International Journal of Pediatric Otorhinolaryngology (2003) 67, 1179—1183
Otitis media with effusion and histopathologic properties of adenoid tissue Hasan Yasan*, Harun Doˇ gru, Mustafa Tüz, Özden Çandir, Kemal Uygur, Murat Yarikta¸ s Ear, Nose and Throat—Head and Neck Surgery Department, School of Medicine, Süleyman Demirel University, Isparta, Turkey Received 25 March 2003 ; received in revised form 28 June 2003; accepted 29 June 2003
KEYWORDS Metaplasia; Squamous epithelization; Middle ear effusion; Adenoid tissue
Summary Objective: Adenoidectomy is being generally used for the treatment of otitis media with effusion (OME). The purpose of current study was to determine objectively the significance of the histopathology of adenoid tissue on the development of otitis media with effusion. Methods: The records of all the patients operated on with the diagnosis of adenoid enlargement with or without OME were reviewed and pathologic specimen were re-evaluated regarding histopathological properties by one pathologist unfamiliar with the diagnosis. Sixty-one patients with adenoid hyperplasia were enrolled in the study group, 38 males and 23 females. Age ranged between 3 and 13 years (mean age was 7.03 ± 3.26 years). All the patients of study group were those operated on due to the adenoid hyperplasia and uni- or bilateral OME. Control group was composed of 39 male and 26 female patients (age range was between 3 and 13 years, and mean age was 7.06 ± 3.04 years) with solely adenoid hyperplasia. Results: The squamous metaplasia was present in 47 (77%) and 14 (22%) patients of study and control groups, respectively. The fibrosis of connective tissue interspersed follicles of adenoid was present in 29 (48%) and 6 (9%) patients of study and control groups, respectively. The statistical analysis revealed a significant prevalence of squamous metaplasia (P < 0.001) and fibrosis of connective tissue interspersed follicles of adenoid (P < 0.001) for a surgical indication of adenoid hyperplasia with OME than for without OME. The prevalence of other parameters was not significantly different between two groups. Conclusions: Adenoid tissue not only exerts an obstructive influence on the eustachian tube lumen when enlarged, but also impedes (hinders) mucociliary drainage of the middle ear by the way of non-ciliated metaplastic epithelium and fibrosis of connective tissue. © 2003 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Otitis media with effusion (OME) is one of the most common causes of hearing loss in school-age chil*Corresponding author. Present address: Modernevler Mah. 142.cad, Çevreyolu Nurlu Apt. D17, 32200 Isparta, Turkey. Tel.: +90-246-2112300; fax: +90-246-2371762. E-mail address:
[email protected] (H. Yasan).
dren and the second most important disease causing loss of hearing in the general population [1]. Adenoid plays an important role in upper respiratory tract immunological defence mechanisms [2]. Besides this, in the state of enlargement the adenoid maintains its function despite age [3]. Although the role of adenoid hyperplasia in the development of OME is a matter of some debate [4], it has long been recognised as an important factor in
0165-5876/$ — see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0165-5876(03)00222-2
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the pathogenesis of otitis media with effusion [5]. For this reason, adenoidectomy has become one of the most common surgical procedures performed today, whether performed alone or in conjunction with insertion of pressure equalisation tubes or tonsillectomy [6]. Although the adenoid tissue is covered by a pseudo-stratified ciliated columnar epithelium, it may display some metaplasia especially of squamous type, that may effect the mucociliary activity. Destruction of ciliated epithelium mucociliary degeneration may be related with OME by means of decreased middle ear function [7]. The purpose of this study was to determine the relationship between histopathologic properties of adenoid tissue and OME.
