involvement of the pancreas by secondary malignancies is a well - documented , yet uncommon occurrence , accounting for 415% of all malignancies in the pancreas found at autopsy . these secondary tumors often present as a single or multiple masses in patients with or without a known history of malignancy . in some cases , secondary neoplasms may share morphologic features with primary pancreatic neoplasms , thus imposing a diagnostic challenge . the distinction of primary pancreatic neoplasms from metastatic disease has a significant impact on patient clinical management . most metastatic diseases involving the pancreas are treated with non - surgical approaches , although surgical resection is being increasingly performed for isolated metastases to the pancreas . endoscopic ultrasound - guided fine needle aspiration ( eus - fna ) has emerged as a safe and favorable method for evaluating pancreatic lesions . the diagnostic performance of fna for primary pancreatic tumors , primarily ductal adenocarcinoma , has a sensitivity ranging from 58% to 92% and specificity ranging from 93% to 100% . however , there are only few reports in the literature that address the use of fna in secondary tumors involving the pancreas . in this retrospective study , we reviewed our institutional experience in diagnosing secondary malignancies involving the pancreas via eus - fna and discuss diagnostic clues and pitfalls for these lesions . a computer - based data search was conducted to identify all eus - fna of pancreatic masses performed at our institution over a 7-year period from july 2005 to june 2012 . exclusive peripancreatic masses or masses that arose from nearby organs and locally invaded to the pancreas were excluded . for the cases selected , we reviewed clinical data , imaging study reports , cytologic diagnosis , ancillary studies , and surgical follow - up if available . the clinical characteristics included age , sex , history of malignancy , and latency period since the initial diagnosis of malignancy . the imaging characteristics of the pancreatic lesion(s ) included size , site , solitary versus multiple lesions , and the presence of synchronous extra - pancreatic lesions . direct smears were prepared and stained with diff - quik ( dade diagnostics , west monroe , la , usa ) after air - drying or with papanicolaou stain after alcohol fixation . the remaining aspirate was collected in cyto - rich red fixative ( bd diagnostics , franklin lakes , nj , usa ) and processed for cell block . hematoxylin and eosin stained sections were used for additional morphologic evaluation . in selective cases , the cell block sections were used for immunocytochemical studies or molecular tests . in cases cytologically suspicious for lymphoproliferative disorders , part of the aspirate was saved in rpmi preservative and submitted for flow cytometric studies . out of 1346 pancreatic eus - fna cases performed between july 2005 and june 2012 , 31 patients ( 2.3% ) were eventually diagnosed with metastatic malignancy to the pancreas or secondary involvement of the pancreas by a hematologic malignancy . out of these 31 patients , 19 were male ( 61% ) and 12 were female ( 39% ) [ table 1 ] . the average age at diagnosis was 66 years ( ranging from 49 to 86 years ) . in these patients , the latency period between the primary diagnosis of malignancy and the development of pancreatic lesions ranges from 6 months to 19 years with an average of 5.9 years . the patients with metastatic renal cell carcinoma ( rcc ) had the longest latency period , averaging 11.8 years . clinical and imaging characters of secondary tumors involving the pancreas secondary tumors presented as a solitary lesion in the pancreas in 17 cases , while the remaining 14 cases had multiple pancreatic lesions [ table 1 ] . in 6 of 14 cases with multiple pancreatic lesions , the pancreatic lesions were located in the body / tail region in 18 cases and in the head / uncinate process in 12 cases . the size of the pancreatic lesions was recorded in 28 cases with an average of 4.3 cm ( ranging from 1.1 to 10 cm ) . the final diagnoses of these secondary tumors were metastatic carcinoma ( 24 cases , 77% ) , lymphoproliferative disorder ( 4 cases , 13% ) , and metastatic sarcoma ( 3 cases , 10% ) [ table 2 ] . the metastatic carcinomas included rcc ( 8 cases ) , nonsmall cell lung cancer ( nsclc , 4 cases ) , small cell lung cancer ( sclc , 3 cases ) , colorectal carcinoma ( 2 cases ) , adenocarcinoma of the breast ( 2 cases ) , esophageal carcinoma ( 1 case ) , ovarian carcinoma ( 1 cases ) , cervical carcinoma ( 1 case ) , urothelial carcinoma ( 1 case ) , and merkel cell carcinoma ( 1 case ) . the lymphoproliferative disorders included diffuse large b - cell lymphoma ( dlbcl , 2 cases ) and plasma cell neoplasm ( 2 cases ) . cytological diagnoses , ancillary studies , follow - up and final diagnosis of secondary tumors involving