Original Article
Cytologic Categorization of Pancreatic Neoplastic
Mucinous Cysts With an Assessment of the Risk of
Malignancy: A Retrospective Study Based on the
Papanicolaou Society of Cytopathology Guidelines
Amber L. Smith MD; Fadi W. Abdul-Karim MD, MEd; and Abha Goyal MD
BACKGROUND: Cytology plays a pivotal role in the preoperative diagnosis of pancreatic cysts. Here the Papanicolaou
Society of Cytopathology (Pap Society) guidelines were used to reclassify and assess the malignancy risk of cytology
diagnoses of histologically proven pancreatic neoplastic mucinous cysts. METHODS: A database search (January 2000 to
June 2014) was performed for pancreatic neoplastic mucinous cyst resections with endoscopic ultrasound–guided fineneedle aspiration within the preceding year. Histologic diagnoses were reclassified according to the 2010 Word Health
Organization criteria. For atypical/suspicious/positive cytology diagnoses, the cytology slides were reviewed, blinded to
the histologic diagnoses. The cysts were reclassified according to the Pap Society guidelines, and the findings were correlated with the histology. RESULTS: One hundred thirty-eight cases of pancreatic neoplastic mucinous cysts were
retrieved. Eleven cases with atypical/suspicious cytology diagnoses with unavailable slides were excluded. The remaining
127 cases included 81 intraductal papillary mucinous neoplasms and 46 mucinous cystic neoplasms. The sensitivity of
cytology for the diagnosis of neoplastic mucinous cysts was 76.4%. The sensitivity, specificity, and accuracy of cytology
for the diagnosis of malignancy (high-grade dysplasia or worse) were 48.3%, 94.9%, and 84.3%, respectively. The risk of
malignancy was 17.4% for the nondiagnostic category, 0% for the negative category, 13% for the neoplastic category,
63.6% for the atypical category, 80% for the suspicious category, and 100% for a positive diagnosis. CONCLUSIONS: This
study reveals that the Pap Society guidelines allow the accurate categorization of pancreatic neoplastic mucinous cysts
with cytology. The diagnostic categories (from negative to positive) are associated with an increasing risk of malignancy,
C 2015 Ameriand this can further aid in patient management and risk stratification. Cancer Cytopathol 2016;124:285-93. V
can Cancer Society.
KEY WORDS: cyst; endoscopic ultrasound; fine-needle aspiration; mucinous; pancreas; Papanicolaou Society guidelines;
risk of malignancy.
INTRODUCTION
With the widespread use of high-resolution abdominal imaging, the detection of pancreatic cysts, many of which
are incidental, has considerably increased.1,2 A significant proportion of these cysts, up to 55% in 1 study, are
composed of neoplastic mucinous cysts, that is, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), which may require surgical intervention.3
Currently, endoscopic ultrasound guided–fine needle aspiration (EUS-FNA) plays a pivotal role in the diagnosis and characterization of solid and cystic pancreatic masses.4–7 In terms of the evaluation of pancreatic cysts, the
role of the cytopathologist is 2-fold: to establish whether the cyst is mucinous or nonmucinous and to determine
Corresponding author: Abha Goyal, MD, Department of Pathology, Cleveland Clinic, 9500 Euclid Avenue, L25, Cleveland, OH 44195; Fax: (216)
445-3707; abgoyal@yahoo.com
Department of Pathology, Cleveland Clinic, Cleveland, Ohio
Received: August 25, 2015; Revised: October 27, 2015; Accepted: October 28, 2015
Published online November 30, 2015 in Wiley Online Library (wileyonlinelibrary.com)
DOI: 10.1002/cncy.21657, wileyonlinelibrary.com
Cancer Cytopathology
April 2016
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Original Article
whether there is any high-grade atypia or worse. Such a cytologic evaluation is critical in making clinical management
decisions.8,9 The 2012 international consensus guidelines for
the management of pancreatic mucinous neoplasms incorporate EUS-FNA into the management algorithm.10
Until recently, there was no standardized scheme for
reporting pancreatic cytology. The Papanicolaou Society of
Cytopathology (Pap Society) has proposed a reporting terminology and classification for pancreatic cytology. This
proposed scheme includes 6 categories: “nondiagnostic,”
“negative for malignancy,” “atypical,” “neoplastic,”
“suspicious for malignancy,” and “positive” or “malignant.”