2. Methods and materials One hundred and twenty-six patients, of both sexes and ranging from 3 to 13 years of age, with adenoid hyperplasia with or without ventilation tube (VT) insertion were enrolled to this study. The study group included 61 patients (38 males and 23 females) who undergone adenoidectomy with VT insertion (37 bilateral and 24 unilateral) due to adenoid hyperplasia and OME. On the other hand, control group included 65 age-matched patients (39 males and 26 females) who undergone adenoidectomy without VT insertion, due to adenoid hyperplasia, which caused obstructive symptoms. Patients were excluded if they had adenoidectomy with tonsillectomy, allergic rhinitis, nasal polyp, craniofacial problems such as cleft palate, repeated VT insertion and dry tap at operation. In this study, all patients were operated on, from January 1997 to January 2001, at the ENT clinic of Süleyman Demirel University, Isparta, Turkey. All the patients from both groups were operated under general anaesthesia. Besides adenoidectomy, patients of study group were undergone Paparella type II (1.27 mm i.d.) silicon ventilation tube insertion to one or both tympanic membranes (into the antero-inferior quadrant of tympanic membrane) after the fluid aspiration from myringotomy ostium. Diagnosis of adenoid hyperplasia was based on complaints, conventional radiography, and if possible, nasal endoscopic findings with 2.7 mm straight 0◦ and oblique 30◦ endoscopes (Storz Hopkins rigid telescope, Germany). Diagnosis of OME was based on at least three successive monthly examinations with otomicroscopy, timpanometry and if possible, audiometry. The criteria for the tube placement were as follows: (1) continuous conductive hearing loss with over 20 dB air bone gap; (2) retracted and
Fig. 1 Magnification of adenoid tissue showing squamous cell metaplasia on the right (A) and a transitional zone (arrow) between normal (B) and metaplastic epithelia (haematoxylin—eosin, original magnification 100×).
glue coloured tympanic membrane with type B tympanogram; and (3) resistance to conservative therapy with medication and politzerisation. Histopathologically analysed material was adenoids removed on the basis of hyperplasia, which caused obstructive symptoms and/or OME occurrence. All resected adenoids were fixed in formalin, embedded in paraffin and finally prepared serial microscopic slides were stained with haematoxylin— eosin. Then, these stained histopathologic specimens of adenoid tissue of both groups were randomly re-evaluated with light microscopy (Nikon Optiphod-B) by the same pathologist unfamiliar with the primary diagnosis. The squamous metaplasia of surface epithelium (Fig. 1), fibrosis of interfollicular connective tissue (Fig. 2), plasmocyte infiltration, polymorphonuclear leucocyte infiltration, parakeratosis, stromal edema, lymphocyte infiltration, mucous gland hyperplasia, and vascular proliferation were recorded. Statistical evaluation was performed by using the SPSS program. Analysis of variance, chi-square (χ2 ) test with Yate’s correction was applied when indicated. Comparison was made using Fisher’s exact test when the case number was small.
3. Results The age of the patients ranged from 3 to 13 years (mean 7.03 ± 3.26 years), and from 3 to 13 years (mean 7.06 ± 3.04 years) for study and control
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Table 1 Frequency of histopathological findings of adenoid tissue in two groups Histopathology
Group I (study group; n = 61)
Group II (control; n = 65)
P-value × 2 and Fisher’s exact
Squamous cell metaplasia Plasmocyte infiltration Polymorphonuclear leucocyte infiltration Fibrosis of interfollicular connective tissue Parakeratosis Stromal edema Lymphocyte infiltration Mucous gland hyperplasia Vascular proliferation
47 25 41 29 2 3 21 12 5
14 26 47 6 4 5 19 15 8
0.000 0.910 0.533 0.000 0.681a 0.719a 0.531 0.642 0.563a
(77.0) (40.9) (67.2) (47.5) (3.2) (4.9) (34.4) (19.6) (8.1)
(21.5) (42.6) (72.3) (9.2) (6.1) (7.6) (29.2) (23.1) (12.3)
The values given in parentheses are in percentage. a Comparison was made with Fisher’s exact test.
groups, respectively. There was no significant difference between two groups related to age, sex, and the duration of preoperative complaints. Squamous cell metaplasia was detected in 47 of 61 cases (77%) in the study group and 14 of 65 cases (21.5%) in the control group. Fibrosis of interfollicular connective tissue was detected in 29 of 61 cases (47.5%) in the study group and 6 of 65 cases (9.2%) in the control group (Table 1). In the study group (adenoidectomy with VT insertion), squamous cell metaplasia of the adenoid surface epithelium and fibrosis of interfollicular connective tissue in adenoid mass were significantly higher than those of control (adenoidectomy without ventilation tube VT insertion) (P < 0.001). Squamous cell metapla-
Fig. 2 Magnification of adenoid tissue showing fibrosis of interfollicular connective tissue (haematoxylin—eosin, original magnification 100×).
sia and fibrosis of interfollicular connective tissue in adenoid are more prevalent in children undergoing adenoidectomy for adenoid hyperplasia and OME than those only for adenoidectomy. On the other hand, there was no statistically significant difference between two groups regarding plasmocyte infiltration (P = 0.910), polymorphonuclear leucocyte infiltration (P = 0.533), parakeratosis (P = 0.681), stromal edema (P = 0.719), lymphocyte infiltration (P = 0.531), mucous gland hyperplasia (P = 0.642) and vascular proliferation (P = 0.563) (Table 1).
