Mandatory Second Opinion in Cytopathology

Article (PDF Available)inCancer 117(2):82-91 · April 2009with21 Reads
DOI: 10.1002/cncy.20019 · Source: PubMed
Abstract
Mandatory review of outside pathologic material is intended to detect interpretive errors that may have a clinically significant impact on patient care. Prior to definitive treatment of referred patients, the University of Iowa Carver College of Medicine requires a review of pertinent pathologic material previously obtained at outside institutions. The aims of this study were to determine if this local standard of practice has a measurable impact on patient care. The pathologic diagnoses of 499 second opinion cytology cases seen at the University of Iowa Carver College of Medicine were studied. Each second opinion was classified as "no diagnostic disagreement", "minor disagreement", or "major disagreement" with respect to the originating institution's interpretation. The clinical impact of major disagreement cases was determined by pathologic and clinical follow-up via chart review. Second opinion cytology resulted in 37 cases (7.4% of total cases) with major diagnostic disagreements. Clinical and pathologic follow-up was available in 30 of the major disagreement cases; second opinion diagnosis was better supported in 22 of these cases compared to the outside diagnosis. The second opinion in 6 major disagreement cases prompted changes in clinical management. Major disagreements in second opinion cytology are common, likely reflective of the challenges inherent in the interpretation of cytologic specimens. Although mandatory second opinion of outside cytologic material prompted changes in clinical management in only a small fraction of cases (1.2%), this rate was similar to those previously published for surgical pathology second opinion. These findings support the notion that mandatory second opinion policy as an important part of patient care.
1 Figures

Full-text (PDF)

Available from: Michael B Cohen, Oct 06, 2014
Mandatory Second Opinion in
Cytopathology
Nathan Lueck, MD, Chris Jensen, MD, Michael B. Cohen, MD
1
, and Jamie A. Weydert, MD
BACKGROUND: Mandatory review of outside pathologic material is intended to detect interpretive errors
that may have a clinically significant impact on patient care. Prior to definitive treatment of referred
patients, the University of Iowa Carver College of Medicine requires a review of pertinent pathologic mate-
rial previously obtained at outside institutions. The aims of this study were to determine if this local stand-
ard of practice has a measurable impact on patient care. METHODS: The pathologic diagnoses of 499
second opinion cytology cases seen at the University of Iowa Carver College of Medicine were studied.
Each second opinion was classified as ‘‘no diagnostic disagreement’’, ‘‘minor disagreement’’, or ‘‘major dis-
agreement’’ with respect to the originating institution’s interpretation. The clinical impact of major dis-
agreement cases was determined by pathologic and clinical follow-up via chart review. RESULTS: Second
opinion cytology resulted in 37 cases (7.4% of total cases) with major diagnostic disagreements. Clinical
and pathologic follow-up was available in 30 of the major disagreement cases; second opinion diagnosis
was better supported in 22 of these cases compared to the outside diagnosis. The second opinion in 6
major disagreement cases prompted changes in clinical management. CONCLUSIONS: Major disagree-
ments in second opinion cytology are common, likely reflective of the challenges inherent in the interpreta-
tion of cytologic specimens. Although mandatory second opinion of outside cytologic material prompted
changes in clinical management in only a small fraction of cases (1.2%), this rate was similar to those previ-
ously published for surgical pathology second opinion. These findings support the notion that mandatory
second opinion policy as an important part of patient care. Cancer (Cancer Cytopathol) 2009;117:82–91.
V
C2009 American Cancer Society.
KEY WORDS: second opinion, cytopathology, patient care, disagreement.
In 1993, the Association of Directors of Anatomic and Surgical Pathology recommended a standard prac-
tice of second opinion review of pathologic material for referred patients before definitive treatment, and
many healthcare institutions have since adopted such a policy.
1
A survey by Gupta and Layfield published
in 2000 found that 50% of participating hospitals had a mandatory second opinion policy, and 38%
encouraged second opinion review but did not have a formal policy in place.
2
Several studies have exam-
ined the impact of second opinion review in surgical pathology since the early 1990s, with diagnostic dis-
agreement rates ranging from 0.25% to 24%, and several of these studies have demonstrated that patient
care is indeed directly altered by the process of second opinion review.
3-10
There have been relatively few
studies investigating the impact of second opinion review of cytologic specimen material. Of these, most
are limited to specific organs or use cytologic specimens as a subset of broader-scope studies examining all
Received: July 2, 2008; Revised: December 16, 2008; Accepted: December 17, 2008
Published online: February 23, 2009 V
C2009 American Cancer Society
DOI: 10.1002/cncy.20019, www.interscience.wiley.com
Corresponding author: Jamie A. Weydert, MD, University of Iowa Hospitals and Clinics, 5239C RCP, 200 Hawkins Drive, Iowa City, IA 52242; Fax:
(319) 384-8053; jamie-weydert@uiowa.edu
Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa
82 Cancer Cytopathology April 25, 2009
Contemporary Issue
referred anatomic pathology material.