The neoplastic category has been further subdivided into
“neoplastic: benign” and “neoplastic: other.” Aside from
low-grade malignancies such as pancreatic neuroendocrine
tumors and solid pseudopapillary neoplasms, the neoplastic: other category includes premalignant neoplastic mucinous cysts (ie, IPMNs and MCNs) with low-,
intermediate-, or high-grade dysplasia. For neoplastic mucinous cysts without overt malignant features, a 2-tiered
approach is recommended by the Pap Society for grading
cellular atypia: low-grade atypia and high-grade atypia.
Low-grade atypia usually correlates with low-grade dysplasia or intermediate-grade dysplasia on histologic follow-up,
and high-grade atypia is usually associated with high-grade
dysplasia or worse on histologic follow-up.11,12
This new classification aims to allow better communication between the pathologists and the clinicians to
aid in the management and treatment of pancreatic
lesions. However, there is limited information regarding
the practical utility of these guidelines and the risk of
malignancy associated with the different diagnostic categories. Our study was aimed at using the Pap Society
guidelines to categorize pancreatic neoplastic mucinous
cysts retrospectively and to stratify the risk of malignancy
on the basis of such a categorization.
MATERIALS AND METHODS
This study was approved by the institutional review board
at the Cleveland Clinic. A retrospective database search
was performed from January 1, 2000 to June 30, 2014 for
resections of pancreatic mucinous neoplasms (ie, IPMNs
and MCNs). Only cases with EUS-FNA within the year
preceding the resection were included.
The cytologic and histologic diagnoses were recorded
from the pathology reports. For cases with atypical, suspi286
cious, or positive cytology diagnoses, the fine-needle aspiration (FNA) slides were reviewed, blinded to the histologic
diagnoses, and were categorized according to the Pap Society guidelines. The cytology slides from cases that had
been initially categorized as negative or nondiagnostic were
not reviewed. Histologic diagnoses were reclassified according to the 2010 World Health Organization classification
of tumors of the digestive system as IPMN or MCN with
low-/intermediate-/high-grade dysplasia or an associated
invasive carcinoma.13
Patient demographic and clinical information and
cyst fluid analysis data were obtained from the electronic medical record. The cysts were reclassified
according to the Pap Society guidelines. Cysts with a
carcinoembryonic antigen (CEA) level 192 ng/mL or
with abundant extracellular, thick, colloid-type mucin
or neoplastic mucinous epithelium were considered to
be mucinous and were placed in the neoplastic: other
category. Cysts with nonspecific cyst contents with an
absence of extracellular mucin and neoplastic mucinous
epithelium, low CEA levels (<192 ng/mL) and high
amylase levels (>250 U/L) were considered negative.
Cysts with acellular aspirates or nonspecific cyst
contents with an absence of extracellular mucin/neoplastic mucinous epithelium, without any helpful ancillary studies (ie, amylase level < 250 U/L and CEA
level < 192 ng/mL), or without available CEA levels
were considered to be nondiagnostic.
The cytology slides from cysts that were initially
classified as atypical, suspicious, or positive were categorized as follows upon review. Those with diagnostic
high-grade atypia were categorized as neoplastic: other
with high-grade atypia. The cysts with low-grade atypia
upon re-review were classified as neoplastic: other. Cysts
with high-grade atypia and background coagulative
necrosis with features insufficient for a positive-formalignancy diagnosis were classified as suspicious for
malignancy. Cysts with sufficient cellularity to make an
adenocarcinoma diagnosis were classified as positive for
malignancy.
On the basis of the aforementioned classification, the
sensitivity of cytology for the diagnosis of neoplastic mucinous cysts was calculated. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy
of cytology for the diagnosis of malignancy (high-grade
dysplasia or worse) were also calculated. The nondiagnostic
cases were included in all these calculations. The absolute
Cancer Cytopathology
April 2016
Cytology of Pancreatic Mucinous Cysts/Smith et al
risk of malignancy for each category was computed as
follows:
Absolute risk of malignancy 5
Number of malignant cases on histologic
follow-up 4 Total number of cases
RESULTS
One hundred thirty-eight cases of pancreatic neoplastic
mucinous cysts met the study criteria. Eleven cases with
initial atypical/suspicious cytology diagnoses with slides
unavailable for review were excluded from further analysis.
Among the remaining 127 cases, there were 81 IPMNs
and 46 MCNs.
