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Evaluation with breast scintigraphy of breast lesions of indeterminate significance after conventional triple diagnostic approach
The Breast (1999) 8, 270–272 © 1999 Harcourt Publisher Ltd
ORIGINAL ARTICLE
Evaluation with breast scintigraphy of breast lesions of indeterminate significance after conventional triple diagnostic approach S. . Ciatto, A. Castagnoli* and G. Cappelli* Presidio Prevenzione Oncologica, and *Department of Nuclear Medicine, Careggi Hospital, Florence, Italy S U M M A R Y. The role of breast scintigraphy in the evaluation of 30 women with an uncertain diagnosis following triple assessment was investigated. Scintigraphy was positive in 7 of 13 cancers and 3 of 17 benign lesions and dubious in 1 of 13 cancers and 2 of 17 benign lesions. Sensitivity ranged from 61.5% to 53.8% depending whether dubious lesions were designated as positive or negative. This study shows that breast scintigraphy is not sufficiently sensitive or specific to use in the evaluation of lesions of uncertain diagnosis following triple assessment. © Harcourt Publishers Ltd
and a positive report at FNAC the positive predictive value (PPV) for cancer is over 99%6 and there is no need for any additional diagnostic test. Similarly, a lesion with a benign appearance on palpation and imaging and a negative FNAC, is associated with a negative predictive value of 99%1 and no extra test is required to exclude the need for a biopsy. From the existing literature reports it is not possible to define what exactly is the ‘additional’ contribution of BS in a subset of cases of uncertain diagnosis following triple assessment, and to judge what is the advantage in terms of sparing unnecessary benign biopsies if BS were used as a discriminant for biopsy in such cases. Thus, we have designed a prospective study, where cases of uncertain diagnosis in whom biopsy was advised were examined with BS.
INTRODUCTION The conventional diagnostic approach to breast abnormalities is based on triple diagnosis, that is a combination of palpation, imaging (mammography and/or ultrasonography) and fine needle aspiration cytology (FNAC).1 Although such an approach allows for high diagnostic accuracy (>95%), a minority of cases are still of uncertain diagnostic interpretation and undergo percutaneous or open biopsy to obtain a histological diagnosis. Benign biopsies are not frequent2 but they are costly, may cause psychological discomfort, and the surgical outcomes may have a negative cosmetic impact or cause diagnostic problems during subsequent mammographic examinations. Several new diagnostic methods have been proposed over recent years, e.g. colour-Doppler ultrasonography and magnetic resonance imaging to reduce unnecessary benign biopsies. Breast scintigraphy (BS) using a variety of tracers has been proposed for such a purpose3–5 and good results have been reported in terms of diagnostic accuracy. Unfortunately, in almost all published studies, BS has not been tested on the type of patients in whom it might have a role in clinical practice. In fact, literature reports deal with consecutive series of breast abnormalities, for most of which a reliable diagnosis has already been achieved with triple diagnosis. For example, in the presence of a lesion with strong suspicion of malignancy on palpation and imaging
MATERIALS AND METHODS We selected for the study subjects with breast abnormalities of uncertain diagnosis in whom biopsy had been advised. All cases had been examined by palpation, imaging (mammography and/or ultrasonography), and FNAC. For study purposes the diagnostic reports of different tests were coded as negative/benign or suspicious/positive, inadequate cases at FNAC being assumed as negatives. ‘Uncertain diagnosis’ was defined as the absence of strong suspicion in all tests, with a negative or benign report on at least one test. BS was performed in the Department of Nuclear Medicine of Careggi Hospital prior to biopsy. The tracer used was 99mTc Sestamibi, a lypophilic cation complex
Address correspondence to: Stefano Ciatto MD, Centro Studio Prevenzione Oncologica, Viale A. Volta 171, I-50131 Florence, Italy. Tel.: +39 055 5012214; fax +39 055 5001623; E-mail [email protected]
270
Evaluation with breast scintigraphy of breast lesions of indeterminate significance 271 formerly used as a myocardial perfusion agent and recently proposed for BS with good results reported in terms of diagnostic accuracy.3,5 Scintigraphic images were recorded by a gamma camera starting 15 minutes after i.v. injection of 666 MBq of the tracer. Two views were taken routinely, namely: a) a planar anterior view of the thorax, with the patient in a supine position with both arms raised over the head; and b) a lateral view of the breast under investigation with the patient in a recumbent position and the breast hanging down lateral to the pallet of the camera, and the ipsilateral arm raised above the head. BS reports were given blind of the results of other tests. Diagnostic codes were: a) negative (evidence of tracer correlated with the normal activity of soft tissues; b) dubious (faint uptake); or c) positive (area of increased uptake of the tracer clearly identified as a hot spot). Histological diagnosis was the gold standard and was obtained either by percutaneous core biopsy or by open surgical biopsy. The diagnostic accuracy of BS (sensitivity, specificity, negative and positive predictive value) was then calculated, assuming dubious reports at BS alternatively as negative or positive. We calculated also the ratio of: a) unnecessary benign biopsies which would have been spared; to b) malignant biopsies which would have been delayed if BS was used as a discriminant for biopsy.
