a carcinoma ex pleomorphic adenoma ( cxpa ) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma . minor salivary gland cxpas of the nasal cavity are exceedingly rare , with only 6 documented in the literature . we present a 7th case : an unusual pedunculated intranasal cxpa , which had a favorable outcome after a wide endoscopic excision and the longest follow - up period reported to date . the clinical features , immunohistochemical characteristics , treatment choices , and disease outcomes of the intranasal cxpas reported in previous studies are also reviewed . this case demonstrates the importance of considering the possibility of cxpa in the differential diagnosis of minor salivary gland malignancies in the nasal cavity . a carcinoma ex pleomorphic adenoma ( cxpa ) is an uncommon epithelial malignancy that develops in a preexisting pleomorphic adenoma ( pa ) . the carcinoma may arise from the epithelial or myoepithelial component ( or both ) of a pa . the most frequently affected site is the parotid gland , followed by the submandibular gland . the signs and symptoms most frequently encountered are a painless mass that exhibits little change over a long duration , and then exhibits sudden , rapid growth . the exact etiologic factors associated with the malignant transformation of a benign pa remain unclear . exposure to radiation and the development or accumulation of genetic instabilities within a long - standing tumor are considered to be potential factors in this transformation . the incidence of malignant transformation of persistent or recurrent pa increases from 1.5% after 5 years to 10% after 15 years . cxpas rarely affect the minor salivary glands , constituting approximately 2.6% of all minor salivary gland tumors and 18% of all minor salivary gland malignancies . minor salivary gland cxpas often develop in the oral cavity and the oropharynx ; the soft and hard palate are the most common sites . in addition to these locations , cxpas have been reported in the buccal mucosa , the upper lip , lacrimal gland , and nasal cavity . unusual sites of cxpas , such as the trachea and breast , have also been described . tumors arising from the seromucinous glands of the sinonasal region are histologically similar to tumors of the major salivary glands ; however , the majority of them are malignant . minor salivary gland tumors of the sinonasal tract generally have a favorable overall survival rate , despite a high rate of recurrence . nevertheless , minor salivary gland malignancies of the sinonasal tract have a poorer prognosis compared with their oral cavity counterparts because of their different biological behavior , a higher incidence of more aggressive adenoid cystic carcinoma , the complex anatomy of their location , and a relative delay in their diagnosis . similar lesions in the nasal cavity have been regarded as  medical curiosities .  only 6 cases , we add a unique case of cxpa that arose in the nasal cavity of a 46-year - old female patient , namely a pedunculated presentation of cxpa that had undifferentiated and squamous carcinomatous components as malignancies . this case entailed a 24-month follow - up after a wide endoscopic excision and had a favorable clinical outcome . a 46-year - old woman presented to an otorhinolaryngology department with intermittent left - sided epistaxis for 1 month . no enlarged cervical lymph nodes were noted , and the remaining physical examination was unremarkable . nasal endoscopy revealed a well - defined , solitary , irregular - surfaced , friable mass that exhibited contact bleeding and was located in the left nasal cavity . 1 ) . computed tomography revealed an expansile soft tissue mass 1.8  cm in diameter at the anterior part of the left nasal cavity without destruction of the surrounding bone structure ( fig . the patient underwent an endoscopic excision . the surgical specimen ( 2.2    1.5    1.3  cm ) was a pedunculated , well - circumscribed , encapsulated , myxoid , rubbery mass that exhibited a fleshy cut surface upon sectioning ( fig . microscopic examination produced biphasic epithelial images that showed an admixture of surface neoplastic squamous epithelial cells and underlying mixed components of spindle- to polygonal - shaped pleomorphic myoepithelial cells and myxoid stroma ( fig . the surface squamous epithelium showed hyperchromatic and pleomorphic cells with the immunoreactivity for p63 , which were identified as squamous cell carcinoma . the underlying mixed components showed that some foci of the epithelial cells abruptly transitioned to neoplastic cells that had an increased nuclear - cytoplasm ratio , a markedly elevated mitotic rate ( 45/10 high - power field ) , and highly pleomorphic hyperchromatic nuclei arranged in either solid or loose hemorrhagic patterns ( fig . the surface neoplastic squamous epithelium was immunoreactive for p63 and bcl-2 but the underlying different patterns of neoplasms were immunoreactive for ck7 , vimentin , p63 , bcl-2 , gfap , and sma ( fig . because of the mixed epithelium and myoepithelium and the presence of the myxoid stroma , cxpa