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A review of false negative mammography in a symptomatic population
Clinical Radiology (1991) 44, 13-15
A Review of False Negative Mammography in a Symptomatic Population M. G. WALLIS, M. T. WALSH and J. R. LEE
The General Hospital, Birmingham A review of the mammograms of 871 patients with breast cancer from a symptomatic clinic performed at the General Hospital, Birmingham between 1980 and 1988 revealed an overall false negative rate of 8.6%. There has been a steady fall in the number of cancers missed per year from the commencement of review, and this reduction has been more consistent with improvements in radiographic equipment and technique, particularly the introduction of a radiographic grid. In half of the cases the tumour was missed because no radiological abnormality was detectable, even on reviewing the films, and this rate has remained remarkably stable over the study period, emphasizing the importance of a clinical examination in symptomatic women. Comparison of the histological diagnoses revealed similar percentages of ductal carcinomas, 89.6% in the true positive group compared with 85% in the false negative group. Of the false negative carcinomas, 5.5% were medullary tumours compared to 0.8% in the true positive group. Wallis, M.G., Walsh, M.T. & Lee, J.R. (1991). Clinical Radiology 44, 13-15. A
Review of False Negative Mammography in a Symptomatic Population
Mammographic technique and equipment have improved greatly over the past 10 years and the introduction of radiographic grids has improved the sharpness of breast images. In order to determine whether these improvements have increased the accuracy of reporting, we undertook a retrospective analysis of mammography in symptomatic women.
13
"/////z
12 11
y/////, "//////,
~ 10
* In 1986 a bucky grid was installed and radiographer training was introduced
7///
/ / / / / / /
"./././././..4
METHOD A symptomatic mammography service is.provided at the General Hospital, Birmingham using a C G R Senographe which was upgraded to a C G R Senographe 500T in 1983. In 1986 a palladium filter and Bucky radiographic grid were installed. Kodak Min R film was used until 1983 when it was changed to Kodak OM1. All films are reported by one consultant radiologist (J.R.L.). In order to identify the false negative reports (cancer histologically diagnosed within one year of a negative radiological report) we reviewed the reports of all mammograms performed between January 1980 and September 1988. They were cross-referenced with the histological diagnoses of breast carcinoma from the records of the pathology department and the false negative mammograms were identified. The radiographs of these patients were independently reviewed by two of the authors (M.G.W. and M.T.W.). The date of birth, date of mammogram and date of first positive pathology diagnosis, either by fine needle aspiration cytology, transcutaneous core biopsy or open surgical resection, were recorded. Any radiological findings were documented, including an estimate of the background breast pattern, namely fatty or dense/glandular. An estimate of the principal cause _~br the false negative report was determined. If the two reviewers disagreed the least flattering report was recorded. Correspondence to: Dr J. R. Lee, X-ray Department, The General Hospital, Steelhouse Lane, Birmingham B4 6NH.
1980
1981 1982
1983
1984
1985
1986 1987 1988
Year
Fig. 1 - The variation of false negative rates of each year of the study.
RESULTS During the period of study 8731 mammograms were performed and 871 patients with breast cancer were identified as having had a pre-operative mammogram. In 75 cases the radiological report failed to indicate the possibility of a malignant lesion giving an overalt false negative rate of 8.6%. As can be seen from Fig. 1 the yearly rate varied but there was a general downward trend more marked since 1986 when a Bucky grid was installed and increased radiographic supervision was instituted. The age of the patients with true positive reports 57.2 + / - 10.0 years did not differ significantly from that of the group with false negative reports 4 7 . 4 + / - 1 1 . 8 years ( m e a n + / - o n e standard deviation). Comparison of the histological diagnoses showed that 89.6% of the cancers in the true positive group were ductal in origin compared to 85% in the false negative group. However, significantly more medullary carcinomas were present in the false negative group 5.5% compared with 0.8% in the true positive group (Z2, P < 0.001). Of the 75 cases, 72 were available for review. There was disagreement between the two reviewers in only six cases.