Table 1 Diagnostic report (1=negative/benign, 2=suspicious/positive) at palpation (P), mammography (RX), ultrasonography (US), cytology (FNAC), breast scintigraphy (BS: 1=negative, 2=dubious, 3=positive) and histology (pT for cancer cases) in 30 cases enrolled in the study
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Age (Years)
P
US
RX
FNAC
BS
Histology
42 46 69 59 77 64 52 54 62 51 55 58 73 43 52 57 43 41 27 48 51 73 49 34 79 47 50 50 30 30
1 2 2 2 2 2 1 1 1 2 1 2 2 1 1 2 2 2 2 1 1 2 1 2 1 2 1 2 2 2
2 2 1 2 2 1 1 1 1 2 1 1 2 1 2 2 2 1 2 1 2 1 1 2 1 1 1 1 2 1
1 1 1 1 2 2 2 2 2 2 2 2 1 2 1 1 1 2 – 2 1 2 1 – 2 1 1 1 1 –
2 2 2 1 1 1 1 2 2 1 1 2 2 1 1 1 1 1 1 2 1 1 2 1 1 2 2 1 1 2
3 3 2 1 1 3 1 3 1 3 1 3 3 3 1 1 1 2 2 1 1 1 3 1 3 1 1 1 1 1
pT1b, cribriform pT2, ductal pT1b, papillary pT1b, ductal pT1c, ductal PT1c, ductal pT1b, ductal pT1c, ductal pTis, ductal pT1c, ductal pT1b, ductal pT2, ductal pTx, ductal fibroadenoma fibrosis, scar fibrolipoma fibrocysic disease fibroadenoma fibrocystic disease fibroadenoma fibrocystic disease fibrocystic disease fibroadenoma fibrocystic disease chronic mastitis fibrocystic disease fibroadenoma fibroadenoma fibrocystic disease fibroadenoma
RESULTS Thirty cases were recruited in the study from November 1996 to January 1998. Final histologic diagnosis was benign in 17 and malignant in 13. Table 1 shows the results of different tests and the final histology. BS was positive in 7 and dubious in 1 of 13 cancers and was positive in 3 or dubious in 2 of 17 benign cases. When dubious reports at BS were assumed as positives, sensitivity was 61.5%, specificity was 70.5%, negative predictive value was 70.5%, positive predictive value was 61.5%, and the ratio of spared benign biopsies to delayed malignant biopsies was 12:5. If dubious reports at BS were assumed as negatives, the corresponding values would have been: sensitivity 53.8%, specificity 82.3%, negative predictive value 70%, positive predictive value 70%, ratio of spared benign biopsies to delayed malignant biopsies 14:6.
DISCUSSION The present series is of limited size as would be expected for selected cases of uncertain interpretation following accurate triple diagnostic approach. Nevertheless, although
the number of studied cases does not allow precise evaluation of BS accuracy, it is quite clear that BS is neither sensitive enough nor suffiently specific, to be used in the group of patients studied. These findings contrast with other reports of BS,5 using the same tracer, but differences can be explained as they are dealing with different lesions, selected according to different criteria. It is evident from other studies that the sensitivity of BS is related to tumour size, with a low sensitivity being reported for non-palpable lesions.4,5 In the present series most cancer cases were below 2 cm in diameter, and a smaller average size might account for a lower sensitivity with respect to other series. An association of sensitivity to tumour size was evident in our series, with 5 of 6 pTis/pT1b cases being negative or dubious at BS, as compared to 1 of 6 pT1c/pT2 cases. The results of our study are particularly disappointing as we selected cases in which we needed some ‘diagnostic help’ from additional tests, as the triple diagnostic approach gave uncertain results. Had we used BS as a discriminant for biopsy, we would have reduced unnecessary benign biopsies by at least 70% but we would have delayed biopsy in at least 38% of cancers.
