Simultaneous Non-Functioning

Simone Maurea
, Antonio Corvino
, Massimo Imbriaco
, Giuseppe Avitabile
Pierpaolo Mainenti
, Luigi Camera
, Gennaro Galizia
, Marco Salvatore
Department of Biomorphological and Functional Sciences (DSBMF),
University Federico II of Napoli (UNINA), Biostructures and Bioimages Institution (IBB),
National Research Council (CNR); SDN Foundation (IRCCS).
Divisions of Surgical Oncology, F Magrassi A Lanzara Department of Clinical and Experimental
Medicine and Surgery, Second University of Naples School of Medicine. Naples, Italy
Context Thanks to the wide use of diagnostic imaging modalities, multiple primary malignancies are being diagnosed more
frequently and different associations of malignancies have been reported in this setting. Case report In this paper, we describe the
case of a patient with non-functioning well-differentiated neuroendocrine carcinoma of the head of the pancreas associated with
extra-hepatic cholangiocarcinoma, in which an early diagnosis using magnetic resonance imaging allowed a good outcome.
Conclusion The simultaneous association of neuroendocrine pancreatic tumors and cholangiocarcinoma has not yet been described;
however, this association should be considered and, due to the high contrast of magnetic resonance imaging, this technique is
recommended in such patient in order to reach an accurate diagnosis.
To the best of our knowledge, simultaneous cholangio-
carcinomas and neuroendocrine pancreatic tumors in
the same patient have not yet been reported. However,
the occurrence of two or more primary malignant
tumors arising in the same patient is the well-accepted
definition of multiple primary malignancies; the
incidence of these lesions is being increasingly noted
due to the wide use of diagnostic imaging modalities
and different associations of tumor lesions have been
reported [1, 2].
We describe the case of a patient with extra-hepatic
cholangiocarcinoma associated with a non-functioning
well-differentiated neuroendocrine carcinoma of the
head of the pancreas with low grade malignancy, in
which MR imaging detected both tumor lesions and led
to the decision to perform surgery.
A 55-year-old male with a previous history of recurrent
abdominal pain, jaundice and a significant increase in
cholestasis laboratory indices underwent ERCP with
positioning of a biliary stent in the middle third of the
extra-hepatic common bile duct since a significant
biliary stenosis had been found. Four months later, the
patient was admitted to our institution without evidence
of significant clinical symptoms to account for the
nature of the biliary stenosis. Since the patient was
stented, an initial evaluation revealed no obstructive
jaundice; the conjunctivae were anicteric in the absence
of hepatomegaly; his abdomen was soft, non-tender
and not distended with normal bowel sounds; the
gallbladder was not palpable and Murphy’s sign was
negative. The remaining physical examination was
unremarkable. He had no significant comorbidities;
conventional laboratory evaluation as well as tumor
markers (CA 19-9, CA 125, CEA, and alpha-
fetoprotein) were normal. The patient initially
underwent abdominal ultrasound which demonstrated
slightly intra-hepatic bile duct dilatation especially in
the left liver; the common bile duct was dilated (10.4
mm) and the presence of the previously positioned
stent was visible; the liver echo-pattern appeared
Received February 7th, 2011 - Accepted March 25th, 2011
Key words Diagnostic Imaging; Magnetic Resonance Imaging;
Neoplasms, Multiple Primary
Correspondence Simone Maurea
Dipartimento di Scienze Biomorfologiche e Funzionali; Università
degli Studi di Napoli Federico II; via S. Pansini; 80131 Naples;
Phone: +39-81.746.3560/2039; Fax: +39-81.545.7081
Document URL

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JOP. Journal of the Pancreas - - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577]
MR imaging was successively performed to evaluate
and characterize the nature of the biliary stenosis by
acquiring axial and coronal T1- and T2-weighted
with/without fat saturation images integrated with
MRCP T2-weighted hydro-cholangiographic sequences.
