the hemodynamic effects of pericardial fluid accumulation are the result of increased intrapericardial pressure , leading to impaired diastolic filling and a low cardiac stroke volume , which is potentially life - threatening .
it is known that non - small cell lung cancer ( nsclc ) patients harboring epidermal growth factor receptor ( egfr ) mutations are responsive to egfr tyrosine kinase inhibitors ( egfr - tkis ) such as gefitinib and erlotinib [ 1 , 2 ] .
egfr - tkis have been found to have a significant impact in nsclc patients with egfr mutations [ 13 ] .
several prospective trials have shown the tumor response rates to gefitinib therapy to be approximately 75% in patients with tumors harboring egfr mutations [ 46 ] . however , despite the initial dramatic tumor shrinkage , the tumors of most patients subsequently become resistant to egfr - tkis and eventually relapse .
we herein report the case of a patient with recurrence - related carcinomatous pericarditis arising from a secondary resistant mutation , t790 m , that could be detected in the pericardial effusion .
a 75-year - old japanese male was admitted to our hospital complaining of lumbago , which had persisted for one month .
he was an ex - smoker , and had type ii diabetes , hypertension and ileus .
chest computed tomography ( ct ) revealed a 37-mm diameter mass lesion in the left lower lobe of his lung .
we diagnosed the patient to have lung cancer with multiple bone metastases , brain metastasis , and liver metastasis ( ct2an0m1b , stage iv ) .
after the patient provided informed consent , we analyzed the specimen obtained from the tblb for egfr mutations .
the patient was treated with cisplatin and pemetrexed as a first - line chemotherapy ; however , after one cycle of the treatment , he developed paralysis of his left leg , and this symptom was rapidly progressive . therefore , an emergency operation was performed for posterior lumbar interbody fusion . as second - line chemotherapy ,
one month later , the size of both the primary lesion and the bone metastases were found to have decreased .
three months later , he developed dyspnea at rest and edema . furthermore , he had severe dyspnea and orthopnea , with a resting heart rate of 160170 beats / min and a blood pressure of 63/43 mm hg .
his temperature was 36.8c , and his arterial oxygen saturation was 88.0% on room air . a physical examination revealed distant heart sounds and a significantly distended internal jugular vein to the jaw level .
chest radiographs showed cardiomegaly with an increased cardiothoracic ratio and bilateral pleural effusion ( fig .
2a ) . a ct scan of the chest revealed a large pericardial effusion ( fig . 2b ) .
an emergency echocardiogram confirmed the presence of a large pericardial effusion , together with evidence of diastolic collapse of the right artrium , ventricle and left atrium , consistent with cardiac tamponade ( fig . 2c ) .
the patient underwent pericardiocentesis of 520 ml of malignant sanguineous fluid , and placement of a pericardial drain , while having removed 1,100 ml of sanguineous fluid , in which adenocarcinoma was detected ( fig .
egfr mutation analysis was performed in this pericardial effusion , and both the 18-base pair deletion in exon 19 and a second mutation , t790 m in exon 20 , were detected ( fig .
the patient temporarily recovered from the state of shock and survived for one month after drainage .
one is that the recurrence manifested as cardiac tamponade due to the presence of malignant pericardial effusion of nsclc after erlotinib therapy . in a large retrospective analysis of autopsies with
confirmed primary malignancies , metastases to the heart and pericardium were present in 10% of patients .
lung cancer is the most frequent cause of malignant pericardial effusion , accounting for approximately 4774% of cases , and adenocardinoma was the most frequent histological type associated with the condition . on the other hand , only approximately 2.5% of lung cancer patients
develop carcinomatous pericarditis . in this case , the patient had an egfr mutation with an 18-base pair deletion , and initially had a good response to treatment with an egfr - tki .
the central nervous system is a frequent site of disease recurrence in patients with nsclc after an initial response to egfr - tkis .
however , cardiac tamponade due to carcinomatous pericarditis as the recurrence site has not been reported previously for patients treated with egfr - tkis such as gefitinib or erlotinib .
therefore , we consider that we have herein reported an extremely rare case of an unusual metastatic recurrence site .
the mechanism of metastasis to the heart , like that to other organs , can be by direct contiguous growth , hematogeneous dissemination , or vascular growth along the vena cava , pulmonary veins , or lympatic channels .
the pericardial fluid collection is thought to result from the lymphatic obstruction of fluid from the pericardial sac . in this case
, it was thought to be caused by hematogeneous dissemination , since a chest ct scan showed no mediastinal lymph node invasion .
one of the most interesting findings of this case was the fact that the pericardial effusion acted as a surrogate tissue .
dna in pleural effusion fluid and cerebrospinal fluid , as well as serum dna , can be used to detect egfr mutations , and it has been known that these samples can show evidence of egfr mutations [ 1214 ] . however , it was unknown whether other samples , including pericardial effusion , could be useful for detecting egfr mutations . to our knowledge , this is the first report to detect the resistant mutation t790 m in pericardial effusion .
cardiac tamponade caused by carcinomatous pericarditis is a potentially life - threatening complication , and is a medical emergency caused by fluid accumulation around the cardiac chambers that influence cardiac output .
therefore , it is very difficult to obtain a sufficient tumor sample by a transbronchial tumor biopsy in such a case .
we suggest that the egfr mutation status in the pericardial effusion may therefore be useful as a predictor of the response to egfr - tkis for the patients with pericardial tamponade as the first manifestation .
further validation with a large number of cases will be needed to confirm that the detection of egfr mutations in pericardial effusion can be used to predict the response of the cancer to treatment .
 we report the case of a japanese male with epidermal growth factor receptor tyrosine kinase inhibitor ( egfr - tki)-sensitive lung adenocarcinoma , who had an egfr mutation and presented in the emergency department with acute cardiac tamponade as the recurrence during egfr - tki therapy . 
 we could detect a second mutation , t790 m in exon 20 in the pericardial effusion . 
 this is the first report to detect the resistant mutation t790 m in pericardial effusion . 
 we suggest that the pericardial effusion may therefore be useful as surrogate tissue for detecting egfr mutation . 
Introduction
Case Report
Discussion
Disclosure Statement