The cytologic evaluation of serous effusions may be challenging for a number of reasons. Distinction of benign, reactive conditions from malignancy represents the main focus when examining these specimens. The morphologic diagnosis of malignancy may be difficult due to the relative paucity of abnormal cells. In other situations, cellularity is not an issue, but the ability to confidently identify a second, foreign (i.e., tumor) population within a background mesothelial cells on the basis of cytomorphologic features alone may pose problems. Cases with definitive morphologic evidence of malignancy may require additional studies in order to determine the tumor subtype and, in the case of carcinoma, the primary site of origin. Cases in which a definitive and precise diagnosis of malignancy is made may be optimal candidates for further molecular testing in order to gain prognostic information and guide personal therapeutic decisions. Finally, while an inflammatory or infectious condition can be suggested on the basis of cellular components and associated background elements, the identification of causative agent(s) may be difficult without additional studies. In all of these situations, the use of ancillary studies and techniques is critical; their utility and appropriate application are the subject of this review.

1.
Fetsch
PA
,
Abati
A
.
Immunocytochemistry in effusion cytology: a contemporary review
.
Cancer
.
2001
Oct
;
93
(
5
):
293
308
.
[PubMed]
0008-543X
2.
Abati
A
,
Fetsch
P
,
Filie
A
.
If cells could talk. The application of new techniques to cytopathology
.
Clin Lab Med
.
1998
Sep
;
18
(
3
):
561
83
.
[PubMed]
0272-2712
3.
Nadji
M
,
Ganjei
P
,
Morales
A
.
Immunocytochemistry in contemporary cytology: the technique and its application
.
Lab Med
.
1994
;
25
(
8
):
502
8
. 0007-5027
4.
Leong
AS
,
Suthipintawong
C
,
Vinyuvat
S
.
Immunostaining of cytologic preparations: a review of technical problems
.
Appl Immunohistochem
.
1999
;
7
(
3
):
214
20
.
5.
Leung
SW
,
Bédard
YC
.
Immunocytochemical staining on ThinPrep processed smears
.
Mod Pathol
.
1996
Mar
;
9
(
3
):
304
6
.
[PubMed]
0893-3952
6.
Han
AC
,
Filstein
MR
,
Hunt
JV
,
Soler
AP
,
Knudsen
KA
,
Salazar
H
.
N-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas: a ThinPrep immunocytochemical study
.
Cancer
.
1999
Apr
;
87
(
2
):
83
6
.
[PubMed]
0008-543X
7.
Fetsch
PA
,
Brosky
K
,
Simsir
S
, et al.
Comparison of three commonly used cytologic preparations in effusion immunocytochemistry
.
Mod Pathol
.
2001
;
14
:
52A
.0893-3952
8.
Nance
KV
,
Silverman
JF
.
The utility of ancillary techniques in effusion cytology
.
Diagn Cytopathol
.
1992
;
8
(
2
):
185
9
.
[PubMed]
8755-1039
9.
Silverman
JF
,
Nance
K
,
Phillips
B
,
Norris
HT
.
The use of immunoperoxidase panels for the cytologic diagnosis of malignancy in serous effusions
.
Diagn Cytopathol
.
1987
Jun
;
3
(
2
):
134
40
.
[PubMed]
8755-1039
10.
Cibas
ES
,
Corson
JM
,
Pinkus
GS
.
The distinction of adenocarcinoma from malignant mesothelioma in cell blocks of effusions: the role of routine mucin histochemistry and immunohistochemical assessment of carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, and milk fat globule-derived antigen
.
Hum Pathol
.
1987
Jan
;
18
(
1
):
67
74
.
[PubMed]
0046-8177
11.
McCaughey
WT
,
Colby
TV
,
Battifora
H
,
Churg
A
,
Corson
JM
,
Greenberg
SD
, et al.
Diagnosis of diffuse malignant mesothelioma: experience of a US/Canadian Mesothelioma Panel
.
Mod Pathol
.
1991
May
;
4
(
3
):
342
53
.
[PubMed]
0893-3952
12.
Parwani
AV
,
Chan
TY
,
Ali
SZ
.
Significance of psammoma bodies in serous cavity fluid: a cytopathologic analysis
.
Cancer
.
2004
Apr
;
102
(
2
):
87
91
.
[PubMed]
0008-543X
13.
Fanning
J
,
Markuly
SN
,
Hindman
TL
,
Galle
PC
,
McRae
MA
,
Visnesky
PM
, et al.
False positive malignant peritoneal cytology and psammoma bodies in benign gynecologic disease
.
J Reprod Med
.
1996
Jul
;
41
(
7
):
504
8
.
[PubMed]
0024-7758
14.
Beaty
MW
,
Fetsch
P
,
Wilder
AM
,
Marincola
F
,
Abati
A
.
Effusion cytology of malignant melanoma. A morphologic and immunocytochemical analysis including application of the MART-1 antibody
.
Cancer
.
1997
Feb
;
81
(
1
):
57
63
.
[PubMed]
0008-543X
15.
Fetsch
PA
,
Marincola
FM
,
Filie
A
,
Hijazi
YM
,
Kleiner
DE
,
Abati
A
.
Melanoma-associated antigen recognized by T cells (MART-1): the advent of a preferred immunocytochemical antibody for the diagnosis of metastatic malignant melanoma with fine-needle aspiration
.
Cancer
.
1999
Feb
;
87
(
1
):
37
42
.
[PubMed]
0008-543X
16.
Kho-Duffin
J
,
Tao
LC
,
Cramer
H
,
Catellier
MJ
,
Irons
D
,
Ng
P
.
