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Annals of Surgical Oncology 9:982-987 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Changes in Breast Cancer Therapy Because of Pathology Second Opinions

Valerie L. Staradub, MD, Kathleen A. Messenger, BS, Nanjiang Hao, MS, Elizabeth L. Wiley, MD and Monica Morrow, MD

From the Lynn Sage Comprehensive Breast Program (KAM), Departments of Surgery (VLS, MM), Pathology (ELW), and Preventive Medicine (NH), Northwestern University School of Medicine, Chicago, Illinois.

Correspondence: Address correspondence and reprint requests to: Valerie L. Staradub, MD, Galter 10-105, 201 E. Huron St., Chicago, IL 60611; Fax: 312-695-4956; E-mail: vstaradu{at}nmff.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Examination of pathology slides is a routine part of a breast cancer second opinion. The purpose of this study was to determine how often the pathologic second opinion (1) altered the diagnosis and (2) resulted in a change in the surgical procedure.

Methods: Patients presenting between 1997 and 2001 for a second opinion after a biopsy diagnosis of breast cancer (invasive or noninvasive) were included in this study.

Results: There were 340 patients presenting for second opinions regarding 346 breast cancers. Sixty-eight pathologic second opinions (20%) did not result in any change in pathology or prognostic factors, whereas in the remaining 80%, some change occurred. Major changes that altered surgical therapy occurred in 7.8% of cases, and pathology review provided additional prognostic information in 40%. Changes were more common in in situ carcinoma than invasive carcinoma (P = .004), but biopsy type (core vs. excisional biopsy) was not a significant predictor of change in pathologic information.

Conclusions: This study confirms the benefit of a pathology second opinion to improve preoperative estimates of prognosis and to determine the appropriate surgical procedure. Missing information on grade and histological subtype was responsible for a large number of cases, suggesting a need for widespread application of standardization and quality improvement in pathology reporting.

Key Words: Breast cancer • Pathology • Second opinion • Surgical therapy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The 1992 National Health Interview Survey found that 55.7% of cancer patients sought a second opinion, and the use of second opinions was most frequent among breast cancer patients (odds ratio, 2.1; 95% confidence interval, 1.2–3.7).1 In most tertiary care centers, a second opinion includes a review of the initial pathology by a pathologist with interest and expertise in breast cancer, adding both time and expense to the second-opinion process.

There has been considerable debate regarding the utility of the routine review of all pathologic diagnoses by a second pathologist,2–8 with opinions ranging from little utility for routine pathologic review2 to a need for mandatory review of every case.6–8 Few studies, however, separate their cases by diagnostic category.

The purpose of this study was to determine how often the pathologic diagnosis of invasive or in situ breast cancer was altered by pathology second opinion at a tertiary care institution, as well as to determine how often information provided by the pathology second opinion changed the definitive surgical procedure. A secondary purpose of the study was to determine how often the pathology second opinion changed prognostic or histological information.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients presenting to the Lynn Sage Breast Center between 1997 and 2001 for a second surgical opinion after a diagnosis of breast cancer were identified from a prospectively maintained database. Patients with cancer diagnoses of invasive carcinoma, ductal carcinoma-in-situ (DCIS), or lobular carcinoma-in-situ (LCIS) made by excisional biopsy, core needle biopsy, or fine-needle aspiration were included in the study. Biopsy material from the outside institution was reviewed by a pathologist with an interest in breast pathology before the patient’s clinic visit, and a written report was issued. Our interpretation was compared with the outside institution’s reading. For the purposes of this study, major changes were characterized as (1) failure to confirm the diagnosis of malignancy, (2) a change in diagnosis from invasive to noninvasive carcinoma or the converse, or (3) a change in diagnosis that would alter the recommended surgical procedure (i.e., margin status positive to negative). Margins were called positive if tumor cells touched an inked surface.

Minor changes were defined as those that could alter prognosis but would not result in a change in the recommended surgical procedure. These included changes in the histological type of invasive carcinoma or DCIS. Special attention was paid to the diagnosis of favorable histological types, such as tubular and colloid carcinoma, because recommendations for adjuvant therapy in this subset of patients differ from those in patients with other types of breast cancer. Changes in tumor grade were also quantitated, with special attention paid to differentiation between grade 1 and other grades, because these may influence recommendations for adjuvant therapy, such as the use of radiotherapy in DCIS or systemic treatment with endocrine therapy alone.

