Somatic PRKAR1A mutation in sporadic atrial myxoma with cerebral parenchymal metastases: a case report

Abstract

BackgroundAtrial myxomas are generally considered benign neoplasms. The majority of tumors are sporadic and less than 10% are associated with an autosomal dominant condition known as the Carney complex, which is most often caused by germline mutation in the gene PRKAR1A. Whether this gene plays a role in the development of sporadic myxomas has been an area of debate, although recent studies have suggested that some fraction of sporadic tumors also carry mutations in PRKARIA. Extra-cardiac complications of atrial myxoma include dissemination of tumor to the brain; however, the dissemination of viable invasive tumor cells is exceedingly rare.Case presentationWe present here a 48-year-old white woman who developed multiple intracranial hemorrhagic lesions secondary to tumor embolism that progressed to ‘false’ aneurysm formation and invasion through the vascular wall into brain parenchyma 7 months after resection of an atrial myxoma. Whole exome sequencing of her tumor revealed multiple mutations in PRKAR1A not found in her germline deoxyribonucleic acid (DNA), suggesting that the myxoma in this patient was sporadic.ConclusionsOur patient illustrates that mutations in PRKAR1A may be found in sporadic lesions. Whether the presence of this mutation affects the clinical behavior of sporadic tumors and increases risk for metastasis is not clear. Regardless, the protein kinase A pathway which is regulated by PRKAR1A represents a possible target for treatment in patients with metastatic cardiac myxomas harboring mutations in the PRKARIA gene.

Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin‐6 and matrix metalloproteinases

“…Although the mechanisms of embolization of a benign tumor and metastasis of an invasive malignancy are fundamentally different, the appearance of multiple lesions at a distant site in the setting of a cardiac myxoma has occasionally been referred to (erroneously) in the literature as “metastasis.” 17,18 Since the first description made by Rankin et al ., in 1978, 19 our comprehensive review revealed 36 histologically established cases of intracerebral embolization associated with parenchymal brain invasion from a benign left atrial myxoma (Table 1). 10,14,18–51 A careful review of the cases confirmed that three patients have been reported twice, 14,19,20,23,24,28 six patients had unavailable histological proof, 37,52–56 and four apparent primary cardiac sarcomas were erroneously reported as a cardiac myxoma 57–60 . In one case, the original report could not be located, 61 and another report described embolic myxoma cells in the leptomeninges without evidence of parenchymal seeding 62 …”

“…Histological evaluation of primary tumor frequently reveals benign cardiac myxomas with prominent papillary surface projections. 19,24,29,49 Occasionally, cardiac myxofibrosarcomas 64 or metastatic adenocarcinomas 10,30 might resemble cardiac myxomas. Based on these circumstances, calretinin immunohistochemistry is paramount for the proper identification of embolic cardiac myxomas.…”

“…In our review, only seven of 36 cases evaluated calretinin expression in the infiltrative tumor cells. 35,39,43,45,47,49 Although the mechanism of the brain parenchymal seeding after complete local resection of cardiac myxomas has not been elucidated, embolic tumor cells might remain active and invade the wall of the distant vessels. 29,35,39,45 Traditionally, the vasa vasorum has been considered a key element for the embolization of tumor particles.…”

“…Radiotherapy has been frequently conducted for patients with multiple or progressive lesions, with promising results, although clinical follow up managements are limited. 10,32,38,45,47,49,51 Considering that these lesions have persistently active tumor cells, adjuvant chemotherapy would be a reliable option to reduce the risk of extracardiac seeding. However, no previous information on experiences in the management of this therapeutic option in cardiac myxomas is available.…”

“…Despite multiple parenchymal seeding, the histology of the primary and embolic tumor infiltrates remains benign without evidence for malignant transformation. Histological evaluation of primary tumor frequently reveals benign cardiac myxomas with prominent papillary surface projections 19,24,29,49 . Occasionally, cardiac myxofibrosarcomas 64 or metastatic adenocarcinomas 10,30 might resemble cardiac myxomas.…”