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Duodenal carcinoid with carcinoid syndrome

Article  in  BMJ Case Reports · January 2014

DOI: 10.1136/bcr-2013-202159 · Source: PubMed

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 Rare disease

CASE REPORT

Duodenal carcinoid with carcinoid syndrome

Ravikiran Naalla, Kamesh Konchada, Odaiyappan Kannappan,
Ramachandra Lingadakai

Department of General
Surgery, Kasturba Hospital,
Manipal University, Manipal,
Karnataka, India
Correspondence to
Dr Ravikiran Naalla,
ravi_2488@yahoo.co.in
SUMMARY
Carcinoid tumours are uncommon well-differentiated
neuroendocrine tumours. Primary duodenal carcinoids
account for less than 2% of all gastrointestinal
carcinoids. Duodenal carcinoids are seldom associated
with carcinoid syndrome. We report a rare case of
duodenal carcinoid presenting as a carcinoid syndrome in
a middle-aged man with upper abdominal pain, hot
flushes, diarrhoea and dry cough. Endoscopy-guided
biopsy and 24 h urine 5-hydroxyindoleacetic acid
(5-HIAA) proved the diagnosis. He was further
evaluated and managed with definitive surgical
treatment.
multiple nodules in the first and second parts of
the duodenum (figure 1). Contrast-enhanced CT
(CECT) of the abdomen showed homogeneously
enhancing long segment wall thickening of the
first, second, third and fourth parts of the duode-
num (figure 2) and there were no hepatic metasta-
ses. The chest X-ray and two-dimensional
echocardiogram were normal. Endoscopic biopsy
revealed duodenal carcinoid and was positive for
chromogranin A.
DIFFERENTIAL DIAGNOSIS
Irritable bowel syndrome, pancreatic islet cell
tumour and pheochromocytoma.

BACKGROUND TREATMENT
Carcinoid tumours are rare and belong to the amine The patient was symptomatic. Multiple tumours
precursor uptake and decarboxylation system of were present in all parts of the duodenum and the
tumours. They represent <1% of the visceral malig- size of the tumour and depth of invasion could not
nancies and gastrointestinal tract carcinoids and reliably predict the presence of lymph nodal metasta-
account for 85% of carcinoid tumours. They com- sis. Hence, the patient underwent Whipple’s pancrea-
monly arise in the small intestine and the terminal ticoduodenectomy and regional lymphadenectomy.
60 cm of ileum is the commonest location. They The pharmacological agents were effective but not
most likely metastatise to the liver or have bulky definitive. The patient did not receive any chemo-
disease to produce the carcinoid syndrome. therapy because its benefits are not proved.
Serotonin, histamine, kinins, prostaglandins and
other hormonally active tumour products are the
humoral mediators of carcinoid syndrome. The duo- OUTCOME AND FOLLOW-UP
denum is an unusual site for the carcinoid tumour, Postoperative stay was uneventful. Serum bilirubin
moreover its association with carcinoid syndrome is gradually settled to normal levels. Histopathological
extremely rare and probably this may be the first evaluation revealed a well-differentiated neuroendo-
case report. crine tumour (NET) (malignant carcinoid) with
metastasis to the supra-pancreatic lymph node. The
CASE PRESENTATION
A 40-year-old man presented with intermittent
upper abdominal pain for 4 months, episodic hot
flushes involving the face and upper chest for
2 months and watery stools 5–6 episodes per day
for 1 month. He had dry cough for 8 days. He had
no comorbid illnesses and the family history was
not significant. He had mild icterus, his blood pres-
sure and cardiac evaluation was normal. Rest of the
systemic examinations did not reveal significant
findings.

To cite: Naalla R,
Konchada K, Kannappan O,
et al. BMJ Case Rep
Published online: [please
include Day Month Year]
doi:10.1136/bcr-2013-
202159
INVESTIGATIONS
The patient had predominant direct hyperbilirubi-
nemia with normal levels of liver enzymes, serum
amylase and lipase were within normal limits and
rest of the haematological and biochemical blood
parameters were within normal limits. Ultrasound Figure 1 Oesophagogastroduodenoscopic image
of the abdomen revealed duodenal wall thicken- showing multiple nodular swellings in the second part of
ing. Oesophagogastroduodenoscopy showed the duodenum.

