European Journal of N u c l e a r
Eur. J. Nucl. Med. 2, 1 7 9 - 1 8 1 (1977)
Medicine © by Springer-Verlag 1977
False Positive Bone Scan in Bone Tumors of the Lower Limb Dario Casara 1, Pietro de Besi 2, Mario Fiorentino 2, Adriano Fornasiero 2, Pierluigi Melanotte 3, Giorgio Palfi 2, Paola Sperandio z, and Orazio Vinante 2 1 Divisione di Radioterapia e Medicina Nucleare, Ospedale Civile di Padova 2 Divisione di Oncologia, Ospedale Civile di Padova 3 Clinica Ortopedica, Universit/t di Padova
Abstract. When examined using bone scanning agents, eight out of nine patients with lower limb malignancy, and neither of two affected in the upper limb showed a pathologic focus of isotope uptake in an area distal to the tumor. On pathologic examination the positive findings proved false. Such misleading results were found to be avoidable if a tumor-seeking agent instead of a bone scanning one is used.
The usefulness of this procedure for primary bone tumors has been more recently recognized by orthopedic surgeons and radiotherapists for two purposes: 1) Detecting bone metastases (or multiple primaries) of the bone tumor [3, 6] 2) Defining the extension of local involvement in view of such procedures as local radiation (especially with surdosage or local resection) associated with endoprothesis [1].
Introduction
Material and Methods
Bone scanning has been extensively used for secondary bone malignancies in our institution for 10 years.
The isotopes more usually employed in this particular field have been those following the metabolism of the bone components (Ca ions and phosphates, sTmsr, 99mTc-labeled phosphate compounds). W h e n we used these isotopes, there were interesting and reliable results for trunk and superior limb tumors, but with tumors
For offprints contact." Dr. Mario Fiorentino, Divisione di Oncologia, Ospedale Civile di Padova, Padova, Italy Table 1
Patient
Sex
Age
Tumor type a
Tumor location
Tumor-seeking agent b scan
Bone scan T u m o r area
Distal area (foot or hand)
1 2 3 4 5
D.E. B.C. B.G. C.G. C.P.
F F M M F
17 14 20 21 9
OS OS OS OS OS
Femur Femur Femur Femur Femur
+ + + + ÷
+ + + + +
6
T.A.
M
20
OS
Femur
+
+
7
S.A.
F
26
RCS
Femur
+
+
8
S.R.
M
11
EW
Tibia
+
+
9
G.M.
F
13
OS
Femur
+
-
10
Z.R.
M
17
OS
Humerus
-}-
-
11
P.C.
M
10
EW
Humerus
+
-
a b
T u m o r area
+ +
Distal area (foot or hand)
-(STCo BLM) - ( 5 7 C o BLM)
{+
- ( 6 7 G a citrate) - ( 5 7 C 0 BLM)
+ {+
- (99mTc BLM) - ( 5 7 C o BLM) - (99mTc BLM)
{;
-(STCo BLM) - (99mTc BLM)
+
OS = Osteogenic osteosarcoma; RCS = Primitive reticulum cell sarcoma of bone; EW = Ewing's sarcoma B L M = Bleomycin
-(STCo BLM)
180
D. Casara et al. : False Positive Bone Scan in Bone Tumors
Fig. l. Patient no 3 99mTCphosphate scan
Fig. 2. Same patient 99roTe Bleomycin scan obtained two days later
localized in the thigh or leg (most of them in the knee area) we regularly noted two foci of increased isotope uptake, one being the tumour area, and one in the foot. Table 1 gives details of the patients and diagnoses. Up to now nine such patients have been observed; only one of them had no increased uptake in the foot. In each case the pathologist did not discover any tumor in the foot of the removed limb. After the false positive finding had been detected in several patients, we checked the abnormal uptake with a second scan, performed with more specific 'tumor-seeking' agents. Radioactive bleomycin was used (99mTc-labeled, 57Co-labeled, or both) and in one patient 67Ga citrate was also used (see Table 1).