14
CLINICAL RADIOLOGY
Table 1 - Analysis of the principal cases identified as being responsible for missed cancer
5 (7%) Poor technique
[ 36 (50%) Not visualized [
17 (24%) Normal appearances 14 (19%) Dense parenchyma
72 cases reviewed
4 (6%) Obvious oversight
20 (28%) Observer error [
16 (22%) Indirect signs
11 (15 % ) No criteria of malignancy 5 (lO°k,) Other
D
Poor radiographic technique
[~
Dense breast 'Normal mammogram'
=°6 6 o= 23
~o
radiographer could palpate this but was unable to show it on the film. The reasons for false negative reports in every year is shown in Figs 2 and 3. Over the period of study the number of cancers missed due to observer error has reduced. Additionally, no cancer was missed because of obvious oversight after 1984.
"~ 4
~6 DISCUSSION E 2 z 0
1980 1981 1982 1983 1984 1985 1986 1987 1988 Year
Fig. 2 - Cause of false negative report: variation in "no radiological abnormality' with time.
6
R
[~1 No criteria of i i malignancy ff'/'/'A Subtle or indirect v//A signs • Obvious oversight
i -o ~c~
E$
Z
0
1980
1981 1982 1983
1984
1985 1986
1987 1988
Year Fig. 3 - Cause of false negative report: variation in observer error with time.
The reasons for a false negative report were arranged into four groups (Table 1). Five cases were,classified into a miscellaneous group as they did not readily fit into the three principal groupings. In two patients the radiological signs were interpreted as being due to the previous surgical procedure and both were subsequently found to have local recurrence. In neither patient had mammography been performed previously. One patient had an illdefined density but this was considered by the reporting radiologist to be remote from the area indicated by the clinician. In the fourth case the mammographic abnormality was interpreted as fat necrosis. The final patient had a palpable mass lesion attached to the chest wall. The
The retrospective identification of false negative results is difficult in a symptomatic mammographic service. Patients may move away from the hospital environment, seek other opinion or consult a second surgeon. We, therefore, accept that our data is likely to represent an underestimation of the numbers of breast cancers missed by mammography. A follow-up period of one year was chosen in order to maximize the number of cancers actually missed and to minimize the number of newly developing cancers. The pathology records were used as a primary source of information as these were computerized for the study period and therefore easily accessible and likely to be more complete. We knew from previous discussion that there is substantial time lag between diagnosis and registration with our local cancer registry. The number of carcinomas missed by mammography varies widely in the literature from 3 % (Egan, 1960) to 34.4% (Mann et al., 1983). Comparison between studies is difficult as the populations considered may vary from screening of asymptomatic patients (Baines et al., 1986) to symptomatic patients referred for mammography (Egan, 1960; Kalisher, 1979). The study of Mann et al. (1983) was based on palpable breast abnormality only. Two studies have results approximating our own. Martin et al. (1979) reported a figure of 8.8% in a screened population from four North American centres and Cahill et al. in 1981, on reviewing 323 consecutive patients with breast cancer, found 9.3% of the patients had negative mammograms. Very high false negative rates are reported by surgeons looking at series of palpable cancers, e.g. Mann et al. (1983) 34.4% and Edeiken (1988) 22%. The lowest false negative rates, however, tend to be published by radiologists; Egan (1960) reported 3% and Kalisher (1979) 4.2%. It is interesting to speculate whether this is purely due to the perspective and interest of the authors. As can be seen from Fig. 1 there has been an overall steady fall in the number of missed cancers from the start of the study. Some of these can be attributable to improvement in equipment and radiographic technique. The improvement has been more consistent with the introduction of a radiographic Bucky grid. This device
FALSE NEGATIVE MAMMOGRAPHY IN A SYMPTOMATIC POPULATION
