Comparison of 1st opinion and 2nd opinion histopathology from dogs and cats with cancer
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Transcript of Comparison of 1st opinion and 2nd opinion histopathology from dogs and cats with cancer
Original Article DOI: 10.1111/j.1476-5829.2009.00203.x
Comparison of first-opinion andsecond-opinion histopathologyfrom dogs and cats with cancer:430 cases (2001–2008)
R. C. Regan1, K. M. Rassnick1, C. E. Balkman1, D. B. Bailey1∗ and S. P.McDonough2
1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA2Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
AbstractSecond-opinion histopathology is intended to detect clinically significant discrepancies that have a
direct impact on patient care. We sought to determine if this practice at our institution affected
patient management and prognosis. First- and second-opinion histopathology reports from cases
were retrospectively reviewed. Reports were considered to be in diagnostic agreement, partial
diagnostic disagreement or complete diagnostic disagreement. Four hundred and thirty cases were
studied. In 70% of cases there was a diagnostic agreement. In 20% of cases, there was partial
diagnostic disagreement, where diagnoses were the same but information such as grade or
lymphatic and/or vascular invasion was changed. In 10% of cases, complete diagnostic disagreement
resulted from a change in degree of malignancy (malignant to benign, or converse; 7%) or a change
in cell type (3%). In 17% of the cases evaluated, the histopathology review prompted a change in
treatment or prognosis. These findings support the use of second-opinion histopathology as an
important part of patient care.
Keywordsbiopsy; cancer; diagnosis;histopathology; neoplasia;tumour
Introduction
In human medicine, second-opinion tumour
histopathology is a patient safety practice whereby
pathology material from one institution is reviewed
at the treating institution before the initiation of
any major therapy. The main purpose of inter-
nal histopathology review is to uncover erroneous
pathological diagnoses and thus avoid unneces-
sary or inappropriate treatments.1 Although review
of the same material by two different hospitals
might be perceived as redundant and unneces-
sary, mandatory second-opinion histopathology
consistently uncovers discrepancies and has a
∗Present address: Oradell Animal Hospital, Paramus, NJ,USA.
profound impact on patient management and
prognosis. Several studies have reported major diag-
nostic changes in a small but meaningful number
of cases. Abt et al.2 found that 5.8% (45 of 777)
of cases reviewed had a change in histopathologi-
cal diagnosis that was clinically significant. Kronz
et al.3 found that second-opinion histopathology
resulted in a changed diagnosis in 1.4% of cases
in their prospective study of more than 6000
cases. In a retrospective study covering a 1-year
period, Tsung4 noted major diagnostic disagree-
ment in 5.2% (35 of 673) of consecutive cases.
In each of these studies, the majority of these
changes were a conversion between benign to
malignant or a substantial modification of tumour
classification.
Correspondence address:Department of ClinicalSciences College ofVeterinary MedicineBox 31, Ithaca, New York,14853, USAe-mail: [email protected]
© 2009 Blackwell Publishing Ltd 1
2 R. C. Regan et al.
While the discrepancy rate comparing the
original diagnosis from the submitting institution
with the second-opinion diagnosis rendered by
the referral institution is relatively small, it is
high enough that the Association of Directors of
Anatomic Surgical Pathology has recommended
institutional consultation as a standard practice.5
A survey by Gupta and Layfield6 found that 50%
of participating hospitals had a mandatory second-
opinion policy, and 38% encourage a second review
of outside materials. Academic health centers were
more likely to require or encourage second opinion
in anatomic pathology.6
The Clinical Veterinary Oncology Service of
the Sprecher Institute for Comparative Cancer
Research at Cornell University College of Veterinary
Medicine makes a concerted effort to obtain
and review all pertinent original histopathological
materials from patients before developing or
recommending a treatment plan. These reviews
are performed by the board-certified anatomic
pathologists within the Department of Biomedical
Sciences at Cornell University College of Veterinary
Medicine, and the results are documented in
standard pathology reports. The purpose of this
retrospective study was to determine the frequency
of discordant diagnoses of our second-opinion
histopathology review and its impact on patient
care.
