BackgroundKawasaki disease is recognized as the most common cause of acquired heart disease in children in the developed world. Clinical, epidemiologic, and pathologic evidence supports an infectious agent, likely entering through the lung. Pathologic studies proposing an acute coronary arteritis followed by healing fail to account for the complex vasculopathy and clinical course.Methodology/Principal FindingsSpecimens from 32 autopsies, 8 cardiac transplants, and an excised coronary aneurysm were studied by light (n=41) and transmission electron microscopy (n=7). Three characteristic vasculopathic processes were identified in coronary (CA) and non-coronary arteries: acute self-limited necrotizing arteritis (NA), subacute/chronic (SA/C) vasculitis, and luminal myofibroblastic proliferation (LMP). NA is a synchronous neutrophilic process of the endothelium, beginning and ending within the first two weeks of fever onset, and progressively destroying the wall into the adventitia causing saccular aneurysms, which can thrombose or rupture. SA/C vasculitis is an asynchronous process that can commence within the first two weeks onward, starting in the adventitia/perivascular tissue and variably inflaming/damaging the wall during progression to the lumen. Besides fusiform and saccular aneurysms that can thrombose, SA/C vasculitis likely causes the transition of medial and adventitial smooth muscle cells (SMC) into classic myofibroblasts, which combined with their matrix products and inflammation create progressive stenosing luminal lesions (SA/C-LMP). Remote LMP apparently results from circulating factors. Veins, pulmonary arteries, and aorta can develop subclinical SA/C vasculitis and SA/C-LMP, but not NA. The earliest death (day 10) had both CA SA/C vasculitis and SA/C-LMP, and an “eosinophilic-type” myocarditis.Conclusions/SignificanceNA is the only self-limiting process of the three, is responsible for the earliest morbidity/mortality, and is consistent with acute viral infection. SA/C vasculitis can begin as early as NA, but can occur/persist for months to years; LMP causes progressive arterial stenosis and thrombosis and is composed of unique SMC-derived pathologic myofibroblasts.

Glycogen storage diseases (GSD) affect primarily the liver, skeletal muscle, heart, and sometimes the central nervous system and the kidneys. These unique diseases are quite varied in age of onset of symptoms, morbidity, and mortality. Glycogen storage diseases are classified according to their individual enzyme deficiency. Each of these enzymes regulates synthesis or degradation of glycogen. Interestingly, there is great phenotypic variation and variable clinical courses even when a specific enzyme is altered by mutation. Depending on the specific mutation in an enzyme, a GSD patient may have a favorable or unfavorable prognosis. With neonatal or infantile forms, some GSDs lead to death within the first year of life, whereas other glycogen storage diseases are relatively asymptomatic or may cause only exercise intolerance. The paper provides a brief review and update of glycogen storage diseases, with respect to clinical features, genetic abnormalities, pathologic features, and treatment.

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Angiomyolipoma occurs rarely in the liver, with only 25 previous cases being reported in the English literature. The article describes two additional cases, one of which was multicentric, with results of ultrastructural and immunocytochemical studies. Many of the tumor cells contained numerous electron-dense granules, some with transverse striations like those found in melanosomes. Both tumors stained positively for S-100 protein and melanoma-specific antibody HMB-45. One case also expressed vimentin and neuron-specific enolase. Both were negative for cytokeratin, carcinoembryonic antigen, alpha-fetoprotein, desmin, muscle-specific actin, factor VIII antigen, and chromogranin. Comparison of our ultrastructural findings with those of classic renal angiomyolipoma raises the possibility that the melanosomelike structures may represent renin granules rather than melanosomes, although the latter are not excluded. Expression of HMB-45 in angiomyolipoma has important biologic and diagnostic implications, whether or not it reflects melanocytic differentiation.

To clarify salient issues pertaining to histiocytosis X--a syndrome that includes Letterer-Siwe disease, Hand-Schuller-Christian disease, and eosinophilic granuloma--the authors review the epidemiologic data and the histologic, morphologic, and clinical bases for diagnosis and prognosis. Histiocytes are defined and their possible histogenesis outlined, and Langerhans cells, which may be a leading element in active lesions, are characterized. The authors outline hypothetic pathogenetic schema, which they recommend be tested by recently developed immunologic and genetic means, since histiocytosis X, at least in its disseminated form, remains an unpredictable disease for which there is no proven effective therapy.