Abstract
Pancreatic cysts are increasingly detected on imaging studies. Accurate determination of the cyst type is important to provide appropriate care for the patients. It is also very clear that not one single modality can provide adequate diagnostic information. A multidisciplinary approach is the key to the diagnosis of pancreatic cysts. In this setting, the role of ancillary testing, which includes biochemical testing (carcinoembryonic antigen and amylase levels in the cyst), molecular testing (e.g., KRAS, GNAS, VHL, and CTNB1), and/or immunohistochemical tests are very important to obtain an accurate diagnosis. This review will discuss helpful ancillary tests in common pancreatic cyst neoplasms and how to approach the diagnosis of pancreatic cysts.
References
1.
Brugge
WR
. Pancreatic fine needle aspiration: to do or not to do?
JOP
. 2004
Jul
;5
(4
):282
–8
.
[PubMed]
1590-85772.
Jhala
NC
, Jhala
DN
, Chhieng
DC
, Eloubeidi
MA
, Eltoum
IA
. Endoscopic ultrasound-guided fine-needle aspiration. A cytopathologist’s perspective
. Am J Clin Pathol
. 2003
Sep
;120
(3
):351
–67
.
[PubMed]
0002-91733.
Pitman
MB
, Deshpande
V
. Endoscopic ultrasound-guided fine needle aspiration cytology of the pancreas: a morphological and multimodal approach to the diagnosis of solid and cystic mass lesions
. Cytopathology
. 2007
Dec
;18
(6
):331
–47
.
[PubMed]
0956-55074.
Jais
B
, Rebours
V
, Malleo
G
, Salvia
R
, Fontana
M
, Maggino
L
, et al. Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)
. Gut
. 2016
Feb
;65
(2
):305
–12
.
[PubMed]
0017-57495.
Reid
MD
, Choi
H
, Balci
S
, Akkas
G
, Adsay
V
. Serous cystic neoplasms of the pancreas: clinicopathologic and molecular characteristics
. Semin Diagn Pathol
. 2014
Nov
;31
(6
):475
–83
.
[PubMed]
0740-25706.
Ahmad
NA
, Kochman
ML
, Brensinger
C
, Brugge
WR
, Faigel
DO
, Gress
FG
, et al. Interobserver agreement among endosonographers for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions
. Gastrointest Endosc
. 2003
Jul
;58
(1
):59
–64
.
[PubMed]
0016-51077.
Belsley
NA
, Pitman
MB
, Lauwers
GY
, Brugge
WR
, Deshpande
V
. Serous cystadenoma of the pancreas: limitations and pitfalls of endoscopic ultrasound-guided fine-needle aspiration biopsy
. Cancer
. 2008
Apr
;114
(2
):102
–10
.
[PubMed]
0008-543X8.
Lal
A
, Bourtsos
EP
, DeFrias
DV
, Nemcek
AA
, Nayar
R
. Microcystic adenoma of the pancreas: clinical, radiologic, and cytologic features
. Cancer
. 2004
Oct
;102
(5
):288
–94
.
[PubMed]
0008-543X9.
Lastra
R
, Jhala
D
, Ahmad
N
, Jhala
N
. Brunner glands: A major pitfall in assessing endoscopic ultrasound guided fine needle aspiration samples ofthe pancreas
. Pathol Case Rev
. 2015
;20
(4
):182
–5
. 1082-978410.
Collins
BT
. Serous cystadenoma of the pancreas with endoscopic ultrasound fine needle aspiration biopsy and surgical correlation
. Acta Cytol
. 2013
;57
(3
):241
–51
.
[PubMed]
0001-554711.
Lilo
MT
, VandenBussche
CJ
, Allison
DB
, Lennon
AM
, Younes
BK
, Hruban
RH
, et al. Serous Cystadenoma of the Pancreas: Potentials and Pitfalls of a Preoperative Cytopathologic Diagnosis
. Acta Cytol
. 2017
;61
(1
):27
–33
.
[PubMed]
0001-554712.
Lewandrowski
KB
, Southern
JF
, Pins
MR
, Compton
CC
, Warshaw
AL
. Cyst fluid analysis in the differential diagnosis of pancreatic cysts. A comparison of pseudocysts, serous cystadenomas, mucinous cystic neoplasms, and mucinous cystadenocarcinoma
. Ann Surg
. 1993
Jan
;217
(1
):41
–7
.
[PubMed]
0003-493213.
Cizginer
S
, Turner
BG
, Bilge
AR
, Karaca
C
, Pitman
MB
, Brugge
WR
. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts
. Pancreas
. 2011
Oct
;40
(7
):1024
–8
.
[PubMed]
0885-317714.
