T H E AMERICAN JOURNAL OF CLINICAL
PATHOLOGY
Vol. 39, N o . 2, p p . 137-147
F e b r u a r y , 1963
C o p y r i g h t © 1963 b y T h e Williams & Wilkins Co.
Printed in
U.S.A.
LONG SURVIVAL WITH ISLET CELL CARCINOMA OF T H E
PANCREAS
JULES A. KERNEN, M.D., CAPT., USAR; GEORGE SCOFIELD, M.D., CAI-T., USAR; CHARLES
KOUCKY, M.D., CAI-T., USAR; ROBERTO E. BENITEZ, M.D., LT. COU, USA; AND
LAUREN V. ACKERMAN, M.D.
Fifth U.S. Army Medical Laboratory, St. Louis, Missouri; the U.S. Army Hospital, Fori Leonard Wood,
Missouri; and the Division of Surgical Pathology, Washington University School of Medicine, St. Louis,
Missouri
There are conflicting opinions with
regard to the prognosis and length of survival of patients with carcinoma of the
islets of Langerhans. This is in contrast
to the universally poor prognosis of patients with adenocarcinoma of the exocrine
portion of the pancreas, among whom approximately 50 per cent die within 6 months
of the onset of symptoms, 3 and approximately 90 per cent within 1 year after the
diagnosis is made.1 The interpretation of
survival in patients with malignant tumors
of the islets of Langerhans is complicated
by the difficulty in establishing definite
histologic criteria for malignancy in these
tumors. Islet cell tumors should be regarded as malignant only with proved
metastases or with aggressive infiltrative
growth into the surrounding tissue. Capsular
invasion, blood vessel invasion, mitotic
activity, and cellular pleomorphism are
not definite criteria of malignancy; tumors
manifesting these characteristics are of
intermediate type and have been classified
as questionably malignant.22 They are not
further considered here.
Frantz 11 reviewed 5 reported cases of
islet cell carcinoma with proved metastases
and emphasized that all of these cases were
fulminating ones of short duration. Duff8
concluded that islet cell carcinoma of the
Received, May 3,1962; revision received, August
17; accepted for publication November 5.
Dr. Kernen was Chief of the Pathology Division
and Dr. Benitez is Commanding Officer of the
Fifth U. S. Army Medical Laboratory. Dr. Scofield
was Chief of the Laboratory Service and Dr.
Koucky was an Attending Surgeon at the U. S.
Army Hospital, Fort Leonard Wood, Missouri.
Dr. Ackerman is Professor of Surgical Pathology
at Washington University School of Medicine.
Present address of Dr. Kernen and Dr. Scofield
is 102 Medical Arts Building; Birmingham 5,
Alabama.
pancreas is a rather rapidly growing tumor
that spreads quickly from the pancreas
into neighboring structures and metastasizes
widely by way of botli lymphatic and blood
channels. Ackerman and del Regato 1 stated
that islet cell carcinomas usually have a
rapid clinical course and a hopeless prognosis. Mcintosh and associates17 reported
that in functioning islet cell carcinoma
with metastases, death occurs in most
instances a short time after the diagnosis
has been made.
On the other hand, Flinn and co-workers1*
said that islet cell carcinomas are often
slow to grow and slow to metastasize.
Howard and associates, in an extensive
review,16 pointed out that islet cell carcinomas may occasionally be slow-growing
tumors. Porter and Frantz 19 stated that
functioning malignant tumors of the islet
cells are usually rapid-growing and have a
short clinical course, whereas the histologically similar, nonfunctioning islet cell
carcinomas are clinically much more benign,
and the patients live for long periods of
time, even after metastases to the liver
have been documented. They believed,
therefore, that the uncontrollable liyperinsulinism of the functioning islet cell
carcinomas, rather than the site and complications of the primary tumor and its
metastases, leads to the rapid downhill
course.
