Multiple Cardiac Metastases from a Nonfunctioning Pancreatic Neuroendocrine Tumor
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. He had no relevant medical history. Findings on physical examination revealed the following: body temperature, 36.8℃; blood pressure, 130/75 mm Hg; and pulse rate, 60 per minute. Heart sounds were normal, without murmur, rubs, or gallops. 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/µL; and platelet count, 196,000/µL. 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 µU/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 chest radiography were normal. Findings on computed tomography (CT) of the abdomen revealed two relatively well-marginated inhomogeneous low-attenuation masses, one measuring 7.3×8.8 cm in the head of the pancreas and the other measuring 12.0×9.2 cm in the tail (), 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 (). Transthoracic echocardiography showed multiple areas of well-circumscribed echogenic masses in the left pericardium, with myocardial involvement (), but with preserved left ventricular function. No associated valvular abnormality was observed, and no intracardiac shunt was detected by contrast study.\nAn ultrasonographically-guided needle biopsy was performed on the mass in the tail of the pancreas. The tumor showed a nesting growth pattern with monotonous cells. Most tumor cells had centrally-located nuclei with moderate amounts of amphophilic cytoplasm. Nuclei were generally round to oval in shape, with coarsely clumped chromatin by hematoxylin and eoxin staining (). 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) (), and CD56 (1:150, Leica) (), 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.\nThe 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. However, the patient's tumorrelated abdominal symptoms worsened. 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. The patient's general condition deteriorated to Eastern Cooperative Oncology Group performance status 3.