The pathogenesis of so-called cardiac rhabdomyoma in swine: a histological, immunohistochemical and ultrastructural study.

To determine whether cardiac rhabdomyoma (CR) is a hamartoma of fetal cardiac myocyte, we investigated five cases of CRs that spontaneously developed in five 6-month-old hybrid swine with histological, immunohistochemical, and ultrastructural techniques. The cases were four multiple and one solitary neoplasms, which appeared as intraventricular nodules of various sizes without any congenital malformations. Histologically, the large ovoid CR cells with an occasional spiderweb appearance showed a transition from normal-looking cardiac myocytes or rarely from Purkinje cells, but no mitotic figures. Besides large amounts of glycogen, the CR cells contained many PAS-negative, large cytoplasmic vacuoles filled with eosinophilic or fibrillar substance. Immunohistochemically, the CR cells showed intense positivity for desmin and variable positivities for vimentin, alpha-atrial naturiuretic peptide, and proliferating cell nuclear antigen. These positivities were not seen in adjacent cardiac myocytes. Cytokeratin was negative in the CR cells but was positive in fetal cardiac myocytes of early gestation. Rod-like or granular positivity for alpha-actinin in the CR cells was similar to that in nemaline myopathy. Ultrastructurally, the CR cells contained myofibrils that frequently showed myofibrillar degeneration and produced large intracytoplasmic vacuoles. These myofibrils often mingled with nemaline bodies and leptofibrils that continued to the Z bands. T-systems, sarcoplasmic reticulum, and intercalated discs, which are specific features of postnatal cardiac myocytes, were sometimes observed in the CR cells. Increase of glycogen and mitochondria and appearance of atrial-specific granules associated with the Golgi apparatus were other features noted. The present findings have not been reported, even in human CR. From these new observations with the recent report on the occurrence of CR in neonatal piglets, swine CR does not belong to the entity of hamartoma but may be a congenital dysplasia of the perinatal cardiac tissues with myofibrillar degeneration, affecting mainly cardiac myocytes and rarely Purkinje cells. The various immunophenotypic changes including proliferating cell nuclear antigen and the increase and appearance of cytoplasmic elements compared with mature cardiac myocytes can be interpreted as reactive or regenerative changes due to myofibrillar degeneration.