tracheobronchopathia osteoplastica - thorax.bmj.com · (ozaena) has been associated (larsen, 1937)....

Thorax (1968), 23, 105.

Tracheobronchopathia osteoplasticaIts relationship to primary tracheobronchial amyloidosis

A. SAKULA

From Redhill General Hospital, Surrey

An uncommon case of tracheobronchopathia osteoplastica in a 52-year-old woman is reported,the fifth example of this condition to be published in the British literature. The bronchoscopicfeature of bony hardness of the bronchial wall was initially suggestive of bronchial neoplasm.The histological feature of bony deposits (containing marrow showing active haemopoiesis) inthe submucosa of the lower trachea and major bronchi was superimposed on a background ofprimary localized amyloid infiltration, and yet the bronchoscopic findings and the naked-eyemorbid anatomical appearance suggested tracheobronchopathia osteoplastica. A study of thereported cases of tracheobronchopathia osteoplastica on the one hand, and of primary localizedtracheobronchial amyloidosis on the other, reveals considerable similarity and overlap betweenthe two conditions. It is postulated that some, if not all, cases of tracheobronchopathia osteo-plastica are merely the advanced ossified stage of primary localized amyloidosis of the lowerrespiratory tract.

Cases of ossification occurring in the wall of thetrachea and bronchi have been reported duringthe past hundred years. Most of these have beenexamples of so-called tracheopathia (or tracheo-bronchopathia) osteoplastica, a rare condition ofwhich only 125 cases have been reported through-out the world, four having been described in theBritish literature. The English physician, Wilks(1857), was the first to give an account of 'ossificdeposits in the larynx, trachea and bronchi' in a38-year-old man who died of pulmonary tubercu-losis. Further descriptions of the conditionappeared (Muckleston, 1909), and Aschoff (1910)named it tracheopathia osteoplastica. In moderntimes Dalgaard (1947, 1955) once again drewattention to the condition. The second British casereport was by Bowen (1959), and two further caseshave since been described, by Salm (1961) and byBaird and Macartney (1966). Secrest, Kendig, andBeland (1964) suggested that it was more accurateto call the condition tracheobronchopathia osteo-plastica.

Ossification in the wall of the trachea andbronchi has also been described in primarytracheobronchial localized amyloid infiltrations or'tumours'. The first case of primary amyloidtracheo- and broncho-stenosis was reported byBalser (1883), and since then further examples ofthe condition have been published from other

countries (Falconer, 1938 ; Whitwell, 1953). Themost recent comprehensive British papers on thesubject have been written by Prowse (1958) andProwse and Elliott (1963).There has been considerable speculation as to

the nature of tracheobronchopathia osteoplastica,and many theories have been advanced regardingits aetiology. In the reported descriptions of thebronchoscopic and histological appearances oftracheobronchopathia osteoplastica on the onehand, and of primary tracheobronchial amyloid-osis with ossification on the other, there has oftenbeen a striking similarity and overlap between thetwo conditions. Thus, in the case of tracheo-bronchopathia osteoplastica described by Shuttle-worth, Self, and Pershing (1960), the broncho-scopic appearances were identical with thosedescribed by other authors for primary tracheo-bronchial amyloidosis, and amyloid was demon-strated histologically in their case.

In the case described here, the fifth example oftracheobronchopathia osteoplastica to be recordedin the British literature, amyloid was demonstratedhistologically. The hypothesis is presented thatmany, if not all, cases of so-called tracheobroncho-pathia osteoplastica are merely the advancedossified stage of primary tracheobronchialamyloidosis.

