1974 Tumors of the Nasopharynx in Tunisia an Anatomic and Clinical Study Based on 143 Cases

8/6/2019 1974 Tumors of the Nasopharynx in Tunisia an Anatomic and Clinical Study Based on 143 Cases

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T U M O R S OF THE N A S O P H A RY N X I N T U N I S I AAn A n a t o m i c a n d Clinical S tudy Based o n 143 Cases

M . C A M M O U N , . VOCTHOERNER,ND N . MOURALI

This study is based on 143 instances of malignant nasopharyngeal tumors ob-served at the National Cancer Institute in Tunisia. This is the most commontumor in Tunisia. The ages of the patients varied between 10 and 78 years, thepeak ages being between 50 and 59 years, and between the ages of 10 and 19years (14.6% under age of 16 years). So-called lyniphoepitheliomas were theprevalent tumor type in the younger age group.

HE RELATIVE FREQUENCY OF CANCER OF THE

T asopharynx in Tunisia has been men-tioned by Chadli4 and Zaouche.18 Th e epi-demiologic study of cancer of the cavum bythe International Cancer Union1 does notmention this frequency. In Europe, the inci-dence is low, about 0.2'y0of all malignant tu-mors. However, it is high in other parts ofthe world, especially south of China: HongKong, Formosa, Malay, and Singapore. InHong Kong, 124 cases per million inhabitantshave been recorded, 25 times the number esti-mated by Godtfresden in Denmark and Swe-den.7Our material consisted of 143 nasopharyn-geal tumors observed and treated at the Na-tional Cancer Institute from March 10, 1969to March 22 , 1971. All the patients were Mos-lems, and all were Tunisians, except for threewho were Libyans. Among the Tunisian hos-pitals, the National Cancer Institute is theonly one to have a telecobalt installation, sonearly every patient treated by irradiation hasbeen seen at this Institute.

We had histologic confirmation on every pa-tient except for two, for whom we had only ahistologic report. In three others, in spite otobvious symptoms of nasopharyngeal cancer,the biopsy was negative, but the histologic ex-amination of the cervical adenopathy showedtypical metastases from the cavum. In 24 pa-tients, we obtained biopsies of both the cavumand lymph nodes, which made it possible tomake a comparative histologic study. Ordi-nary stains were used for all the biopsies(Hemalum eosine-safran). Reticulin stain wasemployed in the less-differentiated cancers;

From the National Cancer Institute, Tunis, Tunisia.Received for publication May 1 7 , 1973.

mucicarmin was also used, as was PAS in sus-picious cases of glandular cancers.

Every patient (except two who refused) re-ceived radiotherapy. For 24 , there were nofurther therapeutic resources; 4 were givenpalliation.

There were 102 males and 41 females. Theage of the patients varied between 10 and 78years; the average age for men was 44.6, andfor women 42.7. The peak incidence wasreached between 50 and 59 years for bothsexes, but there was also a high frequency inpatients between 10 and 19 years; 21 casesunder 16 years represented 14.6sy0 of the en-tire group. The age curve was the same forboth sexes. (Fig. 1).

Th e general nasopharyngeal cancer inci-dence in Tunisia is difficult to establish. Thisis an undeveloped country, where the healthfacilities, especially in the country, are insuffi-cient. There are probably many people withcancer who die without ever having seen aphysician. For 1970, we estimate that theremight be an incidence of 2.05 cancers per100,000 inhabitants (personal communicationfrom D. Muir.)Cancer of the nasopharynx is the most fre-quent malignant tumor of the otdaryngologicarea. In 1970, the National Cancer Institutereported 78 cancers of the cavum, 61 of thelarynx, and 20 of the tongue and mouth. Dur-ing this same year, 1050 cases of cancer weretreated: 7.390/, were of the nasopharynx;10.1% in men and 7.3a/, in women. They rep-resented 38.80/, of all cancers in men and53.4% in women (42.3% for both sexes).

