Comparison of 1st opinion and 2nd opinion histopathology from dogs and cats with cancer

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Original Article DOI: 10.1111/j.1476-5829.2009.00203.x Comparison of first-opinion and second-opinion histopathology from dogs and cats with cancer: 430 cases (2001 – 2008) R. C. Regan 1 , K. M. Rassnick 1 , C. E. Balkman 1 , D. B. Bailey 1and S. P. McDonough 2 1 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA 2 Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA Abstract Second-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. Keywords biopsy; 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, Tsung 4 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 Clinical Sciences College of Veterinary Medicine Box 31, Ithaca, New York, 14853, USA e-mail: [email protected] © 2009 Blackwell Publishing Ltd 1

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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.

References

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