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Histochemical and ultrastructural studies in fibrodysplasia ossificans progressiva (myositis ossificans progressiva).
By light microscopy the subdermal nodule of a patient with fibrodysplasia ossificans progressiva (FOP) had a fibromatoid histologic appearance. The cytoplasm of the cells stained strongly for mannose-rich glycoprotein with the concanavalin A-horseradish peroxidase (con A-HRP) method. The tumors also exhibited abundant hyaluronidase-digestible mucopolysaccharide in the interstitium with various basic staining reagents. This material appeared to consist principally of hyaluronic acid or chondroitin sulfate with few or mainly masked sulfate esters. At the ultrastructural level, cells interpreted as the tumor cells in the subdermal nodule from the patient displayed extremely hyperplastic granular reticulum and well-developed Golgi elements and appeared very active in synthesis and secretion of protein. The material in the dilated cisternae of the granular reticulum stained for glycoprotein with the con-A-HRP method. Macrophages which comprised the other main cell type in the nodules commonly contacted the tumor cells and occasionally evidenced engulfment of these cells. The intercellular matrix of the nonossified subdermal nodule exhibited greatly increased mucosubstance and, by electron microscopy, showed an unusual network of dialyzed iron-reactive acid muco-substance in the interstitium.
Elevated prostaglandin production in cultured cells from a patient with fibrodysplasia ossificans progressiva.
Prostaglandin E production was measured in cells cultured from both a fibromatoid lesion and a normal area of skin in a patient with fibrodysplasia ossificans progressiva. The synthesis of prostaglandin E-like material (iPGE) was ten- to twenty-fold greater in cells cultured from the patient's fibromatoid lesion than in fibroblasts obtained from her normal skin. Addition of indomethacin in vitro resulted in a greater than 95% reduction of iPGE production in both cell cultures. These observations appear to warrant further investigation in additional patients, with this disease.
Studies on alkaline phosphatase activity cultured cells from a patient with fibrodysplasia ossificans progressiva.
The cytoplasm of tumor cells from a subdermal nodule in a patient with fibrodysplasia ossificans progressiva (FOP) exhibited intense enzymatic activity in cryostat sections processed for demonstration of alkaline phosphatase. Nuclear heterochromatin and nucleoli, particularly in the area of the dense component, also showed strong reactivity. Finely minced blocks from the lesion of the patient with FOP revealed lighter reactivity which, in the tumor cells, avoided membrane limited spaces and appeared to be confined to hyaloplasm. Extracellular spaces disclosed very little or no reactivity and specimens from the patient's uninvolved skin lacked staining. The tumor cells from the subdermal nodule did not exhibit increased acid phosphatase activity. Cells (L-FOP) derived from a subdermal nodule and grown by tissue culture techniques also synthesized large amounts of prostaglandin E-like material and alkaline phosphatase. The amounts of prostaglandin E-like material synthesized by these L-FOP cells was reduced by more than 31 per cent by the antiinflammatory drugs indomethacin and sodium meclofenmate. Also, the production of alkaline phosphatase by these L-FOP cells was reduced by more than 40 per cent by ethane-1-hydroxyl-1,1-diphosphonate. Addition of prostaglandin E to nonlesion cells did not result in increased alkaline phosphatase activity.