Đăng ký Đăng nhập
Trang chủ Ikeda2003...

Tài liệu Ikeda2003

.PDF
10
168
54

Mô tả:

Radiology Breast Imaging Debra M. Ikeda, MD Robyn L. Birdwell, MD Kathryn F. O’Shaughnessy, PhD R. James Brenner, MD, JD Edward A. Sickles, MD Index term: Breast neoplasms, diagnosis, 00.32, 00.30 Published online before print 10.1148/radiol.2262011634 Radiology 2003; 226:494 –503 Abbreviations: BI-RADS ⫽ Breast Imaging Reporting and Data System DCIS ⫽ ductal carcinoma in situ 1 From the Department of Radiology, Stanford University Medical Center, Rm S-068A, 300 Pasteur Dr, Stanford, CA 94305-5105 (D.M.I., R.L.B.); R2Technology, Sunnyvale, Calif (K.F.O.); Tower–St Johns Imaging Eisenberg Keefer Breast Center, John Wayne Cancer Institute, St John’s Health Center, Santa Monica, Calif (R.J.B.); and Department of Radiology, University of California, San Francisco (E.A.S.). From the 1999 RSNA scientific assembly. Received October 5, 2001; revision requested December 18; revision received March 14, 2002; accepted July 24. Address correspondence to D.M.I. Analysis of 172 Subtle Findings on Prior Normal Mammograms in Women with Breast Cancer Detected at Follow-up Screening1 PURPOSE: To retrospectively review nonspecific findings on prior screening mammograms to determine what features were most often deemed normal or benign despite the development of breast cancer in the same location detected at follow-up screening. MATERIALS AND METHODS: Four hundred ninety-three pairs of consecutive mammographic findings were collected from 13 institutions, consisting of initial normal screening findings and a subsequent finding of cancer at screening (mean interval between examinations, 14.6 months). One designated radiologist reviewed each pair of mammograms and determined that 286 findings were judged visible at prior examination in locations where cancer later developed. Five blinded radiologists independently reviewed the prior findings in these 286 cases, identifying 169 mammograms (172 cancers) with findings so subtle that none or only one or two of the five radiologists recommended screening recall. Two unblinded radiologists reviewed the initial and subsequent findings and recorded descriptors and assessments for each finding and subjective factors influencing why, although the lesion was perceptible, it might have been undetected or not recalled. RESULTS: Of 172 cancers, 129 (75%) were invasive (112 T1 tumors and 17 T2 tumors or higher; median diameter, 10 mm), and 43 (25%) were ductal carcinoma in situ (median size, 10 mm). On the prior mammograms, 80% (137 of 172) of these cancers had subtle nonspecific findings where cancer later developed, and most were assessed as being normal or benign in appearance. CONCLUSION: There is a subset of cancers that display perceptible but nonspecific mammographic findings that do not warrant recall, as judged by both a majority of blinded radiologists and by unblinded reviewers. We believe failure to act on these nonspecific findings prospectively does not necessarily constitute interpretation below a reasonable standard of care. © Author contributions: Guarantor of integrity of entire study, D.M.I.; study concepts and design, D.M.I., R.J.B.; literature research, D.M.I., R.L.B., E.A.S., R.J.B.; clinical studies, D.M.I., R.L.B., K.F.O.; data acquisition, D.M.I., R.L.B., K.F.O.; data analysis/interpretation, D.M.I., R.L.B., E.A.S., K.F.O.; statistical analysis, D.M.I., K.F.O.; manuscript preparation, D.M.I., R.L.B., E.A.S., R.J.B.; manuscript definition of intellectual content, all authors; manuscript editing, D.M.I., R.L.B., E.A.S., R.J.B.; manuscript revision/review and final version approval, all authors. © RSNA, 2002 494 RSNA, 2002 Investigators in retrospective studies of missed breast cancers categorize previous mammograms with normal findings into mammograms in which the cancer is radiographically occult (33%–58%) and mammograms in which a finding is perceptible but was undetected or misinterpreted (1– 4). The latter category can be further subdivided into errors in perception (overlooked mammographic features of cancer) and errors in analysis (misinterpretation of perceptible mammographic abnormalities). At screening mammography, failure to act on classic or atypical findings of cancer is usually due to errors in perception or analysis. On the other hand, failure to act on nonspecific mammographic findings is not tantamount to an error in judgment. In contrast to typical errors of detection or analysis, nondetection or nonaction with regard to nonspecific findings occurs because there are no classic or atypical signs of cancer to detect. Simply put, there are no abnormal findings to be overlooked or missed. Perceived Radiology but nonspecific mammographic findings would correctly be interpreted as normal or benign. Few reports on missed cancers in the radiology literature describe nonspecific findings. The terms for nonspecific findings are often mentioned in reports of missed cancers, but the nonspecific findings are often grouped with other categories of missed cancers (4– 6). In reviews (1– 4,6) of prior mammograms that showed cancer at the time of screening or at time intervals between screenings, investigators named these findings “nonspecific signs,” “minimal signs present,” or “unspecific appearances” or grouped nonspecific findings with “unrecognized signs.” For purposes of the present study, we named this last category “nonspecific findings,” defined as perceptible normal or benign mammographic findings where cancer later developed. Examples of such nonspecific findings included