4,5,11-15
To our
knowledge, there are no studies that have examined the
clinical consequences or validation of second opinion
review of cytologic material independent of anatomic site.
In this study, we sought to classify diagnostic dis-
agreements in referred cytopathology material based on
the level of pathologic disagreement and the potential for
change in clinical care based on the second opinion inter-
pretation, followed by chart review validation. We then
attempted to ascertain the impact on patient care of clini-
cally significant interpretative disagreements by examin-
ing the rate at which medical, surgical, and prognostic
decisions were changed based on the second opinion
interpretation. Our results indicate clinically significant
disagreements in a relatively high percentage of all cases
reviewed; much higher, in fact, than the rates of clinically
significant disagreements in many surgical pathologic sec-
ond opinion reviews reported in the literature. In addi-
tion, there was a small but important fraction of cases
with clinically significant interpretive disagreements that
directly prompted a change in patient care. Clinical and
pathologic follow-up of these major disagreements vali-
dated the second opinion interpretation most of the time.
However, the originating institution’s interpretation was
validated in a minority of cases. Therefore, second opin-
ion review of cytopathology should be considered a useful
patient care practice in academic medical centers, with the
recognition that second opinion does not necessarily
reflect the gold standard in all cases.
MATERIALS AND METHODS
Outside Slide Review at the University of
Iowa Hospitals and Clinics
At the University of Iowa Hospitals and Clinics (UIHC),
our institution mandates ‘‘when tissues have been
removed at other institutions. . .to be used as a basis for
developing, recommending, or continuing a treatment
plan. . .the tissues shall be sent to the Pathology Labora-
tory for a formal examination before implementing the
treatment plan. . .’’ (University of Iowa Hospitals and
Clinics Bylaws, Rules, and Regulations, Article VIII, Sec-
tion 8). Therefore, many patients seen by our clinicians
for referral care or second opinion have outside pathology
studies (OSS) that are reviewed by our pathologists in the
division of anatomic pathology.
The requisite outside pathology materials reviewed
are the glass slides and the pathology report(s). Outside
cytopathology cases are distributed to the cytopathologists
in our division, and an interpretation is rendered. Our
cytopathologists are all board certified by the American
Board of Pathology (ABP), and all practice both surgical
pathology and cytopathology in our institution. With the
exception of one, our cytopathologists are also subspeci-
alty board certified in cytopathology by the ABP.
Review of OSS Reports and Definition of
Level of Agreement
We retrieved 499 OSS cytology reports at UIHC dating
from January 2005 to December 2005 and January 2007
to July 2007. All reports were reviewed by 2 of the authors
(N.L. and J.A.W.); neither reviewer was the pathologist of
record (ie, signout pathologist) of these second opinion
cases. The originating institution’s report (outside inter-
pretation) and the second opinion report from UIHC
were compared, and cases were classified as no interpretive
disagreement, minor interpretive disagreement, and
major interpretive disagreement. Two methods were used
to classify the level of interpretive agreement or disagree-
ment. If both the outside pathologist and the second opin-
ion pathologist used diagnostic terms in the spectrum of
benign/normal, atypical, suspicious, or malignant, we
used a 2-step discrepancy rule to define a major disagree-
ment. For example, if a lung nodule aspirate was inter-
preted as ‘‘atypical cells’’ on the outside, but was called
‘‘carcinoma’’ on second opinion, the disagreement would
be considered major. A minor interpretive disagreement
was defined as a 1-step difference between the 2 opinions
on the benign-to-malignant scale. Although most case
interpretations used the nomenclature of the benign/atyp-
ical/suspicious/malignant classification, interpretations of
cytologic material from some anatomic sites—most nota-
bly thyroid and uterine cervix—did not fit well into this
scheme. In those cases, major interpretive disagreements
were defined as a difference in opinion with the potential
for significant change in treatment or prognosis as deter-
mined by the authors, using the prevailing local standards
of practice within our institution. For example, the out-
side fine needle aspirate interpretation of a thyroid nodule
Second Opinion Cytopathology/Lueck et al
Cancer Cytopathology April 25, 2009 83
was diagnosed as follicular neoplasm, whereas our second
opinion was benign nodule. Note that for the purposes of
this study, the interpretation of follicular neoplasm and
follicular lesion were considered equivalent. The designa-
tion of follicular neoplasm/lesion does not fit well into the
benign-to-malignant scale, but the difference between the
2 interpretations may have an impact on surgical manage-
ment, as ‘‘follicular neoplasm/lesion’’ would certainly be
triaged to a surgical resection at our institution, whereas
‘‘benign nodule’’ would allow for a recommendation of
nonsurgical follow-up. Similar challenges in classification
were encountered in screening cervical cytology tests.
Although the level of interpretative difference between
high-grade squamous intraepithelial lesion and low-grade
squamous intraepithelial lesion may be seen as a 1-step
discrepancy, the difference in subsequent management—
frequently the difference between an excisional procedure
and careful clinical follow-up—necessitated classification
of such differences as major disagreements.
