DOI: 10.1148/rg.281075015
RadioGraphics 2008;28:277-283
© RSNA, 2008
Best Cases from the AFIP
Osteosarcoma of the Femur with Skip, Lymph Node, and Lung Metastases1
Tjeerd Zwaga, MD,
Judith V. M. G. Bovée, MD, PhD, and
Herman M. Kroon, MD, PhD
1 From the Department of Radiology, Kennemer Gasthuis, Teaching Hospital, Boerhaavelaan 22, 2035 RC Haarlem, the Netherlands (T.Z.); and Departments of Pathology (J.V.M.G.B.) and Radiology (H.M.K.), Leiden University Medical Center, Leiden, the Netherlands. Received February 1, 2007; revision requested March 16 and received May 15; accepted May 16. All authors have no financial relationships to disclose.
Address correspondence to T.Z. (e-mail: tzwaga{at}orange.nl).
 |
History
|
|---|
A 13-year-old boy presented to his primary care physician with a history of intermittent and progressive left knee pain over the past 18 months. There was no history of trauma, fever, or other joint abnormality. Physical examination revealed mild soft-tissue swelling in the knee with no restricted range of motion. The patient’s laboratory results were normal except for elevated levels of lactate dehydrogenase and alkaline phosphatase and a slightly elevated level of serum calcium. The initial radiograph demonstrated a sclerotic lesion in the distal femoral metaphysis. The patient was referred to our hospital for further evaluation. Magnetic resonance (MR) imaging, bone scintigraphy, chest computed tomography (CT), and biopsy were performed.
|
Imaging Findings
|
|---|
Radiography of the knee demonstrated a predominantly sclerotic bone-forming lesion of the left distal femur that extended from the metaphysis into the adjacent diaphysis (Fig 1). Although the distal margin of the lesion seemed demarcated by the physis, sclerotic foci were also noted in the epiphysis. These foci were highly suggestive of skip metastases. MR imaging and pathologic analysis indicated that the foci were separated from the primary tumor and were not the result of tumor spread through the physis. Calcified masses posterior to the knee were noted within the soft tissue adjacent to the cortex by way of direct soft-tissue extension through the cortex. More peripheral areas of sclerosis in the soft tissue were suggestive of regional lymph node involvement.
View larger version (149K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1a. Initial lateral (presented in mirror view for correlation with MR images) (a) and anteroposterior (b) radiographs of the left knee show extensive mineralized osteoid throughout the osteoblastic lesion in the distal femur with involvement of the anterior, posterior, and medial cortex (arrowheads). Areas of opacity suggestive of skip lesions are seen in the epiphysis (curved arrow), and mineralized osteoid is seen in the posterior soft tissues (straight arrows in a).
|
|
View larger version (111K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1b. Initial lateral (presented in mirror view for correlation with MR images) (a) and anteroposterior (b) radiographs of the left knee show extensive mineralized osteoid throughout the osteoblastic lesion in the distal femur with involvement of the anterior, posterior, and medial cortex (arrowheads). Areas of opacity suggestive of skip lesions are seen in the epiphysis (curved arrow), and mineralized osteoid is seen in the posterior soft tissues (straight arrows in a).
|
|
At bone scintigraphy, high uptake of technetium 99m (99mTc) methylene diphosphonate was seen in the distal part of the left femur and in the left inguinal region (Fig 2). Subsequent ultrasonography (US) showed a subcutaneous hyperechoic lesion with acoustic shadowing in the same inguinal region (Fig 3), and radiography of the pelvis demonstrated a small ossified structure projecting over the left hip (Fig 4).
View larger version (31K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2. Bone scan demonstrates increased focal radionuclide uptake in the distal femoral diaphysis, metaphysis, and epiphysis (arrowhead), as well as in the left inguinal region (arrow).
|
|
View larger version (167K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4. Radiograph of the left hip demonstrates mineralized osteoid in the inguinal region (arrows). The lesion projects over the medial part of the acetabulum. Findings from bone scintigraphy, US, and radiography are suggestive of a lymph node metastasis. At pathologic analysis, the surgical specimen showed osteoid-producing cells with pre-existing lymphoid tissue.
|
|
MR images revealed the mass in the distal femur, which had an intermediate to low signal intensity with all pulse sequences and which represented the areas of bone formation (Fig 5). The oval to round lesions in the epiphysis and soft tissues also had an intermediate to low signal intensity (Fig 5a), which corresponded with the sclerotic lesions demonstrated on radiographs.