the pancreas the correct cytological diagnoses were rendered in 29 out of 31 cases ( 94% ) while two cases were misclassified as primary pancreatic carcinomas [ table 2 ] . in 18 out of the 29 cases with correct cytological diagnoses , ancillary studies were used to reach the final diagnosis . the ancillary studies included immunostaining ( 16 cases ) and flow cytometry ( 2 cases ) . the remaining 11 cases with no ancillary testing were solely diagnosed based on morphological features . all of these 11 patients had a known prior history of malignancy in which histologic morphology was available to compare with that seen in the cytological material . these 11 cases included rcc ( 3 cases ) , nsclc ( 2 cases ) , ductal carcinoma of the breast ( 2 cases ) , small cell carcinoma of the lung ( 1 case ) , plasma cell neoplasm ( 1 case ) , esophageal adenocarcinoma ( 1 case ) , and urothelial carcinoma ( 1 case ) . the 2 cases that were misclassified as primary pancreatic malignancies had no known prior history of malignancy . in both cases , ancillary testing was not performed . one patient ( patient # 6 ) had a solitary pancreatic lesion in the body / tail region . the imaging finding of a 2 cm lesion in the left kidney was not provided to the cytopathologist at the time of biopsy and cytological evaluation . a distal partial pancreatectomy was performed , and histological examination showed a metastatic rcc [ figure 1 ] . the second patient ( patient # 30 ) a core needle biopsy was performed , and the diagnosis of well - differentiated liposarcoma was rendered [ figure 2 ] . in addition , there was a patient ( patient # 31 ) who presented with a solitary mass in the body of pancreas . the aspirate revealed poorly differentiated malignant neoplasm with uncertain cell lineage by both morphologic and immunophenotypic analysis . a follow - up bone biopsy showed synovial sarcoma , which was positive for syt gene rearrangement [ figure 3 ] . cytomorphologic features and surgical follow - up of metastatic renal cell carcinoma that was initially misclassified pancreatic adenocarcinoma . the aspirates showed clusters of tumor cells with vacuolated cytoplasm ( a ) diff - quik , 40 , and lipid droplets in the cytoplasm ( b ) diff - quick , 40 . the surgical follow - up showed tumor cells with eosinophilic ( c ) h and e , 20 and clear cytoplasm ( d ) h and e , 20 cytomorphologic features and surgical follow - up of liposarcoma that was initially misclassified carcinoma with glandular features . the aspirates showed dyscohesive tumor cells admixed with myxoid / collagenous stroma ( a ) diff - quik , 20 and ( c ) papanicolaou , 20 . the tumor cells had eccentrically located nuclei ( b ) diff - quik , 40 . the surgical follow - up showed scattered tumor cells embedded in myxoid / collagenous stroma ( d ) h and e , 40 cytomorphologic features and surgical follow - up of synovial sarcoma that was initially diagnosed as unclassified malignant neoplasm . the aspirates showed pleomorphic tumor cells with hyperchromatic nuclei ( a ) diff - quik , 40 , and ( b ) papanicolaou , 20 . the surgical follow - up showed sheets of tumor cells with pleomorphic nuclei and prominent nucleoli ( c ) h and e , 40 . fluorescence in situ hybridization for syt gene rearrangement demonstrated split green - orange or isolated green signals ( arrows ) ( d ) fluorescence in situ hybridization image , 80 involvement of the pancreas by secondary tumors including carcinomas , sarcomas , and hematological malignancies is a well - documented , yet uncommon occurrence . autopsy studies have shown the incidence of pancreatic involvement by secondary tumors to be in the range of 415% . both studies included tumors that involved the pancreas by direct invasion from nearby organs . this involvement can present as a well - defined solitary mass versus a more diffuse involvement at multiple sites of the pancreas as seen on different imaging modalities . few reports in the literature have tried to establish a characteristic radiologic appearance of primary pancreatic tumors versus metastatic lesions . reported that the presence of well - defined borders was significantly associated with metastatic lesions . however , tumor size , echogenicity , location , and lesion number were not found to be significantly different between primary pancreatic tumors versus metastatic tumors , suggesting that by imaging alone , it is not possible to differentiate primary pancreatic neoplasms from metastatic tumors . the tumors in our series represented solitary or multiple masses with similar frequencies and showed no preferential location . as the treatment and prognosis could be significantly different , it is imperative to render an accurate diagnosis . a number of previous studies have repeatedly shown high sensitivity and specificity of cytological examination for primary pancreatic neoplasms . few reports have also demonstrated the