T U M O R S OF T H E NASOPHARYNX I N TUNISIA

A n Anatomic a n d Clinical Study Based o n 143 Cases

M. CAMMOUN, AND N. MOURALI
G. VOCTHOERNER,

This study is based on 143 instances of malignant nasopharyngeal tumors ob-

served at the National Cancer Institute in Tunisia. This is the most common
tumor in Tunisia. The ages of the patients varied between 10 and 78 years, the
peak ages being between 50 and 59 years, and between the ages of 10 and 19
years (14.6% under age of 16 years). So-called lyniphoepitheliomas were the
prevalent tumor type in the younger age group.

T HE RELATIVE FREQUENCY OF CANCER OF THE

nasopharynx in Tunisia has been men-
tioned by Chadli4 and Zaouche.18 T h e epi-
demiologic study of cancer of the cavum by
the International Cancer Union1 does not
mention this frequency. I n Europe, the inci-
dence is low, about 0.2'y0 of all malignant tu-
mors. However, it is high in other parts of
the world, especially south of China: Hong
Kong, Formosa, Malay, and Singapore. In
Hong Kong, 124 cases per million inhabitants
have been recorded, 25 times the number esti-
mated by Godtfresden in Denmark and Swe-
den.7
Our material consisted of 143 nasopharyn-
geal tumors observed and treated at the Na-
tional Cancer Institute from March 10, 1969
to March 22, 1971. All the patients were Mos-
lems, and all were Tunisians, except for three
who were Libyans. Among the Tunisian hos-
pitals, the National Cancer Institute is the
only one to have a telecobalt installation, so
nearly every patient treated by irradiation has
been seen a t this Institute.
We had histologic confirmation on every pa-
tient except for two, for whom we had only a
histologic report. In three others, in spite ot
obvious symptoms of nasopharyngeal cancer,
the biopsy was negative, but the histologic ex-
amination of the cervical adenopathy showed
typical metastases from the cavum. I n 24 pa-
tients, we obtained biopsies of both the cavum
and lymph nodes, which made it possible to
make a comparative histologic study. Ordi-
nary stains were used for all the biopsies
(Hemalum eosine-safran). Reticulin stain was
employed in the less-differentiated cancers;
From the National Cancer Institute, Tunis, Tunisia.
Received for publication May 17, 1973.
184
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 no
further therapeutic resources; 4 were given
palliation.
There were 102 males and 41 females. T h e
age of the patients varied between 10 and 78
years; the average age for men was 44.6, and
for women 42.7. T h e peak incidence was
reached between 50 and 59 years for both
sexes, but there was also a high frequency in
patients between 10 and 19 years; 21 cases
under 16 years represented 14.6sy0 of the en-
tire group. T h e age curve was the same for
both sexes. (Fig. 1).
T h e general nasopharyngeal cancer inci-
dence in Tunisia is difficult to establish. This
is an undeveloped country, where the health
facilities, especially in the country, are insuffi-
cient. There are probably many people with
cancer who die without ever having seen a
physician. For 1970, we estimate that there
might be an incidence of 2.05 cancers per
100,000 inhabitants (personal communication
from D. Muir.)
Cancer of the nasopharynx is the most fre-
quent malignant tumor of the otdaryngologic
area. In 1970, the National Cancer Institute
reported 78 cancers of the cavum, 61 of the
larynx, and 20 of the tongue and mouth. Dur-
ing this same year, 1050 cases of cancer were
treated: 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 and
53.4% in women (42.3% for both sexes).
T h e geographical distribution on the map
(Fig. 2) illustrates the proportional incidence
of cancer of the nasopharynx related to the
density of the population. T h e northern Gov-
No. 1 TUMORSCammoiin et al.
NASOPHARYNGEAL . 185

a FEMALES
adenopathy, epistaxis, nasal obstruction, audi-
tory problems, and neurologic disorders such
40
0 MALES as 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 often
when the patient is seen there are numerous
clinical findings. Table 1 shows the number of
patients with adenitis (Fig. 3). In at least 24
30 cases, the histologic examination of the biopsy
of a cervical lymph node led to the search for
and discovery of a nasopharyngeal tumor. The
ordinary clinical signs of a neoplasm of the
cavum were insignificant or absent. In 22 pa-
tients, there were enlarged cervical nodes
2( without any alteration of the cavum. These
lymph node metastases were often first treated
as tuberculous adenites. The neurologic signs
may be dominant, and thus the patient may
be treated for a relatively long time period in
neurology before he visits an otolaryngologist.
1c T h e lesion of the base of the skull was noticed
in onIy 18 cases, some at clinical examination
and others during its evolution by radiologic
examination. This bony involvement was ac-

0 -
1-19 20-29 30-3: 10-5960.69 7069 AGE

FIG. 1 . Distribution of cases by age and sex

ernorats Provinces are more densely inhabited

than those in the center and south. However,
it is interesting to note that this incidence
seems relatively lower in the region of Sfax,
the second most important town in Tunisia
and the most populated Governorat after
Tunis and Sousse. This is not due to an insuf-
ficient sanitary installation, because Sfax has
an excellent health service and has regular
consultations and histologic examinations for
all biopsies.

