peptic (contact granuloma of the larynx · for angioma20 or contact granuloma. it may be...

J Clin Pathol 1989;42:800-804

Peptic (contact ulcer) granuloma of the larynxT L MIKOFrom the Department of Pathology, University Medical School ofDebrecen, Debrecen, Hungary

SUMMARY Review of published work and analysis of clinical data and pathology of four biopsyspecimens from two patients with laryngeal contact granuloma showed that its peptic origin wasderived from a gastro-oesophago-laryngeal reflux. It is proposed that the term "peptic granuloma"should be given to this phenomenon. This term is given further support on account of the spectacularrecovery of the laryngeal lesion following antacid and antireflux treatment, rather than thetraditional method of using vocal rest and speech therapy, assumed to be the best way of treating aresult of mechanical irritation, the previously accepted cause of laryngeal contact granuloma.

Contact ulcer granuloma of the larynx is common in oesophageal reflux was shown on x-ray picture. Thepublished reports on laryngology,'1'8 but reports on its clinical features were, however, unequivocal, so that apathology are scarce.'10 Several suggestions for its repeated x-ray examination was considered to beaetiology have been put forward. Mechanical stress unnecessary. The treatment of hyperacidity and refluxhas been the generally accepted cause, but treatment oesophagitis resulted in complete recovery of thefor this has given poor results and the lesion is prone to laryngeal lesion in two months. After another fiverecur after surgery. More recent reports"2 142 have months the patient was lost to follow up. It was latershown that patients with contact ulcer may have learnt that after having neglected to take the pres-oesophageal dysfunction as well. Analysis of the cribed treatment his symptoms recurred. In a countyavailable data on this condition shows a role for hospital a third "polypectomy" was carried out oneregurgitated gastric juice. year after the second surgery. Histological examina-

This study aims to describe the pathology of the so- tion showed that the contact granuloma was fibrouscalled contact ulcer granuloma of the larynx, a with a thickened epithelium (fig 2). The anti-refluxcondition of which pathologists should be aware. regimen was restarted; he has been free of symptomsSuccessful interpretation of the laryngeal specimen for five years.may draw the clinician's attention to an underlying,frequently hidden gastro-oesophageal disorder. CASE 2

A 54 year old motor mechanic who had never beenCase reports intubated presented with increasing hoarseness over

three months. A spherical mass of 3-4 mm in diameterCASE I removed from the left vocal process was histologicallyA 48 year old manager complained of hoarseness confirmed as contact granuloma (fig 3). He was notedwhich had been getting progressively worse for several to be softly spoken. For one year he had experiencedmonths. He had never been intubated. A mass the size the appearance of some acidic material in his throatof a french bean was removed in fragments from his after consuming spicy food. One week after the biopsyright vocal process of the arytenoid cartilage. It was an x-ray picture showed that he had gastro-thought to be an ulcerated polyp of the vascular type. oesophageal reflux. As a result of conservative anti-In spite of voice rest it recurred and was again excised refiux measures his symptoms resolved and thefour months later. Identical morphologcal detail and laryngeal biopsy site disappeared in two weeks. Hislocation of the lesions prompted the diagnosis of larynx has been normal for three years.contact ulcer granuloma (fig 1). Questioned about hisdigestive history, the patient stated that he hadsymptoms of reflux oesophagitis. A month after the Aetiologysecond operation a barium meal picture showed achronic duodenal ulcer and hyperacidity, but no Jackson was the first to emphasise that the aetiology of

this disease, which occurs mainly in middle aged men,Accepted for publication 31 March 1989 is the mechanical impact of overforceful adduction of

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Fig 1 Basicfeatures oflaryngealpeptic gramduoma (case 1, second biopsy specimen). (a) Low power view shows ulceratednon-specific granulation tissue bulging over the original surface. The preserved squamous epithelium of the vocal cord isdiscernible at the bottom. (Haematoxylin and eosin.) (b) A characteristicfeature is the central core ofcapillaries covered by alayer offibroblasts and a necroticfibrinous mass. Inflammatory cells are scattered evenly throughout the lesion.(Haematoxylin and eosin.) (c) The tangentially cut capillary area shows lumina ofsimilar calibre covered by plumpendothelial cells resembling capillary haemangioma. (Haematoxylin and van Gieson.)



