Skeletal Radiol (1991) 20:624-627
Skeletal Radiology
Case report 703 Paul N. Olson, M.D. 1'2, Lee Prewitt, M.D. t, Harry J. Griffiths, M.D. 1'2, and Blair Cherkna, M.D. 1 1 Minneapolis Children's Medical Center, 2 University of Minnesota, Minneapolis, Minnesota, U S A
Imaging studies
Fig. 1A, B. AP and lateral views of right knee show a large soft-tissue mass containing patchy areas of ossification as well as
discrete periosteal reaction on the medial aspect of the distal end of the femur. Note loss of definition of the medial metaphyseal cortex and patchy areas of increased density within the bone itself
Address reprint requests to : Paul N. Olson,
M.D., and Harry J. Griffiths, M.D., Box 292 U M H C , University of Minnesota, Minneapolis, M N 55455, U S A 9 1991 International Skeletal Society
Fig. 2. An M R (Tl-weighted sequence) scan demonstrates a large soft-tissue mass sur-
rounding the distal end of the right femur. The normal signal of the distal metaphysis and epiphysis has been replaced by a mixed signal density with focal areas of signal void. The growth plate has been broached. However, a similar lesion can be seen in the distal end of the left femur with an accompanying soft-tissue mass. Focal bone marrow lesions are also noted
P.N. Olson et al. : Case report 703
625
Fig. 3A-C. Bone scans show multiple areas of increased uptake throughout the skeleton as well as the large mass in and around the distal end of the right femur Fig. 4A, B. MRI scans of the spine demonstrate multiple areas of involvement in the vertebral bodies with a soft-tissue mass adjacent to the anterior margin of TI as well as epidural spread at TI, T3 and particularly at T8 (arrows). Note also partial collapse of a number of vertebral bodies
Clinical information The patient is an 11-year-old girl who had complained of pain in the right knee for 2 months. The plain radiographs obtained (Fig. 1) at that time demonstrated a patchy increase in bone density within the juxtametaphyseal and metaphyseal areas with an associated soft-tissue mass, which contained amorphous foci of ossification. A discrete periosteal reaction just proximal to the tumor was noted. An MR scan was performed to evaluate the lesion further (Fig. 2), and a large mass was identified, orig-
inating within the bone and containing central necrosis. Two similar but smaller lesions were seen in the distal metaphysis of the left femur. Multifocal areas of abnormal bone marrow signal were also present bilaterally in both femurs and tibias. A bone scan was then performed with technetium 99m methylene diphosphonate ( 9 9 m T c - M D P ) , which demonstrated multiple loci of increased radiotracer activity (Fig. 3) not only in the distal end of the right femur but also in the proximal end of each tibia, the distal end of the left femur, and throughout the skull, ribcage, spine, and upper segments
of the humeri. Subsequently, a CT scan of the chest and abdomen, a MR image of the brain and spine (Fig. 4), and a skeletal survey were performed. These images demonstrated further foci of disease, including multiple soft-tissue masses involving the vertebral bodies and epidural spaces of the cervical, thoracic, and lumbar spine. Tumor was also found to involve the middle cranial fossa and the left lateral orbit. Multiple pulmonary nodules were identified without significant lymphadenopathy. No significant adenopathy was noted within the abdomen, and the spleen was not enlarged.
626
Diagnosis: Multifocal osteosarcoma The differential diagnosis of the initial femoral lesion included osteogenic sarcoma, Ewing's sarcoma, lymphoma, and metastases. A biopsy from the right femoral mass showed a high-grade malignant neoplasm. Several histological patterns were present (Figs. 5, 6). Some
Fig. 5. The celtular area from the right femoral mass shows numerous abnormal cells, mitoses, and matrix Fig. 6. Perithelial areas of the femoral mass show cellular tumor with numerous mitoses, hyperchromatism, and an eosinophilic matrix Fig. 7. Biopsy from the left iliac crest shows marked osteoid formation within the tumor Fig. 8. Biopsy from the right iliac crest shows a cellular malignant tumor
P.N. Olson et al. : Case report 703 sections showed epithelioid cells arranged in nests with islands of palestaining matrix which became more prominent away from the cellular areas. Tumor cells were concentrated in the vascular spaces, producing a perithelial appearance. The matrix appeared convoluted and showed reticulated calcification. Basophilic spiculated calcification was present in the osteoid matrix. Multinucleated giant cells were noted focally, and mitotic activity was abundant throughout the lesions. Sections from the biopsy of the iliac crest bone marrow showed abundant tumor (Figs. 7, 8). In many areas, the marrow space was completely filled with tumor, which had histological similarities to the sections from the right femoral lesion. Abundant osteoid was also present in several sections.
