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Knee Pain in a 14-Year-Old Girl

DiCaprio, Matthew, R*; Lindskog, Dieter, M*; Husted, David; Reith, John; Scarborough, Mark, T*

Clinical Orthopaedics and Related Research: June 2005 - Volume 435 - Issue - p 267-275
doi: 10.1097/01.blo.0000150577.14047.01
Orthopaedic • Radiology • Pathology Conference
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From the *Department of Orthopaedics and Rehabilitation, ‡Department of Pathology, and †College of Medicine, University of Florida, Gainesville, FL.

Each author certifies that he has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his institution has approved the reporting of this case report, that all investigations were conducted in conformity with ethical principles of research, and that informed consent was obtained.

Correspondence to: Matthew R. DiCaprio, MD, Schenectady Regional Orthopaedic Associates, 530 Liberty Street, Schenectady, NY 12305. Phone: 518-382-7225; Fax: 518-382-7203; E-mail: dicaprio@bellsouth.net.

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HISTORY AND PHYSICAL EXAMINATION

A 14-year-old Caucasian girl presented with a complaint of left knee pain for the past 4 months. Plain radiographs of the left knee showed a lesion in the distal femur. Magnetic resonance images (MRIs) were obtained to further characterize the lesion, and the patient was referred to our institution for additional evaluation and treatment.

At presentation to our clinic, she described intermittent left knee pain, which had progressively increased in severity and had become persistent over the past 4 months. She reported the presence of swelling, and developed a palpable mass during the latter portion of that time. She described the pain as achy in nature, which was worse at night and after physical exertion. The patient denied any history of trauma or injury to the affected knee. Her past medical and surgical history were unremarkable and she denied any constitutional symptoms such as fever, chills, or weight loss.

Physical examination revealed a healthy adolescent girl with an antalgic gait. Examination of her left lower extremity showed a palpable, tender mass over the distal anteromedial aspect of her left thigh. There were no skin changes. She had full pain-free ROM of her knee, and no ligamentous instability. No knee effusion was present. Her extremity was neurovascularly intact, with normal sensation and muscle strength. There was no popliteal or inguinal lymphadenopathy.

Plain radiographs, bone scans, computed axial tomography (CT) images, and MRI scans of the distal femur show the character of the lesion and its relationship to surrounding structures (Figs 1-4). Based on the history, physical examination, and imaging studies, what is the differential diagnosis?

Fig 1.

Fig 1.

Fig 2.

Fig 2.

Fig 3.

Fig 3.

Fig 4.

Fig 4.

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IMAGING INTERPRETATION

Plain radiographs of the left knee showed a radiodense metaphyseal lesion of the distal femur, with subtle cortical irregularity and periosteal reaction along the proximal medial margin (Fig 1). Computed tomography images of the distal femur better characterized the radiodense lesion, which extended approximately 10 cm proximal to the joint line. Irregular cortical permeation was seen medially, with marked periosteal reaction (Fig 2). Multiplanar, multisequence MRI scans revealed a 9.5 × 4.5 × 2.4-cm area of abnormal signal in the distal left femur (Fig 3). The lesion entirely replaced the patient’s medial femoral condyle and abutted the articular surface of the femur without obvious intraarticular extension. The proximal extent of the lesion was observed by the sharp demarcation of normal fatty marrow approximately 9.5 cm proximal to the joint line on coronal images. A majority of the lesion was of intermediate-signal to low-signal intensity on both T1-weighted and T2-weighted images. Scattered areas within the lesion, the periphery of the lesion, and the soft tissue extension all had high-signal intensities on T2-weighted images. A 1-cm juxtacortical soft tissue mass extending from the medial aspect of the distal femur was observed well on MRI scans and was enhanced with the administration of gadolinium (Fig 3C arrowhead = soft tissue mass; arrow = periosteal elevation).

Bone scintigraphy scans identified an intense concentration of radiotracer in the left distal femur (Fig 4). There was no evidence of satellites, local skip lesions, or distant skeletal metastases.