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Fig 2 Late stage ofpeptic gramdoma showingfibrotic Fig 3 The peptic grandoma ispartialy covered with newlygranulation tissue with wide capillaries andfocal chronic formed epithelium (case 2). Note the typical layering at theinflammation (case 1, third biopsy specimen). The thick top and the total absence ofany lobular arrangement.epithelial covering is complete and shows (Haematoxylin and eosin.)pseudoepitheliomatous hyperplasia. (Haematoxylin andeosin.)

the arytenoids during phonation.' He coined the term"contact ulcer". After a while, granulation tissueemerges from the edges of the ulcer, so New andDevine termed it "contact ulcer granuloma".6 Damageto the mucoperichondrium, which covers the vocalprocess, by phonation at low frequencies, by coughingand clearing of the throat was described by von Ledenand Moore,'" but no direct association was madebetween these factors and the contact ulcer. Contactulcer is also rare in actors who use their voices a lot."Vocal therapy and repeated excisions have proved tobe of little benefit as the lesion either stubbornlypersists or recurs.'1 16

The three patients reported by Cherry and Mar-gulies'2 who were refractory to voice rest, vocalrehabilitation, antibiotics and steroids, had gastro-oesophageal reflux and peptic oesophagitis. The sym-

ptoms of peptic oesophagitis were so mild that thepatients did not complain. Treatment of the gastro-oesophageal disorder alone resulted in a permanentrecovery of the laryngeal changes within a maximumof six months. The authors suggested that the acidicreflux was an additional pathogenic factor and thatthis material caused the breakdown of the vocal chordmucosa, stimulating the production of granulationtissue. The possibility of regurgitated material reach-ing the respiratory system has also been described,23 24and in 16% ofsuch cases respiratory symptoms are theonly sign of gastro-oesophageal reflux.23

In 1978 Goldberg et al described a recurring laryn-geal granuloma in a patient with gastro-oesophagealregurgitation,2' unaware of the reflux theory of thecontact granuloma.

Cinematographic and cineradiographic studies led

Miko



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Laryngeal peptic granuloma

Ward and his colleagues in 1980 to state that thecontact ulcers and granulomas were the result ofhabitual throat clearing, secondary to either a localirritation of the larynx from nasal secretions or, moreoften, by regurgitated gastric juice at night as a resultof hiatus hernia.'4 Ohman et al verified 32 cases ofoesophageal dysfunction and 11 active gastro-duodenal ulcers in 43 patients with contact ulcer usingcomplex methods.'6 Clinical signs of oesophagealdysfunction were present in less than one third of thecases.

Observations on the pathogenetic role of refluxedgastric juice in chronic posterior laryngitis have alsobeen made.2526 In 1982 Ward and Berci consideredchronic non-specific pharyngitis, laryngitis, contactulcers and granulomas to be members of the samespectrum.' There have been attempts to differentiate"hyperacidic" and "hyperfunctional" gran-ulomata'5 17; as well as vocal ulcer and vocal chordgranuloma,'8 but with little conclusive evidence todate.

Morphology

The lesion usually appears as a unilateral cup-likedepression on the vocal process mucosa' 20 and mayalso occur on the posterior commissure; the term"posterior commissure ulcer" is therefore also used.'9Histological examination shows that the ulcer iscovered with tissue debris, inflammatory exudate, andgranulation tissue and rarely reaches the underlyingcartilage.6 Shortly afterwards, granulation tissuegrows from the edges and exuberant non-specificgranulation tissue is superimposed, which is friable onremoval. Pathologists usually see this form in biopsyspecimen (figs 1 and 3). The lesion is divided into threeparts. The basal portion, the bulkiest, is composed ofnewly formed capillaries. The deepest area usuallycontains collagen fibres, the amount of whichdecreases more superficially where the capillarylumina are narrower and are covered by plumpendothelium. The interstitium may be pigmented withhaemosiderin. The capillaries disappear rather abrup-tly and the middle layer almost exclusively comprisesfibroblasts arranged radially. The thickness of thefibrinous exudate covering the surface is variable andcontains tissue debris. A moderate amount of neutro-phils are present in all portions of the lesion and ascanty infiltration of lymphocytes and eosinophilsmay also be evident (figs lb and c). The tip ofthe vocalprocess of the arytenoid may be necrotic and loosecartilage may appear in the granuloma as well.Sometimes pseudoepitheliomatous hyperplasiasurrounds the lesion. Long standing granulomas (fig2) may be fibrous with a few blood vessels, the wholecovered by epithelium.671"

