Asteroid Bodies in Silicone‐induced Granuloma are Ubiquitinated

Asteroid bodies, or star‐shaped inclusions, have been described in multinucleated giant cells in sarcoidosis and in a broad spectrum of granulomatous inflammations. The bodies are well characterized at the light and electron microscopic levels (1,2). Cain and Kraus(1) demonstrated by immunofluorescence that asteroid bodies consist predominantly of vimentin filaments and that lesser amounts of microtubules are involved in the formation of the bodies, but their nature is still obscure. We examined asteroid bodies by immunohistochemistry using various antibodies, and found that the bodies were stained with ubiquitin but they were not stained by other antibodies including vimentin. A 55‐year‐old Japanese woman developed sarcoidosis (bilateral hilar lymphoadenopathy, left‐sided lower cranial nerve palsies (VIII, IX, X), vestibular ataxia, elevated levels of angiotensin converting enzyme (31.8 U/ml) and lysozyme (12.4mcg/ml) in the serum, and negative tuberculin skin test) 22 years after mammoplasty. Two separate biopsies of bilateral breast nodules were examined with light, immunohistochemical and electron microscopic methods. Light microscopic examinations revealed that their morphology consisted of granuloma with many multinucleated giant cells. Immunohisto‐chemically, formalin‐fixed, paraffin‐embedded sections were stained by the avidine‐biotin‐peroxidase method, and counterstained with hematoxylin. Antibodies included anti‐ubiquitin antiserum (Chemicon, USA, monoclonal, 1: 1000), anti‐swine vimentin (Dako, Denmark, monoclonal, 1: 200), anti‐desmin (Dakopatts, Denmark, polyclonal, 1: loo), anti‐actin (Advance, Tokyo, poly‐clonal, 1: 200), anti‐MAPS (Sigma, USA. polyclonal, 1: 400), anti‐a tubulin (Sigma, USA, monoclonal, 1: 4000), and anti‐8 tubulin (Sigma, USA, monoclonal, 1: 800). lmmunohistochemical studies revealed that asteroid bodies in the giant cells were positive for ubiquitin (Fig. la). However, asteroid bodies were negative for all of the remaining antibodies including antibody to swine vimentin (Fig. lb, arrow). Diffuse positive reactions were seen in the cytoplasms of multinucleated giant cells for swine vimentin (Fig. 1b) and desmin. Electron microscopy revealed that asteroid bodies consisted of accumulations of filaments each approximately 10–20 nm thick. Biopsied specimens analyzed by infrared spectrophotometry disclosed that the injected material was polydimethylsiloxane. Our immunohistochemical study revealed that the cytoplasm of multinucleated giant cells contained several filamentous structures. However, asteroid bodies were negative for those filaments, so we could not confirm the origin of the bodies by immunohistochemistry. Ubiquitin has been associated with abnormal cytoplasmic filaments mainly in degenerative diseases of the central nervous system (3). Regarding other systems, Mallory bodies of alcoholic liver disease and cytoplasmic inclusions in myopathy were also ubiquitinated (4). All of those inclusions contained intermediate filament proteins. Our findings suggest that asteroid bodies, at least in our case, did not consist of simple accumulations of filamentous structures, but are more complex structures in which ubiquitin‐related cytoskeletal abnormalities are present. More asteroid bodies in other granulomas must be examined to confirm our suggestion.