focal densities or benign-appearing calcifications occurring in the location where cancer later developed that were so nonspecific for malignancy that prospective recall from screening mammography was not warranted. The purpose of our study was to retrospectively review these nonspecific findings on prior screening mammograms to determine what features were most often deemed normal or benign despite the development of breast cancer in the same location detected at follow-up screening. MATERIALS AND METHODS Case Selection Methods of mammogram collection have been previously described (7,8). Briefly, 13 U.S. facilities certified according to the Mammography Quality Standards Act (community-based hospitals, health maintenance organizations, and academic mammography centers) provided 1,083 consecutive biopsy-proven cases of cancer detected on screening mammograms in asymptomatic women between 1994 and 1996 (7,8). Institutional review board approval for use of these cases was obtained from each institution. Informed patient consent was not required. Mean patient age was 62.3 years (range, 40 – 86 years). The 1,083 screening mammograms that showed cancer were evaluated by one of the 13 facility radiologists who, with knowledge of the biopsy-proven cancer location, marked the cancer location on the screening mammograms on which the cancer was detected by using two transparent film overlays, one for each view. Volume 226 䡠 Number 2 TABLE 1 Interpretation and Detection Factors Recorded for 172 Subtle Findings on Prior Screening Mammograms No. of Factors Cited for Possible Miss Factor Interpretation factors Normal-appearing tissue Benign-appearing calcifications Too few calcifications Lucent areas Other similar calcifications Finding too small to prompt work-up Detection factors Finding seen on only one view Overlooked calcifications Multiple findings Finding at edge of glandular tissue Distracting lesions Dense breast Finding obscured by overlying tissue or vessels Finding at image edge Large breast Technical factors 92 (53) 53 (31) 40 (23) 29 (17) 21 (12) 12 (7) 37 (22) 29 (17) 22 (13) 21 (12) 19 (11) 18 (10) 13 (8) 12 (7) 6 (3) 31 (18) Note.—Numbers in parentheses are percentages. Findings were reviewed by unblinded reviewers (D.M.I., R.L.B.). Multiple factors recorded for each finding. Four hundred ninety-three of the 1,083 cases with prior screening mammograms were available for review. The mean time between examinations was 14.6 months (range, 9–24 months). Sixty-two of these 493 cases were excluded because of prior breast surgery that resulted in scars or findings affected by metallic skin markers. Four other cases were excluded because the original mammograms were needed at the facility site before the end of our study, leaving a total of 427 cases in the study cohort. One of three board-certified radiologists, other than the facility radiologists, reviewed the 427 cases to determine if the cancers were visible in retrospect on the prior mammograms. One radiologist reviewed 242 mammograms, one radiologist reviewed 103 mammograms, and one radiologist reviewed 82 mammograms. Each radiologist used the previously created film overlays to locate the cancer on the mammograms. The overlay was then superimposed on the prior mammograms with normal findings. If a perceptible finding was deemed visible on the prior mammogram, the radiologist marked the location of the retrospectively visible finding by using a second set of transparent film overlays, creating a reference location of the subsequent cancer on the prior mammogram. Findings were judged visible on the prior mammograms in locations where cancer later developed in 286 of the 427 (67%) cases. The 286 prior mammograms were divided into four sets, each with approximately 75 cases. Forty-five addi- tional cases were added to each case set: five cases in which no abnormalities could been seen on the prior mammograms, 20 cases with small subtle cancers, and 20 cases with normal findings (confirmed by means of at least one subsequent mammographic examination with normal findings in the following 2 years). To determine if the normal findings on the prior mammograms should have been evaluated further, four groups of five radiologists performed a blinded review of the four case sets. The radiologists were unaware of the study purpose and the case mix. These 20 radiologists (10 with a primary focus in mammographic interpretation) were all certified according to the Mammography Quality Standards Act, had practiced radiology for a mean of 17 years (range, 3–35 years), and had read a mean of 300 screening mammograms per month (range, 40 –1,000). Each radiologist independently assessed approximately 120 cases and categorized them according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) (9). BI-RADS categories 1 and 2 indicated normal or benign findings, and categories 0, 4, and 5 indicated abnormal findings. The use of category 3 (probably benign) was discouraged; however, the data showed 16 category 3 cases, which were grouped with the category 1 and 2 cases for purposes of our study. For clarity, we will refer to cases that the majority of five radiologists assessed as having a BI-RADS category of 0, 4, or 5 as abnormal, mean- Analysis of Subtle Findings on Prior Mammograms 䡠 495 TABLE 2 Comparison of BI-RADS Categories at Unblinded Review with Number of Recalls Made by Five Blinded Radiologists for 169 Mammograms with 172 Findings Radiology BI-RADS Category No. of Radiologists to Make Recalls Zero One Two Total No. of Cases No. of Findings 0 1 2 4 80 (47) 51 (31) 38 (22) 82 51 39 9 10 15 31 14 5 42 27 18 0 0 1 169 (100) 172 34 50 87 1 Note.