Cytologic diagnosis of malignant mesothelioma, with particular emphasis on the epithelial noncohesive cell type
.
Diagn Cytopathol
.
1999
Feb
;
20
(
2
):
57
62
.
[PubMed]
8755-1039
17.
Ordóñez
NG
.
Value of calretinin immunostaining in differentiating epithelial mesothelioma from lung adenocarcinoma
.
Mod Pathol
.
1998
Oct
;
11
(
10
):
929
33
.
[PubMed]
0893-3952
18.
Shield
PW
,
Callan
JJ
,
Devine
PL
.
Markers for metastatic adenocarcinoma in serous effusion specimens
.
Diagn Cytopathol
.
1994
;
11
(
3
):
237
45
.
[PubMed]
8755-1039
19.
Brockstedt
U
,
Gulyas
M
,
Dobra
K
,
Dejmek
A
,
Hjerpe
A
.
An optimized battery of eight antibodies that can distinguish most cases of epithelial mesothelioma from adenocarcinoma
.
Am J Clin Pathol
.
2000
Aug
;
114
(
2
):
203
9
.
[PubMed]
0002-9173
20.
Moran
CA
,
Wick
MR
,
Suster
S
.
The role of immunohistochemistry in the diagnosis of malignant mesothelioma
.
Semin Diagn Pathol
.
2000
Aug
;
17
(
3
):
178
83
.
[PubMed]
0740-2570
21.
Paintal
A
,
Raparia
K
,
Zakowski
MF
,
Nayar
R
.
The diagnosis of malignant mesothelioma in effusion cytology: a reappraisal and results of a multi-institution survey
.
Cancer Cytopathol
.
2013
Dec
;
121
(
12
):
703
7
.
[PubMed]
1934-662X
22.
Marchevsky
AM
.
Application of immunohistochemistry to the diagnosis of malignant mesothelioma
.
Arch Pathol Lab Med
.
2008
Mar
;
132
(
3
):
397
401
.
[PubMed]
1543-2165
23.
Yaziji
H
,
Battifora
H
,
Barry
TS
,
Hwang
HC
,
Bacchi
CE
,
McIntosh
MW
, et al.
Evaluation of 12 antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma: identification of a three-antibody immunohistochemical panel with maximal sensitivity and specificity
.
Mod Pathol
.
2006
Apr
;
19
(
4
):
514
23
.
[PubMed]
0893-3952
24.
Davidson
B
,
Nielsen
S
,
Christensen
J
,
Asschenfeldt
P
,
Berner
A
,
Risberg
B
, et al.
The role of desmin and N-cadherin in effusion cytology: a comparative study using established markers of mesothelial and epithelial cells
.
Am J Surg Pathol
.
2001
Nov
;
25
(
11
):
1405
12
.
[PubMed]
0147-5185
25.
Hasteh
F
,
Lin
GY
,
Weidner
N
,
Michael
CW
.
The use of immunohistochemistry to distinguish reactive mesothelial cells from malignant mesothelioma in cytologic effusions
.
Cancer Cytopathol
.
2010
Apr
;
118
(
2
):
90
6
.
[PubMed]
1934-662X
26.
Hwang
HC
,
Sheffield
BS
,
Rodriguez
S
,
Thompson
K
,
Tse
CH
,
Gown
AM
, et al.
Utility of BAP1 immunohistochemistry and p16 (CDKN2A) FISH in the diagnosis of malignant mesothelioma in effusion cytology specimens
.
Am J Surg Pathol
.
2016
Jan
;
40
(
1
):
120
6
.
[PubMed]
0147-5185
27.
Testa
JR
,
Cheung
M
,
Pei
J
,
Below
JE
,
Tan
Y
,
Sementino
E
, et al.
Germline BAP1 mutations predispose to malignant mesothelioma
.
Nat Genet
.
2011
Aug
;
43
(
10
):
1022
5
.
[PubMed]
1061-4036
28.
Murali
R
,
Wiesner
T
,
Scolyer
RA
.
Tumours associated with BAP1 mutations
.
Pathology
.
2013
Feb
;
45
(
2
):
116
26
.
[PubMed]
0031-3025
29.
Nasu
M
,
Emi
M
,
Pastorino
S
,
Tanji
M
,
Powers
A
,
Luk
H
, et al.
High Incidence of Somatic BAP1 alterations in sporadic malignant mesothelioma
.
J Thorac Oncol
.
2015
Apr
;
10
(
4
):
565
76
.
[PubMed]
1556-0864
30.
Hecht
JL
,
Pinkus
JL
,
Weinstein
LJ
,
Pinkus
GS
.
The value of thyroid transcription factor-1 in cytologic preparations as a marker for metastatic adenocarcinoma of lung origin
.
Am J Clin Pathol
.
2001
Oct
;
116
(
4
):
483
8
.
[PubMed]
0002-9173
31.
Ng
WK
,
Chow
JC
,
Ng
PK
.
Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens
.
Cancer
.
2002
Feb
;
96
(
1
):
43
8
.
[PubMed]
0008-543X
32.
Werling
RW
,
Yaziji
H
,
Bacchi
CE
,
Gown
AM
.
CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas
.
Am J Surg Pathol
.
2003
Mar
;
27
(
3
):
303
10
.
[PubMed]
0147-5185
33.
Genega
EM
,
Ghebremichael
M
,
Najarian
R
,
Fu
Y
,
Wang
Y
,
Argani
P
, et al.
Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade
.
Am J Clin Pathol
.
2010
Dec
;
134
(
6
):
873
9
.
[PubMed]
0002-9173
34.