In particular, the patient received 900 mL of
superparamagnetic oral contrast material (Lumirem®,
Guerbet, Paris, France) 20 min before the study. Post-
contrast acquisition was performed after the intra-
venous administration of gadolinium diethylenetriamine
pentaacetic acid (DTPA) in a volume of 20 mL with 2
mL/s acquiring T1 fast-field echo short-time inversion
recovery (FFE-STIR) images. In particular, cross-
sectional T1- and T2-weighted and MR cholangio-
graphy sequences showed dilatation of the biliary tree
including the intrahepatic ducts, primarily of the left
hepatic lobe and the common hepatic duct.
Furthermore, MR images showed a lengthy stricture
with luminal flow-signal preserved, irregular margins
as well as abrupt and asymmetric narrowing in the
middle third and intra-pancreatic segment of the
common bile duct (Figure 1). A solid lesion along the
common bile duct, at same level of the stricture,
appearing as circumferential wall-thickening with a
firm component projecting into the duct lumen, was
also detected (Figure 2); after the administration of
contrast medium, the lesion did not show significant
enhancement in the arterial phase; however, late-phase
images showed non-homogeneous enhancement
(Figure 3). There was no evidence of positive lymph
nodes or metastatic disease; the characteristics of the
MR images were suggestive of a malignant primary
stenosis probably by extra-hepatic cholangiocarcinoma.
Furthermore, MR views demonstrated mild
enlargement of the pancreas associated with a non-
homogeneous signal intensity of the pancreatic tissue
Figure 1. Conventional turbo spin eco T2-weighted coronal (a.) and
cholangiopancreatography (b.) magnetic resonance sequences. MR
views show a lengthy stricture with abrupt and asymmetric
narrowing in the middle and lower third of the common bile duct; the
proximal biliary tree is dilated.
Figure 2. Cross-sectional T2-weighted fat-suppressed images. Axial
T2-weighted turbo spin eco short-time inversion recovery (STIR)
sequences show a circumferential wall-thickening of the common
bile duct with a firm component projecting into the lumen.
Figure 3. T1-weighted fast-field echo short-time inversion recovery
(FFE STIR) post-contrast image shows a solid lesion with
inhomogeneous late-phase enhancement (at the level of the intra-
pancreatic biliary tract); moreover, MRI demonstrates mild
enlargement diffusely involving the head of the pancreas associated
with inhomogeneous signal intensity of the pancreatic tissue due to
the presence of a hypointense nodule (arrow).

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JOP. Journal of the Pancreas - - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577]
due to the presence of a hypointense nodule (Figure 3).
A second ERCP examination was subsequently
performed, which revealed a stricture immediately
above and at the level of the intra-pancreatic common
bile duct and the biliary stent was removed; brush
cytology did not reveal atypical cells and the final
report was not indicative of malignancy. 
Although no definite demonstration of malignancy was
obtained, on the basis of MR findings which were
highly suggestive of a malignant stenosis, the patient
underwent surgical treatment: a Whipple’s pancreatico-
duodenectomy with end-to-side gastrojejunostomy, T-
L hepaticojejunostomy and T-L pancreaticojejuno-
stomy were carried out. The resected specimens were
submitted to the Department of Surgical Pathology for
histological evaluation; they included the distal
stomach, the duodenum, part of the proximal jejunum,
part of the pancreas (head, neck and uncinate process)
and the distal biliary tree (distal common hepatic duct,
gallbladder and cystic duct). Histological examination
revealed well-differentiated distal common bile duct
adenocarcinoma, which was confined to the muscular
wall without infiltrating the pancreatic head and other
surrounding tissues; the margins were tumor free and
there was no vascular invasion; all loco-regional lymph
nodes were negative for malignancy. According to the
TNM classification system, the tumor was staged as
pT1 N0 M0, stage 1A. Macroscopically, a solid, yellow
ochre, well-defined lesion measuring 0.4 cm was found
within the pancreatic head; the surgical margins were
clear. Microscopic examination of the regional lymph
nodes near the mass revealed that they were all
hyperplastic. Immunocytochemistry showed that the
tumor cells were positive for chromogranin A,
synaptophysin and neuron-specific enolase; moreover,
the tumor tissue showed a negative reaction to
vimentin. The final pathology report classified the
tumor as a non-functioning well-differentiated
neuroendocrine carcinoma of the pancreas. After the
surgical procedure, the patient was managed according
to standard postoperative procedure; the short-term
postoperative course was complicated by
gastrointestinal bleeding requiring arterial embolization
and intra-abdominal drainage. The patient was
discharged one month after initial admission; the
patient has remained disease free for more than one
year after the initial diagnosis.