The histologic pattern of islet cell carcinoma resembles that of the islets of
Langerhans, and the individual cells resemble normal islet cells, except for the
presence of varying degrees of nuclear
pleomorphism and mitotic activity. The
neoplastic cells are arranged in cords or
sheets between delicate vascular channels.
According to the classification of Sieracki
and associates,22 the tumors are described
137
Vol. 89
KERNEN JET AL.
TABLE 1
R E P O R T E D C A S E S OF L O N G SURVIVAL W I T H I S L E T C E L L CARCINOMA
Intractable
Peptic
Ulcers
Age
HyperSex insulinism
Brunschwig and
co-workers 5 - 7
32
M
Yes
No
Frantz 1 2
69
M
No
No
Breslin 4 and
Howard and
co-workers 1 6
Nadal 1 8 and
Whipple 2 6
35
F
No
No
53
F
No
No
Sailer and
Zinninger 20
40
F
No
Yes
Nadal 1 8
48
F
No
No
Zollinger and
co-workers 2 6 , 27
B a u m g a r t n e r and
Reynolds 2 *
19
F
No
Yes
67
F
Yes
No
Warren 2 4 *
11
F
No
No
Warren 2 4
Adult
Ellison 9
57
F
No
Yes
Shaw 21 *
49
M
Yes
No
M c i n t o s h and
co-workers 17
35
M
Yes
No
Our Case 1
52
M
Yes
No
Author
No
Duration of Symptoms
before Diagnosis
Survival after Pathologic Evidence of
Islet Cell Carcinoma
Died—51 mo. after biopsy of prim a r y tumor, 47 mo. after resection (infiltrated stomach and
j e j u n u m ) , 16 mo. after biopsy of
hepatic metastases
Died—6 yr. after biopsy of hepatic
metastases (primary u n k n o w n ) ;
p r i m a r y found a t autopsy
10 mo.—pruritus, Alive—4 yr. after biopsy of nonresectable t u m o r (metastases in
jaundice
lymph node)
2 mo.—pain, weight Died—10 yr. after resection (infilt r a t e d common bile d u c t ) , 5 yr.
loss
after hepatic metastases evident
clinically (biopsy and autopsy refused)
8 yr.—abdominal Died—46 mo. after partial pancreatectomy (lymph node metaspain; 2-3 yr.—
tasis), 3 mo. after biopsy of heabdominal mass
patic metastasis
None—discovered
Died—8 yr. after pancreaticoduoat cholecystecdenectomy (diagnosis of islet cell
tomy
" a d e n o m a " ) , 3 mo. after biopsy
of hepatic metastasis
3 yr.—abdominal Alive—5 yr. after resection of prim a r y (metastasis in lymph node)
pain
8 yr.—dizzy spells Died—3 yr. after partial pancreatectomy (metastases in lymph
nodes), 1}^ yr. after biopsy of
hepatic metastases
3 mo.—abdominal Alive—S]/2 yr. after pancreaticoswelling and pain
duodenectomy
(invaded
duodenum)
Died—5 yr. after pancreaticoduodenectomy
10 yr.—epigastric Died—4 yr. after, partial pancreatectomy (diagnosis of " a d e n o pain
c a r c i n o m a " ) ; autopsy revealed
hepatic metastases of islet cell
carcinoma (slides of primary reviewed and diagnosis changed)
Manj r years—syn- Alive—8 yr. after partial pancreacope; 2-3 yr.—
tectomy (lymph node metasabdominal pain
tases)
10
yr.—syncope, Alive—15 yr. after resection, 5 yr.
after first of 3 excisions of hepatic
convulsions
metastases
Died—9 yr. after resection, 9 mo.
