Multiple carcinoids in the duodenum, pancreas and stomach accompanied with type A gastritis: a case report.

Abstract

We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy. During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids, respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum. The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case, and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.

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PO Box 2345, Beijing 100023, China World J Gastroenterol 2007 April 21; 13(15): 2247-2249
www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
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Multiple carcinoids in the duodenum, pancreas and stomach
accompanied with type A gastritis: A case report
Takeo Bamba, Shin-ichi Kosugi, Tatsuo Kanda, Toshihiro Tsubono, Yasuo Sakai, Nobuyuki Musha, Noriko Ishihara,
Katsuyoshi Hatakeyama
CASE REPORT
Takeo Bamba, Shin-ichi Kosugi, Tatsuo Kanda, Katsuyoshi
Hatakeyama, Division of Digestive and General Surgery, Niigata
University Graduate School of Medical and Dental Sciences,
Japan
Toshihiro Tsubono, Yasuo Sakai, Nobuyuki Musha, Division
of Surgery, Saiseikai Niigata Daini Hospital, Japan
Noriko Ishihara, Division of Pathology, Saiseikai Niigata Daini
Hospital, Japan
Correspondence to: Takeo Bamba, Division of Digestive and
General Surgery, Niigata University Graduate School of Medical
and Dental Sciences.1-757 Asahimachi-dori, Niigata City
951-8510, Japan. banbantak@msn.com
Telephone: +81-25-2272228
Received: 2007-01-14 Accepted: 2007-02-14
Abstract
We report a case of multiple duodenal, pancreatic, and
gastric carcinoids. A 67-year old woman was admitted
to our hospital for treatment of a duodenal carcinoid.
Laboratory tests revealed that the patient was associated
with macrocytic anemia and hypergastrinemia, and
type A gastritis was shown by gastrofiberscopy.
During surgery, another tumor was incidentally
found in the head of the pancreas. The tumors in the
duodenum and pancreas were completely excised by
pancreatoduodenectomy and immunohistologically
diagnosed as gastrin-and serotonin-producing carcinoids,
respectively. Pathological examination revealed that
in addition to the grossly found carcinoids, there were
subclinical carcinoids, one of which was an endocrine
cell micronest, located in the stomach and duodenum.
The tumors in the duodenum, pancreas, and stomach
showed different characteristics from one another
morphologically and immunochemically. Although no
definitive evidence has been obtained, some sort of
genetic anomaly may have been involved in this case,
and hypergastrinemia due to duodenal gastrinoma may
induce multiple gastric carcinoids.
© 2007 The WJG Press. All rights reserved.
Key words: Carcinoid; Stomach; Duodenum; Pancreas;
Type A gastritis
Bamba T, Kosugi S, Kanda T, Tsubono T, Sakai Y, Musha
N, Ishihara N, Hatakeyama K. Multiple carcinoids in the
duodenum, pancreas and stomach accompanied with type
A gastritis: A case report. World J Gastroenterol 2007;
13(15):2247-2249
http://www.wjgnet.com/1007-9327/13/2247.asp
INTRODUCTION
Gastrointestinal carcinoids are relatively rare tumors and
usually occur singly. According to the organ distribution
of carcinoid tumors as determined by an analysis of 11842
reported cases[1], the frequencies of occurrence of gastric,
duodenal, and pancreatic carcinoids are 8.3%, 11.6%, and
1.1%, respectively. Therefore, the likelihood that multiple
primary carcinoids would occur simultaneously in these
organs is quite low. Recently, researchers have accumulated
clinical evidence of gastric carcinoid associated with type
A gastritis, which frequently leads to multiple tumors[2,3].
We report here a case of multiple primary carcinoids in the
duodenum, pancreas, and stomach that was associated with
type A gastritis. We also discuss the possible mechanisms
underlying the occurrence of multiple carcinoids in our
case with reference to a review of the literature.
CASE REPORT
On June 5, 2001, a 67-year old woman with no subjective
symptoms was admitted to Saiseikai Niigata Daini
Hospital for a detailed examination and treatment of a
duodenal tumor. A submucosal tumor in the duodenum
of the patient had been followed up by a family doctor
since 1997. The patient had a 30-year history of bronchial
asthma treatment but no particular family history of
anemia, hypercalcemia, pituitary tumor, and malignant
diseases. Hematological examination on admission showed
macrocytic anemia (RBC: 230 × 104/mm3; Hb: 8.8 mg/dL;
MCV: 113.0 μm3) with a low vitamin B12 level (below 100
pg/mL). The blood calcium level was normal (9.0 mg/dL).
