J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from

J. clin. Patn. (1956), 9, 229.

THE PATHOLOGY OF BY

I. FRIEDMANN From the Department of Pathology of the Institute of Laryngology and Otology, London

(RECEIVED FOR PUBLICATION NOVEMBER 11, 1955)

Knowledge of the pathology of otitis media is 350 Cases of Chronic conflicting in spite of the vast amount of relevant Evidence of inflammatory changes has been literature. noted in 270 cases. In 80 specimens there was One of the objects of the present investigation no evidence of and they were rejected has been to re-examine this field in relation to the for this study (these were cortical bone chips). question as to whether the pathology of otitis The positive findings were (1) granulation tissue media and maistoiditis has changed since the in the bone fragments; (2) signs of bone recon- advent of the antibiotics as often suggested. For struction; (3) mucosal changes; (4) aural chole- this purpose bone-chips removed at recent mas- steatoma; (5) cholesterol-. toidectomy operations have been studied. (1) Granulations when present lay freely, covered the bone fragments, or filled the cells, the antrum, or eroded bone. They consisted of non- Materials and Methods specific inflammatory granulation tissue infiltrated Three hundred and seventy five samples of bone by plasmacytes, lymphocytes and enclosing gland- copyright. chips removed at mastoidectomy operations were like structures. The granulations were on the decalcified, embedded in paraffin-wax, and sec- whole identical with the structure of the so-called tioned. Sections were stained with haemotoxylin and aural eosin, Van-Gieson, Gram, Ziehl-Neelsen, and Mas- polyp. son's trichrome. The periodic-acid-Schiff reaction (2) There was much evidence of reconstruction was used for the demonstration of mucus-secreting of bone indicated by dark-blue staining lines of apposition of various thickness resembling the sur-

cells or glands. http://jcp.bmj.com/ face of glaciers (Fig. 6), and irregular cement lines forming an intricate mosaic pattern (Figs. 7 and 8). 25Cases of Acute Mastoiditis (3) The mucosa of the mastoid cells whether The number of acute was, as ex- oedematous or fibrotic was infiltrated by round pected, fairly small. The pathological changes cells and frequently lined by ciliated columnar were, however, intensive and characteristic. epithelium which formed gland-like structures (Figs. 9 and 10). The " glands" contained mucus In the early stages the mucosa of the air cells giving a positive periodic-acid-Schiff reaction. on September 24, 2021 by guest. Protected was congested and swollen, lined with flat or (4) Stratified squamous epithelium, lining chole- cuboidal cells (Fig. 1). The lumen was filled with steatoma cavities, was often seen covering the pus, replaced later by fibrous granulation tissue bone chips (Fig. 11). From the inverted keratin- (Figs. 2 and 3). There was evidence of osteoclastic ized surface, multiple layers of epidermoid kerat- activity and already, at an early stage about five inized epithelium were desquamated filling the to 10 days after infection, of intensive formation cavity proper. Sometimes only of new bone (Figs. 3, 4, and 5). fragments of keratinized matter surrounded by There was great variation in a given specimen giant cells were found (Fig. 12). and neighbouring mastoid air-cells presented (5) Frequently no true epidermoid cholestea- different stages from suppuration to fibroblastic toma was found but only rich deposits of choles- organization and ossification. terol crystals surrounded by giant cells embedded In some cases, of streptococcal aetiology, there in fibrous granulation tissue (Figs. 13 and 14). was considerable haemorrhage and destruction of bone. Equally, an occasional acute case caused by Discussion B. proteus showed evidence of widespread It has been suggested that the pathology of suppuration. otitis media may have undergone some basic J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from copyright.

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FIn. 4 FIG. 1(1224 54).-Mastoid cell showing congested muicosa and healthy laminated bone. Haematoxylin and eosin, 150. FIG. 2 (837 53).-Acute mastoiditis (10 days' history). Note pus- filled mastoid cell, thickened lining. Haematoxylin and eosin, x 45. FIG. 3.Neighbouring mastoid cell showing fibrous organization and intensive new-bone formatin. Haematoxylin and eosin. 30. As Fig. 2. FIG. 4 (1582 53).-Acute mastoiditis (14 days' history). Newly formed reticular bone obliteratingell. Haematoxylin and eosin, FIG. 2 60. J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from

FIo. 5 (120/55).-Acute mastoiditis (10 days', history), showing 'network of reticular bone replacing fibrous granulation tissue. ,* Haematoxylin and eosin, x 95. S copyright. http://jcp.bmj.com/

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FIG. 6 (441/53).-Glacier-like arrangement of lines of apposition. Haematoxylin and eosin, x 52.