malignancies (no u p t a k e observed in the two hands examined; uptake observed in eight out of nine feet) and of the different functional implications o f a t u m o r in the upper part a n d / o r midjoint o f the arm or leg. The h a n d is still used, at least for some auxiliary movement, even when shoulder or elbow m o v e m e n t is impaired. The foot has only a support function, which is usually lost if the remaining part of the leg is damaged. Functional a t r o p h y or decalcification f r o m unloading is accordingly m u c h m o r e likely to occur in the feet than in the hands, according to data already k n o w n [2]. U p t a k e o f b o n e tracers is consequently increased in the small bones of the foot because of the negative balance and increased turnover of minerals due to the reduced weight-bearing. F u r t h e r investigations to make this proposed m e c h a n i s m m o r e clear are n o w running in our institution in view o f the fact that a loss o f minerals is not evidenced by plain r a d i o g r a p h y in the examined feet.
Results With the second g r o u p of radiopharmaceuticals none o f the patients showed any a b n o r m a l uptake outside the t u m o r area; in particular the feet did not take up significant a m o u n t s o f the tracer. Table 1 shows relevant data on these patients (Cases 1 to 9) and on 2 other patients with malignancies o f the upper limb (Cases 10 and 11). Figures 1 and 2 show the false positive uptake o f Case 3 with 99mTc p h o s p h a t e and, for comparison, the picture obtained 2 days later f r o m the same patient with 99mTc-labeled bleomycin.
Discussion O u r view o f the described p h e n o m e n o n takes account of the different behavior o f u p p e r and lower limb
Conclusions In the search for t u m o r extension a n d / o r metastases o f b o n e sarcomas o f the lower extremities m a n y false positives (eight out of nine in our experience) m a y be obtained when using b o n e scanning tracers.
D. Casara et al. : False Positive Bone Scan in Bone Tumors
The routine use of these agents cannot be discarded, because of their general low cost and ease of management, but contrary to the assumption of e.g., Frankel et al. [3], every apparent uptake in the foot when there is tumor in the upper part of the leg should immediately be checked with more specific tumor-seeking agents and/or methods. The claim that a high uptake index [5, 6] (> 1.5 in comparison with the homologous contralateral segment) is a diagnostic criterion for malignancy in bone scan should be rejected, as some of the feet we examined had an uptake of 1.6. Only a tumor-seeking agent scan should be relied upon, at least for the lower extremities when the thigh or knee is affected.
181 2. Ducassou, D., Leccia, F., Pigneux, J., Blanquet, P.: Le pyrophosphate de sodium marqu~ au 99mTc dans l'+tude des cancers primitifs et secondaires des os. Radioaktive Isotope in Klinik und Forschung, Band 11, S. 346, Mfinchen-Berlin-Wien: Urban & Schwarzenberg 1975 3. Frankel, R.S., Jones, A.E., Cohen, J.A., Johnson, K.W., Johnston, G.S.: Clinical Correlations of 6VGa and skeletal wholebody radionuclide studies with radiography in Ewing's sarcoma. Radiology 110, 597q508 (1974) 4. Jaffe, N.: Ost~osarcomes. In: La Strat6gie du Traitement des Cancers. Semaine Immunocanc~rologique de Villejuif-Paris (21-25 Juin 1976) 5. Laughlin, J.S., Ritter, F.W., Dwyer, A.J., Mayer, K., Greenberg, E.J., Dimick, A.B.: Development and application of quantitative and computer-analyzed counting and scanning. Cancer 25, 395-405 (1970) 6. Perelli, R., Ferlin, G. : Quantitative bone scanning. La Ricerca Clin. Lab. 5, 263-274 (1975)
References
1. Baum, S., Davenport, J.H., Silver, L.: Response to radiation therapy of osseous lesions detected on radioisotope bone scans. Amer. J. Roentgenol. 105, 137 141 (1969)
Note Added in Proof
Five further patients have been studied since submitting the original: in 3/3 affected in the lower limb we have observed a false positive " b o n e " scan; in 2/2 upper limb the " b o n e " and the '"tumor" scan gave superimposable findings.