In this paper, we report the particular case of a patient
with multiple tumors in which a new association of
malignancies was found; in fact, a small non-
functioning neuroendocrine pancreatic tumor was
found simultaneously with an extra-hepatic
cholangiocarcinoma. In our patient, MR imaging was
able to detect both tumor lesions allowing appropriate
and timely surgical treatment, although a proven
cytological diagnosis was not available; in this regard,
the MR imaging characteristics were highly suggestive
of a malignant stenosis caused by an extra-hepatic
cholangiocarcinoma as well as of small pancreatic
nodules and, thus, significant enough to suggest
surgical treatment.
The first report regarding multiple primary
malignancies was in 1889 by Billroth who described a
patient with a spinocellular epithelioma of the right ear
and a gastric carcinoma [3]. Since that time, multiple
primary malignancies have been the object of medical
research [2]; in particular, the technical innovation of
diagnostic imaging has been employed in this setting
and, thus, several distinct associations have been
described [4].
The occurrence of a second tumor in patients with
pancreatic cancer is described [5, 6, 7, 8]; in particular,
in these studies, patients with intraductal papillary
mucinous carcinoma had second malignancies in other
organs in percentages ranging from 7 to 30%; however,
only a single case of simultaneous cholangiocarcinoma
was reported [8]. Conversely, the most frequently
associated tumors were gastric and colorectal cancers,
followed by pulmonary neoplasms. The tumor
association that we observed in our report is different
since the pancreatic lesion consisted of a different
histological type represented by neuroendocrine tissue.
In the case presented, MR imaging detected the two
tumor lesions which were located in the same
anatomical region, the superior abdomen; in particular,
the small neuroendocrine pancreatic tumor was barely
visible only on the post-contrast T1-weighted images
as a nodular area of hypo-intensity. This finding is not
surprising since the majority of such tumors after
contrast administration show hyperintensity in the
arterial phase because they are hypervascularized [9,
10, 11] but, in our patient, the post-contrast MR images
were acquired only in the late phase and thus the lesion
appeared hypointense. On the other hand, MR images
clearly demonstrated a malignant stenosis of the main
biliary extra-hepatic duct with significantly reduced
biliary flow on T2-hydrographic sequences and
abnormal concentric solid tissue at the same level.
Although brush cytology samples from ERCP were not
diagnostic for biliary malignancy, the patient
underwent a Whipple’s pancreaticoduodenectomy
since the MR features were highly suspicious of a
malignant biliary stenosis. Histological examination of
the surgical specimens confirmed the MR suspicion of
malignant lesions represented by a neuroendocrine
pancreatic tumor and an extra-hepatic cholangio-
Regarding the ERCP management of our patient, some
observations need to be made. First, why was the
patient stented during his initial evaluation without a
precise diagnosis? The clinical explanation for this
procedure was the need to resolve the significant
biliary stenosis; this approach is frequently performed
in daily practice, but it is important to point out that
biliary stenting without an exact diagnosis should be
avoided. Furthermore, in our patient, a delay of four
months between the first stenting and definitive
treatment occurred. This is a certainly long interval for

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JOP. Journal of the Pancreas - - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577]
malignant disease and, hence, such a time gap should
be absolutely avoided in favor of timely appropriate
treatment. Finally, why was ERCP repeated during the
second clinical evaluation after MR imaging? In this
regard, the invasive endoscopic procedure was
performed since MR findings suggested a malignant
biliary stenosis and a cytological confirmation was thus
In conclusion, a neuroendocrine pancreatic tumor and
an extra-hepatic cholangiocarcinoma may occur
simultaneously; this association should thus be
considered in multiple primary malignancies. In this
setting, MR imaging is recommended since its high
contrast capability allows the early detection of tumor
lesions enabling appropriate and timely treatment to be
carried out.
Conflicts of interest The authors have no potential
conflicts of interest
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