The geographical distribution on the map(Fig. 2) illustrates the proportional incidenceof cancer of the nasopharynx related to thedensity of the population. T he northern Gov-

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No. 1 NASOPHARYNGEALUMORSC a m m o i i n et al. 185

40

30

2(

1c

0

a EMALES0 ALES

1-19 20-29 0-3: -10-5960.69 7069 AG EFIG. 1 . Distribution of cases by age and sex

ernorats Provinces are more densely inhabitedthan those in the center and south. However,it is interesting to note that this incidenceseems relatively lower in the region of Sfax,the second most important town in Tunisiaand the most populated Governorat afterTunis and Sousse. This is not due to an insuf-ficient sanitary installation, because Sfax hasan excellent health service and has regularconsultations and histologic examinations forall biopsies.

CLINICALSPECTSThere are many advanced cases of cancer of

the nasopharynx for which all therapeutic in-tervention is useless (about 16%). The hid-den time, i.e., the time between the manifes-tation of the tumor and the day the patientcomes for the first consultation is not easy toestablish: in 30 cases this could not be deter-mined, but it was about 8 months in other pa-tients. The times ranged between 8 days and 4years.The most frequent clinical signs are cervical

adenopathy, epistaxis, nasal obstruction, audi-tory problems, and neurologic disorders suchas paralysis of the cranial nerves, headaches,and trismus. Rarely, a single sign, such as par-alysis of the 6th nerve, may be the first indica-tion of a nasopharyngeal cancer, but oftenwhen the patient is seen there are numerousclinical findings. Table 1 shows the number ofpatients with adenitis (Fig. 3) . In at least 24cases, the histologic examination of the biopsyof a cervical lymph node led to the search forand discovery of a nasopharyngeal tumor. Th eordinary clinical signs of a neoplasm of thecavum were insignificant or absent. In 22 pa-tients, there were enlarged cervical nodeswithout any alteration of the cavum. Theselymph node metastases were often first treatedas tuberculous adenites. The neurologic signsmay be dominant, and thus the patient maybe treated for a relatively long time period inneurology before he visits an otolaryngologist.T h e lesion of the base of the skull was noticedin onIy 18 cases, some at clinical examinationand others during its evolution by radiologicexamination. This bony involvement was ac-

FIG. 2 . Map of geographical distribution illustratingthe proportional incidence of cancer of the naso-pharynx related to the density of the population.


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186 CANCERanTABLE . The Most Frequent Clinical Signs ofNasopharyngeai Tumors in TunisiaCervical adenopathy 86Auditory signs 67Nasal obstruction 61Epistaxis 64Neurologic signs; injury of thecranial nerves 28

companied by neurologic signs in only five pa-tients. The precise location of the tumor wasnot always identified (104 cases); in 24, thetumor occupied the whole cavum. Table 2shows the possible locations of the neoplasms,the roof and lateral walls being the most fre-quent areas (56.~37~nd 59%).

PATHOOG YFungiform tumors made up about 811%of

the entire series. Only 11 cases showed infiltra-tion or ulceration. In five patients, the clinicalexamination of the cavum was not remarka-ble. Th e tumor was not described macroscopi-cally in 5 0 cases (35%), because a tight trismusexcluded examination.Histopathology: Epitheliomas were dividedas follows: 1. Differentiated epidermoid carci-noma; 2. Undifferentiated epidermoid carci-noma; 3. Nasopharyngeal type carcinoma(which we consider typical for this location; 4.Anaplastic carcinoma.1. The differentiated epidermoid carcinomais a cancer in which the squamous structure i sobvious (22 or 17.7%) (Fig. 4).2. The undifferentiated epidermoid carci-noma largely resembles the malpighian mu-cosa which is without any keratinization, andthe cells of which (instead of being always po-lyhedral) can be spindle-shaped (Fig. 5),

iinry 1974 Vol. 33rounded, or ovoid. The cells demonstrated adefinite cellular border. They showed trabecu-lar and lobular patterns, sometimes with base-ment membrane. This kind of tumor can beseen at any level of the malpighian layer orparamalpighian layer, especially in the cervix,esophagus, and the oral cavity. They represent42.5% of all epitheliomas (5 3 cases).