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In contrast, the vocal chord polyp may affect theentire length of the membranous chord in accordancewith the length of Reinke's space, but is usuallysituated more anteriorly. Its structure depends on thefate of the initial exudate and the connective tissuereaction. Ingrowths of blood vessels may produce apredominantly vascular tissue which may be mistakenfor angioma20 or contact granuloma. It may beextensively ulcerated and may contain haemosiderin,like contact granuloma. The stromal oedema and thenumerous, randomly distributed cavernous bloodvessels, typical of polyps, distinguish it from thecontact granuloma. Sinusoid-like lumina are rarelyseen in the latter, but when this does happen they arefound in the centre of the deepest region.True laryngeal angiomata are excessively rare. Most

of the lesions that have been so diagnosed wereprobably polyps of the vascular type.20 Infraglotticand supraglottic aggressive haemangiomas occasion-ally found in children and adolescents?0 present nodiferential diagnostic problem in this context. Accord-ing to Mills et al,27 the diagnostic criterion for pyogenicgranuloma is a distinctly lobular arrangement; thusthe term "lobular capillary hemangioma" has beensuggested. The authors found no such lesion in 68vascular changes studied in tissue from the larynx andtrachea.Intubation granuloma heals spontaneously in all

but 1-2% of cases. It is usually found on the vocalprocess of the arytenoids. The histological detail issimilar to that of contact granuloma,'0 and after awhile it may also be covered by epithelium.628 Assum-ing a similar pathogenesis for all these lesions, Jacksonlumped them together.7 Why contact granulomapersists, however, is unknown: a subclinical gastro-oesophageal reflux might be a contributory factor.

Discussion

A similar aetiology has been proposed both forcontact granuloma and laryngeal polyp'671011'4 des-pite the quite different location, pattern of reaction,and contrasting results of speech therapy. Vocal stresscannot be accepted as the aetiology of contact gran-uloma. It is worth noting that several authors havenoticed the disease typically occurring in tense,ambitious people-that is, prone to ulcers,6' andJackson reported that several of his patients hadcomplained of waking up at night choking on andcoughing up secretions in the larynx.'

After the association between contact granulomaand the gastro-oesophageal reflux had been recog-nised'2 the lesion was attributed to throat clearing14and an enhanced coughing reflex evoked by regur-gitation.'6 But these authors neglected to take intoconsideration the numerous patients without reflux



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804 Miko

but long standing coughing and throat clearing whodid not have laryngeal granuloma. It now seems likelythat coughing and throat clearing are not causal butsecondary factors because of the vicinity of thegranuloma to the chords. Direct contact of the gastricjuice on the laryngeal mucosa is more likely, but of arather more severe kind than Cherry and Marguliesindicated.'2 The regurgitated acid and bile passing intothe larynx principally bathes the dorsal portion of thevocal chords. In this region the mucoperichondriumcovering the vocal processes is the most vulnerable andthis may influence localisation. This feature, however,is generally considered to be secondary because thelaryngeal disorder is curable by treating only thereflux,'2"2' in accordance with the findings in ourcases. The mechanical origin is all the more unlikelybecause ofthe occurrence of the lesion on the posteriorcommissure,'7 19 where mechanical impact could not bean important factor. Furthermore, the primary role ofgastric juice has been documented by experimentallyproducing an identical lesion in dogs.13

I would therefore suggest that the term "pepticgranuloma" is the most appropriate because antacidand anti-reflux treatment provides a reliable cure.

I am indebted to Professor L Michaels for hisconstructive comments. Dr G Sotonyi and Dr GKrajczar kindly provided the third biopsy specimen ofcase I and that of 2.