View larger version (116K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5a. (a) Sagittal T1-weighted MR image (repetition time msec/echo time msec = 600/7) shows the predominantly low signal intensity of the mineralized osteoid in the medulla; the posterior cortex shows destruction (arrowhead). Distally, the tumor is bordered by the physis. Skip lesions with almost identical signal intensity are located in the epiphysis (curved arrow). An oval soft-tissue lesion with intermediate signal intensity (straight arrow) corresponding to the mineralized lesion visible on the lateral conventional radiograph, and compatible with a lymph node metastasis, is seen. The joint space is not involved. (b) Sagittal gadolinium-enhanced fat-suppressed T1-weighted MR image (500/7) shows an oval tumor with peripheral enhancement in the soft tissues, indicating a lymph node metastasis (straight arrow). The areas with low signal intensity in the metaphysis represent the areas of dense bone formation (*). The high signal intensity surrounding the tumor reflects areas of nonossified tumor and edema in the bone marrow and surrounding soft tissues (arrowheads).
|
|
View larger version (99K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5b. (a) Sagittal T1-weighted MR image (repetition time msec/echo time msec = 600/7) shows the predominantly low signal intensity of the mineralized osteoid in the medulla; the posterior cortex shows destruction (arrowhead). Distally, the tumor is bordered by the physis. Skip lesions with almost identical signal intensity are located in the epiphysis (curved arrow). An oval soft-tissue lesion with intermediate signal intensity (straight arrow) corresponding to the mineralized lesion visible on the lateral conventional radiograph, and compatible with a lymph node metastasis, is seen. The joint space is not involved. (b) Sagittal gadolinium-enhanced fat-suppressed T1-weighted MR image (500/7) shows an oval tumor with peripheral enhancement in the soft tissues, indicating a lymph node metastasis (straight arrow). The areas with low signal intensity in the metaphysis represent the areas of dense bone formation (*). The high signal intensity surrounding the tumor reflects areas of nonossified tumor and edema in the bone marrow and surrounding soft tissues (arrowheads).
|
|
The sagittal T1-weighted MR image demonstrated the abnormal signal intensity of the ventral and dorsal cortex, thus suggesting cortical involvement. The cortex showed a high signal intensity on the gadolinium-enhanced T1-weighted spectral presaturation with inversion recovery (SPIR) image (Fig 5b), a finding that supported cortical involvement.
The intact subarticular bone and cartilage of the epiphysis, the absence of tumor extension along the cruciate ligaments, and the presence of only a minute amount of joint effusion all indicated that there was no joint involvement.
Biopsy of the femoral lesion was performed because of a suspected intramedullary osteosarcoma. After 2 months of preoperative chemotherapy, radiography was repeated and progressive sclerosis of the lesions was seen (Fig 6). In addition, the lateral view showed a new, small soft-tissue ossification dorsal to the femoral diaphysis. Initially, pulmonary metastases were excluded based on CT findings, but CT was repeated before the distal femur was resected, and revealed three small ossified pulmonary nodules that were resected and proved to be metastases (Fig 7).
View larger version (103K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6. Lateral radiograph obtained after 2 months of preoperative chemotherapy shows progressive sclerosis of the lesions in the metaphysis, skip metastases in the epiphysis (curved arrows), and a lymph node metastasis in the soft tissues (straight arrow). Small soft-tissue calcification is seen dorsal to the femoral diaphysis (arrowhead), a finding indicative of lymphatic spread.
|
|
|
Pathologic Evaluation
|
|---|
The specimen obtained at the initial fluoroscopy-guided biopsy of the metaphyseal part of the femoral tumor demonstrated a variably cellular proliferation of moderately pleomorphic cells forming a condensed osteoid matrix that was consistent with high-grade osteoblastic osteosarcoma (Fig 8). Two months after the biopsy, the primary tumor was resected. In addition, the palpable lymph node in the left groin was removed and proved to be involved by metastatic disease (Fig 9).