Classification of Second Opinion Data
The numbers of minor and major disagreements were
enumerated and segregated into generic specimen types
including: fluids (ie, washes, brushes, and scrapings), nee-
dle aspiration biopsies, and exfoliative cervical-vaginal cy-
tology (CVC). Furthermore, CVC cases were separated
into those performed as a screening procedure and those
performed as a diagnostic procedure; a specimen taken
from a postmenopausal woman for uterine bleeding
would be an example of a diagnostic, or complaint-
specific, procedure. This categorization of CVC was nec-
essary, as similar interpretative differences in each setting
(screening vs diagnostic) may not have similar clinical
impact on therapy and follow-up. Review of any accom-
panying histologic material by the second opinion cytopa-
thologist at the time of cytology slide review was
documented. In some instances, cytologic material from
>1 anatomic site or cytologic material from different
dates of collection from the same patient was reviewed
concurrently. If cytologic specimens from different ana-
tomic sites were collected on the same day—for example,
bronchial brush specimens from the right and left bron-
chus obtained during the same bronchoscopic proce-
dure—those specimens would be enumerated as a single
case. However, if cytologic specimens from the same site
were collected on different days—for example, 3 voided
urine specimens collected at 6-month intervals—each case
was considered separately.
Chart Review Investigation of Major
Disagreements
Chart review of OSS cases characterized as major interpre-
tive disagreements was performed to determine: 1) the
clinical impact of the revised diagnosis; 2) the number of
cases that prompted changes in treatment as a result of the
changed diagnosis; and 3) validation of the second opin-
ion. For purposes of second opinion validation, the inter-
pretation closest to the diagnosis based on subsequent
histologic material was deemed correct. For example, an
outside institution’s interpretation of a bronchial brush
was ‘‘atypical,’’ and the second opinion was ‘‘suspicious’’;
carcinoma was detected in subsequent endobronchial
biopsies; therefore, the second opinion would be sup-
ported as the more correct interpretation.
RESULTS
There was no interpretive disagreement in 407 of 499
(81.6%) cases. Minor disagreements comprised 55 cases
(11.0%), and major disagreements comprised 37 cases
(7.4%). Of the cases with major disagreements, 33 came
from community hospitals and laboratories, 1 case came
from a community hospital after obtaining consulting
opinions from another academic center, and 3 cases came
directly from academic health centers. Clinical and/or
pathologic follow-up was available for 30 of the 37 major
disagreement cases; the second opinion interpretation was
better supported in 22 cases (73.3%), the outside original
opinion was better supported in 4 cases (13.3%), and
both the outside and second opinions were equally sup-
ported in 4 cases (13.3%). The second opinion interpreta-
tion in 6 of the 37 cases with a major disagreement (1.2%
of total cases reviewed) prompted changes in the clinical
management of the patient. Pathologic or clinical follow-
up was available for 5 of the 6 cases that prompted a
change in the clinical management as a result of the sec-
ond opinion (Fig. 1). The second opinion was validated
in all 5 of these cases. In 10 of 37 (27.0%) cases with
major disagreements, the second opinion cytopathologist
concurrently reviewed histologic material. However,
Contemporary Issue
84 Cancer Cytopathology April 25, 2009
histologic material was not concurrently reviewed in any
of the 6 cases in which changes in clinical management
were made. Tables 1 to 3 summarize the number of major
interpretive disagreements with respect to specimen type,
anatomic site, and whether there was a change in clinical
management.
Of the 37 cases with a major interpretive disagree-
ment, thyroid fine needle aspirate, CVC (screening proce-
dures only), and urine cytology were the most common
specimens to yield a major interpretive disagreement (9 of
37 [24.3%], 7 of 37 [18.9%], and 6 of 37 [16.2%], respec-
tively). Other anatomic sites and specimens that displayed
significant disagreements in 3 or fewer cases included:
parotid aspirate, lung aspirate, liver aspirate, pancreas aspi-
rate, retroperitoneal aspirate, neck aspirate, bronchial brush-
ing,pleuralfluid,andperitonealscraping.Ofthe6cases
with major disagreements that prompted changes in clinical
management, 3 were thyroid fine needle aspirations, 2 were
cervical-vaginal cytology (screening procedures), and 1 was
a parotid fine needle aspiration (Table 4).
DISCUSSION
The subject of diagnostic error has been a point of empha-
sis in cytopathology for over 2 decades, due in part to the
public’s perception of deficiencies in pathologic interpre-
tation of cervicovaginal screening samples.
16
More
recently, the controversial mandate by the Center for
Medicare and Medicaid Services for mandatory cytology
proficiency testing has also added vigor to the debate
regarding the most appropriate manner to ensure
FIGURE 1. A schematic represents cases with diagnostic disagreement.