—Numbers in parentheses are percentages. Data were reviewed by unblinded reviewers (D.M.I., R.L.B.). TABLE 3 172 Findings on Prior Screening Mammograms, Stratified for BI-RADS Categories at Unblinded Review and Invasive Cancers versus DCIS BI-RADS Category 0 or 4 Finding No. of Findings Focal island of normal tissue 0 Benign-appearing calcifications 21 (60) Few benign-appearing calcifications 0 Mass 7 (20) Density only on one view 4 (11) Mass with calcifications 3 (9) Other 0 Total 35 Cancer Type BI-RADS Category 1 or 2 No. of Findings Cancer Type NA 11 DCIS, 10 invasive 65 (47) 2 DCIS, 63 invasive 23 (17) 12 DCIS, 11 invasive NA 7 Invasive 1 DCIS, 3 invasive 1 DCIS, 2 invasive NA 24 (18) 4 (3) 5 (4) 0 16 (12) 13 DCIS, 22 invasive 137 15 DCIS, 9 invasive 4 Invasive 5 Invasive NA 1 DCIS, 15 invasive 30 DCIS, 107 invasive Note.—Numbers in parentheses are percentages. NA ⫽ not applicable. Data were reviewed by unblinded reviewers (D.M.I., R.L.B.). ing the finding required immediate action. We will refer to cases that the majority of radiologists judged as having a BI-RADS category of 1, 2, or 3 as normal, meaning that the findings were normal or benign or did not require immediate action. The blinded radiologists were provided with patient age and shown only the prior mammograms with normal findings (mammograms obtained 9 –24 months before the cancer was diagnosed at screening). They were not provided with any mammograms obtained earlier. The blinded radiologists had 84% mean sensitivity for cancer detection in the 20 cases with subtle findings that were added to each case set and 81% mean specificity for the 20 normal cases added to each case set. Mammograms with three or more abnormal findings at the reference location as judged by the five blinded radiologists were considered to have cancers that were initially missed. The rationale is that if a majority of radiologists in a blinded review interpreted the findings as needing immediate work-up, then the finding was prospectively missed (8). 496 䡠 Radiology 䡠 February 2003 One hundred twelve mammograms were judged as having abnormal findings according to these criteria by a majority of the radiologists and were excluded. Three or more of the five blinded radiologists judged the findings on the remaining 174 mammograms as normal, benign, or requiring no immediate workup. We classified these mammograms as having nonspecific findings by using the rationale that if a majority of radiologists in a blinded review interpreted the findings as normal, then the finding was very subtle, normal, or benign in appearance. Five of the 174 mammograms with nonspecific findings had incomplete or missing data and were excluded. The remaining 169 mammograms with 172 cancers constituted our final study group. At the time of the initial study, all mammograms were digitized with an LS85 digitizer (Lumisys, Sunnyvale, Calif) at 50-␮m resolution and printed with an Imation HQ969 laser printer (Imation Enterprises, St Paul, Minn) at 12 bits per pixel and 100-␮m resolution. These digitized images were then printed on film for subsequent case review. Unblinded Radiologist Case Review The purpose of the unblinded review was to have radiologists who specialized in breast imaging and who knew the reference location of the subsequent cancer assess the findings independently, to retrospectively reconfirm BI-RADS categories, to categorize the appearance of each finding, and to determine the reasons why the findings were so nonspecific as to merit prospective assessments of BIRADS categories 1, 2, and 3 by a majority of the blinded radiologists. Two radiologists (D.M.I., R.L.B.) who specialized in breast imaging jointly reviewed the 169 mammograms in an unblinded review to categorize the findings and to assess possible reasons for nondetection and nonaction at initial assessment. To ensure that the digital copies were of sufficient quality for analysis, 20 original mammograms selected to include both masses (n ⫽ 12) and calcifications (n ⫽ 8) were recalled from the facility sites and compared side by side with the copies on dedicated mammography alternators. The original mammogram and the copies were rated by the two radiologists for image quality with a numerical rating of 1–5 (1 ⫽ unable to read, 3 ⫽ acceptable, and 5 ⫽ good) and a narrative description of mass or calcification visibility. The average quality ratings for the original images (4.5) and for the copies (4.4) were similar. The narrative descriptions indicated that the copy quality did not compromise mass or calcification detection, which further supports the acceptability of using image copies for our study. To assess the mammographic characteristics of the visible findings, the 169 prior mammogram copies with normal findings, subsequent follow-up mammograms on which the cancers were detected, and the clear reference overlays were reviewed with a two-tiered dedicated motorized mammography alternator with bright lights and magnifying Ikeda et al Radiology Figure 1. Focal island of normal tissue rated as BI-RADS category 1 at unblinded review and cited for recall by only one of five radiologists at blinded review. (a) Craniocaudal and (b) mediolateral oblique views in a 64-year-old woman show a focal region of normal-appearing glandular tissue (arrow) perceived on the mediolateral oblique view only. Note that the finding has lucent areas within it. Thirteen months later, (c) craniocaudal and (d) mediolateral oblique mammograms show a 1.0-cm suspicious