pancreatic neuroendocrine tumors ( pnets ) are low- to intermediate - grade neoplasms , which are considered to arise from pancreatic islets and are relatively rare . the incidence and prevalence of metastatic pnets are increasing , and currently represent 1.3% of all cases of pancreatic cancer in incidence and 10% of cases in prevalence [ 1 - 3 ] . pnets are classified as functional ( 10 - 30% of tumors ) or nonfunctional ( 50 - 80% ) . functional pnets are usually associated with a hormonal syndrome due to hormone - excess . by contrast , all symptoms of nonfunctional pnets are associated with the tumor per se . therefore , some small or undetectable primary functional pnets may present with severe symptoms , whereas nonfunctional pnets almost always present late in the disease course with large tumors that are usually metastatic . intrathoracic metastases from pnets are encountered infrequently ; however , cardiac metastasis has not been previously reported . a 56-year - old male presented to the clinic in december 2008 , with a two - week history of a progressively enlarging palpable mass in the left lower abdomen , abdominal pain , and dyspepsia . findings on physical examination revealed the following : body temperature , 36.8 ; blood pressure , 130/75 mm hg ; and pulse rate , 60 per minute . however , on abdominal examination , a firm , fixed mass measuring 7 cm in size , without tenderness or rebound tenderness , was found in the left lower abdomen . after extensive history taking and physical examination , no clinical symptoms or signs of a hormone - excess were observed . results of laboratory tests were as follows : hemoglobin , 13.0 g / dl ; white cell count , 4,000/l ; and platelet count , 196,000/l . blood chemistry findings were as follows : alanine aminotransferase , 23 iu / l ; aspartate aminotransferase , 12 iu / l ; total bilirubin , 0.3 mg / dl ; and alkaline phosphatase , 132 iu / l . levels of serum tumor markers were as follows : carcinoembryonic antigen ( cea ) , 21.19 u / ml ; cancer antigen 19 - 9 , 1.51 ng / ml ; and neuron - specific enolase , 9.75 ng / ml . hormone levels were within the normal range ( gastrin , 162.0 pg / ml ; fasting insulin , 21.4 u / ml ; glucagon , 83.4 pg / ml ; somatostatin , 8.8 pg / ml ; and corticotrophin , 58.1 pg / ml ) . a 12-lead electrocardiography showed sinus bradycardia ( ventricular rate , 53 beats per minute ) with nonspecific st segment and t wave changes . findings on computed tomography ( ct ) of the abdomen revealed two relatively well - marginated inhomogeneous low - attenuation masses , one measuring 7.38.8 cm in the head of the pancreas and the other measuring 12.09.2 cm in the tail ( fig . 1 ) , with multiple enlarged lymph nodes in the peripancreatic area . a ct scan of the pelvis showed bone destruction in the left pelvic bone . a chest ct scan showed multiple enhancing heterogeneous masses distributed in the left pericardium ( fig . 2 ) . transthoracic echocardiography showed multiple areas of well - circumscribed echogenic masses in the left pericardium , with myocardial involvement ( fig . no associated valvular abnormality was observed , and no intracardiac shunt was detected by contrast study . an ultrasonographically - guided needle biopsy was performed on the mass in the tail of the pancreas . nuclei were generally round to oval in shape , with coarsely clumped chromatin by hematoxylin and eoxin staining ( fig . immunohistochemical staining showed that tumor cells were positive for pancytokeratin ( 1:300 , leica , newcastle upon tyne , uk ) , synaptophysin ( 1:200 , neomarkers , fremont , ca ) , chromogranin ( 1:200 , leica ) ( fig . 4c ) , but negative for vimentin ( solid - pseudopapillary neoplasm marker , 1:200 , dako , glostrup , denmark ) , leukocyte common antigen ( hematopoietic neoplasm marker , 1:100 , dako ) , and cea ( pancreatic ductal adenocarcinoma marker , 1:200 , leica ) . the proliferation index ( ki-67 ) and mitosis of the neoplastic cells were approximately 15% and < 2/10 high power field , respectively . accordingly , based on histological and immunohistochemical findings , a diagnosis of grade 2 well - differentiated pnet was made . a percutaneous biopsy of the tumor in the left ventricular apical pericardium was performed using a xiphoid approach ; results matched the pathologic findings in the pancreatic mass . therefore , the patient was diagnosed as having nonfunctioning malignant pnet with multiple metastases , including cardiac metastases . the patient was treated with six courses of etoposide and cisplatin chemotherapy and achieved stable disease status according to the response evaluation criteria in solid tumors ( recist ) guidelines due the patient 's economic circumstances , further treatment with anti - tumor therapy , such as streptozocin or molecular targeting agents , was discontinued , however , the patient continued to receive the best supportive care , including pain control . at 16 months follow - up from the date of diagnosis ( in april 2010 ) , the patient underwent percutaneous transhepatic biliary drainage followed by insertion of a biliary stent for treatment of a common bile duct obstruction caused by the presence of progressive pancreatic masses . at 33 months from the date of initial diagnosis ( september 2011 ) , the patient developed chest discomfort and exertional dyspnea , and his abdominal and left hip pain , as well as his anorexia , worsened . in principle , all malignant tumors can metastasize to the heart . in fact , cardiac metastatic disease is more common than primary heart tumors , and its incidence has increased during recent decades due to the prolonged survival of patients with cancer and the increased prevalence of the disease in the general population [ 7 - 9 ] . neoplasms that most commonly metastasize to the heart include malignant melanoma , lymphoma , and leukemia ; however , overall numbers are greater for breast and lung cancer , reflecting their higher incidence . in pnet , the liver is the most commonly invaded organ by direct extension or metastasis , followed by regional lymph nodes , and bone , whereas cardiac metastasis from pnet has not been previously reported . the heart is rarely the first site for metastases , and they are usually only found later when diffuse involvement of other organs has already occurred . tumor cells can metastasize to the heart and pericardium by one of four different pathways : lymphatic , hematogenous , direct extension , or transvenous extension via the superior or inferior vena cava . lymphatic spread often gives rise to pericardial metastases , whereas hematogenous spread has a propensity to migrate to myocardium . tumors that are in close proximity to the heart , such as bronchial , breast , and esophageal tumors , usually spread by direct extension and give rise to pericardial disease . the most common site of cardiac involvement is the pericardium , with frequencies ranging from 62% to 81% , whereas myocardial or endocardial involvement is rare . in the case described here , metastatic cardiac involvement of pnet occurred in a disseminated setting with regional lymph node and bone metastases , and , via lymphatic spread , multiple pericardial metastases with myocardial involvement . in such cases , cardiac metastases are usually asymptomatic because the masses are small and do not affect cardiac function . when present , clinical signs and symptoms of cardiac metastases are extremely variable , depending on the site and intensity of involvement . symptoms include dyspnea or tachypnea , and clinical signs include systolic heart murmur , peripheral edema , and pleural or pericardial effusion . hypotension , peripheral cyanosis , pulsus paradoxus , and venous congestion are also hallmarks of clinical diagnosis . cardiac metastases can cause disturbances of atrial and ventricular heart rhythm , as well as conduction defects . pericardial involvement can lead to development of pericarditis with pericardial effusion , which may compromise hemodynamics . although cardiac metastases cause mild symptoms , more extensive spread of tumors to the pericardium or to other cardiac sites may lead to production of dramatic clinical patterns , resulting in occurrence of medical emergencies and sudden death , unlike other metastatic sites . in the case described here , the diagnosis of cardiac metastases resulted from an incidental finding during a metastatic work - up ; there were no early cardiac symptoms . approximately three years from the initial diagnosis , the patient 's cardiac symptoms were chest discomfort and dyspnea on exertion . no standard treatment modality has been established for cardiac metastases , and , because most patients have disseminated disease , the treatment is generally primary tumor systemic therapy . therefore , treatment of cardiac metastases is mainly confined to palliation of cardiac symptoms , which may improve the quality of life of affected patients . surgical resection is only indicated in exceptional cases of solitary intracavitary heart metastases that obliterate cardiac chambers or cause valvular obstruction . malignant pericardial effusion , especially cardiac tamponade , requires percutaneous pericardiocentesis within a short period of time . radiotherapy for treatment of cardiac metastases should be used with caution as it may lead to fibrosis of the lung or myocardium , and may be associated with disturbance of the conduction system and pericarditis . the chemotherapeutic agents doxorubicin , daunorubicin , and high - dose cyclophosphamide have cardiotoxic side effects , which may induce recalcitrant myocardial failure . systemic chemotherapy for advanced pnets has been studied in many clinical trials over the past three decades ; however , despite a multitude of publications , debate over its efficacy continues . streptozocin alone or in combination with doxorubicin remains the only chemotherapeutic agent approved for treatment of advanced pnets ; however , it is associated with considerable adverse events . recent large prospective trials have shown that the molecular targeting agent , sunitinib , a multi - target receptor tyrosine kinase inhibitor , and the mammalian target of rapamycin inhibitor , everolimus , has promising antitumor activity [ 12 , 13 ] . due to his economic circumstances , our patient was not treated with streptozocin or a molecular targeting agent , and instead received etoposide and cisplatin but failed to respond . nevertheless , he has been relatively well for the last 33 months ; patients with pnets can live with metastatic disease for several years . this report describes a case of nonfunctioning pnet with multiple metastases to previously undescribed cardiac sites . although rare , pnet has the potential to metastasize to the heart or pericardium , and , for patients with pnets who present with new cardiac symptoms or signs , whether based on history or physical examination , the clinician should be alert to the possibility of cardiac metastases .
pancreatic neuroendocrine tumors ( pnets ) are rare neoplasms , which most commonly metastasize to the liver . 
 however , intrathoracic metastases from pnets are encountered infrequently . 
 this report describes a case of nonfunctioning pnet with multiple cardiac metastases . a 56-year - old male presented with a palpable abdominal mass that showed progressive enlargement . 
 findings on computed tomography ( ct ) of the abdomen revealed two relatively well - marginated inhomogeneous low - attenuation masses , one in the head of the pancreas and the other in the tail . 
 multiple enhancing masses in the left pericardium with myocardial involvement were observed on chest ct and transthoracic echocardiography . 
 needle biopsies were performed on the mass in the tail of the pancreas and the left ventricular apical pericardium ; histologic examination by hematoxylin and eosin morphology and immunohistochemical staining showed pnet in both . 
 this is the first report of pnet with multiple cardiac metastases to previously undescribed metastatic sites .