Second Opinion Cytopathology/Lueck et al
Cancer Cytopathology April 25, 2009 85
delivery of the best patient care in the diagnostic cyto-
pathology realm. Nongynecological cytopathology,
although a bit more hidden from the public eye, is a rap-
idly growing area within cytopathology because of the
increasing availability of new image-guided aspiration
procedures, such as endoscopic and bronchoscopic ultra-
sound. In this context, it is important to consider ways
to detect and minimize interpretative diagnostic errors
on the part of the pathologist, and thereby improve
patient care in a clinically relevant manner. To reduce
diagnostic error, one needs a reasonable definition of
error; a universal definition has proven rather elusive in
the context of anatomic pathology. An assessment of
diagnostic accuracy—meaning how close to the truth a
diagnostic interpretation may be—is often quite diffi-
cult.
17,18
Subsequent pathologic and clinical follow-up
are the best available gold standards to determine accu-
racy of cytopathologic diagnosis; however, it is not a
practical way to reduce real-time errors in the delivery of
healthcare to an individual patient. Second opinion pa-
thology, in contrast, is a method to assess precision, or
interobserver reproducibility, in diagnostic cytopathol-
ogy, and thus represents a potential surrogate for accu-
racy. The advantage of second opinion cytopathology is
that it can be performed before definitive clinical man-
agement, with the caveat that reproducibility of a diag-
nosis is not always equivalent to diagnostic accuracy.
In the present study, we attempted to determine
whether it is possible to reasonably assess cytopathologic
interpretative precision in the context of mandatory sec-
ond opinion, and whether second opinion in cytopathol-
ogy is a worthwhile patient care endeavor. We found
major interpretive disagreements in 7.4% of cases
reviewed. This rate is similar to Layfield et al’s study,
which found an 8% major discrepancy rate in a review of
146 outside cytology cases; this rate is much lower than
the 21% discordant diagnosis rate in cytology cases
reported by Abt et al.
4,11
Rates of clinically significant dis-
agreements upon second opinion review range widely in
surgical pathology investigations, but tend to be lower
than those reported in cytopathology.
3-15
A recent review
of surgical pathology second opinion cases within our
own institution found a major disagreement rate of 2.3%,
similar to other major diagnostic disagreement rates for
surgical pathology material reported in the literature.
10
The reasons for higher discrepancy rates in cytopathology
versus surgical pathology are likely multifactorial. First,
assessment of diagnostic interpretative precision in cyto-
pathology is more difficult than in surgical pathology.
Cytologic interpretations can certainly be definitive,
Table 1. Major Disagreement Cases, Fluids
Specimen
Type and/or
Anatomic Site
Outside Diagnosis Second Opinion
Diagnosis
Clinicopathologic
Follow-up
Documented
Change in
Management
Pleural fluid Adenocarcinoma Small cell carcinoma Repeat cytology: small
cell carcinoma
None
Pleural fluid Adenocarcinoma Atypical None N/A
Bronchial brush Small cell carcinoma Suspicious for small cell
carcinoma
Subsequent biopsy: small
cell carcinoma
None
Voided urine No tumor identified Suspicious None N/A
Voided urine Atypical Urothelial carcinoma None N/A
Ureter brushing No tumor identified Urothelial carcinoma Subsequent brushings:
urothelial carcinoma
None
Voided urine No tumor identified Urothelial carcinoma Subsequent urine cytology:
urothelial carcinoma
None
Voided urine No tumor identified Urothelial carcinoma Subsequent urine cytology:
urothelial carcinoma
None
Ureter brushing No tumor identified Urothelial carcinoma Subsequent ureter brush
was atypical
None
Bronchial brush Adenocarcinoma Suspicious for
adenocarcinoma
Biopsy: carcinoma None
Diaphragm, pelvic,
and gutter scraping
Benign Peritoneal tumor of low
malignant potential*
Surgical procedure
previously performed
None
N/A indicates not applicable.
* Denotes cases in which histologic material was concurrently reviewed with cytologic material.