Materials and methods
Data collection
A retrospective review of all cases with a confirmed
or presumptive diagnosis of cancer that were
referred to the Sprecher Institute for Comparative
Cancer Medicine at Cornell University College
of Veterinary Medicine between December 2001
and December 2008 was performed. Only cases
that had first-opinion biopsy reports and second-
opinion biopsy reviews performed at the request of
the treating veterinary oncologists were included.
Data collected from the biopsy reports included
first-opinion institution and pathologist, second-
opinion pathologist, species, organ affected, biopsy
method, morphological diagnosis, special stains
and/or immunohistochemistry (IHC) performed,
tumour grade, and evidence of lymphatic and/or
vascular invasion. Completeness of excision was not
recorded as tissue blocks were not always available
for all cases undergoing pathological review. For all
cases with diagnostic disagreements (see definition
below), follow-up information to ascertain the
correctness of the diagnosis was recorded when
available.
Definitions
Pathology reports were compared and separated
into three categories. Reports were considered
to be in diagnostic agreement if the first and
second opinions were in agreement or had only
minimal differences in terminology that did not
affect the intent of the diagnosis. Reports were
considered to be in partial diagnostic disagreement
if the morphological diagnosis was the same but
information such as tumour subtype, histological
grading, or lymphatic and/or vascular invasion was
changed or only included in one of the opinions.
Reports were considered to be in complete
diagnostic disagreement if there was a change from
benign to malignant, from malignant to benign,
and/or from one tumour type to another that
has a substantially different biological behaviour
[epithelial, mesenchymal (excluding round cell and
melanocytic), round cell (excluding lymphoma),
lymphoma, melanocytic].
As all diagnostic disagreements are not neces-
sarily clinically relevant, discrepancies were also
categorized as major and minor diagnostic dis-
agreements. A major diagnostic disagreement was
defined as a change with potential for a major
change in treatment and/or prognosis (e.g. a change
from a grade II mast cell tumour to a grade III
mast cell tumour). Minor diagnostic disagreements
were changes judged to have minimal impact on
treatment and/or prognosis (e.g. a change from
a low grade fibrosarcoma to a low grade myx-
osarcoma). If there were multiple discrepancies
between the reports for a given biopsy, each discrep-
ancy was considered independently of the others.
By definition, all tumours in complete diagnostic
disagreement also were in major diagnostic dis-
agreement. Tumours in partial disagreement could
be in either major or minor diagnostic disagree-
ment depending on the clinical impact of the
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
Second-opinion histopathology 3
change(s). For purposes of the study, the clini-
cal impact of change(s) in the pathology reports on
treatment recommendations and prognostic infor-
mation were based solely on the reports themselves.
As complete clinical information was not available
for all patients, information such as tumour size,
stage, ability of the primary tumour to be surgi-
cally resected, or patient performance status was
not considered. All treatment recommendations
and prognoses were based on available standards
of care. When there was no established standard
of care, treatment for a particular tumour type, or
when there were no studies to define accurately
prognosis for a particular tumour type, treatment
recommendations and estimates of prognosis were
provided by the consensus of three of the co-authors
(K. M. R, C. E. B and D. B. B).
Data analysis
Summary statistics were used to describe the num-
ber of samples in agreement, partial disagreement
and complete disagreement. They were also used
to describe the major and minor disagreements.
Chi-square tests were used to analyse relation-
ships between major diagnostic disagreements and
biopsy methods (incisional versus excisional), types
of tumours (epithelial, mesenchymal, round cell,
lymphoma, melanocytic), and species. All analyses
were two-sided, and P ≤ 0.05 was considered sig-
nificant. Statistical calculations were performed by
the use of a computer software program (SPSS
10, Statistical Analytical Software, Chicago, IL,
USA).