4. Discussion OME characterised by the presence of middle ear effusion for 3 months or more and the general absence of gross signs of infection is the commonest cause of deafness in children in developed world [8]. It is a multi-factorial, common, asymptomatic and silent disease, especially during infancy [9]. Adenoids may contribute to the formation of OME in two ways: a mechanical obstruction due to increased adenoid mass or a local inflammatory reaction in the eustachian tubes and the middle ear caused by release of inflammatory mediators [10]. Adenoid hyperplasia or chronic adenoiditis may cause significant problems requiring adenoidectomy in situations in which the tonsils themselves are not diseased and are not contributing to symptomatology [11]. It is advocated that adenoidectomy is an effective procedure for the treatment of medically resistant OME [12]. Besides the well-known ways of formation of OME, we consider that histopathological features of adenoid tissue may influence pathogenesis of OME. In our study, we have included the patients with adenoid hyperplasia without tonsillar and any
1182 other upper respiratory tract pathology in order to determine the pure effect of adenoid tissue itself. Mucociliary clearance process clears secretions and particulate matter from the middle ear into the nasopharynx via the eustachian tube [13]. Impairment of the mucociliary clearance system interferes with the drainage of middle ear effusions into the nasopharynx and results in chronic OME [14]. Under chronic inflammatory stimulation, metaplasia mainly consists of the progressive substitution of ciliated cells with cells equipped with apical microvilli and microplicae, which is considered the first step of a shift towards the appearance of cuboidal and eventually squamous epithelium which represents an irreversible stage. In metaplastic conditions ciliated cells are blocked in their capacity to produce cilia as a consequence of a transcriptional blockade. Metaplastic epithelium, the formation of which is probably a defence response, loses its ability to play a role in the homeostasis of blood flow [15—17]. Metaplasia of respiratory epithelium to squamous type impairs the function of involved area leading to upper and lower respiratory tract disorders. The adenoid is covered by a stratified ciliated columnar epithelium that is plicated to form numerous surface folds. Our observations have demonstrated that the metaplasia of pseudo-stratified ciliated epithelium and fibrosis of interfollicular connective tissue of adenoid may contribute the impairment of the drainage function of middle ear. Chole [18] hypothesised that Vitamin A deficiency disrupts the mucociliary clearing mechanism in the middle ear and eustachian tube by means of focal squamous metaplasia, and leads to effusion and otitis media. What the important is to prevent the formation of metaplasia and fibrosis. Kohlhaufl et al. [19] claimed to reverse the metaplastic respiratory epithelium (bronchial epithelium) by administration of retinyl palmitate inhalation. Further treatment modalities reversing the metaplastic epithelium (such as retinyl palmitate inhalation) should be investigated in order to manage negative effects of squamous metaplasia on OME. We supposed that fibrosis of interfollicular connective tissue of adenoid may impair the lymphatic drainage of nearby tissues. This possible mechanism, which needs to be further evaluated, may have some role on the pathogenesis of OME. Since this is a postulate, further prospective studies are required to clarify this mechanism. These findings encouraged us to hypothesise that squamous cell metaplasia and fibrosis of interfollicular connective
H. Yasan et al. tissue in adenoid may have some unfavourable effects on the pathogenesis of OME.
5. Conclusions In our study, squamous cell metaplasia and increased fibrosis of interfollicular connective tissue of adenoid seem to be more prevalent in the development of OME. The patients undergoing only adenoidectomy, demonstrating squamous cell metaplasia and fibrosis of interfollicular connective tissue histopathologically, should be further followed in long-term process. All the factors leading to the formation of squamous cell metaplasia of the adenoid epithelium and to increased fibrosis of interfollicular connective tissue must be evaluated by various studies. Further studies are necessary for the exact role of these histopathologic findings of adenoid on the etiopathogenesis and course of OME. Then, management modalities with these histopathologic properties of adenoid tissue should be developed.