Contemporary Issue
86 Cancer Cytopathology April 25, 2009
endpoint anatomic diagnoses, but pathologists often use
equivocations and descriptive nomenclature to convey an
interpretative cytopathologic impression. Cytologic inter-
pretations frequently use modifiers such as ‘‘atypical’’ and
‘‘suspicious for’’ that are less prevalent in surgical pathol-
ogy diagnoses. These modifiers are rarely standardized or
well defined, and can be open to different interpretations
among referral pathologists and clinicians. Furthermore,
Table 2. Major Disagreement Cases, Aspirations
Specimen
Type and/or
Anatomic Site
Outside
Diagnosis
Second Opinion
Diagnosis
Clinicopathologic
Follow-up
Documented
Change
in
Management
Thyroid Papillary
carcinoma
Hyperplastic nodule* Thyroidectomy: hyper-
plastic nodule
None
Thyroid Benign Suspicious for follicular
neoplasm*
Thyroidectomy: follicular
variant of papillary
carcinoma
None
Lung Suspicious Squamous cell
carcinoma*
Lobectomy: squamous
cell carcinoma
None
Lung Mesothelioma Atypical None N/A
Liver Adenocarcinoma Atypical Biopsy: adenocarcinoma None
Parotid Favor carcinoma† Squamous cell
carcinoma
Repeat FNA: squamous
cell carcinoma
None
Thyroid Cannot exclude
follicular
neoplasm
Benign nodule None Yes, patient
avoided
surgical
excision
Thyroid Cannot exclude
follicular
neoplasm
Benign nodule Repeat FNA: benign
nodule
None
Parotid Nondiagnostic Suspicious Repeat FNA: squamous-
cell carcinoma
None
Retroperitoneal
lymph node
Atypical Lymphoma None N/A
Thyroid Suspicious for fol-
licular
neoplasm
Benign nodule Lobectomy: nodular
hyperplasia
None
Thyroid Follicular
neoplasm
Benign nodule Thyroidectomy: micro-
scopic follicular variant
of papillar carcinoma
None
Parotid Possible pleomor-
phic
adenoma
Basosquamous
carcinoma
Parotidectomy and neck
dissection: squamous
cell carcinoma
Yes, patient under-
went
staging
procedure
Thyroid Multinodular goiter Nondiagnostic Thyroidectomy: multinod-
ular goiter
None
Thyroid Follicular
neoplasm
Benign nodule >1 y clinical follow-up
with no change in
nodule
Yes, patient
avoided
surgical
excision
Thyroid Follicular
neoplasm
Benign nodule >2 y clinical follow-up
with no change in
nodule
Yes, patient
avoided surgical
excision
Lung Small cell
carcinoma
Suspicious None N/A
Pancreas No malignancy Adenocarcinoma Repeat FNA:
adenocarcinoma
None
Neck Atypical Squamous cell
carcinoma*
Biopsy: squamous cell
carcinoma
None
N/A indicates not applicable; FNA, fine needle aspiration.
* Denotes cases in which histologic material was concurrently reviewed with cytologic material.
† Outside interpretation favored carcinoma, but a differential diagnosis listed in the diagnostic comment included benign entities.
Second Opinion Cytopathology/Lueck et al
Cancer Cytopathology April 25, 2009 87
attempts to assign cytologic interpretations to limited, dis-
crete categories such as benign, atypical, suspicious, or
malignant may artificially simplify interpretations that
were purposely made open-ended. Consequently, assess-
ment of concordance in studies similar to our own may
result in a higher rate of perceived major disagreements
that, in reality, were only minor disagreements. As an
illustration of the difficulty in defining concordance
based on a 4-tiered scale within cytopathology, we can
examine 2 cases of bronchial brushings that were
included in our study. In 2 bronchial brushing cases clas-
sified as major disagreements, the outside interpretations
were within the ‘‘malignant’’ category, whereas the corre-
sponding second opinions were within the ‘‘suspicious’’
category, a 1-step difference that a priori would only
have been coded as a minor disagreement. However,
because of the prevailing local standards of practice
within our institution, this difference is best classified as
a major disagreement, as ‘‘suspicious’’ in this particular
clinical context would have prompted a repeat diagnostic
procedure to firmly establish a cancer diagnosis, whereas
a ‘‘malignant’’ interpretation on cytology at our institu-
tion would allow for the option of definitive surgical
and/or medical management.
Table 3. Major Disagreement Cases, Cervicovaginal Cytology (Papanicolaou Tests)
Outside
Diagnosis
Second
Opinion
Diagnosis*
Clinicopathologic
Follow-up
Documented Change
in Management
LSIL HSIL* Biopsy: CIN III None
HSIL LSIL Biopsy: CIN I Yes, patient avoided excisional
procedure
HSIL LSIL Biopsy: CIN I Yes, patient avoided excisional
procedure
Negative Adenocarcinoma in situ* Hysterectomy: endocervical
adenocarcinoma
None
HSIL Squamous cell carcinoma* Surgical excision: squamous cell
carcinoma
None
Negative AGUS* Hysterectomy: endocervical
adenocarcinoma
None
AGUS HSIL Excision procedure: CIN I None
LSIL indicates low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia; AGUS, atypi-
cal glandular cells of undetermined significance.
* Denotes cases in which histologic material was concurrently reviewed with cytologic material.
Table 4. Cases Prompting a Change in Clinical Management
Anatomic Site Outside
Diagnosis
Second
Opinion
Diagnosis
Clinicopathologic
Follow-up
Documented
Change in
Management
Thyroid Cannot exclude follic-
ular neoplasm
Benign nodule None Patient avoided surgical
excision
Thyroid Follicular neoplasm Benign nodule >1 y clinical follow-up
with no change
Patient avoided surgical
excision
Thyroid Follicular neoplasm Benign nodule >2 y clinical follow-up
with no change
Patient avoided surgical
excision
Parotid Possible
pleomorphic
adenoma
Basosquamous
carcinoma
Parotidectomy and neck
dissection: squamous
cell carcinoma
Patient underwent staging
procedure
Uterine cervix HSIL LSIL Biopsy: CIN I Patient avoided excisional
procedure
Uterine cervix HSIL LSIL Biopsy: CIN I Patient avoided excisional
procedure
LSIL indicates low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia.