Refereoces

I Jackson C. Contact ulcer of the larynx. Ann Otol Rhinol Laryngol1928;37:227-30.

2 Jackson CL. Etiology and treatment ofcontact ulcer of the larynx.Laryngoscope 1933;43:718-21.

3 Jackson C, Jackson CL. Contact ulcer of the larynx. ArchOtolaryngol 1935;22:1-15.

4 Woodruff GH. Contact ulcers of the larynx. JAMA1936;106:1562-9.

5 Peacher G, Holinger P. Contact ulcer of the larynx; the role of re-education. Arch Otolaryngol 1947;46:617-23.

6 New GB, Devine KD. Contact ulcer granuloma. Ann Otol RhinolLaryngol 1949;58:548-58.

7 Jackson C. Contact ulcer granuloma and other laryngeal com-plications of endotracheal anesthesia. Anesthesiology1953;14:425-36.

8 Baker DC Jr. Contact ulcer of the larynx. Laryngoscope1954;64:73-8.

9 Holinger PH, Johnston KC. Contact ulcer of the larynx. JAMA1960;172:51 1-5.

10 von Leden H, Moore P. Contact ulcer of the larynx. ArchOtolaryngol 1960;72:746-52.

11 Brodnitz FS. Contact ulcer of the larynx. Arch Otolaryngol1961;74:90-100.

12 Cherry J, Margulies SI. Contact ulcer of the larynx. Laryngoscope1968;78:1937-40.

13 Delahunty JE, Cherry J. Experimentally produced vocal cordgranulomas. Laryngoscope 1968;78:1941-7.

14 Ward PH, Zwitman D, Hanson D, Berci G. Contact ulcers andgranulomas of the larynx: new insights into their etiology as abasis for more rational treatment. Otolaryngol Head Neck Surg1980;88:262-9.

15 Bloch CS, Gould WJ, Hirano M. Effect of voice therapy oncontact granuloma of the vocal fold. Ann Otol Rhinol Laryngol1981;90:48-52.

16 (Ohman L, Tibbling J, Olofsson J, Ericsson G. Esophagealdysfunction in patients with contact ulcer of the larynx. AnnOtol Rhinol Laryngol 1983;92:228-30.

17 Feder RJ, Michell MJ. Hyperfunctional, hyperacidic and intuba-tion granulomas. Arch Otolaryngol 1984;110:582-4.

18 Benjamin B, Croxon G. Vocal cord granulomas. Ann Otol RhinolLaryngol 1985;94:538-41.

19 Rosai J. Ackerman's surgical pathology. St Louis: CV Mosby,1981.

20 Michaels L. Ear nose and throat histopathology. Heidelberg:Springer Verlag, 1987.

21 Goldberg M, Noyek AM, Pritzker KPH. Laryngeal granulomasecondary to gastro-esophageal reflux. J Otolaryngol1978;7:196-202.

22 Ward PH, Berci G. Observations on the pathogenesis of chronicnon-specific pharyngitis and laryngitis. Laryngoscope1982;92:1377-82.

23 Urschel H, Paulson DL. Gastroesophageal reflux and hiatalhernias complicating therapy. J Thorac Cardiovasc Surg1967;53:21-32.

24 Barish CF, Wu WC, Castell DO. Respiratory complications ofgastroesophageal reflux. Arch Intern Med 1985;145:1882-8.

25 Delahunty JE. Acid laryngitis. J Laryngol Otol 1972;86:335-42.26 Kambil V, Radsel Z. Acid posterior laryngitis: Aetiology, his-

tology, diagnosis and treatment. J Laryngol Otol 1984;98:1237-40.

27 Mills SE, Cooper PH, Fechner RE. Lobular capillary heman-gioma: the underlying lesion ofpyogenic granuloma. Am JSurgPathol 1980;4:471-9.

28 Snow JC, Harano M, Balogh K. Post-intubation granuloma ofthelarynx. Anesthesia and Analgesia 1966;45:425-9.

Requests for reprints to: Dr T L Miko, Armaver HansenResearch Institute, POB 1005, Addis Ababa, Ethiopia.



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