Thorax (1961), 16, 78.

INTRATHORACIC TUMOURS OF CAROTID BODY TYPE

(CHEMODECTOMA)BY

J. D. BARRIEFrom the Department of Pathology, Victoria Infirmary, Glasgow

(RECEIVED FOR PUBLICATION SEPTEMBER 1, 1960)

Intrathoracic tumours of carotid body type

were identified by Lattes, who reported two cases

in 1950. Since then only 10 further cases havebeen recorded, either because of their genuinerarity or from the infrequency of their recogni-tion. A more complete knowledge of the normaldistribution of chemoreceptor tissue shouldresult from a study of such neoplasms, and it istherefore of more than academic interest that theseshould be classified correctly.

TERMINOLOGYGaffney (1953), in describing jugular bulb

tumours, suggested that their structure was prob-ably that of a chemoreceptor organ. AcceptingLeCompte's (1948) view that tumours of thecarotid body, which is the best defined and themost adequately studied of the chemoreceptororgans, reproduce in general the structure of theparent tissue, Gaffney further suggested that thisgroup of neoplasms might be designated collec-tively by the term " receptoma."

Mulligan (1950) described as a chemodectoma" a neoplasm consisting of chemoreceptor (chemo-dector) cells, which are associated with thedistribution of parasympathetic nerves and whichoriginate either in the adventitia of blood vesselsin structures intimately connected with afferentnerve fibres or which occur along the branches or

in the ganglia of the glossopharyngeal and vagusnerves." Lattes and Waltner (1949) preferred" non-chromaffin paraganglioma," the designa-tion " non-chromaffin " to distinguish this type oftumour from the paraganglioma of sympatheticnervous tissue. The term "paraganglion" hadbeen used to include a number of diverse struc-tures ranging from the adrenal medulla to theglomus coccygeum, but, in 1950, Lattes clarifiedthe position with the following classification.

I True paraganglia (sympathetic)(a) Adrenal medulla(b) Chromaffin cell nests associated with the

visceral sympathetic ganglia, especiallyalong the thoraco-lumbar chain and thepelvic plexuses

11 Non-chromaffin paraganglia (parasympathetic)(a) Carotid and aortic arch bodies(b) Glomus jugulare(c) Ganglion nodosum of vagus(d) Ciliary body(e) Miscellaneous: other less constant

mediastinal chemoreceptors, isolatedgroups in the retroperitoneal area, groin,and thigh

III Carotid and aortic sinusesIV Neuromyoarterial glomera

The carotid and aortic sinuses function aspressure receptors, and the neuromyoarterialglomera form well-defined groups which will notbe considered further in the present paper. Inaddition to the different anatomical sites of thelarger chemoreceptor organs other points of con-trast between groups I and II are summarized inTable I.

TABLE I

True Paraganglia

Common embryological originwith ganglion cells of thesympathetic nervous system,i.e., sympathochromaffin cellsof neural crest

Efferent sympathetic motor inner-vation

Positive chromaffin reaction

Secretion of epinephrine or

similar substance

"Non-chromaffin " Paraganglia

Development associated withparaganglia of cervical andsacral parasympathetic nerves,branchial arch vessels, andlarge arteries of the limbs

Afferent sensory innervation,probably parasympathetic

Usually negative chromaffin reac-tion

No hormonal secretion

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INTRATHORACIC TUMOURS OF CAROTID BODY TYPE (CHEMODECTOMA) 79

Willis (1953) stated that the chromaffin reactionvaries not only from tumour to tumour but evenfrom one part to another of the same growth, andconsequently the term "non-chromaffin " para-ganglioma is not ideal. It is, however, in commonuse and it can include histologically similargrowths in the ganglion nodosum and glomusjugulare (Simpson and Dallachy, 1958), in theperitoneal tissues, groin, and thigh, and in otherisolated sites (Smetana and Scott, 1951). Until thefunction of each of these different tissues is clari-fied it seems advisable to restrict the use of theterm chemodectoma to tumours arising in organsof which the chemoreceptor activity is wellestablished.

ANATOMYThe distribution of the known chemoreceptor

tissue in the head, neck and chest is shown inFig. 1. The aortic arch bodies number at leastfour: (1) Near the pulmonary end of theobliterated ductus arteriosus; (2) near the originof the left coronary artery; (3) at the bifurcationof the innominate artery or lateral to the originof the right subclavian artery; (4) on the antero-lateral surface of the left side of the aortic archnear the root of the left subclavian artery.As has already been stressed, not all the

chemoreceptor tissue has been accurately charted,and according to Duncan and McDonald (1951)there is no reason why mediastinal tumours shouldalways be situated precisely at the previouslyreported sites.