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CASE REPORT

A married woman aged 52, with two children, wasfirst seen in February, 1962. She had never smokedor had a job involving dust or other hazards to therespiratory tract. She had always had recurrentepisodes of bronchitis, sometimes associated withwheeziness, but there had not been any serious nasalor sinus disorder. During the past 18 months, how-ever, her breathing had become 'noisy', even whenshe was not troubled by cough or sputum. She hadbecome more easily dyspnoeic on effort, but withoutany chest pain or haemoptysis. She was obese, anddespite dietetic advice she remained overweight. Herother previous illness was an attack of thrombo-phlebitis of a leg vein seven years previously.On clinical examination she was overweight at

13 st. 7 lb. (86 kg.). Her 'noisy breathing' was from aninspiratory stridor arising behind the suprasternalnotch. The pharynx and thyroid gland seemed normal,there was no finger clubbing, the chest wall movednormally, and the breath sounds were normal. Theheart seemed normal (B.P. 160/80 mm. Hg) and theurine was normal. Blood count: Hb 14-7 g./100 ml.,W.B.C. 5,800 per 100 ml. (polymorphonuclear leuco-cytes 60%, lymphocytes 36%, monocytes 4%).The chest radiograph showed a virtually normal

appearance, with no suggestion of undue calcification

or ossification of the trachea or major bronchi ineither the postero-anterior or lateral films (Fig. 1).

Indirect laryngoscopy showed a normal larynx,subsequently confirmed at bronchoscopy, where therewas a grossly rugose thickening of the mucosa in-volving the trachea and extending chiefly into theright main bronchus. In the latter the thickeninginvolved the posterior and lateral surfaces, but theanterior portion appeared to be clear. As the broncho-scope was passed, the wall of the lower trachea, themain carina, and the orifices to the main bronchiappeared to be bony hard and rigid, so that theinstrument could not be passed into either mainbronchus. Biopsies were taken from the main carinaand the orifice of the right main bronchus and werereported as showing necrotic material, with no sug-gestion of neoplasm. Examination of the biopsy byZiehl-Neelsen staining showed no acid-alcohol-fastbacilli. Despite the negative histological report, adiagnosis of inoperable primary bronchial carcinomawas made, and radiotherapy was not advised.Nine months later, in December 1962, she collapsed

after a severe bout of coughing and was brought tohospital as an emergency, comatose, dyspnoeic, andcyanosed. The heart was rapid at 140 per minute andregular; B.P. 120/90 mm. Hg. The breath soundswere weak, but crepitations and a loud wheeze wereaudible over both lungs. The electrocardiogram

FIG. 1. Radiograph of chest on 14.3.62.

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showed no evidence of myocardial infarction. Hercondition rapidly deteriorated, and 20 minutes afterarrival at hospital cardiac arrest occurred. Despite allattempts at resuscitation, including the aspiration of aconsiderable quantity of blood-stained mucus fromthe right lung, she died.

NECROPSY FINDINGS The heart showed dilatation ofthe right ventricle with moderate atheroma of thecoronary arteries. The liver, kidneys, and brain werecongested, and there were gallstones in the gall-bladder. There was no evidence of amyloidosis affect-ing any organ. The lungs were oedematous. Therewas a stenosis of the lower trachea and major bronchi,resulting from gross thickening of their walls. Thisprocess extended as far as the main subdivisions ofthe main bronchi. On attempting to slit open the lowertrachea and bronchi, the scissors cut through thebony hard walls with difficulty.

Radiographs of the necropsy specimen of thetrachea and bronchi showed clearly the abnormalsubmucosal calcification and ossification (Fig. 2).

FIG. 2. Radiograph ofnecropsy specimen oflower tracheaand bronchi, showing submucosal thickening, calcification,and ossification.

Histological examination of sections of the tracheaand bronchus (Fig. 3) showed the lining columnarepithelium, where present, to be thrown into irregularfolds, there being but little lining epithelium remain-ing in the trachea. Beneath this epithelium, especiallyin the section of the bronchus, there was aninflammatory infiltrate consisting of plasma cells anda few lymphocytes. The submucosa of both thetrachea and bronchus was markedly thickened andwas, for the most part, replaced by masses of hyalinematerial giving the staining reactions for amyloid.Scattered irregularly throughout this material were

islands of atypical cartilage and bone, in a few ofwhich there were areas of haemopoietic tissue (Fig.4). Some of these areas of atypical cartilage appearedto be intimately associated with the normal carti-laginous rings. There was no evidence of amyloid inthe walls of the small vessels.