Gurel
B
,
Ali
TZ
,
Montgomery
EA
,
Begum
S
,
Hicks
J
,
Goggins
M
, et al.
NKX3.1 as a marker of prostatic origin in metastatic tumors
.
Am J Surg Pathol
.
2010
Aug
;
34
(
8
):
1097
105
.
[PubMed]
0147-5185
35.
Shield
PW
,
Papadimos
DJ
,
Walsh
MD
.
GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens
.
Cancer Cytopathol
.
2014
Apr
;
122
(
4
):
307
12
.
[PubMed]
1934-662X
36.
Liu
H
,
Shi
J
,
Wilkerson
ML
,
Lin
F
.
Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas
.
Am J Clin Pathol
.
2012
Jul
;
138
(
1
):
57
64
.
[PubMed]
0002-9173
37.
Waters
L
,
Crumley
S
,
Truong
L
,
Mody
D
,
Coffey
D
.
PAX2 and PAX8: useful markers for metastatic effusions
.
Acta Cytol
.
2014
;
58
(
1
):
60
6
.
[PubMed]
0001-5547
38.
Kerr
KM
,
Nicolson
MC
.
Non-small cell lung cancer, PD-L1, and the pathologist
.
Arch Pathol Lab Med
.
2016
Mar
;
140
(
3
):
249
54
.
[PubMed]
0003-9985
39.
Brahmer
JR
.
Harnessing the immune system for the treatment of non-small-cell lung cancer
.
J Clin Oncol
.
2013
Mar
;
31
(
8
):
1021
8
.
[PubMed]
0732-183X
40.
Villaruz
LC
,
Kalyan
A
,
Zarour
H
,
Socinski
MA
.
Immunotherapy in lung cancer
.
Transl Lung Cancer Res
.
2014
Feb
;
3
(
1
):
2
14
.
[PubMed]
2218-6751
41.
Kerr
KM
,
Tsao
MS
,
Nicholson
AG
,
Yatabe
Y
,
Wistuba
II
,
Hirsch
FR
;
IASLC Pathology Committee
.
Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer: in what state is this art?
J Thorac Oncol
.
2015
Jul
;
10
(
7
):
985
9
.
[PubMed]
1556-0864
42.
Yang
CY
,
Lin
MW
,
Chang
YL
,
Wu
CT
,
Yang
PC
.
Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes
.
Eur J Cancer
.
2014
May
;
50
(
7
):
1361
9
.
[PubMed]
0959-8049
43.
Velcheti
V
,
Schalper
KA
,
Carvajal
DE
,
Anagnostou
VK
,
Syrigos
KN
,
Sznol
M
, et al.
Programmed death ligand-1 expression in non-small cell lung cancer
.
Lab Invest
.
2014
Jan
;
94
(
1
):
107
16
.
[PubMed]
0023-6837
44.
Herbst
RS
,
Soria
JC
,
Kowanetz
M
,
Fine
GD
,
Hamid
O
,
Gordon
MS
, et al.
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
.
Nature
.
2014
Nov
;
515
(
7528
):
563
7
.
[PubMed]
0028-0836
45.
VanderLaan
PA
.
Molecular markers: implications for cytopathology and specimen collection
.
Cancer Cytopathol
.
2015
Aug
;
123
(
8
):
454
60
.
[PubMed]
1934-662X
46.
Lindeman
NI
,
Cagle
PT
,
Beasley
MB
,
Chitale
DA
,
Dacic
S
,
Giaccone
G
, et al.
Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
.
Arch Pathol Lab Med
.
2013
Jun
;
137
(
6
):
828
60
.
[PubMed]
0003-9985
47.
Shaw
AT
,
Ou
SH
,
Bang
YJ
,
Camidge
DR
,
Solomon
BJ
,
Salgia
R
, et al.
Crizotinib in ROS1-rearranged non-small-cell lung cancer
.
N Engl J Med
.
2014
Nov
;
371
(
21
):
1963
71
.
[PubMed]
0028-4793
48.
Pisapia
P
,
Lozano
MD
,
Vigliar
E
,
Bellevicine
C
,
Pepe
F
,
Malapelle
U
, et al.
ALK and ROS1 testing on lung cancer cytologic samples: perspectives
.
Cancer Cytopathol
.
2017
Nov
;
125
(
11
):
817
30
.
[PubMed]
1934-662X
49.
Shabaik
A
,
Lin
G
,
Peterson
M
,
Hasteh
F
,
Tipps
A
,
Datnow
B
, et al.
Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma
.
Diagn Cytopathol
.
2011
May
;
39
(
5
):
328
32
.
[PubMed]
8755-1039
50.
Fetsch
PA
,
Abati
A
.
The effects of antibody clone and pretreatment method on the results of HER2 immunostaining in cytologic samples of metastatic breast cancer: A query and a review of the literature
.
Diagn Cytopathol
.
2007
Jun
;
35
(
6
):
319
28
.
[PubMed]
8755-1039
51.
Hanley
KZ
,
Birdsong
GG
,
Cohen
C
,
Siddiqui
MT
.
Immunohistochemical detection of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression in breast carcinomas: comparison on cell block, needle-core, and tissue block preparations
.
Cancer
.
2009
Aug
;
117
(
4
):
279
88
.
[PubMed]
0008-543X
52.
Williams
SL
,
Birdsong
GG
,
Cohen
C
,
Siddiqui
MT
.
Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations
.
Int J Clin Exp Pathol
.
2009
;
2
(
5
):
476
80
.
[PubMed]
1936-2625
53.