Results
Characteristics of cases submitted for secondopinion
In the period between December 2001 and
December 2008, 3571 cases were referred to
the Sprecher Institute for Comparative Cancer
Research at Cornell University College of Veterinary
Medicine. The clinical oncologists requested 450
histopathology reviews for confirmation of the
diagnoses; 20 biopsies were excluded from the
study because of missing reports. Four hundred
and thirty biopsies (370 unique samples from
326 dogs and 60 unique samples from 53 cats),
representing 11% of cases seen during this time,
were included in this study. The distribution
of cases according to primary tumour site is
shown in Table 1. Excisional biopsy was the most
common technique and was used in 301 (70%)
of cases; the diagnosis was made from incisional
biopsy in 129 (30%) cases. The 430 cases in
this study had the first opinion rendered by one
of 75 pathologists from 25 different diagnostic
laboratories (19 commercial laboratories and 6
university pathology services). A second opinion
of the pathological material was provided by at least
one of 14 board-certified anatomic pathologists
at our institution during the study period. Glass
slides (or paraffin blocks when available) were
distributed to the surgical pathologist on duty, and
a formal anatomic interpretation was rendered. In
many cases, consultation with another pathologist
with the appropriate subspecialty interest (e.g.
haemolymphatic pathology, dermatopathology)
was sought at the request of the on-duty pathologist.
The material reviewed by our pathologists consisted
solely of haematoxylin–eosin stained slides in 400
cases. At the request and discretion of the on-
duty pathologist, additional special stains, including
IHC, were used in 30 cases.
Table 1. Organ site distribution of 430 biopsies undergoingsecond-opinion review
Tumour siteNumber of canine
samplesNumber of feline
samples
Skin/subcutaneous 216 25
Oral cavity 61 10
Lymph node 23 1
Nasal cavity 10 5
Mammary gland 9 5
Bone 12 1
Gastrointestinal tract 8 4
Anal sac 7 2
Thyroid gland 4 1
Spleen 5 0
Salivary gland 3 2
Liver 1 3
Uterus 3 0
Ovary 2 0
Other sitesa 6 1
aOther sites represented by only one biopsy sample includekidney, urinary bladder, joint, parathyroid, gall bladder, andretroperitoneal space (canine) and pancreas (feline).
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
4 R. C. Regan et al.
Frequencies of discrepancies in diagnosis
There was diagnostic agreement in 301 (70%) cases
reviewed. In 86 (20%) cases, there was partial
diagnostic disagreement. The majority of these
cases involved differences in the terminology used
to describe the same disease process, discordant
or incomplete tumour grading, or incomplete
information regarding the presence or absence
of lymphovascular tumour emboli. Complete
diagnostic disagreement was noted in 43 (10%)
cases: a change from malignant to benign in 24
cases (6%), the converse in 5 cases (1%) and a
change in cell type in 14 cases (3%). Partial and
complete diagnostic disagreements are depicted in
Tables 2 and 3.
Minor disagreements (information judged to
have minimal impact on treatment and/or prog-
nosis) were noted in 61 cases; 7 cases had more
than 1 minor disagreement (Table 4). Fifty-four
(13%) cases had only minor disagreements, with
no major disagreements.
Major disagreements comprised 75 (17%) cases.
Forty-three (57% of major changes) were changes
also classified as complete disagreements, whereas
the remaining 32 (43%) were partial disagreements.
Excluding a change in the histological grading
of canine mast cell tumours or soft tissue
sarcomas, there were 52 (12% of all cases) major
disagreements. Of all the 75 major disagreements,
the second-opinion interpretation prompted either
a change in the treatment plan (26 cases),
prognosis (4 cases) or both treatment and prognosis
(45 cases). One biopsy had two major disagreements
(grade II mast cell tumour, first opinion changed to
grade III mast cell tumour with lymphovascular
tumour emboli). Seven biopsies with major
disagreements also had minor disagreements.
IHC or special stains aided in reaching a
diagnosis in eight of the 75 cases with major
disagreements. Major disagreements are depicted
in Table 5.
