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paragangliomas ( pg ) are the neoplasms arising from clusters of neuroendocrine cells in association with sympathetic and parasympathetic nervous system .
these tumors include pheochromocytoma , carotid body tumor and other extra - adrenal paragangliomas ( eap ) , which have a widespread distribution .
the use of fine - needle aspiration ( fna ) in the diagnosis of paraganglioma has been controversial due to potential risk of hemorrhage within the lesion and precipitating a hypertensive crisis .
however , when eap is not suspected clinically due to lack of typical presentation , fna is often used as a diagnostic modality for initial workup .
the clinical differential diagnoses of eap in the head and neck region include lymphadenopathy , branchial cleft cyst , carotid artery aneurysm , carcinoma thyroid , and neural tumors .
eap poses a diagnostic challenge because of its widespread anatomic distribution , subtle clinical manifestations and a variety of morphologic patterns .
the aim of this study is to describe the cytological findings of eap and discuss the differential diagnoses .
seven cases cytologically diagnosed as eap over a period of 10 years ( 2003 - 2012 ) were retrieved .
only one case presenting as superficial swelling in right upper cervical region was clinically suspected to be carotid body tumor .
the superficial swellings were aspirated directly , and the retroperitoneal masses were aspirated under ultrasound guidance using 22-gauge lumbar puncture needle fitted to a 10 ml syringe .
smears were reviewed for cellularity , architectural pattern , cell shape , cytoplasm , nuclear features , and background .
the age range was 25 - 75 years ( mean 48.76 years ) , four patients were males and three were females .
the sites involved were carotid body region ( four cases ) , para - aortic region ( two cases ) and para - pharyngeal space ( one case ) .
clinical details and radiologic findings in extra - adrenal paraganglioma ( n = 7 ) the smears were cellular in five cases , while two cases were paucicellular [ table 2 ] .
the tumor cells were singly scattered and in clusters with focal acinar formations [ figure 1a ] .
the cells were mostly round to oval , polygonal with plasmacytoid appearance at places [ figure 1b ] .
the nuclei were single or multiple , pleomorphic with bland nuclear chromatin and prominent nucleoli in all cases .
irregular nuclear membranes and grooves were observed in three cases , with the presence of intranuclear inclusions in two and nuclear budding in one case [ figure 1c ] .
smears from extra - adrenal paraganglioma showing : ( a ) rich cellularity with the presence of cell clusters and dispersed cells ( mgg , 200 ) , ( b ) round to polygonal cells with nuclear pleomorphism , abundant granular cytoplasm and a few binucleated cells ( arrow ) ( mgg , 400 ) , ( c ) prominent intranuclear cytoplasmic inclusion ( arrow ) ( mgg , 600 ) and a cell with nuclear budding ( inset ) ( mgg , 600 ) , ( d ) cell block preparation with clusters of tumor cells on the left side ( h and e , 100 ) and immunohistochemistry for chromogranin with strong cytoplasmic positivity on the right side ( ihc , 400 ) spectrum of cellular details in extra - adrenal paraganglioma ( n = 7 ) histopathologic examination was done in five cases .
sections showed solid tumor with typical organoid pattern and pseudo - rosettes were seen in one case .
the tumor cells were large polygonal cells with cellular and nuclear pleomorphism and abundant granular cytoplasm .
all cases showed cytoplasmic immunopositivity for chromogranin and a final diagnosis of eap was made .
two cases were finally diagnosed as carotid body tumor on doppler ultrasound vascular imaging and computed tomography ( ct ) angiography .
one case was clinically suspected to be carotid body tumor based on ultrasound findings prior to the fna procedure .
the smears were cellular in five cases , while two cases were paucicellular [ table 2 ] .
the tumor cells were singly scattered and in clusters with focal acinar formations [ figure 1a ] .
the cells were mostly round to oval , polygonal with plasmacytoid appearance at places [ figure 1b ] . one case with a para - aortic mass showed prominent spindling of tumor cells .
the nuclei were single or multiple , pleomorphic with bland nuclear chromatin and prominent nucleoli in all cases .
irregular nuclear membranes and grooves were observed in three cases , with the presence of intranuclear inclusions in two and nuclear budding in one case [ figure 1c ] .
smears from extra - adrenal paraganglioma showing : ( a ) rich cellularity with the presence of cell clusters and dispersed cells ( mgg , 200 ) , ( b ) round to polygonal cells with nuclear pleomorphism , abundant granular cytoplasm and a few binucleated cells ( arrow ) ( mgg , 400 ) , ( c ) prominent intranuclear cytoplasmic inclusion ( arrow ) ( mgg , 600 ) and a cell with nuclear budding ( inset ) ( mgg , 600 ) , ( d ) cell block preparation with clusters of tumor cells on the left side ( h and e , 100 ) and immunohistochemistry for chromogranin with strong cytoplasmic positivity on the right side ( ihc , 400 ) spectrum of cellular details in extra - adrenal paraganglioma ( n = 7 )
sections showed solid tumor with typical organoid pattern and pseudo - rosettes were seen in one case .
the tumor cells were large polygonal cells with cellular and nuclear pleomorphism and abundant granular cytoplasm .