was originally designed to improve the penetration and visualization of dense breasts but in common with many radiologists we now use this routinely for all mammograms even in patients with translucent breasts because of the resultant improved image quality. It is difficult to know how much of the improvement is due to the increasing experience of radiologists. This study is unusual in that all the mammograms were reported by a single radiologist, which must give some greater uniformity of reporting. Over the study period the ratio of benign to malignant disease in impalpable lesions requiring localization has remained stable at approximately 3 : 2 which would suggest that experience is relatively of lesser importance in this series. This is in keeping with the findings of Edeiken (1988) and the Nijmegen workers (Peeters et al., 1989) who reported no improvement with time. On the other hand, an improvement in diagnostic accuracy with time has been noted by others (Sickles, 1985). Other studies specifically looking at reasons why cancers are missed have categorized the causes in a similar way as this review but minor differences make accurate comparison difficult (Kalisher, 1979; Martin et al., 1979; Cahill et al., 1981). In the present series no abnormality was seen on review in half of our patients. This accords with Kalisher (1979) who classified 52% to this group but two other studies (Martin et al., 1979; Cahill et al., 1981) recorded 30% and 33% respectively. Little improvement can be made by radiologists in this respect apart from insisting on exemplary radiographic technique. This group can therefore be classified as unavoidable errors when poor technique is excluded. Figure 2 shows that the number of lesions missed in dense breasts has decreased, probably due to technical improvements to equipment and particularly to the introduction of a Bucky grid. The number of false negative mammograms considered to be 'normal' even on review in the knowledge of the presence of a subsequently histologically proven carcinoma has remained remarkably stable over the period of review. Radiologists should ensure that the recipient of reports is aware that a 'normal' report does not preclude the presence of a cancer. Observer error and lesions seen but reported as benign are the responsibility of the radiologist. Figure 3 shows how this has altered with time. One would expect that
15
radiologist experience, radiographer training and technical improvement should all affect this and it appears there has been a steady improvement. Other studies however (Edeiken, 1988; Peeters et al., 1989) have not shown this. Perhaps in the Nijmegen screening programme the variables were at their optimum at the start. Subtle or indirect signs of malignancy are described well in standard texts including Tabar and Dean (1985). In our study the following were identified as being important signs: asymmetrical density, minor stromal distortion, skin thickening, loss of outline of the pectoral margin. Errors due to these causes have also decreased with time, reflecting increasing experience of the radiologist. There was a greater proportion of medullary neoplasms in the false negative group compared to the true positive group. This is not surprising as these tumours classically may have smooth outlines and mimic benign lesions.
REFERENCES Baines, C J, Miller, AB, Wall, C, McFarlane, DV, Simor, IS & Jong R (1986). Sensitivity and specificity of first screen mammography in the Canadian national breast screening study. Radiology, 160, 295-298. Cahill, CJ, Boulter, PS, Gibbs, NM & Price, JL (1981). Features of mammographieally negative breast tumours. British Journal of Surgery, 68, 882-884. Edeiken, S (1988). Mammography and palpable cancer of the breast. Cancer, 61, 263-265. Egan, RL (1960). Experience with mammography in a turnout institution. Radiology, 75, 894-900. Kalisher, L (1979). Factors influencing false negative rates in xeromammography. Radiology, 133, 297-301. Mann, BD, Giutiano, AE, Bassett, LW, Barber, MS, Haullauer W & Morton, DL (1983). Delayed diagnosis of breast cancer as a result of normal mammograms. Archives of Surgery, 118, 23-24. Martin, JE, Moskowitz, M & Milbrath, JR (1979). Breast cancer missed by mammography. American Journal of Roentgenology, 132, 737739. Peeters, PHM, Verbeek, ALM, Hendricks, JHCL & Van Bon, MJH (1989). Screening for breast cancer in Nijmegen. Report of six screening rounds, 1975-1986. International Journal of Cancer, 43, 226-230. Sickles, EA (1985). Breast imaging: a view from the present to the future. Diagnostic Imaging in Clinical Medicine, 54, 118-125. Tabar, L & Dean, PB (1985). Teaching Atlas of Mammography, 2nd edition. George Thieme Verlag, Stuttgart.
