Keywords
mass-forming chronic pancreatitis - pancreatic ductal adenocarcinoma - dystrophic
calcifications - computed tomography - PET/CT - histopathology
Introduction
Mass-forming chronic pancreatitis is commonly noted in elderly patients with head
of the pancreas being the most common location.[1] On histopathology, progressive interstitial fibrosis with chronic inflammatory infiltrate
is the characteristic finding. However, pancreatic ductal adenocarcinoma presents
in the same age group with similar clinical findings that makes the differentiation
between these entities diagnostically challenging. Pancreatic ductal adenocarcinoma
is a hypovascular tumor with ill-defined margins that may not deform the contours
of the pancreas and is characterized by marked interstitial fibrosis. On imaging,
difficulties arise when pancreatic ductal adenocarcinoma occurs on a background of
pre-existing fibrosis as seen in chronic pancreatitis. On positron emission tomography/computed
tomography (PET/CT), malignant lesions generally demonstrate avid fluorodeoxyglucose
(FDG) uptake, whereas most benign lesions are characterized by normal or minimally
increased FDG accumulation. Focal areas of abnormally increased FDG uptake are considered
suspicious for malignant disease, and in many cases, metabolic alterations precede
the morphologic changes associated with malignant tumors such pancreatic ductal adenocarcinoma.
Case Report
A 60-year-old male presented to the department of general surgery with complaints
of jaundice for 4 weeks. He gave a history of chronic alcoholism since the age of
30 years and was immunocompromised with recently diagnosed type-2 diabetes mellitus.
Clinical examination revealed moderate hepatomegaly. Liver function tests were deranged
with elevated serum aspartate transaminase at 97 U/L (0–31), serum alanine transaminase
at 241 U/L (0–37), serum alkaline phosphatase at 682 U/L (35–104), and serum total
bilirubin at 5.4 mg/dL (0–1). Serum CA 19–9 was elevated at 1,382 U/mL (0–37); α-fetoprotein
was normal at 1.41 ng/mL. Serum immunoglobulin G4 (IgG4) was normal at 42 mg/dL (1–290).
The patient was referred for ultrasonography of the abdomen that demonstrated a hypoechoic
mass lesion in the uncinate process and pancreatic head with foci of calcifications.
There was associated atrophy of the pancreas and dilatation of the main pancreatic
duct([Fig. 1]) Further, contrast-enhanced computed tomography (CECT) revealed a 5 × 4 × 6 cm (anteroposterior [AP] × mediolateral [ML] × craniocaudal [CC])
hypoenhancing mass in the uncinate process and head of pancreas with mild upstream
dilatation of the common bile duct and intrahepatic biliary radicle dilatation. The
mass lesion demonstrated exuberant cauliflower like parenchymal calcification without
evidence of ductal dilatation ([Fig. 2A]). Pancreatic body and tail were atrophic and were displaced posterosuperior by the
mass lesion ([Fig. 2B]). Main pancreatic duct showed dilatation. PET/CT imaging demonstrated a soft tissue
mass with indistinct boundaries in the head and uncinate process of the pancreas with
a maximum standardized uptake value (SUV) of 4.59. Due to marked elevation of serum
CA-19–9 levels, the patient underwent pylorus-preserving pancreaticoduodenectomy on
high suspicion of pancreatic ductal adenocarcinoma, although calcifications are not
a diagnostic feature. Gross pathology of the resected specimen revealed an infiltrating
mass lesion in the uncinate process and head of pancreas. Histopathology revealed
periductal inflammation with fibrosis, dilatation of the main pancreatic duct and
intralobular fibrosis, consistent with features of chronic pancreatitis ([Fig. 3]). As the patient was immunocompromised, low-dose oral prednisone was initiated for
5 days to avoid recurrence of pancreatitis and the patient recovered well within 4
weeks of starting conservative treatment with nonsteroidal anti-inflammatory drugs,
pancreatic enzyme supplements and intravenous fluid resuscitation for preventing dehydration.
Liver function tests were reported as normal following completion of treatment.
Fig. 1 Longitudinal ultrasonography image demonstrating a hypoechoic mass lesion involving
the uncinate process and pancreatic head with foci of calcifications. There is associated
atrophy of the pancreas and dilated main pancreatic duct.
Fig. 2 (A) Axial computed tomography image in the arterial phase demonstrating a lobulated
hypoenhancing mass lesion involving the uncinate process and head of pancreas with
exuberant cauliflower like dystrophic calcifications. (B) Coronal reformatted computed tomography image in the portal venous phase demonstrating
posterosuperior displacement of the pancreatic body and tail by the mass lesion in
the uncinate process and pancreatic head. Note the atrophic pancreas with dilated
main pancreatic duct consistent with features of chronic pancreatitis.