Berliner
JA
,
Janssen
M
,
McLatchie
C
. The use of scanning electron microscopy in the diagnosis of malignancy in human serous effusions. In:
Johari
O
,
Becker
PP
, editors
.
Scanning Electron Microscopy 1978/2
.
Chicago
:
Scanning Electron Microscopy, Inc.
;
1978
.
54.
Domagala
W
,
Koss
LG
. Configuration of surfaces of cells in effusion by scanning electron microscopy. In:
Koss
LG
,
Coleman
DV
, editors
.
Advances in Clinical Cytology
.
London
:
Butterworths
;
1981
.
55.
Domagala
W
,
Woyke
S
.
Transmission and scanning electron microscopic studies of cells in effusions
.
Acta Cytol
.
1975
May-Jun
;
19
(
3
):
214
24
.
[PubMed]
0001-5547
56.
Gondos
B
,
Lai
CE
,
King
EB
.
Distinction between atypical mesothelial cells and malignant cells by scanning electron microscopy
.
Acta Cytol
.
1979
Jul-Aug
;
23
(
4
):
321
6
.
[PubMed]
0001-5547
57.
Hanna
W
,
Kahn
HJ
.
The ultrastructure of metastatic adenocarcinoma in serous fluids. An aid in identification of the primary site of the neoplasm
.
Acta Cytol
.
1985
May-Jun
;
29
(
3
):
202
10
.
[PubMed]
0001-5547
58.
Herrera
GA
,
Wilkerson
JA
.
Ultrastructural studies of malignant cells in fluids
.
Diagn Cytopathol
.
1985
Oct-Dec
;
1
(
4
):
272
85
.
[PubMed]
8755-1039
59.
Hultgren
S
,
Hidvegi
DF
.
Improved transmission electron microscopy technique for the study of cytologic material
.
Acta Cytol
.
1985
Mar-Apr
;
29
(
2
):
179
83
.
[PubMed]
0001-5547
60.
Kaneshima
S
,
Kiyasu
Y
,
Kudo
H
,
Koga
S
,
Tanaka
K
.
An application of scanning electron microscopy to cytodiagnosis of pleural and peritoneal fluids. Comparative observation of the same cells by light microscopy and scanning electron microscopy
.
Acta Cytol
.
1978
Nov-Dec
;
22
(
6
):
490
9
.
[PubMed]
0001-5547
61.
Domínguez-Malagón
H
,
Cano-Valdez
AM
,
González-Carrillo
C
,
Campos-Salgado
YE
,
Lara-Garcia
A
,
Lopez-Mejia
M
, et al.
Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma
.
Ultrastruct Pathol
.
2016
Sep-Oct
;
40
(
5
):
254
60
.
[PubMed]
0191-3123
62.
Ordonez
N
,
Mackay
B
.
The roles of immunohistochemistry and electron microscopy in distinguishing epithelial mesothelioma of the pleura from adenocarcinoma
.
Adv Anat Pathol
.
1996
;
3
(
5
):
273
93
. 1072-4109
63.
Oczypok
EA
,
Oury
TD
.
Electron microscopy remains the gold standard for the diagnosis of epithelial malignant mesothelioma: a case study
.
Ultrastruct Pathol
.
2015
Apr
;
39
(
2
):
153
8
.
[PubMed]
0191-3123
64.
Ng
WK
,
Yau
BW
,
Ma
L
.
Diagnostic utility and limitations of electron microscopy in effusion fluid cytology smears
.
Diagn Cytopathol
.
2003
Jul
;
29
(
1
):
46
8
.
[PubMed]
8755-1039
65.
Coleman
DV
,
Russell
WJ
,
Hodgson
J
,
Pe
T
,
Mowbray
JF
.
Human papovavirus in Papanicolaou smears of urinary sediment detected by transmission electron microscopy
.
J Clin Pathol
.
1977
Nov
;
30
(
11
):
1015
20
.
[PubMed]
0021-9746
66.
Hills
E
,
Laverty
CR
.
Electron microscopic detection of papilloma virus particles in selected koilocytotic cells in a routine cervical smear
.
Acta Cytol
.
1979
Jan-Feb
;
23
(
1
):
53
6
.
[PubMed]
0001-5547
67.
Ahmed
RA
,
Marrie
TJ
,
Huang
JQ
.
Thoracic empyema in patients with community-acquired pneumonia
.
Am J Med
.
2006
Oct
;
119
(
10
):
877
83
.
[PubMed]
0002-9343
68.
Lippi
G
,
Danese
E
,
Cervellin
G
,
Montagnana
M
.
Laboratory diagnostics of spontaneous bacterial peritonitis
.
Clin Chim Acta
.
2014
Mar
;
430
:
164
70
.
[PubMed]
0009-8981
69.
Chen
ML
,
Yu
WC
,
Lam
CW
,
Au
KM
,
Kong
FY
,
Chan
AY
.
Diagnostic value of pleural fluid adenosine deaminase activity in tuberculous pleurisy
.
Clin Chim Acta
.
2004
Mar
;
341
(
1-2
):
101
7
.
[PubMed]
0009-8981
70.
Theron
G
,
Peter
J
,
Calligaro
G
,
Meldau
R
,
Hanrahan
C
,
Khalfey
H
, et al.
Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments
.
Sci Rep
.
2014
Jul
;
4
(
1
):
5658
.
[PubMed]
2045-2322
71.
Diaz
JH
.
Paragonimiasis acquired in the United States: native and nonnative species
.
Clin Microbiol Rev
.
2013
Jul
;
26
(
3
):
493
504
.
[PubMed]
0893-8512
72.
Yenkeshwar
PN
,
Kumbhalkar
DT
,
Bobhate
SK
.