A Review of False Negative Mammography in a Symptomatic Population M. G. WALLIS, M. T. WALSH and J. R. LEE
The General Hospital, Birmingham A review of the mammograms of 871 patients with breast cancer from a symptomatic clinic performed at the General Hospital, Birmingham between 1980 and 1988 revealed an overall false negative rate of 8.6%. There has been a steady fall in the number of cancers missed per year from the commencement of review, and this reduction has been more consistent with improvements in radiographic equipment and technique, particularly the introduction of a radiographic grid. In half of the cases the tumour was missed because no radiological abnormality was detectable, even on reviewing the films, and this rate has remained remarkably stable over the study period, emphasizing the importance of a clinical examination in symptomatic women. Comparison of the histological diagnoses revealed similar percentages of ductal carcinomas, 89.6% in the true positive group compared with 85% in the false negative group. Of the false negative carcinomas, 5.5% were medullary tumours compared to 0.8% in the true positive group. Wallis, M.G., Walsh, M.T. & Lee, J.R. (1991). Clinical Radiology 44, 13-15. A
Review of False Negative Mammography in a Symptomatic Population
Mammographic technique and equipment have improved greatly over the past 10 years and the introduction of radiographic grids has improved the sharpness of breast images. In order to determine whether these improvements have increased the accuracy of reporting, we undertook a retrospective analysis of mammography in symptomatic women.
13
"/////z
12 11
y/////, "//////,
~ 10
* In 1986 a bucky grid was installed and radiographer training was introduced
7///
/ / / / / / /
"./././././..4
METHOD A symptomatic mammography service is.provided at the General Hospital, Birmingham using a C G R Senographe which was upgraded to a C G R Senographe 500T in 1983. In 1986 a palladium filter and Bucky radiographic grid were installed. Kodak Min R film was used until 1983 when it was changed to Kodak OM1. All films are reported by one consultant radiologist (J.R.L.). In order to identify the false negative reports (cancer histologically diagnosed within one year of a negative radiological report) we reviewed the reports of all mammograms performed between January 1980 and September 1988. They were cross-referenced with the histological diagnoses of breast carcinoma from the records of the pathology department and the false negative mammograms were identified. The radiographs of these patients were independently reviewed by two of the authors (M.G.W. and M.T.W.). The date of birth, date of mammogram and date of first positive pathology diagnosis, either by fine needle aspiration cytology, transcutaneous core biopsy or open surgical resection, were recorded. Any radiological findings were documented, including an estimate of the background breast pattern, namely fatty or dense/glandular. An estimate of the principal cause _~br the false negative report was determined. If the two reviewers disagreed the least flattering report was recorded. Correspondence to: Dr J. R. Lee, X-ray Department, The General Hospital, Steelhouse Lane, Birmingham B4 6NH.
1980
1981 1982
1983
1984
1985
1986 1987 1988
Year
Fig. 1 - The variation of false negative rates of each year of the study.
RESULTS During the period of study 8731 mammograms were performed and 871 patients with breast cancer were identified as having had a pre-operative mammogram. In 75 cases the radiological report failed to indicate the possibility of a malignant lesion giving an overalt false negative rate of 8.6%. As can be seen from Fig. 1 the yearly rate varied but there was a general downward trend more marked since 1986 when a Bucky grid was installed and increased radiographic supervision was instituted. The age of the patients with true positive reports 57.2 + / - 10.0 years did not differ significantly from that of the group with false negative reports 4 7 . 4 + / - 1 1 . 8 years ( m e a n + / - o n e standard deviation). Comparison of the histological diagnoses showed that 89.6% of the cancers in the true positive group were ductal in origin compared to 85% in the false negative group. However, significantly more medullary carcinomas were present in the false negative group 5.5% compared with 0.8% in the true positive group (Z2, P < 0.001). Of the 75 cases, 72 were available for review. There was disagreement between the two reviewers in only six cases.
