Symptoms of fatigue and history of breast cancer raise clinicians’ concerns over development of a new primary cancer.
Ms. Q, a 70-year-old retired clinician, presented with a six-month history of weight loss (30 lb), falling down, fatigue, anorexia, low-grade fevers, and bloody stools. Her medical history was significant for mitral valve prolapse; infective endocarditis (IE) as a child; breast cancer in 1996 (stage 1) treated with segmental mastectomy, adjuvant radiation, and tamoxifen; osteoporosis; anemia; and thyroidectomy.
She reported no use of tobacco, alcohol, or illicit drugs. Her most recent colonoscopy (two years ago) was normal. Her medications included levothyroxine, ibandronate (Boniva), liothyronine (Cytomel), St. John’s wort, turmeric, ginger root, and citrus bioflavonoid.
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Examination
Ms. Q’s vital signs were BP 100/56 mm Hg, pulse 84 beats per minute, respiration rate 18 breaths per minute, temperature 36.1°C, oxygen saturation 90% on 5L by nasal cannula, height 159 cm, and weight 45.3 kg. On physical examination, she was a well-developed, slightly emaciated female in no acute distress. Her speech was clear; her skin was pale, warm, and dry; and she was alert and oriented to person, time, and place. Extraocular motion was within normal limits, and pupils were equal, round, and reactive to light and accommodation. Oral mucosa was pale and moist. Auscultation revealed regular heart rate and rhythm without murmurs or heaves. First and second heart sounds were heard. Her lungs were clear to auscultation; respirations were not labored. A 4-cm×3-cm nontender, nonmobile, right axillary mass was present. The patient’s abdomen was concave and nontender; bowel sounds were normal. There were no masses or organomegaly. Neurologic examination showed an ataxic stance and gait to the right. Grips were equal and strong. Loss of proprioception was observed.
Stools were grossly positive for blood. Labs revealed hemoglobin 7.2 g/dL, hematocrit 21.1%, WBCs 9.6×109/L, neutrophils 7.79×109/L, mean corpuscular volume 91.4 fL, international normalized ratio 1.31, and thyroid-stimulating hormone 0.11 µIU/mL. No abnormalities were seen in her electrolytes or liver function tests. A peripheral blood smear was negative as were blood cultures for bacteria, fungal cultures, and coccidioidomycosis.
Diagnosis
The patient’s history was worrisome for metastasis of her breast cancer from 12 years ago or possibly a new primary cancer. Esophagogastroduodenscopy showed a mass in the stomach, and biopsy revealed metastatic signet-ring cell adenocarcinoma of the breast. A whole-body scan revealed multiple suspicious areas for metastasis. A CT of the brain showed numerous low-density lesions. MRI of the brain demonstrated punctuate emboli in the frontal, parietal, and occipital lobes, as well as in the cerebellum.
A transesophageal echocardiogram (TEE) showed a very large aortic valve and tricuspid valve vegetation (marantic endocarditis) (Figure 1). Ms. Q’s findings supported a widely metastatic breast adenocarcinoma to the stomach, right axilla, left sacrum, long bones, and brain. Her blood cultures were negative, and no other infectious process was found. The underlying ataxia and fatigue, as well as her chronic and acute anemia and marantic endocarditis, were attributed to the metastatic breast cancer.
Analysis
Ms. Q’s case was quite challenging. Her symptoms and diagnosis were multifactorial. Nonbacterial thrombotic endocarditis (NBTE) is a rare form of endocarditis found in patients with advanced malignancy and collagen vascular disorders. Most cases are not diagnosed until autopsy. Ms. Q’s chronic anemia was caused not only by the stomach metastasis, but also by bone marrow suppression from the bony metastasis.
Stage 1 breast cancer that is both estrogen receptor- and progesterone receptor-positive rarely metastasizes to the heart or stomach. In Ms. Q’s case, there was an initial concern for IE, stroke, intracranial hemorrhage, and meningitis, but further investigation ruled these out.
Discussion
NBTE, or marantic endocarditis, is characterized by formation of sterile platelet and fibrin thrombi on cardiac valves and adjacent endocardium. The condition was first identified in 1888. The most common malignancies associated with NBTE are breast, lung, prostate, and colon. The disorder often presents with symptoms of pulmonary or systemic embolization.
TEE is required for detection of valvular lesions. NBTE is often confused with IE, so blood cultures must be done. It is uncommon to have two valves involved. The presence of cardiac vegetations by TEE in NBTE is undistinguishable from IE. In both conditions, heart murmurs are heard a majority of the time (but not always, as seen in Ms. Q’s case). IE typically presents with heart murmur, fever, leukocytosis, bacteremia, and vegetations. In contrast, NBTE typically presents with heart murmur and vegetation. Most commonly affected is the mitral valve, followed by the aortic, tricuspid, and pulmonary valves.
Treatment
NBTE has a high mortality. Treatment includes anticoagulation with unfractioned heparin, followed by surgical valve replacement. Patients with advanced malignancy often are not candidates for surgery, so palliative treatment is given. Unfortunately, because of acute GI bleeding due to Ms. Q’s stomach cancer and her chronic anemia from bone marrow suppression, anticoagulation therapy was not an option. She was offered palliative radiation therapy because her cerebellar metastasis ruled out chemotherapy.
As this case illustrates, providers must be cognizant of paraneoplastic processes in the setting of emboli. While antemortem diagnosis of NBTE is rare, a diagnosis is important because of its impact on treatment and may be beneficial to decrease ischemic events. Identification of NBTE will help tailor future treatments for patients.
Ms. Q and her family decided against further testing or treatment, and she was transferred to an inpatient hospice facility where she died two days later. Ms. York is a nurse practitioner, and Dr. Karlin is an oncologist at the Mayo Clinic in Phoenix.
Read on
- Lopez JA, Ross RS, Fishbein MC, Siegel RJ. Nonbacterial thrombotic endocarditis: a review. Am Heart J. 1987;113:773-784.
- Eiken PW, Edwards WD, Tazelaar HD, et al. Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985-2000. Mayo Clin Proc. 2001;76:1204-1212.
- Borowski A, Ghodsizad A, Cohnen M, Gams E. Recurrent embolism in the course of marantic endocarditis. Ann Thorac Surg. 2005;79:2145-2147.
- Fanale MA, Zeldenrust SR, Moynihan TJ. Some unusual complications of malignancies: case 2. Marantic endocarditis in advanced cancer. J Clin Oncol. 2002;20:4111-4114.