View larger version (146K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 9. Photomicrograph (original magnification, x200) of the inguinal lymph node metastasis of osteosarcoma shows the deposition of osteoid (arrowheads) by tumor cells and pre-existing lymphoid tissue (*).
|
|
The resected specimen of the left distal femur showed a white tumor of osteoid consistency that measured 7.1 cm across the largest diameter (Fig 10). The cortex was destroyed and the tumor had invaded through the epiphyseal plate. Several tumor foci were located in the epiphysis with no continuation with the primary tumor. The subchondral bone and overlying cartilage were not breached, indicating that the tumor did not extend into the knee joint. In addition, a tumor nodule was found in the more dorsal soft tissues. A separate tissue specimen, originating from soft tissues at the level of the midshaft of the femur and clinically regarded as a lymph node, was also submitted to the pathology laboratory, and it contained a white nodule with a 0.5-cm diameter and an osteoid consistency. Microscopic images demonstrated a tumor with extensive osteoid deposition. Although there were large areas of necrosis, viable cells were diffusely found, with nuclear hyperchromasia and pleomorphism constituting more than 10% of the tumor volume. The response to chemotherapy, therefore, was considered poor according to Huvos criteria (1): There was no cartilaginous differentiation, the tumor extended into the soft tissues and through the epiphyseal plate, the resection margins were free of tumor, and both soft-tissue nodules contained vital tumor cells (no pre-existing lymph node tissue was seen). After the primary tumor was resected, three nodules (each less than 1 cm in diameter) were resected from the lower lobe of the left lung. They contained largely necrotic tumor with only a few viable tumor cells.
View larger version (125K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 10. Photograph of the resected specimen of the left distal femur shows a white tumor resulting from osteoid formation. The bulk of the tumor is located in the marrow (*). Soft-tissue extension by way of cortical destruction is seen posteriorly (straight arrows), and multiple skip lesions are found below the epiphyseal plate (white arrowheads). At least one of the skip lesions does not contact the physis (black arrowheads). In addition, a separate tumor nodule is found in soft tissues more dorsally, representing a lymph node metastasis (curved arrow).
|
|
|
Discussion
|
|---|
Osteosarcoma is defined as a malignant tumor characterized by the formation of osteoid tissue by tumor cells. It is the most common primary malignant bone tumor in children and adolescents, although malignant bone tumors account for only 3%–5% of all cancers diagnosed in children under 15 years of age (2). High-grade sclerosing osteosarcoma is an unusual histologic variant of osteosarcoma characterized by dense and compact deposition of osteoid and bone. The cellularity in certain areas can be low, making its recognition difficult. It is not associated with a specific clinical behavior or prognosis and is therefore regarded as a subtype of conventional osteosarcoma (1). Close to 10% of primary osteosarcomas are tremendously rich in osteoid and bone production (3).
Most conventional osteosarcomas manifest in children and young adults between 10 and 25 years of age, with a male-to-female ratio of approximately 1.5:1–2:1 (2,4,5). The metaphysis of long tubular bones is most frequently affected (specifically around the knee), especially the distal femur (40%–45% of cases), as in our patient. The proximal part of the tibia and humerus are also commonly involved, followed by the proximal part of the femur and pelvis (4,5).
Although primary epiphyseal involvement is rare, secondary involvement is common (up to 80% of patients) due to transphyseal spread (6). In our patient, the tumor extended through the epiphyseal plate, but skip metastases were also found in the epiphysis. Skip metastases are foci of tumor cells within the same bone as the primary lesion but are separated from the primary focus by normal intervening marrow. Skip metastases of osteosarcomas are less common than formerly thought, found in 1.5%–6.5% of patients, according to two recent studies (7,8). Kager et al (7) reported skip metastases in the epiphysis in only one of 1765 patients with newly diagnosed high-grade osteosarcoma.
