Acta Otolaryngol (Stockh) 1990; 110: 450-458
Histopathological Observations in Chronic Maxillary Sinusitis PONTUS STIERNA and BENGT CARLSOO From the Department of Otorhinolaryngology, Karolinska Institute, Huddinge Hospital, S-14186 Huddinge. Sweden
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Stiema P, Carlsoo B. Histopathological observations in chronic maxillary sinusitis. Acta Otolaryngologica (Stockh) 1990; 110: 450458. Biopsy samples from the maxillary sinus mucosa of patients with purulent, non-purulent and recurrent sinusitis were studied histologically and compared with those from a maxillary sinus of patients with no previous history of sinus disease on the side of sampling. Basement membrane thickening, atypical gland formation, goblet cell hyperplasia, mononuclear inflammatory cell infiltration and subepithelial oedema were observed in all groups irrespective of the appearance of the effusion. Although the inflammatory variables in selected areas of the rnucosa seemed to show an increase in severity with the increasingly severe forms of sinusitis, neither the endoscopic mucosal appearance nor the nature of the sinus effusion corresponded to any specific histological pattern. Key words: sinus mucosa, histology, chronic sinusitis, effusion.
INTRODUCTION Bauer (1) found a correlation between the findings at endoscopic sinus examination and the histopathological features of the biopsies obtained from the maxillary sinus. Subsequent studies have not, however, been able to confirm these observations (2, 3) and, in fact the histology varies between different areas of one and the same sinus (4). Except in a study of bacterial invasion of the maxillary sinus mucosa (51, the relationship between histopathological changes and the nature of the sinus secretion has not previously been investigated. In a recent report from our department the accumulation of anaerobic metabolites in the sinus mucosa and secretion in purulent and non-purulent sinusitis was described (6). In purulent sinus secretion there was lactate accumulation as a result of leucocyte metabolism. The increase in mucosal lactate is probably related to the blood flow and diffusion properties of the mucosa and to leucocyte infiltration. Since the histological pattern in the maxillary sinus mucosa shows no definite correlation either with the macroscopical appearance of the mucosa or with the clinical picture, we decided to evaluate the morphological changes occurring in human chronic sinusitis and compare them with the nature of the secretion (purulenthon-purulent). Patients with recurrent maxillary sinusitis, or with a macroscopical sinus abnormality, and without any evidence of actual effusion were also included in the study.
MATERIAL Sixty-two biopsy specimens of human maxillary sinus mucosa were obtained from 47 patients with chronic or recurrent sinusitis admitted to the Department of Otorhinolaryngology, Huddinge University Hospital, for nasal or sinus surgery. Six patients had a medical history of nasal hyperreactivity. In 15 patients specimens were taken from both maxillary sinuses. The method of sampling of sinus mucosa was approved by the Human Ethics Committee of Huddinge University Hospital. The patients were divided into four groups according to preoperative history and peroperative findings.
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Acta Otolaryngol (Stockh) 110
Chronic maxillary sinusitis
Group A . Eleven patients with macroscopically normal mucosa at sinoscopy and with no previous history of infection of this maxillary sinus were selected. X-rays of the biopsied sinuses were completely normal in all instances. These patients were admitted for sinoscopy of a contralateral, non-infected, mucosal disorder or for surgery of the nasal septum. Eleven samples of maxillary sinus mucosa were collected. Group B . Fifteen patients with mostly a history of recurrent sinusitis but without current accumulation of secretion were included in this group. Most sinuses appeared macroscopically close to normal, except for localized lesions of the sinus mucosa. The sinus mucosa in three maxillary sinuses was polypoid. The diagnosis in 1 1 maxillary sinuses was recurrent sinusitis. Group B is in the text referred to as the group with “recurrent sinusitis”. Seventeen samples of maxillary sinus mucosa were collected. Group C . All patients in this group exhibited non-purulent secretion at operation. The macroscopical appearance varied from slight mucosal changes to polypoid lesions. The sinus mucosa in I5 maxillary sinuses was polypoid. Six patients suffered from nasal polyposis. Twenty-one samples of maxillary sinus mucosa were collected. Group D . The sinuses in this group of 13 patients displayed a muco-purulent or purulent secretion. The macroscopical picture varied within the same sinus cavity and the mucosa was often thick and reddish; occasionally it was polypoid or sometimes even necrotic. In 7 sinuses the mucosa was polypoid and 2 patients also suffered from nasal polyposis. Thirteen samples of sinus mucosa were collected. Most samples were taken during sinoscopy through the canine fossa (group A l l sinuses, group B 17 sinuses, group C 18 sinuses. group D 6 sinuses). Stortz sinoscopy equipment with a biopsy forceps was used for mucosal sampling. In the other patients the Caldwell-Luc approach was used (group C 3 sinuses, group D 7 sinuses). All biopsies were taken from the rear wall of the maxillary sinus, close to the site of sampling for determination of energy metabolites in a previous study (6). Sinus mucosa with advanced changes was generally avoided. Mucosal areas with polyps or apparent necrosis were thus excluded.