272
The Breast
It is evident that any evaluation of the diagnostic role of BS must first define what we ask to this technique. If, as we believe, the only advantage of BS would be that of reducing unnecessary benign biopsies in cases with a low expected positive predictive value at triple approach, our experience does not support the role of BS in this situation. Most of the biopsies which would be spared by BS are actually core biopsies, not surgical open biopsies and as this is likely to become the standard procedure for lesions of uncertain diagnosis with a low expected yield of cancer there is little role for BS. Core biopsy is simple and cheap, cheaper than BS (the cost of core biopsy in our setting is about $100 US) and its accuracy is extremely high.7 It is evident that BS does not represent a valid alternative to core biopsy either in terms of either cost or of diagnostic accuracy.
References 1. Layfield L J, Glasgow B J, Cramer H. Fine needle aspiration in the management of breast masses. Pathol Ann 1989; 24: 23–62. 2. Ciatto S, Rosselli Del Turco M, Marrazzo A, et al. Time trends of benign/malignant breast biopsy ratios: a multicenter Italian study, Tumori 1996; 82: 325–328. 3. Rebollo A C, Torres-Avisbal M, Espinosa J E et al. Evaluation of palpable breast masses with 201TL scintigraphy. Br J Radiol 1995; 68: 1052–1057. 4. Piccolo S, Lastoria S, Muto P et al. Scintimammography with 99TcMDP in the detection of primary breast cancer. Nuclear Medicine 1997; 41: 225–230. 5. Khalkali L, Iraniha S, Diggles L E et al. Scintimammography: the new role of technetium-99m Sestamibi imaging for the diagnosis of breast carcinoma. Nuclear Medicine 1997; 41: 231–239. 6. Ciatto S, Cariaggi P, Bulgaresi P et al. Fine needle aspiration cytology of the breast: review of 9533 consecutive cases. Breast 1993; 2: 87–90. 7. Parker S H, Burbanck F, Jackman R J et al. Percutaneous large-core breast biopsy. A multiinstitutional study. Radiology 1994; 193: 359–365.
ORIGINAL ARTICLE
Evaluation with breast scintigraphy of breast lesions of indeterminate significance after conventional triple diagnostic approach S. . Ciatto, A. Castagnoli* and G. Cappelli* Presidio Prevenzione Oncologica, and *Department of Nuclear Medicine, Careggi Hospital, Florence, Italy S U M M A R Y. The role of breast scintigraphy in the evaluation of 30 women with an uncertain diagnosis following triple assessment was investigated. Scintigraphy was positive in 7 of 13 cancers and 3 of 17 benign lesions and dubious in 1 of 13 cancers and 2 of 17 benign lesions. Sensitivity ranged from 61.5% to 53.8% depending whether dubious lesions were designated as positive or negative. This study shows that breast scintigraphy is not sufficiently sensitive or specific to use in the evaluation of lesions of uncertain diagnosis following triple assessment. © Harcourt Publishers Ltd
and a positive report at FNAC the positive predictive value (PPV) for cancer is over 99%6 and there is no need for any additional diagnostic test. Similarly, a lesion with a benign appearance on palpation and imaging and a negative FNAC, is associated with a negative predictive value of 99%1 and no extra test is required to exclude the need for a biopsy. From the existing literature reports it is not possible to define what exactly is the ‘additional’ contribution of BS in a subset of cases of uncertain diagnosis following triple assessment, and to judge what is the advantage in terms of sparing unnecessary benign biopsies if BS were used as a discriminant for biopsy in such cases. Thus, we have designed a prospective study, where cases of uncertain diagnosis in whom biopsy was advised were examined with BS.