Microfilariae in fine needle aspirates: a report of 22 cases
.
Indian J Pathol Microbiol
.
2006
Jul
;
49
(
3
):
365
9
.
[PubMed]
0377-4929
73.
O’Leary
TJ
.
Flow cytometry in diagnostic cytology
.
Diagn Cytopathol
.
1998
Jan
;
18
(
1
):
41
6
.
[PubMed]
8755-1039
74.
Dey
P
.
Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin’s lymphomas on fine needle aspiration cytology
.
Cytopathology
.
2006
Oct
;
17
(
5
):
275
87
.
[PubMed]
0956-5507
75.
Meda
BA
,
Buss
DH
,
Woodruff
RD
,
Cappellari
JO
,
Rainer
RO
,
Powell
BL
, et al.
Diagnosis and subclassification of primary and recurrent lymphoma. The usefulness and limitations of combined fine-needle aspiration cytomorphology and flow cytometry
.
Am J Clin Pathol
.
2000
May
;
113
(
5
):
688
99
.
[PubMed]
0002-9173
76.
Sandhaus
LM
.
Fine-needle aspiration cytology in the diagnosis of lymphoma. The next step
.
Am J Clin Pathol
.
2000
May
;
113
(
5
):
623
7
.
[PubMed]
0002-9173
77.
Moriarty
AT
,
Wiersema
L
,
Snyder
W
,
Kotylo
PK
,
McCloskey
DW
.
Immunophenotyping of cytologic specimens by flow cytometry
.
Diagn Cytopathol
.
1993
;
9
(
3
):
252
8
.
[PubMed]
8755-1039
78.
Cibas
ES
,
Malkin
MG
,
Posner
JB
,
Melamed
MR
.
Detection of DNA abnormalities by flow cytometry in cells from cerebrospinal fluid
.
Am J Clin Pathol
.
1987
Nov
;
88
(
5
):
570
7
.
[PubMed]
0002-9173
79.
Redner
A
,
Melamed
MR
,
Andreeff
M
.
Detection of central nervous system relapse in acute leukemia by multiparameter flow cytometry of DNA, RNA, and CALLA
.
Ann N Y Acad Sci
.
1986
;
468
1 Clinical Cyto
:
241
55
.
[PubMed]
0077-8923
80.
Dunphy
CH
,
Ramos
R
.
Combining fine-needle aspiration and flow cytometric immunophenotyping in evaluation of nodal and extranodal sites for possible lymphoma: a retrospective review
.
Diagn Cytopathol
.
1997
Mar
;
16
(
3
):
200
6
.
[PubMed]
8755-1039
81.
Ravinsky
E
,
Morales
C
,
Kutryk
E
,
Chrobak
A
,
Paraskevas
F
.
Cytodiagnosis of lymphoid proliferations by fine needle aspiration biopsy. Adjunctive value of flow cytometry
.
Acta Cytol
.
1999
Nov-Dec
;
43
(
6
):
1070
8
.
[PubMed]
0001-5547
82.
Young
NA
,
Al-Saleem
TI
,
Ehya
H
,
Smith
MR
.
Utilization of fine-needle aspiration cytology and flow cytometry in the diagnosis and subclassification of primary and recurrent lymphoma
.
Cancer
.
1998
Aug
;
84
(
4
):
252
61
.
[PubMed]
0008-543X
83.
Das
DK
.
Serous effusions in malignant lymphomas: a review
.
Diagn Cytopathol
.
2006
May
;
34
(
5
):
335
47
.
[PubMed]
8755-1039
84.
Simsir
A
,
Fetsch
P
,
Stetler-Stevenson
M
,
Abati
A
.
Immunophenotypic analysis of non-Hodgkin’s lymphomas in cytologic specimens: a correlative study of immunocytochemical and flow cytometric techniques
.
Diagn Cytopathol
.
1999
May
;
20
(
5
):
278
84
.
[PubMed]
8755-1039
85.
Yu
GH
,
Vergara
N
,
Moore
EM
,
King
RL
.
Use of flow cytometry in the diagnosis of lymphoproliferative disorders in fluid specimens
.
Diagn Cytopathol
.
2014
Aug
;
42
(
8
):
664
70
.
[PubMed]
8755-1039
86.
Stetler-Stevenson
MA
,
Yuan
CM
. Flow cytometry. In:
Jaffe
ES
,
Harris
NL
,
Vardiman
JW
,
Campo
E
,
Arber
D
, editors
.
Hematopathology
.
Philadelphia
:
Elsevier Saunders
;
2011
.
87.
Kussick
SJ
,
Kalnoski
M
,
Braziel
RM
,
Wood
BL
.
Prominent clonal B-cell populations identified by flow cytometry in histologically reactive lymphoid proliferations
.
Am J Clin Pathol
.
2004
Apr
;
121
(
4
):
464
72
.
[PubMed]
0002-9173
88.
Tembhare
P
,
Yuan
CM
,
Morris
JC
,
Janik
JE
,
Filie
AC
,
Stetler-Stevenson
M
.
Flow cytometric immunophenotypic assessment of T-cell clonality by vβ repertoire analysis in fine-needle aspirates and cerebrospinal fluid
.
Am J Clin Pathol
.
2012
Feb
;
137
(
2
):
220
6
.
[PubMed]
0002-9173
89.
Kesler
MV
,
Paranjape
GS
,
Asplund
SL
,
McKenna
RW
,
Jamal
S
,
Kroft
SH
.
Anaplastic large cell lymphoma: a flow cytometric analysis of 29 cases
.
Am J Clin Pathol
.