Discussion Multifocal osteogenic sarcoma is a relatively rare entity and until recently had been evaluated only in case reports [1, 2, 4]. A slight male predominance exists among younger patients ( < 18 years old), and a much greater male predominance is present, approximately 3 : 1, among older patients ( > 18 years old). The most frequently encountered sites of the primary lesion (in decreasing order of frequency) are as follows: the distal end of the femur, the proximal end of the tibia, the proximal end of the femur together with the pelvis and the proximal end of the humerus [2, 4]. Symmetry of the sites for multiple lesions is often noted, although asymmetry has also been seen. Pulmonary metastases are regularly identified at presentation as well [5].
P.N. Otson et al. : Case report 703 The prognosis for patients with multifocal osteogenic sarcoma is poor, with most surviving only a few months beyond diagnosis [2, 4]. Two major theories exist in the literature regarding the multifocality o f osteogenic sarcoma [1, 2, 6]. These include: (a) multisite lesions arising simultaneously, presumably all representing multiple, synchronous, primary lesions; (b) single-site origin, with one dominant site and then early and rapidly progressive metastatic disease. The most commonly quoted classification of multifocal osteogenic sarcoma is that o f Amstutz [1] : Type I - Patients < 18 years of age with multiple, synchronously occurring bone lesions with rapid progression within 5 months of diagnosis. Type II - Patients > 18 years of age with multiple, synchronously occurring bone lesions arising within 5 m o n t h s o f presentation with a dominant mass. Type IIIa - Patients of any age with early metachronous metastatic bone lesions appearing 5-24 months after diagnosis. Type III b - Patients o f any age with late metachronous metastatic bone lesions appearing more than 24 months after diagnosis. Hooper et al. [4] recently reviewed 690 cases o f osteogenic sarcoma from the Armed Forces Institute o f Pathology and described 29 cases o f multi-
627 focal osteogenic osteosarcoma or osteosarcomatosis type I and type II. They concluded that the most likely etiology of these multifocal cases was a dominant mass with early metastatic disease [4]. Multifocal skeletal disease has been reported infrequently. However, 29 of 690 cases reported by Hooper et al. [4] and 16 of 600 cases reviewed by Dahlin and Coventry [2] were of the multifocal subtype of osteosarcoma. In an autopsy series carried out by Jeffree et al., 14 of 29 patients with apparently solitary lesions were found to have multifocal disease [5]. The reason for this lack o f identification may include the absence of overall skeletal surveys or radionuclide bone scans. The importance of bone scanning in evaluating patients for metastatic bone disease has been emphasized by Goldstein et al. [3] and McKillop et al. [6], who detected a relatively high prevalence of new or metastatic disease early (16%-36%). In addition, chest CT scans are necessary for the evaluation of pulmonary metastases, as conventional radiographs do not have the sensitivity for demonstrating small pulmonary metastases. We have recently evaluated the role of CT in the detection of metastatic disease and correlated its findings with surgical exploration and plain film radiography in several patients. A greater
Fig. 9A, B. Repeat AP and lateral views of the distal end of the femur 2 months later show marked progression of disease with patchy areas of increased density throughout all the bones visualized. The soft-tissue mass adjacent to the right femur has not only grown considerably in size but contains more areas of patchy ossification
number of lesions was detectable by CT than on plain films. It was also found at surgery for resection of the metastatic loci that more small lesions were identified, further supporting the theory o f a primary lesion with early metastatic disease. Two months following the diagnosis, the patient was started on chemotherapy which included ifosfamide, etoposide, and mesna alternating with high dose methotrexate. Despite the therapy, she developed new skeletal lesions and demonstrated enlargement of the existing lesions (Fig. 9). A second course o f chemotherapy was begun, but the lesions continued to grow in size and number, although she remains alive 6 months after presentation. In summary, there are two theories concerning the origin o f multifocat osteogenic sateoma: In one, the lesions all arise synchronously as multiple, simultaneously appearing, primary tumors, and in the other, there appears to be one dominant site with early and rapidly progressive metastatic disease. We believe that our patient fits into the second group with a primary right (distal-end) femoral osteogenic sarcoma with early and rapid metastatis. Bone scan, chest CT, and M R I examinations played an essential role in the initial evaluation and follow-up o f this patient with osteosarcomatosis. The multiple modalities also offered a greater sensitivity in the detection and for the surveillance o f the progression of the condition.