all cases showed cytoplasmic immunopositivity for chromogranin and a final diagnosis of eap was made .
two cases were finally diagnosed as carotid body tumor on doppler ultrasound vascular imaging and computed tomography ( ct ) angiography .
one case was clinically suspected to be carotid body tumor based on ultrasound findings prior to the fna procedure .
a substantial number of eaps are nonfunctional ; hence , a correct clinical diagnosis is seldom made .
fna may be a first - line of investigation in such cases and help in arriving at a preliminary or final diagnosis .
eap are uncommon neoplasms , known to occur in a wide variety of anatomic sites . among eap ,
carotid body region is the most common site as in the present series , followed by the retroperitoneum and mediastinum .
majority have a dispersed cell population with acinar / rosette formations of round to oval , plasmacytoid or spindle shaped cells with considerable anisokaryosis .
abundant cytoplasm with red granules , vacuolization and indistinct cytoplasmic borders can not be overemphasized .
the background is hemorrhagic in most of the cases . in our series , all cases showed clusters and singly scattered round to polygonal cells with pleomorphic nuclei and moderate to abundant cytoplasm with fine pink granularity .
in addition , acinar formation , nuclear grooves , inclusions , membrane irregularity , budding , and nucleoli were also seen .
varma et al . have reported nuclear budding in 8 out of 12 cytologically diagnosed cases of pg .
the cytologic differentiation of paraganglioma from other entities is a herculean task due to varied anatomic locations and tremendous cellular pleomorphism noted in these tumors . in the neck region
, it can be difficult to differentiate paraganglioma from thyroid neoplasms , neurogenic tumors and metastatic carcinoma .
acinar structures in paraganglioma can be mistaken for the follicles seen in follicular neoplasm of the thyroid .
occasional cases of paraganglioma may show intranuclear cytoplasmic inclusions as seen in papillary carcinoma thyroid .
presence of papillae and optically clear nuclei in papillary carcinoma thyroid are discriminating morphological features .
plasmacytoid appearance and intracytoplasmic reddish - pink granules in paraganglionic tumors may lead to a misdiagnosis of medullary carcinoma thyroid .
a misdiagnosis of neurogenic tumor is not unlikely when there is predominance of ovoid or spindle shaped nuclei in some pg .
the uniform and benign looking chromatin pattern of the nucleus in paraganglioma helps in distinguishing it from metastatic carcinoma . in the retroperitoneal location ,
differential diagnoses include epithelial tumors such as renal cell carcinoma , adrenal cortical tumor , carcinoid tumor , islet - cell tumor , chordoma , and metastatic adenocarcinoma .
in renal cell carcinoma , the cytoplasm is less fragile with more prominent vacuolization and cell borders are well - defined .
adrenal cortical tumors show a lipid background and are comparatively less pleomorphic with tiny lipid droplets in the cytoplasm .
the cytomorphologic features of chordoma are quite characteristic and show physaliferous cells in the background of chondroid matrix .
occasionally , hepatocellular carcinoma , neurogenic tumors , sarcomas and melanoma may also enter into the differential diagnosis .
radioimaging studies like ultrasound , ct scan with enhancement , magnetic resonance imaging and vascular imaging studies ; like doppler ultrasound and selective digital subtraction angiography are useful adjuncts to cytomorphology .
these studies help in exact localization of eap and also define their relation with major blood vessels .
cytomorphologic features like dispersed cell population with acinar pattern , plasmacytoid cells with salt and pepper nuclear chromatin and abundant granular vacuolated cytoplasm with indistinct cytoplasmic borders suggest a diagnosis of eap .
background : paraganglioma is a rare tumor arising from clusters of neuroendocrine cells in association with sympathetic and parasympathetic nervous system . it poses a diagnostic challenge because of its widespread anatomic distribution , subtle clinical manifestations , and a variety of morphologic patterns.aim:the aim of this study is to have an insight into the diverse morphologic spectrum of extra - adrenal paraganglioma ( eap).materials and methods : a retrospective analysis of seven cytologically diagnosed cases of eap over a period of 10 years was performed . 
 there were five superficial swellings and two deep seated retroperitoneal masses . 
 the superficial swellings were aspirated directly , and the retroperitoneal masses were aspirated under ultrasound guidance using 22-gauge lumbar puncture needle fitted to a 10 ml syringe . 
 smears were reviewed for cellularity , pattern , cell shape , cytoplasm , nuclear features , and background.results:the age of patients ranged from 25 to 75 years ; four patients were males and three were females . 
 sites involved were carotid body region ( four cases ) , para - pharyngeal space ( one case ) and para - aortic region ( two cases ) . 
 all the cases yielded hemorrhagic material on fine - needle aspiration . 
 smears showed scattered and clusters of cells and loosely cohesive acini of tumor cells . 
 cells were round to polygonal with pleomorphic nuclei , granular chromatin , inconspicuous nucleoli , and moderate to abundant cytoplasm containing fine pink granules and vacuolations . 
 the cases were confirmed on radiology and histopathology.conclusion:the cytologic features in eap along with pertinent clinicoradiologic findings help in making an accurate preoperative diagnosis of an otherwise rare tumor .