Naalla R, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202159 1

 Rare disease
Figure 2 Contrast-enhanced CT abdomen axial cut image showing
homogeneously enhancing long segment wall thickening of the
duodenum (surrounded by white arrows).
patient is asymptomatic on 1 year follow-up with no evidence of
recurrence and distant metastasis.
DISCUSSION
Neuroendocrine neoplasms, defined as epithelial neoplasms
with predominant neuroendocrine differentiation, can arise in
most organs. NETs of the digestive system are relatively rare.
These tumours were traditionally referred to as carcinoid and
pancreatic neuroendocrine (islet cell) tumours. The greatest inci-
dence of carcinoids is noted in the gastrointestinal tract
(67.5%), followed by the bronchopulmonary system (25.3%)
and the rest are found in the thymus, liver, pancreas, ovaries,
prostate and kidneys. Within the gastrointestinal tract, most car-
cinoid tumours occur in the small intestine (41.8%), rectum
(27.4%), appendix (24.1%) and stomach (8.7%).1
Primary duodenal carcinoids account for less than 2% of all
gastrointestinal carcinoids.2 The incidence of the duodenal car-
cinoid is the highest in the first part and decreases distally (2nd,
3rd and 4th). The lesions are usually solitary; multiple lesions
involving different parts of the duodenum are rare. In our case,
multiple nodular lesions of varying sizes (3 mm–2.5 cm) were
present in the first and second parts of the duodenum with
thickening of the third and fourth parts of the duodenum
(figure 3). One nodule was close to the ampullary region, which
was suspected to cause elevated bilirubin levels. Although indo-
lent the most common symptoms are jaundice, abdominal pain,
pancreatitis and weight loss,3 two of which were present in our
patient.
The most common systemic manifestation of carcinoid
tumours is the carcinoid syndrome. Serotonin, histamine, kinins,
prostaglandins and other hormonally active tumour products
are the humoral mediators of carcinoid syndrome. Flushing and
diarrhoea are the two most common symptoms, occurring in up
to 73–89%. Diarrhoea usually occurs with flushing. The cardiac
disease is due to the formation of fibrotic plaques (serotonin
mediated) involving the endocardium leading to stenosis and
insufficiency of tricuspid/pulmonary valve ending in heart
failure usually seen in patients with metastatic disease. Less
common clinical manifestations include asthma-like symptoms
and pellagra-like skin lesions (these tumours use tryptophan as
the source for serotonin production, which limits the available
tryptophan for niacin synthesis which results in niacin defi-
ciency). Once the tumour invades the serosa and involves the
retroperitoneum it causes severe desmoplastic reaction leading
to retroperitoneal fibrosis and subsequent urethral obstruction,
2 Naalla R, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202159
Figure 3 Pancreaticoduodenectomy specimen with cut open segment
of the duodenum (white arrows) showing multiple nodules, gallbladder
(black arrow).
peyronie’s disease of the penis, intra-abdominal fibrosis and
occlusion of the mesenteric arteries or veins. In patients with
duodenal carcinoid, carcinoid syndrome may occur in 4%.4 Our
patient had typical features of carcinoid syndrome which is rare.
Occasionally, carcinoid tumours can produce the adrenocortico-
tropic hormone, growth-hormone-releasing hormone and cause
Cushing syndrome and acromegaly, respectively, this distinct
entity is known as atypical carcinoid syndrome.
The neuroendocrine markers, chromogranin A and 5-HIAA,
in serum and urine, respectively, may be useful for the diagno-
sis.5 6 The measurement of 5-HIAA is used most frequently. It
has 73% sensitivity and 100% specificity for carcinoid syn-
drome. The urinary 5-HIAA value more than 9 mg/24 h in
patients without malabsorption and more than 30 mg/24 h with
malabsorption is considered pathognomonic of carcinoid syn-
drome. Our patient had a urinary 5-HIAA of 15.5 mg/24 h
which is high. Serum chromogranin A levels are elevated in
56–100% of patients with carcinoid tumours, and the level
correlates with the tumour bulk. Fasting plasma 5-HIAA, plate-
let 5-hydroxytryptamine (5-HT), urinary 5-HT and urinary
tryptophan (5-HPT) can also be used for the diagnosis of carcin-
oid syndrome. Oesophagogastroduodenoscopy is the most
useful method for diagnosis of the duodenal carcinoid. To
improve the diagnostic index of the carcinoid tumour deeper
and multiple biopsies are required. CECT and MRI do not
usually identify small primary tumours, but may indicate liver
and/or mesenteric metastases.7 Endoscopic ultrasonography
(EUS) can define the tumour size, level of wall invasion and the
presence of regional lymphatic metastases.7 Indium-111 or
metaiodobenzylguanidine scan can identify carcinoid tumours.
Endoscopic removal or surgery is the ideal treatment for duo-
denal carcinoids. Tumours up to 1 cm in the submucosa away
from the periampullary region without lymph nodes metastases
on EUS or CT and no mitotic figures exhibit indolent behaviour
and no metastases. In such cases, endoscopic removal is the pre-
ferred treatment for these lesions.8 9