References 1. Amstutz HC (1969) Multiple osteogenic sarcomata: metastatic or multicentric? Cancer 24: 923 2. Dahlin DC, Coventry MB (1967) Osteogenic sarcoma: a study of 600cases. J Bone Joint Surg [Am] 49:101 3. Goldstein H, McNeil BJ, Zufall E, Jaffe N, Treves S (1980) Changing indications for bone scintigraphy in patients with osteosarcoma. Radiology 135 : 177 4. Hooper KD, Moser RP, Haseman DB, Sweet DE, Madewetl JE, Kransdorf MJ (1990) Osteosarcomatosis. Radiology 175:223 5. Jeffree GM, Price CH, Sissons HA (1975) The metastatic patterns of osteogenic sarcoma. Br J Cancer 32: 87 6. McKillop JH, Etcubanas E, Goris ML (t981) The indications for and limitations of bone scintigraphy in osteogenic sarcoma: a review of 55patients. Cancer 48:1133
Skeletal Radiology
Case report 703 Paul N. Olson, M.D. 1'2, Lee Prewitt, M.D. t, Harry J. Griffiths, M.D. 1'2, and Blair Cherkna, M.D. 1 1 Minneapolis Children's Medical Center, 2 University of Minnesota, Minneapolis, Minnesota, U S A
Imaging studies
Fig. 1A, B. AP and lateral views of right knee show a large soft-tissue mass containing patchy areas of ossification as well as
discrete periosteal reaction on the medial aspect of the distal end of the femur. Note loss of definition of the medial metaphyseal cortex and patchy areas of increased density within the bone itself
Address reprint requests to : Paul N. Olson,
M.D., and Harry J. Griffiths, M.D., Box 292 U M H C , University of Minnesota, Minneapolis, M N 55455, U S A 9 1991 International Skeletal Society
Fig. 2. An M R (Tl-weighted sequence) scan demonstrates a large soft-tissue mass sur-
rounding the distal end of the right femur. The normal signal of the distal metaphysis and epiphysis has been replaced by a mixed signal density with focal areas of signal void. The growth plate has been broached. However, a similar lesion can be seen in the distal end of the left femur with an accompanying soft-tissue mass. Focal bone marrow lesions are also noted
P.N. Olson et al. : Case report 703
625
Fig. 3A-C. Bone scans show multiple areas of increased uptake throughout the skeleton as well as the large mass in and around the distal end of the right femur Fig. 4A, B. MRI scans of the spine demonstrate multiple areas of involvement in the vertebral bodies with a soft-tissue mass adjacent to the anterior margin of TI as well as epidural spread at TI, T3 and particularly at T8 (arrows). Note also partial collapse of a number of vertebral bodies
Clinical information The patient is an 11-year-old girl who had complained of pain in the right knee for 2 months. The plain radiographs obtained (Fig. 1) at that time demonstrated a patchy increase in bone density within the juxtametaphyseal and metaphyseal areas with an associated soft-tissue mass, which contained amorphous foci of ossification. A discrete periosteal reaction just proximal to the tumor was noted. An MR scan was performed to evaluate the lesion further (Fig. 2), and a large mass was identified, orig-