14
CLINICAL RADIOLOGY
Table 1 - Analysis of the principal cases identified as being responsible for missed cancer
5 (7%) Poor technique
[ 36 (50%) Not visualized [
17 (24%) Normal appearances 14 (19%) Dense parenchyma
72 cases reviewed
4 (6%) Obvious oversight
20 (28%) Observer error [
16 (22%) Indirect signs
11 (15 % ) No criteria of malignancy 5 (lO°k,) Other
D
Poor radiographic technique
[~
Dense breast 'Normal mammogram'
=°6 6 o= 23
~o
radiographer could palpate this but was unable to show it on the film. The reasons for false negative reports in every year is shown in Figs 2 and 3. Over the period of study the number of cancers missed due to observer error has reduced. Additionally, no cancer was missed because of obvious oversight after 1984.
"~ 4
~6 DISCUSSION E 2 z 0
1980 1981 1982 1983 1984 1985 1986 1987 1988 Year
Fig. 2 - Cause of false negative report: variation in "no radiological abnormality' with time.
6
R
[~1 No criteria of i i malignancy ff'/'/'A Subtle or indirect v//A signs • Obvious oversight
i -o ~c~
E$
Z
0
1980
1981 1982 1983
1984
1985 1986
1987 1988
Year Fig. 3 - Cause of false negative report: variation in observer error with time.
The reasons for a false negative report were arranged into four groups (Table 1). Five cases were,classified into a miscellaneous group as they did not readily fit into the three principal groupings. In two patients the radiological signs were interpreted as being due to the previous surgical procedure and both were subsequently found to have local recurrence. In neither patient had mammography been performed previously. One patient had an illdefined density but this was considered by the reporting radiologist to be remote from the area indicated by the clinician. In the fourth case the mammographic abnormality was interpreted as fat necrosis. The final patient had a palpable mass lesion attached to the chest wall. The
The retrospective identification of false negative results is difficult in a symptomatic mammographic service. Patients may move away from the hospital environment, seek other opinion or consult a second surgeon. We, therefore, accept that our data is likely to represent an underestimation of the numbers of breast cancers missed by mammography. A follow-up period of one year was chosen in order to maximize the number of cancers actually missed and to minimize the number of newly developing cancers. The pathology records were used as a primary source of information as these were computerized for the study period and therefore easily accessible and likely to be more complete. We knew from previous discussion that there is substantial time lag between diagnosis and registration with our local cancer registry. The number of carcinomas missed by mammography varies widely in the literature from 3 % (Egan, 1960) to 34.4% (Mann et al., 1983). Comparison between studies is difficult as the populations considered may vary from screening of asymptomatic patients (Baines et al., 1986) to symptomatic patients referred for mammography (Egan, 1960; Kalisher, 1979). The study of Mann et al. (1983) was based on palpable breast abnormality only. Two studies have results approximating our own. Martin et al. (1979) reported a figure of 8.8% in a screened population from four North American centres and Cahill et al. in 1981, on reviewing 323 consecutive patients with breast cancer, found 9.3% of the patients had negative mammograms. Very high false negative rates are reported by surgeons looking at series of palpable cancers, e.g. Mann et al. (1983) 34.4% and Edeiken (1988) 22%. The lowest false negative rates, however, tend to be published by radiologists; Egan (1960) reported 3% and Kalisher (1979) 4.2%. It is interesting to speculate whether this is purely due to the perspective and interest of the authors. As can be seen from Fig. 1 there has been an overall steady fall in the number of missed cancers from the start of the study. Some of these can be attributable to improvement in equipment and radiographic technique. The improvement has been more consistent with the introduction of a radiographic Bucky grid. This device
FALSE NEGATIVE MAMMOGRAPHY IN A SYMPTOMATIC POPULATION