Fig. 3 Histopathology image demonstrating duct dilatation, fibrosis, and pancreatic tissue
necrosis with parenchymal calcifications consistent with features of chronic pancreatitis
(hematoxylin and eosin, ×200).
Discussion
Mass-forming chronic pancreatitis accounts for 30% of cases of chronic pancreatitis.[2] Due to common clinical features and imaging findings, diagnostic differentiation
of mass-forming chronic pancreatitis and pancreatic ductal adenocarcinoma can sometimes
be more of a diagnostic dilemma. Approximately 33% of patients with mass-forming chronic
pancreatitis have been reported to have undergone pancreatic resection because the
entity was misdiagnosed as pancreatic ductal adenocarcinoma.[3] However, there is no need for surgical intervention in mass-forming chronic pancreatitis
and the entity usually responds well with a short course of steroids. Preoperative
differentiation between mass-forming chronic pancreatitis and pancreatic ductal adenocarcinoma
is of importance as clinical management varies.
CT is the imaging investigation of choice for characterization of mass lesions of
the pancreas and for preoperative staging. On CT, mass-forming chronic pancreatitis
appears as a lobulated hypodense and hypoenhancing mass with approximately 70% located
in the pancreatic head.[4] However, pancreatic ductal adenocarcinoma appears as hypodense infiltrating mass
lesion commonly located in the head of pancreas and is noted to shows delayed enhancement
due to relative hypovascularity of the tumor. CT characterization of morphological
features is often the preliminary step in providing a differential diagnosis of mass-forming
chronic pancreatitis or pancreatic ductal adenocarcinoma. Duct penetration sign on
CT helps support a diagnosis of mass-forming chronic pancreatitis over pancreatic
ductal adenocarcinoma.[5]
Clinically, obstructive jaundice secondary to sclerosing cholangitis is the commonest
presenting complaint in patients with mass-forming chronic pancreatitis. Jaundice
associated with chronic pancreatitis is often waxing and waning type as opposed to
jaundice secondary to pancreatic ductal adenocarcinoma cancer that typically increases
with time. Elevated IgG4 levels were reported to be a specific diagnostic marker in
chronic autoimmune pancreatitis.[6] However, 10% of patients with pancreatic ductal adenocarcinoma and cholangiocarcinoma
are positive for elevated IgG4 levels.[7] CA19–9 tumor marker was considered to be specific for pancreatic ductal adenocarcinoma.
However, CA19–9 levels are elevated in approximately 47 to 73% of cases with chronic
pancreatitis.[8] Combined measurement of serum IgG4 and CA19–9 levels might increase the diagnostic
accuracy to pancreatic ductal adenocarcinoma from mass-forming chronic pancreatitis.
On CECT, mass-forming chronic pancreatitis and pancreatic ductal adenocarcinoma are
visualized as hypoenhancing mass lesion in the arterial and portal venous phases that
demonstrates homogeneous enhancement on delayed phase. The clinical features, laboratory
investigations, and imaging findings are highly nonspecific in differentiating the
above two entities and diagnosis is usually relied on findings of histopathology of
the resected specimen. Differences between the two entities are shown in [Table 1].
Table 1
Differentiation of chronic mass-forming pancreatitis from pancreatic ductal adenocarcinoma
|
Parameter
|
Mass-forming chronic pancreatitis
|
Pancreatic ductal adenocarcinoma
|
|
Laboratory results
|
|
Serum amylase and lipase
|
Usually elevated
|
May cause elevation in blood amylase and lipase due to impingement of the tumor on
the duct system
|
|
Serum CA 19–9 levels
|
Not related
|
Elevated serum cancer antigen 19–9 levels
|
|
Serum IgG4 levels
|
Elevated in the autoimmune form of chronic pancreatitis
|
Occasionally elevated
|
|
Ultrasonography findings
|
|
Location
|
Pancreatic head
|
Head and uncinate process
|
|
Margins
|
Ill-defined
|
Ill-defined
|
|
Double duct sign
|
Occasionally present
|
Commonly present
|
|
Pancreatic ductal system
|
Dilated unobstructed main duct
|
Abrupt truncation with upstream dilatation of main duct
|
|
Calcifications
|
Commonly present
|
Occasionally present
|
|
Vascular invasion
|
Occasionally present
|
Commonly present
|
|
Bile duct dilatation
|
Occasionally present
|
Commonly present
|
|
Cystic necrosis (collection)
|
Commonly present
|
Occasionally present
|
|
Glandular atrophy
|
Commonly present
|
Occasionally present
|
|
Lymph nodal enlargement
|
Commonly peripancreatic reactive nodes
|
Peri-pancreatic, porta hepatis, and para-aortic nodes
|
|
Metastases
|
Never
|
Commonly to liver, lung, peritoneum, adrenal, bone and distant nodes
|
|
FDG PET/CT findings
|
|
Mean SUV (early phase—1 hour)
|
3.4
|
4.8
|
|
Maximal SUV at 1 hour
|
4.6
|
6.9
|
|
Mean SUV (delayed phase—2 hours)
|
4.8
|
5.6
|
|
Maximal SUV at 2 hours
|
6.8
|
7.6
|
|
Histopathology findings
|
Diffuse glandular atrophy, ductal dilatation with ductal calcifications
|
Infiltrating mass with ductal and vascular invasion
|
Abbreviations: FDG PET/CT, fluorodeoxyglucose-positron emission tomography/computed
tomography; IgG4, immunoglobulin G4; SUV, standardized uptake value.