PHYSIOLOGYThe chemoreceptor organs are stimulated by

oxygen lack, but not until the oxygen tension ofthe arterial blood reaches a relatively low level.They constitute a protection against anoxia, sincethe effect of oxygen lack on the respiratory centreis depression rather than stimulation. Schmidt,Dumke, and Dripps (1939) believe that the chemo-receptors do not play a role in the control ofrespiration under ordinary physiological condi-tions, but in anoxic states the reflex response ofthe chemoreceptors is of the highest importance.Comroe and Schmidt (1938) regard the chemo-receptor mechanism as a form of respiratorycontrol which serves as a last line of defenceagainst respiratory failure.No convincing evidence that non-chromaffin

paragangliomas are functional is as yet forth-coming, and it seems unlikely that assistance indiagnosis will be found in abnormalities ofrespiration or blood chemistry,

FIG. 1.-Diagram of chemoreceptor organs and their anatomicalrelationships. Modified from a diagram (Fig. 26, Cancer, 3,667-694, 1950) obtained through the courtesy of R. Lattes, afterJ. D. Boyd (Contr. Embryol. Carnegie Inst., 26, 1-31, 1937).By courtesy of Dr. P. M. LeCompte.

CASE REPORTSCASE 1.-During necropsy on a 62-year-old man,

who died of virus pneumonia in 1958, the tumour wasdiscovered in the pericardium overlying the rightauricle. It measured 3.5 x 2.5 x 1.5 cm., the surfacewas nodular, and on section it was firm, rubbery, andyellowish brown; intersecting bands of fibrous tissueproduced a lobulated appearance and a single area ofdegeneration was present.The position of the tumour corresponded to that

described by Davis and Randall (1954), and this raisesthe interesting possibility that this is yet anothernormal site for chemoreceptor tissue.

Microscopic Appearances.-The cells were looselyarranged in large masses subdivided by strands offibrous tissue (Fig. 2). The vascularity of the growthwas striking; the larger vessels ran in the supportingstroma, but a number of dilated sinusoids were presentamongst the cells, as were innumerable small vascularspaces (Fig. 3): some of the walls of the latter showedearly hyaline change. Generally the vessels werethin walled and were in close contact with the tumourcells, which tended to be grouped around the bloodspaces or to form small alveolar structures; thesewere well demonstrated by silver impregnation, the

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80 J. D. BARRIE

FIG. 2.-Case 1. Broad bands of collagen divide the tumour into FIG. 3.-Case l. Two large sinusoids and many small blood vesselslarge alveolar masses. Picro-Mallory, x50. are visible. Picro-Mallory, x 130.

FIG. 4.-Case 1. Nests of cells enclosed by reticulin fibres. Reticulin,x 400.

*'-~~~~~AMIWh 1M." -#kiFIG. 5.-Case 1. The two contrasting cellular components: the more

numerous large vesicular cells and the small cells with uniformldense nuclei. Haematoxylin and eosin. x800.

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INTRATHORACIC TUMOURS OF CAROTID BODY TYPE (CHEMODECTOMA) 81

FIG. 6.-Case 2. Antero-posterior radiograph. Dense circumscribedshadow in left upper lung field.

FIG. 7.-Case 2. Left lateral radiograph. Tumour visualized abovethe heart shadow, anterior to aorta.

FIG. 8.-Case 2. The excised tumour enveloped in fine connective FIG. 9.-Case 2. The cut surface of the tumour. Strands of fibroustissue. The lobulated structure is clear. tissue separate the masses of neoplastic cells.

M......

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reticulin fibres enclosing nests of 12 to 20 cells butnot passing between the individual elements (Fig. 4).Two fairly distinct cell types were recognizable (Fig.5), the larger with round or oval vesicular nucleusand a moderate amount of finely granular, faintlyeosinophilic cytoplasm, the smaller characterized byits dense, almost pyknotic, nucleus which was often T.

eccentrically placed. No mitoses or atypical cellforms were identified. Vascular invasion was absent,and no nerve fibres were seen. The degenerate areawas composed of old blood clot, with deposits ofhaemosiderin, much of it phagocytosed.CASE 2. The second tumour was discovered

incidentally in a woman of 51 years during a massminiature radiography campaign in May, 1958. Thepatient's only relevant history was of an indigestion-like discomfort behind the sternum.On admission to the Thoracic Unit at Mearnskirk