3. The nasopharyngeal type carcinoma(NPTC) is a peculiar neoplasm of the cavumin that its fundamental histologic feature iscellular. T he tumor cells borders are not defi-nite, their nuclei are clear, and chromatin isscarce. Th e nuclei look holed. They exhibitoften two or three distinct nucleoli. They maybe spindle-cell, rounded, or polyhedric. T h esyncytial aspect and the poor chromatin of thenuclei are the fundamental features. Thestroma varies sometimes; it is lymphoid, fib-rous, or granular, and inflammatory (Figs. 6-8). We had 49 cases, (39% of all the epithe-liomas).

4. Th ere were only two cases each of adeno-carcinoma and anaplastic epithelioma. Amongthe hematosarcomas there were four reticulo-sarcomas, two lymphosarcomas (Fig. 9), andone plasmocytoma. Eight epitheliomas werenot classified, either because the biopsy wastoo small, or because we did not receive thehistologic slides.Th e distribution of the histologic types ac-cording to age i s interesting. There was onlyone patient under 40 with differentiated epi-dermoid carcinoma. This held true also forthe undifferentiated carcinomas: nine casesunder 53 years of age. On the other hand, thenasopharyngeal type carcinoma is more fre-quent in younger people, 28 of 42 patientswere under 40, and all the patients under 20years of age had this type of tumor.

FIG.3. Clinical pho-tograph of a youngboy with involvementof the high cervicallymph nodes, a typicallocation for metastaticcarcinoma from thenasopharynx.


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No. 1 NASOPHARYNGEALUMORSCammoun et al . 187TABLE. Observed Sites of t h e T u m o r

Late ral walls 62 59%To p roof 59 56%Poster ior wall 34 3 2 . 5 0 / ,Floor 24 23 %T h e w hole c a vum 24 23%I t is seldom th a t the tu mo r a ffects a precise place i nexcluding others . I t is most ly riding over severa l a t t hesame t ime .

DISCUSSIONThe incidence of nasopharyngeal cancer in

Tunisia seems high, it appears to be a.bout2.05 per 100,000 inhabitants in 1 year. Thisfrequency is probably higher inasmuch asmany cases are not recognized or diagnosed.

Tunisia is not the only country in NorthAfrica with a high incidence. In Algeria, Man-souri et al. observed 105 cancers of the cavumout of 613 between 1962 and 1967. Sitbon, a tthe M. and P. Curie Center of Algiers, re-ported 145 between 1950 and 1960. Personal

information in Morocco led us to believe thatthere is a high incidence there also.

In Europe, the average incidence per100,000 inhabitants is low: 0.7 for men and0.4 for women (these statistics were quoted byGodtfredsen for the northern countries as re-ported by Muir). Although the frequency issignificantly higher in Tunisia than in Eu-rope, it does not reach that of the Far Eastwhere the average yearly incidence of naso-pharyngeal cancers in Hong Kong is 12.4 per100,000 inhabitants,' with the same percent-age for Formosa and Singapore.

Our peak age curve in comparison with thatof Hong Kong shows a slight divergence: forTunisia it is between 50 and 59 years, forHong Kong between 40 and 44 years. TheChinese evidently do not have another peakbetween 10 and 20 years as we do in Tunisia.In this latter younger age group were 14.6%of our cases, whereas in the quoted series fromthe Far East there were in Formosa 13 casesout of 1000 (l%).I7 Muir in Singapore re-

FIG. 4. Photomicrograph of keratinizing squamous cancer in a male 54 years of age (747)(X150, W.U. NG. 73-456).


