The Journal of the Arkansas Medical Society Med Journal Sept 2019 FInal 2 | Page 11

100,000), 1,2,3 includes tumors arising from the GI
tract (GNET) and Pancreas (PNET). Within the GI
tract, these are found commonly in small bowel
and appendix, followed by rectum and stomach 4 .
Duodenal occurrence of NETs is very rare and
represents only 2-3% of all NETs. 4,5 Most of these
tumors are small, submucosal masses 5,6 and are
divided into five types: duodenal gastrinomas,
duodenal somatostatinomas, nonfunctioning
NETs, ganglioytic paragangliomas, and poorly
differentiated NE carcinomas. They may occur
sporadically or in association with Multiple
Endocrine Neoplasia (MEN-1) and Zollinger-Ellison
Syndrome (ZES). The tumor seen in our patient was
a nonfunctioning NET.
Although the old term carcinoid sounds
benign, these tumors are capable of local
and distant metastasis. The most common
presentation is abdominal pain, but presentation
may vary from nonspecific dyspepsia to GI
bleeding. 5,6 Given the indolent and slow-growing
nature of these tumors, NETs may remain
asymptomatic until they grow large or may be
incidentally discovered on imaging or endoscopy.
In our case, patient had intractable nausea, likely
due to intermittent, low-grade outlet obstruction
from the tumor growing in duodenal wall.
Routine imaging, including CT and MRI, can
detect large-sized NETs and also metastases but
fails to reliably detect smaller submucosal lesions. 7
In such scenarios, EUS is the most useful diagnostic
modality to detect accurately the tissue of origin, as
in our patient, which may be difficult at times with
conventional imaging. EUS serves well in defining
the size of tumor, level of invasion, histology by
FNA, and regional lymph-node metastasis. 4,7,8
Additionally, serum chromogranin levels are seen
elevated in 80% of the tumors. 9 In addition to
cross-sectional imaging and EUS, somatostatin
» » This is a very uncommon presentation,
but teaches endoscopists to investigate
thoughtfully such purportedly trivial complaints
to unravel unexpected findings, like NETs.
» » EUS is an irreplaceable asset in investigation of
submucosal masses and can help differentiate
the tissue of origin even in cases where cross-
sectional imaging fails.
References
Image 4: CD56 immunohistochemical
stain showing diffuse membranous
positivity of tumor cells.
scintigraphy (SRS) is valuable in identifying
small, metastatic lesions, owing to the increased
expression of somatostatin receptors by these
tumors. 10,11 Histologically, NETs stain positive for
pan-sensitive neuroendocrine markers, including
Chromogranin A, synaptophysin, and neuron-
specific enolase. 10 Moreover, Ki-67 level, which
measures the proliferative capacity of the tumor
cells, is measured to grade the tumors according
to the WHO classification, which determines the
overall prognosis. 12 If the Ki-67 index is <2%,
tumors are graded into G1, 2-20% into grade 2,
and >20% into G3.
Management of NETs depends on size and
grade of tumor and extent of metastasis. Small,
submucosal tumors of < 1cm without any regional
lymph node involvement can be safely removed
by endoscopic resection. For larger tumors, full
thickness excision is needed either by laparoscopy
or laparotomy. Alternative therapy (medical) is
considered for non-resectable, metastatic tumors
or high-risk surgical candidates, which may
include somatostatin analogues, interferon, and
chemotherapy, 13,14 (all evolving fields). Radiation
therapy (external beam radiotherapy; EBRT)
may be considered for palliative purposes and
is suitable for patients with increased uptake
of specific radionucleotide agents (like I-MIBG).
Additional modalities, including radiofrequency
ablation or hepatic artery embolization, may
be needed for management of non-resectable
hepatic metastatic lesions and for symptomatic
control of functional NETs.
Learning points
Image 3: Synaptophysin
immunohistochemical stain showing
diffuse positive cytoplasmic and
membranous staining of tumor cells.
» » Duodenal NETs are rare, slow growing, and
may have insidious presentation, like our
patient with nausea, which was likely due to
intermittent, low-grade-outlet obstruction.
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Contact AMS for a complete list of references.
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