2 yr.—syncope
after biopsy of hepatic metastases
5 mo.—syncope
Feb. 1968
LONG SURVIVAL WITH ISLET CELL CARCINOMA
139
TABLE 1—Continued
Intractable
Peptic
Ulcers
Age
IfyperSex insulinism
Our Case 2
58
F
No
Yes
Our Case 3
35
M
No
No
Author
Duration of Symptoms
before Diagnosis
5 yr.—anemia, abdominal
pain,
rectal bleeding
6 yr.—hematemesis, abdominal
pain
Survival after Pathologic Evidence of
Islet Cell Carcinoma
Died—103^ yr. after pancreaticoduodenectomy; autopsy revealed
hepatic metastases
Alive—13 yr. after partial pancreatectomy; 9 mo. after biopsy of
hepatic metastases
Follow-up brought up to date by means of personal communication from the author.
as having an "islet pattern" if the cords of
neoplastic cells between the vascular channels are 1 to 4 cells in width, and as having a
"basaloid" pattern when the cords or sheets
are 5 or more cells in width. Characteristically, there are foci of hyalinized stroma.
Although blood vessel and lymphatic
invasion may be present, metastases or
aggressive infiltrative growth into surrounding tissues are the only definitive
criteria of malignancy.
A review of the literature has revealed
13 individual case reports of long survival
with histologically proved islet cell carcinomas. These are summarized in Table
1. We are adding 3 additional case reports
of patients with islet cell carcinoma who
survived for many years. These 3 are
summarized at the end of Table 1.
REPORTS OF CASES
Case 1
1:1. H., a 52-year-old white man, was
admitted to Barnes Hospital in June of
1933. Be complained of a 2-year history
of frequent painless episodes of loss of
consciousness. He had learned to avert
the attacks, when he felt them impending,
by drinking coffee with sugar or a Coca
Cola. He frequently became incontinent
and often suffered injuries by falling during
these attacks. In recent months, the attacks had increased in frequency, sometimes
several occurring in 1 day. He also noted
some loss of memory and progressive generalized weakness, accompanied by headaches and joint pain. His family history
was not contributory. Physical examination
was unremarkable.
Two attacks characterized by unconsciousness, incontinence, sweating, and
clonic movements of the head and extremities occurred during the first day of
hospitalization. Blood sugars obtained
during these attacks were found to be 15
mg. per 100 ml. and 22 mg. per 100 ml.,
respectively. The attacks were terminated
in 30 sec. by means of administering 6
ml. of 50 per cent glucose intravenously.
Further repetition was averted by means
of carbohydrate feedings every 2 hr. A
glucose tolerance test again revealed fasting
hypoglycemia that reached a peak of 131
mg. per 100 ml. in 3 hr. and thereafter
returned to low levels. Spinal fluid sugar
was 47 mg. per 100 ml., and proteins were
78 mg. per 100 ml. Laboratory studies were
otherwise normal.
On July 6, 1933, an abdominal exploration was performed. A 10-cm. mass was
removed from the head and body of the
pancreas. The liver appeared normal.
No gross evidence of extension or metastasis
was seen. The patient's postoperative course
was unremarkable and was not punctuated
by any hypoglycemic attacks. All multiple
blood sugars were higher than 90 mg. per
100 ml. The patient was discharged on the
thirtieth postoperative clay, remarkably
improved.
Pathologic examination of the tumor
revealed that it weighed 500 Gm., was
encapsulated, and grossly appeared to have
been completely removed. It varied in
color from yellow-gray to purple. On cut
140
KERNEN ET
surface, the tissue was of 2 types. In some
areas, it was soft and homogeneous, and
in other areas it was calcified and hard.
Microscopically, the cells resembled islet
cells and were in an islet pattern in some
areas and a basaloid22 pattern in others
(Fig. 1). It was later revealed that rare
cells contained cytoplasmic granules that
stained with aldehyde-fuchsin. There were
large hyaline areas of stroma between the
cells, especially in areas manifesting an
islet pattern. Giant cells and cells with
large hyperchromatic nuclei were seen
frequently. Mitotic figures were rare.
Lymphatic vessel invasion was present.
Although a diagnosis of islet cell adenoma
of the pancreas was made, it was thought
at the time that there might be a low grade
malignancy in view of the occurrence of
clumps of tumor cells in several blood
vessels.