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188 CANCERanuary 1974 VOl. 43

ported 8 out of 974 cases (0.870);10 nd Ho inHong Kong reported no more than 15 out of1438 (170).7t seems that the Caucasian childis more susceptible than the Oriental child.The statistics compiled by Martin and Bladyin the United States corroborate this impres-sion. They found in a series of 87 cases that9% were under 15 years of age, and 18%under 30 years of age. They believe that thiskind of cancer affects the child much moreoften that any other kind of cancer of the res-piratory and digestive tracts. The number of

FIG. 5. Photomicro-graph of a nasopha-r y ng e a l c a nc e r i nwhich the individualcells have a spindle-like pattern (~100).

affected men is three times that of women,which corresponds to the findings of otherauthors.709

From the clinical point of view, there doesnot seem to be a notable difference in thosecountries with a high incidence. Scarcelyknown clinically in Tunisia., the nasopharyn-geal cancer is often discovered too late. Theclinical aspect is the same as that seen in theFar East,7 in Europe,ll and in the Unitedstate^.^ Cervical adenopathy is easily noticedon the first examination, and should lead to a

FIG. 6. This tumorhas a somewhat syn-c y t i a l a s pe c t w i t hscattered lymphocytes(x250).


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No. 1 NASOPHARYNGEALUMORS C a m m o u n e t al. 189

FIG. 7. Photomicrograph of so-called lymphoepithelioma in a female 45 years of age. Noteprominent nucleoli and lymphocytic infiltrate (2766) (X350, W.U. Neg. 73-458).

systematic examination of the cavum. T he lo-cation of the tumor appears most often in thelateral and posterior walls.

From the pathologic point of view, the na-sopharyngeal cancer appears frequently as afungating tumor, but also as a diffuse submu-cous infiltration, somewhat deforming thewalls. At times the macroscopic examinationis negative, leading to several successive biop-sies done blindly.T he histopathology of this type of tumor isdebatable. Several classifications have beenproposed. Shu Yeh, after about 1,000biopsies,created a very detailed classification which in-cluded 9 histologic types. After having studiedthis classification as it related to prognosis, hefound tha t survival did not depend on the his-tologic types, and finally retained only two;the classic epidermoid epithelioma, and theundifferentiated epidermoid epithelioma.

We believe that the lymphoepithelioma ofRegaud and Schmincke is debatable and doesnot seem to be an established entity.e~15~17Teoh argues against the existence of such a

histologic entity based on his study of 32 ne-cropsies. The lymphoid tissue, intimatelymixed with the epithelioma spans, does notappear in the visceral metastases. YehI7 foundthat the tumor cells of the lymphoepitheliomawere similar to the cells of the transitional cellepithelioma described by Cappell.3 He notedseveral biopsies in which the lymphoepithe-lioma and transitional cell epithelioma weresituated side by side. He demonstrated withbiopsies taken from people in good health andof al l ages, that the lymphoid tissue was al-ways present, and as such, it was an integralpart of the nasopharyngeal mucosa. So it is tobe expected that the epithelioma cells aremore or less lost in this tissue.

A comparison between the nasopharyngealand lymph node biopsies on the same patientshows that the important lymphoid elementin the cavum can be absent and substituted bya fibrous tissue on the adenopathic level. Thecontrary is also true: a fibrous stroma on thenasopharyngeal level can be lymphoid type inthe invaded lymph node. Furthermore, in the


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190 CANCERanuary 1974 VOl. 33

FIG. 8. Photomicro-g r a p h of a tu morwith the characteristicn u c l ear ap p earan ce(X400).

same biopsy, the histologic aspect can varyfrom one zone to another, seen especially inthe larger fragments.various histologic types, such as the differen-

tiated epidermoid epithelioma, the undifferen-tiated epithelioma, and the transitional cellepithelioma, may all be found in the same ad-

Besides the lymphoepithelioma debate, the enopathy or in the same nasopharyngealbiopsy. We have a typical example of these

FIG. 9. Photomicrograph of a lymphosarcoma of the nasopharynx of a male 68 years of age(619) ( ~ 6 0 0 , .U . Neg. 73-457).