Brugge
WR
, Lewandrowski
K
, Lee-Lewandrowski
E
, Centeno
BA
, Szydlo
T
, Regan
S
, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study
. Gastroenterology
. 2004
May
;126
(5
):1330
–6
.
[PubMed]
0016-508515.
Salomao
M
, Remotti
H
, Allendorf
JD
, Poneros
JM
, Sethi
A
, Gonda
TA
, et al. Fine-needle aspirations of pancreatic serous cystadenomas: improving diagnostic yield with cell blocks and α-inhibin immunohistochemistry
. Cancer Cytopathol
. 2014
Jan
;122
(1
):33
–9
.
[PubMed]
1934-662X16.
Wu
J
, Jiao
Y
, Dal Molin
M
, Maitra
A
, de Wilde
RF
, Wood
LD
, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways
. Proc Natl Acad Sci USA
. 2011
Dec
;108
(52
):21188
–93
.
[PubMed]
0027-842417.
Basturk
O
, Hong
SM
, Wood
LD
, Adsay
NV
, Albores-Saavedra
J
, Biankin
AV
, et al.; Baltimore Consensus Meeting
. A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas
. Am J Surg Pathol
. 2015
Dec
;39
(12
):1730
–41
.
[PubMed]
0147-518518.
Emerson
RE
, Randolph
ML
, Cramer
HM
. Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of intraductal papillary mucinous neoplasm of the pancreas is highly predictive of pancreatic neoplasia
. Diagn Cytopathol
. 2006
Jul
;34
(7
):457
–62
.
[PubMed]
8755-103919.
Zhai
J
, Sarkar
R
, Ylagan
L
. Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation
. Diagn Cytopathol
. 2006
Nov
;34
(11
):724
–30
.
[PubMed]
8755-103920.
Michaels
PJ
, Brachtel
EF
, Bounds
BC
, Brugge
WR
, Pitman
MB
. Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade
. Cancer
. 2006
Jun
;108
(3
):163
–73
.
[PubMed]
0008-543X21.
Pitman
MB
, Michaels
PJ
, Deshpande
V
, Brugge
WR
, Bounds
BC
. Cytological and cyst fluid analysis of small ([{LT}] or =3 cm) branch duct intraductal papillary mucinous neoplasms adds value to patient management decisions
. Pancreatology
. 2008
;8
(3
):277
–84
.
[PubMed]
1424-390322.
Genevay
M
, Mino-Kenudson
M
, Yaeger
K
, Konstantinidis
IT
, Ferrone
CR
, Thayer
S
, et al. Cytology adds value to imaging studies for risk assessment of malignancy in pancreatic mucinous cysts
. Ann Surg
. 2011
Dec
;254
(6
):977
–83
.
[PubMed]
0003-493223.
Pitman
MB
, Centeno
BA
, Daglilar
ES
, Brugge
WR
, Mino-Kenudson
M
. Cytological criteria of high-grade epithelial atypia in the cyst fluid of pancreatic intraductal papillary mucinous neoplasms
. Cancer Cytopathol
. 2014
Jan
;122
(1
):40
–7
.
[PubMed]
1934-662X24.
Sigel
CS
, Edelweiss
M
, Tong
LC
, Magda
J
, Oen
H
, Sigel
KM
, et al. Low interobserver agreement in cytology grading of mucinous pancreatic neoplasms
. Cancer Cytopathol
. 2014
.
[PubMed]
1934-662X25.
Park
WG
, Mascarenhas
R
, Palaez-Luna
M
, Smyrk
TC
, O’Kane
D
, Clain
JE
, et al. Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts
. Pancreas
. 2011
Jan
;40
(1
):42
–5
.
[PubMed]
0885-317726.
van der Waaij
LA
, van Dullemen
HM
, Porte
RJ
. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis
. Gastrointest Endosc
. 2005
Sep
;62
(3
):383
–9
.
[PubMed]
0016-510727.
Jin
D
, Small
AJ
, Vollmer
CM
, Jhala
N
, Furth
EE
, Ginnsberg
G
, et al. A lower cyst fluid CEA cut-off increases diangostic accuracy in identifying mucinous pancreatic cystic lesions.
Journal of the Pancreas.
2015
;16
(3
):271
–7
.28.
Layfield
LJ
, Ehya
H
, Filie
AC
, Hruban
RH
, Jhala
N
, Joseph
L
, et al.; Papanicolaou Society of Cytopathology
. Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the Papanicolaou Society of Cytopathology guidelines for pancreatobiliary cytology
. Diagn Cytopathol
. 2014
Apr
;42
(4
):351
–62
.
[PubMed]
8755-103929.