After the surgery in 1933 the patient
remained in good health for 8 years, until
July of 1941, when hypoglycemic attacks
were again experienced; they now occurred
once or twice a week. On the patient's
readmission to the hospital, fasting blood
sugars were 44 mg. per 100 ml. and 21 mg.
per 100 ml. An exploratory laparotomy was
performed on December 13, 1941. A large
mass was found at the site of the pancreas,
from which tissue for a biopsy was removed.
Biopsies were also performed on several
liver nodules. The tumor of the pancreas
grossly infiltrated the surrounding tissue
and could not be removed. The biopsy
from the pancreas revealed recurrent islet
cell carcinoma; the liver nodules were
metastatic tumor of similar appearance.
The original tumor was reviewed, and the
diagnosis changed to islet cell carcinoma.
The metastatic tumor appeared more
anaplastic than the primary tumor that
had been removed 8 years previously;
there were wide variations in nuclear size,
giant nuclei, and considerable mitotic
activity.
The patient was discharged after an
uneventful postoperative course. He experienced no further episodes of hypoglycemia; the reason for this is unknown.
He died in 1942, 9 years after excision of
Vol. 39
AL.
the primary pancreatic tumor and 9 months
after biopsy of the metastatic tumor. An
autopsy was not performed.
Case 2
F. H., a 58-year-old white woman, was
first admitted to Barnes Hospital in August
of 1943. She reported a 5-year history of
anemia, cramping abdominal pain, rectal
bleeding, and a 40-lb. weight loss. The
rectal bleeding and weakness had become
more severe during the 6 to 8 months prior
to admission. Her appetite had become
poor. A gastrointestinal series of tests made
elsewhere, 9 months before admission, was
said to have been negative. Liver and iron
therapy had been unsuccessful, but the
weakness was relieved by blood transfusions. She had no symptoms of hypoglycemia.
Physical examination revealed a very
pale woman. There was an irregular 6-cm.
mass palpable in the right upper abdominal quadrant. I t was firm, not mobile, and
discrete from an apparently nonenlarged
liver. Pelvic and rectal examinations were
unremarkable, as was the remainder of
the physical examination. The hemoglobin
was 7.7 Gm., and the white blood cell count
was 5000. Urinalysis was negative, and
stool was negative for occult blood. Blood
sugar determination was not made preoperatively; other laboratory studies were
unremarkable. Proctoscopic examination
was negative. A barium enema revealed a
filling defect at the hepatic flexure and
complete obstruction to retrograde filling.
On August 31, 1943, the patient's abdomen was explored, and a firm mass was
exposed in the head of the pancreas. Most of
the pancreas was resected, together with
the entire duodenum, the distal half of the
stomach, and the common bile duct.
Gastrojejunostomy, cholecystojejunostomy,
and pancreatojejunostomy were performed.
The postoperative course was uneventful
except for slight icterus and atelectasis.
Postoperatively, the blood sugar was 83
and 85 mg. per 100 ml. on 2 occasions.
The patient was discharged in October
1943.
Pathologic examination of the stomach
^V''i>
-.ill.' ' ??. ' ^K»flB»^~*'?*^S
l r io. 1 (upper). Case 1. Basaloid pattern in the primary islet cell carcinoma of the pancreas. Hematoxylin and eosin. X 140.
Kia. 2 (lower). Case 2. Islet pattern in the primary islet cell carcinoma of the pancreas. Hematoxylin
and eosin. X 140.
141
142
KERNEN ET
was unremarkable. Distal to the ampulla
of Vater, in the duodenum, was a deep,
punched-out ulcer crater, 1.5 cm. in diameter. It had a necrotic base that was
continuous with a large, firm, nodular,
well encapsulated mass in the head of the
pancreas. The cut surface of this mass was
gritty, granular, and gray-pink, and was
arranged in lobules separated by septums of
thin connective tissue. There was no evidence of gross extension beyond the capsule,
and the tumor appeared grossly to have
been completely removed. The common bile
duct ran through the tumor; however, it
was not occluded, and the tumor did not
appear to have invaded the wall of the duct.