2007
Aug
;
128
(
2
):
314
22
.
[PubMed]
0002-9173
90.
Ceyhan
BB
,
Demiralp
E
,
Celikel
T
.
Analysis of pleural effusions using flow cytometry
.
Respiration
.
1996
;
63
(
1
):
17
24
.
[PubMed]
0025-7931
91.
Saha
I
,
Dey
P
,
Vhora
H
,
Nijhawan
R
.
Role of DNA flow cytometry and image cytometry on effusion fluid
.
Diagn Cytopathol
.
2000
Feb
;
22
(
2
):
81
5
.
[PubMed]
8755-1039
92.
Krishan
A
,
Ganjei-Azar
P
,
Jorda
M
,
Hamelik
RM
,
Reis
IM
,
Nadji
M
.
Detection of tumor cells in body cavity fluids by flow cytometric and immunocytochemical analysis
.
Diagn Cytopathol
.
2006
Aug
;
34
(
8
):
528
41
.
[PubMed]
8755-1039
93.
Kentrou
NA
,
Tsagarakis
NJ
,
Tzanetou
K
,
Damala
M
,
Papadimitriou
KA
,
Skoumi
D
, et al.
An improved flow cytometric assay for detection and discrimination between malignant cells and atypical mesothelial cells, in serous cavity effusions
.
Cytometry B Clin Cytom
.
2011
Sep
;
80
(
5
):
324
34
.
[PubMed]
1552-4949
94.
Croonen
AM
,
van der Valk
P
,
Herman
CJ
,
Lindeman
J
.
Cytology, immunopathology and flow cytometry in the diagnosis of pleural and peritoneal effusions
.
Lab Invest
.
1988
Jun
;
58
(
6
):
725
32
.
[PubMed]
0023-6837
95.
Nabeshima
K
,
Matsumoto
S
,
Hamasaki
M
,
Hida
T
,
Kamei
T
,
Hiroshima
K
, et al.
Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations
.
Diagn Cytopathol
.
2016
Sep
;
44
(
9
):
774
80
.
[PubMed]
8755-1039
96.
Husain
AN
,
Colby
TV
,
Ordóñez
NG
,
Krausz
T
,
Borczuk
A
,
Cagle
PT
, et al.
Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group
.
Arch Pathol Lab Med
.
2009
Aug
;
133
(
8
):
1317
31
.
[PubMed]
1543-2165
97.
Husain
AN
,
Colby
T
,
Ordonez
N
,
Krausz
T
,
Attanoos
R
,
Beasley
MB
, et al.;
International Mesothelioma Interest Group
.
Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group
.
Arch Pathol Lab Med
.
2013
May
;
137
(
5
):
647
67
.
[PubMed]
0003-9985
98.
Cheng
JQ
,
Jhanwar
SC
,
Klein
WM
,
Bell
DW
,
Lee
WC
,
Altomare
DA
, et al.
p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma
.
Cancer Res
.
1994
Nov
;
54
(
21
):
5547
51
.
[PubMed]
0008-5472
99.
Illei
PB
,
Ladanyi
M
,
Rusch
VW
,
Zakowski
MF
.
The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions
.
Cancer
.
2003
Feb
;
99
(
1
):
51
6
.
[PubMed]
0008-543X
100.
Chiosea
S
,
Krasinskas
A
,
Cagle
PT
,
Mitchell
KA
,
Zander
DS
,
Dacic
S
.
Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas
.
Mod Pathol
.
2008
Jun
;
21
(
6
):
742
7
.
[PubMed]
0893-3952
101.
Onofre
FB
,
Onofre
AS
,
Pomjanski
N
,
Buckstegge
B
,
Grote
HJ
,
Böcking
A
.
9p21 Deletion in the diagnosis of malignant mesothelioma in serous effusions additional to immunocytochemistry, DNA-ICM, and AgNOR analysis
.
Cancer
.
2008
Jun
;
114
(
3
):
204
15
.
[PubMed]
0008-543X
102.
Dacic
S
,
Kothmaier
H
,
Land
S
,
Shuai
Y
,
Halbwedl
I
,
Morbini
P
, et al.
Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas
.
Virchows Arch
.
2008
Dec
;
453
(
6
):
627
35
.
[PubMed]
0945-6317
103.
Takeda
M
,
Kasai
T
,
Enomoto
Y
,
Takano
M
,
Morita
K
,
Kadota
E
, et al.
9p21 deletion in the diagnosis of malignant mesothelioma, using fluorescence in situ hybridization analysis
.
Pathol Int
.
2010
May
;
60
(
5
):
395
9
.
[PubMed]
1320-5463
104.
Chung
CT
,
Santos
GC
,
Hwang
DM
,
Ludkovski
O
,
Pintilie
M
,
Squire
JA
, et al.
FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma
.
J Clin Pathol
.
2010
Jul
;
63
(
7
):
630
4
.
[PubMed]
0021-9746
105.
Monaco
SE
,
Shuai
Y
,
Bansal
M
,
Krasinskas
AM
,
Dacic
S
.
The diagnostic utility of p16 FISH and GLUT-1 immunohistochemical analysis in mesothelial proliferations
.
Am J Clin Pathol
.
2011
Apr
;
135
(
4
):
619
27
.
[PubMed]
0002-9173
106.
Wu
D
,
Hiroshima
K
,
Matsumoto
S
,
Nabeshima
K
,
Yusa
T
,
Ozaki
D
, et al.
Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis
.
Am J Clin Pathol
.
2013
Jan
;
139
(
1
):
39
46
.
[PubMed]
0002-9173
107.