DISCUSSION

The essential features of tracheobronchopathiaosteoplastica are the deposits of calcification andossification, often with foci of bone marrow andactive haemopoiesis, demonstrable in the sub-mucosa of the trachea and bronchi. This must, ofcourse, be distinguished from the changes incartilage seen in the tracheobronchial tree withage or with conditions such as Paget's disease ofbone (Shanks and Kerley, 1962), as well as fromother causes of foci of ossification seen in thelung parenchyma, as in mitral stenosis.Although the case described here was in a

woman, tracheobronchopathia osteoplasticausually occurs in men, in the fifth or sixth decades.Occasionally, no definite symptoms are recognizedduring life, and the condition is discoveredincidentally at necropsy. Usually, however, a'noisy' chest with an inspiratory as well asexpiratory element (due more to stridor than tobronchospasm) is a feature for a number of years.There may be haemoptysis or a pulmonary seg-mental infection. In some cases rhinitis atrophica(ozaena) has been associated (Larsen, 1937). Plainchest radiographs will not show any evidence ofthe tracheobronchial condition, but tomographsmay reveal the lesions narrowing the lumen ofthe trachea -and bronchi (Howland and Good,1958).

Naturally, bronchial neoplasm is often suspectedin these circumstances (Flick, 1950), and broncho-scopy will be performed. The hardness of thetracheal wall, and the almost gritty bony feel asthe bronchoscope passes, may confirm the clinicalsuspicion of bronchial neoplasm, but the bonyspicules projecting under the apparently intactnormal mucosa are characteristic (Huzly, 1960),and the bronchial biopsy, which is often techni-cally difficult as the forceps tend to slip on thebony tissue (Carr and Olsen, 1954), does not showevidence of neoplasm.However, primary amyloidosis of the lower

respiratory tract needs also to be differentiated.The symptoms in this condition resemble closelythose found in tracheobronchopathia osteoplastica,and the bronchoscopic findings may be similar,too. The essential feature of these amyloid infiltra-

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a^:.: .,^ . s .... i,FIG. 3. Histology of portion of trachea (x7 5). Marked thickening of submucosa, replaced by hyaline materialgiving amyloid stain. Islands of atypical cartilage and bone seen to be intimately associated in places with thenormal cartilaginous rings.

tions and 'tumours' is that they are confined tothe larynx, trachea, or bronchi, occasionally in thelung parenchyma, but there is no evidence of ageneralized systemic amyloidosis, either primaryor secondary. As already indicated above, and aswill be discussed further below, the differentiationof the two conditions may be academic, since theossification in primary amyloidosis may be respon-sible for so-called tracheobronchopathia osteo-plastica.

AETIOLOGY OF TRACHEOBRONCHOPATHIA OSTEO-PLASTICA Many theories have been advanced toexplain the histogenesis of tracheobronchopathiaosteoplastica (see Clerf, 1944).

Congenital deformity This explanation wasoriginally advanced by Ribbert (1895). Theyoungest reported case was in a girl aged 12 years.

After careful consideration of the evidence this-theory was rejected by Dalgaard (1947) and byHempel and Glaser (1958).

Chronic infection Often there is evidence ofassociated chronic infection and inflammation,resulting from chronic bronchitis. In the firstdescription by Wilks (1857) there was an associa-tion with phthisis. Syphilis has also been suggestedas a cause. However, histological examinationusually reveals a normal tracheobronchial mucosa,overlying the abnormal calcification and ossifica-tion in the submucosa. It is therefore unlikely thatchronic infection is the cause of the condition.

Chemical or mechanical irritations In the casedescribed by Jackson and Jackson (1932) chemicalfumes were incriminated, and Jepsen and S0rensen(1960) ascribed the cause of their case of tracheo-

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FIG. 4. Same section as in Fig. 3 (x 28). Area of submucosal cartilage and bone formation containinghaemopoietic tissue.

bronchopathia osteoplastica associated with ozaenato certain oil vapours. However, in the majorityof cases described no such an association has beendemonstrated.

Metabolic disturbance Hempel and Glaser (1958)postulated that the bony islet development wasdue to metabolic and local inflammatory disturb-ances, leading to acidosis, hyaline swelling,transformation to cartilage, and then bone forma-tion. This armchair speculation has been rejectedby Spencer (1962), who emphasizes that there isno alteration in calcium or phosphorus meta-bolism and no connexion with pulmonarycalcinosis.