mass (arrows) in the same location. Biopsy results indicated grade II invasive ductal carcinoma. lenses available for use. The four-view prior mammogram with normal findings and the reference overlay were displayed on the top row, and the mammogram showing the cancer 9 –24 months later with the reference overlay were displayed on the bottom row. At the time of case review, although the location of the subsequent cancer was available on the followup mammograms, no patient information, examination dates, or pathologic data were available to the reviewers. The perceptible finding identified with the reference overlay on the prior mammogram was analyzed according to finding type, diameter, location, and depth Volume 226 䡠 Number 2 within the breast. Breast density was also recorded. Each finding was categorized by using the BI-RADS lexicon for masses and calcifications and BI-RADS categories 0 –5, excluding BI-RADS category 3 (9). As we endeavored to fully describe all findings, we added several non–BI-RADS terms to describe the normal and benign findings not addressed in the lexicon. Terms for nonspecific findings included focal islands of normal-appearing tissue, benign-appearing calcifications, few benign-appearing calcifications, and densities. Otherwise, findings were characterized by using the BI-RADS lexicon when possible. The term that best described the major character of the perceived finding was chosen as the finding type. To explain possible reasons why the findings were originally interpreted as normal, we (D.M.I., R.L.B.) recorded features that might have led to dismissal of the finding, including an appearance of focal normal tissue, benign-appearing calcifications, too few calcifications to prompt patient recall, lucent lines within the finding that simulated intermixed fat or crossed Cooper ligaments, other similar calcifications in the breast, or findings too small to prompt work-up. We also recorded features that may have led to nonperception or nondetection of the Analysis of Subtle Findings on Prior Mammograms 䡠 497 Radiology Figure 2. Benign-appearing area, too small to prompt recall, rated as BI-RADS category 2 at unblinded review and recalled by no radiologists at blinded review. (a) Craniocaudal and (b) mediolateral oblique mammograms in a 64-year-old woman show a 3-mm round dense area (arrows) in the upper inner quadrant of the right breast. Twelve months later, (c) craniocaudal and (d) mediolateral oblique mammograms show a 7-mm mass (arrows) in the same location. Biopsy results indicated grade III invasive ductal carcinoma. finding, including findings seen on only one view, subtle clusters of calcifications, multiple findings in the breast, a single benign but prominent and distracting lesion, a finding located at the edge of the glandular tissue or at the edge of the image, dense breast tissue, focal overlying breast tissue or blood vessels that might obscure the finding, and a very large breast in which small lesions might be missed. Multiple factors were recorded for each lesion, if appropriate. 498 䡠 Radiology 䡠 February 2003 We reviewed the pathology reports for each cancer that was subsequently detected on the follow-up screening mammogram and compared each subtle finding on the prior mammogram with the subsequent cancer type and grade. Statistical Analysis A ␹2 test for concordance (CHITEST Function; Microsoft Excel, Redmond, Wash) was prepared to determine if more invasive carcinomas developed in recalled versus nonrecalled cases. RESULTS The 169 patients had an average age of 62.3 years, with 16 (9%) patients aged 40 – 49 years, 50 (30%) aged 50 –59 years, 58 (34%) aged 60 – 69 years, 40 (24%) aged 70 –79 years, and five (3%) aged 80 years or older. In 9% (16 of 169) of cases, Ikeda et al Radiology the breast tissue was assessed as fatty, 46% (78 of 169) had scattered fibroglandular densities, 32% (54 of 169) had heterogeneously dense tissue, and 12% (21 of 169) had extremely dense tissue. One hundred seventy-two cancers were detected at follow-up screening mammography in the 169 patients. The average time between the prior screening examination with normal findings and the cancer diagnosis assigned at follow-up screening was 14.6 months (range, 9 –24 months). Forty-three (25%) of the 172 cancers were ductal carcinoma in situ (DCIS), and the remaining 129 (75%) were invasive cancers at the time of diagnosis. The median lesion size of DCIS was 10 mm (range, 2–75 mm). Twenty-four of 43 (56%) DCIS sizes were obtained from the pathology report, and the rest were obtained from the mammographic measurement of abnormal calcifications. The median lesion size of invasive cancers was 10 mm (range, 1–55 mm). One hundred nineteen of 129 (92%) invasive cancer sizes were obtained from the pathology report, and the rest were obtained from measurement of the abnormal finding on mammograms. Of invasive cancers, 112 were T1 tumors, and 17 were T2 or higher. Of 104 women with invasive cancer and known axillary node status, 22 (21%) had lymph nodes positive for metastatic disease. Table 1 summarizes features that might have contributed to nondetection of findings as judged at unblinded review. Table 2 summarizes the number of cases and findings recalled by the five blinded radiologists compared with those recalled by the unblinded experts. All five blinded radiologists rated nearly half (80 cases, 47%) of the 169 cases as normal at review. Fifty-one of the 169 cases (30%) were rated as normal by four of the five blinded radiologists, and 38 of 169 (22%) were rated as normal by three of