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Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016
Pernicious Anaemia with Gastric Carcinoids
Shaik Jani Basha1, NR Shetty2, Harshad Devarbhavi3
Abstract
We report the case of a 42 year male with history of chronic anaemia who
was found to have pernicious anaemia with beta thalassemia trait and had
on esophago-gastric-duodenoscopy, gastric carcinoids with gastric atrophy.
Pernicious anaemia and gastric carcinoids occurring simultaneously in a
single individual is rare. Our case emphasises the need for esophago-gastricduodenoscopy in cases of pernicious anaemia.
Introduction
B
oth pernicious anaemia and
gastric carcinoids occurring
simultaneously in a single individual
is rare. Our case is probably the first
one from India.
Case Report
A 4 2 ye a r m a l e p r e s e n t e d w i t h
p r o g r e s s i ve s y m p t o m s o f f a t i g u e
of 6 months duration. He gave no
history of any other symptom including
hematemesis or malena. His past
h i s t o r y wa s s i g n i f i ca n t f o r se ve r e
anaemia (Hb-2.9) 5 yrs ago for which he
had received blood transfusions. In the
intervening period he was apparently
well. Six months before admission he
was operated for deep vein thrombosis
(details were not available). Physical
examination and systemic examination
was unremarkable except for pallor.
Laboratory investigations showed
the following: haemoglobin – 4.6 gm/dl
(13-16 gm/dl), white blood cells– 6,500/
µL (4000-11000/µL), platelet count –
172,000/µL (150,000-400,000/ µL), serum
ferritin- 234.67 ng/ml (12-300 ng/mL),
iron– 136.6 ug/dl (65 to 176 μg/dL),
total iron binding capacity– 250.3 ug/
dl (240–450 μg/dL), unsaturated iron
binding capacity– 113.7 ug/dl (150-375
ug/dl), vitamin B12- 63.27pg/dl (200-900
pg/dl), serum folate - 15.49 ng/dl (3.6-20
ng/dl).
Peripheral smear (Figure 1) showed
marked anisopoikilocytosis with
admixture of microcytic hypochromic
red cells, macrocytes including
macroovalocytes and hypersegmented
polymorphs. He underwent esophagogastric-duodenoscopy for cause of
anaemia which showed multiple tiny
nodules (~5 mm) with summit erosions
suggestive of gastric carcinoids (Figure
2). Gastric mucosa was also remarkable
for prominent sub-epithelial vessels
suggestive of gastric atrophy (Figure
3). Endoscopic gastric nodule biopsies
obtained showed enterochromaffin-like
cell hyperplasia which was positive
for chromogranin and synaptophysin
(Figures 4 and 5) thereby confirming
gastric carcinoids or neuroendocrine
tumour.
He underwent further investigations
including anti parietal cell antibody
and anti-intrinsic factor antibody
w h i c h we r e b o t h p o s i t i ve . S e r u m
chromogranin A levels were 227.5 mg/
ml (36.4 µg/L). Serum gastrin level was
1597 pg/ml (0-200 pg/ml). Intrinsic
F a c t o r B l o c k i n g A n t i b o d y ( I F B A)
was 15.3 (equivocal). Haemoglobin
electrophoresis was suggestive of beta
thalassemia Trait and HbA2 was 5.6%
(1.5-3.1%).
A diagnosis of severe vitamin B12
deficiency secondary to pernicious
anaemia with atrophic gastritis
and gastric carcinoid was made. he
was treated with daily injection of
methylcobalamin 1 mg intramuscular
for a week followed by weekly injection
for a month and then monthly injection.
Discussion
Pe r n i c i o u s a n a e m i a 1 i s a r a r e
autoimmune disorder which is common
in African or European population 2 but
rare in the Indian population. There
is no clear data available regarding
the incidence of pernicious anaemia
in Indian population although it is
354 per 1,00,000 population in Southwestern American Indians.3 It is
known that patients with pernicious
anaemia have a higher risk to develop
gastrointestinal malignancies such
as gastric adenocarcinoma, carcinoid
tumours, or oesophageal squamous
cell carcinoma. 4 Our case was one such,
with concomitant pernicious anemia
and gastric carcinoids.
As the gastric nodules were small
( ~ 5 m m ) e n d o s c o p i c r e s e c t i o n wa s
not recommended. Instead regular
surveillance was planned. Our patient
also appeared to have type I gastric
carcinoid which is characterized by the
triad of hypergastrinemia, the presence
of anti-parietal cell antibodies and
macrocytic anaemia. The other two
types are as follows: type II develops
in patients with combined Multiple
Endocrine Neoplasia type 1 and the
Zollinger–Ellison syndrome, and type
III is sporadic.5 The incidence of
metastases is less than 5%. 6 Another
concern is the development of
concomitant gastric adenocarcinoma,
which was reported to occur in up
to 6% of patients with type 1 gastric
carcinoid tumours. 7 Therefore regular
annual endoscopic examination was
recommended to our patient. The
American Society for Gastrointestinal
Endoscopy recommends a single
endoscopic evaluation at the diagnosis
of pernicious anaemia. 8 This is largely
to confirm gastritis and rule out
gastric carcinoid and other gastric
cancers, since patients with pernicious
anaemia are at increased risk for such
cancers and to ensure that no single
lesion is enlarging. Gastric resection
is recommended for any large lesions
>1.5 to 2 cm or lesions that have deeply
penetrated the stomach wall into the
submucosa or muscularis. 9 Antrectomy
which leads to the disappearance of
hyperplastic G-cells, is sufficient to
reduce circulating gastrin to a level
1
Resident, 2Consultant, Dept of General Medicine, 3Consultant, Dept of Gastroenterology, Kokilaben Dhirubhai Ambani Hospital
and Research Centre, Mumbai, Maharashtra
Received: 30.09.2014; Accepted: 10.06.2015
Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016
Fig. 1: Peripheral smear H and E stain:
hypersegmented polymorphs
Fig. 3: OGD scopy shows thin subepithelial blood vessels
suggestive of atrophic gastritis
77
Fig. 5: Chromogranin A positive
enterochromaffin-like cell
hyperplasia
References
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Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide
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2. Wun Chan JC, Yu Liu HS, Sang Kho BC et al. Pernicious
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3. Sievers ML, Metzger AL, Goldberg LS, Fudenberg HH.
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Fig. 2: Gastric nodule of 6 mm size
with erosions at its summit
suggestive of gastric carcinoid
t h a t do e s n o t p r o mo t e si g n i f i c a n t
ECL cell hyperplasia, thus leading to
carcinoid regression and inhibiting
additional carcinoid formation. 10,11 If
carcinoid tumours do not regress after
an antrectomy, additional monitoring
is necessary and a total gastrectomy
should be considered. Co-incidentally
our patient had thalassemia trait along
with pernicious anaemia.
In our case response to administered
v i t a m i n B 1 2 wa s s a t i s f a c t o r y a n d
Fig. 4: Synaptophysin positive
enterochromaffin-like cell
hyperplasia
without further blood transfusion
his haemoglobin rose to 12.3 gm/dl.
Given the discrete nature of the gastric
nodules, an endoscopic submucosal
resection may be considered if the sizes
increase to >1.5 or 2 cm.
Conclusion
We emphasise the need for screening
upper GI endoscopy in all patients
of pernicious anaemia to rule out
underlying gastric pathology.
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