METHODS The specimens of the maxillary sinus mucosa were immediately fixed in buffered 10% formalin. Paraffin sections, 5 pm thick, were stained with haematoxylin-eosin, PAS alcian blue (pH 2 . 5 ) , the van Gieson connective tissue stain or toluidine blue (pH 1.0). Two or more biopsy specimens were obtained from most patients. Sections from different levels of the mucosal sample were examined. Five sections from each patient were examined. The histological changes were recorded by an independent histopathologist without any clinical information on the cases in question. Semiquantitative grading (0, I , 2 , 3) was performed concerning the following variables: goblet cell density, subepithelial thickening, eosinophilia, number of inflammatory cells, oedema, thickness of the mucosa, and fibrosis. Polypoid formation and submucous glands were designated a s - and +. The grading of the coded histological material was performed by an independent histopathologist without knowledge of the origin of samples. RESULTS From the whole biopsy series only three specimens were found unsuitable for examination. The results of the gradings of the histological variahbles are summarized in Table I . There was no specific pathological entity that was found exclusively in only one of the groups, and the listed histopathological features could also be observed in some specimens obtained from “normal” sinus mucosa.
45 1
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452 P . Stierna and B . Carlsoo
Acta Otolarvneol (Stockhl I10
Fig. I . Sinus mucosa from a patient without any history of sinus disease. The epithelium consists of a single layer of pseudostratified ciliated columnar epithelium with few goblet cells. No glands and few scattered leucocytes are seen in the lamina propria. Alcian blue. PAS, ~ 6 4 0 .
The maxillary sinus mucosa is thinner and less specialized than that found in the nasal cavity and contains fewer goblet cells. The surface is smooth and covered by a single layer of pseudostratified ciliated columnar epithelium, and the basement membrane is delicate (Fig. 1). The lamina propria is rather thin and is composed of a superficial loose connective tissue layer and a deep compact layer, which fuses imperceptibly with the underlying
Table I. Results of the semiquantitative gruding of d~yerentgroups
the
m r ~ o s a lbiopsies in the f o ~ r
The grading of the studied variables was 0111213 o r -I+. The number of specimens with different gradings within each group is indicated
Goblet cells 0/1/2/3 Subepithelial thicken. 0111213 Eosinophilia 0111213 Inflammatory cells 0111213 Oedema 0111213 Fibrosis 0111213 Squamous cell metaplasia -I+ Polypoid -I+ Submucous glands -I+
Group A
Group B
Group C
Group D
normal (n=ll)
recurrent (n=17)
non-purulent ( n = 19)
purulent (n= 12)
1151312 9121010 I01I /o/o 5/6/0/0 91 11010 8/2/0/0 I I10 I110
01314110 3181412 8131412 0/8/8/ I 2151712 12131110 I710 I116 I115
3141514 5161214 s151514 0161914 2121617 1511111I 1712 1216 I414
3/4/31I 112121I 316121 I 01 It318 0/0/417 6/41I10 I012 418 I111
1011
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Chronic maxillary sinusitis
Fig. 2 . Sinus mucosa from a patient with recurrent sinusitis. A marked goblet cell hyperplasia is evident, and the lamina propria appears somewhat oedematous. Alcian blue, PAS, X200.
Fig. 3. Sinus mucosa from a patient with recurrent sinusitis. The epithelium appears hyperplastic and contains numerous goblet cells. A marked subepithelial thickening as well as a slight lymphocytic infiltration is also evident. Alcian blue, PAS, ~ 6 4 0 .
453
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Acta Otolaryngol (Stockh) 110
Fig. 4. Sinus mucosa from a patient with chronic purulent sinusitis. The inflammatory cell infiltration is pronounced including marked round cell infiltration around a submucosal gland. Alcian blue, PAS, x 100.