Contemporary Issue
88 Cancer Cytopathology April 25, 2009
Second, in many instances and anatomic sites, cytol-
ogy is not intended to be the final diagnostic threshold
before definitive treatment. The cytologic interpretation
may used as a triage tool, directing clinicians to watch and
wait, treat, or obtain histologic material depending on the
clinical scenario. Cytopathology is also used as a screening
test, and therefore higher disagreement rates may be both
expected and acceptable. Finally, in our study, outside
referral cases at our institutions were only reviewed by
pathologists with specialty training in cytology. In most
instances, the outside cases were from community pathol-
ogists whose general practice may not routinely encounter
nongynecologic cytology specimens. Although commu-
nity pathologist exposure to surgical pathology material
may also be variable, it is likely the average community
pathologist has more experience with surgical pathology
specimens than cytology specimens. Lower disagreement
rates may have been encountered if referral material was
originally reviewed by specialists in cytopathology.
Of the 37 cases with a major interpretive disagree-
ment, clinical management was changed based on the sec-
ond review opinion in 6 cases (1.2% of total cases
reviewed). Three of these cases were thyroid fine needle
aspirates. In each case, the outside interpretation was ‘‘fol-
licular neoplasm,’’ or ‘‘cannot exclude follicular neo-
plasm,’’ and the second opinion was ‘‘benign nodule.’’ As
a result of the second opinion, in each of these cases, a
total thyroidectomy or lobectomy was not performed. In
2 of 3 cases, the patients have been followed up for >2
years with normal exams, laboratory studies, and serial
imaging, as well as repeat benign fine needle aspiration in
1 case; in these 2 cases, then, the second opinion was vali-
dated. In the third case, the patient had not yet followed
up clinically, so validation of the second opinion cannot
be assessed. It should be noted that in 1 thyroid aspirate
case with a major diagnostic disagreement, the outside
diagnosis was follicular neoplasm, and the second opinion
review was benign nodule with cystic change. In most
cases, this interpretive difference at our institution would
result in close clinical follow-up instead of surgical man-
agement. However, because of the size of the nodule, a
thyroidectomy was performed, and subsequent histologic
examination revealed a microscopic focus of follicular var-
iant of papillary carcinoma separate and distinct from the
large cystic nodule. Although the originating institution
in this case was credited as having the more correct inter-
pretation, this was almost certainly a sampling issue. The
cytologic material reviewed sampled the dominant nod-
ule, which on histologic follow-up was confirmed as a
cystic benign nodule. This case again demonstrates the
difficultly in truly determining the correct interpretation,
particularly in thyroid aspirates, where sampling may play
an enormous role in diagnosis and subsequent treatment.
There were 2 screening cervicovaginal cytology cases
in which clinical management was changed based on the
second opinion. In each case, the outside interpretation of
a Papanicolaou (Pap) test was high-grade squamous intra-
epithelial lesion, and subsequent cervical biopsy material
showed mild squamous dysplasia (cervical intraepithelial
neoplasia I). Had the Pap test not been reviewed, an exci-
sional procedure of the cervix would be indicated, as a
high-grade lesion may have been missed on colposcopy.
Instead, on second opinion review both Pap tests were
interpreted as low-grade squamous intraepithelial lesions,
and the patients were spared an excisional procedure as a
result of concordant Pap and biopsy results. In the last
case, in which clinical management was changed based on
the second opinion, a fine needle aspiration of a parotid
mass was interpreted as a possible pleomorphic adenoma
by the originating institution and as carcinoma at our
institution after review. After additional fine needle aspi-
rations of the mass and neck lymph nodes were performed
at our institution showing squamous cell carcinoma, a
parotidectomy with neck dissection was performed.
In each of the cases described above, there was an
evident change in clinical management, but why were
there only 6 examples in which clinical management was
changed, when our study revealed 37 cases with a major
interpretive disagreement? First, there were only 30 of 37
cases with follow-up documented in our institution’s
computer medical record. Second, a change in clinical
management was only recorded if the clinician docu-
mented a clinical plan before review of the cytologic mate-
rial and then documented a change in that plan after
review. In many instances, review of the cytologic material
had occurred before the patient’s clinic appointment, and
any changes in clinical management that may have been
prompted by interpretive disagreements between the out-
side interpretation and second opinion were not docu-
mented in the patient’s medical record. Third, referral
cytologic material may have corresponding histologic
material that is more diagnostically definitive. For
Second Opinion Cytopathology/Lueck et al
Cancer Cytopathology April 25, 2009 89
example, bronchial brushing and endobronchial biopsies
from a patient may both be sent for second opinion
review. Although there may be a major disagreement
between the originating institution’s interpretation of be-
nign and a review interpretation of suspicious or malig-
nant on bronchial cytology, that disagreement is moot
and unlikely to change clinical management if the endo-
bronchial biopsy carries a diagnosis of carcinoma on both
the outside pathology report and the referral report.