Among the 81 patients with IPMNs, there were 44
women and 37 men. The average age of the patients was
67 years (range, 44-87 years). Forty-one (50.6%) were
located in the proximal pancreas (26 in the head, 13 in the
uncinate, and 2 in the genu), and the remaining 40
(49.4%) were located in the distal pancreas (22 in the
body and 18 in the tail). All but 1 of the 46 MCNs were
diagnosed in women. The average age of the patients was
54 years (range, 29-79 years). Forty-three of the MCNs
(93.5%) were located in the distal pancreas (19 in the
body and 24 in the tail), and 3 (6.5%) were located in the
proximal pancreas (2 in the head and 1 in the uncinate).
Cytology and Cyst Fluid Biochemistry
Seventy-eight cases (61.4%) had both ThinPrep preparations and direct smears available for cytologic assessment,
44 (34.6%) cases had ThinPrep preparations only, and the
remaining 5 (3.9%) had smears only. Cytology was diagnostic of a neoplastic mucinous cyst in 74 cases (58.3%;
Fig. 1A-D).
CEA levels were available in 85 cases (66.9%). Fiftynine of these cases (69.4%) exhibited a CEA level 192 ng/mL (range, 194.9-176,600 ng/mL; median,
1743.2 ng/mL), which was considered diagnostic of a
mucinous cyst. Of the 78 cases that were categorized as
neoplastic: other, the CEA level was 192 ng/mL in 53
cases, < 192 ng/mL in 6 cases, and unavailable in the
remaining 19 cases. Of the 19 cases with high-grade atypia
or worse, CEA was 192 ng/mL in 6 cases, < 192 ng/mL
in 2 cases, and unavailable in the remaining 11 cases.
Ninety-seven cases (76.4%) had either diagnostic
cytology or a CEA level diagnostic of a mucinous cyst.
Cancer Cytopathology
April 2016
CEA alone was diagnostic of a mucinous cyst in 23 cases
(18.1%), and cytology alone was diagnostic in 38 cases
(29.9%).
According to the criteria outlined in the Materials
and Methods section, 7 cysts (5.5%) were categorized as
negative, and 23 cysts (18.1%) were considered to be nondiagnostic. Of the cases that were diagnosed as a mucinous
cyst, 78 (61.4%) were categorized as neoplastic: other, 11
(8.7%) were categorized as neoplastic: other with highgrade atypia, 5 (3.9%) were categorized as suspicious for
malignancy, and 3 (2.4%) were categorized as positive for
malignancy (Fig. 2A-2D). The revised categorization of
the study cases (based on cytology and CEA levels) is
depicted in comparison with the original cytology categorization in Table 1.
Histologic Correlation and Risk of Malignancy
Of the 127 cases in our study, 29 (22.8%) were malignant
on histologic follow-up: 25 IPMNs (15 with high-grade
dysplasia and 10 with associated invasive carcinoma) and 4
MCNs (2 with high-grade dysplasia and 2 with associated
invasive carcinoma). The remaining 98 cases (77.2%) were
considered benign for the purposes of this study: 56
IPMNs (17 with intermediate-grade dysplasia and 39 with
low-grade dysplasia) and 42 MCNs (4 with intermediategrade dysplasia and 38 with low-grade dysplasia).
With the cytologic diagnosis of high-grade atypia or
worse, 14 malignant cases (48.3%) were detected: 6
IPMNs with an associated invasive carcinoma, 7 IPMNs
with high-grade dysplasia, and 1 MCN with high-grade
dysplasia. With this diagnosis, cytology misclassified 5
benign neoplasms as malignant: 1 IPMN with low-grade
dysplasia, 1 IPMN with intermediate-grade dysplasia, 2
MCNs with low-grade dysplasia, and 1 MCN with
intermediate-grade dysplasia.
With a positive cytology diagnosis, 3 malignancies
(10.3%) were detected: all IPMNs with an associated invasive carcinoma.
The diagnostic accuracy of cytology for malignancy
was 84.3% with a diagnosis of high-grade atypia or worse
and 75.6% with a positive diagnosis. The specificity of
cytology for malignancy was 94.9% with a diagnosis of
high-grade atypia or worse and 100% with a positive diagnosis. The absolute risk of malignancy for each cytologic
category along with the histologic follow-up is shown in
Table 2.
287
Original Article
Figure 1. Cytologic features of a pancreatic neoplastic mucinous cyst with histologic correlation. (A) Thick, colloid-like mucin
characteristic of a neoplastic mucinous cyst (Papanicolaou stain, 3 400). (B) On surgical resection, this was a main-duct intraductal papillary mucinous neoplasm with intestinal-type epithelium and intermediate-grade dysplasia (H & E stain, 3 200). (C) Mucinous epithelium with low-grade atypia against a background of thick mucin (Papanicolaou stain, 3 400). (D) On histologic
follow-up, it was a branch-duct intraductal papillary mucinous neoplasm with gastric foveolar-type epithelium with low-grade
dysplasia (H & E, 3 200).