Frank
R
, Li
S
, Ahmad
NA
, Sepulveda
AR
, Jhala
NC
. Mesothelin expression in pancreatic mucinous cysts
. Am J Clin Pathol
. 2014
Sep
;142
(3
):313
–9
.
[PubMed]
0002-917330.
Khalid
A
, McGrath
KM
, Zahid
M
, Wilson
M
, Brody
D
, Swalsky
P
, et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology
. Clin Gastroenterol Hepatol
. 2005
Oct
;3
(10
):967
–73
.
[PubMed]
1542-356531.
Schoedel
KE
, Finkelstein
SD
, Ohori
NP
. K-Ras and microsatellite marker analysis of fine-needle aspirates from intraductal papillary mucinous neoplasms of the pancreas
. Diagn Cytopathol
. 2006
Sep
;34
(9
):605
–8
.
[PubMed]
8755-103932.
Wu
J
, Matthaei
H
, Maitra
A
, Dal Molin
M
, Wood
LD
, Eshleman
JR
, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development
. Sci Transl Med
. 2011
Jul
;3
(92
):92ra66
.
[PubMed]
1946-623433.
Kadayifci
A
, Atar
M
, Wang
JL
, Forcione
DG
, Casey
BW
, Pitman
MB
, et al. Value of adding GNAS testing to pancreatic cyst fluid KRAS and carcinoembryonic antigen analysis for the diagnosis of intraductal papillary mucinous neoplasms
. Dig Endosc
. 2017
Jan
;29
(1
):111
–7
.
[PubMed]
0915-563534.
Springer
S
, Wang
Y
, Dal Molin
M
, Masica
DL
, Jiao
Y
, Kinde
I
, et al. A combination of molecular markers and clinical features improve the classification of pancreatic cysts
. Gastroenterology
. 2015
Nov
;149
(6
):1501
–10
.
[PubMed]
0016-508535.
Rosenbaum
MW
, Jones
M
, Dudley
JC
, Le
LP
, Iafrate
AJ
, Pitman
MB
. Next-generation sequencing adds value to the preoperative diagnosis of pancreatic cysts
. Cancer Cytopathol
. 2017
Jan
;125
(1
):41
–7
.
[PubMed]
1934-662X36.
Faias
S
, Duarte
M
, Albuquerque
C
, da Silva
JP
, Fonseca
R
, Roque
R
, et al. Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA
. Dig Dis Sci
. 2018
Sep
;63
(9
):2351
–61
.
[PubMed]
0163-211637.
Liu
X
, Rauch
TM
, Siegal
GP
, Jhala
N
. Solid-pseudopapillary neoplasm of the pancreas: three cases with a literature review
. Appl Immunohistochem Mol Morphol
. 2006
Dec
;14
(4
):445
–53
.
[PubMed]
1541-201638.
Jhala
N
, Siegal
GP
, Jhala
D
. Large, clear cytoplasmic vacuolation: an under-recognized cytologic clue to distinguish solid pseudopapillary neoplasms of the pancreas from pancreatic endocrine neoplasms on fine-needle aspiration
. Cancer
. 2008
Aug
;114
(4
):249
–54
.
[PubMed]
0008-543X39.
Jhala
N
, Siegal
GP
, Jhala
D
. Fine Needle Aspiration: A powerful modality in preoperative diangosis of solid pseudopapillary neoplasm of the pancreas
. Pathol Case Rev
. 2007
;12
(4
):170
–6
. 1082-978440.
Canberk
S
, Elcin
BB
, Uludokumaci
A
, Uygun
N
, Gulsen
F
. Clear cell variant of solid pseudopapillary neoplasm of pancreas diagnosed by fine needle aspiration: A case report and review of the literature
. Cytojournal
. 2013
Dec
;10
(1
):26
.
[PubMed]
1742-641341.
Zhao
P
, deBrito
P
, Ozdemirli
M
, Sidawy
MK
. Solid-pseudopapillary neoplasm of the pancreas: awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors
. Diagn Cytopathol
. 2013
Oct
;41
(10
):889
–95
.
[PubMed]
8755-103942.
Burford
H
, Baloch
Z
, Liu
X
, Jhala
D
, Siegal
GP
, Jhala
N
. E-cadherin/beta-catenin and CD10: a limited immunohistochemical panel to distinguish pancreatic endocrine neoplasm from solid pseudopapillary neoplasm of the pancreas on endoscopic ultrasound-guided fine-needle aspirates of the pancreas
. Am J Clin Pathol
. 2009
Dec
;132
(6
):831
–9
.
[PubMed]
0002-917343.
Tanigawa
M
, Nakayama
M
, Taira
T
, Hattori
S
, Mihara
Y
, Kondo
R
, et al. Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor
. Med Mol Morphol
. 2018
Mar
;51
(1
):32
–40
.
