Cardiac myxoma (CM) is the most frequent primary cardiac tumor, representing the 83% of all the neoplasms of this type. The incidence of CM in autopsies has been estimated at 0.03%1. They may be isolated or sporadic, or instead familial or part of a syndrome, such as the Carney complex. In CMs, mutations inactivating the tumor suppressor gene PRKAR1A—both in sporadic and familiar forms—are very common. The PRKAR1A gene encodes the regulatory subunit type 1α (R1α) of the protein kinase A (PKA)2,3.
The majority of CMs grow in the left atrium, mainly in the region of the fossa ovalis. In fact, for a long time, such tumors were thought to arise from microscopic endocardial/endothelial structures known as Prichard structures, i.e. little endocardial deformities with capillary spaces lined with plump endothelial cells, located in the interatrial septum1.
Moreover, CMs are mainly detected in females with a mean age at the diagnosis of about 50 years. When CMs are part of the Carney complex (CC) syndrome, they can occur among people younger than 50, and emerge in multiple sites of the heart3.
Grossly, the appearance of CMs is that of smooth, round, and compact masses or, alternatively, of friable and villous vegetation. The location and general characteristics of CMs are important factors for many clinical aspects of the disease: in fact, such neoplasms may cause strokes, peripheral embolisms, syncope, or sudden death. Conversely, true metastases are considered extremely rare2,4.
Constitutional symptoms like fever, high erythrocyte sedimentation rate and anemia can be present. Furthermore, CMs can occasionally produce interleukins 6 (an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine) and dense and heterogeneous systems of adaptive and innate immunity cells5,6.
Microscopically, CM is a neoplasm composed of plump and stellate cells, and of morphologically bland mesenchymal cells set in the myxoid stroma.
Myxoma cells, in turn, may form rings, cords and nests that are often closely associated with capillaries. Interestingly, vascular channels often appear to develop from myxomatous structures2.
Sub-endothelial reservoir cells or cardiomyocyte progenitors have been formerly suggested as possible precursors of CMs cells.
Another possible origin of CMs is the Cardiac Neural Crests (CNCs), suggested from the expression of calretinin in the tumor cells. The hypothesis of CNCs as origin of CMs is also supported by the expression of other markers such as Ubiquitin carboxyl-terminal hydrolase isozyme L1 (PGP9.5), S100 proteins and neuron-specific enolase (NSE), semaphorin3C and plexinA23,7,8.
Since, at the best of our knowledge, there is not reported evidence in literature of circulating cardiac myxoma cells (CCMCs), in this work we have studied a series of 10 sporadic cardiac tumors using a peripheral blood culture method9,10,11,12,13,14,15—recognized as effective for the search for circulating tumor cells.
To date, most studies on CM have focused on the characterization of tumor cells in situ, therefore a next step is the profiling of the liquid biopsy to produce valuable orthogonal data for the definition of this ambiguous pathology.
The multiparametric approach proposed here in the CM integrates multiple tumors and stromal phenotypes—such as endothelial cells—based on blood to produce an informative profile of the tumor that can be acquired presurgical. To test the technical feasibility of such an approach, we undertook a pilot study using blood samples from a small cohort of CM patients. Each blood sample was analyzed for the presence of CTCs, and CECs and compared with data obtained from PDX models, and these data were used to generate an overview profile of multiparameter liquid biopsy specific for patients with CM.