DISCUSSION
The diagnostic tools and management options for pancreatic neoplastic mucinous cysts have evolved over time.
Imaging techniques, including computed tomography
(CT) scanning and magnetic resonance imaging (MRI),
play an important role in the initial workup of these
cysts.14,15 Endoscopic ultrasound (EUS) offers a higher
resolution than CT and MRI because of the close proximity of the transducer to the pancreas. As such, EUS is usually performed for a detailed evaluation of the cyst if the
CT/MRI findings are indeterminate. In addition, EUS
allows real-time sampling of the cyst through FNA.15–17
EUS with or without FNA is reportedly more accurate
288
than CT and MRI in predicting a cyst to be neoplastic and
more accurate than CT in predicting malignancy in small
cysts.18
EUS-FNA of pancreatic cysts yields material not only
for cytologic assessment but also for biochemical and
molecular analysis. The cytologic diagnosis for a neoplastic
mucinous cyst depends on the presence of extracellular
thick mucin and/or neoplastic mucinous epithelium with
varying degrees of atypia. However, based on cytomorphology alone, the sensitivity of EUS-FNA for the diagnosis of neoplastic mucinous cyst ranges from 34.5% to
63%, and the accuracy is reportedly 59%.19,20 Cyst fluid
biochemical analysis, including tumor marker CEA and
Cancer Cytopathology
April 2016
Cytology of Pancreatic Mucinous Cysts/Smith et al
Figure 2. Cytologic features of pancreatic neoplastic mucinous cysts with high-grade atypia or worse with histologic correlation.
(A) Atypical cells with a high nuclear-cytoplasmic ratio, hyperchromasia, and irregular nuclear membranes characteristic of highgrade atypia. On surgical resection, this intraductal papillary mucinous neoplasm exhibited high-grade dysplasia (Papanicolaou
stain, 3 400). (B) High-grade atypia cells against a background of coagulative necrosis (features suspicious for adenocarcinoma).
On histologic follow-up, there were foci of invasive adenocarcinoma associated with this intraductal papillary mucinous neoplasm
(Papanicolaou stain, 3 200). (C) Adenocarcinoma of a tubular type arising in an intraductal papillary mucinous neoplasm. Note
the thick mucin in the background (Papanicolaou stain, 3 400). (D) Surgical resection revealed an invasive adenocarcinoma in
association with an intraductal papillary mucinous neoplasm (H & E, 3 200).
amylase levels, adds further information to cytologic analysis. The cooperative pancreatic cyst study reported that a
cyst fluid CEA level 192 ng/mL exhibited an accuracy of
79% for classifying a cyst as mucinous.19 The cyst fluid
amylase level in combination with CEA can also aid in the
differentiation between mucinous and nonmucinous cysts.
An amylase level < 250 U/L and a CEA level > 800 ng/
mL are unlikely to be associated with a pseudocyst.21
Molecular analysis can further add value to the information
obtained by cytologic and biochemical analysis. In accordance with the Pancreatic Cyst Fluid DNA Analysis
(PANDA) study, a combination of CEA and KRAS mutaCancer Cytopathology
April 2016
tional testing increased the sensitivity of CEA alone from
67% to 84% for detecting a mucinous cyst.22 Sawhney
et al23 reported a sensitivity and a specificity of 100% for
the classification of a mucinous cyst when CEA and molecular analysis were combined. Also, the combination of
GNAS and KRAS testing has been reported to be highly
sensitive (84%) and specific (98%) for the diagnosis of
IPMNs.24
As is apparent from the previous discussion, a purely
cytologic approach is inferior to an integrated approach of
cytology with ancillary testing in diagnosing a neoplastic
mucinous cyst of the pancreas. Until recently, there had
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Original Article
TABLE 1. Revised Cytology Categorization in Comparison With the Original Diagnoses
New Category
Previous Category
Diagnostic Basis
Nondiagnostic (n 5 23)
Negative (n 5 19)
Nondiagnostic (n 5 4)
Negative (n 5 7)
Negative (n 5 7)
Neoplastic: other (with low-grade atypia) (n 5 78)
Negative (n 5 67)
Atypical (n 5 9)
Positive (n 5 1)
Nondiagnostic (n 5 1)
Atypical (n 5 8)
Suspicious (n 5 3)
Suspicious (n 5 3)
Atypical (n 5 2)
Positive (n 5 3)
Cytology: nonspecific
CEA: low or NA
Amylase: low
Cytology: nonspecific cyst contents
CEA: low
Amylase: high
Cytology (n 5 25)
CEA: high (n 5 23)
Cytology and CEA (n 5 30)
Neoplastic: other with high-grade atypia (n 5 11)
Suspicious for malignancy (n 5 5)
Positive for malignancy (n 5 3)
Cytology
Cytology
Cytology
Cytology
Cytology
Cytology
(n 5 7)
and high CEA (n 5 4)
(n 5 4)
and high CEA (n 5 1)
(n 5 2)
and high CEA (n 5 1)
Abbreviation: CEA, carcinoembryonic antigen; NA, not available.
