small cell lung cancer ( sclc ) accounts for 20 - 25% of all bronchogenic carcinomas and is associated with the poorest 5-year survival of all histologic types .
it represents a group of highly malignant tumors , giving rise to early and widespread metastasis at the time of diagnosis at sites such as lymph nodes , adrenal glands , liver , lung , brain and bones .
the pancreas is a relatively infrequent site of metastasis from this neoplasm , and reports on metastatic small cell carcinoma ( scc ) in the pancreas , either of pulmonary or extrapulmonary origin , to be diagnosed by fine needle aspiration ( fna ) cytology are very rare.[46 ] here , we report a case that was diagnosed as metastatic scc by ultrasound ( us)-guided fna cytology and immunocytochemical studies of a pancreatic mass .
a 66-year - old man , a heavy smoker , presented with persistent cough , weight loss and superior vena cava syndrome . computerized tomography ( ct )
ct scan of the abdomen showed a mass in the pancreatic tail , suggestive of metastasis from a primary in the lung .
grnwald  giemsa ( mgg ) stain and wet - fixed smears in 95% ethanol were stained by papanicolaou method .
the smears were highly cellular and contained small , round tumor cells with scanty cytoplasm , which showed extensive nuclear molding [ figure 1a and b ] .
the nuclei of the tumor cells were round to oval and had salt and pepper type chromatin .
some singly dispersed neoplastic cells resembled lymphoma cells and were accompanied by a few cytoplasmic fragments [ figure 1c ] .
most of the tumor cells were found to have a positive reaction for pan - cytokeratin [ figure 1d ] , and a variable number were positive for neurone - specific enolase [ figure 1e ] and chromogranin a. occasional tumor cells were positive for synaptophysin , but all were negative for leukocyte common antigen . based on cytomorphology and immunocytochemistry , the diagnosis was metastatic scc .
metastatic small cell carcinoma : ultrasound - guided fna of a pancreatic mass in a 66-year - old man : cytomorphological features and immunocytochemical stainings on fna smears .
( a ) the neoplastic cells show nuclear molding and have round to oval nuclei with a salt and pepper type chromatin pattern ( papanicolaou , 400 ) .
( b ) highly cellular smear show small , round tumor cells with scanty cytoplasm , extensive nuclear molding , and mitotic activity ( mgg , 400 ) .
( c ) dissociated lymphoma - like tumor cells along with a few cytoplasmic fragments resembling lymphoglandular bodies are observed ( mgg , 1000 ) .
( d ) positive reaction for cytokeratin in most of the tumor cells ( ck , 400 ) ( e ) positive reaction for neurone - specific enolase in a few neoplastic cells , including rare large cells ( nse , 1000 ) the patient was subjected to trans - bronchial needle aspiration ( tbna ) and biopsy .
the tbna smears were non - diagnostic but trans - bronchial needle biopsy contained tissue fragments containing bronchial glands , closely associated with aggregates of small , round blue tumor cells .
the tumor cells were positive for chromogranin a , synaptophysin , cd57 and cytokeratin ( ck ) , but staining for cd 20 and cd3 was negative .
metastatic involvement of the pancreas is an infrequent clinical condition . on searching medical records of 850 patients with lung cancer , maeno et al . identified 26 ( 3.1% ) patients with pancreatic metastasis .
yoon et al . reported 53 pathologically proven metastatic tumors of the pancreas ( mtps ) ; the primary malignancies were renal cell carcinoma ( n=14 ) , gastric cancer ( n=11 ) , colorectal cancer ( n=5 ) , lymphoma ( n=4 ) , non - sclc ( n=3 ) , gastrointestinal stromal tumor ( n=2 ) , melanoma ( n=2 ) , sclc ( n=2 ) , gallbladder cancer ( n=2 ) and one case each of hepatocellular carcinoma , thymic carcinoid , liposarcoma , cholangiocarcinoma , osteosarcoma , breast cancer , duodenal cancer and ovarian cancer . among 20 non - hematological metastases in the pancreas evaluated by fna , volmar et al . observed 9 renal - cell carcinomas , 3 melanomas , 2 pulmonary small - cell carcinomas , 2 breast carcinomas and one each case of prostate carcinoma , colon adenocarcinoma , pulmonary squamous cell carcinoma and gastrointestinal stromal tumor .