References [1] A. Rinaldo, A. Ferlito, The pathology and clinical features of ‘‘glue ear’’: a review, Eur. Arch. Otorhinolaryngol. 257 (2000) 300—303. [2] Y. Harabuchi, M. Hamamoto, H. Kodama, A. Kataura, Spontaneous immunoglobulin production by adenoidal and tonsillar lymphocytes in relation to age and otitis media with effusion, Int. J. Pediatr. Otorhinolaryngol. 35 (1996) 117— 125. [3] M. Musiatowicz, J. Wysocka, E. Kasprzycka, E. Hassmann, Lymphocyte subpopulations in hypertrophied adenoid in children, Int. J. Pediatr. Otorhinolaryngol. 59 (2001) 7—13. [4] J. Sade, The nasopharynx, J. Laryngol. Otol. 108 (1994) 95—100. [5] A.R. Maw, Chronic otitis media with effusion (glue ear) and adenotonsillectomy: prospective randomised controlled study, Br. Med. J. 287 (1983) 1586—1588. [6] K. Rodriguez, N. Murray, J.L. Guarisco, Power-assisted partial adenoidectomy, Laryngoscope 112 (2002) 26—28. [7] M.M. Kiroglu, K. Ozbilgin, B. Aydoˇ gan, F. Kiroglu, O. Tap, M. Kaya, et al., Adenoids and otitis media with effusion: a morphological study, Am. J. Otolaryngol. 19 (1998) 244— 250. [8] J. Davidson, M.L. Hyde, P.W. Alberti, Epidemiologic patterns in childhood hearing loss: a review, Int. J. Pediatr. Otorhinolaryngol. 17 (1989) 239—266. [9] J. Engel, L. Anteunis, A. Volovics, J. Hendriks, E. Marres, Int. J. Pediatr. Otorhinolaryngol. 48 (1999) 239—249. [10] M.P. Collins, M.K. Chuch, K.N. Bkhschi, J. Osborne, Adenoid histamine and its possible relationship to secretory otitis media, J. Laryngol. Otol. 99 (1985) 685—691. [11] G.A. Gates, Acute otitis media and otitis media with effusion, in: C.W. Cummings, J.M. Fredrickson, L.A. Harker, C.J. Krause, M.A. Richardson, D.E. Schuller (Eds.),
Otitis media with effusion and histopathologic properties of adenoid tissue
[12] [13] [14] [15]
[16]
Otolaryngology Head & Neck Surgery, vol. V, third ed., Mosby, St. Louis, 1998, pp. 461—462. M. Suzuki, T. Watanabe, G. Mogi, Clinical, bacterial, and histological study of adenoids in children, Am. J. Otolaryngol. 20 (1999) 85—90. G.A. Gates, C.A. Avery, T.J. Prihoda, Effect of adenoidectomy upon children with chronic otitis media with effusion, Laryngoscope 98 (1988) 58—63. M.H. Chung, J.Y. Choi, W.S. Lee, H.N. Kim, J.H. Yoon, Compositional difference in middle ear effusion: mucous versus serous, Laryngoscope 112 (2002) 152—155. M. Gulisano, S. Pacini, M. Ruggiero, A. Pacini, A.N. Delrio, P. Pacini, In vitro effects of some differentiation inductors in metaplastic epithelium of the human nasal cavity, Cell Tissue Res. 285 (1996) 119—125. M. Gulisano, T. Barni, G. Fantoni, G. Polli, P. Porzio, G. Vannelli, et al., Presence and location of endothelin and
1183
endothelin-binding sites in human nasal mucosa under normal and metaplastic conditions, Cell Tissue Res. 293 (1998) 509—516. [17] M. Boysen, The surface of the human nasal mucosa. I. Ciliated cells and metaplastic epithelium in normal individuals. A correlated study by scanning/transmission electron and light microscopy, Virchows Arch. Cell Pathol. 40 (1982) 279—294. [18] R.A. Chole, Squamous metaplasia of the middle ear mucosa during Vitamin A deprivation, Otolaryngol. Head Neck Surg. 87 (1979) 837—844. [19] M. Kohlhaufl, K. Haussinger, F. Stanzel, A. Markus, J. Tritschler, A. Muhlhofer, et al., Inhalation of aerosolized Vitamin A: reversibility of metaplasia and dysplasia of human respiratory epithelia. A prospective pilot study, Eur. J. Med. Res. 7 (2002) 72—78.