Chris T. Oeconomopoulos, M.D.
Department of Pediatric Surgery, and the Mallory Institute of Pathology, Boston City Hospital
134
B
EGER1 first described the tumor of theappendix which has come to be known
as argentaffinoma. Since then an increasing
number of cases have been reported in
adults, representing 70’ of all appendiceal
tumors.2 Argentaffinomas of the appendix
are extremely uncommon in children.
Early 4 stated that
argentaffino-mas may occur at any age from 10 days.
Recently authors disputed this dictum
be-cause no references were attached.
Stowens6 states that a striking feature of
the mucosa of the entire digestive tract in
children is the absence of argentaffin cells,
a regular component of the mucosa in the
adult. The youngest child in which he was
able to find argentaffin cells, and even then
quite scattered, was 4 years of age.
From our search in the available
litera-tune we were able to find only five cases of
appendiceal argentaffin cell tumors in the
pediatric age group, two 10-year olds, a boy
and a girl,5 a 12-year-old boy,7 a 9-year-old
boy8 and an 11-year-old girl.9
Although argentaffinomas are rare in
chil-dren, it is probable that some have been
overlooked and that many unreported cases
exist. Because the literature contains few
reports of these tumors in childhood, it
seemed worthwhile to report on three cases
of appendiceal argentaffinomas. These were
identified in a review of the pathologic
ma-terial from a series of 1,799 appendices
re-moved from children under the age of 14
years at the Boston City Hospital from 1940
to 1960; an incidence of 0.16%.
Case
CASE REPORTS
G.A., a 12-year-old white male, was
ad-mitted to the hospital because of severe right
lower quadrant pain, nausea, vomiting and
diarrhea of 30-hours duration. He had had
re-current episodes of abdominal pain for 5 years
as often as six times a month and had been
admitted to Boston City Hospital on two
previous occasions with this complaint.
The family history was noncontributory.
Physical examination revealed a
healthy-appearing child in no acute distress with
nor-mal skin colon, blood pressure 110/60, pulse
112, respirations 24, and temperature 102#{176}F
(38.9#{176}C). Except for this elevation of
tern-perature, the pertinent physical findings were
limited to the abdomen. It was soft but there
was marked tenderness localized to the right
lower quadrant. Bowel sounds were normal.
Rectal examination revealed moderate
tender-ness on the right.
Laboratory examination revealed a leukocyte
count of 5,900/mm3 with normal differential.
Hemoglobin was 13.8 grn/100 ml, urinalysis
was normal.
The diagnosis of subacute appendicitis was
made and an appendectomy performed. The
postoperative course was uneventful.
Pathologic examination revealed an appendix
6 cm long and 2 cm in its greatest diameter.
The senosa was a dull pink-gray with enlarged
blood vessels. On cut section the lumen was
seen to be patent except at the distal portion,
which was filled with a yellow-orange
submu-cosal mass measuring 3 by 5 mm in diameter
and did not appear to involve the muscular
coat. No evidence of ulceration, hemorrhage or
perforation was seen. Microscopically the
le-sion had the characteristics of an argentaffinoma
(Figs. 1-3).
Case 2
J.C., a 13-year-old white male, was admitted
to the hospital for the first time because of
mild penumbilical pain, nausea and vomiting
for 4 days.
The history revealed that he had had right
lower lobe pneumonia a year prior to
admis-sion and upper respiratory infection 10
ADDRESS: 818 Harrison Avenue, Boston 18, Massachusetts.
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5months later. The family history was non-contributory.
Physical examination revealed a rather thin, pale, acutely ill youngster. The blood pressure
was 112/70, pulse 90, respirations 28, and
temperature 102#{176}F (38.9#{176}C). There were bronchial sounds in the right posterior chest. The heart was normal. The abdomen showed
slight distention. There was tenderness with
spasm in the right lower quadrant and bowel
sounds were hypoactive. Rectal examination
revealed tenderness on the right.
Laboratory data included a leukocyte count
of 24,000/mm3 with 90% neutrophils and a hematocrit of 44%. Urinalysis was within nor-mal limits. Chest roentgenogram showed an
area suspicious of old tuberculosis in the right
upper lobe.
A diagnosis of acute appendicitis with
per-foration was made and an appendectomy per-formed. The postoperative course was un-eventful.
On pathologic examination the appendix
measured 7 cm long and 1.5 cm in its greatest
diameter. On cut section a tumor mass was
found near the distal end occluding the lumen
(Fig. 4). It was firm and tan-yellow. Grossly the tumor did not infiltrate any layer.
Micro-scopically the mass had the typical picture of argentaffinoma without invasion.
Case 3
R.P., a 9-year-old Negro female, was
ad-mitted to the hospital because of abdominal pain, nausea and vomiting of 5-days
dura-tion. There was a history of having gnawed
on window sills and wall plaster at the age of
2 years. Three months prior to admission, she
had had an episode of abdominal pain asso-ciated with diarrhea. On the day of admission, she was seen by the family physician who made
a diagnosis of enteritis. The family history was
noncontributory.
Physical examination revealed an acutely
ill girl with a blood pressure of 96/60, pulse
120, respirations 30, and temperature 101#{176}F (38.3#{176}C). The positive findings were limited to the abdomen which was diffusely tender and had no audible peristalsis. On rectal examina-tion a large globular mass could be palpated in the pouch of Douglas.
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tissue. (Phosphotungstic acid-hematoxylin, x 700)
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hemoglo-bin 14 gm/100 ml, urine normal except for 3+
acetone.
A diagnosis of acute appendicitis was made.
The appendix was found to be perforated
and there was generalized peritonitis. Appen-dectomv was performed. The postoperative
course was uneventful.