[PubMed]
1860-148044.
Woo
CG
, Choi
SY
, Kwak
JJ
, Chin
S
, Kim
HK
. Clear cell neuroendocrine tumor of the pancreas in von Hippel-Lindau disease: a case report and literature review
. Neuro Endocrinol Lett
. 2017
May
;38
(2
):83
–6
.
[PubMed]
0172-780X45.
Albores-Saavedra
J
. Acinar cystadenoma of the pancreas: a previously undescribed tumor
. Ann Diagn Pathol
. 2002
Apr
;6
(2
):113
–5
.
[PubMed]
1092-913446.
Singhi
AD
, Norwood
S
, Liu
TC
, Sharma
R
, Wolfgang
CL
, Schulick
RD
, et al. Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?
Am J Surg Pathol
. 2013
Sep
;37
(9
):1329
–35
.
[PubMed]
0147-518547.
Zamboni
G
, Terris
B
, Scarpa
A
, Kosmahl
M
, Capelli
P
, Klimstra
DS
, et al. Acinar cell cystadenoma of the pancreas: a new entity?
Am J Surg Pathol
. 2002
Jun
;26
(6
):698
–704
.
[PubMed]
0147-518548.
Khor
TS
, Badizadegan
K
, Ferrone
C
, Fernández-del Castillo
C
, Desai
GS
, Saenz
A
, et al. Acinar cystadenoma of the pancreas: a clinicopathologic study of 10 cases including multilocular lesions with mural nodules
. Am J Surg Pathol
. 2012
Nov
;36
(11
):1579
–91
.
[PubMed]
0147-518549.
Yergiyev
O
, Krishnamurti
U
, Mohanty
A
, Thakkar
S
, Gurram
K
, Silverman
JF
. Fine needle aspiration cytology of acinar cell cystadenoma of the pancreas
. Acta Cytol
. 2014
;58
(3
):297
–302
.
[PubMed]
0001-554750.
Cosgrove
N
, DiPalma
J
, Katz
D
, Kowalski
T
. A Rare Case of Acinar Cell Cystadenoma in a 14-Year-Old Adolescent: A Case Report
. Case Rep Pancreat Cancer
. 2016
Jan
;2
(1
):3
–5
.
[PubMed]
2379-989751.
Jhala
N
, Jhala
D
. Cytology primer for endosnographers 4TH ed2019
.52.
Tanaka
M
, Fernández-Del Castillo
C
, Kamisawa
T
, Jang
JY
, Levy
P
, Ohtsuka
T
, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas
. Pancreatology
. 2017
Sep - Oct
;17
(5
):738
–53
.
[PubMed]
1424-390353.
Zhang
ML
, Arpin
RN
, Brugge
WR
, Forcione
DG
, Basar
O
, Pitman
MB
. Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts
. Cancer Cytopathol
. 2018
Jun
;126
(6
):414
–20
.
[PubMed]
1934-662X54.
Basar
O
, Yuksel
O
, Yang
DJ
, Samarasena
J
, Forcione
D
, DiMaio
CJ
, et al. Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts
. Gastrointest Endosc
. 2018
Jul
;88
(1
):79
–86
.
[PubMed]
0016-510755.
Lévy
P
, Rebours
V
. The Role of Endoscopic Ultrasound in the Diagnosis of Cystic Lesions of the Pancreas
. Visc Med
. 2018
Jul
;34
(3
):192
–6
.
[PubMed]
2297-472556.
Kadayifci
A
, Atar
M
, Basar
O
, Forcione
DG
, Brugge
WR
. Needle-Based Confocal Laser Endomicroscopy for Evaluation of Cystic Neoplasms of the Pancreas
. Dig Dis Sci
. 2017
May
;62
(5
):1346
–53
.
[PubMed]
0163-211657.
Lee
LS
, Andersen
DK
, Ashida
R
, Brugge
WR
, Canto
MI
, Chang
KJ
, et al. EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop
. Gastrointest Endosc
. 2017
Nov
;86
(5
):768
–78
.
[PubMed]
0016-510758.
Rhim
AD
, Thege
FI
, Santana
SM
, Lannin
TB
, Saha
TN
, Tsai
S
, et al. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions
. Gastroenterology
. 2014
Mar
;146
(3
):647
–51
.
[PubMed]
0016-508559.
Jones
M
, Zheng
Z
, Wang
J
, Dudley
J
, Albanese
E
, Kadayifci
A
, et al. Impact of next-generation sequencing on the clinical diagnosis of pancreatic cysts
. Gastrointest Endosc
. 2016
Jan
;83
(1
):140
–8
.
[PubMed]
0016-5107© 2019 S. Karger AG, Basel
2019
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