periosteum to form a dense periosteal layer, the mucoperiosteum. The comparatively few mucosal glands are generally only found in the region of the ostia (7). Areas of marked goblet cell hyperplasia were evident in some specimens (Fig. 2) but in general only the mucosa from patients with recurrent sinusitis showed an increase in goblet cell density, and this increase was slight. In groups C and D the goblet cell density appeared the same as in normal sinus mucosa. Subepithelial thickening (Fig. 3), a finding often associated with an increase in eosinophils in this study, was frequently found in patients with recurrent and non-purulent sinusitis. Increased infiltration of inflammatory cells was observed in all three pathological groups, but was most pronounced in patients with purulent secretion (Fig. 4). Oedema of varying extent was noted in all pathological groups and followed the pattern of inflammatory cell infiltration. In the purulent group rather heavy subepithelial oedema was found in all rnucosal samples. This was also detected macroscopically, as an increase in thickness of the mucosa. Metachromatic mast cells were observed in three of the specimens from the purulent group. Fibrosis was not a prominent finding in any of the biopsies. Polypoid formation of the mucosa was seen in all pathological groups. Glands were infrequently observed, but occurred in all groups. Squamous cell metaplasia was only found in the non-purulent and purulent groups (Fig. 5 ) . Hyperplasia of the epithelium and the formation of atypical glands were also encountered (Fig. 6). Increased vascularization was also noted in some specimens with heavy inflammatory cell infiltration. DISCUSSION The increase of retained mucous in chronic sinusitis is probably the result of a reduction of ciliary activity accompanied by enhanced mucus production derived from newly formed
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Chronic maxillary sinusitis 455
Fig. 5 . Sinus mucosa from a patient with chronic non- purulent sinusitis illustrating focal squamous cell metaplasia with keratinization. Slight fibrosis as well as inflammatory cell infiltration of the lamina propria is also seen. Htx-eosin, x 100.
Fig. 6. Sinus mucosa from a patient with chronic purulent sinusitis showing atypical gland formation. The dilated glandular lumen, with hyperplastic epithelium, is tilled with mucus. Alcian blue, PAS, X 100.
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456 P . Stierna and B . Carlsoo
Acta Otolaryngol (Stockh) I10
mucous glands in the mucosa (8). Chronic sinusitis has been studied histologically with both light and electron microsopy, and several classifications have been proposed. On the basis of the inflammatory response, most authors distinguish four main types of histological changes in chronic maxillary sinusitis (3, 9, 10): 1) oedematous or hyperplastic, 2) infiltrative or granulating. 3) fibrous and 4) a mixed type. However, several histological types are frequently found in one and the same speciment of the mucosa ( I 1). Furthermore, there appears to be no characteristic histological finding that is correlated to the macroscopical picture found at operation (2, 3, 12), an observation further substantiated in the present investigation. In the present study of human maxillary sinus mucosa an attempt was made to correlate the histopathological features to the nature of the sinus effusion. When taking the biopsy specimens, areas of macroscopically less advanced changes were selected. Most authors have reported an increased number of goblet cells in chronic inflammation of the maxillary sinus (13, 14). However, in a quantitative histological examination of the sinus mucosa, Tos & Mogensen (8) found that the goblet cell density in chronic sinusitis was significantly lower than in the normal mucosa, whereas the gland density was six times that in the normal maxillary sinus, In the present study marked goblet cell hyperplasia was noted in certain specimens from each group, whereas in others the number of goblet cells appeared to be fairly normal or even reduced. In several specimens, especially in groups B and C, subepithelial thickening was found, and this was often accompanied by an increased number of eosinophils. This thickening has been interpreted as a thickening and hyalinization of the basement membrane (7), and can also be observed in the nasal mucosa in children with frequent infections (15). Such thickening of the basement membrane might impair the transport of fluid, nutrients and protective factors across the epithelium (15), thus making the mucosa less able to resist subsequent microbiological stress and less capable of self-repair following inflammation. The basement membrane is composed of a thin basal lamina and a network of reticular fibrils (16). In ultrastructural studies, the basal lamina is sometimes called the basement membrane. Ohashi & Nakai (17) report that in a functional and ultrastructural study of the sinus mucosa in chronic sinusitis, they did not observe thickening of the basement membrane. They found that the continuity of the basement membrane was maintained in most cases, except in mucosal membrane samples in which the ciliary function was extremely poor and where the mucosal epithelium consisted of undifferentiated cells. The basement membrane in these cases was often indistinct. Future ultrastructural and immunohistochemical studies may reveal the cause and nature of the basement membrane thickening observed in the nasal and sinus mucosa. In all three pathological groups there was an increased number of inflammatory cells. These were mostly lymphocytes, plasma cells and occasionally some polymorphonuclear granulocytes. This composition indicates the chronic nature of the inflammatory response. In atrophic or sclerosizing sinusitis the mucosa consists of a scarred lamina propria which is either denuded of covering epithelium or covered by metaplastic squamous epithelium (7). Hyperplasia of the epithelium and an increase in the number of submucosal glands were observed in the three pathological groups with no obvious difference between them. No pronounced fibrosis of the mucosa was observed in any of the specimens. Squamous cell metaplasia was only found in four patients with a chronic sinusitis. We did not find any severe dysplasia in any of these specimens. However, this metaplasia has been proposed to be a possible precancerous lesion. Sakai observed that more than 80% of patients with cancer of the maxillary sinus had a medical history of chronic maxillary sinusitis. In a Japanese population the decline in cancer incidence rate of maxillary sinus cancer closely follows a decrease in the prevalence rate of chronic maxillary sinusitis (18).