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No. 1 NASOPHARYNGEALUMORSCammoun et al. 191three histologic forms in the same lymph nodemetastasis. We do not think that these mor-phological types are unchanging entities.Surely there must be transitions from one formto another. Nevertheless, for every pathologistworking in areas where this kind of cancer isfrequent, the diagnosis of a single lymph nodebiopsy should point most surely to a primarynasopharyngeal origin. We have noticed sev-eral times that study of these metastases ledthe pathologist toward the cavum. Indeed,there exists a certain morphological individu-ality of this type of cancer. The transitionalcell epithelioma as described by Cappell seemsspecific for cancer of the nasopharynx. Its fun-damental histologic aspect is not constructivebut cellular. Th e tumor cells have a clear nu-clei with sparse chromatin (holed), butshowing always one or two nucleoli. Th ei r cy-toplasm is clear and granular, and their bor-ders vague and indeterminate. They form al-veolar structures resembling protoplasmicsyncytium. T h e stroma can be fibrous, lym-phoid, granular, or inflammatory. Th is form ofcancer should be called nasopharyngeal-typeepithelioma because it is not found in anyother part of the body.

Clinically, it is seen often in young adults,especially in children. Of 24 patients under 20years of age, 16 showed this histologic type,while 5 were undifferentiated epitheliomas, (3of the biopsies were too small to be classified).These nasopharyngeal type epitheliomas r e presented 76% of the cancers among adoles-cents and children.

The anaplastic form (only two cases in ourseries), is often difficult to distinguish from re-ticulum cell sarcoma. Th e evolution of thedisease in our two cases showed that they weretrue epitheliomas.

Other malignant tumors of the cavum arerare. We had only two adenocarcinomas, sixhematosarcomas, and one plasmocytoma.

Various authors have noted the influence ofrace with regard to this tumor: American au-thors have reported a high incidence amongAmerican-born Chinese.16 T h e MongolianRace seems to be especially predisposed, so i t

is difficult to explain why cancer is so scarce inJapan,lu and why in Tunisia, which is inhab-ited by Caucasian people, it is so frequent.Bailar thinks that the environmental factorcombined with the racial factor might explainthis frequency.1

The discovery of the high incidence of naso-pharyngeal cancer in Tunisia raises an etio-logic problem, and the hypotheses advancedto date have not explained our findings. Simi-larly, neither the racial nor the environmentalfactor explain i t satisfactorily. Recently, G. deTh e demonstrated a type of herpes virus seenin certain cells of culture tissue of nasopharyn-geal carcinoma in China. This suggests thepossibility of a viral basis which better ex-plains the frequency of this cancer amongsuch diverse populations.

SUMMARYThis study is based on 143 anatomo-clinical

observations of malignant nasopharyngeal tu-mors observed over a 2-year period at the Na-tional Cancer Institute of Tunisia.

The average age of the patients was 44.6years. Two peaks were noticed on the agecurve; between 50 and 59 years, and between10 and 19 years (14.60/, were under 16). Therewas a clear predominance of males (102 men,41 women). Th e general incidence of the naso-pharyngeal cancer in Tunisia can be esti-mated to be 2.05 cases per 100,000 population.

A study of the geographic distributionshowed a relation between incidence and pop-ulation density.

From the clinical point of view, cervical ad-enopathy was a significant symptom. Histolog-ically, there was a specific morphological typeof nasopharyngeal epithelioma often seen inyoung patients. There did not seem to be anotable difference between the epithelioma ofthe cavum in Tunisia and that of SoutheastAsia, but there was a higher frequency amongchildren in Tunisia. T he racial factor did notseem to be important. A type of herpes virusmight be the origin of this kind of cancer.