The occurrence of clinically detectable lymph node metastases in osteosarcoma is rare, ranging from 2.3% to 10% of patients (9,10). Although lymph node metastases are more common in osteoblastic primary osteosarcoma than in other histologic subtypes, deposition of metastatic osteoid tissue in lymph nodes to such a degree that it can be appreciated at conventional radiography is extremely unusual (9,11). However, mineralized metastases of osteosarcoma that can be visualized with CT, US, MR imaging, or conventional radiography appear to show uptake at bone scintigraphy (12). In our patient, the inguinal osteoid metastases also showed uptake on bone scintiscans, as well as features of calcification on US images.
Bone scintigraphy is most useful for evaluating distant osseous and extraosseous metastases. Osteosarcomas typically show increased uptake of radioisotopes on scintiscans obtained with 99mTc methylene diphosphonate.
CT is the best modality for early detection of metastases in the lung, which is involved in 80% of cases of metastatic disease. CT is limited, however, in evaluating the primary tumor and tumor extent.
Radiography is the initial imaging modality of choice for evaluating osteosarcomas. Approximately 90% of tumors produce sufficient mineralized osteoid matrix to be visible as an amorphous or cloudy area of opacity. The appearance of the tumor can vary from purely osteolytic to entirely osteoblastic because the amount of mineralized matrix varies. The aggressive nature of the tumor is often reflected by permeative cortical involvement and cortical breakthrough without expansion. Periosteal reaction is usually present and can include Codman triangles, a sunburst appearance, and multilaminated or hair-on-end patterns.
MR imaging should be used for further evaluation and local staging of osteosarcomas; its superior contrast resolution allows the extension of tumor into the soft tissues and bone marrow to be determined (6,13–16). T1-weighted spin-echo imaging is the most accurate pulse sequence for identifying the intraosseous extent. The use of fat suppression techniques such as short inversion-time inversion recovery (STIR) sequences or SPIR sequences, however, can cause tumor extent to be overestimated because of adjacent edema (16). Epiphyseal extension can be accurately determined with both T1-weighted and fat suppression techniques such as STIR and SPIR, with T1-weighted sequences being slightly more specific and STIR and SPIR sequences slightly more sensitive (13).
MR imaging is also the most accurate modality in evaluating extraosseous tumor extent, including analysis of the tumor in relation to the adjacent joint, the muscle compartment, and the neurovascular bundle (17–19). Skip metastases are best analyzed with long-axis imaging of the entire affected bone (7). Identifying skip metastases is important, both for defining local extent of the tumor and for prognostic reasons, as patients with skip metastases are more likely to also have distant metastases, which correspond to a lower 5-year survival rate than for those who do not (8).
Although joint involvement by osteosarcoma is uncommon because articular cartilage is a relative barrier to tumor invasion, it can occur. The tumor can invade across the articular cartilage, spread across or around the osseoustendinous junction of the cruciate ligaments, or extend under the capsule insertion at the margin of the articular cartilage. Joint involvement can be reliably excluded with a preoperative MR imaging study before an intra-articular resection is performed (17,18).
Patients with osteosarcomas usually present with nonspecific pain and soft-tissue swelling, as in our case. The radiologic differential diagnosis for osteosarcoma includes any lesion that produces osteoid matrix, such as osteoblastoma. Even a healing fissure or fracture can show periosteal reaction or a fuzzy sclerosis. Osteomyelitis, Langerhans cell histiocytosis, cortical desmoid, and chondrosarcomas should also be considered.
A biopsy is required for histologic confirmation and must be planned in consultation with the patient’s orthopedic surgeon to reduce the risk of tissue contamination, which can result in amputation of the affected limb, and allow limb-sparing surgery.
The treatment of osteosarcomas begins with preoperative neoadjuvant chemotherapy to eradicate micrometastases and reduce viable tumor volume. Although the type of surgical procedure performed depends on many factors, limb-sparing surgery with tumor resection and functional reconstruction can be performed in approximately 90% of osteosarcoma patients. The 5-year event-free survival rate of patients with localized disease is up to 70%, but the prognosis for patients who present with metastatic disease is still poor, with a 5-year survival rate of approximately 30% (20). Ten months after the initial diagnosis of osteosarcoma, our patient is free of new metastases or local recurrence after limb-sparing surgery and metastasectomy of the pulmonary and lymph node metastases. A modular prosthesis was used to reconstruct the knee joint after the distal part of the femur was resected, which resulted in good function of the left limb.
|
Footnotes
|
|---|
Abbreviations: SPIR = spectral presaturation with inversion recovery, STIR = short inversion-time inversion recovery
Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
|
References
|
|---|
- Raymond AK, Ayala AG, Knuutila S. Conventional osteosarcoma. In: Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization classification of tumours: pathology and genetics of tumours, soft tissue and bone. Lyon, France: IARC Press, 2002; 264–270.