utility of eus - fna in evaluating secondary pancreatic malignancies . the reported incidence of secondary malignancies diagnosed by pancreatic fna ranges from 1% to 11% . in our series , the calculated incidence was 2.3% based on 1346 pancreatic eus - fna cases , which is within the reported range . the diagnostic accuracy rate of eus - fna could be variable with one report being 89% . in the current study , we rendered a correct diagnosis in 29 of 31 cases ( 94% ) , a higher diagnostic accuracy rate than previously reported in the literature . most of our patients ( 74% ) had a documented prior history of malignancy and had prior surgical specimens available for morphological comparison . it is important not to discount a remote history of malignancy because the latency for the development of pancreas metastasis could be as long as more than 20 years after initial diagnosis . our two cases that were misdiagnosed from the patients who had no documented history of malignancy . second , at our institution , all eus - fna procedures for solid pancreatic masses are performed with rapid on - site evaluation either by a cytopathologist or a cytotechnologist . third , ancillary studies may be required for rendering a diagnosis or classification of secondary tumors , especially in cases without a prior history of malignancy . the rapid on - site evaluation also allows the cytopathologist or cytotechnologist to triage specimens for performing ancillary studies . in the current series , ancillary studies were performed in 18 of 31 cases ( 58% ) , including immunostaining ( 16 cases ) and flow cytometry ( 2 cases ) . the present study showed that metastatic carcinomas were the most common secondary tumors , seen in 24 of 31 cases ( 77% ) , which is similar to that previously reported . correct diagnosis and accurate classification of metastatic carcinomas rely on knowledge of the patient 's malignancy history , careful evaluation of morphologic features , and performance of immunocytochemical studies if indicated . since the metastatic carcinomas could be morphologically diverse and originate from a number of organs , the patient 's prior history along with the morphologic features of the current specimen may provide clues for selection of immunostaining markers . eight metastatic carcinomas ( 33% ) in our series were rcc , in which six patients had prior history and were treated with nephrectomy . these cases except one were correctly diagnosed based on the characteristic morphology and in some cases , the confirming immunostains . more recently , pax8 , a pan - renal marker and caix , a clear cell rcc maker , have been recommended for the work - up of metastatic rcc . the importance of rendering the accurate diagnosis in these patients has been highlighted by the reports showing that a solitary rcc metastasis had a better prognosis than primary adenocarcinoma of the pancreas and metastatic rcc was associated with prolonged survival as compared to other metastatic tumors to the pancreas . the outcome of partial pancreatectomy in these patients has also been shown to be excellent . metastatic carcinoma of the lung has been reported to be as high as 42% in an autopsied case series . seven of our twenty - four cases were metastatic lung cancers , including adenocarcinoma ( 4 cases ) and sclc ( 3 cases ) . metastatic lung adenocarcinoma has overlapping morphology with primary pancreatic adenocarcinoma , the most common malignancy in the pancreas . primary small cell carcinoma , although rare , could be seen in the pancreas and should be included in the differential diagnosis metastatic small cell carcinoma . prior history of lung cancers including sclc would be of great help for suggesting a metastasis . all of our patients with metastatic lung cancer had an either prior history or current biopsy to suggest a lung primary . thyroid transcription factor-1 ( ttf-1 ) is a relatively specific marker for adenocarcinoma of the lung with a reasonable sensitivity and should be included in the workup if suspecting a metastatic lung adenocarcinoma . the panel for small cell carcinoma should include neuroendocrine markers such as chromogranin , synaptophysin , cd56 as well as ttf-1 . in cases with negative ttf-1 , napsin a may add additional diagnostic value . although the vast majority of sclcs stain positive for ttf-1 , the positivity of ttf-1 has been reported in small cell carcinoma of extra - pulmonary origins . therefore , the clinical history and presentation may provide additional help in determining the possible primary sites . other less commonly seen metastatic carcinomas in our series included colon , breast , esophagus , ovary , cervix , bladder , and merkel cell carcinoma . all of these patients had a documented history of malignancy and immunostains were performed in 3 cases to substantiate the diagnosis . , secondary lymphoproliferative disorders were seen in 4 cases , including dlbcl and plasma cell neoplasm , 2 cases each . the diagnosis of dlbcl was rendered based on the cytomorphologic features , immunophenotypic features by immunostaining or flow cytometry , as well as the results of concurrent tissue biopsies . previous studies have repeatedly demonstrated that ancillary studies are required to render a primary diagnosis and classification of lymphomas . rapid on - site evaluation is cruial in this circumstance , which helps procure specimen and recommend tissue biopsy if necessary . the two patients with plasma cell neoplasm had prior history , and the tumors showed characteristic cytomorphologic features , which may be sufficient for a diagnosis . a variety of metastatic sarcomas have been reported in the literature , including leimyosarcoma , angiosarcoma , rhabdomyosarcoma , chondromosarcoma , liposarcoma , and malignant fibrous histocytoma . in our series , one patient had a history of dedifferentiated chondrosarcoma of the scapula and presented with multiple pancreatic masses and extrapancreatic masses . based on the clinical history , morphologic comparison , and immunostaining results , the diagnosis of metastatic chondrosarcoma was rendered . the third patient presented with a solitary pancreatic mass , the biopsy of which showed poorly differentiated neoplasm with negative immunostaining for cytokeratin , cd45 , and melan a. the follow - up bone biopsy revealed synovial sarcoma , confirmed by syt gene rearrangement . in our series the distal pancreatectomy showed metastatic clear cell rcc with focal eosinophilic features , which appeared to be overlapping , at least focally , with the features of adenocarcinoma [ figure 1 ] . the second case ( patient # 30 ) showed dyscohesive or single tumor cells had eccentrically located hyperchromatic nuclei , which was interpreted as glandular differentiation . the myxoid / collagenous stroma present on the original aspirate specimen was underappreciated during initial cytological evaluation [ figure 2 ] . in both of these two cases , the patients have not known the previous history of malignancy and no ancillary studies were performed on cytological specimens . in summary , secondary tumors involving the pancreas are uncommon , which can be accurately diagnosed by eus - fna . provision of detailed clinical history and close communication with clinicians is imperative . in the setting of absent or unknown clinical history of previous neoplasia , recognition of cytomorphologic features , and unusual for primary pancreatic neoplasms should prompt further workup . in addition to the recognition of a prior history of malignancy , rapid on - site evaluation , and ancillary studies may help improve the diagnostic performance of secondary malignancies involving the pancreas . all authors of this article declare that we qualify for authorship as defined by the icmje http://www.icmje.org/#author . eus - fna - endoscopic ultrasound - guided fine needle aspiration ttf-1 - thyroid transcription factor-1 . 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 .
background : pancreatic masses may seldom represent a metastasis or secondary involvement by lymphoproliferative disorders . 
 recognition of this uncommon occurrence may help render an accurate diagnosis and avoid diagnostic pitfalls during endoscopic ultrasound - guided fine needle aspiration ( eus - fna ) . in this study 
 , we review our experience in diagnosing secondary tumors involving the pancreas.materials and methods : the electronic database of cytopathology archives was searched for cases of secondary tumors involving the pancreas at our institution and a total of 31 cases were identified . 
 the corresponding clinical presentations , imaging study findings , cytological diagnoses , the results of ancillary studies , and surgical follow - up , if available , were reviewed.results:nineteen of the patients were male and 12 female , with a mean age of 66 years . 
 twenty - three patients ( 74% ) had a prior history of malignancy , with the latency ranging from 6 months to 19 years . 
 the secondary tumors involving the pancreas included metastatic carcinoma ( 24 cases ) , metastatic sarcoma ( 3 cases ) , diffuse large b - cell lymphoma ( 2 cases ) , and plasma cell neoplasm ( 2 cases ) . 
 the most common metastatic tumors were renal cell carcinoma ( 8 cases ) and lung carcinoma ( 7 cases ) . 
 correct diagnoses were rendered in 29 cases ( 94% ) . 
 the remaining two cases were misclassified as primary pancreatic carcinoma . in both cases , 
 the patients had no known history of malignancy , and no ancillary studies were performed.conclusions:secondary tumors involving the pancreas can be accurately diagnosed by eus - fna . recognizing uncommon cytomorphologic features , knowing prior history of malignancy , and performing ancillary studies are the keys to improve diagnostic performance and avoid diagnostic pitfalls .