For tumours of 1–2 cm when the tumour invasion of the duo-
denal wall goes beyond the submucosal layer the best treatment
is transduodenal full-thickness resection5 using laparotomy or
laparoscopy.10 However, regardless of the depth of invasion
tumours smaller than 2 cm correlated with curability by endo-
scopic resection because duodenal carcinoids that were smaller
than 2 cm were not metastatic.11
For carcinoid tumours larger than 2 cm, a full-thickness resec-
tion with a regional lymphadenectomy is recommended, espe-
cially when lymph node involvement detected by EUS/CT/MRI
or mitotic index is higher than two mitotic figures per high-
power field. Ampullary and periampullary duodenal carcinoids
deserve special consideration because they differ clinically, histo-
logically and immunohistochemically from carcinoid tumours
that occur elsewhere in the duodenum.12 Although their rarity
precludes the establishment of any definitive natural history,
these tumours appear to behave unpredictably and might be
viewed as a distinct category of the carcinoid tumour
when treatment options are being considered.11 Compared
with tumours in other duodenal sites, even small (<1 cm)
ampullary and periampullary carcinoid tumours exhibit dis-
tinctly different aggressive behaviour, and may metastasise
early.12 13 Radical surgical treatment of pancreaticoduodenal
resection is favoured.14 Our patient underwent Whipple’s pan-
creaticoduodenectomy and regional lymphadenectomy.
It is important to prevent the occurrence of carcinoid crisis, a
life-threatening form of carcinoid syndrome that may be trig-
gered by tumour manipulation (eg, biopsy and surgery) or by
anaesthesia. Carcinoid crisis results from the release of an over-
whelming amount of biologically active compounds from the
tumour. The predominant symptom is wide blood pressure fluc-
tuations with predominance of hypotension. Administration of
octreotide prior to resection reduces the incidence of carcinoid
crisis.15
Independent risk factors for metastases are described based
on the histopathological features16 like invasion of the muscular
layer, size greater than 2 cm and presence of more than two
mitotic figures per high-power field.
Patients should be followed up by monitoring serum chromo-
granin. Other useful methods are urinary 5-HIAA, EUS, CT,
MRI, somatostatin receptor scintigraphy and occasionally
11C-5-hydroxy-tryptophan (11C-5-HTP) positron emission
tomography.
In patients with liver metastases synthetic analogues of som-
atostatin (octreotide, lanreotide) are now the most widely used
agents to control the symptoms in patients with carcinoid syn-
drome. They stabilise the disease and reduce the growth of
metastases. However, a surgical resection17 and/or cytoreductive
techniques may improve carcinoid syndrome symptoms to
improve the quality of life and increase survival.6
The role of systemic chemotherapy in patients with metastatic
carcinoid is unclear, and year 2012 guidelines from the
European Neuroendocrine Tumor Society recommends against
its use in these patients.18 Consensus-based guidelines from the
National Comprehensive Cancer Network suggest that antican-
cer agents such as capecitabine, dacarbazine, 5-FU, interferon α
(IFNα) and temozolomide can be used in patients with progres-
sive metastases from carcinoid for whom there are no other
treatment options. However, no chemotherapy drug or regimen
has demonstrated an overall survival benefit or progression-free
survival.
Naalla R, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202159
Rare disease
Learning points
▸ Duodenal carcinoids are rare and their association with
typical carcinoid syndrome is extremely uncommon.
▸ Although rare, one must have a high index of suspicion on
carcinoid syndrome in patients presenting with vague
multisystemic symptoms.
▸ Duodenal carcinoids are easy to diagnose and with
appropriate surgical management reoccurrence and
progression of the disease is less likely.
▸ One should be aware of prevention and management of
carcinoid crisis.
Contributors RN was involved in writing and editing the article. KK and OK were
involved in data collection and background work. RL was involved in the final
approval of the article.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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