- Stiller CA, Bielack SS, Jundt G, Steliarova-Foucher E. Bone tumours in European children and adolescents, 1978–1997: report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006;42(13):2124–2135.[CrossRef][Medline]
- Mirra JM, Kameda N, Rosen G, Eckardt J. Primary osteosarcoma of toe phalanx: first documented case—review of osteosarcoma of short tubular bones. Am J Surg Pathol 1988;12(4):300–307.[Medline]
- Dahlin DC, Coventry MB. Osteogenic sarcoma: a study of six hundred cases. J Bone Joint Surg Am 1967;49(1):101–110.[Abstract/Free Full Text]
- Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002; 20(3):776–790.[Abstract/Free Full Text]
- Norton KI, Hermann G, Abdelwahab IF, Klein MJ, Granowetter LF, Rabinowitz JG. Epiphyseal involvement in osteosarcoma. Radiology 1991; 180(3):813–816.[Abstract/Free Full Text]
- Kager L, Zoubek A, Kastner U, et al. Skip metastases in osteosarcoma: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 2006;24(10):1535–1541.[Abstract/Free Full Text]
- Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;426:92–96.[CrossRef][Medline]
- Tobias JD, Pratt CB, Parham DM, Green AA, Rao B. The significance of calcified regional lymph nodes at the time of diagnosis of osteosarcoma. Orthopedics 1985;8(1):49–52.[Medline]
- Caceres E, Zaharia M, Calderon R. Incidence of regional lymph node metastasis in operable osteogenic sarcoma. Semin Surg Oncol 1990;6(4):231–233.[CrossRef][Medline]
- Madsen EH. Lymph node metastases from osteoblastic osteogenic sarcoma visible on plain films. Skeletal Radiol 1979;4(4):216–218.[CrossRef][Medline]
- Kim SJ, Choi JA, Lee SH, et al. Imaging findings of extrapulmonary metastases of osteosarcoma. Clin Imaging 2004;28(4):291–300.[CrossRef][Medline]
- Hoffer FA, Nikanorov AY, Reddick WE, et al. Accuracy of MR imaging for detecting epiphyseal extension of osteosarcoma. Pediatr Radiol 2000; 30(5):289–298.[CrossRef][Medline]
- Hogeboom WR, Hoekstra HJ, Mooyaart EL, et al. MRI or CT in the preoperative diagnosis of bone tumours. Eur J Surg Oncol 1992;18(1):67–72.[Medline]
- O’Flanagan SJ, Stack JP, McGee HM, Dervan P, Hurson B. Imaging of intramedullary tumour spread in osteosarcoma: a comparison of techniques. J Bone Joint Surg Br 1991;73(6):998–1001.[Medline]
- Onikul E, Fletcher BD, Parham DM, Chen G. Accuracy of MR imaging for estimating intraosseous extent of osteosarcoma. AJR Am J Roentgenol 1996;167(5):1211–1215.[Abstract/Free Full Text]
- Quan GM, Slavin JL, Schlicht SM, Smith PJ, Powell GJ, Choong PF. Osteosarcoma near joints: assessment and implications. J Surg Oncol 2005; 91(3):159–166.[CrossRef][Medline]
- Schima W, Amann G, Stiglbauer R, et al. Preoperative staging of osteosarcoma: efficacy of MR imaging in detecting joint involvement. AJR Am J Roentgenol 1994;163(5):1171–1175.[Abstract/Free Full Text]
- van Trommel MF, Kroon HM, Bloem JL, Hogendoorn PC, Taminiau AH. MR imaging based strategies in limb salvage surgery for osteosarcoma of the distal femur. Skeletal Radiol 1997;26(11): 636–641.[CrossRef][Medline]
- Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 2006; 32(6):423–436.[CrossRef][Medline]
Top
History
Imaging Findings