REFERENCES1. Bailar, J.: Nasopharyngeal cancer in white popu- 2. Cappell, D. F. : On lympho-epithbl ioma of naso-lations-A world-w ide survey. I n Cancer of the Naso - pharynx and tonsils. J. P at h o l . Bacterial. 3949-64 ,pharynx: A symposium Organized by the InternationalUnion Against C ancer, mono graph series, vol. 1 , C. S . 3. --: Pathology of the nasopharyngeal tumors.Muir and K. Shamugaratnan, Eds., Copenhagen, J. Lnryngol. O t o l . 53:55-580, 1938.Munksgaard, 1967. 4.Chadli, A., and Ph ilippe, E.: La physionomie du

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192 CANCERanuary 1974 VOl. 33cancer en Tunisie. Archives de I'lnstitut Pasteur deTunis 37:397,441, 1960.

5. Godfredsen, E.: Cited by Ho.: Ophtalmology andneurology symptoms of malignant naso-pharyngeal tu-mors, a clinical study comprising 454 cases. with specialreference to histopathology and possibility of earlierrecognition. Acta. Psychiatr . Scand. [Suppl .] 34: 1-323,1944.6. Hawser, I. J., and Brownell, D. H.: Malignantneoplasms of nasopharynx. J A M A 11~2467 , 473, 1938.7. Ho, H. C.: Nasopharyngeal carcinoma in H ongKong. In Cancer of the Naso-pharynx; A SymposiumOrganized by the International Union Against Cancer,Monograph series, vol. 1, C. S. Muir and K. Shamugar-atnan, Eds. Copenhagen, Munksgaard, 1967; pp. 58-63.8. Mansouri et al.: Difficulties et erreurs de diagnos-tic dans les tumeurs malignes du cavum. T u n i s . M e d .9. Martin, H. E., and Baldy, J. V.: Cancer of the na-sopharynx. Arch. Oto la tyngol . 32:692-727, 1940.10. Muir, C. S., and Shamugartnan, K.: The inci-dence of nasopharyngeal cancer in Singapore. In Can-cer of the Nasopharynx; A Symposium Organized bythe International Union Against Cancer, monograph

1:81-83, 1968.

series vol. 1, C. S . Muir and K. Shamugaratnan, Eds.Copenhagen, Munksgaard, 1967; pp. 47-53.11. Nelsen, J.: Roentgen treatment of malignant tu-mors of nasopharynx. Acta Radiol . 26: 133-154, 1945.12. Regaud.: Personal communication cited by Rev-erchon and Coutard.13. Reverchon and Coutard: LymphoQpith&liomade l'hypopharynx trait6 par roentgentherapie sans

rkaction notable du pharynx et du larynx. Bull. M L m .SOC. Franq. Oto-Rh ino-Laryngol . 34:209-214, 1921.14. Sitbon, J.: La cancer du cavum en Algbrie. Bull.Alg . Carcinol. 2:385, 1959.15. Teoh, T. B.: Epidmmoid carcinoma of nasophar-ynx among Chinese study of 31 necropsies. J. Puthol .Bacteriol . 73:451-465, 1957.16. Vaeth, J. M.: Nasopharyngeal malignant tu-mo rs -8 2 consecutive patients treated in a period of 22years. Radio logy 742366372, 1960.17. Yeh, Shu: A histological classification of carcino-mas of the nasopharynx with a critical review as to ex-istence of lymphoepitheliomas. Cancer 15:895-920,1962.18. Zaouche, A.: Les tumeurs malignes de la sphhreO.R.L. en Tunisie. Th&e de Mkdecine facultt deMkdecine de Paris. 37:397-441, 1960.

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1974 Tumors of the Nasopharynx in Tunisia an Anatomic and Clinical Study Based on 143 Cases