For cases with diagnostic disagreements, follow-
up information to ascertain the correctness of the
diagnosis was recorded when available. Pathological
follow-up was available for 13 of the 75 major
disagreement cases; the second opinion was
Table 2. Partial and complete diagnostic disagreements after review of 370 histopathology samples from 326 dogs
Diagnostic change
Cell typeNumber ofcases (%)
Subtypenumbera (%)
Gradenumber (%)
Vesselinvasion
number (%)
Degree ofmalignancynumber (%)
Cell typenumber (%)
Mesenchymal 119
Partial disagreement 30 (25%) 14 (12%) 19 (17%) 2 (2%) NA NA
Complete disagreement 19 (16%) NAb NA NA 10 (9%) 9 (8%)
Epithelial 57
Partial disagreement 14 (25%) 8 (7%) 3 (3%) 5 (4%) NA NA
Complete disagreement 5 (9%) NA NA NA 5 (4%) 0
Round cell 120
Partial disagreement 18 (15%) 0 18 (16%) 1 (1%) NA NA
Complete disagreement 6 (5%) NA NA NA 2 (2%) 4 (4%)
Melanocytic 30
Partial disagreement 10 (33%) 4 (4%) 4 (4%) 2 (2%) NA NA
Complete disagreement 2 (7%) NA NA NA 2 (2%) 0
Lymphoma 26
Partial disagreement 1 (4%) 0 0 1 (1%) NA NA
Complete disagreement 4 (15%) NA NA NA 4 (3%) 0
No neoplasia 18
Partial disagreement 0 (0%) 0 0 0 NA NA
Complete disagreement 5 (3%) NA NA NA 5 (4%) 0
One hundred and thirteen biopsies had disagreements and some biopsies had more than one diagnostic change.aSubtype, meaning a change between tumour types within the broader category, such as a change from fibrosarcoma tomyxosarcoma.bNA, not applicable.
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
Second-opinion histopathology 5
Table 3. Partial and complete diagnostic disagreements after review of 60 histopathology samples from 53 cats
Diagnostic change
Cell typeNumber ofcases (%)
Subtypenumber (%)a
Gradenumber (%)
Vesselinvasion
number (%)
Degree ofmalignancynumber (%)
Cell typenumber (%)
Mesenchymal 24
Partial disagreement 7 (29%) 3 (19%) 6 (38%) NA NA NA
Complete disagreement 1 (4%) NAb NA 0 0 1 (6%)
Epithelial 22
Partial disagreement 6 (27%) 5 (31%) 0 1 (6%) NA NA
Complete disagreement 1 (5%) NA NA NA 1 (6%) 0
Round cell 3
Partial disagreement 0 (0%) 0 0 0 NA NA
Complete disagreement 0 (0%) NA NA NA 0 0
Melanocytic 1
Partial disagreement 0 (0%) 0 0 0 NA NA
Complete disagreement 0 (0%) NA NA NA 0 0
Lymphoma 7
Partial disagreement 1 (14%) 1 (6%) 0 0 NA NA
Complete disagreement 0 (0%) NA NA NA 0 0
No neoplasia 3
Partial disagreement 0 (0%) 0 0 0 NA NA
Complete disagreement 0 (0%) NA NA NA 0 0
Sixteen biopsies had disagreements and some biopsies had more than one diagnostic change.aSubtype, meaning a change between tumour types within the broader category, such as a change from fibrosarcoma tomyxosarcoma.bNA, not applicable.
supported in 9 cases. In four cases, the follow-
up information appeared to support the first
opinion over the second opinion (Table 6). IHC
contributed to the final diagnosis in eight cases
with major changes. In 22 other cases in which
IHC was used, it was used for cases with only
minor changes (15 cases), or was not conclusive
(7 cases).
The potential effect of biopsy method, tumour
type and species on the likelihood of a major
diagnostic disagreement was examined. Major
disagreements were significantly associated with
species; 72 of 370 (19%) canine biopsies had
major disagreements whereas three of 60 (5%)
feline biopsies had major disagreements (P =0.005). There was no association between major
disagreements and type of tumour (regardless of
species, P = 0.86); however, major disagreements
among mesenchymal tumours were more frequent
in dogs (24 of 119, 20%) than in cats (1 of
24, 4%; P = 0.05). There was no association
between major disagreements and biopsy method
(P = 0.34).