ASPECTS
CLINICAL
There 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 patient
comes for the first consultation is not easy to
establish: 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 4
FIG. 2. Map of geographical distribution illustrating
years. the proportional incidence of cancer of the naso-
The most frequent clinical signs are cervical pharynx related to the density of the population.
186 Jan iinry 1974
CANCER
TABLE1. The Most Frequent Clinical Signs of
Nasopharyngeai Tumors in Tunisia
Cervical adenopathy 86
Auditory signs 67
Nasal obstruction 61
Epistaxis 64
Neurologic signs; injury of the
cranial nerves 28
companied by neurologic signs in only five pa-
tients. T h e precise location of the tumor was
not always identified (104 cases); in 24, the
tumor occupied the whole cavum. Table 2
shows the possible locations of the neoplasms,
the roof and lateral walls being the most fre-
quent areas (56.~37~ and 59%).
PATHO
LOGY
Fungiform tumors made up about 811%of
the entire series. Only 11 cases showed infiltra-
tion or ulceration. In five patients, the clinical
examination of the cavum was not remarka-
ble. T h e tumor was not described macroscopi-
cally in 50 cases (35%), because a tight trismus
excluded examination.
Histopathology: Epitheliomas were divided
as 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. T h e differentiated epidermoid carcinoma
is a cancer in which the squamous structure is
obvious (22 or 17.7%) (Fig. 4).
2. T h e undifferentiated epidermoid carci-
noma largely resembles the malpighian mu-
cosa which is without any keratinization, and
the cells of which (instead of being always po-
lyhedral) can be spindle-shaped (Fig. 5),
Vol. 33
rounded, or ovoid. T h e cells demonstrated a
definite cellular border. They showed trabecu-
lar and lobular patterns, sometimes with base-
ment membrane. This kind of tumor can be
seen at any level of the malpighian layer or
paramalpighian layer, especially in the cervix,
esophagus, and the oral cavity. They represent
42.5% of all epitheliomas (53 cases).
3. T h e nasopharyngeal type carcinoma
(NPTC) is a peculiar neoplasm of the cavum
in that its fundamental histologic feature is
cellular. T h e tumor cells’ borders are not defi-
nite, their nuclei are clear, and chromatin is
scarce. T h e nuclei look “holed.” They exhibit
often two or three distinct nucleoli. They may
be spindle-cell, rounded, or polyhedric. T h e
syncytial aspect and the poor chromatin of the
nuclei are the fundamental features. T h e
stroma varies sometimes; i t is lymphoid, fib-
rous, or granular, and inflammatory (Figs. 6-
8). We had 49 cases, (39% of all the epithe-
liomas).
4. There were only two cases each of adeno-
carcinoma and anaplastic epithelioma. Among
the hematosarcomas there were four reticulo-
sarcomas, two lymphosarcomas (Fig. 9), and
one plasmocytoma. Eight epitheliomas were
not classified, either because the biopsy was
too small, or because we did not receive the
histologic slides.
T h e distribution of the histologic types ac-
cording to age is interesting. There was only
one patient under 40 with differentiated epi-
dermoid carcinoma. This held true also for
the undifferentiated carcinomas: nine cases
under 53 years of age. On the other hand, the
nasopharyngeal type carcinoma is more fre-
quent in younger people, 28 of 42 patients
were under 40, and all the patients under 20
years of age had this type of tumor.
FIG. 3. Clinical pho-
tograph of a young
boy with involvement
of the high cervical
lymph nodes, a typical
location for metastatic
carcinoma from the
nasopharynx.
No. 1 TUMORSCammoun et al.
NASOPHARYNGEAL - 187
TABLE
2. Observed Sites of the Tumor information in Morocco led us to believe that
Lateral walls 62 59% there is a high incidence there also.
Top roof 59 56% I n Europe, the average incidence per
Posterior wall 34 32.50/, 100,000 inhabitants is low: 0.7 for men and
Floor 24 23 % 0.4 for women (these statistics were quoted by
The whole cavum 24 23% Godtfredsen for the northern countries as re-
ported by Muir). Although the frequency is
I t is seldom that the tumor affects a precise place i n
excluding others. I t is mostly riding over several a t the significantly higher in Tunisia than in Eu-
same time. rope, i t does not reach that of the Far East
where the average yearly incidence of naso-
DISCUSSION pharyngeal cancers in Hong Kong is 12.4 per
100,000 inhabitants,' with the same percent-
T h e incidence of nasopharyngeal cancer in age for Formosa and Singapore.
Tunisia seems high, it appears to be a.bout Our peak age curve in comparison with that
2.05 per 100,000 inhabitants in 1 year. This of Hong Kong shows a slight divergence: for
frequency is probably higher inasmuch as Tunisia it is between 50 and 59 years, for
many cases are not recognized o r diagnosed. Hong Kong between 40 and 44 years. T h e
Tunisia is not the only country in North Chinese evidently do not have another peak
Africa with a high incidence. I n Algeria, Man- between 10 and 20 years as we do in Tunisia.
souri et al. observed 105 cancers of the cavum I n this latter younger age group were 14.6%
out of 613 between 1962 and 1967. Sitbon, at of our cases, whereas in the quoted series from
the M. and P. Curie Center of Algiers, re- the Far East there were in Formosa 13 cases
ported 145 between 1950 and 1960. Personal out 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).
188 CANCERJanuary 1974 VOl. 43