Microscopically it was an islet cell tumor.
The cells in most areas were arranged in
basaloid22 or islet pattern (Fig. 2); in a fewsmall foci, a tubular pattern was evident.
In some areas, the cells were more anaplastic
than in others; there was cellular and
nuclear variability and more frequent
mitoses in these areas. Aldehyde-fuchsin
stain for beta granules later proved to be
negative. Extensive hyalinized stroma was
present. There were small scattered foci of
necrosis and hemorrhage. There was focal
invasion of lymphatics and blood vessels,
and the capsule was also invaded; the mass
was originally diagnosed as a possibly
malignant islet cell tumor.
The patient was well for 9 months, when
she again had such symptoms of ulcer as
epigastric pain, weight loss, fatigue, and
melena. She was admitted a second time
in May of 1945. Examination revealed a
hard, egg-sized mass palpable in the epigastrium. Fasting blood sugar was 68 mg.
per 100 ml. At operation the mass was
found to be matted omentum with fat
necrosis. There was a 10-cm. marginal
ulcer at the gastrojejunal anastomosis.
The remaining pancreas was normal. A
lymph node biopsy was performed; there
was no gross or - microscopic evidence of
jtumor. Partial gastrectomy and another
Igastrojejunostomy were, performed. Nineteen months later, in January 1947, the
patient was hospitalized once more, having
again developed an ulcer at the gastrojejunal anastomosis. After resection of the
AL.
Vol. 39
ulcer and part of the remaining stomach, a
new gastrojejunostomy with subdiaphragmatic vagotomy was performed; no tumor
was found. During the ensuing years the
patient's weight fell to 80 lbs., and she
developed pancreatic insufficiency with
malnutrition and diabetes mellitus. She
was readmitted in June of 1949 for chills,
fever, and jaundice, secondary to cholangitis, which subsided very slowly. Blood
sugar was 206 mg. per 100 ml., and a diabetic regimen was instituted.
She was again hospitalized in August of
1953 because of recurrent chills, fever,
weakness, and malnutrition. She also developed a severe urinary infection resulting
from Proteus. The liver was enlarged, and
a large irregular mass was palpable in the
right upper abdominal quadrant. This was
believed to be recurrent tumor, but no
biopsy was performed. Stools were fatty
and bulky. The final hospital admission was
in January of 1954. It was necessitated by
repeated episodes of chills and fever, during
which the temperature rose to 105 F. On
admission, the patient was found to have a
pneumonitis of the right lower lobe and
was treated with penicillin. Slie deteriorated
rapidly, became very weak, and developed
a foul diarrhea, which was interpreted as
evidence of severe pancreatic insufficiency.
Physical examination revealed a nodular
enlarged liver. Fasting blood sugar was
550 mg. per 100 ml., and nonprotein
nitrogen, 160 mg. per 100 ml. The patient
became increasingly febrile and weak and
died on January 29, 1954, 1Q]4, years after
excision of the primary islet cell carcinoma.
Autopsy revealed a wasted, elderly white
woman. The liver weighed 2700 Gm. and
extended to the level of the iliac crest. It
contained many tumor nodules, varying in
size from a few millimeters to several
centimeters. The intrahepatic biliary tree
was greatly dilated and contained stones
and pus. The microscopic appearance of
the tumor in the liver was similar to that of
the primary islet cell carcinoma removed in
1943. Aldehyde-fuchsin stain revealed rare
beta granules in the cytoplasm of the tumor
cells. The cholecystojejunostomy was intact
and patent, but distal to the cystic duct in
•
**%•
''',!
'«<*!
vfl
Ik
FIG. 3 (upper). Case 3. Perineural lymphatic invasion associated with the primary islet cell
carcinoma of the pancreas. Hematoxylin and eosin. X 300.
FIG. 4 (lower). Case 3. Metastatic islet cell carcinoma in the liver. Hematoxylin and eosin.