If an individual patient had both a major change and a minor change after the pathology reports were compared, only the major change was quantitated. Two major changes in a single case, that is, a change in lesion characterization plus a change in margin status, were both quantitated, because each had the capacity to change a different aspect of the surgical therapy. However, in tabulating the percentage of total cases that had major changes, each cancer was counted only once. Statistical comparisons between the two groups were performed with Fisher’s exact test.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
There were 340 patients with 346 cancers included in this study. Two hundred forty-two of the cancers were classified as invasive, 81 were DCIS, and 23 were LCIS. Most patients (92%) had their initial pathology interpretation at a community hospital. Excisional breast biopsy was the most common diagnostic technique, used in 217 (63%) of cases. The remaining diagnoses were made from core cutting needle biopsy specimens (32%), fine-needle aspiration (4%), or lymph node biopsy (1%).

Major Changes
There were 30 major changes in pathology involving 27 (7.8%) of the 346 cases reviewed. In three cases, two major changes were noted, one involving histology and the other involving margins. In one case, a patient initially diagnosed with DCIS, the diagnosis of malignancy was not confirmed by our review. Differing opinions regarding the presence of invasive carcinoma accounted for 13 (43.3%) of the major changes in our study. These were evenly distributed between cases initially diagnosed as invasive carcinoma and found to contain only DCIS on review (n = 7) and cases initially diagnosed as DCIS and then found to have unreported areas of invasion (n = 6). In 10 of these 13 cases, the specimen being evaluated was an excisional breast biopsy, and the size of the malignant lesions ranged from 2 mm to 5.5 cm. Five changes in diagnosis were cases that involved diagnostic uncertainty on the part of either the referring or the consulting pathologist. Invasion was confirmed in two cases in which it had not been definitively identified on the initial pathology report. Two cases that were initially called DCIS had the possibility of invasion raised on review. In one case that had been called invasive carcinoma, the diagnosis was changed to DCIS with possible invasion. Three of the five cases involving diagnostic uncertainty were core biopsy specimens.

Margin status was assessed in the initial pathology report in 212 of the 217 excisional biopsies. In 16 cases (4.6% of total, or 7.5% of those with assessable margins), margin status was changed by pathology review. In 10 cases, margins called positive were found to be negative, and in 6, the opposite change was noted. The major pathology changes are listed in Table 1.


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  		TABLE 1. Major changes in pathologic diagnosis
 
Neither tumor type (invasive vs. DCIS) nor biopsy type (core cutting needle biopsy vs. surgical biopsy) was a significant predictor of the likelihood of identifying a major pathologic change (Table 2). Margin status was not included in the analysis of biopsy type, because core biopsy is not designed to achieve a complete excision with assessable margins.


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  		TABLE 2. The role of tumor type and biopsy type in predicting change in pathologic opinion
 
Minor Changes
Changes in prognostic information resulted from the pathology review in 92 (38%) of 242 invasive cancers and 46 (57%) of 81 cases of DCIS. Failure to include grade on the initial pathology report was the most common change, seen in 17.4% of invasive cancers and 35.8% of DCIS cases. Changes between grade 1 and other grades occurred in 7.4% of invasive cancers and 11.1% of in situ carcinomas (Table 3). Missing information for grade or histological subtype was the only change made on pathology review in 13% of cases.


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  		TABLE 3. Minor changes in prognostic information
 
Changes involving cases with assigned histological subtypes are listed in Table 3. Histological subtype was reported at the time of the primary surgical opinion in 87% of cases. Changes in subtype occurred in 25.2% of invasive carcinomas, with 18 cases (7.4%) involving a change to or from a particularly favorable subtype (tubular or colloid). A change in subtype at the second pathologic opinion was more common in DCIS, occurring in 44.4% of the cases, and the addition of DCIS to or the deletion of DCIS from a diagnosis of invasive cancer was seen in 43 cases (17.8%).