FIG. 5. Photomicro-
graph of a nasopha-
ryngeal cancer i n
which the individual
cells have a spindle-
like pattern (~100).

ported 8 out of 974 cases (0.870);10and Ho in
Hong Kong reported no more than 15 out of
1438 (170).7 It seems that the Caucasian child
is more susceptible than the Oriental child.
T h e statistics compiled by Martin and Blady
in the United States corroborate this impres-
sion. They found in a series of 87 cases that
9% were under 15 years of age, and 18%
under 30 years of age. They believe that this
kind of cancer affects the child much more
often that any other kind of cancer of the res-
piratory and digestive tracts. T h e number of
affected men is three times that of women,
which corresponds to the findings of other
authors.709
From the clinical point of view, there does
not seem to be a notable difference in those
countries with a high incidence. Scarcely
known clinically in Tunisia., the nasopharyn-
geal cancer is often discovered too late. T h e
clinical aspect is the same as that seen in the
Far East,7 in Europe,ll and in the United
state^.^ Cervical adenopathy is easily noticed
on the first examination, and should lead to a

FIG. 6. This tumor

has a somewhat syn-
cytial aspect with
scattered lymphocytes
(x250).
No. 1 NASOPHARYNGEAL -
TUMORS C a m m o u n et al. 189

FIG. 7. Photomicrograph of so-called lymphoepithelioma in a female 45 years of age. Note

prominent nucleoli and lymphocytic infiltrate (2766) (X350, W.U. Neg. 73-458).

systematic examination of the cavum. T h e lo- histologic entity based on his study of 32 ne-
cation of the tumor appears most often in the cropsies. T h e lymphoid tissue, intimately
lateral and posterior walls. mixed with the epithelioma spans, does not
From the pathologic point of view, the na- appear in the visceral metastases. YehI7 found
sopharyngeal cancer appears frequently as a that the tumor cells of the lymphoepithelioma
fungating tumor, but also as a diffuse submu- were similar to the cells of the transitional cell
cous infiltration, somewhat deforming the epithelioma described by Cappell.3 He noted
walls. At times the macroscopic examination several biopsies in which the lymphoepithe-
is negative, leading to several successive biop- lioma and transitional cell epithelioma were
sies done “blindly.” situated side by side. He demonstrated with
T h e histopathology of this type of tumor is biopsies taken from people in good health and
debatable. Several classifications have been of all ages, that the lymphoid tissue was al-
proposed. Shu Yeh, after about 1,000 biopsies, ways present, and as such, it was an integral
created a very detailed classification which in- part of the nasopharyngeal mucosa. So it is to
cluded 9 histologic types. After having studied be expected that the epithelioma cells are
this classification as it related to prognosis, he more or less lost in this tissue.
found that survival did not depend on the his- A comparison between the nasopharyngeal
tologic types, and finally retained only two; and lymph node biopsies on the same patient
the classic epidermoid epithelioma, and the shows that the important lymphoid element
undifferentiated epidermoid epithelioma. in the cavum can be absent and substituted by
W e believe that the lymphoepithelioma of a fibrous tissue on the adenopathic level. T h e
Regaud and Schmincke is debatable and does contrary is also true: a fibrous stroma on the
not seem to be an established entity.e~15~17nasopharyngeal level can be lymphoid type in
Teoh argues against the existence of such a the invaded lymph node. Furthermore, in the
190 CANCERJanuary 1974 VOl. 33