Discussion
Several human studies have investigated the fre-
quency and characteristics of discrepancies between
original and referral pathological diagnoses.1 – 4,7 – 9
This is one of the first studies to evaluate the
impact of second-opinion histopathology in veteri-
nary oncology; disagreements in 30% of reviewed
cases were found. Rates of diagnostic discrepan-
cies in human studies vary substantially, possibly
reflective of how diagnostic variation is defined
in each study.2,4,8 Many factors can contribute to
discrepancies between first-opinion and second-
opinion histopathology reviews, such as subjective
grading, use of different grading schemes, lack of
pertinent and/or complete clinical information,
lack of uniform terminology, varying levels of
expertise of different pathologists and diagnostic
misinterpretation.
Most human studies, and one veterinary study, of
second-opinion pathology are limited to cases from
specific organs or neoplastic processes suspected
to be more prone to diagnostic discrepancies.7 – 12
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
6 R. C. Regan et al.
Table 4. Minor disagreements resulting from second-opinion histopathology review of 430 biopsies from canine and felineoncology patients
Type of change First opinion Second opinionNumber ofcases (%)
Tumour subtype – – 35 (57%)
Change in grade
Lowa or intermediate gradeb No grade given 11 (18%)
No grade given Lowc, intermediated or high gradee 8 (13%)
Intermediate grade Low gradef 3 (5%)
Intermediate grade feline soft tissuesarcoma
High grade feline soft tissue sarcoma 1 (2%)
High grade nasal soft tissue sarcoma Intermediate grade nasal soft tissuesarcoma
1 (2%)
High grade canine retroperitonealhaemangiosarcoma
No grade given caninehaemangiosarcoma
1 (2%)
Small cell indolent lymphoma Small cell intermediate gradelymphoma
1 (2%)
Vessel invasion
Negative Positiveg 6 (10%)
Positive (canine oral melanoma) Negative (canine oral melanoma) 1 (2%)
There were 61 cases with 68 minor histological disagreements.aThis category contains canine soft tissue sarcomas and a canine mammary tumour.bThis category contains canine soft tissue sarcomas, one feline soft tissue sarcoma, one canine subcutaneous haemangiosarcoma,one canine oral squamous cell carcinoma, one canine oral sarcoma and one canine ceruminous gland adenocarcinoma.cThis category contains a feline soft tissue sarcoma.dThis category contains canine soft tissue sarcomas and one canine oral sarcoma.eThis category contains a feline soft tissue sarcoma.f This category contains canine and feline soft tissue sarcomas.gThis category contains two canine lymphomas, one canine grade III soft tissue sarcoma, one canine splenic haemangiosarcoma,one canine subcutaneous round cell tumour and one feline tumour of unknown histogenesis (sarcoma first opinion, carcinomasecond opinion).
Fewer studies, such as that reported herein, have
a global range of specimens, more reflective of a
general surgical pathology practice.3,4,13 As samples
from the present study were from more than 20
different organ systems, an evaluation of a possible
association between anatomic site and a chance of
diagnostic disagreement was not possible.
Most second-opinion diagnostic discrepancies
were partial diagnostic disagreements; the mor-
phological diagnosis was the same but some infor-
mation was changed in 86 of the 129 disagreements
(20% of all cases reviewed). A change in grade of
canine mast cell tumours and soft tissue sarcomas
accounted for 23 of the 86 partial diagnostic dis-
agreements (5% of all cases). Although there are
well-defined criteria for grading these tumours,14,15
there can be variability on how these criteria are
applied by different pathologists. In a study of 10
pathologists, for example, the mean agreement rate
on the grade of mast cell tumours was 62%.16
A similar study has not been carried out for canine
soft tissue sarcomas; however, a study on interob-
server variation when grading human soft tissue
sarcomas showed an agreement rate of 75%.17
When second-opinion pathology with respect to
histological grade of human soft tissue sarcomas was
examined, there was a discrepancy rate of 10%.18
Although some human studies on second-opinion
pathology did not factor intentionally change in
histological grade into rates of disagreement
(because of its presumed subjectivity),4 we believed
it was important to address these types of discrep-
ancies in the present study as they might have a
clinical impact.