Fourth, there were several instances in which there was a
delay in diagnosis because of missed malignancies by out-
side review of cytologic material that were detected and
subsequently diagnosed as malignant. For example, a
patient with cytologic evaluation of multiple voided urine
samples had carcinoma cells missed on the first urine anal-
ysis that were detected on second opinion review, but a
subsequent specimen collected 6 months later was diag-
nosed as carcinoma by the originating institution. In cases
such as these, no formal change in treatment plan was
made at our institution, despite a significant time in delay
of diagnosis. Finally, the outside material was reviewed or
the second opinion interpretation was rendered after ini-
tiation of treatment in a small minority of cases.
Interestingly, the rate at which clinical management
changes were made based on second opinion of cytology
material review (1.2%) was nearly identical to a recent
review of surgical pathology second opinion cases within
our own institution (clinical management change in
1.21% of total cases reviewed), but there are important
differences leading to these final percentages.
10
In the sur-
gical pathology cases, there was a lower rate of major dis-
agreements (2.3%), but of those cases with a major
disagreement, there was a higher likelihood that clinical
management would be changed, such that >50% of the
cases with a major disagreement resulted in a change in
clinical management. Conversely, in the cytology cases,
there was a much higher rate of major disagreements
(7.4%), but a smaller percentage of major disagreements
lead to changes in clinical management (16.2%). This
again highlights the inherent differences between cytology
and surgical pathology. Cytologic specimens are more
likely than surgical pathology material to be used as a tri-
age or screening tool to guide clinicians in a treatment
algorithm.
Second opinion pathology is costly in terms of path-
ologists’ time. One approach to reduce the number of
cases reviewed would be to limit review to problematic
sites. Indeed, our study would seem to suggest that, based
on the rate of change in clinical management, thyroid and
cervicovaginal cytology would be problematic sites and
are critical for review, whereas review of other specimen
types and anatomic sites would be less critical. However,
prospective review and real-time discussions with clini-
cians at the time of cytologic material review may result in
a higher rate of major disagreements that were not uncov-
ered by our investigation. In turn, other specimen types or
anatomic sites may be revealed to be just as critical for
review. Until those prospective studies are carried out to
definitively categorize low-risk cytologic material, it seems
prudent not to restrict mandatory review to select ana-
tomic sites, despite increased burden on pathologists’
time.
In summary, we have shown that mandatory second
opinion in an academic center is a useful patient care tool.
We were able to demonstrate that clinicians do change
clinical management based on second opinion review,
albeit not uniformly. A continued review of outside mate-
rial of all anatomic sites is also supported by our findings.
Conflict of Interest Disclosures
The authors made no disclosures.
References
1. Association of Directors of Anatomic and Surgical Pathol-
ogy. Consultations in surgical pathology. Am J Surg Pathol.
1993;17:743-745.
2. Gupta D, Layfield LJ. Prevalence of inter-institutional ana-
tomic pathology slide review. Am J Surg Pathol. 2000;24:
280-284.
3. Kronz JD, Westra WH, Epstein JI. Mandatory second
opinion surgical pathology at a large referral hospital. Can-
cer. 1999;86:2426-2435.
4. Abt AB, Abt LG, Olt GJ. The effect of interinstitution ana-
tomic pathology consultation on patient care. Arch Pathol
Lab Med. 1995;119:514-517.
5. Weir MM, Jan E, Colgan TJ. Interinstitutional pathology
consultations. Am J Clin Pathol. 2003;120:405-412.
6. Tsung JSH. Institutional pathology consultation. Am J Surg
Pathol. 2004;28:399-402.
7. Renshaw AA. Measuring and reporting errors in surgical
pathology: lessons from gynecologic cytology. Am J Clin
Pathol. 2001;115:338-341.
Contemporary Issue
90 Cancer Cytopathology April 25, 2009
8. Westra WH, Kronz JD, Eisele DW. The impact of second
opinion surgical pathology on the practice of head and
neck surgery: a decade experience at a large referral hospital.
Head Neck. 2002;24:684-693.
9. Kronz JD, Westra WH. The role of second opinion pa-
thology in the management of lesions of the head and
neck. Curr Opin Otolaryngol Head Neck Surg. 2005;13:81-
84.
10. Manion E, Cohen MB, Weydert J. Mandatory second
opinion in surgical pathology referral material. Am J Surg
Pathol. 2008;32:732-737.
11. Layfield LJ, Jones C, Rowe L, Gopez EV. Institutional
review of outside cytology materials: a retrospective analysis
of 2 institutions’ experiences. Diag Cytopathol. 2002;26:
45-48.
12. Tan YY, Kebebew E, Reiff E, et al. Does routine consulta-
tion of thyroid fine-needle aspiration cytology change surgi-
cal management? J Am Coll Surg. 2007;205:8-12.
13. Raab SS, Grzybicki DM, Janosky JE, et al. Clinical impact
and frequency of anatomic pathology errors in cancer diag-
noses. Cancer. 2005;104:2205-2213.
14. Baloch ZW, Hendreen S, Gupta PK, et al. Interinstitu-
tional review of thyroid fine needle aspirations: impact on
clinical management of thyroid nodules. Diagn Cytopathol.
2001;25:231-234.