X 140.
143
144
K E R N E N ET
the remnant of the common bile duct was a
2-cm. stone. Sections of the liver manifested
severe acute and chronic cholangitis. There
was no evidence of recurrent tumor in
the region of the pancreas; metastases were
confined to the liver.
Case 3
M.M., a 35-year-old white man, was
admitted to Barnes Hospital in March
1948 for evaluation of a 6-year history of
repeated episodes of hematemesis and
abdominal pain. The volume of blood
vomited never had exceeded 1 cupful.
Nevertheless, he had received a total of
5 blood transfusions during this period.
Numerous x-ray studies had been negative.
During one of the bleeding episodes in
May 1945, he also had jaundice, chills,
and fever. He had lost 30 lb. in weight in
the previous 3 years. He had no symptoms
of hypoglycemia.
Physical examination revealed a palpable
mass below the left costal margin, which
was thought to be the spleen. The liver was
palpable approximately 2 cm. below the
right costal margin. There was slight
tenderness in the epigastrium, the left
upper quadrant, and the left costovertebral
angle. Laboratory studies were within
normal limit's, except that gastric analysis
revealed 66 mEq. of free acid per 12 hr.;
blood sugar was 98 mg. per 100 ml., and
amylase, 133 mg. per 100 ml. Barium enema
revealed a filling defect at the splenic
flexure of the colon. There was no radiologic
evidence of esophageal varices or of any
gastric or duodenal lesion. At operation in
March of 1948, a mass involving the tail
of the pancreas, the splenic flexure of the
colon, the left adrenal gland, and the spleen
was remove'd en bloc. No cause for the
hematemesis was found. The postoperative
course was uncomplicated.
Pathologic studies revealed extensive
fibrosis binding together the colon, pancreas,
and left adrenal gland. This was secondary
to acute and chronic diverticulitis of the
colon; however, within the tail of the
pancreas there was a 2-cm. area of induration with poorly denned margins. Microscopic examination of this area revealed an
AL.
Vol. 89
infiltrating carcinoma in an area of fibrosis
and atrophic acini. There was considerable
variation in nuclear size, and some of the
nuclei were large and hyperchromatic;
mitotic activity was slight. There were
many areas of perineural lymphatic invasion (Fig. 3); no metastases were found
in the lymph nodes, and the tumor did not
extend beyond the pancreas. At the time,
a pathologic diagnosis of adenocarcinoma
of the pancreas was made.
During the interval between 1948 and
1960, the patient was in good health except
for the development of mild diabetes
mellitus, controlled by diet and later by
administration of Orinase. During this
period he had no further episodes of hematemesis and no further abdominal pain.
In June of 1950, a small postoperative
ventral hernia was repaired. During this
operation the peritoneal cavity was explored, and no evidence of recurrent tumor
or of peptic ulcer was found.
During the summer of 1960, the patient
began to have attacks of pain in the right
upper quadrant that lasted for 3 or 4 days.
He had chills and fever, but no jaundice
or change in color of stool or urine. He was
admitted to the U. S. Army Hospital, Fort
Leonard Wood, Missouri, in October 1960,
because of this pain. He denied any episodes of weakness or fainting spells. Laboratory tests were normal except for blood
sugar, which was 210 mg. per 100 ml.
Physical examination revealed a thin white
man. A tender liver was palpable 3 cm.
below the right costal margin. A gastrointestinal x-ray series revealed evidence of a
focal mucosal lesion of the lesser curvature
of the stomach, thought to be either a gastric
ulcer or gastric carcinoma.
On October 18, 1960, an exploratory
laparotomy was performed. There were
multiple peritoneal adhesions. The stomach
was opened, and no abnormalities were
seen. The gallbladder was unremarkable.
After multiple adhesions were lysed, 3
large hard nodules were felt in the liver,
involving both lobes; tissue for biopsy was
removed from 1 of these. Examination of
the duodenum revealed no abnormality.