Matsumoto
S
,
Nabeshima
K
,
Kamei
T
,
Hiroshima
K
,
Kawahara
K
,
Hata
S
, et al.
Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology
.
Cancer Cytopathol
.
2013
Aug
;
121
(
8
):
415
22
.
[PubMed]
1934-662X
108.
Hida
T
,
Matsumoto
S
,
Hamasaki
M
,
Kawahara
K
,
Tsujimura
T
,
Hiroshima
K
, et al.
Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue
.
Cancer Sci
.
2015
Nov
;
106
(
11
):
1635
41
.
[PubMed]
1347-9032
109.
Fiegl
M
,
Kaufmann
H
,
Zojer
N
,
Schuster
R
,
Wiener
H
,
Müllauer
L
, et al.
Malignant cell detection by fluorescence in situ hybridization (FISH) in effusions from patients with carcinoma
.
Hum Pathol
.
2000
Apr
;
31
(
4
):
448
55
.
[PubMed]
0046-8177
110.
Fiegl
M
,
Massoner
A
,
Haun
M
,
Sturm
W
,
Kaufmann
H
,
Hack
R
, et al.
Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH)
.
Br J Cancer
.
2004
Aug
;
91
(
3
):
558
63
.
[PubMed]
0007-0920
111.
National Comprehensive Cancer Network
. NCCN guidelines: non-small cell lung cancer (version 6.
2018
). Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed October 1, 2018.
112.
National Comprehensive Cancer Network
. NCCN guidelines: colon cancer (version 3.
2018
). Available from: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed October 1, 2018.
113.
National Comprehensive Cancer Network
. NCCN guidelines: melanoma (version 3.
2018
). Available from: https://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed October 1, 2018.
114.
Lindeman
NI
,
Cagle
PT
,
Aisner
DL
,
Arcila
ME
,
Beasley
MB
,
Bernicker
EH
, et al.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology
.
Arch Pathol Lab Med
.
2018
Mar
;
142
(
3
):
321
46
.
[PubMed]
0003-9985
115.
Tao
JJ
,
Schram
AM
,
Hyman
DM
.
Basket studies: redefining clinical trials in the era of genome-driven oncology
.
Annu Rev Med
.
2018
Jan
;
69
(
1
):
319
31
.
[PubMed]
0066-4219
116.
Betz
BL
,
Dixon
CA
,
Weigelin
HC
,
Knoepp
SM
,
Roh
MH
.
The use of stained cytologic direct smears for ALK gene rearrangement analysis of lung adenocarcinoma
.
Cancer Cytopathol
.
2013
Sep
;
121
(
9
):
489
99
.
[PubMed]
1934-662X
117.
Minca
EC
,
Lanigan
CP
,
Reynolds
JP
,
Wang
Z
,
Ma
PC
,
Cicenia
J
, et al.
ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material
.
J Thorac Oncol
.
2014
Apr
;
9
(
4
):
464
8
.
[PubMed]
1556-0864
118.
Lozano
MD
,
Zulueta
JJ
,
Echeveste
JI
,
Gúrpide
A
,
Seijo
LM
,
Martín-Algarra
S
, et al.
Assessment of epidermal growth factor receptor and K-ras mutation status in cytological stained smears of non-small cell lung cancer patients: correlation with clinical outcomes
.
Oncologist
.
2011
;
16
(
6
):
877
85
.
[PubMed]
1083-7159
119.
Bellevicine
C
,
Malapelle
U
,
Vigliar
E
,
de Luca
C
,
Troncone
G
.
Epidermal growth factor receptor test performed on liquid-based cytology lung samples: experience of an academic referral center
.
Acta Cytol
.
2014
;
58
(
6
):
589
94
.
[PubMed]
0001-5547
120.
Min
KW
,
Kim
WS
,
Jang
SJ
,
Choi
YD
,
Chang
S
,
Jung
SH
, et al.;
Korean Cardiopulmonary Pathology Study Group
.
MassARRAY, pyrosequencing, and PNA clamping for EGFR mutation detection in lung cancer tissue and cytological samples: a multicenter study
.
J Cancer Res Clin Oncol
.
2016
Oct
;
142
(
10
):
2209
16
.
[PubMed]
0171-5216
121.
Frampton
GM
,
Fichtenholtz
A
,
Otto
GA
,
Wang
K
,
Downing
SR
,
He
J
, et al.
Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing
.
Nat Biotechnol
.
2013
Nov
;
31
(
11
):
1023
31
.
[PubMed]
1087-0156
122.
Drilon
A
,
Wang
L
,
Arcila
ME
,
Balasubramanian
S
,
Greenbowe
JR
,
Ross
JS
, et al.
Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches
.
Clin Cancer Res
.
2015
Aug
;
21
(
16
):
3631
9
.
[PubMed]
1078-0432
123.
Scarpa
A
,
Sikora
K
,
Fassan
M
,
Rachiglio
AM
,
Cappellesso
R
,
Antonello
D
, et al.
Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel
.
PLoS One
.
2013
Nov
;
8
(
11
):
e80478
.
[PubMed]
1932-6203
124.
Endris
V
,
Penzel
R
,
Warth
A
,
Muckenhuber
A
,
Schirmacher
P
,
Stenzinger
A
, et al.
Molecular diagnostic profiling of lung cancer specimens with a semiconductor-based massive parallel sequencing approach: feasibility, costs, and performance compared with conventional sequencing
.
J Mol Diagn
.
2013
Nov
;
15
(
6
):
765
75
.
[PubMed]
1525-1578
125.
Jennings
L
,
Van Deerlin
VM
,
Gulley
ML
;
College of American Pathologists Molecular Pathology Resource Committee
.