was diagnosed . we performed a wide endoscopic excision of the remaining mucoperichondrium of the nasal septum and a subsequent left middle turbinectomy . a residual tumor was found in the nasal septum , measuring 0.2    0.2    0.15  cm , with a depth of 0.15  cm . the surgical margins were microscopically negative for tumor cells ; the carcinoma extended to within 0.2  cm of the closest margin . the patient received no adjuvant therapies and no signs of recurrence or distant metastasis were observed after 24 months of follow - up ( fig . axial and coronal noncontrast computed tomographic image of the nose and paranasal sinuses showing an expansile soft tissue mass in the left nasal cavity ( white arrows ) . ( b ) microscopic examination revealed the heterogeneity of the tumor ( hematoxylin and eosin , 40 ) . ( a ) the surface squamous epithelium showed hyperchomatic and pleomorphic neoplastic cells ( 200 ) . ( b ) myxoid stroma with relatively bland - looking nuclei was noted in the adjacent part of the neoplasm ( 200 ) . ( c ) the cellular solid area of the underlying carcinoma ex pleomorphic adenoma was composed of hyperchromatic cells ( 100 ) . ( d ) some foci displayed a loose hemorrhagic pattern with occasional enlarge pleomorphic neoplastic cells ( 200 ) . ( a ) ck7 , ( b ) vimentin , ( e ) gfap , and ( f ) sma were negative in the surface squamous carcinoma but positive in the underlying cxpa . however , ( c ) p63 and ( d ) bcl-2 were immunoreactive in both the surface squamous carcinoma and underlying cxpa . the term  malignant mixed tumor  can refer to 3 different subtypes , namely cxpas , true malignant mixed tumors ( carcinosarcomas ) , and metastasizing mixed tumors . most cases , such as that of our patient , belong to the first category . a cxpa is a malignant epithelial neoplasm arising in a benign tumor ( pa ) . tumors of this variety constitute approximately 3.6% to 4% of all salivary gland neoplasms and 12% of all salivary gland malignancies . although most cxpas occur in the major salivary glands , typically in the parotid gland , cases arising from the minor salivary glands of the oral cavity and oropharynx account for approximately 17.5% of the armed forces institute of pathology series . cxpas are subclassified into 3 main categories by the world health organization on the basis of the degree of invasion of the carcinoma beyond the pa capsule , namely invasive ( > 1.5  mm invasion from the tumor capsule into adjacent tissues ) , minimally invasive ( 1.5  mm penetration of the malignant component into extracapsular tissue ) , and noninvasive . di palma proposed an alternative classification of cxpas into 2 clinically relevant categories : early cxpas and widely invasive cxpas . widely invasive cxpas include any cxpa with an invasion of more than 6  mm . a cxpa is diagnosed by examination under a microscope , in addition to the consideration of patient history . the presence of an infiltrative and destructive growth pattern of carcinoma in juxtaposition with a pa is the diagnostic criterion for cxpa . in approximately 75% of cases , cxpas arise in a pa that is apparent in the surgical specimen . however , the proportion of the malignant component varies widely , and in certain instances , ascertaining the location of the original benign pa is difficult . diagnosis of a cxpa depends on a careful sampling of the tumor after resection to locate any coexisting benign adenomatous component . the malignant components most commonly observed in cxpas are adenocarcinomas ( not otherwise specified ) . almost all other malignant varieties of salivary gland tumors have been described ( e.g. , undifferentiated carcinoma , squamous cell carcinoma , mucoepidermoid carcinoma , salivary duct carcinoma , adenoid cystic carcinoma , small cell carcinoma , and myoepithelial carcinoma ) . until the past decade , the genuine malignancies of these early changes in pas were confirmed using immunohistochemical and molecular genetic analysis of the human epidermal growth factor receptor 2 ( her-2 ) and tp53 genes . her-2 and tp53 genes and proteins are involved in the early stages of the malignant transformation of pas . furthermore , the immunohistochemical overexpressions of her-2 , p53 protein , and the mib-1 proliferation marker could be used as targets to identify malignant areas in pas . cxpas of the nasal cavity are exceedingly rare , with only 6 prior cases documented in the literature ( table 1 ) . the most common presenting symptoms in the reported cases are intermittent nasal bleeding and unilateral nasal obstruction . the average age of the affected patients was 55.7 years , approximately a decade older than the average age of patients with pa of the nasal cavity . all reported cases have involved a surgical procedure as an initial treatment modality , such as a wide excision through lateral rhinotomy , partial or medial maxillectomy , or craniofacial resection . however , the unique presentation of a pedunculated , well - encapsulated nasal mass in our patient resulted in our utilizing a wide endoscopic excision . in a recent meta - analysis , rawal et al demonstrated that the overall 2- and 5-year survival rates associated with endoscopic removal of sinonasal malignancies were comparable to , and sometimes greater than , those published for the open resection of sinonasal malignancies . the survival rates of endoscopic endonasal resection seemed to correlate more strongly with cancer grading than with cancer staging . on the basis of a retrospective study , chen et al proposed that surgery followed by postoperative radiation therapy should be the standard of care for patients with cxpa of the parotid gland . however , this conclusion may not apply to intranasal cxpas because of the different biological behavior of the sinonasal tract and a high degree of heterogeneity in cancer subtypes . therefore , only 2 out of the 7 documented cases of intranasal cxpas have involved adjuvant radiotherapy . because of the short follow - up period of the reported cases , the role of postoperative radiotherapy in the prognosis of intranasal cxpas is inconclusive . however , although the number of cases is small , notable trends can be observed . cxpas mainly affect women , and 6 out of the 7 reported cases of intranasal cxpas , including that of our patient , presented in women . most cases ( 5 out of 7 ) of intranasal cxpa involved the nasal septum , and only 1 case originated in the lateral nasal wall ; the other case originated in the nasal floor . moreover , the malignant component of cxpas found in the nasal cavity apparently tends to consist of various combinations of differentiations . for instance , freeman et al reported a case of intranasal cxpa involving the presence of adenoid cystic and squamous carcinomatous differentiation . chimona et al presented another case of nasal cxpa that exhibited squamous and mucoepidermoid carcinoma . in the present case , we identified both undifferentiated and squamous carcinomatous components in the surgical specimen . cxpas with double differentiation of the carcinomatous component have also been reported in minor salivary gland cxpas arising from the palate and buccal mucosa . histopathological factors relating to the prognosis of cxpas were discussed by weiler et al . however , whether intranasal cxpas share the same prognosis significance is uncertain , because an insufficient number of cases with long - term follow - up have been reported to lead to any meaningful conclusions about their clinical behavior . because of close margins and concerns about local recurrence , postoperative radiation therapy was advised for our patient ; nevertheless , she chose close follow - ups instead of receiving adjuvant radiation therapy . no evidence of local recurrence or distant metastasis was found after 24 months of follow - ups . although cxpa was diagnosed in the present case , the mixed patterns and immunoreactive results were notably unusual . the main differential diagnosis was polymorphous low - grade adenocarcinoma ( plga ) because of the different patterns in the tumor . the morphological patterns typically include lobular solid nests admixed with cribriform , trabecular , and focal papillary cystic areas . the tumor stroma is composed of fibrous tissue that shows varying degrees of hyalinization and myxoid change . although many factors of cxpa and plga overlap , the presence of myxoid stroma , immunoreactivity for gfap , and an apparent mixture of surface carcinoma types contributed to the final diagnosis of cxpa . in summary , we present a rare case of pedunculated intranasal cxpa with a favorable outcome after a wide endoscopic excision and the longest follow - up period published to date . this case demonstrates the importance of considering the possibility of cxpa in the differential diagnosis of minor salivary gland malignancies in the nasal cavity . we identified a predominance of cases in women , a tendency to originate in the nasal septum , and the characteristic of double differentiation of the carcinomatous component of the reported intranasal cxpas . because of their extremely low incidence , information about the natural course , prognosis , and treatment of intranasal cxpas can currently be extrapolated from the published data regarding tumors of the same type that are located in the major salivary glands .
abstractbackground : a carcinoma ex pleomorphic adenoma ( cxpa ) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma . the parotid gland is the most common location of cxpas . 
 minor salivary gland cxpas of the nasal cavity are exceedingly rare , with only 6 documented in the literature.methods and result : we present a 7th case : an unusual pedunculated intranasal cxpa , which had a favorable outcome after a wide endoscopic excision and the longest follow - up period reported to date . 
 the clinical features , immunohistochemical characteristics , treatment choices , and disease outcomes of the intranasal cxpas reported in previous studies are also reviewed.conclusion:this case demonstrates the importance of considering the possibility of cxpa in the differential diagnosis of minor salivary gland malignancies in the nasal cavity .