paragangliomas ( pgls ) are uncommon tumors ( incidence 1 - 2 per 100,000 ) and based on their locations , the tumors are often given special designations . only three percent ( 3% ) of all pgls occur within the head and neck of which the majority are located in the carotid body ( carotid body tumors ) , temporal - bone / middle - ear ( glomus jugulare ) , and the vagus nerves in the neck ( vagal pgls ) .
ninety percent of the head and neck pgls are sporadic , only 10% are hereditary in nature .
parasympathetic extra - adrenal pgls are located predominantly in the head and neck ; and about 95% of such tumors are nonsecretory in nature .
in contrast with the sympathetic pgls , the parasympathetic extra - adrenal pgls are more often familial and less likely to be malignant .
the diagnosis of hereditary pgl syndrome is based on physical examination , family history , imaging studies , biochemical testing , and molecular genetic testing for the mutations , involving the subunits of succinate dehydrogenase , a mitochondrial enzyme . in this article
, we describe a patient with pgl presenting as a parotid gland mass which turned out to be a diagnostic dilemma in the initial fine needle aspiration ( fna ) due to its unexpected location . to our knowledge ,
the patient was a 56-year - old woman , with a history of unrepaired tetralogy of fallot and eisenmenger 's syndrome , who was admitted to our medical center with atrial flutter / atrial fibrillation , palpitations , and possible cerebrovascular accident due to the congenital heart disease .
magnetic resonance angiography ( mra ) evaluation of the head and neck showed an incidental right parotid gland mass .
subsequent ultrasound of this area showed a 2.0  1.5 cm solid tumor located in the deep within the parotid gland , which was presumed to be a pleomorphic adenoma .
cytological evaluation of the initial fna smears showed moderate cellularity consisting of atypical epithelioid cells in disorganized groups , strips , and single cells .
the atypical cells showed enlarged nuclei with variably granular chromatin , occasional nucleoli , anisonucleosis , and scant delicate cytoplasm [ figure 1a and b ] .
rare salivary gland acinar and ductal cells were noted as small groups in the blood - tinted background . since the cell block was paucicellular , two of the papanicolaou - stained slides were re - stained for synaptophysin and keratin by immunohistochemistry ( ihc ) .
the positive immunostain of the cells for synaptophysin [ figure 1c ] was compatible with a tumor of neuroendocrine origin .
subsequently , a diagnosis of  atypical cells present , suspicious for neuroendocrine tumor  was rendered .
composite photomicrographs of the tumor showing epithelioid cells arranged in a group with granular chromatins ( a , fna pap stain , 40 obj . ) ; pleomorphic nuclei with nucleoli ( b , fna diff - quick stain , 100 obj . ) ; and cells with positive staining for synaptophysin ( c , fna , 100 obj . ) .
the histological section of the tumor ( d , h and e , 40 obj . ) shows epithelioid or chief cells which are arranged in a pseudoalveolar pattern ( zellballen ) nested in a vascular stroma which were positive for synaptophysin but negative for cytokeratin .
hyperchromatic spindle shaped sustentacular cells are at the periphery of the chief cell nests ( arrows ) .
they were only positive for s-100 on the basis of diagnosis of neuroendocrine tumor by fna , a total parotidectomy and neck dissection was performed . during the surgery ,
the 2.0 cm mass was confirmed to be in the central portion of the deep lobe of the parotid gland . on gross examination ,
the tumor was a red - pink , firm , well - circumscribed mass , measuring 2.2  1.5  1.4 cm .
histological evaluation of the surgical specimen [ figure 1d ] showed epithelioid cells arranged in an alveolar pattern in nests surrounded by capillary networks .
a second type of cell was seen at the periphery of the nests which was more of a spindle shape .
the nested ( chief ) cells were positive for chromogranin and synaptophysin , while negative for keratin and s-100 .
a final histological diagnosis of pgl was made based on the characteristic morphology and immunohistochemical stains .
an incidental metastatic papillary thyroid carcinoma was identified in one of twenty - one dissected lymph nodes .
this finding led to a subsequent ultrasound of the thyroid gland which revealed a previously unknown sub - centimeter mass with calcifications suspicious for papillary thyroid carcinoma . due to the urgent cardiac problem of the patient ,
most of the parotid gland tumors ( 80% ) are benign comprising of pleomorphic adenoma and warthin 's tumor , both in solid and cystic forms .
remaining entities include oncocytoma , basal cell adenoma , and ductal papilloma in the benign category .
mucoepidermoid carcinoma , polymorphous low - grade adenocarcinoma , acinic cell carcinoma , adenoid cystic carcinoma , malignant mixed tumor , and squamous cell carcinoma are amongst the malignant category .
pgls most commonly present as an asymptomatic palpable mass in the anterior triangle of the neck .
the mass is usually slow growing and can easily be confused by the clinicians for a lymph node or other head and neck tumors .