Recommended principles and practices for validating clinical molecular pathology tests
.
Arch Pathol Lab Med
.
2009
May
;
133
(
5
):
743
55
.
[PubMed]
1543-2165
126.
Jennings
LJ
,
Arcila
ME
,
Corless
C
,
Kamel-Reid
S
,
Lubin
IM
,
Pfeifer
J
, et al.
Guidelines for validation of next-generation sequencing-based oncology panels: a joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists
.
J Mol Diagn
.
2017
May
;
19
(
3
):
341
65
.
[PubMed]
1525-1578
127.
Heymann
JJ
,
Bulman
WA
,
Maxfield
RA
,
Powell
CA
,
Halmos
B
,
Sonett
J
, et al.
Molecular testing guidelines for lung adenocarcinoma: utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples
.
Cytojournal
.
2014
May
;
11
(
1
):
12
.
[PubMed]
1742-6413
128.
Jain
D
,
Mathur
SR
,
Iyer
VK
.
Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies
.
Cytopathology
.
2014
Dec
;
25
(
6
):
356
71
.
[PubMed]
0956-5507
129.
Srinivasan
M
,
Sedmak
D
,
Jewell
S
.
Effect of fixatives and tissue processing on the content and integrity of nucleic acids
.
Am J Pathol
.
2002
Dec
;
161
(
6
):
1961
71
.
[PubMed]
0002-9440
130.
Williams
C
,
Pontén
F
,
Moberg
C
,
Söderkvist
P
,
Uhlén
M
,
Pontén
J
, et al.
A high frequency of sequence alterations is due to formalin fixation of archival specimens
.
Am J Pathol
.
1999
Nov
;
155
(
5
):
1467
71
.
[PubMed]
0002-9440
131.
Gailey
MP
,
Stence
AA
,
Jensen
CS
,
Ma
D
.
Multiplatform comparison of molecular oncology tests performed on cytology specimens and formalin-fixed, paraffin-embedded tissue
.
Cancer Cytopathol
.
2015
Jan
;
123
(
1
):
30
9
.
[PubMed]
1934-662X
132.
Treece
AL
,
Montgomery
ND
,
Patel
NM
,
Civalier
CJ
,
Dodd
LG
,
Gulley
ML
, et al.
FNA smears as a potential source of DNA for targeted next-generation sequencing of lung adenocarcinomas
.
Cancer Cytopathol
.
2016
Jun
;
124
(
6
):
406
14
.
[PubMed]
1934-662X
133.
Roy-Chowdhuri
S
,
Chen
H
,
Singh
RR
,
Krishnamurthy
S
,
Patel
KP
,
Routbort
MJ
, et al.
Concurrent fine needle aspirations and core needle biopsies: a comparative study of substrates for next-generation sequencing in solid organ malignancies
.
Mod Pathol
.
2017
Apr
;
30
(
4
):
499
508
.
[PubMed]
0893-3952
134.
Hwang
DH
,
Garcia
EP
,
Ducar
MD
,
Cibas
ES
,
Sholl
LM
.
Next-generation sequencing of cytologic preparations: an analysis of quality metrics
.
Cancer Cytopathol
.
2017
Oct
;
125
(
10
):
786
94
.
[PubMed]
1934-662X
135.
Martini
M
,
Capodimonti
S
,
Cenci
T
,
Bilotta
M
,
Fadda
G
,
Larocca
LM
, et al.
To obtain more with less: cytologic samples with ancillary molecular techniques—the useful role of liquid-based cytology
.
Arch Pathol Lab Med
.
2018
Mar
;
142
(
3
):
299
307
.
[PubMed]
0003-9985
136.
Wei
S
,
Lieberman
D
,
Morrissette
JJ
,
Baloch
ZW
,
Roth
DB
,
McGrath
C
.
Using “residual” FNA rinse and body fluid specimens for next-generation sequencing: an institutional experience
.
Cancer Cytopathol
.
2016
May
;
124
(
5
):
324
9
.
[PubMed]
1934-662X
137.
Bellevicine
C
,
Malapelle
U
,
Vigliar
E
,
Pisapia
P
,
Vita
G
,
Troncone
G
.
How to prepare cytological samples for molecular testing
.
J Clin Pathol
.
2017
Oct
;
70
(
10
):
819
26
.
[PubMed]
0021-9746
138.
da Cunha Santos
G
,
Saieg
MA
.
Preanalytic specimen triage: Smears, cell blocks, cytospin preparations, transport media, and cytobanking
.
Cancer Cytopathol
.
2017
Jun
;
125
S6
:
455
64
.
[PubMed]
1934-662X
139.
Roy-Chowdhuri
S
,
Stewart
J
.
Preanalytical variables in cytology: lessons learned from next-generation sequencing—the MD Anderson experience
.
Arch Pathol Lab Med
.
2016
;
140
(
11
):
1191
9
. 0003-9985
140.
Tian
SK
,
Killian
JK
,
Rekhtman
N
,
Benayed
R
,
Middha
S
,
Ladanyi
M
, et al.
Optimizing workflows and processing of cytologic samples for comprehensive analysis by next-generation sequencing: Memorial Sloan Kettering Cancer Center experience
.
Arch Pathol Lab Med
.
2016
Sep
;
140
(
11
):
1200
5
.
[PubMed]
0003-9985
141.
Fassan
M
.
Molecular Diagnostics in Pathology: time for a next-generation pathologist?
Arch Pathol Lab Med
.
2018
Mar
;
142
(
3
):
313
20
.
[PubMed]
0003-9985
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.