The principal motivation for second-opinion
pathology is to improve patient care by the detection
of interpretative errors before beginning definitive
clinical management. Complete diagnostic dis-
agreements occurred in 43 biopsy samples (10%
of all samples reviewed). The second-opinion diag-
nosis, however, does not a priori represent the ‘gold
standard’ or ‘correct’ interpretation. The diagnostic
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
Second-opinion histopathology 7
Table 5. Major disagreements and effects on therapy and prognosis resulting from second-opinion histopathology review of430 biopsies from canine and feline oncology patients
Type of change First opinion Second opinion
Number ofcases (% of
majordisagreements)
Treatmentchange
Prognosischangea
↑ or ↓Benign versus
malignant
Invasive/malignant Noninvasive/benign 24 (30%) Yes ↑Noninvasive/benign Invasive/malignant 5 (6%) Yes ↓
Change in grade
Low grade mast cell tumour Intermediate grade mast celltumour
1 (1%) Yes ↓
Intermediate grade mast celltumour
Low grade mast cell tumour 4 (5%) Yes ↑
Intermediate grade High gradeb 9 (11%) Yes ↓High grade Intermediate gradec 7 (9%) Yes ↑High grade lymphoma Indolent lymphoma 3 (4%) Yes ↑No grade given High graded 2 (3%) Yes ↓
Vessel invasion
Negative Positivee 5 (6%) Yes None
Negative (canine mammarytumour)
Positive (canine mammarytumour)
1 (1%) Yes ↓
Negative (feline mammarytumour)
Positive (feline mammarytumour)
1 (1%) None ↓
Change in tumourtype
Epithelioid sarcoma Basal cell carcinoma 1 (1%) Unknown ↑Undifferentiated sarcoma Squamous cell carcinoma 1 (1%) Yes ↑Histiocytic sarcoma Lymphoma 1 (1%) Yes ↑Chondrosarcoma Osteosarcoma 1 (1%) Yes ↓Poorly differentiated round
cell tumourPlasmacytoma 1 (1%) Yes ↑
Plasmacytoma Lymphoma 1 (1%) Yes ↓Round cell tumour Lymphoma 1 (1%) Yes Unknown
High grade sarcoma Histiocytic sarcoma 1 (1%) Yes None
Intermediate grade sarcoma Histiocytic sarcoma 1 (1%) Yes ↓Undifferentiated sarcoma Haemangiosarcoma 1 (1%) Yes None
Undifferentiated oral sarcoma Melanoma 1 (1%) Yes None
Round cell tumour Histiocytic sarcoma 1 (1%) Yes Unknown
Histiocytic sarcoma Melanoma 1 (1%) Yes None
Plasmacytoma Histiocytic sarcoma 1 (1%) Yes ↓aUp arrow, potential improvement in prognosis, down arrow, potentially worse prognosis.bThis category contains canine mast cell tumours and canine soft tissue sarcomas.cThis category contains canine mast cell tumour and canine soft tissue sarcoma.dThis category contains canine soft tissue sarcomas.eThis category contains a ceruminous gland adenocarcinoma, sweat gland carcinoma, and mast cell tumour and canine anal sacadenocarcinomas.