TABLE 2. Cytologic Categories With Histologic Correlation and Risk of Malignancy
Histologic Follow-Up, No.
Cytologic Diagnostic Category
Nondiagnostic (n 5 23)
Negative (n 5 7)
Neoplastic: other (with low-grade atypia) (n 5 78)
Neoplastic with HG atypia (n 5 11)
Suspicious for adenocarcinoma (n 5 5)
Positive for adenocarcinoma (n 5 3)
Total
LG Dysplasia
IG Dysplasia
HG Dysplasia
Adenocarcinoma
13
6
56
3
0
0
78
6
1
12
1
1
0
21
0
0
8
6
2
0
16
4
0
2
1
2
3
12
Absolute Risk of
Malignancy, %
17
0
13
64
80
100
Abbreviations: IG, intermediate grade; HG, high-grade; LG, low-grade.
been no standardized guidelines for the cytopathologist to
report pancreaticobiliary cytology with an integrated
approach. The Pap Society advocates a multidisciplinary
approach for the diagnosis of pancreatic lesions and recommends the incorporation of all available relevant ancillary
data to make a cytologic diagnosis.11,12,25
For the diagnosis of neoplastic mucinous cysts in our
study, the sensitivity of cytology only was 58.3%, which is
comparable to the results of other studies.20 For the cases
with available CEA levels, a CEA level 192 ng/mL exhibited a sensitivity of 69.4%. Similarly to our results, Brugge
et al19 and Sawhney et al23 showed that for the diagnosis
of a mucinous cyst, a CEA value 192 ng/mL had a sensitivity of 73% and 82%, respectively. With the incorporation of the CEA levels, the diagnostic sensitivity of
cytology rose to 76.4% in our study with an increment of
18.1%. However, it is important to note that cytology by
itself was diagnostic in 38 cases (29.9%) for which CEA
levels were low or unavailable. A recent meta-analysis
290
regarding the diagnostic accuracy of EUS-FNA also
revealed that a combined cytology and biomarker approach
is essential for differentiation between mucinous and nonmucinous cysts.26 Our findings confirm that CEA levels
are complementary to cytology in the diagnosis of a mucinous cyst and support the Pap Society recommendation of
including the ancillary study results in cytology practice.
After establishing that a cyst is mucinous, the other
significant determination that needs to be made is whether
the cyst is malignant (ie, it harbors high-grade dysplasia or
an invasive carcinoma) or not. With the current sophisticated imaging techniques, the distinction between aggressive and nonaggressive cysts can be made with reasonable
accuracy (reportedly 64%-86% for CT and 73%-91% for
MRI).17,27–29 However, EUS-FNA with a cytologic assessment plays an important role in characterizing cysts that
are not overtly malignant on imaging.15,16,18 Pitman et al8
have shown that on the basis of cytology, high-risk mucinous cysts can be most accurately recognized by the
Cancer Cytopathology
April 2016
Cytology of Pancreatic Mucinous Cysts/Smith et al
identification of epithelial cells with high-grade atypia.