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FIG. 8 (1998i54).-Sclerotic bone fragment showing irregular cement lines. Haematoxylin and eosin, x 325. J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from

FIG. 9 (181/53).-Sclerotic bone lined by pseudostratified ciliated columnar epithelium. Haematoxylin and eosin, x 490. FIG. 10 (1693,154).-Gland in granulation tissue. Haematoxylin and eosin, x 400.

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?r .4 I Adof 4 .1& _X ;d w -4v4 _1 w Note epidermoid squamous epithelium and lamellated keratinized material in the lumen. Haematoxylin and eosin, x 72. J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from

234 1. FRIEDMANN

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FIG. 12 (279 55).-Chronic inflammatory granulation tissue containing lamellated " cholesteatomatous" material surrounded by foreign-body giant cells. Haematoxylin and eosin, 150. copyright. http://jcp.bmj.com/ on September 24, 2021 by guest. Protected

FIG. 13(1251 53).-Chronic otitis and mastoiditis. Chronic inflammatory granulation tissue with cholesterol granuloma. Haematoxylin and eosin, >x 72. J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from

THE PATHOLOGY OF OTITIS MEDIA 235 copyright. 4,9APP,

FIG. 14 (865!53).-Chronic otitis and mastoiditis with cholesterol granuloma. Hatematoxylin and eosin, x 110. http://jcp.bmj.com/ change in recent years, and that the success of Bone Formation and Bone Reconstruction the antibiotic treatment of the disease might have been due in some degree to changes of the patho- Evidence has been presented in this paper first logy of otitis media. of all of conspicuous new bone formation in acute The histopathology of human otitis media and and chronic mastoiditis. This was found in almost mastoiditis has been studied in detail by, among every instance of acute mastoiditis. Equally, in on September 24, 2021 by guest. Protected others, Stewart (1928), who gave a detailed descrip- bone-chips obtained from mastoidectomy opera- tion of the clinical, bacteriological, and histologi- tions for chronic otitis new bone formation and cal conditions found in 50 cases of acute mastoid- signs of bone reconstruction occurred regularly. itis. Stewart's material consisted of bone-chips of An interesting feature of the bone-fragments in diseased tissue removed by the Schwartze opera- chronic otitis was the bizarre irregularity of the tion. At about the same time Lange (1928) ex- cement Lnes which produced a mosaic-like pattern amined about 100 temporal bones showing various resembling that found in Paget's disease. This is stages of the disease. Both authors agree in their evidence of bone reconstruction developing in the description of the pathological changes in the course of infection and leading to osteosclerosis. mastoid cell. This pattern is sufficiently characteristic to assist From the present investigations it can be stated in the differentiation of sclerotic bone from healthy that my observations do not differ fundamentally compact bone; ceteris paribus in the differentia- from those of Stewart and Lange. Nevertheless, tion of a sclerotic mastoid process rendered acellu- some of my principal findings merit discussion as lar through infection from a congenital compact their significance has not been fully appreciated or ivory mastoid process with intact Haversian (Watkyn-Thomas, 1953). systems in the latter. J Clin Pathol: first published as 10.1136/jcp.9.3.229 on 1 August 1956. Downloaded from