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Chronic maxillary sinusitis
Macroscopically, polyps of the antral mucosa were frequently found in the purulent and non-purulent groups. The development of these polyps of the antrum appears to be the result of the general inflammatory reaction, as there appears to be no close correlation between the occurrence of polyps in the maxillary antrum and that of nasal polyps. Mann & Dao Trong (3) reported that endoscopic sinus observations are questionable indications for surgery without histological confirmation, and in fact Wayoff et al. (19) consider that conventional histopathology of the sinus is a criterion for the therapeutic indication. On the other hand, Tos & Mogensen (8) could not divide their material into distinct histological groups with certainty, since they found oedema, polyp formation and leucocyte infiltration in almost all chronic maxillary sinuses. Moreover, Moesner et al. (2) found no histological picture that was characteristic for either group of sinoscopic picture of 1 1 1 consecutive sinoscopic biopsies from patients suffering from sinusitis. In the present report the inflammatory variables studied seemed to show an increase in severity of the inflammatory picture, from recurrent, non-purulent to purulent sinusitis. A predominance of purulent secretion is a strong indication of extensive infection, but as found in the present investigation the nature of the effusion is not reflected in any specific histological pattern of the mucosa. Furthermore, the inflammatory reaction can be very localized and, as pointed out by Hosemann & Wigand (4), the pathological response of the mucosa can vary considerably between different areas of the same sinus and the chronic inflammatory process is influenced by local pathogenetic factors.
ACKNOWLEDGEMENTS The authors wish to thank Professor Lars Hammarstrom, Department of Oral Pathology, for examining and grading the coded histological material. This study was supported by grants from the Swedish Medical Research Council (project No. 00749), the Swedish Society of Medicine, the Ragnar and Torsten Soderberg Research Fund, the Swedish Society of Medical Sciences and the Swedish Otolaryngological Society for Rhinological Research.
REFERENCES I . Bauer E. Die normale und pathologische Histologie der Kieferhohlenschleimhaut. Mschr Ohrenheilkd 1960; 94: 43-52. 2. Moesner J. Illum P, Jeppesen F. Sinoscopical biopsy in maxillary sinusitis. Acta Otolaryngol (Stockh) 1974; 78: 113-7. 3. Mann W, Trong HD. Vergleichende endoskopische und histologische Befunde bei chronischer Sinusitis. HNO 1979; 27: 345-7. 4. Hosemann W, Wigand ME. Ortliche Unterschiede im Gewebebild der chronisch-hyperplastischen Nasennebenhohlenschleimhaut. HNO 1985; 33: 31 1-5. 5. Lundberg C, Engquist S. Localization of bacteria and the cause of tissue destruction in maxillary sinusitis. Acta Otolaryngol (Stockh) 1984; Suppl 407: 30-2. 6. Johansson P, Kumlien J, Soderlund K, Hultman E. Experimental acute sinusitis in rabbits. Energy metabolism in sinus mucosa and secretion. Acta Otolaryngol (Stockh) 1988; 106: 460-7. 7. Nostrand van AWP, Goodman WS. Pathologic aspects of mucosal lesions of the maxillary sinus. In: Noyek AM, Zizmor J , eds. The otolaryngologic clinics of North America. Symposium on the maxillary sinus. Vol 9 , No I . Philadelphia, London, Toronto: W.B. Saunders, 1976: 21-34. 8. Tos M, Mogensen C. Mucus production in chronic maxillary sinusitis. A quantitative histopathological study. Acta Otolaryngol (Stockh) 1984: 97: 151-9. 9. Manasse, P. Uber Nebenhohlenoperationen. Z Hals-Nas-Ohrenheilkd 1923; 4: 473-89. 10. Schall RA. The histology and chronic inflammation of the nasal mucous membrane. Ann Otol 1933; 42: 15-38. 11. Kohn K. Nase und Nasennebenhohlen. In: Doerr W, Seifert G , Uehlinger E, eds. Spezielle pathologische Anatomie. Band 4. Berlin, Heidelberg, New York: Springer-Verlag, 1969: 70-82.