The fasting serum gastrin level was extremely high (1630
pg/mL). Serum serotonin and urine 5-hydroxyindole
acetic acid concentrations were within the normal range
(63 μg/dL and 5.70 ng/mL, respectively). Gastrointestinal
endoscopy showed a sessile tumor with a diameter of
nearly 18 mm and covered by intact mucosa at the upper
curve of the duodenal bulb, as well as extensive mucosal
atrophy in the fundus of the stomach corresponding
to type A gastritis. The tumor in the duodenum was
diagnosed as a carcinoid by histological examination of
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biopsy specimens. Computed tomography scans showed
no metastasis and no other tumor in the abdomen.
On July 2, 2001, the patient underwent surgery to excise
the duodenal carcinoid. During the operation, however,
another tumor about 1 cm in size was incidentally found
in the head of the pancreas. Pathological examination
using frozen sections revealed that the tumor was an
endocrine neoplasm. Both tumors were completely excised
by pancreatoduodenectomy. The serum gastrin level
returned to normal postoperatively. Presently, the patient
has survived for 47 mo since the surgery with no sign of
recurrence.
Pathological examination of an excised specimen
revealed that the endocrine neoplasm in the pancreatic
head was a carcinoid. Furthermore, a detailed examination
using serial sections revealed that there were four
subclinical carcinoid tumors that were smaller than 2 mm
in size in the antrum and duodenum. Thus, 6 carcinoid
tumors, one of which was endocrine cell micronest
(ECM)[4], were present in the excised specimen (2 in the
duodenum, 1 in the pancreas, and 3 in the stomach).
Histologically, the grossly found tumor in the duodenum
showed an anastomotic ribbon-like appearance, and the
interstitum was composed of enriched vasculature (Figure
1A). The carcinoid in the pancreas showed a palisade-
like arrangement and relatively dense connective tissues
in the intersitium (Figure 1B). On the other hand, the
tumor nests in the gastric carcinoids exhibited a vesicular
appearance (Figure 1C). That is, the carcinoids in the three
organs differed from one another histomorphologically.
Furthermore, we characterized the tumors in the
duodenum, pancreas and stomach by immunohistochemical
analysis using anti-human gastrin polyclonal antibody
(DAKO, Japan) and anti-human serotonin polyclonal
antibody (DAKO, Japan). The tumor cells in the duodenal
carcinoid were strongly positive (Figure 2A) for gastrin
and very weakly positive for serotonin. Conversely, the
carcinoid in the pancreas was weakly positive for gastrin
and strongly positive for serotonin (Figure 2B). On
the other hand, a carcinoid tumor in the stomach was
unequivocally negative for the two hormones. Thus, the
carcinoid tumors in the duodenum, pancreas, and stomach
also showed different endocrinological features from one
another. The pathological and immunochemical features
of the six tumors are summarized in Table 1.
DISCUSSION
We reported a case of multiple carcinoids that showed
different histomorphological and immunohistological
characteristics. Rindi et al[5] have classified gastric carcinoids
into the following three types: (1) those that arise in a
background of type A gastritis, (2) those associated with
Zollinger-Ellison syndrome, usually in combination with
multiple endocrine neoplasia type 1 (MEN1), and (3)
those that occur sporadically. Based on an analysis of 1094
gastric carcinoid cases that were reported in the literature,
the incidence of multiple tumors is 16.7% in patients not
associated with type A gastritis[6]. On the other hand, in
patients associated with type A gastritis, the incidence is
64.0%, which is significantly higher than that in patients
not associated with type A gastritis. The presumed
mechanism underlying the occurrence of multiple gastric
carcinoids in type A gastritis is as follows: a low or no
acid state caused by mucosal atrophy in the fundic gland
region induces hyperplasia of gastrin-producing cells
in the gastric antrum through feedback, which causes
a rise of blood gastrin levels. Then, the unusually and
constantly high levels of gastrin stimulate the proliferation
of enterochromaffin-like (ECL) cells in the stomach. It is
thought that hyperplasia and the subsequent tumorigenic
Table 1 Summary of the pathological and immunohistochemical
features of the six tumors surgically excised
Tumor Site Size (mm) Gastrin Serotonin
Carcinoid
Carcinoid
Carcinoid
Carcinoid
Carcinoid
ECM
Duodenum
Pancreas
Stomach
Stomach
Duodenum
Stomach
14 × 13
15 × 13
1.2
1.8
0.5
≤ 0.1
+++
+ (slightly)
-
NA
NA
NA
+ (slightly)
+++
-
NA
NA
NA
NA: not analyzed; ECM: endocrine cell micronest.
