solid pseudopapillary neoplasm ( spn ) is an indolent epithelial tumor with a low malignant potential that occurs predominantly in females with a mean age of 28 years .
the clear cell variant of spn is even more unusual with only six papers reported in the english literature .
we present the cytologic features of clear cell variant of spn with the broad differential diagnosis and a review of past studies .
ultrasonogram showed a solid / cystic mass , 2.6 cm in diameter , in the tail of the pancreas .
percutaneous ultrasound - guided fine needle aspiration biopsy ( fnab ) was performed using a 22-gauge needle .
the excess material was fixed in an alcohol - formalin solution for cell block preparation and paraffin sections were stained by hematoxylin and eosin .
the material was highly cellular and consisted of a monotonous population of loosely cohesive small to medium - sized , round to cuboidal epithelioid cells exhibiting high nuclear / cytoplasmic ratio , finely granular  salt and pepper  chromatin and nuclear grooves .
pseudopapillary structures with arborizing capillaries and metachromic core on diff - quik - stained smears were lined by epithelioid cells .
acinar and rosette - like formations , as well as single neoplastic cells were observed [ figure 1 ] .
many tumor cells exhibited single or multiple clear cytoplasmic vacuoles , displacing the nucleus [ figures 2 and 3 ] .
the vacuoles were well - defined and variable in size , producing coin - shaped empty spaces in the cytoplasm [ figures 4 and 5 ] .
coin - shaped vacuoles were mimicking signet - ring appearance on the cell - block [ figures 6 and 7 ] .
periodic acid - schiff ( pas ) and mucicarmine stains were negative on the cell block sections .
typical complex - branching pseudopapillary structures surrounded with single and/or loosely cohesive neoplastic cells ( pap , smear ) the clear vacuoles were often single but numerous clear vacuoles were also observed both in neoplastic groups and single , discohesive , plasmocytoid neoplastic cells ( diff - quik , smears ) small groups of cells with clear cell vacuoles in variable sized ( diff - quik , smear ) intracytoplasmic vacuoles are well defined like coin  shaped ( diff - quik , smears ) vacuoles can be seen often and easily in diff - quik stained smears ( diff - quik , smears ) the vacuoles can be seen foamy to clear on cell block preparation ( h and e , cell block ) the vacuoles can mimick signet - ring appearance on cell block preparation ( h and e , cell block ) tumor cells showed strong nuclear staining for -catenin and cytoplasmic staining for vimentin and cd10 [ figures 810 ] .
neoplastic cells shows nuclear immuno reactivity with beta - catenin ( cell block ) strong cytoplasmic immuno reactivity with vimentin antibody ( cell block ) cd10 also showed strong cytoplasmic immuno reactivity similar to vimentin ( cell block )
spn is a rare tumor , which accounts for 1 - 3% of all non - endocrine tumors of the pancreas .
this tumor tends to occur in young adult females and is generally localized in the body and tail of the pancreas .
many theories have been hypothesized for the origin of the tumor including small duct epithelium , acinar cells , endocrine cells , totipotential stem cells or primitive cells capable of both exocrine and endocrine differentiation along with genital ridge - related cells that being incorporated into the pancreas during early embryogenesis .
massive necrosis results in cyst formation in these tumors , while viable tumor cells loosely adhere to the blood vessels , giving the appearance of pseudopapillary formation .
differential diagnosis of spn includes other solid , cystic and low grade malignant pancreatic neoplasms such as mucinous tumors , serous cystadenoma , neuroendocrine tumors , acinar cell carcinoma ( acc ) and pancreatoblastoma ( pb ) . the combination of cytomorphologic features with pseudopapillary formation , myxohyaline change in vessels and cell degeneration produces various patterns such as acinar , trabecular , pseudorosette and single discohesive cells .
immunocytochemistry is a highly useful tool in the differential diagnosis of this tumor . in the present case , striking intracytoplasmic vacuoles
clear cell dominated pattern spn was first described in 2006 by albores - saavedra et al .