the five blinded radiologists (Table 2). At unblinded review, with knowledge of the subsequent cancer location, the two unblinded radiologists would have recalled 35 (20%) of the 172 findings, rating them as BI-RADS category 0 or 4 (Table 2). Twenty-six of these 35 cases (74%) would have required immediate action as judged by one or two of the five blinded radiologists. At unblinded review, the remaining 137 (80%) of the 172 findings were considered normal or benign, even in retrospect, by the two unblinded radiologists, and all of these findings were judged as BI-RADS category 1 and 2 with knowledge of the subsequent cancer location. None of the five blinded Volume 226 䡠 Number 2 Figure 3. Benign-appearing calcifications that could be easily overlooked, rated as BI-RADS category 2 at unblinded review and recalled by no radiologists at blinded review. Magnification of (a) craniocaudal and (b) mediolateral oblique mammograms in a 69-year-old woman show three benign-appearing calcifications (arrows). Fourteen months later, (c) craniocaudal and (d) mediolateral oblique mammograms show a 4-mm cluster of pleomorphic calcifications (arrows) in the same location. Biopsy results indicated DCIS with an intermediate grade. radiologists would have recalled 73 (53%) of these 137 findings. Table 3 summarizes the types of findings considered normal on prior screening mammograms, stratified into cases interpreted as normal in retrospect at unblinded repeat review (137 findings) and recall cases at unblinded repeat review (35 findings). The two categories of unblinded normal and recall cases are further subdivided into invasive cancers and DCIS found subsequently for each type of finding. Findings at unblinded repeat review showed a marked difference in the 137 normal findings versus the 35 recall findings. Of the 137 normal findings confirmed at unblinded review, the most common finding was a focal island of normal tissue (65 findings, 47% of normal findings) (Figs 1, 2), followed by few benign-appearing calcifications (24 findings, 18%) (Fig 3), a benign-appearing calcification cluster (23 findings, 17%), densities seen on only one view (five findings, 4%), masses (four findings, 3%) (Fig 4), and other findings (16 findings, 12%; primarily asymmetric densities, subtle possible distortion, and dilated duct). None of these findings had suspicious features for cancer; specifically, there were no pleomorphic calcifications, suspicious mass margins or shapes, or other findings suspicious for cancer. At unblinded repeat review, 35 cases needed recall in retrospect. In contradistinction to the 137 normal cases, the 35 recall cases contained no focal islands of normal tissue or few benign-appearing calcifications. Most (21 findings, 60%) of the unblinded recall findings were composed of benign-appearing calcifications Analysis of Subtle Findings on Prior Mammograms 䡠 499 Radiology Figure 4. Benign-appearing mass rated as BI-RADS category 2 at unblinded review that was recalled by no radiologists at blinded review. (a) Craniocaudal and (b) mediolateral oblique mammograms in a 64-year-old woman show several benign-appearing equal-density masses, with one of the masses (arrows) in the area of interest. Subsequent screening (c) craniocaudal and (d) mediolateral mammograms obtained 14 months later show a 1-cm mass (arrows) in the left breast, which was pathologically proven to be grade I invasive ductal carcinoma with cribriform and micropapillary DCIS. that also contained some pleomorphic forms (Fig 5), seven masses (20%) that had suspicious margins or shapes (Fig 6), and four densities (11%) that were seen on only one view but had suspicious features that warranted recall on the basis of only that projection. To determine if invasive cancers developed more frequently in the unblinded recall group versus the normal group, we analyzed cancer types developing at the site of unblinded BI-RADS category 0 and 4 findings compared with those developing at the site of BI-RADS category 1 and 2 findings (Tables 3, 4). Invasive carcino500 䡠 Radiology 䡠 February 2003 mas subsequently developed at the site of 63% (22 of 35 cancers) of the unblinded recall findings and also at the site of 78% (107 of 137 cancers) of the normal findings. Results of the ␹2 test were not significant (P ⫽ .06) for this comparison. Table 4 summarizes the results of the unblinded repeat review regarding interpretation and detection factors that may have led to nonrecall. Multiple interpretation and detection factors were recorded for each finding (mean, 2.7 factors). These results have been further stratified for invasive cancers versus DCIS and for unblinded recall cases versus nor- mal cases. Multiple interpretation and detection factors were recorded for each finding (mean, 2.7 factors). There was a difference between factors related to normal findings on the prior screening mammograms of the 129 invasive cancers compared with those of the 43 DCIS cases (Table 4). Most of the 129 invasive cancers (88 of 129, 68%) looked like normal tissue on the prior mammogram; others were seen on only one view (28 of 129, 22%) or had lucent lines that simulated fat running through the finding (26 of 129, 20%). In contradistinction, the findings in the 43 DCIS cases were domIkeda et al Radiology inated by microcalcifications—specifically, benign-appearing calcifications (30 of 43, 70%), too few calcifications to prompt recall (23 of 43, 53%), or small clusters that may have been overlooked (16 of 43, 37%). DISCUSSION False-negative findings on screening mammograms contribute to