Hospital on July 7, 1958, the peripheral blood picture

I~~~~~~~~~~~~~~~~~~~~~~~~~~~m

c1' 11. -Case 2. Thie pattern is very similaA t Mptwo cell types are distinct. Picro-

FIG. 10.-Case 2. Vascular pattern, well-marked hyalinization ofvessel walls. Picro-Mallory, x 130.

was normal, and the Wassermann and Meinickereactions were negative. Mycobacteriumn tuberculosiswas not isolated. Further chest radiographs showeda sharply defined shadow invading the left upper lungfield from the mediastinum: it was not associatedwith the arch of the aorta (Figs. 6 and 7).At operation in August a solid tumour (Figs. 8 and

9) was found lying anterior to the aorta and commoncarotid vessels and displacing the phrenic nervelaterally. It had no definite pedicle and was easilyshelled out.

Within a week the lung had re-expanded, and thepatient was discharged a fortnight later; her generalcondition and chest radiographs were satisfactory twomonths afterwards.

ar to that in Case I and the-Mallory,. 8)00.

-,#. i I* e ^

FIG. 12.-Case 2. Smaller cell nests enclosed by reticulin fibres.Reticulin x 800.

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INTRATHORACIC TUMOURS OF CAR OTID BODY TYPE (CHEMODECTOMA) 83

Grossly, the surgical specimen was a lobulated solidtumour measuring 7 x 6 x 5.5 cm. It was a greyish-brown colour when fixed and section revealed firm,fleshy tissue flecked with areas of haemorrhage.

Microscopic A ppearances. -The structure wasessentially the same as that described in Case l; themost obvious contrast, however, was the veryadvanced hyaline change (Fig. 10) which had occurredaround the vessels. These appearances were verylike those of Lattes' third case (Case 1, Table lI) andthey were considered to be later stages of the processnoted in the first case now described. The two celltypes were again present (Fig. 11) and the reticulinpattern was similar (Fig. 12), though the alveoli tendedto be smaller than those of the first neoplasm; anorigin from an aortic arch body was presumed.

The salient features of the two cases nowreported and of 12 others traced in the literatureare summarized in Table I1.

DIFFERENTIAL DIAGNOSIS

This may be straighforward if the tumour arisesat a recognized site, but may be difficult if thesituation is unusual. To the naked eye theseneoplasms are brown, tan, grey, or bluish-red,with a slightly lobulated surface. Commonly theyare enveloped in fine connective tissue which isoften very vascular. The value of immediatediagnosis by frozen section is stressed byMcDonald, Aufderheide, and Fuller (1954), who

TABLE IISALIENT FEATURES OF PRESENr SERIES AND OF CASES COLLECTED FROM THE LIrERATURE

Case, Sex, Authors Site Sizeand Age of Tumour and Weight

I M 59 Lattes (1950) Essentially intra- Resected cervicalthoracic portion 80 g.

2 M 35 ,, ,, Aortic arch body, 1-2 cm. diameterone of 3 tumours

3 M 22 Monro (1950) Presumed aortico- Not statedpulmonary glomus

4 M 18 Duncan and Right costoverte- 7 x 5 x 4 cm.,McDonald bral sulcus 50 g.(1951)

5 F 33 ,, ,, Right costoverte- Not statedbral sulcus

6 F 67 Davies and Attached to pern- 6 x 4 x 3 cm.Randall cardium over R.(1954) auricle

7 F 38 McDonald etal. Superior 7'v'7x 35 cm.,(1954) mediastinum 70 g.

8 M 79 MacDonald Around L. sub- 5 cm. diameter(1956) clavian artery

distal to thyro-cervical axis

9 M 7 Gillis el ,1/. On anterolateral 4 cm. diameter(1956) aspect of lower

lobe of rightlung

10 M 30 Shaw and 9th left interspace 1-0 x 5 cm.Kennedy in paravertebral(1956) gutter

II F 31 Mendelow and Anterior superior 12 x 8 v 5 cm.Slobodkin mediastinum(1957)

12 M 53 Heppleston Periphery of right 4x 3 b 3 cm.(1958) lung

13 M 63 Barrie (1961) Attached to peri- 3 5 x25 ,:1-5 cm.cardium overright auricle

14 F 51 ,. ,. Aortic arch body 7 6 x 5-5 cm.

G

Methodof Discovery Treatment

Swelling in neck Thoracicoperationfor 14 years abandoned; risk

of haemorrhage

At necropsy -

Biopsy of supra- X-irradiation (400clavicular meta- r) to supraclavi-stasis cular region