Degenerative process Hiebaum (1934) and, morerecently, Delord (1954) ascribed the changeessentially to a metaplasia of the tracheobronchialwall, but due to functional changes associatedwith ageing.

Ecchondrosis and exostosis The earlier writers(Virchow, 1863) considered the condition to bedue to a cartilaginous outgrowth from the normaltracheal rings, these outgrowths becoming ossifiedand forming 'ostomata'. The fact that the bonyspicules tend to be absent from the membranousportion of the trachea and bronchi tended tosupport this explanation. Liebow (1952) describedmultiple ecchondrosis in the trachea with or with-out secondary ossification. Recently, Baird andMacartney (1966) have supported the originalVirchow theory. However, the fact that the sub-mucosal bony islets appear to be predominantlybony and do not represent merely secondaryossification makes it unlikely that the conditiondevelops from ecchondrosis. Moreover, the bonyspicules may overlie the interspaces between thetracheal rings and appear not to be connectedwith them.

Metaplasia of elastic tissue Aschoff (1910) main-tained that the condition was a systemic disease

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of the tissues in the region of the internal elasticmembrane in the submucosa of the trachea andmajor bronchbi, and he named it tracheo-pathia osteoplastica. The fusion of the bony isletsand the tracheal rings, which is sometimes seen,

he explained as a coincidental or secondaryphenomenon. Dalgaard (1947) attempted toexpand the Aschoff hypothesis further, anddescribed how the elastic fibre cells were trans-formed to elastic cartilage by metaplasia. Thesecartilage cells then grew into islets of cartilage,which became calcified, and were then invaded byconnective tissue including blood vessels, with theproduction of bone marrow cavities lined byosteoblasts, resulting in bone formation. Dalgaard(1955) demonstrated in one patient that even

further metaplasia might occur, leading tobronchial carcinoma as a complication. Thistheory does not explain the absence of bonyspicules over the membranous portions of thetrachea or bronchi, where elastic fibres predomi-nate, and the presence of active bone marrow cellsin the bony islets means that the metaplasia musthave arisen from undifferentiated uncommittedmesenchymal cells (Freund, 1914).

RELATIONSHIP TO PRIMARY TRACHEOBRONCHIALAMYLoDOSIS From the above consideration ofthe various theories attempting to explain thenature of tracheobronchopathia osteoplastica it isevident that no completely satisfactory cause hasbeen demonstrated. As already suggested, severalof the cases described in the literature as tracheo-bronchopatbia osteoplastica must, in fact, havebeen examples of primary amyloidosis localized tothe lower respiratory tract (Shuttleworth et al.,1960). Similarly, in a case described by Prowse(1958), the bronchoscopic appearance of primaryamyloidosis appeared to be identical with thatseen in tracheobronchopathia osteoplastica. Prowseand Elliott (1963) also demonstrated the sub-mucosal bony islets enclosing bone marrow spaces

and foci of active haemopoiesis in their cases ofprimary tracheobronchial amyloidosis. In thereports of cases of tracheobronchopathia osteo-plastica, no specific mention has usually beenmade of an attempt to demonstrate amyloid. Ithink that the apparent overlap between thesetwo conditions may well indicate a common

aetiology and suggest that the condition oftracheobronchopathia osteoplastica is intimatelyconnected with primary localized amyloidosis ofthe lower respiratory tract and probably repre-

sents a late stage of that condition.

I should like to thank Mr. R. Rowlandson for thebronchoscopy report, and Dr. T. N. Gledhill for thehistological report.

REFERENCES

Aschoff, L. (1910). tber Tracheopathia osteoplastica. Verh. dtsch.path. Ges., 14, 125.

Baird, R. B., and Macartney, J. N. (1966). Tracheopathia osteo-plastica. Thorax, 21, 321.

Balser,W. (1883). Tracheo- und Bronchostenose mit Amyloid in derWandung der Luftwege. Virchows Arch. path. Anat., 91, 67.

Bowen, D. A. L. (1959). Tracheopathia osteoplastica. J.clin. Path.,12,435.