increased breast cancer mortality rates (1,4). Our population differs from that in many prior investigations of false-negative mammographic findings because we focused on nonspecific findings that are perceptible and detectable but that are so normal or benign in appearance that most would not be recalled, even in retrospect. Indeed, three, four, or all five blinded radiologists interpreted any given case in this study population as normal or benign or not needing immediate recall. Results of our unblinded repeat review confirmed a subset of cases with findings that were still judged as normal or benign by radiologists who specialize in breast imaging and who knew the location and appearance of the subsequent cancer. Thus, our data set differs substantially from that in most studies that focus on detection errors or misinterpretation of abnormal findings. The results of our study demonstrate that there are subsets of perceptible but nonspecific findings on prior mammograms that should not be considered observer or interpretation errors. These nonspecific findings are composed mostly of densities that are indistinguishable from randomly distributed islands of fibroglandular tissue or scattered groups of tiny calcifications that most commonly represent fibrocystic change. Even though 137 of such findings were not recalled by a majority of five blinded radiologists and were judged as normal or benign at unblinded repeat review, 107 invasive cancers (78%) and 30 cases of DCIS (22%) developed at the same location as the subtle finding and were detected on follow-up screening mammograms 9 –24 months later. Few investigators describe nonspecific normal or benign findings on prior screening mammograms to serve as a comparison for our study. Unrecognized mammographic findings are often composed of both nonspecific findings and atypical but misinterpreted features of breast cancer. The minimal signs reported by van Dijck et al (10) comprised vague densities in 15 of 32 (47%) cases, Volume 226 䡠 Number 2 Figure 5. (a) Craniocaudal mammogram in a 62-year-old woman with clustered microcalcifications (arrow) in the right breast, which were rated as BI-RADS category 0 at unblinded review and were recalled by only one of five radiologists at blinded review. (b) Screening craniocaudal mammogram obtained 13 months later shows a 1.2-cm DCIS, seen as pleomorphic calcifications (arrow). densities in five (16%), microcalcifications in eight (25%), densities and microcalcifications in one (3%), and architectural distortion in three (9%). Similarly, our 137 nonspecific findings confirmed at unblinded review mostly comprised noncalcified findings, such as focal islands of fibroglandular tissue, masses, and densities (74 of 137, 54%), while fewer findings comprised calcifications (47 of 137, 34%). In a previous study, Ikeda et al (4) found 21 (22%) slightly abnormal findings that showed nonspecific signs in 96 interval cancers, including six nonspecific densities, four asymmetries, four benign-appearing calcification clusters, and four benign masses. Similar to those in the present study, the nonspecific signs of cancer in the study of Ikeda et al (4) were dominated by benign-appearing soft-tissue findings. In two studies in which recall from mammographic screening would not be recommended, results were similar to ours. Wolverton and Sickles (5) prospectively evaluated 583 “doubtful mammographic findings” on screening mammograms in 382 women, in which all findings but one (low-grade DCIS) were normal at a mean follow-up interval of 30 months. Of note, most of their doubtful mammographic findings were composed of benign-appearing calcifications (48%), while the rest were noncalcified nodules (22%), vague densities (18%), asymmetries (7%), or a combination of findings (2%) that were interpreted as benign. The authors concluded that almost all of these prospectively marked benign findings were benign and inconsequential. Maes et al (6) reviewed nonspecific minimal signs (vague densities with an unsharp border, less than six clustered indefinable microcalcifications, and subtle architectural distortions) in a large population in the Netherlands to determine the frequency of recall and the effect these findings had on the screening program. Their nonspecific minimal signs were found in 53 (11%) of 500 women with normal or benign mammographic findings. The authors concluded that, on the basis of breast cancer prevalence and incidence in the Netherlands, the additional risk of such women developing breast cancer is about 0.5% and that regular mammographic screening, rather than recall, is a reasonable option. The results of these two studies show that nonspecific findings occur frequently in mammographic screening programs and that most do not represent cancer. One limitation of our study was the lack of even older mammograms for comparison with the prior screening mammograms with normal findings. It is conceivable that comparison with these older mammograms might have shown that the nonspecific normal findings on our prior mammograms may have been either developing or new, warranting recall. We simply cannot tell or predict which of these cases could have been in this category. On the other hand, if the finding had been shown on an initial screening mammogram, as was simulated during the blinded review by the five radiologists, most radiologists would have interpreted the finding as normal. This shows that our case set contained findings that were very subtle or appeared benign or normal. Analysis of Subtle Findings on Prior Mammograms 