Minor changes were more likely to be found in cases of DCIS than invasive carcinoma (57% vs. 38%; P = .004). Similarly, DCIS was more likely to have no grade (36% vs. 17%; P < .001) or no histological subtype (9% vs. 1.7%; P < .001) reported on the initial pathology report than invasive carcinoma. Biopsy type was not a significant predictor of minor changes in pathology reports (Table 3).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Studies indicate that most general surgical pathologists accurately diagnose 80% to 90% of the cases that they see.6,7,9 Kronz et al.9 evaluated changes in diagnosis after an in-house second pathologic opinion and found a 1.4% rate of significant change in diagnosis in breast cancer cases, most frequently between DCIS with invasion and DCIS alone. This was similar to the overall rate of major changes in diagnosis among all specimen types. This situation is somewhat different, however, from pathologic review of outside slides by a treating institution. The percentage of cases with a major change in pathologic opinion seems to be higher when diagnoses are compared between institutions. This difference is due in part to differences in boundaries set by groups of pathologists regarding grading and types of carcinomas.10,11 In our study, we noted a 4% incidence of major changes in diagnosis. As in the report of Kronz et al.,9 the most common disagreement was over the presence or absence of invasion in the setting of DCIS, with a change from a malignant to a benign diagnosis in only a single case.

The Association of Directors of Anatomic and Surgical Pathology has formally recommended that a review of outside surgical material at the treating institution be standard policy.12 This was reiterated by a consensus conference panel, which stated that when a second therapeutic opinion based on a tissue diagnosis made elsewhere is sought, the diagnosis should be confirmed by a second pathologic opinion at the treating institution.13 However, not all institutions have a requirement for such review.14 Our study confirms the importance of review of outside biopsy materials, with major changes affecting surgical therapy noted in 7.8% of patients. These findings are similar to those reported by Abt et al.,15 who reviewed all interinstitutional consultations at the Hershey Medical Center in Pennsylvania for one calendar year. Eighty-eight percent of the biopsies reviewed were for suspected malignant disease, and some level of important disagreement was seen in 71 (9.1%) of 777 cases. It is interesting to note that the 1-year clinical follow-up of these cases demonstrated that in 4 of the 71 cases, the initial outside diagnosis was correct, and in 1, neither the initial diagnosis nor the second opinion diagnosis was correct. In the remaining patients with divergent diagnoses, the second opinion diagnosis seemed to have been correct on the basis of the patient’s subsequent clinical course. The diagnostic disagreements among pathology opinions resulted in changes in therapy or clinical evaluation in 45 (63%) of the 71 patients, including alterations in the surgical plan or chemotherapy regimen, performance of a repeat biopsy, or additional pathologic consultation.

Similar percentages of discrepancies among pathologic diagnoses have been reported in several smaller studies. Malhotra et al.16 reported an overall rate of cancer-related discordances requiring a change in clinical evaluation or therapy of 10.1%, and a study of second pathologic opinion in cancer cases from the United Kingdom noted a 31% alteration in diagnosis (including making a confident diagnosis where there was previously no definite diagnosis).17 In this United Kingdom study, a number of cases initially diagnosed as benign were found to be malignant on review. Benign diagnoses are seldom subjected to a second opinion, so the rate of underdiagnosis of malignant lesions, particularly with in situ disease, is largely unknown.

There are few studies that focus specifically on second opinions for breast pathology. Chang et al.18 noted a major difference in interpretation leading to a change in therapy in 3 (4%) of 75 breast cases reviewed at the University of Pennsylvania multidisciplinary breast center. Two of these cases included changes between LCIS and atypical lobular hyperplasia, and the other case was a change from DCIS with close margins to DCIS with microinvasion and involved margins.