Chronic pancreatitis is characterized by evolution of irreversible structural and
functional irregularities such as atrophy of pancreas, main pancreatic duct dilatation,
marked fibrosis causing stricturing of the duct, and occasionally inflammatory mass-formation
located in the region of pancreatic head that happens to be most common site of occurrence
of pancreatic ductal adenocarcinoma. The inflammatory mass-forming chronic pancreatitis
may cause stenosis of the common bile duct, main pancreatic duct, and duodenum, and
even cause encasement of the vessels by the mass lesion. In such cases, the duct penetration
sign on CT serves as the key differentiator between the two entities.
Approximately 60% of patients with chronic pancreatitis display parenchymal calcifications
on imaging.[9] Although ductal calcifications are most commonly encountered in chronic pancreatitis,
a combination of ductal calcifications with parenchymal calcifications, glandular
atrophy and cystic changes is highly specific for the diagnosis of chronic pancreatitis.
However, intraductal papillary mucinous neoplasms, neuroendocrine tumors, and occasional
cases of pancreatic ductal adenocarcinoma may show spotted calcifications.[10] Although majority of calcifications related to chronic pancreatitis are ductal,
occurrence of diffuse parenchymal calcifications is related to pancreatic ductal adenocarcinoma.
A strong suspicion of pancreatic ductal adenocarcinoma should be made when there is
fresh appearance of mass lesion on a background of chronic pancreatitis that reportedly
causes displacement of calcifications. In the above-mentioned scenario, the differential
diagnoses to be considered are mass-forming chronic pancreatitis, pancreatic ductal
adenocarcinoma, autoimmune pancreatitis, neuroendocrine tumors of the pancreas, and
solid pseudopapillary epithelial neoplasm.
Malignant lesions generally demonstrate avid FDG uptake, whereas most benign lesions
are characterized by normal or minimally increased FDG accumulation. Mass-forming
chronic pancreatitis is an exception to the above rule and it is possible to achieve
the differential diagnosis between pancreatic adenocarcinoma and mass-forming pancreatitis
by comparing the heights of SUVs in FDG PET/CT in the early phase.[11] But it is difficult to achieve the differential diagnosis between pancreatic ductal
adenocarcinoma and mass-forming chronic pancreatitis by comparing the time course
of SUVs in the early and delayed phase in PET/CT.[12] FDG PET/CT shows limited efficacy for differentiating pancreatic adenocarcinoma
from mass-forming pancreatitis and their images should be cautiously evaluated for
differentiating both diseases. Moreover, false-positive and false-negative results
also may occur with FDG PET, and its inherent low spatial resolution may interfere
with precise anatomic localization of findings. Relatively higher levels of ionizing
radiation are also a consideration in whole-body PET. Likewise, long scanning times
may affect patient compliance and increase patient motion. Finally, quantification
and reproducibility of SUV may be inaccurate because of noise attenuation correction
methods. Kato et al[12] performed a study on 47 patients with pancreatic masses, 33 of which were cases
of pancreatic adenocarcinoma, 14 of which were cases of mass-forming chronic pancreatitis
and found considerable overlapping between the SUVmax values of both entities. The
findings of their study were comparable to the SUVmax value of the mass lesion in
the current report.
Conclusion
In patients presenting with obstructive jaundice and a mass lesion commonly located
in the pancreatic head, mass-forming chronic pancreatitis should be considered in
the differential diagnosis. Duct penetration sign on computed tomography should favor
the diagnosis of mass-forming chronic pancreatitis over pancreatic ductal adenocarcinoma.
Imaging characteristics of mass-forming chronic pancreatitis and pancreatic ductal
adenocarcinoma may be very similar and often histopathology holds the key for precise
and accurate diagnosis of the entity that can drastically affect the patient management.
Mass-forming chronic pancreatitis remains a diagnostic challenge and mass lesions
of the head of pancreas should be reviewed with suspicion especially in patients with
a background history of chronic pancreatitis. FDG PET/CT can be reliably used for
tissue characterization of mass-forming chronic pancreatitis and for monitoring disease
response following treatment.