䡠 501 Radiology Figure 6. (a) Mediolateral oblique (left) and craniocaudal (right) mammograms in a 75-year-old woman with a subtle spiculated mass (arrows) in the right breast. The mass was rated as BI-RADS category 0 at unblinded review and was recalled by only one of five radiologists at blinded review. (b) Mediolateral oblique (left) and craniocaudal (right) mammograms obtained 12 months later show a larger spiculated mass (arrows). Note that the mass is slightly more anterior on the mediolateral oblique view than on the mediolateral oblique view in a because of differences in obliquity. Pathologic findings showed a 1.5-cm invasive lobular carcinoma. Another limitation of the current study is the second retrospective unblinded review that was necessary to characterize each subtle finding in this case set and to reconfirm BI-RADS categories. Unblinded retrospective reviews inherently lead to unintentional bias and may have led to the higher number of abnormal readings not evident in the initial blinded review by the five radiologists. Harvey et al (11) showed that nonpalpable breast cancers are often detected in retrospect on prior mammograms but that retrospective reviewers de502 䡠 Radiology 䡠 February 2003 scribed the findings as suspicious more often than did blinded reviewers, a difference that was statistically significant. In their retrospective study, blinded reviewers were shown 73 prior mammograms with normal findings in patients who subsequently developed cancer, 30 (41%) of whom had mammographic evidence of cancer. The blinded reviewers interpreted these remaining 43 (59%) mammograms as normal, but retrospective reviewers found evidence of cancer (mostly asymmetric densities) on 25 mammograms (34%). Thus, it is not surprising that our unblinded review resulted in 35 suspicious findings in retrospect, likely because of the increased tendency of retrospective reviewers to detect abnormalities on mammographic review. A possible criticism of our study is the initial grouping of BI-RADS category 3 cases with the BI-RADS category 1 and 2 cases. The 16 BI-RADS category 3 readings were a small percentage of all blinded readings, consisting of 1.8% (16 of 845) of all the readings in the 169 cases by the five radiologists. While this practice was discouraged in the initial blinded review, some radiologists still rated a few cases as BI-RADS category 3. We do not endorse this practice for clinical use, and in our practices, we do not allow final categorization of cases into BI-RADS category 3 without a recall from screening and a diagnostic work-up. For purposes of the present study, we grouped the 16 BI-RADS category 3 cases with BI-RADS category 1 and 2 cases by reasoning that these categories constituted findings that required no immediate action. Thus, one of the purposes of the second unblinded review was to have the two radiologists reconfirm overall BI-RADS categories. In this way, we could search for those findings that constituted BI-RADS category 1 and 2 cases at repeat review with the understanding that there are unintentional study biases introduced (addressed in the previous paragraph). Interpretive error, involving either detection or diagnosis of breast cancer, is the most common reason that radiologists are sued for malpractice (11). At issue in such cases of alleged negligence is whether the abnormality identified on a prior mammogram should have been recalled or diagnosed as a suspicious finding by a reasonable and prudent radiologist practicing under similar circumstances (12). The essential element of such an analysis concerns foreseeable outcome; namely, is it reasonably foreseeable that the mammographic finding in question represents evidence of malignancy (13)? Conversely, is it reasonably foreseeable that the mammographic finding in question does not represent evidence of malignancy? The law requires neither a warranty of certainty nor accuracy, but it does require a reasonable approach (12,14,15). The results of our study provide a basis for indicating which types of lesions may in fact represent cancer but which lack reasonable foreseeable outcome in a medicolegal context to necessarily prompt further evaluation because they are so nonspecific and are more likely to represent benign findings and normal variants. Expert witIkeda et al Radiology TABLE 4 Interpretation and Detection Factors for 172 Findings on Prior Screening Mammograms, Stratified for BI-RADS Categories at Unblinded Review and Invasive Cancers versus DCIS BI-RADS Category 0 or 4 Factor Interpretation factors Normal-appearing tissue Benign-appearing calcifications Too few calcifications Lucent areas Other similar calcifications Finding too small to prompt work-up Detection factors Seen on only one view Overlooked calcifications Multiple findings Finding at edge of glandular tissue Distracting lesions Dense breast Finding obscured by overlying tissue or vessels Finding at image edge Large breast Technical factors No. of Factors No. of Findings (n ⫽ 35) 92 (53) 53 (31) 40 (23) 29 (17) 21 (12) 12 (7) 7 (20) 10 (29) 7 (20) 9 (26) 2 (6) 4 (11) 1 6 3 2 2 1 DCIS, DCIS, DCIS, DCIS, DCIS DCIS, 37 (22) 29 (17) 22 (13) 21 (12) 19 (11) 18 (10) 13 (8) 12 (7) 6 (3) 31 (18) 5 (14) 16 (46) 6 (17) 9 (26) 5 (14) 3 (9) 6 (17) 6 (17) 5 (14) 7 (20) 2 9 2 2 2 3 2 3 2 4 BI-RADS Category 1 or 2 No. of Findings (n ⫽ 137) Cancer Type 3 invasive 85 (62) 43 (31) 33 (24) 20 (15) 19 (14) 8 (6) 3 DCIS, 82 invasive 24 DCIS, 19 invasive 20 DCIS, 13 invasive 1 DCIS, 19 invasive 7 DCIS, 12 invasive 4 DCIS, 4 invasive DCIS, 3 invasive DCIS, 7 invasive DCIS, 4 invasive DCIS, 7 invasive DCIS, 3 invasive Invasive DCIS, 4 invasive DCIS, 3 invasive DCIS, 3 invasive DCIS, 3 invasive 32 (23) 13 (9) 16 (12) 12 (9) 14 (10) 15 (11) 7 (5) 6 (4) 1 (1) 24 (18) 7 DCIS, 25 invasive 7 DCIS, 6 invasive 1 DCIS, 15 invasive 12 Invasive 3 DCIS, 11 invasive 3 DCIS, 12 invasive 7 Invasive 3 DCIS, 3 invasive 1 Invasive 10 DCIS, 14 invasive Cancer Type 6 4 4 7 invasive invasive invasive invasive Note.