reported 17 metastatic malignancies to pancreas , which accounted for 0.73% of all pancreatic fnas .
the primary sites included eight renal cell carcinomas , four lymphomas , two squamous cell carcinomas ( one from the lung and the other from the esophagus ) , one medullary thyroid carcinoma , one alveolar rhabdomyosarcoma and an sclc .
the sclc includes three morphologic categories in paraffin sections : ( 1 ) scc , ( 2 ) mixed small cell / large cell and ( 3 ) combined scc . in our case , the smears were made mostly of small cells , interspersed with occasional large cells .
the neoplastic cells had scant cytoplasm and stippled or salt - and - pepper type chromatin .
nuclear molding was conspicuous and scattered cells with paranuclear blue inclusions or apoptotic bodies were present throughout the smear .
extreme nuclear molding by clusters of small tumor cells is considered to be the most characteristic presentation of scc ; moreover , paranuclear blue inclusions , which are 1 - 4 m spherical inclusions demonstrated by romanowsky stain , may act as a diagnostically useful finding . according to arora
, nuclear molding , cell size and scant , basophilic cytoplasm were highly sensitive and specific for distinguishing scc from non - scc ( nscc ) .
other features , such as salt - and - pepper chromatin , crush artifact and apoptotic bodies , had also significantly high specificity ; however , their low sensitivity precluded their usefulness in separating scc from nscc .
difficulties may be observed in differentiating metastatic scc from other small round cell tumors and primary pancreatic scc from metastatic scc . in the present case , we observed dissociation of neoplastic cells and presence of cytoplasmic fragments resembling lymphoglandular bodies , which are common features of non - hodgkin lymphoma , but can be observed in a small percentage in other small round cell tumors . under such situations , a panel of immunohistochemical stains can be useful in differentiating scc from various other small cell neoplasms . in practical work - up of scc , immunohistochemistry is useful to discern scc from high - grade lymphoma ; scc labels with antibodies to high molecular weight cytokeratins , but not with antibodies to leukocyte common antigen ( cd45 ) . in our case ,
the neoplastic cells in fna smears were ck+ and stain for lca showed negative reaction , thus excluding the possibility of non - hodgkin lymphoma .
the most common immuno profile of metastatic ssc from a lung primary is positive staining with cytokeratin 7 and thyroid transcription factor ( ttf)-1 and no reaction to ck20 .
however , immunohistochemical studies are found to have limited value in distinguishing a primary site from metastatic scc . according to lin et al .
, immunohistochemistry has not proven useful in distinguishing primary periampullary scc from metastatic sclc . although , a high percentage of lung primary cancer expresses ttf-1 , this marker has variable positivity in patients with extrapulmonary scc , and the expression of ttf-1 has not been well explored in pancreatic scc , with only one negative reported case in literature to date .
moreover , cytokeratin ( ck7 and ck20 ) switching can occur in the natural history of pulmonary ssc . in our case ,
the pancreatic fna cytology was diagnosed as metastatic scc , which was positive for pan - ck , neurone - specific enolase , chromogranin a and synaptophysin .
however , the immunohistochemical/ immunocytochemical panels did not include ck7 , ck20 and ttf-1 , which could have further confirmed the primary lung cancer .
 small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis . 
 however , the pancreas is a relatively infrequent site of metastasis by this neoplasm , and there are only occasional reports on its fine needle aspiration ( fna ) cytology diagnosis . a 66-year - old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail . 
 ultrasound - guided fna smears from the pancreatic mass contained small , round tumor cells with extensive nuclear molding . 
 the cytodiagnosis was metastatic small cell carcinoma . 
 immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin , chromogranin a , neurone - specific enolase and synaptophysin but negative for leukocyte common antigen . 
 the trans - bronchial needle aspiration was non - diagnostic , but biopsy was suspicious of a small cell carcinoma . 
 this case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma , diagnosed by fna cytology . 
Introduction
Case Report
Discussion