INTRODUCTION The conventional diagnostic approach to breast abnormalities is based on triple diagnosis, that is a combination of palpation, imaging (mammography and/or ultrasonography) and fine needle aspiration cytology (FNAC).1 Although such an approach allows for high diagnostic accuracy (>95%), a minority of cases are still of uncertain diagnostic interpretation and undergo percutaneous or open biopsy to obtain a histological diagnosis. Benign biopsies are not frequent2 but they are costly, may cause psychological discomfort, and the surgical outcomes may have a negative cosmetic impact or cause diagnostic problems during subsequent mammographic examinations. Several new diagnostic methods have been proposed over recent years, e.g. colour-Doppler ultrasonography and magnetic resonance imaging to reduce unnecessary benign biopsies. Breast scintigraphy (BS) using a variety of tracers has been proposed for such a purpose3–5 and good results have been reported in terms of diagnostic accuracy. Unfortunately, in almost all published studies, BS has not been tested on the type of patients in whom it might have a role in clinical practice. In fact, literature reports deal with consecutive series of breast abnormalities, for most of which a reliable diagnosis has already been achieved with triple diagnosis. For example, in the presence of a lesion with strong suspicion of malignancy on palpation and imaging
MATERIALS AND METHODS We selected for the study subjects with breast abnormalities of uncertain diagnosis in whom biopsy had been advised. All cases had been examined by palpation, imaging (mammography and/or ultrasonography), and FNAC. For study purposes the diagnostic reports of different tests were coded as negative/benign or suspicious/positive, inadequate cases at FNAC being assumed as negatives. ‘Uncertain diagnosis’ was defined as the absence of strong suspicion in all tests, with a negative or benign report on at least one test. BS was performed in the Department of Nuclear Medicine of Careggi Hospital prior to biopsy. The tracer used was 99mTc Sestamibi, a lypophilic cation complex
Address correspondence to: Stefano Ciatto MD, Centro Studio Prevenzione Oncologica, Viale A. Volta 171, I-50131 Florence, Italy. Tel.: +39 055 5012214; fax +39 055 5001623; E-mail [email protected]
270
Evaluation with breast scintigraphy of breast lesions of indeterminate significance 271 formerly used as a myocardial perfusion agent and recently proposed for BS with good results reported in terms of diagnostic accuracy.3,5 Scintigraphic images were recorded by a gamma camera starting 15 minutes after i.v. injection of 666 MBq of the tracer. Two views were taken routinely, namely: a) a planar anterior view of the thorax, with the patient in a supine position with both arms raised over the head; and b) a lateral view of the breast under investigation with the patient in a recumbent position and the breast hanging down lateral to the pallet of the camera, and the ipsilateral arm raised above the head. BS reports were given blind of the results of other tests. Diagnostic codes were: a) negative (evidence of tracer correlated with the normal activity of soft tissues; b) dubious (faint uptake); or c) positive (area of increased uptake of the tracer clearly identified as a hot spot). Histological diagnosis was the gold standard and was obtained either by percutaneous core biopsy or by open surgical biopsy. The diagnostic accuracy of BS (sensitivity, specificity, negative and positive predictive value) was then calculated, assuming dubious reports at BS alternatively as negative or positive. We calculated also the ratio of: a) unnecessary benign biopsies which would have been spared; to b) malignant biopsies which would have been delayed if BS was used as a discriminant for biopsy.
Table 1 Diagnostic report (1=negative/benign, 2=suspicious/positive) at palpation (P), mammography (RX), ultrasonography (US), cytology (FNAC), breast scintigraphy (BS: 1=negative, 2=dubious, 3=positive) and histology (pT for cancer cases) in 30 cases enrolled in the study
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Age (Years)
P
US
RX
FNAC
BS
Histology
42 46 69 59 77 64 52 54 62 51 55 58 73 43 52 57 43 41 27 48 51 73 49 34 79 47 50 50 30 30
1 2 2 2 2 2 1 1 1 2 1 2 2 1 1 2 2 2 2 1 1 2 1 2 1 2 1 2 2 2
2 2 1 2 2 1 1 1 1 2 1 1 2 1 2 2 2 1 2 1 2 1 1 2 1 1 1 1 2 1
1 1 1 1 2 2 2 2 2 2 2 2 1 2 1 1 1 2 – 2 1 2 1 – 2 1 1 1 1 –
2 2 2 1 1 1 1 2 2 1 1 2 2 1 1 1 1 1 1 2 1 1 2 1 1 2 2 1 1 2
3 3 2 1 1 3 1 3 1 3 1 3 3 3 1 1 1 2 2 1 1 1 3 1 3 1 1 1 1 1
pT1b, cribriform pT2, ductal pT1b, papillary pT1b, ductal pT1c, ductal PT1c, ductal pT1b, ductal pT1c, ductal pTis, ductal pT1c, ductal pT1b, ductal pT2, ductal pTx, ductal fibroadenoma fibrosis, scar fibrolipoma fibrocysic disease fibroadenoma fibrocystic disease fibroadenoma fibrocystic disease fibrocystic disease fibroadenoma fibrocystic disease chronic mastitis fibrocystic disease fibroadenoma fibroadenoma fibrocystic disease fibroadenoma
RESULTS Thirty cases were recruited in the study from November 1996 to January 1998. Final histologic diagnosis was benign in 17 and malignant in 13. Table 1 shows the results of different tests and the final histology. BS was positive in 7 and dubious in 1 of 13 cancers and was positive in 3 or dubious in 2 of 17 benign cases. When dubious reports at BS were assumed as positives, sensitivity was 61.5%, specificity was 70.5%, negative predictive value was 70.5%, positive predictive value was 61.5%, and the ratio of spared benign biopsies to delayed malignant biopsies was 12:5. If dubious reports at BS were assumed as negatives, the corresponding values would have been: sensitivity 53.8%, specificity 82.3%, negative predictive value 70%, positive predictive value 70%, ratio of spared benign biopsies to delayed malignant biopsies 14:6.