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12. Schatzle W. Histologische, histochemische und klinische Untersuchungen bei verschiedenen Formen der chronischen Sinusitis maxillaris. Annales Universitatis Saraviensis 1963; 10: 17 1-229. 13. Burton PA, Dixon MF. A comparison of changes in the mucous glands and goblet cells of nasal, sinus, and bronchial mucosa. Thorax 1969; 24: 180-5. 14. Albegger KW. Banale Entziindungen der Nase und der Nasennebenhohlen. In: Berendes J, Link R, Zollner F, eds. Hals-Nasen-Ohrenheilkunde. Vol I . Stuttgart: Thieme, 1977: I I. 15. Petruson B, Hansson H-A. Nasal mucosal changes in children with frequent infections. Arch Otolaryngol 1987; 113: 1294-1300. 16. Rhodin JAG, ed. Histology. A text and atlas. London, Toronto, New York: Oxford University Press, 1974: 148-50. 17. Ohashi Y, Nakai Y. Functional and morphological pathology of chronic sinusitis mucous membrane. Acta Otolaryngol (Stockh) 1983; Suppl 397: 11-48. 18. Hiyama T, Oshima A, Hanai A et al. Chronic maxillary sinusitis and the epidemiology of cancer of the maxillary sinus. In: Reznik G, Stinson SF, eds. Nasal tumours in animals and man. Vol. 1. Boca Raton, Florida: CRC Press Inc., 1983: 137-50. 19. Wayoff M , Parache RM, Bodelet B, Gaze1 P. Etude histpathologique des sinusites chroniques. Acta Otorhinolaryngol Belg 1983; 37: 595602. Manuscript received February 2 , 1990; accepted April 6 , 1990
Address for correspendence: Pontus Stierna, Department of Otorhinolaryngology, Karolinska Institute, Huddinge Hospital, S-14186 Huddinge, Sweden
Histopathological Observations in Chronic Maxillary Sinusitis PONTUS STIERNA and BENGT CARLSOO From the Department of Otorhinolaryngology, Karolinska Institute, Huddinge Hospital, S-14186 Huddinge. Sweden
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Stiema P, Carlsoo B. Histopathological observations in chronic maxillary sinusitis. Acta Otolaryngologica (Stockh) 1990; 110: 450458. Biopsy samples from the maxillary sinus mucosa of patients with purulent, non-purulent and recurrent sinusitis were studied histologically and compared with those from a maxillary sinus of patients with no previous history of sinus disease on the side of sampling. Basement membrane thickening, atypical gland formation, goblet cell hyperplasia, mononuclear inflammatory cell infiltration and subepithelial oedema were observed in all groups irrespective of the appearance of the effusion. Although the inflammatory variables in selected areas of the rnucosa seemed to show an increase in severity with the increasingly severe forms of sinusitis, neither the endoscopic mucosal appearance nor the nature of the sinus effusion corresponded to any specific histological pattern. Key words: sinus mucosa, histology, chronic sinusitis, effusion.
INTRODUCTION Bauer (1) found a correlation between the findings at endoscopic sinus examination and the histopathological features of the biopsies obtained from the maxillary sinus. Subsequent studies have not, however, been able to confirm these observations (2, 3) and, in fact the histology varies between different areas of one and the same sinus (4). Except in a study of bacterial invasion of the maxillary sinus mucosa (51, the relationship between histopathological changes and the nature of the sinus secretion has not previously been investigated. In a recent report from our department the accumulation of anaerobic metabolites in the sinus mucosa and secretion in purulent and non-purulent sinusitis was described (6). In purulent sinus secretion there was lactate accumulation as a result of leucocyte metabolism. The increase in mucosal lactate is probably related to the blood flow and diffusion properties of the mucosa and to leucocyte infiltration. Since the histological pattern in the maxillary sinus mucosa shows no definite correlation either with the macroscopical appearance of the mucosa or with the clinical picture, we decided to evaluate the morphological changes occurring in human chronic sinusitis and compare them with the nature of the secretion (purulenthon-purulent). Patients with recurrent maxillary sinusitis, or with a macroscopical sinus abnormality, and without any evidence of actual effusion were also included in the study.
MATERIAL Sixty-two biopsy specimens of human maxillary sinus mucosa were obtained from 47 patients with chronic or recurrent sinusitis admitted to the Department of Otorhinolaryngology, Huddinge University Hospital, for nasal or sinus surgery. Six patients had a medical history of nasal hyperreactivity. In 15 patients specimens were taken from both maxillary sinuses. The method of sampling of sinus mucosa was approved by the Human Ethics Committee of Huddinge University Hospital. The patients were divided into four groups according to preoperative history and peroperative findings.