There was no evidence of recurrent tumor
Feb. 1963
LONG SURVIVAL WITH ISLET CELL CARCINOMA
145
Hospital since 1948; this would suggest
that a high percentage of cases of islet cell
carcinoma may survive for long periods.
It must be emphasized that the periods
of survival reported extend only from the
time of pathologic proof of the existence
of the islet cell carcinoma. Many of these
patients had symptoms, such as hypoglycemia or abdominal pain, for long
periods, even years, before the tumor was
found and studied pathologically. This
suggests that the true length of survival
with tumor may be even longer than indicated. In none of our 3 cases was there any
pathologic evidence of multiple islet cell
tumors in the pancreas that could conceivably complicate interpretation of survival data.
In addition to surviving from 3 to 15
years after pathologic proof of the existence
of an islet cell carcinoma, several of the 13
patients reported in the literature lived for
long periods of time with known hepatic
metastasis, 1 for 6 years,12 and 1" still
alive 5 years after the first of 3 surgical
excisions of hepatic metastases. One of our
patients (Case 3) was still alive and feeling
very well 9 months after a biopsy of liver
DISCUSSION
metastasis.
These 3 cases of long survival with islet
It has been suggested that, in cases of
cell carcinoma of the pancreas are added long-term survival with islet cell carcinoma,
to 13 others previously reported in the the tumors are nonfunctioning ones,19
literature and outlined above. All 13 pa- and that patients with hyperinsulinism die
tients survived for at least 3 years; the more rapidly because of its debilitating
longest previously reported survival follow- metabolic effect. Four of the 13 cases from
ing histologic proof of an islet cell carcinoma the literature were associated with clinical
was 15 years.17 Six of the 13 were still alive hyperinsulinism,2, 6> 17,21 including that of
when their cases were reported in the litera- the man who is still alive and well, but
ture, including the one who survived for having persistent hypoglycemic attacks,
15 years. Follow-up data on these cases 15 years after removal of the primary tumor
was brought up to date by personal com- and 5 years after the first of 3 operations
munication with the authors; one of the for removal of hepatic metastases. One of
patients has died since his case was origi- our cases (Case 1) was a functioning islet
nally reported.2 Two of our 3 new patients cell carcinoma with hyperinsulinism; the
died 9 years and 10}^ years, respectively, patient died 9 years after removal of the
after excision of the primary tumor in the primary tumor. These cases would indicate
pancreas. The third patient is still alive and that not even a functioning islet cell carfeeling well 13 years after excision of the cinoma with hyperinsulinism is incomprimary tumor. It is of interest to note that patible with survival for many years.
only 2 other cases of proved islet cell
One of our cases (Case 2) represents an
carcinoma have been diagnosed in the
example of the Zollinger-Ellison syndrome—
Surgical Pathology Laboratory of Barnes
in this instance, a nonfunctioning islet cell
in the region of the pancreas. The postoperative course was unremarkable. In
November of 1960, the patient had one
episode of pain in the right upper quadrant
associated with fever.
The liver biopsy revealed a metastasis
with the typical microscopic pattern of
islet cell carcinoma (Fig. 4). The cells
resembled islet cells and formed compact
sheets of basaloid pattern 22 in most areas.
There was moderate nuclear variation and
mitoses were infrequent; there were many
focal areas of hyalinized stroma. A review of
the old slides of the pancreatic tumor
removed in 1948 revealed that it was similar
histologically to the hepatic metastasis;
the original diagnosis of adenocarcinoma
was changed to islet cell carcinoma. Aldehyde-fuchsin stain on the primary and
metastatic tumor was negative for beta
granules.
In August of 1961, 13 years after excision
of the primary tumor, and 9 montlis after
biopsy of a hepatic metastasis, the patient
remained well clinically, except for the
continued presence of a palpable liver
nodule.
