - nos ) , and low - grade mucoepidermoid carcinoma [ 1 , 2 , 4 ] . in the first reported case series by skalova et al . , most tumors ( 13/16 cases ) arose in the parotid gland with 3 cases originating in the minor salivary glands . since that seminal paper , some retrospective studies and case reports have been published [ 5 , 6 , 7 , 8 ] . masc arose in the parotid gland in the majority of cases , followed by the submandibular gland and the oral cavity ( soft palate , buccal mucosa , and lip ) [ 2 , 8 , 9 , 10 ] . in this paper , we present the first reported case of masc presenting as a cervical lymph node metastasis of unknown primary site together with a brief review of the literature and discussion of possible appropriate treatments . a 74-year - old male presented with a 2-month history of a painless lump in the left neck . he had a past medical history of hypertension , and his family history was not significant . on physical examination there was a 2  2 cm firm swelling present in the left upper neck , the mobility of which was slightly restricted . sonograms showed that the mass was hypoechoic , 16  14  20 mm in size , and with a relatively regular border . computed tomography showed an enhanced lesion in the left upper neck in contact with the carotid bifurcation and the jugular vein ( fig . 1c ) . based on the fine needle aspiration cytological findings , a possible malignant tumor , such as epithelial - myoepithelial carcinoma or basal cell adenocarcinoma , was suspected , but no definitive diagnosis was given . positron emission tomography / computed tomography ( pet - ct ) revealed fdg avidity in the left - sided neck at a level ii lymph node , the size of which was 21  16 mm . there was no evidence of a primary lesion , including the parotid and submandibular glands , on pet - ct ( fig . further , no tumorous lesions were detected in the mammary gland on pet - ct . therefore , with a provisional diagnosis of suspected cancer of unknown primary site , he underwent left modified radical neck dissection . intraoperatively , the level ii lymph node invaded the internal jugular vein and superior thyroid artery , and these vessels were sacrificed . no random biopsy was performed as there was no possibility that it was a squamous cell carcinoma . the gross resected specimen was yellow - white in color and formed lobular nodules ( fig . histopathological examination revealed a metastatic tumor in the left - sided neck at a level ii lymph node . the tumor consisted of tubular structures containing secretion , papillary - cystic structures , and a solid proliferative component ( fig . the papillary - cystic lesion showed many microcystic structures in the component cells ( fig . 2c ) . immunohistochemical staining showed that the neoplastic cells were negative for p63 and dog1 ( fig . 3c ) . a fluorescence in situ hybridization ( fish ) study with an etv6 ( 12p13 ) no other pathologically positive nodes were detected at other levels in the neck , and there was no tumor in the submandibular gland . we , therefore , made the final diagnosis of a cervical lymph node metastasis of masc from an unknown primary site . no adjuvant therapy was administered as our case showed solitary lymph node metastasis and complete resection was achieved . no local recurrence or metastatic disease has been detected during a follow - up of 9 months . from the literature , masc involves the parotid gland in about 70% of cases , the submandibular gland in about 7% of cases , and other sites , such as the soft palate , buccal mucosa , base of the tongue , and lip , less commonly [ 2 , 810 ] . the tumor presented herein is the first documented case of masc presenting as a cervical lymph node metastasis of unknown primary site . the salient histologic features of masc include solid , microcystic , tubular , and papillary - cystic patterns in varying proportions [ 8 , 1012 ] , and these findings were displayed by the tumor presented herein . in addition , intraluminal and/or intracellular colloid - like secretions that react positively with periodic acid - schiff ( pas ) are often observed histologically in masc [ 6 , 8 , 13 ] . immunohistochemically , masc characteristically shows positive staining for s100 protein and mammaglobin [ 1 , 10 ] . masc may also express gata3 , pancytokeratin , ck7 , ck8 , ck18 , ck19 , epithelial membrane antigen , vimentin , muc1 , muc4 , stat5a , gcdfp15 , and adipophilin [ 1 , 10 ] . masc is typically negative for high - molecular - weight keratin and basal cell / myoepithelial markers , such as calponin , sma , ck5 , ck6 , ck14 , and p63 [ 4 , 10 ] . the most common malignancy reclassified as masc was adc - nos ( 14/37 ) , followed by acicc ( 11/89 ) . there are considerable overlapping histological features between acicc and masc , as both exhibit acinar differentiation and intercalated duct - type cells . a major point of distinction is the presence of pas - positive cytoplasmic zymogen granules , which are observed in acicc [ 8 , 12 ] . in addition , masc stains more reliably for s100 protein , and acicc is not positive for mammaglobin , whereas dog1 stain is positive in the majority of cases of acicc [ 6 , 10 ] . similar to those in previous reports , our case displayed positive staining for s100 protein and gata3 but negative staining for p63 and dog1 . the defining cytogenetic characteristic of masc is the presence of the t(12;15)(q13;q25 ) etv6-ntrk3 translocation , demonstrated by either fish or pcr [ 1 , 8 , 11 ] . we performed a fish study with an etv6 break apart probe for molecular genetic analysis and revealed split signals in 95% of the nuclei . in the study by skalova et al . , all but one of the examined cases ( 13/14 ) were positive for the t(12;15 ) ( etv6-ntrk3 ) fusion transcript , and all examined cases ( 11/11 ) were positive for etv6 gene rearrangement on fish . recently , skalova et al .   reported that , in some cases of masc whose profile was ntrk3 split - negative and etv6 split - positive , unknown ( non - ntrk ) genes appeared to fuse with etv6 ( etv6-x fusion ) . , of the 91 reported cases of masc , only 4 cases of death from disease have been reported , although survival data were variably reported and follow - up was minimal . . however , some cases of masc have the potential for regional and distant metastasis . some authors reported that the risk for regional lymph node metastasis at diagnosis may also be higher in patients with masc than in patients with acicc [ 2 , 8 ] . to date , there is no conclusive evidence that masc should be treated any differently to other low - grade malignant salivary gland cancers . in the review by sethi et al . , the treatment modalities mentioned in the literature included details for 86 patients : 26% of the patients underwent neck dissections , and 20% were given postoperative radiotherapy ( port ) , while 2% received port with chemotherapy . as our case showed a solitary regional metastasis without a detectable primary lesion and complete resection was achieved , we did not choose port and adjuvant chemotherapy . fortunately , the patient presented herein has been free from disease for 9 months . to our knowledge , this is the first case report of masc presenting as a cervical lymph node metastasis of unknown primary site and suggests new properties of masc . as previously described , masc has a capacity for an aggressive course , and the etv6-ntrk3 translocation might provide a potential therapeutic target [ 2 , 15 ] . further investigation is needed to translate targeted molecular therapies into therapeutic options for salivary grand malignancies including masc . we encountered the first case of masc presenting as a cervical lymph node metastasis of unknown primary site . no adjuvant radiotherapy was administered , and no local recurrence or metastatic disease has been detected during the 9-month follow - up period . written informed consent was obtained from the patient for publication of this case report and any accompanying images . none of the authors have any conflicts of interest to declare in association with this study .