Received November 8, 1976
Eur. J. Nucl. Med. 2, 1 7 9 - 1 8 1 (1977)
Medicine © by Springer-Verlag 1977
False Positive Bone Scan in Bone Tumors of the Lower Limb Dario Casara 1, Pietro de Besi 2, Mario Fiorentino 2, Adriano Fornasiero 2, Pierluigi Melanotte 3, Giorgio Palfi 2, Paola Sperandio z, and Orazio Vinante 2 1 Divisione di Radioterapia e Medicina Nucleare, Ospedale Civile di Padova 2 Divisione di Oncologia, Ospedale Civile di Padova 3 Clinica Ortopedica, Universit/t di Padova
Abstract. When examined using bone scanning agents, eight out of nine patients with lower limb malignancy, and neither of two affected in the upper limb showed a pathologic focus of isotope uptake in an area distal to the tumor. On pathologic examination the positive findings proved false. Such misleading results were found to be avoidable if a tumor-seeking agent instead of a bone scanning one is used.
The usefulness of this procedure for primary bone tumors has been more recently recognized by orthopedic surgeons and radiotherapists for two purposes: 1) Detecting bone metastases (or multiple primaries) of the bone tumor [3, 6] 2) Defining the extension of local involvement in view of such procedures as local radiation (especially with surdosage or local resection) associated with endoprothesis [1].
Introduction
Material and Methods
Bone scanning has been extensively used for secondary bone malignancies in our institution for 10 years.
The isotopes more usually employed in this particular field have been those following the metabolism of the bone components (Ca ions and phosphates, sTmsr, 99mTc-labeled phosphate compounds). W h e n we used these isotopes, there were interesting and reliable results for trunk and superior limb tumors, but with tumors
For offprints contact." Dr. Mario Fiorentino, Divisione di Oncologia, Ospedale Civile di Padova, Padova, Italy Table 1
Patient
Sex
Age
Tumor type a
Tumor location
Tumor-seeking agent b scan
Bone scan T u m o r area
Distal area (foot or hand)
1 2 3 4 5
D.E. B.C. B.G. C.G. C.P.
F F M M F
17 14 20 21 9
OS OS OS OS OS
Femur Femur Femur Femur Femur
+ + + + ÷
+ + + + +
6
T.A.
M
20
OS
Femur
+
+
7
S.A.
F
26
RCS
Femur
+
+
8
S.R.
M
11
EW
Tibia
+
+
9
G.M.
F
13
OS
Femur
+
-
10
Z.R.
M
17
OS
Humerus
-}-
-
11
P.C.
M
10
EW
Humerus
+
-
a b
T u m o r area
+ +
Distal area (foot or hand)
-(STCo BLM) - ( 5 7 C o BLM)
{+
- ( 6 7 G a citrate) - ( 5 7 C 0 BLM)
+ {+
- (99mTc BLM) - ( 5 7 C o BLM) - (99mTc BLM)
{;
-(STCo BLM) - (99mTc BLM)
+
OS = Osteogenic osteosarcoma; RCS = Primitive reticulum cell sarcoma of bone; EW = Ewing's sarcoma B L M = Bleomycin
-(STCo BLM)
180
D. Casara et al. : False Positive Bone Scan in Bone Tumors
Fig. l. Patient no 3 99mTCphosphate scan
Fig. 2. Same patient 99roTe Bleomycin scan obtained two days later
localized in the thigh or leg (most of them in the knee area) we regularly noted two foci of increased isotope uptake, one being the tumour area, and one in the foot. Table 1 gives details of the patients and diagnoses. Up to now nine such patients have been observed; only one of them had no increased uptake in the foot. In each case the pathologist did not discover any tumor in the foot of the removed limb. After the false positive finding had been detected in several patients, we checked the abnormal uptake with a second scan, performed with more specific 'tumor-seeking' agents. Radioactive bleomycin was used (99mTc-labeled, 57Co-labeled, or both) and in one patient 67Ga citrate was also used (see Table 1).