sympathetic extra - adrenal pgls are generally confined to the thorax , abdomen , and pelvis , and are typically secretory which produce catecholamines .
the classic radiographic features are homogeneous or heterogeneous hyper - enhancing soft - tissue mass as shown by computed tomography ( ct ) scan ; multiple areas of signal void interspersed with hyperintense foci ( salt - and - pepper appearance ) within tumor mass as shown by magnetic resonance imaging ( mri ) ; and as an intense tumor blush with enlarged feeding arteries by angiography .
the preferred term for tumors of the extra - adrenal paraganglia is  paraganlioma ,  prefaced by the anatomic site of the origin .
tumors arising from the paraganglia of the adrenal medulla are called pheochromocytoma . pgls are highly vascular tumors composed of two types of cells that are arranged in a pseudoalveolar pattern known as zellballen or literally  cell balls  in german .
type i cells , the chief cells , are predominate in pgls and contain catecholamine - bound granules ( positive for synaptophysin and chromogranin ) .
type ii or sustentacular cells stain positive for s-100 , devoid of granules ( negative for synaptophysin and chromogranin ) , and are located at the periphery of the small pseudoalveolar clusters of type i cells .
malignancy can not be determined by cytology or even by histological findings and is only defined when the tumor metastasizes to regional lymph nodes or more distant sites .
nuclear polymorphism , neurovascular invasion , high mitotic indices , and necrosis have been described in both benign and malignant types of the tumors . on cytology ,
the cellularity may range from highly cellular to almost acellular , depending on the amount of contaminating red blood cells during sampling .
the neoplastic cells may have a variable morphology including classically described acinar arrangements with salt - and - pepper chromatin , but can also have spindle and pleomorphic forms with dense granular chromatin .
the differential diagnosis for this cytological pattern varies widely and depends on the morphological pattern of the tumor . aside from the other salivary gland lesions as previously mentioned ,
given the location , one may consider malignant melanoma , follicular variant of thyroid carcinoma and/or adenocarcinoma with an acinar pattern , whereas , a more spindled cell pattern could be suspected for a medullary thyroid carcinoma or even a sarcoma .
a combination of history , tumor location , clinical impression , radiology findings , and confirmatory ihc will assist in identifying the majority of these tumors .
fna biopsy has been performed on numerous occasions to establish a diagnosis of pgl.[1116 ] however , the exact role of fna in diagnosis of these tumors has not been currently established .
the main concern in performing a pre - operative fna on suspected pgls is the risk of hemorrhage and hematoma . in this article not only
are we reporting the first pgl of the parotid gland in the literature , but also would like to emphasize the cytological features of the tumor in fna aiding in the diagnosis .
this case report illustrates the importance of a broad differential diagnoses when confronted with unexpected cytology in an otherwise routine parotid gland fna with emphasis on morphological evaluation and immunohistochemical confirmation .
the second criterion is positivity for chromogranin - a and synaptophysin with negativity for cytokeratin by ihc . in contrast , the cells in the classical neuroendocrine tumors are positive for cytokeratin in a punctate form .
third , presence of a highly - bloody fna background is a characteristic and helpful feature .
it is needless to say that always malignant melanoma should be in the differential diagnoses list .
a simple ihc stain with hmb45 and/or melan - a antibodies will aid to rule out the latter .
the findings in this patient extend the spectrum of the pgls to the parotid and perhaps to all major salivary glands .
close interaction between the pathologists , radiologists , and the surgeons is required to avoid aggressive and unnecessary surgical procedures , such as the lymph node dissection , as it was in this case .
av cytopathology fellow , collected all the data , participated in cytological evaluation , and drafting of manuscript .
nam performed conceptual organization , cytological - histological evaluation , drafted and reviewed the manuscript .
as this is a case report without patient identifiers , approval from the institutional review board ( irb ) is not required at our institution .
to ensure the integrity and highest quality of cytojournal publications , the review process of this manuscript was conducted under a double blind model ( authors are blinded for reviewers and vice versa ) through automatic online system
 paragangliomas ( pgls ) are uncommon tumors . although pgls are known to occur in the head and neck region , especially the carotid body , middle ear , and larynx , involvement of the parotid glands has not been reported . in this article 
 , we report the fine needle aspiration features of tumor in an unusual location , presenting as a parotid gland mass , submitted to pathology for initial diagnosis . 
 the clinical presentation , cytomorphology , and the immunohistochemical features for the diagnosis are described . to our knowledge , this is the first case of paraganglioma of the parotid gland reported in the literature . 
INTRODUCTION
CASE REPORT
DISCUSSION
COMPETING INTERESTS STATEMENT BY ALL AUTHORS
AUTHORSHIP STATEMENT MADE BY ALL AUTHORS
ETHICS STATEMENT BY ALL AUTHORS
EDITORIAL/PEER-REVIEW STATEMENT