The appendix measured 6 cm in length; and there was a swelling near the distal end with
perforation proximal to it and the wall was
hemorrhagic. Due to gangrene, the gross archi-tecture of the distal end was disturbed. Micro-scopic sections showed the presence of a small argentaffinoma in the tip.
DISCUSSION
Gross and Microscopic Appearance
Gosset et al.b0 introduced the term
argentaffinoma because of the affinity of the
cells for silver salts, and they demonstrate
that the Kultchitsky’s cells from which the
tumor springs are topographically most
abundant in the appendix, numerous in the
small intestine, and few in the stomach,
colon and rectum.
Argentaffinomas of the appendix are
usu-ally located in the distal end, producing
nodular bulging of the organ. These tumors
cannot be detected, except by section of the
entire appendix (Fig. 4) and are nearly
always discovered incidentally in the
rou-tine pathologic examination when the
ap-pendix is removed. Argentaffinomas
charac-tenistically form a submucosal, pale yellow,
firm, rubbery mass, which obliterates the
muscularis but may erode the mucosa.
They measured from 0.1 to 1.5 cm or more
in diameter and tend to remain localized.
Histologically they consist of syncytial
masses of moderately mature epithelial
cells, separated by bands of connective
tis-sue
(
Fig. 2) . The cells show poorlyde-fined cytoplasmic borders containing
num-erous acidophilic granules and deeply
baso-philic nuclei, which can be impregnated
by silver. The nests of tumor tissue show
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FIG. 3. The cells of the tumor have a finely granular cytoplasm with deeply basophilic nuclei. (Mallory’saniline-blue, X 1200)
of the cells show vacuolation of the
cyto-plasm by lipoid substance similar to the
ma-terial in the adrenal cortex, which is
respon-sible for the yellowish color.12
Masson13 found that in certain functional
states argentaffin granules might not be
demonstrated. Stout14 explained this
phe-nomenon as due to absence of the
entero-mm
of Erspamer, a substance necessary forthe reduction of silver or chromium salts. In
FIG. 4. Case 2. Both halves of the appendix after longitudinal section. The tumor mass is clearly
our cases routine hematoxyline and eosin,
as well as phosphotungstic
acid-hematoxy-un and Mallory’s aniline-blue stains, were
used. The latter stain sharply demarcates
nuclear details (Fig. 3). It is now generally
recognized that argentaffinomas can be
diag-nosed on morphologic grounds.
Clinical Features, Diagnosis and Treatment
The clinical course of the appendiceal
an-gentaffinoma depends mainly on the size
of the tumor. When the tumor reaches
suffi-cient size to project into the lumen and
produce partial or complete obstruction,
the inflammatory changes of acute or
chronic appendicitis 9 12, 1518 Right
lower quadrant pain, nausea, vomiting and
diarrhea, which occurred in two of our
cases, may be present. The episodes of
diar-rhea in Case 3 was responsible for
obscur-ing the diagnosis of acute appendicitis for
a 5-day period, leading to perforation and
generalized peritonitis.
The correct preoperative diagnosis has
never been made in the reported cases in
children. Even at exploration the lesion can
be easily missed, as happened in all of our
cases.
According to MacDonald19
argentaffi-nomas of the appendix are benign and have
never been known to prove fatal. Systemic
manifestations are extremely unlikely from
appendiceal lesions, and it is important to
differentiate these tumors from the
extra-appendiceal lesions which are usually
ma-lignant and produce an excessive amount
of 5-hydroxytryptamine
(
220-23The presence of excessive serotonin is
clini-cally manifested by patchy areas of
reddish-blue cyanosis of the skin, episodes of
flush-ing, diarrhea and bronchial asthma.24 Biorck
et al.25 were the first to recognize this
en-docrine activity on the part of argentaffin
tumors. They reported a case of a boy 19
years old, in whom cyanosis and pulmonary
stenosis were observed in association with
malignant argentaffinoma. The known
vaso-constrictive action of serotonin may result in
fibrous tissue proliferation within the
endo-cardium.23 In the Boston City Hospital the
cases of congenital pulmonary stenosis
studied by MacDonald et al.26 showed no
lesions similar to those of carcinoid
fibro-stenosis.
Since the liver metabolizes serotonin
(5-hydroxytryptamine) to inactive
5-hy-droxyindoleacetic acid, it is interesting that
the diagnosis of extra-appendiceal
ar-gentaffinomas and metastases from them
may be confirmed by finding abnormal
amounts of 5-hydroxyindoleacetic acid in
the urine.22
The treatment of argentaffinoma of the
appendix in children consists of simple
ap-pendectomy. The prognosis is good. In a
5-year follow-up of two of our cases, there
was no recurrence. The third patient is only
3 months postoperative and is well. X-ray
therapy is not indicated.
Our knowledge is scanty on the malignant
potentialities of these tumors located in the
appendix. That they have appeared to be
benign may be explained by the fact that
they produce early obstruction and
inflam-matory changes in the appendix, leading to
removal prior to metastasis.
SUMMARY
Three cases of argentaffin cell tumors of
the appendix in children are presented. The
condition is rare in childhood.
The correct preoperative diagnosis of
these tumors when located in the appendix
has not been made. They appear to cause an
obstructive appendicitis early in their course.
This results in appendectomy and may
ac-count for lack of metastases in the reported
cases.
The treatment of the appendiceal
car-cinoids consists of simple appendectomy
and the prognosis is the same as for acute
appendicitis.
Acknowledgment
The author acknowledges with gratitude the
suggestions of Drs. John W. Chamberlain,
C. Kenneth Mallory and Richard A.
MacDon-ald in the final preparation of the manuscript;
tumors of the
Sung., 22:568,
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