15. Clary KM, Silverman JF, Liu Y, et al. Cytohistologic dis-
crepancies: a means to improve pathology practice and
patient outcomes. Am J Clin Pathol. 2002;117:567-573.
16. Frable WJ. Error reduction and risk management in cyto-
pathology. Semin Diagn Pathol. 2007;24:77-88.
17. Frable WJ. Surgical pathology—second reviews, institu-
tional reviews, audits and correlations: what’s out there?
Error or diagnostic variation? Arch Pathol Lab Med.
2006;130:620-625.
18. Sirota RL. Defining error in anatomic pathology. Arch
Pathol Lab Med. 2006;130:604-606.
Cancer Cytopathology April 25, 2009 91
Second Opinion Cytopathology/Lueck et al
    • "Furthermore, we specifically assessed the added value of double reading by expert cytopathologists. In these studies as well, high major disagreement rates of thyroid FNA specimens were observed (16.2 to 24.3 %), and in the study of Lueck et al. [32], major discrepancies in urine specimens were the third most common (16.2 %). The high discordance rates in urine and pleural fluid specimens might be partly explained by the lack of standard terminology and the use of inadequate terms, especially for atypical lesions [35]. "
    [Show abstract] [Hide abstract] ABSTRACT: Double reading may be a valuable tool for improving the quality of patient care by restoring diagnostic errors before final sign-out, but standard double reading would significantly increase costs of pathology. The aim of this study was to assess the added value of routine double reading of defined categories of clinical cytology specimens by specialized cytopathologists. Specialized cytopathologists routinely re-diagnosed blinded defined categories of clinical cytology specimens that had been signed out by routine pathologists from January 2012 up to December 2013. Major and minor discordance rates between initial and expert diagnoses were determined, and both diagnoses were validated by comparison with same-site histological follow-up. Initial and expert diagnoses were concordant in 131/218 specimens (60.1 %). Major and minor discordances were present in 28 (12.8 %) and 59 (27.1 %) specimens, respectively. Pleural fluid, thyroid and urine specimens showed the highest major discordance rates (19.4, 19.2 and 16.7 %, respectively). Histological follow-up (where possible) supported the expert diagnosis in 95.5 % of specimens. Our implemented double reading strategy of defined categories of cytology specimens showed major discordance in 12.8 % of specimens. The expert diagnosis was supported in 95.5 % of discordant cases where histological follow-up was available. This indicates that this double reading strategy is worthwhile and contributes to better cytodiagnostics and quality of patient care, especially for suspicious pleural fluid, thyroid and urine specimens. Our results emphasize that cytopathology is a subspecialization of pathology and requires specialized cytopathologists.
    Full-text · Article · Mar 2015
    • "In other oncological and nononcological domains, studies of radiologist second opinions have found discrepancy rates of 11–49% for diagnosis or staging and 7–37% for patient management10111213141516. These rates are similar to those found for expert second opinions in pathology, with reported discrepancy rates of 7–66% (including changes from a benign to a malignant diagnosis or vice versa) resulting in a change in patient management in 1–28%171819202122232425262728. There is much less literature on the effect of expert second opinions in clinical practice, but one study [29] has shown discrepancy rates for diagnosis and patient management of 35% and 67%, respectively. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective Patients with head and neck cancer frequently present to academic tertiary referral centers with imaging studies that have been performed and interpreted elsewhere. At our institution, these outside head and neck imaging studies undergo formal second opinion reporting by a fellowship-trained academic neuroradiologist with expertise in head and neck imaging. The purpose of this study was to determine the impact of this practice on cancer staging and patient management. Methods Our institutional review board approved the retrospective review of randomized original and second opinion reports for 94 consecutive cases of biopsy proven or clinically suspected head and neck cancer in calendar year 2010. Discrepancy rates for staging and recommended patient management were calculated and, for the 32% (30/94) of cases that subsequently went to surgery, the accuracies of the reports were determined relative to the pathologic staging gold standard. Results Following neuroradiologist second opinion review, the cancer stage changed in 56% (53/94) of cases and the recommended management changed in 38% (36/94) of patients with head and neck cancer. When compared to the pathologic staging gold standard, the second opinion was correct 93% (28/30) of the time. Conclusion In a majority of patients with head and neck cancer, neuroradiologist second opinion review of their outside imaging studies resulted in an accurate change in their cancer stage and this frequently led to a change in their management plan.
    Full-text · Article · Jun 2013
    John T Lysack+3 more authors ...
    • "In 1999, The Institute of Medicine report cited a medical error as the cause of death in some 40,000–98,000 Americans each year [8] supporting once more the concept that a further consultation or specialistic SO may be useful and benefit the patient. The expression SO has been widely reported in the fields of histology [9] [10] and pathology [11] [12] [13] [14] [15] [16] [17] [18] [19] where the diagnosis is often difficult and is strongly based on the healthcare professionals' experience. SO on histological specimens is a routinary daily procedure, performed in anatomic pathology practices and it plays a key role in providing the patient with the most accurate diagnosis [20]. "
    Full-text · Article · Mar 2011
Show more