—Numbers in parentheses are percentages. Multiple factors were recorded for each finding. Findings were reviewed by unblinded reviewers (D.M.I., R.L.B.). nesses reviewing cases of alleged negligence must distinguish between nonspecific findings that do not require recall and more important abnormalities that merit prompt additional imaging evaluation. To be fair and reasonable, expert reviews should be conducted in a manner that minimizes interpretation bias by blinding the reviewer to the location, mammographic features, and timing of subsequent cancer (similar to the blinded reviews of the four groups of five radiologists described in our study). In the setting of a medicolegal consultation, this can be achieved most effectively by viewing mammograms in the temporal sequence in which they were obtained and by limiting the reviewer’s access to supporting clinical information to that known by the interpreting radiologist at the time of examination. If prior findings are sufficiently specific and suspicious to prompt recall, failure to do so may fall below a recognized standard of care. However, when mammographic findings are present in the area that later develops more specific features of malignancy, and those earlier findings are nonspecific or subthreshold, the results of our study support the notion that failure to recall the patient does not necessarily fall below the standard of care. Thus, the mere presence of a prior finding in a patient who was not recalled at the time of screening does not constitute medical negligence or unreasonable interpretation, which is the basis for liability in an allegation of malpractice. None of our paVolume 226 䡠 Number 2 tients were recalled prospectively, given the limitations of the study design, and 137 of the cases were judged as having a BI-RADS category of 1 or 2 at unblinded repeat review, supporting the contention that at least some of these findings should not necessarily be recalled. These 137 perceptible but nonspecific findings did not warrant recall as judged by a majority of a group of five blinded radiologists and by two unblinded reviewers, and failure to recall these cases does not constitute diagnostic error. In summary, the results of our study show that there is a class of nonspecific findings that are perceptible on prior screening mammograms that do not warrant recall, and despite their presence in a location where cancer would later develop, we believe failure to identify these findings prospectively does not necessarily constitute interpretation below a reasonable standard of care. 5. 6. 7. 8. 9. 10. 11. References 1. Frisell J, Eklund G, Hellstrom L, Somell A. Analysis of interval breast carcinomas in a randomized screening trial in Stockholm. Breast Cancer Res Treat 1987; 9:219 –225. 2. Holland R, Mravunac M, Hendriks JH, Bekker BV. So-called interval cancers of the breast. Pathologic and radiologic analysis of sixtyfour cases. Cancer 1982; 49:2527–2533. 3. Martin JE, Moskowitz M, Milbrath JR. Breast cancer missed by mammography. AJR Am J Roentgenol 1979; 132:737–739. 4. Ikeda DM, Andersson I, Wattsgard C, Janzon L, Linell F. Interval carcinomas in the Malmo Mammographic Screening Trial: radiographic 12. 13. 14. 15. appearance and prognostic considerations. AJR Am J Roentgenol 1992; 159:287–294. Wolverton DE, Sickles EA. Clinical outcome of doubtful mammographic findings. AJR Am J Roentgenol 1996; 167:1041–1045. Maes RM, Dronkers DJ, Hendriks JH, Thijssen MA, Nab HW. Do non-specific minimal signs in a biennial mammographic breast cancer screening programme need further diagnostic assessment? Br J Radiol 1997; 70:34 –38. Warren Burhenne LJ, Wood SA, D’Orsi CJ, et al. Potential contribution of computer-aided detection to the sensitivity of screening mammography. Radiology 2000; 215:554 –562. Birdwell RL, Ikeda DM, O’Shaughnessy KF, Sickles EA. Mammographic characteristics of 115 missed cancers later detected with screening mammography and the potential utility of computer-aided detection. Radiology 2001; 219:192–202. American College of Radiology. Breast imaging reporting and data system (BI-RADS). 3rd ed. Reston, Va: American College of Radiology, 1998. van Dijck JA, Verbeek AL, Hendriks JH, Holland R. The current detectability of breast cancer in a mammographic screening program: a review of the previous mammograms of interval and screen-detected cancers. Cancer 1993; 72:1933–1938. Harvey JA, Fajardo LL, Innis CA. Previous mammograms in patients with impalpable breast carcinoma: retrospective vs. blinded interpretation. AJR Am J Roentgenol 1993; 161:1167–1172. Physicians Insurers Association of America. Breast cancer study. Rockville, Md: Physicians Insurers Association of America, 1995. Skeffington v Bradley, 366 Mich 552, 115 NW2d, 3030 (Mich 1962). Brenner RJ. Medical legal aspects of breast cancer evaluation and treatment. In: Harris JR, Lippman ME, Hellman S, eds. Diseases of the breast. Philadelphia, Pa: LippincottRaven, 1996; 125–133. Todd v Eitel Hospital, 237 NW2d 357, 79 ALR 3d 907 (Minn 1975). Analysis of Subtle Findings on Prior Mammograms 䡠 503
- Xem thêm -

Tài liệu liên quan

Tài liệu vừa đăng