In a statewide study in New Hampshire, Wells et al.19 distributed a set of slides from representative cases of breast biopsy specimens to 26 pathologists, who categorized lesions as benign, benign with atypia, noninvasive malignant, or invasive malignant. Approximately 9% of the cases were noninvasive malignant processes, and 22% were invasive malignant disease. Eight percent of benign cases were diagnosed as noninvasive malignancy by at least one pathologist, and seven pathologists diagnosed a noninvasive malignancy in two cases when the remainder of the pathologists diagnosed invasive carcinoma. There were two additional cases in which the pathologists were approximately equally divided between diagnoses of invasive versus noninvasive malignancy. There were also two instances in which a diagnosis of invasive cancer was made when most of the diagnoses were benign disease, and there was an additional case in which one pathologist diagnosed benign disease when the remainder diagnosed noninvasive malignancy. The group of pathologists in this study were considered to be general pathologists with no special interest or expertise in breast pathology and could be considered similar to the pathologists initially interpreting the slides of the patients reported in our study. However, differences in diagnoses can occur even among more experienced pathologists. Rosai10 reported the results of a study in which 5 expert breast pathologists reviewed 17 cases of low-grade DCIS, atypical ductal hyperplasia, and ductal hyperplasias, and complete diagnostic agreement was not reached in a single case; 4 of the 5 pathologists agreed in only 3 cases (18%). It is important to note, however, that the cases in this study were all cases considered to be diagnostically challenging, an area in which diagnostic discrepancy is most likely to occur. However, Schnitt et al.11 performed a similar study in which pathologists were given standardized diagnostic criteria for the diagnosis of atypical ductal hyperplasia and low-grade DCIS and reported a much higher level of agreement in diagnosis.

Although it may be difficult to determine whether the original pathologist or the second-opinion pathologist has made the correct diagnosis, we believe that an in-house second opinion offers the surgeon the advantage of a consultation from a pathologist whose diagnostic criteria are familiar to the surgeon and who is accessible for case review. In our study, the pathology review changed surgical therapy in only 7.8% of cases, but for the individual patient, avoiding unnecessary axillary surgery or re-excision lumpectomy is a major benefit.

Minor changes in pathology were seen in a substantially higher percentage of patients. Although a change in tumor grade or subtype is unlikely to change the surgical management of a breast cancer, it has the potential to affect the use of adjuvant radiotherapy and chemohormonal therapy, as well as the choice between endocrine therapy alone and combined chemotherapy and endocrine therapy. Tubular carcinoma and colloid carcinoma are well documented to have a more favorable prognosis than ductal or lobular carcinomas of the same size20 and may be treated with adjuvant endocrine therapy alone.21,22 In our study, either 7.4% of cancers were incorrectly classified as tubular or colloid initially, or this important prognostic subgroup was not recognized on the initial pathology report. Similarly, grade 1 invasive carcinomas of all subtypes have a more favorable outcome than tumors of the same size that are grade 2 or 3,23 yet 7.4% of cases underwent upstaging from or downstaging to grade 1. Histological grade is one factor used to determine the benefit of radiotherapy for patients with intraductal carcinoma,24,25 but we noted grade changes in 21% of DCIS patients. In addition, information on grade was missing from 53% of outside pathology reports, and information on histological subtype was not included in 13% of cases.

Patients diagnosed with DCIS were significantly less likely to have information on grade or histological subtype reported than their counterparts with invasive carcinoma. Our initial assumption was that this might be due to the limited material available in needle core biopsies, the primary method used to diagnose DCIS lesions. However, we observed no correlation between the lack of information on grade or subtype and the type of diagnostic biopsy performed. The College of American Pathologists has attempted to reduce the frequency of incomplete reporting of clinically relevant information by creating a series of synoptic reports for the major cancer sites that can be accessed from their Web site. Standard reporting methods for clinically important parameters have been published for both invasive26,27 and in situ carcinomas.27–29

In summary, we found complete correlation between the initial pathology report and our second-opinion consultation in only 69 (20%) of 346 breast cancer cases. Missing information accounted for a significant number of the changes, but changes that altered the surgical procedure occurred in 7.8% of cases, and additional prognostic information was obtained in 40% of cases. Thus, although failure to confirm a malignant diagnosis occurred only in one case, we believe that the patient and physician time and the costs to the health care system incurred with pathology second opinions for breast cancer are justified by the findings in this study.


   Acknowledgments
 
Supported by the Avon Products Foundation and the Specialized Program of Research Excellence in Breast Cancer, grants P50-CA89018 (MM) and DAMD 17–96–2-6013 (MM).


   Footnotes
 
Presented in part at the Society of Surgical Oncology 55th Annual Cancer Symposium, Denver, Colorado, March 16, 2002.

Review of pathology slides from another institution is a routine component of breast cancer second-opinion consultations. This study examines the benefit of this pathology second opinion in the determination of appropriate surgical therapy, as well as the preoperative estimation of prognosis.

Received for publication March 15, 2002. Accepted for publication July 29, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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