.Routine chest

radiograph inArmy

Routine chestradiograph

At necropsy,

Admitted inlabour; routinechest radiograph

At necropsy

Chest radiographin investigationofanorexia,fever,weight loss, andpallor

Routine chestradiograph;watched for1 year

Routine chestradiograph

Routine chestradiograph; 6years increase insize

At necropsy

Routine chest

Operative excision

Removed atoperation

Enucleated atoperation; bleed-ing troublesome

Removed at opera-tion: recur-rence" radio-resistant

Operative excision

Biopsied; consid-erable haemor-rhage; 2,400 rgiven in 16 doses

Operative excision

*KVMLII-'V LJMaL VCla4LIC CAI.Al:UltIIrad iog raph without significant,

bleeding

Result

No change in tumoursize or patient'scondition 4 monthslater

Died of poliomyelitis

Patient deterioratedover 3 years; dys-pnoea and dyspha-gia; calcified massin liver

Well 6 years later

Vertebral mass andspastic paraplegia14 years later; notbiopsied

Died of suppurativebronchitis andperitonitis

Discharged well on5th post-operativeday; no recurrencementioned

Died; oesophagealvarices, haemo-chromatosis, hepa-toma, syphiliticaortic aneurysm

Local recurrence 2years later; diedshortly afterwards;no necropsy

Patient well 10months later

Patient's conditionand tumour's radio-logical appearancesunchanged "duringseveral months"

No recurrence after3 years

Died of viruspneumonia

Well after 12 months

I

Onerative excisionI

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state that unnecessarily radical surgery can beavoided if the non-chromaffin paraganglioma isnot mistaken for a malignant vascular neoplasm.

Other malignant lesions to be considered arethose arising in nervous tissue, primary and secon-dary tumours of mediastinal lymph nodes, andsingle pulmonary metastases. Non-neoplastic butspace-occupying lesions, such as intrathoracicgoitre and aortic aneurysm, come into thedifferential diagnosis of radiological shadows inthis area, while simple tumours to be distinguishedinclude lipoma, fibroma, chondroma, myxoma,dermoid and other cysts, and benign neurogenictumours. Similar radiological appearances canbe produced by a bronchial adenoma, and thismay present diagnostic difficulties even under themicroscope; Heppleston (1958) considered thatthe intrapulmonary tumour which he reportedcould not be distinguished with certainty from abronchial adenoma of unusual type. This com-ment prompted a review of the 18 bronchialadenomas recorded in this department since 1947,and in two of these there were certain histologicalfeatures which resembled those of a non-chromaffin paraganglioma (Figs. 13, 14, 15, and16). Both these tumours presented as peduncu-lated growths within large bronchi and in neitherinstance was there reason to alter the originaldiagnosis. In this connexion it should be notedthat LeCompte (1948), in his discussion on thehistological appearance of carotid body tumours,used the expression " adenoma-like " to describeonie group of cases. He recognized a "usualtype," an "adenoma-like" and an "angioma-like"structure, but felt that in spite of these variationsthe fundamental pattern appeared to be the same,a group of chief or epithelioid cells surrounded bya. more or less abundant vascular stroma.

HISTOLOGICAL FEATURES.--FoUr main featuresare to be sought in establishing the histologicaldiagnosis of non-chromaffin paraganglioma.

Vasuilarity.-Thi-s is often so intense as tosuggest at first glance that the tumour is angioma-tous in nature. The blood spaces may be largeor small, the walls ill-defined or quite welldeveloped. A peculiar hyaline change around thevessels may be diagnostically helpful but is un-explained ; it is not accompanied by ischaemiceffects such as cellular degeneration or replace-ment fibrosis.

Alveolar Str"clure.-The extent to which thisis developed varies. At its greatest, the tumour isdivided into large, solid alveoli separated by broadbands of collagen in which run the main blood

vessels. Within these alveolar formations the cellsare often grouped in clusters of 12 to 20, and thisarrangement is best demonstrated by reticulinstaining.

Reticulin Pattern.-Characteristically, the reti-culin fibres surround nests of up to a score ofcells, but do not pass between the individualcomponents. Often the reticulin strands appearto radiate outwards from the blood vessels, andGillis, Reynolds. and Merritt (1956) referred to a"basket pattern produced by the interweavingfibres. This typical arrangement has been foundin 12 of the 14 cases listed in Table 11, while inthe other two reports this technique is notmentioned.

