Hemorrhagic Cerebral Metastases Presenting After Complete Resection of Atrial Myxoma: A Case Report with a Favorable Outcome and Review of the Literature

Cardiac myxoma is the most common benign heart tumor. Its complete resection is usually curative; however, sometimes recurs with metastases, exhibiting a malignant potential through mechanisms which remain unclear. The brain is the most frequent metastatic site. With a small number of cases reported in literature, there is currently no standard management for cerebral myxoma metastases, and most of the reported patients have been treated with cere- bral surgery, but postoperative chemotherapy and/or radiation have been attempted. We report a case treated for a benign atrial myxoma, which developed multiple brain metastases, in whom a “wait and see” strategy was adopted, delaying surgery approach with a favorable outcome over a prolonged follow-up period.

Brain; Cardiac myxoma; Metastases

A 72-year-old woman was admitted to the emergency room for acute weakness of the right arm and speech impairment.

Ten months before, she underwent resection of an inter-atrial sep- tal cardiac benign myxoma that has manifested embolizing the left upper limb.

Her past medical history also included resection of VIII right cranial nerve for schwannoma at the age of 52 years, with recurrence of this lesion at the age of 55, with hydrocephalus treated with ventriculoperitoneal shunt and complete resection of the lesion and subsequent radiotherapy.

At the neurological examination the patient was drowsy, with fluent aphasia, mild dysarthria, right hemianopsia and a mild weakness of the right arm. As a consequence of the previous neurosurgery, chronic right facial nerve perifer ical palsy and deafness in the right ear were also observed. The acute neurological deficits persisted only a few hours with subsequent complete remission. Transient neurological symptoms and electroencephalographic focal slowing in the left temporo-occipital regions led us to interpret the neurological symptoms as a focal limited epileptic seizure.

In addition to previous neuroradiological features related to the past neurosurgery, the brain CT scan revealed some hyperdense masses of round shapes in the right occipital and left parietal regions (Figure 1, section 1 a-b), interpreted as hemorrhagic metastatic lesions or, alternatively, as abscesses from opportunistic germs. The brain MRI defined these findings better, revealing one nodular lesion in the right occipital pole and a group of numerous and confluent lesions in the left parietal lobe, surrounded by a vasogenic edema, the largestone located in the left supramarginal gyrus and parieto-temporo-occipital carrefour (section 1 c-f). All lesions presented hemorrhagic components in subacute or chronic phases (section 1e-f, g-h), mildly enhancing gadolinium (section 1 i-l). There were also signs of leptomeningeal hemosiderosis (section 1 g-h).

In the absence of clinical and biohumoral signs of infection, the neuroradiological features supported the diagnosis of metastatic hemorrhagic lesions. Total body CT scans and F18-fluorodeoxyglucose positron emission tomography were both negative for malignan- cy, as well as esophagogastro-and colonoscopy. We have therefore assumed that cerebral lesions were secondary to myxoma. Transe- sophageal echocardiogram demonstrated no recurrence of the tumor.

Given the age of the patient, with an already complex neurosurgical history, the paucisymptomatic presentation of disease, and the site of lesions in eloquent areas, it was preferred not to proceed with surgical options, and to keep a “wait and see” strategy.

Thus, the patient was treated with Dexamethasone 8 mg/die per os for two weeks, which was then slowly tapered down until a low main- tenance dose of 0.5-1 mg/die. She was also treated with Clobazam as an antiepileptic drug.

A second total body CT-PET scan, performed 12 months after the first screening, remains negative.

During the follow-up (42 months since the removal of myxoma, 32 months since detection of cerebral involvement) the clinical situation remained stable. Only a brief epileptic seizure similar to the one described above occurred, and Carbamazepine was started while Clobazam stopped. The series of brain MRIs -performed at 2, 5, 12, 18, months - showed a favorable evolution of the neuroradiological picture with a reduction of nodular lesions, decreasing in both va- sogenic edema and enhancement (Figure 1, section 2 a-b, c-d, i-l). No more acute bleeding was detectable but persistent hemosiderin components both in the parenchymal and subarachnoid space were observed (section 2 g-h). CT scans progressively showed increased hyperdensity in some of the cortico-subcortical left parietal lesions consistent with calcifications (section 2, a-b).

After a complete curative treatment with local resection, myxo- mas can rarely cause metastatic disease to the brain [1-5]. In medical literature, including the present case, there only 35 cases of myxoma cerebral metastases (Table 1), that are described with variable out- comes [1-33], including fatal cases [5-11]. Although a standard man- agement of patients with cerebral myxoma metastases has not been established, the most reported treatment is surgery, with or without adjuvant radiotherapy or chemotherapy [2,5,11-16].

Our report shows a patient who has not been treated with brain surgery or adjuvant therapy that experienced a benign course of disease at prolonged follow-up. Over time, our patient had no substantial changes in the neurological status, while the MRI evidence of reduction of metastases size, blood components and vasogenic edema. In addition, we observed the evolution of some of the hemorrhagic lesions into calcifications, supporting the idea of a change of disease from an evolving to an inactive stage.

Table 1: Reported cases in literature of cardiac myxoma metastasizing to the brain whit relative treatment and outcomes.
Abbreviations: NED: No Evidence of Disease; DOD: Dead of Disease; AWD: Alive With Disease. Modified from Rose at al., Moiyadi et al., and Altundag et al.

The natural history of brain metastases of myxoma is extremely variable, as it may be stable over months, or manifesting with neurological deficits in a brief period of time with fatal outcome [2,5,12,14]. In the series of 27 cases collected by Maas and collegues [12], eight patients did not undergo brain surgery; among these, only two were still alive after a follow up of 63 and 39 months respectively, five died within 8 months on average, one was lost to follow up. The few heterogeneous cases reported so far does not allow to indicate possible factors for disease progression, although the worst prognosis has been observed in patients who had other recurrent sites of disease in addition to the brain, thus underlining a more aggressive disease in these patients [5,14].

Although the mechanisms by which myxoma may have malignant potential have yet to be elucidated, the presence of robust inflamma- tory and vasculitic changes associated with metastatic lesions suggest a strong focal inflammatory reaction induced by myxoma [14,17]. In our case, the good response to corticosteroids suggests a main role of inflammation produced by myxoma, more than a malignant local invasiveness of the tumor. However, this finding must be confirmed -or not- in additional cases.

In conclusion, a “wait and see” strategy with a conservative ap- proach may be considered in patients with myxoma brain metastases, as no strong evidence exists to treat these patients with surgery, radio- or chemotherapy. Anti-inflammatory treatments, monitoring clinical and neuroradiological pictures and seizure controls are appropriate options.

Multicenter studies with uniform multidisciplinary clinical and radiological criteria at the follow-up are needed to better characterized the natural history of brain metastases management in myxoma.