Carr, D. T., and Olsen, A. M; (1954). Tracheopathia osteoplastica.J. Amer. med. Ass., 155, 1563.

Clerf, L. H. (1944). Tracheopathia osteoplastica (osteoma of tbhtrachea). Anni. Otol. (St. Louis), 5S, 839.

Dalgaard, J. B. (1947). Tracheopathia chondro-osteoplastica. Actapath. microbiol. scand., 24, 118.(1955). Lungecancer ved tracheopathia chondro-osteoplastica.Nord. Med., 53, 572.

Delord, M. (1954). Chondromatose tracheo-bronchique.J. fransr.Mid. Chir. thor., 8, 45.

Falconer, B. (1938). Ein Fall von Amyloidtumor der Trachea undder grossen Bronchien mit dyspnoischen Erscheinungen. Actaoto-laryng. (Stockh.), 26, 353.

Flick, J. B. (1950). Pulmonary lesions simulating primary carcinomaof the lung. Surg. Clin. N. Amer., 30, no. 6, 1559.

Freund, A. (1914). Ueber Tracheopathia osteoplastica. Beitr. Anat.Physiol. Path. Therap. Ohr., 8,11.

Hempel, K. J., and Glaser, A. (1958). Zur Pathogenese der Tracheo-pathia chondro-osteoplastica. Vtrchows Arch. path. Anat., 331,36.

Hiebaum, K. (1934). tJber Knochenbildungen in Lunge und Trachea.Frankfurt Z. path., 47,249.

Howland,W. J., and Good, C. A. (1958). The radiographic featuresof tracheopathia osteoplastica. Radiology, 71, 847.

Huzly, A. (1960). An Atlas of Bronchoscopy. Grune and Stratton,New York and London.

Jackson, C., and Jackson, C. L. (1932). Benign tumors of thetrachea and bronchi. J. Amer. med. Ass., 99, 1747.

Jepsen,O., andS0rensen, H. (1960). Tracheopathia osteoplastica andozaena. Acta oto-laryng. (Stockh.), 51, 79.

Larsen, B. (1937). Et Tilfaelde aftracheopathia chondro-osteoplastica.Dansk. Otolaryng. Selsk. Forhandl., 1937-38, p. 11. (Suppl. toHospitalstitende, 81.)

Liebow, A. A. (1952). Tumors of lower respiratory tract. Atlas ofTumor Pathology, Sect. 5. Fasc. 17: Tumors of the Lower Respira-tory Tract, p. 119. Armed Forces Institute of Pathology, Wash-ington, D.C.

Muckleston, H. S. (1909). On so-called 'multiple osteomata' of thetracheal mucous membrane. Laryngoscope (St. Louis), 19, 881.

Prowse, C. B. (1958). Amyloidosis of the lower respiratory tract.Thorax, 13, 308.

-and Elliott, R. I. K. (1963). Diffuse tracheo-bronchial amyloid-osis. Ibid., 18, 326.

Ribbert, D. R. (1895). Ueber die Entstehung der Geschwulste.Dtsch. med. Wschr., 21, 24.

Salm, R. (1961). Tracheopathia osteoplastica. Thorax, 16, 382.Secrest, P. G., Kendig, T. A., and Beland, A. J. (1964). Tracheo-

bronchopathia osteochondroplastica. Amer. J. Med., 36, 815.Shanks, S. G., and Kerley, P. (1962). A Text-book of X-ray Diagnosis,

3rd ed., Vol. 2, pp. 455, 701. H. K. Lewis, London.Shuttleworth, J. S., Self, C. L., and Pershing, H. 5. (1960). Tracheo-

pathia osteoplastica. Ann. intern. Med., 52, 234.

Spencer. H. (1962). Pathology of the Lung, p. 591. Pergamon Presa,Oxford.

Virchow, R. (1863). Die Krankhaften Geschwiuste, Vol. 1, p. 443.Hirschwawd, Berlin.

Whitwell, F. (1953). Localized amyloid infiltrations of the lowerrespiratory tract. Thorax, 8, 309.

Wilks, 5. (1857). Ossific deposits on larynx, trachea and bronchi.Trans. path. Soc. Lond., 8, 88.

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