Cell Morphology.-In size and number thepredominant cell is polyhedral with pale oxyphilicand finely granular cytoplasm; the borders areoften frayed. The nuclei are large, round, or oval,and they stain lightly with basic dyes and have anopen chromatin network. In addition to this"epithelioid" cell, Burman (1956) has describedsmaller cells which are fewer in number butnevertheless quite constant components of thesetumours; their most obvious feature is aneccentric, deeply staining nucleus.No positive chromaffin reaction has been

reported in any of the cases reviewed. Haemo-siderin pigment was identified in the tumoursdescribed by Lattes (1950) and by Mendelow andSlobodkin (1957). Nerve fibres were also notedby Lattes, but Heppleston stated that they wereabsent from the tumour he examined. No nervetissue was found in the present cases, the chrom-affin reaction was negative, and no intracellularglycogen was demonstrated either by the periodic-acid-Schiff reaction or by Best's carmine. Smallamounts of haemosiderin were visualized by thePrussian blue method in the first tumour only;the pigment was confined almost entirely to thefibrous septa.

SUMMARYTwo further cases of intrathoracic tumours of

carotid body type are recorded; one was anincidental finding at necropsy in a man aged 62.the other was discovered during a mass miniatureradiography campaign and was successfullyremoved from a woman of 51 years. The relevantdetails of 12 cases reported in the literature arereviewed, and an account is given of the differen-tial diagnosis of intrathoracic tumours of chemo-receptor tissue, including the radiological, surgical,and histological features. The finding of a second

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INTRATHORACIC TUMOURS OF CAR OTID BODY TYPE (CHEMODECTOMA)

FIG. 13.-Bronchial adenoma. Alveolar pattern and numerous smallblood vessels, some showing early hyalinization of their walls.Masson-Goldner, X 150.

la.ISr.FIG. 15.-Bronchial adenoma. Alveolar pattern and numerous large

and small vascular spaces. Masson-Goldner, x 150.

FIG. 14.-Bronchial adenoma. Same case as Fig. 13, showing reticulin FiG. 16.-Bronchial aden-oma. Same case as Fig. 15, showing reticulinpattern. Reticulin, x 330. pattern. Reticulin, x 330.

H

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intrapericardial tumour at the base of the heartsuggests that this may be a previouslyunrecognized site of chemoreceptor tissue.

I wish to thank Dr. A. A. F. Peel and Mr. R. S.Barclay, by whom these patients were treated, forpermission to publish the clinical details. I am verygrateful to Dr. W. B. Davis and Dr. J. E. Craik fortheir advice on the histology and their encouragementand criticism during the preparation of themanuscript.

I thank the Photographic Department for theillustrations.

REFERENCESBurman, S. 0. (1956). Int. Abstr. Surg., 102, 330.Comroe, J. H., and Schmidt, C. F. (1938). Amer. J. Physiol.,121, 75.Davies, J. R., and Randall, K. J. (1954). J. Path. Bact., 68, 247.

Duncan, D. K., and McDonald, J. R. (1951). Amer. J. clin. Path.,21, 515.

Gaffney, J. C. (1953). J. Path. Bact., 66, 157.Gillis, D. A., Reynolds, D. P., and Merritt, J. W. (1956). Brit. J.

Surg., 43, 585.Heppleston, A. G. (1958). J. Path. Bact., 75, 461.Lattes, R. (1950). Cancer, 3, 667.- and Waltner, J. G. (1949). Ibid., 2, 447.LeCompte, P. M. (1948). Amer. J. Path., 24, 305.-(1951). Atlas of Tumor Pathology, Section IV, Fasc. 16.

Armed Forces Institute of Pathology, Washington, D.C.MacDonald, R. A. (1956). A.M.A. Arch. Path., 62, 107.McDonald, 0. G., Aufderheide, A. C., and Fuller, J. (1954). Ann.

Surg., 140, 254.Mendelow, H., and Slobodkin, M. (1957). Cancer, 10, 1008.Monro, R. S. (1950). Brit. J. Surg., 38, 105.Mulligan, R. M. (1950). Amer. J. Path., 26, 680.Schmidt, C. F., Dumke, P. R., and Dripps, R. D., Jr. (1939). Amer.

J. Physiol., 128, 1.

Shaw, K. M., and Kennedy, J. D. (1956). Thorax, 11, 57.Simpson, I. C., and Dallachy, R. (1958). J. Laryng., 72, 194.Smetana, H. F., and Scott, W. F., Jr. (1951). Milit. Surg., 109, 330.Willis, R. A. (1953). Pathology of Tumours, 2nd ed., p. 872. Butter-

worths, London.

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