inating within the bone and containing central necrosis. Two similar but smaller lesions were seen in the distal metaphysis of the left femur. Multifocal areas of abnormal bone marrow signal were also present bilaterally in both femurs and tibias. A bone scan was then performed with technetium 99m methylene diphosphonate ( 9 9 m T c - M D P ) , which demonstrated multiple loci of increased radiotracer activity (Fig. 3) not only in the distal end of the right femur but also in the proximal end of each tibia, the distal end of the left femur, and throughout the skull, ribcage, spine, and upper segments
of the humeri. Subsequently, a CT scan of the chest and abdomen, a MR image of the brain and spine (Fig. 4), and a skeletal survey were performed. These images demonstrated further foci of disease, including multiple soft-tissue masses involving the vertebral bodies and epidural spaces of the cervical, thoracic, and lumbar spine. Tumor was also found to involve the middle cranial fossa and the left lateral orbit. Multiple pulmonary nodules were identified without significant lymphadenopathy. No significant adenopathy was noted within the abdomen, and the spleen was not enlarged.
626
Diagnosis: Multifocal osteosarcoma The differential diagnosis of the initial femoral lesion included osteogenic sarcoma, Ewing's sarcoma, lymphoma, and metastases. A biopsy from the right femoral mass showed a high-grade malignant neoplasm. Several histological patterns were present (Figs. 5, 6). Some
Fig. 5. The celtular area from the right femoral mass shows numerous abnormal cells, mitoses, and matrix Fig. 6. Perithelial areas of the femoral mass show cellular tumor with numerous mitoses, hyperchromatism, and an eosinophilic matrix Fig. 7. Biopsy from the left iliac crest shows marked osteoid formation within the tumor Fig. 8. Biopsy from the right iliac crest shows a cellular malignant tumor
P.N. Olson et al. : Case report 703 sections showed epithelioid cells arranged in nests with islands of palestaining matrix which became more prominent away from the cellular areas. Tumor cells were concentrated in the vascular spaces, producing a perithelial appearance. The matrix appeared convoluted and showed reticulated calcification. Basophilic spiculated calcification was present in the osteoid matrix. Multinucleated giant cells were noted focally, and mitotic activity was abundant throughout the lesions. Sections from the biopsy of the iliac crest bone marrow showed abundant tumor (Figs. 7, 8). In many areas, the marrow space was completely filled with tumor, which had histological similarities to the sections from the right femoral lesion. Abundant osteoid was also present in several sections.
Discussion Multifocal osteogenic sarcoma is a relatively rare entity and until recently had been evaluated only in case reports [1, 2, 4]. A slight male predominance exists among younger patients ( < 18 years old), and a much greater male predominance is present, approximately 3 : 1, among older patients ( > 18 years old). The most frequently encountered sites of the primary lesion (in decreasing order of frequency) are as follows: the distal end of the femur, the proximal end of the tibia, the proximal end of the femur together with the pelvis and the proximal end of the humerus [2, 4]. Symmetry of the sites for multiple lesions is often noted, although asymmetry has also been seen. Pulmonary metastases are regularly identified at presentation as well [5].