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Acta Otolaryngol (Stockh) 110
Chronic maxillary sinusitis
Group A . Eleven patients with macroscopically normal mucosa at sinoscopy and with no previous history of infection of this maxillary sinus were selected. X-rays of the biopsied sinuses were completely normal in all instances. These patients were admitted for sinoscopy of a contralateral, non-infected, mucosal disorder or for surgery of the nasal septum. Eleven samples of maxillary sinus mucosa were collected. Group B . Fifteen patients with mostly a history of recurrent sinusitis but without current accumulation of secretion were included in this group. Most sinuses appeared macroscopically close to normal, except for localized lesions of the sinus mucosa. The sinus mucosa in three maxillary sinuses was polypoid. The diagnosis in 1 1 maxillary sinuses was recurrent sinusitis. Group B is in the text referred to as the group with “recurrent sinusitis”. Seventeen samples of maxillary sinus mucosa were collected. Group C . All patients in this group exhibited non-purulent secretion at operation. The macroscopical appearance varied from slight mucosal changes to polypoid lesions. The sinus mucosa in I5 maxillary sinuses was polypoid. Six patients suffered from nasal polyposis. Twenty-one samples of maxillary sinus mucosa were collected. Group D . The sinuses in this group of 13 patients displayed a muco-purulent or purulent secretion. The macroscopical picture varied within the same sinus cavity and the mucosa was often thick and reddish; occasionally it was polypoid or sometimes even necrotic. In 7 sinuses the mucosa was polypoid and 2 patients also suffered from nasal polyposis. Thirteen samples of sinus mucosa were collected. Most samples were taken during sinoscopy through the canine fossa (group A l l sinuses, group B 17 sinuses, group C 18 sinuses. group D 6 sinuses). Stortz sinoscopy equipment with a biopsy forceps was used for mucosal sampling. In the other patients the Caldwell-Luc approach was used (group C 3 sinuses, group D 7 sinuses). All biopsies were taken from the rear wall of the maxillary sinus, close to the site of sampling for determination of energy metabolites in a previous study (6). Sinus mucosa with advanced changes was generally avoided. Mucosal areas with polyps or apparent necrosis were thus excluded.
METHODS The specimens of the maxillary sinus mucosa were immediately fixed in buffered 10% formalin. Paraffin sections, 5 pm thick, were stained with haematoxylin-eosin, PAS alcian blue (pH 2 . 5 ) , the van Gieson connective tissue stain or toluidine blue (pH 1.0). Two or more biopsy specimens were obtained from most patients. Sections from different levels of the mucosal sample were examined. Five sections from each patient were examined. The histological changes were recorded by an independent histopathologist without any clinical information on the cases in question. Semiquantitative grading (0, I , 2 , 3) was performed concerning the following variables: goblet cell density, subepithelial thickening, eosinophilia, number of inflammatory cells, oedema, thickness of the mucosa, and fibrosis. Polypoid formation and submucous glands were designated a s - and +. The grading of the coded histological material was performed by an independent histopathologist without knowledge of the origin of samples. RESULTS From the whole biopsy series only three specimens were found unsuitable for examination. The results of the gradings of the histological variahbles are summarized in Table I . There was no specific pathological entity that was found exclusively in only one of the groups, and the listed histopathological features could also be observed in some specimens obtained from “normal” sinus mucosa.
45 1
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452 P . Stierna and B . Carlsoo
Acta Otolarvneol (Stockhl I10
Fig. I . Sinus mucosa from a patient without any history of sinus disease. The epithelium consists of a single layer of pseudostratified ciliated columnar epithelium with few goblet cells. No glands and few scattered leucocytes are seen in the lamina propria. Alcian blue. PAS, ~ 6 4 0 .
The maxillary sinus mucosa is thinner and less specialized than that found in the nasal cavity and contains fewer goblet cells. The surface is smooth and covered by a single layer of pseudostratified ciliated columnar epithelium, and the basement membrane is delicate (Fig. 1). The lamina propria is rather thin and is composed of a superficial loose connective tissue layer and a deep compact layer, which fuses imperceptibly with the underlying
Table I. Results of the semiquantitative gruding of d~yerentgroups
the
m r ~ o s a lbiopsies in the f o ~ r
The grading of the studied variables was 0111213 o r -I+. The number of specimens with different gradings within each group is indicated
Goblet cells 0/1/2/3 Subepithelial thicken. 0111213 Eosinophilia 0111213 Inflammatory cells 0111213 Oedema 0111213 Fibrosis 0111213 Squamous cell metaplasia -I+ Polypoid -I+ Submucous glands -I+
Group A
Group B
Group C
Group D
normal (n=ll)
recurrent (n=17)
non-purulent ( n = 19)
purulent (n= 12)
1151312 9121010 I01I /o/o 5/6/0/0 91 11010 8/2/0/0 I I10 I110
01314110 3181412 8131412 0/8/8/ I 2151712 12131110 I710 I116 I115
3141514 5161214 s151514 0161914 2121617 1511111I 1712 1216 I414
3/4/31I 112121I 316121 I 01 It318 0/0/417 6/41I10 I012 418 I111
1011
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Chronic maxillary sinusitis
Fig. 2 . Sinus mucosa from a patient with recurrent sinusitis. A marked goblet cell hyperplasia is evident, and the lamina propria appears somewhat oedematous. Alcian blue, PAS, X200.
Fig. 3. Sinus mucosa from a patient with recurrent sinusitis. The epithelium appears hyperplastic and contains numerous goblet cells. A marked subepithelial thickening as well as a slight lymphocytic infiltration is also evident. Alcian blue, PAS, ~ 6 4 0 .