malignancies (no u p t a k e observed in the two hands examined; uptake observed in eight out of nine feet) and of the different functional implications o f a t u m o r in the upper part a n d / o r midjoint o f the arm or leg. The h a n d is still used, at least for some auxiliary movement, even when shoulder or elbow m o v e m e n t is impaired. The foot has only a support function, which is usually lost if the remaining part of the leg is damaged. Functional a t r o p h y or decalcification f r o m unloading is accordingly m u c h m o r e likely to occur in the feet than in the hands, according to data already k n o w n [2]. U p t a k e o f b o n e tracers is consequently increased in the small bones of the foot because of the negative balance and increased turnover of minerals due to the reduced weight-bearing. F u r t h e r investigations to make this proposed m e c h a n i s m m o r e clear are n o w running in our institution in view o f the fact that a loss o f minerals is not evidenced by plain r a d i o g r a p h y in the examined feet.
Results With the second g r o u p of radiopharmaceuticals none o f the patients showed any a b n o r m a l uptake outside the t u m o r area; in particular the feet did not take up significant a m o u n t s o f the tracer. Table 1 shows relevant data on these patients (Cases 1 to 9) and on 2 other patients with malignancies o f the upper limb (Cases 10 and 11). Figures 1 and 2 show the false positive uptake o f Case 3 with 99mTc p h o s p h a t e and, for comparison, the picture obtained 2 days later f r o m the same patient with 99mTc-labeled bleomycin.
Discussion O u r view o f the described p h e n o m e n o n takes account of the different behavior o f u p p e r and lower limb
Conclusions In the search for t u m o r extension a n d / o r metastases o f b o n e sarcomas o f the lower extremities m a n y false positives (eight out of nine in our experience) m a y be obtained when using b o n e scanning tracers.
D. Casara et al. : False Positive Bone Scan in Bone Tumors
The routine use of these agents cannot be discarded, because of their general low cost and ease of management, but contrary to the assumption of e.g., Frankel et al. [3], every apparent uptake in the foot when there is tumor in the upper part of the leg should immediately be checked with more specific tumor-seeking agents and/or methods. The claim that a high uptake index [5, 6] (> 1.5 in comparison with the homologous contralateral segment) is a diagnostic criterion for malignancy in bone scan should be rejected, as some of the feet we examined had an uptake of 1.6. Only a tumor-seeking agent scan should be relied upon, at least for the lower extremities when the thigh or knee is affected.
181 2. Ducassou, D., Leccia, F., Pigneux, J., Blanquet, P.: Le pyrophosphate de sodium marqu~ au 99mTc dans l'+tude des cancers primitifs et secondaires des os. Radioaktive Isotope in Klinik und Forschung, Band 11, S. 346, Mfinchen-Berlin-Wien: Urban & Schwarzenberg 1975 3. Frankel, R.S., Jones, A.E., Cohen, J.A., Johnson, K.W., Johnston, G.S.: Clinical Correlations of 6VGa and skeletal wholebody radionuclide studies with radiography in Ewing's sarcoma. Radiology 110, 597q508 (1974) 4. Jaffe, N.: Ost~osarcomes. In: La Strat6gie du Traitement des Cancers. Semaine Immunocanc~rologique de Villejuif-Paris (21-25 Juin 1976) 5. Laughlin, J.S., Ritter, F.W., Dwyer, A.J., Mayer, K., Greenberg, E.J., Dimick, A.B.: Development and application of quantitative and computer-analyzed counting and scanning. Cancer 25, 395-405 (1970) 6. Perelli, R., Ferlin, G. : Quantitative bone scanning. La Ricerca Clin. Lab. 5, 263-274 (1975)
References
1. Baum, S., Davenport, J.H., Silver, L.: Response to radiation therapy of osseous lesions detected on radioisotope bone scans. Amer. J. Roentgenol. 105, 137 141 (1969)
Note Added in Proof
Five further patients have been studied since submitting the original: in 3/3 affected in the lower limb we have observed a false positive " b o n e " scan; in 2/2 upper limb the " b o n e " and the '"tumor" scan gave superimposable findings.
Received November 8, 1976