they demonstrated three cases of spn with classic clinical features ranging in age from 26 to 32 years , in which the tumor cells had cytoplasmic vacuoles .
ultrastructurally , the cytoplasm contained a moderate amount of smooth and rough endoplasmic reticulum but no glycogen particles , lipid , mucin or neurosecretory granules .
the authors stated that the vacuoles were formed by dilatation of the smooth endoplasmic reticulum and mitochondria .
he acclaimed the need to be attentive particularly for endocrine tumors of the pancreas with clear cell morphology while diagnozing .
the latter group of patients , which tend to be von hipple lindau syndrome , also the clear cell cytoplasm in these tumors due to the presence of lipid droplets .
jhala et al . , were first to report the cytologic features of the clear cell variant of spn in 2007 , in a subsequent paper jhala et al .
they concluded that the presence of large clear vacuoles was more in favor of spn than pen .
hav et al . , and tanino et al . , reported one case each of this entity . in a recent report , zhao et al .
, emphasized the diagnostic challenges in the fnab of this variant . beside the classic mimics of spn mentioned above , clear cell variant presents even broader differential diagnosis including primary and metastatic clear cell adenocarcinomas , metastatic renal cell carcinoma , oncocytoma , adrenal cortical tumors , ectopic adrenal tissue in the pancreas and metastatic balloon cell melanoma .
vacuoles can appear foamy in the papanicolaou - stained smears and cell block sections , in contrast to the air - dried , diff -quik stained smears which show  coin - shaped  clear vacuoles .
the foamy appearance can simulate oncocytoma or oncocytic tumors such as the conventional and chromophobe renal cell carcinoma , oncocytic adrenocortical neoplasms and extra adrenal oncocytic paragangliomas .
clear cell spn can be distinguished from its mimics by careful attention to the clinical history , cytomorphologic and architectural features and the histological and immunocytochemical characteristics
. there may be still potential errors due to various presentations which result from the delphic origin of spn .
immunocytochemistry can be the key in these scenarios , being cytokeratin negative and vimentin positive .
intense nuclear staining for -catenin and focal positivity for alpha-1-antitripsin in pas positive globules are highly useful .
there are many additional stains in the literature such as cd10 , progesterone receptors , cyclin d1 , galectin3 etc .
, neuroendocrine markers ; particularly nse , cd56 and synaptophysin can may be expressed by neoplastic cells of spn , but chromogranin a is uniformly negative , which along with the lack of epithelial markers help to differentiate this tumor from pen .
the combination of negative staining for cytokeratins and strong nuclear staining for -catenin is also helpful in distinguishing this tumor from acc and pb , which are well - known mimics of spn .
the most helpful immunocytochemical stains in distinguishing clear cell spn from other pancreatic neoplasms and extra - pancreatic clear cell tumors are demonstrated in table 1 .
immunophenotypic profile of classic type and clear cell variant of spn including its common mimickers to the best of our knowledge , only two previous papers have reported the fnab features of clear cell spn .
we conclude that the clear cell variant of spn can be diagnosed cytologically by careful attention to the cytomorphological criteria , combined with immunocytochemical stains .
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 solid pseudopapillary neoplasm ( spn ) of the pancreas is a rare tumor of uncertain malignant potential , predominantly affecting young adult females . 
 we report a case of clear cell variant of spn , which was diagnosed by fine needle aspiration biopsy . 
 the aspirate was highly cellular and exhibited delicate branching papillary structures with central capillaries covered with several layers of plasmacytoid tumor cells . 
 acinar and rosette - like formations , as well as single neoplastic cells were also observed . 
 an unusual cytologic feature was the presence of large , clear cytoplasmic vacuoles . 
 the diagnosis of spn was confirmed by characteristic immunocytochemical staining pattern including nuclear staining for -catenin , cytoplasmic staining for vimentin and lack of reactivity for cytokeratin . 
INTRODUCTION
CASE REPORT
DISCUSSION
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