Arch Otorhinolaryngol (1983) 238:205-208
Archives of Oto-Rhino-Laryngology 9 Springer-Verlag 1983
Ultrastructure of Multinuclear Giant Cells of a Human Vocal Cord Teflon Granuloma Bengt Carls661, Herbert H. Dedo 2, and Hans Gustafsson 1 1Departments of Otolaryngology and Histology, University of Umegt, S-90185, UmeS, Sweden 2 Department of Otolaryngology, School of Medicine, University of California, San Francisco, USA
Summary. The ultrastructural characteristics of multinuclear foreign-body giant cells (MCG) in a human vocal cord Teflon granuloma are described. The cells were found to contain varying numbers of Teflon particles within their cytoplasm. The particles, rounded or oval in shape, were surrounded by a rather elctron-dense membrane. Numerous lysosomal structures were discerned within the cells. The fine structure of M C G in granulomas induced by foreign materials other than Teflon has already been described in man as well as in several experimental animals, and the Teflon M C G resembled these cells in many respects. No evidence of malignant change was found.
Key words: Teflon granuloma - Vocal cords - Multinucleate giant cells Ultrastructure
Introduction During recent years several case reports have been published on the histological features of Teflon granulomas in human vocal cords, observed by light microscopy. The various stages of tissue response in the larynx have been followed and documented, from a few days after injection to 10 years or more. Some ultrastructural characteristics of vocal cord Teflon granulomas were described in a recent study (Dedo and Carls66 1982). However, in the specimens obtained for that study, no multinuclear foreign body giant cells could be detected. Recently, we obtained further material from a male patient who had had Teflon injected into a vocal cord 1.5 years earlier. An abundance of giant cells were found, and as no ultrastructural description of these cells was available, it was considered of interest to report on the submicroscopic features of multinucleate giant cells of a human vocal cord Teflon granuloma. Offprint requests to: Bengt Carls66, MD, Dept. of Otolaryngology
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Fig. 1. Giant cell with several ingested Teflon particles of varying size. x 3,700
Materials and Methods The technique described by Horn and Dedo (1980) for the removal of Teflon from vocal cords was used. Small tissue specimens were fixed overnight in 1.5% Glutaraldehyde in 0.1% cacodylate buffer, rinsed in buffer and postfixed in 1% OsO4 for 2 h. The specimens were dehydrated in graded ethanol solutions and embedded in Araldite. Thin sections were cut on a LKB ultrotome, counterstained with lead citrate and uranyl acetate and examined in a Philips EM 300 electron microscope.
Results and Discussion A t t h e u l t r a s t r u c t u r a l level, n u m e r o u s m u l t i n u c l e a t e giant cells w e r e d e t e c t e d c o n t a i n i n g T e f l o n p a r t i c l e s within t h e c y t o p l a s m . T h e f o r m , size a n d n u m b e r o f t h e n u c l e i v a r i e d c o n s i d e r a b l y b e t w e e n i n d i v i d u a l giant cells, as well as w i t h i n o n e a n d t h e s a m e cell (Fig. 1). F l a t t e n e d , o v a l o r r o u n d nuclei w e r e f o u n d , together with some having a smooth outline or even a more irregular one. The latter exhibited several invaginations and short irregular extrusions. Furthermore, the nuclei had one or more prominent nucleoli, and nuclear bodies were also f r e q u e n t l y e n c o u n t e r e d . M o r e o v e r , t h e nuclei of M C G w e r e o f t e n b u n c h e d t o g e t h e r , l e a v i n g l a r g e a r e a s of t h e cells d e v o i d o f nuclei. N o m i t o s e s w e r e f o u n d . T h e c e l l u l a r o u t l i n e of g i a n t cells was o f t e n i r r e g u l a r a n d h a d m a n y invaginations and pseudopodia.
