A forty-year-old woman presented with transient left-sided paresthesia for twelve months and a five-month history of recurrent episodes of paroxysmal visual disturbances. Physical examination was remarkable for left superior quadrantanopsia. Extensive diagnostic work-ups, which included lumbar puncture, microbial cultures, and rheumatoid factors, were negative. An initial transthoracic echocardiogram showed no abnormalities. Magnetic resonance imaging (MRI) of the brain revealed an early subacute infarct in the territory of the right posterior cerebral artery, as well as multiple diffuse small infarcts within the frontal lobes and the left parietal cortex. The patient experienced three other neurologic episodes, consisting of headache, left hemiplegia, and involuntary facial twitching. Follow-up computed tomography (CT) and MRI of the brain showed intraparenchymal hemorrhage in the right frontal lobe with edema and a mass effect on the right frontal ventricular horn. A craniotomy was performed for evacuation of the hemorrhage. Pathologic examination showed a myxomatous lesion with aneurysmal formation and hemorrhage. A repeat transesophageal echocardiogram revealed a left atrial myxoma that was subsequently resected.
Two years after the successful cardiac surgery, the patient developed chronic fatigue and progressive pain of the right buttock and anterior hip area. Laboratory testing was remarkable for elevation of the serum IL-6 level (27.56 pg/mL; normal range: 0.31 to 5.00 pg/mL). Pelvic radiographs showed multiple well-defined osteolytic lesions in the right iliac crest and right sacrum (Fig. 1-A). CT scans and MRI revealed large radiolucent lesions in the corresponding areas (Fig. 1-B). A bone scan revealed relatively photopenic lesions (Fig. 1-C), while a whole body 18FDG-PET scan showed numerous FDG avid lesions in the right ilium, right sacrum, bilateral humeri, and left femur, as well as increased tracer uptake in the T8, T10, and L3 vertebral bodies (Fig. 1-D). She underwent resection of the right pelvic and sacral lesions with subsequent improvement of the symptoms. She then developed a sudden onset of severe back pain without neurologic deficits. Radiographs revealed compression fractures of the T10 and T11 levels (Fig. 2-A). CT scan and MRI demonstrated numerous osteolytic spinal lesions and extensive destruction of the T8, T10, and T11 vertebral bodies, with protrusion of the tumor mass into the spinal canal at T11 (Fig. 2-B). The patient underwent anterior resection of the lesions at the T8, T10, and T11 vertebral bodies, with combined anterior and posterior spinal instrumentation and fusion with use of two vertebral cages augmented with poly(methyl methacrylate) (PMMA) from T4 to L1. She also underwent intramedullary nailing of the proximal part of the left femur and right humerus because of large osteolytic lesions. Skeletal survey at the nine-year follow-up showed stable, nonprogressive metastatic lesions. Microscopic examination of the lesions in the right iliac wing, proximal part of the left femur, spine, and right humerus revealed similar findings, characterized by abundant myxoid stroma containing bland spindle and stellate cells (Fig. 3-A). The lesional cells were arranged singly or in small clusters, with a ringlike arrangement around the vessels. They had bland nuclei and abundant eosinophilic cytoplasm without atypia and active mitosis. The neoplastic tissue also contained foamy macrophages with abundant cytoplasmic hemosiderin pigments. The interface between the bone and the lesion consisted of a dense fibrous capsule with bone erosion (Fig. 3-B). Immunohistochemical stains were positive for vimentin and negative for pancytokeratin. CD31 staining highlighted the blood vessels and the surrounding tumor cells. In addition, tumor cells expressed calretinin (Fig. 3-C), a calcium-binding protein used as a specific marker to diagnose cardiac myxoma and differentiate it from mural myxoid thrombi or papillary fibroelastoma7. The findings were consistent with embolic dissemination of atrial myxoma. At the most recent nine-year follow-up, the patient was ambulatory without neurologic deficit, but still experienced mild constitutional symptoms.
We report a case of atrial myxoma with predominantly osteolytic embolic dissemination, markedly elevated levels of serum IL-6, relative photopenia on the 99mTc bone scan, and unusually high 18FDG uptakes on the PET scan. Most myxomas are located in the left atrium, but the right atrium, right ventricle, and left ventricle can also be affected. Tissue culture and electron microscopic studies have demonstrated that atrial myxomas are mesenchymal in origin1. Most cases are sporadic, but approximately 7% are part of the “Carney complex,” which is characterized by the association of myxomas with endocrine overactivity, spotty skin pigmentation, and schwannomas8. Our case did not typify the Carney complex.