was originally designed to improve the penetration and visualization of dense breasts but in common with many radiologists we now use this routinely for all mammograms even in patients with translucent breasts because of the resultant improved image quality. It is difficult to know how much of the improvement is due to the increasing experience of radiologists. This study is unusual in that all the mammograms were reported by a single radiologist, which must give some greater uniformity of reporting. Over the study period the ratio of benign to malignant disease in impalpable lesions requiring localization has remained stable at approximately 3 : 2 which would suggest that experience is relatively of lesser importance in this series. This is in keeping with the findings of Edeiken (1988) and the Nijmegen workers (Peeters et al., 1989) who reported no improvement with time. On the other hand, an improvement in diagnostic accuracy with time has been noted by others (Sickles, 1985). Other studies specifically looking at reasons why cancers are missed have categorized the causes in a similar way as this review but minor differences make accurate comparison difficult (Kalisher, 1979; Martin et al., 1979; Cahill et al., 1981). In the present series no abnormality was seen on review in half of our patients. This accords with Kalisher (1979) who classified 52% to this group but two other studies (Martin et al., 1979; Cahill et al., 1981) recorded 30% and 33% respectively. Little improvement can be made by radiologists in this respect apart from insisting on exemplary radiographic technique. This group can therefore be classified as unavoidable errors when poor technique is excluded. Figure 2 shows that the number of lesions missed in dense breasts has decreased, probably due to technical improvements to equipment and particularly to the introduction of a Bucky grid. The number of false negative mammograms considered to be 'normal' even on review in the knowledge of the presence of a subsequently histologically proven carcinoma has remained remarkably stable over the period of review. Radiologists should ensure that the recipient of reports is aware that a 'normal' report does not preclude the presence of a cancer. Observer error and lesions seen but reported as benign are the responsibility of the radiologist. Figure 3 shows how this has altered with time. One would expect that
15
radiologist experience, radiographer training and technical improvement should all affect this and it appears there has been a steady improvement. Other studies however (Edeiken, 1988; Peeters et al., 1989) have not shown this. Perhaps in the Nijmegen screening programme the variables were at their optimum at the start. Subtle or indirect signs of malignancy are described well in standard texts including Tabar and Dean (1985). In our study the following were identified as being important signs: asymmetrical density, minor stromal distortion, skin thickening, loss of outline of the pectoral margin. Errors due to these causes have also decreased with time, reflecting increasing experience of the radiologist. There was a greater proportion of medullary neoplasms in the false negative group compared to the true positive group. This is not surprising as these tumours classically may have smooth outlines and mimic benign lesions.
REFERENCES Baines, C J, Miller, AB, Wall, C, McFarlane, DV, Simor, IS & Jong R (1986). Sensitivity and specificity of first screen mammography in the Canadian national breast screening study. Radiology, 160, 295-298. Cahill, CJ, Boulter, PS, Gibbs, NM & Price, JL (1981). Features of mammographieally negative breast tumours. British Journal of Surgery, 68, 882-884. Edeiken, S (1988). Mammography and palpable cancer of the breast. Cancer, 61, 263-265. Egan, RL (1960). Experience with mammography in a turnout institution. Radiology, 75, 894-900. Kalisher, L (1979). Factors influencing false negative rates in xeromammography. Radiology, 133, 297-301. Mann, BD, Giutiano, AE, Bassett, LW, Barber, MS, Haullauer W & Morton, DL (1983). Delayed diagnosis of breast cancer as a result of normal mammograms. Archives of Surgery, 118, 23-24. Martin, JE, Moskowitz, M & Milbrath, JR (1979). Breast cancer missed by mammography. American Journal of Roentgenology, 132, 737739. Peeters, PHM, Verbeek, ALM, Hendricks, JHCL & Van Bon, MJH (1989). Screening for breast cancer in Nijmegen. Report of six screening rounds, 1975-1986. International Journal of Cancer, 43, 226-230. Sickles, EA (1985). Breast imaging: a view from the present to the future. Diagnostic Imaging in Clinical Medicine, 54, 118-125. Tabar, L & Dean, PB (1985). Teaching Atlas of Mammography, 2nd edition. George Thieme Verlag, Stuttgart.