FIG. 8. Photomicro-
graph of a tumor
with the characteristic
nuclear appearance
(X400).

same biopsy, the histologic aspect can vary
from one zone to another, seen especially in
the larger fragments.
Besides the lymphoepithelioma debate, the
various histologic types, such as the differen-
tiated epidermoid epithelioma, the undifferen-
tiated epithelioma, and the transitional cell
epithelioma, may all be found in the same ad-
enopathy or i n the same nasopharyngeal
biopsy. 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 0W.U.
, Neg. 73-457).
No. 1 TUMORSCammoun et al.
NASOPHARYNGEAL
three histologic forms in the same lymph node
metastasis. We do not think that these mor-
phological types are unchanging entities.
Surely there must be transitions from one form
to another. Nevertheless, for every pathologist
working in areas where this kind of cancer is
frequent, the diagnosis of a single lymph node
biopsy should point most surely to a primary
nasopharyngeal origin. We have noticed sev-
eral times that study of these metastases led
the pathologist toward the cavum. Indeed,
there exists a certain morphological individu-
ality of this type of cancer. T h e transitional
cell epithelioma as described by Cappell seems
specific for cancer of the nasopharynx. Its fun-
damental histologic aspect is not constructive
but cellular. T h e tumor cells have a clear nu-
clei with sparse chromatin (“holed”), but
showing always one o r two nucleoli. Their cy-
toplasm is clear and granular, and their bor-
ders vague and indeterminate. They form al-
veolar structures resembling protoplasmic
syncytium. T h e stroma can be fibrous, lym-
phoid, granular, or inflammatory. This form of
cancer should be called nasopharyngeal-type
epithelioma because it is not found in any
other part of the body.
Clinically, it is seen often in young adults,
especially in children. Of 24 patients under 20
years of age, 16 showed this histologic type,
while 5 were undifferentiated epitheliomas, (3
of the biopsies were too small to be classified).
These nasopharyngeal type epitheliomas r e p
resented 76% of the cancers among adoles-
cents and children.
T h e anaplastic form (only two cases in our
series), is often difficult to distinguish from re-
ticulum cell sarcoma. T h e evolution of the
disease in our two cases showed that they were
true epitheliomas.
Other malignant tumors of the cavum are
rare. We had only two adenocarcinomas, six
hematosarcomas, and one plasmocytoma.
Various authors have noted the influence of
race with regard to this tumor: American au-
thors have reported a high incidence among
American-born Chinese.16 T h e Mongolian
Race seems to be especially predisposed, so i t
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1. Bailar, J.: Nasopharyngeal cancer in white popu-
lations-A world-wide survey. I n Cancer of the Naso-
pharynx: A symposium Organized by the International
Union Against Cancer, monograph series, vol. 1, C. S .
Muir and K. Shamugaratnan, Eds., Copenhagen,
Munksgaard, 1967.
- 191
is difficult to explain why cancer is so scarce in
Japan,lu and why in Tunisia, which is inhab-
ited by Caucasian people, i t is so frequent.
Bailar thinks that the environmental factor
combined with the racial factor might explain
this frequency.1
T h e discovery of the high incidence of naso-
pharyngeal cancer in Tunisia raises an etio-
logic problem, and the hypotheses advanced
to date have not explained our findings. Simi-
larly, neither the racial nor the environmental
factor explain i t satisfactorily. Recently, G. de
T h e demonstrated a type of herpes virus seen
in certain cells of culture tissue of nasopharyn-
geal carcinoma in China. This suggests the
possibility of a viral basis which better ex-
plains the frequency of this cancer among
such diverse populations.
SUMMARY
This 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.
T h e average age of the patients was 44.6
years. Two peaks were noticed on the age
curve; between 50 and 59 years, and between
10 and 19 years (14.6‘0/, were under 16). There
was a clear predominance of males (102 men,
41 women). T h 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 distribution
showed 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 type
of nasopharyngeal epithelioma often seen in
young patients. There did not seem to be a
notable difference between the epithelioma of
the cavum in Tunisia and that of Southeast
Asia, but there was a higher frequency among
children in Tunisia. T h e racial factor did not
seem to be important. A type of herpes virus
might be the origin of this kind of cancer.
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