14.6
KERNEN ET AL.
carcinoma associated with intractable peptic
ulceration of the duodenal and jejunal
mucosa, necessitating multiple surgical
procedures. The patient survived for l O ^
years after excision of the islet cell carcinoma. Three of the 13 previously reported
cases of long term survival are also examples of the Zollinger-Ellison syndrome; 9 ' 2 0 ' " in fact, 2 were presented in
papers by the authors whose names have
become eponyms for the syndrome.
In 1 of our cases (Case 3) and 1 case in
the literature, 9 the original pathologic
diagnosis of the primary tumor was adenocarcinoma of the pancreas. The slides of
these tumors were only re-examined years
later, after the histologic appearance of the
metastases was found to be that of an islet
cell carcinoma, and only then were the
original diagnoses of adenocarcinoma realized to be in error, inasmuch as the primary
tumors also fulfilled the histologic criteria
for islet cell tumors, as described above.
In the light of this experience, it would be
of great interest to review all of the cases
of long survival with "adenocarcinoma"
of the pancreas, in order to determine if
some of these tumors might not represent
islet cell carcinomas. Our Case 3 was
previously regarded as the only instance
of 5-year survival with adenocarcinoma
of the pancreas from Barnes Hospital.
Inasmuch as it is now realized that this
was a case of islet cell carcinoma, there are
no 5-year survivals with adenocarcinoma
of the pancreas from Barnes Hospital.
SUMMARY
This paper deals with 3 new cases of
long survival with islet cell carcinoma of
the pancreas. The patients survived after
pathologic evidence of the existence of an
islet cell carcinoma for 9 years, 103^ years,
and 13 years, and the latter patient is still
(August 1961) alive and feeling well, despite
known hepatic metastases. One of the 3 cases
was a functioning carcinoma with clinical
hyperinsulinism. Another occurred in a patient exhibiting the Zollinger-Ellison syndrome; he had severe recurrent peptic ulcers
of the duodenum and jejunum. The third
case was originally misdiagnosed as an
Vol.
89
adenocarcinoma of the pancreas. Thirteen
other cases of long survival, previously reported in the literature, are reviewed. It is
concluded that islet cell carcinoma, both
functioning and nonfunctioning, unlike
adenocarcinoma of the pancreas, may be
compatible with long-term survival, even
in the presence of lymph node or hepatic
metastases.
SUMMARIO IN INTERLINGUA
Iste communication reporta 3 nove casos
de prolongate superviventia de patientes con
carcinoma de cellulas insulari del pancreas.
Le patientes superviveva 9, 103/9, e 13 annos
post le establimento de evidentia pathologic
pro le existentia de un carcinoma de cellulas
insulari. Le tertie vive ancora e se trova ben
al tempore del redaction del presente communication (augusto 1961), indespecto de
cognoscite metastases hepatic. Un del 3 casos
esseva un functionante carcinoma con hyperinsulinismo clinic. In un secunde caso il se
tractava de un patiente exhibiente le syndrome de Zollinger-Ellison. Hie habeva sever
recurrente ulceres peptic del duodeno e
jejuno. In le tertie caso le diagnose original
esseva erroneemente de adenocarcinoma del
pancreas. Dece-tres altere casos de prolongate superviventia in iste condition es revistate a base de lor reportos in le litteratura.
Es concludite que carcinoma de cellulas insulari, functionante si ben que non-functionante, es occasionalmente sed in contrasto
con adenocarcinoma del pancreas ben compatibile con un longe superviventia, mesmo
in le presentia de metastases de nodo
lymphatic o hepatic.
Acknowledgments. We appreciate the aid of the
following physicians in securing follow-up information: D r . G. O. Segrest and D r . John Armstead, Mobile, Alabama (Case 1); Dr. R. Cunliffe
Shaw, Preston, England; 2 1 D r . K e n n e t h Warren,
Boston, Massachusetts; 2 4 D r . Conrad J . Baumgartner, Beverly Hills, California; 2 and D r . R. H .
Breslin, D r . H . G. Pritzker, and D r . William
Anderson, Toronto, Canada. 4
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