P.N. Otson et al. : Case report 703 The prognosis for patients with multifocal osteogenic sarcoma is poor, with most surviving only a few months beyond diagnosis [2, 4]. Two major theories exist in the literature regarding the multifocality o f osteogenic sarcoma [1, 2, 6]. These include: (a) multisite lesions arising simultaneously, presumably all representing multiple, synchronous, primary lesions; (b) single-site origin, with one dominant site and then early and rapidly progressive metastatic disease. The most commonly quoted classification of multifocal osteogenic sarcoma is that o f Amstutz [1] : Type I - Patients < 18 years of age with multiple, synchronously occurring bone lesions with rapid progression within 5 months of diagnosis. Type II - Patients > 18 years of age with multiple, synchronously occurring bone lesions arising within 5 m o n t h s o f presentation with a dominant mass. Type IIIa - Patients of any age with early metachronous metastatic bone lesions appearing 5-24 months after diagnosis. Type III b - Patients o f any age with late metachronous metastatic bone lesions appearing more than 24 months after diagnosis. Hooper et al. [4] recently reviewed 690 cases o f osteogenic sarcoma from the Armed Forces Institute o f Pathology and described 29 cases o f multi-
627 focal osteogenic osteosarcoma or osteosarcomatosis type I and type II. They concluded that the most likely etiology of these multifocal cases was a dominant mass with early metastatic disease [4]. Multifocal skeletal disease has been reported infrequently. However, 29 of 690 cases reported by Hooper et al. [4] and 16 of 600 cases reviewed by Dahlin and Coventry [2] were of the multifocal subtype of osteosarcoma. In an autopsy series carried out by Jeffree et al., 14 of 29 patients with apparently solitary lesions were found to have multifocal disease [5]. The reason for this lack o f identification may include the absence of overall skeletal surveys or radionuclide bone scans. The importance of bone scanning in evaluating patients for metastatic bone disease has been emphasized by Goldstein et al. [3] and McKillop et al. [6], who detected a relatively high prevalence of new or metastatic disease early (16%-36%). In addition, chest CT scans are necessary for the evaluation of pulmonary metastases, as conventional radiographs do not have the sensitivity for demonstrating small pulmonary metastases. We have recently evaluated the role of CT in the detection of metastatic disease and correlated its findings with surgical exploration and plain film radiography in several patients. A greater
Fig. 9A, B. Repeat AP and lateral views of the distal end of the femur 2 months later show marked progression of disease with patchy areas of increased density throughout all the bones visualized. The soft-tissue mass adjacent to the right femur has not only grown considerably in size but contains more areas of patchy ossification
number of lesions was detectable by CT than on plain films. It was also found at surgery for resection of the metastatic loci that more small lesions were identified, further supporting the theory o f a primary lesion with early metastatic disease. Two months following the diagnosis, the patient was started on chemotherapy which included ifosfamide, etoposide, and mesna alternating with high dose methotrexate. Despite the therapy, she developed new skeletal lesions and demonstrated enlargement of the existing lesions (Fig. 9). A second course o f chemotherapy was begun, but the lesions continued to grow in size and number, although she remains alive 6 months after presentation. In summary, there are two theories concerning the origin o f multifocat osteogenic sateoma: In one, the lesions all arise synchronously as multiple, simultaneously appearing, primary tumors, and in the other, there appears to be one dominant site with early and rapidly progressive metastatic disease. We believe that our patient fits into the second group with a primary right (distal-end) femoral osteogenic sarcoma with early and rapid metastatis. Bone scan, chest CT, and M R I examinations played an essential role in the initial evaluation and follow-up o f this patient with osteosarcomatosis. The multiple modalities also offered a greater sensitivity in the detection and for the surveillance o f the progression of the condition.
References 1. Amstutz HC (1969) Multiple osteogenic sarcomata: metastatic or multicentric? Cancer 24: 923 2. Dahlin DC, Coventry MB (1967) Osteogenic sarcoma: a study of 600cases. J Bone Joint Surg [Am] 49:101 3. Goldstein H, McNeil BJ, Zufall E, Jaffe N, Treves S (1980) Changing indications for bone scintigraphy in patients with osteosarcoma. Radiology 135 : 177 4. Hooper KD, Moser RP, Haseman DB, Sweet DE, Madewetl JE, Kransdorf MJ (1990) Osteosarcomatosis. Radiology 175:223 5. Jeffree GM, Price CH, Sissons HA (1975) The metastatic patterns of osteogenic sarcoma. Br J Cancer 32: 87 6. McKillop JH, Etcubanas E, Goris ML (t981) The indications for and limitations of bone scintigraphy in osteogenic sarcoma: a review of 55patients. Cancer 48:1133