453
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454 P . Stierna and B . Carlsoo
Acta Otolaryngol (Stockh) 110
Fig. 4. Sinus mucosa from a patient with chronic purulent sinusitis. The inflammatory cell infiltration is pronounced including marked round cell infiltration around a submucosal gland. Alcian blue, PAS, x 100.
periosteum to form a dense periosteal layer, the mucoperiosteum. The comparatively few mucosal glands are generally only found in the region of the ostia (7). Areas of marked goblet cell hyperplasia were evident in some specimens (Fig. 2) but in general only the mucosa from patients with recurrent sinusitis showed an increase in goblet cell density, and this increase was slight. In groups C and D the goblet cell density appeared the same as in normal sinus mucosa. Subepithelial thickening (Fig. 3), a finding often associated with an increase in eosinophils in this study, was frequently found in patients with recurrent and non-purulent sinusitis. Increased infiltration of inflammatory cells was observed in all three pathological groups, but was most pronounced in patients with purulent secretion (Fig. 4). Oedema of varying extent was noted in all pathological groups and followed the pattern of inflammatory cell infiltration. In the purulent group rather heavy subepithelial oedema was found in all rnucosal samples. This was also detected macroscopically, as an increase in thickness of the mucosa. Metachromatic mast cells were observed in three of the specimens from the purulent group. Fibrosis was not a prominent finding in any of the biopsies. Polypoid formation of the mucosa was seen in all pathological groups. Glands were infrequently observed, but occurred in all groups. Squamous cell metaplasia was only found in the non-purulent and purulent groups (Fig. 5 ) . Hyperplasia of the epithelium and the formation of atypical glands were also encountered (Fig. 6). Increased vascularization was also noted in some specimens with heavy inflammatory cell infiltration. DISCUSSION The increase of retained mucous in chronic sinusitis is probably the result of a reduction of ciliary activity accompanied by enhanced mucus production derived from newly formed
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Acta Otolaryngol (Stockh) 110
Chronic maxillary sinusitis 455
Fig. 5 . Sinus mucosa from a patient with chronic non- purulent sinusitis illustrating focal squamous cell metaplasia with keratinization. Slight fibrosis as well as inflammatory cell infiltration of the lamina propria is also seen. Htx-eosin, x 100.
Fig. 6. Sinus mucosa from a patient with chronic purulent sinusitis showing atypical gland formation. The dilated glandular lumen, with hyperplastic epithelium, is tilled with mucus. Alcian blue, PAS, X 100.
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mucous glands in the mucosa (8). Chronic sinusitis has been studied histologically with both light and electron microsopy, and several classifications have been proposed. On the basis of the inflammatory response, most authors distinguish four main types of histological changes in chronic maxillary sinusitis (3, 9, 10): 1) oedematous or hyperplastic, 2) infiltrative or granulating. 3) fibrous and 4) a mixed type. However, several histological types are frequently found in one and the same speciment of the mucosa ( I 1). Furthermore, there appears to be no characteristic histological finding that is correlated to the macroscopical picture found at operation (2, 3, 12), an observation further substantiated in the present investigation. In the present study of human maxillary sinus mucosa an attempt was made to correlate the histopathological features to the nature of the sinus effusion. When taking the biopsy specimens, areas of macroscopically less advanced changes were selected. Most authors have reported an increased number of goblet cells in chronic inflammation of the maxillary sinus (13, 14). However, in a quantitative histological examination of the sinus mucosa, Tos & Mogensen (8) found that the goblet cell density in chronic sinusitis was significantly lower than in the normal mucosa, whereas the gland density was six times that in the normal maxillary sinus, In the present study marked goblet cell hyperplasia was noted in certain specimens from each group, whereas in others the number of goblet cells appeared to be fairly normal or even reduced. In several specimens, especially in groups B and C, subepithelial thickening was found, and this was often accompanied by an increased number of eosinophils. This thickening has been interpreted as a thickening and hyalinization of the basement membrane (7), and can also be observed in the nasal mucosa in children with frequent infections (15). Such thickening of the basement membrane might impair the transport of fluid, nutrients and protective factors across the epithelium (15), thus making the mucosa less able to resist subsequent microbiological stress and less capable of self-repair following inflammation. The basement membrane is composed of a thin basal lamina and a network of reticular fibrils (16). In ultrastructural studies, the basal lamina is sometimes called the basement membrane. Ohashi & Nakai (17) report that in a functional and ultrastructural study of the sinus mucosa in chronic sinusitis, they did not observe thickening of the basement membrane. They found that the continuity of the basement membrane was maintained in most cases, except in mucosal membrane samples in which the ciliary function was extremely poor and where the mucosal epithelium consisted of undifferentiated cells. The basement membrane in these cases was often indistinct. Future ultrastructural and immunohistochemical studies may reveal the cause and nature of the basement membrane thickening observed in the nasal and sinus mucosa. In all three pathological groups there was an increased number of inflammatory cells. These were mostly lymphocytes, plasma cells and occasionally some polymorphonuclear granulocytes. This composition indicates the chronic nature of the inflammatory response. In atrophic or sclerosizing sinusitis the mucosa consists of a scarred lamina propria which is either denuded of covering epithelium or covered by metaplastic squamous epithelium (7). Hyperplasia of the epithelium and an increase in the number of submucosal glands were observed in the three pathological groups with no obvious difference between them. No pronounced fibrosis of the mucosa was observed in any of the specimens. Squamous cell metaplasia was only found in four patients with a chronic sinusitis. We did not find any severe dysplasia in any of these specimens. However, this metaplasia has been proposed to be a possible precancerous lesion. Sakai observed that more than 80% of patients with cancer of the maxillary sinus had a medical history of chronic maxillary sinusitis. In a Japanese population the decline in cancer incidence rate of maxillary sinus cancer closely follows a decrease in the prevalence rate of chronic maxillary sinusitis (18).
