glycogen and Rhabdomyoma

Tuberous sclerosis is a hamartoma syndrome due to mutations in TSC1 or TSC2 in which cardiac rhabdomyomas are seen in approximately 60% of patients. These lesions have an unusual natural history as they are usually most prominent immediately after birth and spontaneously resolve in most cases. To develop a mouse model of this lesion, we used a conditional, floxed allele of Tsc1 and a modified myosin light chain 2v allele in which cre recombinase expression occurs in ventricular myocytes. Mice with ventricular loss of Tsc1 had a median survival of 6 months and developed a dilated cardiomyopathy with the occurrence of scattered foci of enlarged ventricular myocytes. The enlarged cells were periodic acid-Schiff positive indicating the presence of excess glycogen and expressed elevated levels of phospho-S6, similar to findings in patient rhabdomyoma cells. The observations confirm that rhabdomyomas occur through a two hit mechanism of pathogenesis. However, the mice showed no evidence of fetal/neonatal demise, and there was no evidence of proliferation in the lesions. We propose that these differences are due to the timing of loss of Tsc1 in the ventricular myocytes and/or the truncated gestational period in the mouse compared with humans, during which progestational hormones may accentuate the growth of patient rhabdomyomas.

Topics: Alleles; Animals; Cardiac Myosins; Cell Proliferation; Glycogen; Heart Neoplasms; Heart Ventricles; Integrases; Mice; Muscle Cells; Mutation; Myocardium; Myosin Light Chains; Phosphorylation; Rhabdomyoma; Ribosomal Protein S6 Kinases; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tumor Suppressor Proteins

Adult rhabdomyoma is a benign, highly differentiated tumor of skeletal muscle. We observed transverse tubules and triads beside myofilaments in a rhabdomyoma from the submandibular area of a 66-year-old woman. Several types of muscle cells were present. In one, mitochondria abounded; in another, muscle filaments predominated. Myoglobin was also detected in the tumor.

Topics: Aged; Female; Glycogen; Head and Neck Neoplasms; Humans; Mitochondria, Muscle; Myofibrils; Myoglobin; Neck Muscles; Rhabdomyoma

Electron microscopy of a cardiac rhabdomyoma revealed two varieties of cells: (1) typical "spider cells' characterized by few myofibrils and large aggregates of glycogen particles free in the cytoplasm; and (2) cells with more myofibrils, less glycogen, and glycogen within membrane-limited vacuoles. These differences in myofibril development and glycogen content represent two succeeding stages in the early maturation of normal cardiocytes. The vacuoles containing glycogen were interpreted as autophagic and, consequently, active in the glycogen decrease typical of normal maturing cardiocytes. Rhabdomyoma cells did not show the structures, e.g., T system, characteristic of the late normal heart development. This study supports the theory that arrested cardiocyte maturation is a factor in the pathogenesis of cardiac rhabdomyoma.

Topics: Female; Glycogen; Heart Neoplasms; Humans; Myofibrils; Pregnancy; Rhabdomyoma

Topics: Animals; Cholinesterases; Cricetinae; Glycogen; Histocytochemistry; Male; Mesocricetus; Neoplasms, Experimental; Nucleotidases; Rhabdomyoma

Electron microscopic study of a cardiac rhabdomyoma removed at open heart operation revealed large rounded or polygonal cells that contained large amounts of monoparticulate glycogen. Myofibrils in these cells were few and located either subjacent to the plasma membranes or radiating from central areas. Leptofibrils and masses of anomalous Z band material were abundant. Shallow tubular sarcolemmal invaginations and elements of free and junctional sarcoplasmic reticulum were associated with the myofibrils. Desmosomes and nexuses were evident in intercellular junctions, which were extensive and randomly distributed throughout the cell surfaces. It is concluded that cardiac rhabdomyomas probably are hamartomas.

Topics: Cell Membrane; Cell Nucleus; Glycogen; Heart Neoplasms; Humans; Infant; Intercellular Junctions; Myofibrils; Organoids; Rhabdomyoma; Sarcoplasmic Reticulum

Topics: Aged; Glycogen; Humans; Lip Neoplasms; Male; Microscopy, Electron; Mitochondria, Muscle; Myofibrils; Rhabdomyoma

Topics: Animals; Glycogen; Guinea Pigs; Heart Neoplasms; Rhabdomyoma; Rodent Diseases

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adult; Alkaline Phosphatase; Amyloid; Animals; Esterases; Glycogen; Histocytochemistry; Humans; Iron; Lipid Metabolism; Male; Methods; Microscopy, Electron; Mucins; Pharyngeal Neoplasms; Reticulum; Rhabdomyoma; Succinate Dehydrogenase

Topics: Adult; Cytoplasmic Granules; Glycogen; Humans; Male; Microscopy, Electron; Mitochondria; Muscles; Myofibrils; Organoids; Pharyngeal Neoplasms; Rhabdomyoma

Topics: Cardiomegaly; Death, Sudden; Female; Glycogen; Heart Failure; Heart Neoplasms; Humans; Infant; Infant, Newborn; Male; Rhabdomyoma; Rhabdomyosarcoma