An 81-year-old comatose black woman was brought to the medical emergency room with histories of recentonset mental status changes, hypertension, and type II diabetes mellitus for more than 20 years. The following laboratory data on admission suggested an acute myocardial infarction: creatine kinase, 306 U/L (reference range, 26-140 U/L); creatine kinase-MB, 25.58 ng/mL (reference range, 0.00-4.99 ng/mL); creatine kinase-MB mass index, 8.4 (reference range, 0.0-4.9); and troponin T, 0.80 ng/mL (reference range, 0.00-0.10 ng/mL). An initial cranial computed tomographic scan revealed a left posterior parietal infarction. Two days later, an additional cranial computed tomographic scan demonstrated a right anterior cerebral artery occlusion. Intravascular heparin therapy was administered, but the patient's condition deteriorated. The hospital course was complicated by a preterminal disseminated intravascular coagulation, as indicated by a prothrombin time of 20.1 seconds (reference range, 11.5-14.2 seconds); partial thromboplastin time, 37.9 seconds (reference range, 21.7-34.7 seconds); platelet count, 54 X 10^sup 3^/µL (reference range, 150-450 × 10^sup 3^/µL and fibrinogen, 161 mg/dL (reference range, 195-424 mg/dL). The patient died 2 weeks after initial presentation.
Autopsy revealed a 7-cm, poorly differentiated adenocarcinoma (Figure 1) in the pancreatic body and tail with extensive metastasis to liver. Two vegetations (0.6 × 0.6 × 0.8 cm and 0.5 × 0.5 × 0.5 cm) of nonbacterial thrombotic endocarditis attached to the mitral valve (Figure 2, A) were confirmed by microscopic examination (Figure 2, B). Multiple fibrin microthrombi were also seen in the small arteries of the lungs and brain. Serial sectioning of 3 branches of coronary artery showed no evidence of atherosclerosis (Figure 3). Multiple infarcts were identified in the brain (Figure 4, A), including the left occipital and parietal regions, right anterior frontal cerebrum, and left cerebellum, as well as in the myocardium (Figure 4, B). Grossly, wedge-shaped infarcts were noted in the left lung, spleen, and right kidney.
An activated coagulation system in most cancer patients, leading to a hypercoagulable state, was recognized almost 150 years ago. Ever since, the occurrence of venous thrombosis in malignant tumors has been well documented. However, acute arterial thromboembolic occlusion in cancer patients is less often recognized. In a recent series of 311 autopsy cases with pancreatic adenocarcinoma, only 2 cases with arterial thromboembolism were identified.1 Our case demonstrates a unique presentation of cerebral and myocardial thrombotic infarction secondary to pancreatic adenocarcinoma with metastasis. Commonly, cerebral and myocardial infarctions are caused by diffuse atherosclerotic cerebral and coronary disease. No apparent pathologic changes of coronary arteries strongly supported that diffuse thromboembolic phenomena in many organs were due to nonbacterial thrombotic endocarditis.
Many factors are known to induce thrombosis in cancer patients.2 Tumor cells themselves can produce procoagulant substances, such as cysteine proteases and tissue factor. Cysteine proteases can directly activate factor V, while tissue factor initiates an extrinsic coagulation cascade by activating factor VII. Interaction between monocytes or macrophages and malignant tumor cells releases tumor necrosis factor, interleukin-1, and interleukin-6, causing endothelial damage, which provides a surface for initiation of platelet aggregation and subsequent thrombogenesis. Increased synthesis and release of tissue factor from macrophages that interact with tumor cells and decreased hepatic synthesis of anticoagulant proteins, such as protein C and antithrombin III, may also contribute to a thrombophilic state in cancer patients.
1. Schattner A, Klepfish A, Huszar M, Shani A. Two patients with arterial thromboembolism among 311 patients with adenocarcinoma of the pancreas. Am J Med Sci. 2002;324:335-338.
2. Bick RL. Cancer-associated thrombosis. N Engl J Med. 2003;349:109-111.
Lugen Chen, MD, PhD; Yanhua Li, MD; Wondwossen Gebre, MD; Jen H. Lin, MD
Accepted for publication June 29, 2004.
From the Department of Pathology and Laboratory Medicine, Nassau University Medical Center, East Meadow, NY (Drs Chen, Li, Gebre, and Lin); and School of Medicine, State University of New York at Stony Brook (Dr Lin).
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: Jen H. Lin, MD, Department of Pathology and Laboratory Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554 (e-mail: firstname.lastname@example.org).
Copyright College of American Pathologists Nov 2004
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