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Acta Otolaryngol (Stockh) 110
Chronic maxillary sinusitis
Macroscopically, polyps of the antral mucosa were frequently found in the purulent and non-purulent groups. The development of these polyps of the antrum appears to be the result of the general inflammatory reaction, as there appears to be no close correlation between the occurrence of polyps in the maxillary antrum and that of nasal polyps. Mann & Dao Trong (3) reported that endoscopic sinus observations are questionable indications for surgery without histological confirmation, and in fact Wayoff et al. (19) consider that conventional histopathology of the sinus is a criterion for the therapeutic indication. On the other hand, Tos & Mogensen (8) could not divide their material into distinct histological groups with certainty, since they found oedema, polyp formation and leucocyte infiltration in almost all chronic maxillary sinuses. Moreover, Moesner et al. (2) found no histological picture that was characteristic for either group of sinoscopic picture of 1 1 1 consecutive sinoscopic biopsies from patients suffering from sinusitis. In the present report the inflammatory variables studied seemed to show an increase in severity of the inflammatory picture, from recurrent, non-purulent to purulent sinusitis. A predominance of purulent secretion is a strong indication of extensive infection, but as found in the present investigation the nature of the effusion is not reflected in any specific histological pattern of the mucosa. Furthermore, the inflammatory reaction can be very localized and, as pointed out by Hosemann & Wigand (4), the pathological response of the mucosa can vary considerably between different areas of the same sinus and the chronic inflammatory process is influenced by local pathogenetic factors.
ACKNOWLEDGEMENTS The authors wish to thank Professor Lars Hammarstrom, Department of Oral Pathology, for examining and grading the coded histological material. This study was supported by grants from the Swedish Medical Research Council (project No. 00749), the Swedish Society of Medicine, the Ragnar and Torsten Soderberg Research Fund, the Swedish Society of Medical Sciences and the Swedish Otolaryngological Society for Rhinological Research.
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12. Schatzle W. Histologische, histochemische und klinische Untersuchungen bei verschiedenen Formen der chronischen Sinusitis maxillaris. Annales Universitatis Saraviensis 1963; 10: 17 1-229. 13. Burton PA, Dixon MF. A comparison of changes in the mucous glands and goblet cells of nasal, sinus, and bronchial mucosa. Thorax 1969; 24: 180-5. 14. Albegger KW. Banale Entziindungen der Nase und der Nasennebenhohlen. In: Berendes J, Link R, Zollner F, eds. Hals-Nasen-Ohrenheilkunde. Vol I . Stuttgart: Thieme, 1977: I I. 15. Petruson B, Hansson H-A. Nasal mucosal changes in children with frequent infections. Arch Otolaryngol 1987; 113: 1294-1300. 16. Rhodin JAG, ed. Histology. A text and atlas. London, Toronto, New York: Oxford University Press, 1974: 148-50. 17. Ohashi Y, Nakai Y. Functional and morphological pathology of chronic sinusitis mucous membrane. Acta Otolaryngol (Stockh) 1983; Suppl 397: 11-48. 18. Hiyama T, Oshima A, Hanai A et al. Chronic maxillary sinusitis and the epidemiology of cancer of the maxillary sinus. In: Reznik G, Stinson SF, eds. Nasal tumours in animals and man. Vol. 1. Boca Raton, Florida: CRC Press Inc., 1983: 137-50. 19. Wayoff M , Parache RM, Bodelet B, Gaze1 P. Etude histpathologique des sinusites chroniques. Acta Otorhinolaryngol Belg 1983; 37: 595602. Manuscript received February 2 , 1990; accepted April 6 , 1990
Address for correspendence: Pontus Stierna, Department of Otorhinolaryngology, Karolinska Institute, Huddinge Hospital, S-14186 Huddinge, Sweden