AB
Figure 2 Imunohistochemical staining of carcinoids in the duodenum and pancreas
(× 20). A: Gatrin immunostaining showing a quite positive carcinoid in the duodenum;
B: Serotonin immunostaining showing a strongly positive carcinoid in the pancreas.
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2248 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol April 21, 2007 Volume 13 Number 15
A
C
Figure 1 Histological examination of each carcinoid in three organs. A: Duodenal
carcinoid showing anastomotic ribbon-like formation in the interstitium with
predominant blood vessels and only a small amount of connective tissue (HE, ×
10); B: A palisade-like carcinoid in the pancreas, and a moderate amount of fibrous
connective tissue observed in the interstitium (HE, × 20); C: Vesicular carcinoids in
the stomach (arrow) (HE, × 10).
B

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transformation of ECL cells are the cause of multiple
carcinoids[7,8].
Our case was clinically diagnosed as type A gastritis
with pernicious anemia, and the blood gastrin level
was high (1630 pg/mL). Histological examination of
the excised specimen, however, showed no hyperplasia
of gastrin producing cells in the gastric antrum.
Concerning the hypergastrinemia in the present case,
the relevance of a gastrin-producing tumor in the
duodenum should be taken into consideration. Some
of carcinoids are capable of functioning and producing
gastrointestinal hormones. A duodenal carcinoid tumor
in the present case was unequivocally positive for gastrin
in an immunohistochemical analysis. Moreover, the
hypergastrinemia rapidly remitted after excision. These
findings suggest the possibility that hypergastrinemia in
the present case was caused largely by a gastrin-producing
tumor in the duodenum, that is duodenal gastrinoma.
Interestingly, atrophy in the fundic gland region due to
type A gastritis seemed to prevent the typical symptoms
of Zollinger-Ellison syndrome/gastrinoma, such as
refractory peptic ulcer disease, severe diarrhea and gastric
acid hypersecretion. In the present case, all four carcinoid
tumors in the stomach were small and included ECM. It
is likely that ECL cells in the stomach were constitutively
stimulated and consequently transformed into neoplasms.
On the other hand, the relevance of type A gastritis
and/or hypergastrinemia to the development of pancreatic
or duodenal carcinoids remains unclear. Thus, we should
take the genetic background of multiple carcinoids into
consideration. A MEN-1 type genetic anomaly is known
to cause carcinoid tumors as lesions secondary to (1)
pituitary gland tumors, (2) parathyroid gland tumors, and
(3) pancreatic endocrine neoplasms[9]. The causative gene
(MEN-1) has been identified, and the penetration is said
to reach 99% by 50 years of age in autosomal dominant
inheritance. Although no genetic examination was conducted
in this case, it is unlikely that a MEN-1 type genetic anomaly
was related to the multiple carcinoids because our case had
neither family history nor parathyroid gland lesion, that
has a high occurrence rate (90%-100%) and generally
occurs in youth. However, Imamura et al[10] have recently
reported that endocrine neoplasm occurs frequently
in the duodenum and pancreas in gastrinoma patients
with MEN-1 type genetic anomaly, and that gastrinomas
are immunochemically positive for gastrin in the
duodenum and negative for gastrin in the pancreas. This
endocrinological feature of gastrointestinal tumors in
MEN-1 is in agreement with our case. Because carcinoid
is a relatively rare tumor, the chance of multiple primary
carcinoids occurring simultaneously in three organs is
quite small. Therefore, the possibility that an unknown
genetic anomaly similar to the MEN-1 type anomaly may
be involved in the occurrence of multiple carcinoids is
undeniable.
The mechanism underlying the occurrence of multiple
carcinoids in the present case was discussed from various
perspectives. The specific mechanism of multiple carcinoids
would be established by the accumulation of additional
similar cases in the near future.
ACKNOWLEDGMENT
The authors are grateful to Jun Soga, MD, (Professor
Emeritus of Niigata University) for his scientific advice
and critical review.
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