236 1. FRIEDMANN

In the present studies, the controversial prob- ture. There were cholesterol deposits surrounded lem of pneumatization of the human mastoid pro- by foreign-body giant-cells in the granulation cess has only been touched upon. Experimental tissue filling the middle . At operation these evidence (Opheim, 1944; Friedmann, 1955a and b), structures, here called "cholesterol-granuloma " and the bone changes in acute and chronic may often be mistaken for aural cholesteatoma. mastoiditis of man suggest that the conversion of Such cholesterol deposits however, occur also at a pneumatized mastoid process into a sclerotic one other sites of chronic and/or may well be a consequence of infection. haemorrhage (Stewart, 1915; Dible and Davie, 1945) and it may be assumed that their presence Mucosal Changes in the infected cleft is directly con- Two significant mucosal changes were noted nected with the infection. Stratified squamous in chronic otitis media. The lining covering the epithelium, however, has no role in its formation. thickened fibrous stroma infiltrated by inflamma- tory cells has often become a more highly differen- Summary tiated columnar type, forming gland-like structures The pathology of otitis media is described. which produced P. A. S. positive mucus. There is no evidence to support the suggestion The conception of a mucous membrane lining that the basic pathology of otitis media has the mastoid cells is not generally accepted, as changed in the post-penicillin era, when compared normally it lacks some of the properties of the with the findings of authors reported in the pre- typical mucous membrane found in glands and penicillin era. secretory epithelium. Infection takes place in the mucosa of the ear Many observers deny the presence of glands in which is very susceptible to infection by certain the mastoid lining. Ojala (1950) in his material organisms. Bone formation sets in early and, with found only one instance in which gland-like cavi- progression to the chronic phase, there is con- ties were present in the subepithelial tissue. They copyright. epithelium siderable reconstruction of the bone recognizable were lined by stratified high cylindrical by an irregular mosaic pattern of cement lines or consisting almost entirely of goblet cells. lines of apposition. The mucosal lining reverts As shown here, under inflammatory conditions either to a columnar respiratory type, when it at any rate, a true mucous membrane may develop forms gland-like structures, or may be replaced lined by a mucus-secreting epithelium forming by a stratified squamous epithelium forming the gland-like structures. substrate of aural cholesteatoma. pathological http://jcp.bmj.com/ Cholesteatoma Cholesterol deposits surrounded by foreign body giant cells are common in chronic mastoiditis. The flattened cellular lining was frequently re- Such structures, best called cholesterol-granu- placed by stratified squamous epithelium leading loma, should not be mistaken for the true epider- to the formation of the so-called aural chole- moid cholesteatoma. steatoma. It is generally accepted that the patho- It is suggested that the hyperplastic mucosal and genesis of true aural cholesteatoma rests upon the osteoplastic processes observed are not the cause, presence of a stratified squamous epithelium in but the outcome, of otitis. on September 24, 2021 by guest. Protected the middle ear cleft (Tumarkin, 1954). It is the I wish to thank the staff of the Royal National origin of this squamous epithelium that is still in Throat. Nose and Ear Hospital and to the sisters doubt. Experimental evidence has been presented of the operating theatres for their kind co-operation. (Friedmann, 1955b) that migration or extension of My special thanks are due to Mr. E. S. Bird and the stratified squamous epithelium from the ex- Miss V. Shepherd for the sections and to Mr. D. ternal auditory meatus, or from the drum, can pro- Connolly for the photography. duce the effects associated with true epidermoid aural cholesteatoma of man (deposition of lamel- REFERENCES lated, desquamated, keratinized matter). This is Dible, J. H., and Davie, T. B. (1945). Pathology, 2nd ed., p. 2s. Churchill, London. probably the most frequent mechanism of the Friedmann, I. (1955a). J. Larvng., 69, 27. of aural cholesteatoma in man. --(1955b). Ibid., 69, 5S8. development Lange, W. (1928). Z. Hals-. Nasen-u. Ohrenheilk., 20, 3. Ojala, L. (1950). AcIa oto-la-rng. (Stockh.), Suppl. 86. Opheim, 0. (1944). Ibid., Suppl. 54. Cholesterol Granuloma Stewart, J. P. (1928). J. Laryng., 43, 689. Stewart, M. J. (1915). J. Psth. Bart. 19, 305. Besides the true epidermoid aural cholesteatoma, Tumarkin, A. (1954). In Modern Trends in Diseases of the Ear, Nose so the sections and Throat, ed. M. Ellis. p. 153. Butterworth. London. in some cases clinically diagnosed, Watkyn-Thomas, F. W. (1953). Diseases of the Throat, Nose and showed a basically different but characteristic pie- Ear, pp. 688,716,717. Lewis, London.