A 56-yr-old man was admitted to our hospital with a complaint of weight loss (6 kg/3 months), and mild shortness of breath at room air. He denied all past history of smoking, excessive alcohol drinking, or chronic diseases. On physical examination, both sclerae were grossly normal, breathing sound was clear, and no cardiac murmur was heard. Abdominal sound was normoactive, and organomegaly was not clear. Arterial blood gas analysis showed pH 7.45, PaO2 65 mmHg, PaCO2 36 mmHg, and O2 saturation 90%. There was no evidence of cardiomegaly, mass shadow, or pulmonary edema in both lung fields on chest radiograph. Laboratory findings showed alanine aminotransferase of 52 U/L, total bilirubin of 1.53 mg/dL, alkaline phosphatase of 597 U/L, and γ-GTP of 126 U/L. Hepatitis B virus surface antigen and antibody to hepatitis C virus were all negative. To evaluate biochemically abnormal findings, abdominal ultrasonography and dynamic CT scan were performed, which showed an ill-defined, poorly enhanced 6.5×7×7 cm-sized mass with several daughter nodules in the left lobe of the liver (). Tests for tumor markers revealed alfa-fetoprotein of 6.19 ng/mL, CA 19-9 of 773.2 U/mL, and CEA of 615.5 ng/mL. Ultrasonography-guided needle biopsy for the liver mass was performed, and then, the histological findings were compatible with cholangiocarcinoma (). On chest CT scan for both of unexplained mild dyspnea and tumor staging, a low density due to filling defect in the left interlobar pulmonary artery was found without any evidence of other metastatic nodules (). Pulmonary perfusion scan showed multiple perfusion defects in the left lower lung fields (). Echocardiographic examination revealed no evidence of vegetation on the cardiac valves or intracardiac thrombus. Based on the radiological and symptomatic findings of the patient, the diagnosis of pulmonary thromboembolism was made. At the time of diagnosis, coagulation tests showed elevated levels of blood clotting factors, such as D-dimer of 5,690 ng/mL, fibrinogen of 746 mg/dL, fibrinogen degradation product (FDP) of 8.02 µg/mL, and positive IgM anticardiolipin antibody (aCL Ab) of 73 PL (normal limit: <20 PL). The prothrombin time (PT) was 10.8 sec (international neutralization ratio [INR]=0.98), activated partial prothrombin time (aPTT) was 33.2 sec, and other coagulation factors including protein C and S activities, lupus anticoagulant and antithrombin III are all within the normal range. To treat the pulmonary thromboemboli, anticoagulation therapy using low-molecular-weight-heparin (LMWH) in therapeutic dose of 10 IU/kg every 12 hr was given subcutaneously. The patient's symptom was relieved with LMWH treatment over time and the follow up CT scan at 3 weeks after the diagnosis showed an almost complete resolution of the thromboemboli (). Blood oxygenation was also increased to PaO2 of 83 mmHg and O2 saturation of 97%. Follow-up coagulation tests demonstrated the normalization of FDP, D-dimer, and IgM aCL Ab titer, but only a slight decrease in fibrinogen level (). Systemic chemotherapy for the cholangiocarcinoma was performed. The patient has been followed up without further thrombosis during the next 3 months.
A 36-year-old male football player with no significant past medical history recently diagnosed with unprovoked deep venous thrombosis of the lower limb, presented with acute right-sided hemiplegia, hemi-sensory loss, facial upper motor neuron lesion and expressive aphasia. Prior to the presentation, the patient had a history of undocumented fever, but no reported history of chest pain, shortness of breath, weight loss, night sweating, drug abuse, alcohol consumption or family history of similar presentation. With the aid of the above information, the computed tomography (CT) of the brain showed multiple bilateral occipital and frontoparietal areas of hypodensities more on the left cerebral hemisphere. The transthoracic echocardiogram revealed left ventricular ejection fraction of 60%, the presence of masses attached to mitral and aortic valves needed to be evaluated further by tranesophageal echocardiogram (TEE). The TEE showed multiple highly mobile, irregular shape masses attached to right and left coronary cusps of the aortic valve, largest mass measuring 20 × 18 mm2 with eccentric severe aortic regurgitation, no associated abscess or fistula, similar echogenicity mass attached to anterior mitral valve measures 7 × 4 mm2, and posterior mitral valve mass measures 5 × 3 mm2, and there was mild mitral regurgitation and no intracardiac shunt ( and ()). Magnetic resonance imaging (MRI) of the brain ( and ()) revealed multifocal diffusion restrictions involving bilateral high frontal and left thalamus, bilateral occipital lobes, and bilateral cerebellar hemispheres, with no significant mass effect. Forty-eight hours of follow-up CT of the brain confirmed the presence of hemorrhagic transformation. Clinically, the patient showed improvement in the expressive aphasia and the right-sided hemiplegia during the first week of admission. The patient was clinically stable throughout his hospitalization course. The follow-up investigations of all the tests performed on the patient leads to the following conclusions: (1) all blood cultures were negative; (2) Brucella titer and serology for Q fever were negative; (3) markers for tumors came back positive (CA-125 102 U/mL, CA19-9 5247 U/mL, CEA 13.6 U/mL); (4) thrombophilic evaluation, including anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), antiphospholipid antibodies (cardiolipin IgG and IgM), Factor-V Leiden mutation, homocysteine, Protein-S, Protein-C and Antithrombin-III levels, was unremarkable; and (5) CT scan of chest, abdomen and pelvis unveiled the presence of hypovascular hepatic mass having dimensions of 7.8 × 5.7 × 6.4 cm3, which invaded the right portal vein as well as the right hepatic duct with multiple porta hepatis and retroperitoneal lymphadenopathies, thereby leading to an alarming stage of cholangiocarcinoma (). On a similar note, the peripheral right lung showed lesion with central cavitation probably infarction or metastasis, in addition to the presence of bilateral hypodense renal cervical lesions. The patient underwent ultrasound-guided liver biopsy showed well-differentiated adeno-carcinoma, consistent with the diagnosis of cholangiocarcinoma ( and ()).\nThe follow-up transthoracic echocardiogram after 10 days of admission showed the presence of a small calcified aortic valve mass, which measures 6 × 4 mm2, mild aortic and mitral regurgitation and no evidence of mitral valve mass ( and ()). At this stage, upon his and his family request, the patient was transferred to an oncology center in the United States, where he was recommended for palliative treatment. Unfortunately, 6 months later, the patient died.