Ultrastructure of Multinuclear Giant Cells
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Fig. 2. Cytoplasm packed with vesicles of varying density. In several vesicles the tripartite membranes are prominent, x 41,000 The cytoplasm was crowded with organelles but these were not evently dispersed. In certain areas the cytoplasm was crowed with vesicles with diameters between 0.1 ~m and 1 ~m (Fig. 2), whereas in other locations the cytoplasm was devoid of these vesicles. Furthermore, numerous dense bodies were found within the cell cytoplasm. Most of these probably lysosomal dense bodies were rounded or oval in shape, but more irregular forms were also seen. They varied in size and contained inclusions of different substructural patterns. A large number of these bodies exhibited a narrow halo between a homogenous matrix and the tripartite lining membrane (Fig. 2). Many micropinocytotic vesicles were found at the periphery of the M C G cells. Teflon was deposited as rounded or oval granules with diameters ranging from 1 ~m to 15 ~tm. During preparation most of the granules were distorted and lost from the sections. In many cases Teflon material was found only as remnants in the periphery of the granules (Fig. 1). Most of the granules were located intracellularly but they were sometimes also found in the extracellular space. The intracellular Teflon particles were separated from the cytoplasm by a dark-staining vesicle membrane. The R E R was not very extensive but could be identified as flattened channels of varying length. Clusters of free ribosomes were observed. Small rounded or oval mitochondria with complex cristae were found in large quantities in certain areas of the cytoplasm but angular or branched forms were not seen. Whereas in many mitochondria the internal
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structure was intact, s o m e h a d disrupted m e m b r a n e s and distorted cristae and others h a d a matrix so dense that the cristae could not be seen. N o intracellular fibrils could be f o u n d and Golgi complexes, microtubules and centrioles w e r e rarely seen. This is in contrast to M C G cells in o t h e r species. In m a n y instances m a c r o p h a g e s were f o u n d in close contact with the giant cells. T h e ultrastructure of the multinucleate giant cell g r a n u l o m a t a has b e e n studied in m a n (Black and Epstein 1974) as well as in mice, rats, chickens and guinea pigs (Sutton and Weiss 1966; Sutton 1967; M a r i a n o and Spector 1974; P a p a d i m i t r i o u 1974; van der R h e e et al. 1978; P a p a d i m i t r i o u 1979). A r n a u d et al. (1978) described the ultrastructure of p n e u m o c o n i o t i c tissue after inhalation of polyvinyl-chloride. These authors described intact P V C particles ingested by m a c r o p h a g e s . T h e particles had b e e n s u r r o u n d e d by an electron-dense m e m b r a n e . H o w e v e r , no multinucleate cells were described in this study. O u r findings are in a g r e e m e n t with those of o t h e r studies. In certain investigations using experimental animals, h o w e v e r , there was m o r e pron o u n c e d p o l y m o r p h i s m of m i t o c h o n d r i a , with angular and b r a n c h e d forms, as well as a large a m o u n t of intracellular fibrils and centrioles. Mitoses in multinucleate cells have b e e n described, but without evidence of malignant degeneration.
References Arnaud A, Pommier de Santi P, Garbe L, Payan H, Charpin J (1978) Polyvinyl chloride pneumoconiosis. Thorax 33 : 19-25 Black MM, Epstein WL (1974) Formation of multinucleate giant cells in organized epithelioid cell granulomas. Am J Pathol 74/2:263-270 Dedo HH, Carls66 B (1982) Histologic evaluation of Teflon granulomas of human vocal cords: A light and electron microscopic study. Acta Otolaryngol 93:475-484 Horn KL, Dedo HH (1980) Surgical correction of the convex vocal cord after Teflon injection. Laryngoscope 90:281-286 Mariano M, Spector WG (1974) The formation and properties of macrophage polykaryons (inflammatory giant cells). J Pathol 113/1:1-19 Papadimitriou JM, Archer M (1974) The morphology of murine foreign body multinucleate giant cells. J Ultrastruct Res 49:372-386 Papadimitriou JM (1979) The role of resident and exudate macrophages in multinucleate giant cell formation. J Pathol 128:93-97 Rhee HJ van der, van der Burgh-de Winter CPM, Daems WTh (1979) The differentiation of monocytes into macrophages, epithelioid cells, and multinucleated giant cells in subcutaneous granulomas. 1. Fine structure. Cell Tissue Res 197:355-378 Sutton JS (1967) Ultrastructural aspects of in vitro development of monocytes into macrophages, epithelioid cells, and multinucleated giant cells. Natl Cancer Inst Monogr 26:71-141 Sutton JS, Weiss L (1966) Transformation of monocytes in tissue culture into macrophages, epithelioid cells and multinucleated giant cells. An electron microscopic study. J Cell Biol 28 : 303-332 Received April 28, 1983/Accepted May 4, 1983