The Pap Society recommends a 2-tiered approach for
grading cytologic atypia in mucinous cysts when features
suspicious or unequivocal for malignancy are not seen:
low-grade atypia (inclusive of low- and intermediate-grade
dysplasia) and high-grade atypia (inclusive of high-grade
dysplasia and adenocarcinoma).11,12 In terms of molecular
analyses for predicting malignancy in a mucinous cyst,
there are currently insufficient data to warrant their usage
in routine practice.25,30,31
The cytologic recognition of high-grade atypia or
worse in our study resulted in an overall sensitivity of
48.3% and an accuracy of 84.3% for detecting malignancy
in pancreatic mucinous cysts. In comparison, at the threshold of a positive cytology diagnosis, the sensitivity and
accuracy for detecting malignancy were 10.3% and 75.6%,
respectively. These results are similar to those reported in a
study by Pitman et al8 in which high-grade atypical cells
predicted malignancy in mucinous cysts with a sensitivity
of 72% and an accuracy of 80%, and a positive cytology
diagnosis had a sensitivity of 29% and an accuracy of
75%. The higher sensitivity for the detection of malignancy in mucinous cysts in their study may be in part due
to the higher proportion of malignant cases (35.5%) in
their study in contrast to ours (22.8%).8 As shown by these
studies, the cytologic diagnosis of high-grade epithelial
atypia has a higher sensitivity and accuracy for predicting
malignancy in mucinous cysts than a positive cytology
result.
At the threshold of high-grade atypia, the specificity
for the detection of malignancy in our study was 94.9%,
which was less than the specificity of 100% attained with a
positive diagnosis. This was due to 5 cases (including 3
mucinous neoplasms with low-grade dysplasia and 2 with
intermediate-grade dysplasia) that were misclassified as
high-grade atypia or worse on cytology. This cytologic pitfall of misinterpreting intermediate-grade dysplasia and
occasional cases of low-grade dysplasia as high-grade atypia
or worse has also been noted by other authors. Pitman
et al8 reported that high-grade atypical epithelial cells were
identified on cytology in 15% of benign cysts (6 with
moderate dysplasia and 5 with low-grade dysplasia) in their
study. In another study involving 70 EUS-FNAs of pancreatic cysts, the cytologic recognition of high-grade atypia
resulted in 6 false-positive interpretations (4 of which were
mucinous neoplasms with moderate dysplasia).32 An international observer concordance study also concluded that
Cancer Cytopathology
April 2016
intermediate-grade dysplasia is difficult to grade accurately
with cytology.33 This shortcoming of cytologic analysis is
also recognized by the Pap Society guidelines.11,12 Our
findings confirm that the cytologic threshold of high-grade
atypia is most accurate for predicting malignancy in mucinous cysts, but it may result in the resection of some cysts
that are not high-grade.
Another aim of our study was to determine the
risk of malignancy associated with the different diagnostic categories for pancreatic cytology as proposed by
the Pap Society. Our study demonstrates an increasing
risk of malignancy associated with the different categories: 0% for a negative diagnosis, 13% for a neoplastic
diagnosis, 63.6% for an atypical diagnosis, 80% for a
suspicious diagnosis, and 100% for a positive diagnosis.
The nondiagnostic category was associated with a
17.4% risk of malignancy. Our results were similar to
those reported by Layfield et al.34 They reported the
malignancy risk for the benign (negative), atypical, suspicious, malignant, neoplasm, and nondiagnostic categories of the Pap Society as 12.6%, 73.9%, 81.8%,
97.2%, 14.2%, and 21.4%, respectively. Our findings
verify that the categorization proposed by the Pap Society provides valuable information regarding risk stratification for patient management.
There were several limitations to our study. We
did not include the cysts that were managed conservatively in our study to ensure the histologic confirmation
of neoplastic mucinous cysts for all cases. Only cysts
that had undergone resection were included, and this
introduced a verification bias and likely led to an overestimation of the sensitivity of cytology for the diagnosis of a mucinous cyst and for the diagnosis of
malignancy. Also, our study involved the retrospective
application of Pap Society guidelines for the cytologic
diagnosis of pancreatic cysts. It would be more helpful
to apply these guidelines prospectively to assess their
true role in clinical decision making. We do not usually
incorporate molecular testing for the diagnosis of pancreatic cysts at our institution on a routine basis. Hence,
we could not assess the role of molecular markers in
determining whether a cyst was mucinous or malignant
in our study.
In conclusion, the Pap Society guidelines significantly
refined our diagnostic approach to pancreatic mucinous
cysts. They resulted in more meaningful cytologic diagnoses with well-defined criteria and the incorporation of
291
Original Article
ancillary data. The categorization of the mucinous cysts
into different categories on the basis of the presence or
absence of diagnostic material and high-grade atypia or
worse was associated with an increasing risk of malignancy,
and this would have potentially proved instrumental in
clinical management. Future prospective studies could further aid in defining the role of these guidelines in clinical
decision making and risk stratification in the management
of pancreatic neoplastic mucinous cysts.
13.
14.
15.
16.
FUNDING SUPPORT
No specific funding was disclosed.
17.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
18.
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