disagreement might indeed represent interpreta-
tive error within the first-opinion diagnosis, the
second-opinion diagnosis or both. The ideal gold
standard in many of these cases would be to fol-
low the natural history of the disease process that
is under debate, with clinical follow-up. This is
not always possible as in fact, the second opinion
might prompt a change in clinical management that
interferes positively or negatively with the disease
process, therefore precluding definitive assessment
of the true gold standard. Other types of follow-up
information used to determine the accuracy of the
pathological diagnosis might include ‘expert’ opin-
ion, repeat surgical biopsy or IHC. In our study, we
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
8 R. C. Regan et al.
Table 6. Major disagreement cases with follow-up information to ascertain the correctness of the diagnosis
First-opinion diagnosis Second-opinion diagnosis Tumour site Follow-up test(s) Opinion supported
Osteosarcoma Fibrous dysplasia Oral cavity Repeat biopsy First opinion
Histiocytic sarcoma Melanoma Skin Repeat biopsy, IHC, ICC First opinion
Lymphoma Glossitis Oral cavity Repeat biopsy First opinion
Inflammatory bowel disease Lymphoma Intestine Repeat biopsy First opinion
Histiocytic sarcoma Panniculytic T-cell lymphoma Skin IHC Second opinion
Plasmacytoma T-cell lymphoma Oral cavity IHC Second opinion
Lymphoid hyperplasia Small cell lymphoma Lymph node IHC Second opinion
Round cell tumour Nonepitheliotropic lymphoma Skin IHC Second opinion
Undifferentiated sarcoma Haemangiosarcoma Skin IHC Second opinion
Stimulated lymph node Low grade T-cell lymphoma Lymph node PARR, Flow cytometry Second opinion
Undifferentiated sarcoma Histiocytic sarcoma Skin IHC Second opinion
Round cell tumour Plasmacytoma Skin IHC Second opinion
Undifferentiated sarcoma Squamous cell carcinoma Oral cavity IHC Second opinion
ICC, Immunocytochemistry; PARR, PCR for antigen receptor rearrangement. All cases were biopsies from dogs.
were able to obtain pathological follow-up for 13
cases that had major disagreements. This informa-
tion supported the second opinion in nine cases,
and the original opinion in four cases. The impor-
tance of immunohistochemical staining to reach
the final diagnosis cannot be overemphasized.19
It is clear from our results that a second opinion
might not have always prompted a change in the
management of the case. Of the 129 cases in which
disagreements were noted, nearly half were then
classified as minor disagreements (the information
changed between the first and second reports was
judged to have minimal impact on treatment and/or
prognosis).
More concerning are the major, or clinically
significant, discrepancies between the original
pathologist and the second-opinion pathologist
that occurred in 75 of the 129 cases with
disagreements (17% of all cases reviewed). We
do not know if clinicians actually changed
treatment recommendations based on the second-
opinion review, as biopsy reports alone were
used to determine the potential change in
management. Direct communication with the
clinician or complete medical record review
regarding the clinical impact of the different
diagnosis could potentially have changed the
frequency of discrepancies that were considered
to affect patient management.
Canine specimens had significantly more major
disagreements than feline, because of more frequent
major changes in mesenchymal tumours of dogs.
Changes in the histological grade of canine soft
tissue sarcomas (e.g. low or intermediate grade to
high grade, or converse) was classified as a major
disagreement, while a similar change in feline cases
was only classified as a minor disagreement. There
is an accepted association between histological
grade and biological behaviour in canine soft
tissue sarcomas15; the association between grade
and behaviour in feline soft tissue sarcomas is
unclear.20,21 Additionally, because the diagnosis of
injection-site sarcomas in cats is based on history,
anatomic location and histological features, we did
not distinguish between vaccine and non-vaccine
associated sarcomas in this study. In the individual
patient, this distinction might be important because
injection-site sarcomas have been shown to be more
likely to recur after surgical excision.22
There are important limitations in this study.
As previously mentioned, treatment recommen-
dations and prognostic information were based
solely on the pathology report, without regards to
tumour size or stage. The nature of the case mate-
rial reviewed, haematoxylin–eosin stained slides in
the majority of cases, might not have been similar
to that evaluated by the original pathologist, and
fewer slides or sections from different anatomic
areas of the tumour might have affected the inter-
pretation. Finally, the composition of pathologists
who practice within our referral region might have
also influenced the rate of disagreement. Some
received residency training within our depart-
ment of pathology, therefore might have similar
© 2009 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 8, 1, 1–10
Second-opinion histopathology 9
approaches to diagnostic problem-solving in surgi-
cal pathology.
In summary, we found disagreements in
the morphological diagnosis in 30% of the
histopathology reports reviewed, 17% of which
were clinically relevant. This finding supports
the use of second-opinion histopathology as an
important part of patient care.
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