The clinical presentation of atrial myxoma includes a triad of constitutional, obstructive, and embolic symptoms. Constitutional symptoms are related to chronic inflammation-like generalized fatigue and low-grade fever. These symptoms are related to IL-6 secretion by myxoma cells9. Obstructive symptoms, such as fatigue, shortness of breath, or syncope, are secondary to the mitral valve occlusion. Systemic embolization occurs in 40% to 50% of patients10. The emboli may involve the arteries of the central nervous system, heart, kidney, liver, spleen, and extremities. The bulk of the clinical and pathological evidence is in favor of a simple embolic event rather than metastasis. To the best of our knowledge, death associated with widespread visceral and nodal metastases has never been reported. Additionally, the so-called myxoma “metastases” occur in the direction of ventricular blood flow. Myxomas in the left side of the heart disseminate to the systemic circulation, and the lesions from the right side of the heart are transported to the lung11. Skeletal lesions following cardiac myxoma are very rare. Only sporadic cases have been reported in the literature2-6, in patients whose age ranges from thirty-four to fifty-seven years. All but one case6 presented with cerebral infarction or hemorrhage, causing neurologic deficit four to nine years prior to the discovery of bone metastases and cardiac myxoma. Most of the reported cases have shown a single metastatic bone lesion. The metastatic sites included the pubis3, proximal part of the femur6, and temporal bone2. Only two previously reported cases3,4 had multiple bone lesions. No malignant transformation was observed.
The most common myxoid lesions of bone are metastases from myxoid carcinomas of an epithelial origin from intestine, breast, and lung. Metastatic carcinoma usually contains clusters of epithelium with abundant mucin and strong reactivity for cytokeratin markers. Skeletal metastases of myxoid sarcomas are well documented, particularly myxoid liposarcoma, which can be found in unusual extrapulmonary sites of metastasis such as the retroperitoneum or other soft tissues. In addition, myxoid liposarcoma has a high incidence of osseous metastasis with predilection to the spine12. Intraosseous myxoid tumors, including conventional chondrosarcomas, which may have a prominent myxoid stroma, can be distinguished on the basis of imaging by a characteristic pattern of calcification and by S-100 positivity. Metastases from extraskeletal myxoid chondrosarcoma and myxoid liposarcoma can be differentiated by the identification of their specific translocations on cytogenetic analysis13,16. The most common myxoid benign bone tumor is myxoma of the jaw. This entity lacks the perivascular arrangement seen in the atrial myxoma. Primary myxomas of bone outside the jaw are rare, with reported cases affecting the skull base17-19, temporal bone20,21, femur22, humerus23, and toe24. None of these cases were associated with cardiac myxomas or multifocal lesions.
Since Hirano et al.25 first described IL-6 production by cardiac myxomas, subsequent studies have demonstrated that elevation of the IL-6 level is related to tumor size, fever, malaise, weight loss, myalgia, and tumor dissemination9,26-29. These symptoms tend to appear when IL-6 levels exceed the threshold of 9.3 pg/mL30. Patients with cardiac myxomas and IL-6 serum levels higher than 9.3 pg/mL should be screened to rule out peripheral embolic lesions. At the present time, the use of tocilizumab, an anti-IL-6 agent, is being investigated for the treatment of cardiac myxoma31. In our case, the 99mTc-methylene diphosphonate (MDP) bone scan did not reveal the full extent of skeletal dissemination of embolic lesions, while the 18FDG-PET scan showed more accurate distributions. Conventionally, standardized uptake value (SUV) is less than 2 for most benign tumors. Many of the lesions in our case showed SUV uptakes from 2 to 4, suggesting very high metabolic activities. Among benign tumors, fibrous dysplasia and giant cell tumors may show SUV uptakes greater than 2.
In summary, we present an unusual case of multifocal osteolytic embolic lesions caused by a cardiac myxoma. The lesions were associated with a high SUV uptake on PET scan, and the patient had constitutional symptoms related to an elevated serum level of IL-6. The latter may be useful as a screening test for recurrence of cardiac myxoma or in disseminated lesions.