DISCUSSION The present series is of limited size as would be expected for selected cases of uncertain interpretation following accurate triple diagnostic approach. Nevertheless, although
the number of studied cases does not allow precise evaluation of BS accuracy, it is quite clear that BS is neither sensitive enough nor suffiently specific, to be used in the group of patients studied. These findings contrast with other reports of BS,5 using the same tracer, but differences can be explained as they are dealing with different lesions, selected according to different criteria. It is evident from other studies that the sensitivity of BS is related to tumour size, with a low sensitivity being reported for non-palpable lesions.4,5 In the present series most cancer cases were below 2 cm in diameter, and a smaller average size might account for a lower sensitivity with respect to other series. An association of sensitivity to tumour size was evident in our series, with 5 of 6 pTis/pT1b cases being negative or dubious at BS, as compared to 1 of 6 pT1c/pT2 cases. The results of our study are particularly disappointing as we selected cases in which we needed some ‘diagnostic help’ from additional tests, as the triple diagnostic approach gave uncertain results. Had we used BS as a discriminant for biopsy, we would have reduced unnecessary benign biopsies by at least 70% but we would have delayed biopsy in at least 38% of cancers.
272
The Breast
It is evident that any evaluation of the diagnostic role of BS must first define what we ask to this technique. If, as we believe, the only advantage of BS would be that of reducing unnecessary benign biopsies in cases with a low expected positive predictive value at triple approach, our experience does not support the role of BS in this situation. Most of the biopsies which would be spared by BS are actually core biopsies, not surgical open biopsies and as this is likely to become the standard procedure for lesions of uncertain diagnosis with a low expected yield of cancer there is little role for BS. Core biopsy is simple and cheap, cheaper than BS (the cost of core biopsy in our setting is about $100 US) and its accuracy is extremely high.7 It is evident that BS does not represent a valid alternative to core biopsy either in terms of either cost or of diagnostic accuracy.
References 1. Layfield L J, Glasgow B J, Cramer H. Fine needle aspiration in the management of breast masses. Pathol Ann 1989; 24: 23–62. 2. Ciatto S, Rosselli Del Turco M, Marrazzo A, et al. Time trends of benign/malignant breast biopsy ratios: a multicenter Italian study, Tumori 1996; 82: 325–328. 3. Rebollo A C, Torres-Avisbal M, Espinosa J E et al. Evaluation of palpable breast masses with 201TL scintigraphy. Br J Radiol 1995; 68: 1052–1057. 4. Piccolo S, Lastoria S, Muto P et al. Scintimammography with 99TcMDP in the detection of primary breast cancer. Nuclear Medicine 1997; 41: 225–230. 5. Khalkali L, Iraniha S, Diggles L E et al. Scintimammography: the new role of technetium-99m Sestamibi imaging for the diagnosis of breast carcinoma. Nuclear Medicine 1997; 41: 231–239. 6. Ciatto S, Cariaggi P, Bulgaresi P et al. Fine needle aspiration cytology of the breast: review of 9533 consecutive cases. Breast 1993; 2: 87–90. 7. Parker S H, Burbanck F, Jackman R J et al. Percutaneous large-core breast biopsy. A multiinstitutional study. Radiology 1994; 193: 359–365.