A Case of Locally Advanced Breast Cancer Complicated by Pulmonary Tumor Thrombotic Microangiopathy
In May 2009, a 30-year-old woman came to the emergency room (ER) with a five-day history of acute progressive dyspnea on exertion (NYHA class III). In 2007, ductal carcinoma in situ was diagnosed by biopsy during pregnancy. In 2008, after a full-term delivery, findings on fluorodeoxyglucose positron emission tomography computed tomography (CT) and ultrasound of the right breast revealed diffuse microcalcification and skin thickening of the right breast, and metastatic axillary lymph nodes. The patient refused further management and was lost to follow up until the ER visit.\nOn admission, the patient's blood pressure was 126/76 mm Hg, heart rate was 120 beats per min, respiratory rate was 18 breaths per minute, and body temperature was 36.7℃. A chest radiograph showed that the lung field was clear. Results of arterial blood gas analysis in room air indicated hypoxemia: pH 7.446, pCO2 28.2 mm Hg, pO2 44.3 mm Hg, HCO3 19.1 mmol/L, SaO2 76.8%. D-dimers were elevated to 2.59 µg/mL (normal, <0.39 µg/mL) with an elevated troponin I level to 0.24 ng/mL (normal, <0.04 ng/mL) and a brain natriuretic peptide of 774 pg/mL (normal, <100 pg/mL). Diffuse enlargement of the right breast with skin thickening and many enlarged axillary lymph nodes consistent with locally advanced breast cancer was observed on CT.\nOn the second day of admission, the patient was consulted with the cardiology department for possible preoperative cardiac evaluation. An electrocardiogram showed an S1Q3T3 pattern with inverted or flattened T waves in leads V1 through V4. A transthoracic echocardiogram showed normal left ventricular systolic function with right ventricular enlargement and free wall hypokinesia sparing the apex. In addition, the echocardiogram showed typical findings of acute pulmonary thromboembolism with a D-shaped left ventricle, moderate tricuspid regurgitation, and moderate pulmonary hypertension with an estimated right ventricular systolic pressure of 61 mm Hg.\nOther laboratory tests showed the following results: white blood cell 7,900/mm3 with normal differential counts, hemoglobin15.4 g/dL, platelets 144,000/mm3, alanine aminotransferase 50 IU/L (normal, 0 to 40 IU/L), aspartate aminotransferase 218 IU/L (normal, 0 to 40 IU/L), total bilirubin 1.4 mg/dL (normal, 0.2 to 1.2 mg/dL), C-reactive protein 0.81 mg/dL (normal, 0 to 0.30 mg/dL), prothrombin time (PT) international normalized ratio (INR) of 1.36 (normal, 0.8 to 1.2), activated partial thromboplastin time (aPTT) of 45.7 seconds (normal, 27.0 to 45.0 seconds), fibrinogen of 196 mg/dL (normal, 200 to 400 mg/dL), and fibrin degradation products (FDP) of 1 : 2 positive (normal, negative). A peripheral blood smear showed increased numbers of schistocytes and reticulocytes consistent with MAHA ().\nWe measured serum vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in view of preexisting information on VEGF, a critical angiogenic molecule and IL-6, a multifunctional cytokine promoting tumor growth. Serum VEGF levels were 26.9 pg/mL on the second day in the hospital and 9.5 pg/mL on the third day in the hospital (normal, 88.7 to 1,048.7 pg/mL); IL-6 levels were 50.3 pg/mL and 25.6 pg/mL on the second and third days, respectively (normal range, 0.4 to 8.6 pg/mL).\nAnticoagulation therapy with enoxaparin was startedunder the clinical diagnosis of submassive acute pulmonary thromboembolism. While no evidence of pulmonary thromboembolism was observed on pulmonary CT angiography (), an echocardiogram showed acute right ventricular pressure overload (), and a perfusion lung scan showed multiple small wedge-shaped perfusion defects throughout both lungs (). Therefore, with a diagnosis of PTTM based on clinical and laboratory findings, the patient was transferred to the intensive care unit and received 1 mg/kg enoxaparin subcutaneously, 0.05 mg/kg dexamethasone intravenously, and 2 mg warfarin sodium orally.\nOn the third day of admission, repeated transthoracic echocardiogram showed additional significant right ventricular pressure overload with an estimated right ventricular systolic pressure of 60 mm Hg. Abnormal liver function was the result of either passive congestion or hepatic metastasis, although the initial CT did not show definite systemic metastasis. The patient was scheduled to undergo surgical breast biopsy and appropriate chemotherapy, however, her general condition showed rapid deterioration, and she died within 48 hours of admission.