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DIFFERENTIAL DIAGNOSIS

  • Conventional osteosarcoma
  • Ewing’s sarcoma
  • Lymphoma
  • Osteoblastoma
  • Osteomyelitis

An incisional biopsy of the juxtacortical soft tissue mass was performed. Intraoperative frozen-section analysis verified adequate tissue sampling and the remaining specimen was processed for a permanent pathologic evaluation (Figs 5, 6). Based on the history, physical findings, imaging studies, and histologic picture, what is the diagnosis and how should this lesion be treated?

Fig 5.

Fig 5.

Fig 6.

Fig 6.

See page 272 for diagnosis and treatment.

Continuation of ORP conference from page 271.

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HISTOLOGY INTERPRETATION

Microscopic examination of the biopsy specimen showed a tumor composed in part by a cellular neoplasm with a variety of histologic appearances. In some areas, the tumor contained a prominent, variably cellular chondroid matrix containing markedly atypical cells. The chondroid matrix was surrounded by and blended with highly cellular areas containing fine osteoid matrix deposition (Fig 5, 6). The cells contained within the osteoid matrix were highly atypical, and numerous mitotic figures were identified. In other areas, the tumor was composed of long fascicles of pleomorphic, mitotically active spindled cells devoid of osteoid or chondroid matrices.

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DIAGNOSIS

Osteosarcoma (high grade; Musculoskeletal Tumor Society and American Joint Committee on Cancer, AJCC, Stage IIB8)

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DISCUSSION AND TREATMENT

Osteosarcoma is the most common primary bone sarcoma and the third most common malignant tumor in children, exceeded only by leukemia and lymphoma.11,19 By definition, osteosarcoma is a malignant spindle-cell neoplasm in which the malignant cells form osteoid. It is a relatively rare tumor, with fewer than 1000 new cases per year in the United States, with no racial or ethnic influence on the incidence. There is a male predominance of 1.5:1.11

Osteosarcoma and its variants are categorized by location (intramedullary versus surface), histologic composition (osteoblastic, chondroblastic, fibroblastic), degree of cellular differentiation (high grade versus low grade), the number of foci of involvement (single versus multicentric), and the causation of the neoplasm (primary versus secondary).11,12,23,29 Secondary osteosarcoma is known to arise from conditions such as Paget’s disease and radiation exposure (iatrogenic and accidental). Secondary osteosarcoma is typically seen in the fifth and sixth decades of life. Classic (primary high-grade intramedullary) osteosarcoma is commonly seen during the second decade of life, around the period of the adolescent growth spurt.11,12,29

Classic osteosarcoma typically presents with pain about the lesion, with a characteristic progression of the nature of pain from intermittent to persistent over time.11,30 The patient may describe swelling or a palpable mass. Some patients present with a pathologic fracture secondary to marked weakening of the strength of the bone at the site of the lesion.26

Osteosarcoma typically involves the metaphyseal region of long bones in the appendicular skeleton (80% of cases).11,23 These tumors typically originate in the region of most rapid growth and greatest blood flow, the distal femur in 35% of cases, the proximal tibia (20%), and the proximal humerus (10%) are most commonly involved.11,12,23

The characteristic radiographic features are a destructive lesion about the metaphysis with indistinct borders, periosteal elevation, cortical bone destruction, soft tissue extension, and evidence of ossification. Reactive bone adjacent to the lesion can elevate the periosteum and create a radiographic finding referred to as Codman’s triangle. The periosteal reaction may be dense, multilayered, or even show the characteristic, but not pathognomonic, sunburst appearance, with new bone formation appearing as spicules radiating perpendicularly from the involved cortex.23 The radiographic appearance is highly variable, however, a mixed pattern consisting of both radiolucencies and radiodensities most typically is observed.

The most common route of disease metastasis in patients with osteosarcoma is by hematogenous spread to the lungs and, much less commonly, to bone. Approximately 15% of patients have clinically detectable lung metastases at the time of diagnosis.11,19 Bone metastases are present in less than 5% of patients at time of diagnosis.11 It is necessary to evaluate for the presence of distant disease with the use of bone scintigrams and a CT scan of the chest. For local tumor staging MRI and CT provide complementary information useful in planning surgical resection. Computed tomography is useful in assessing the extent of the bone destruction, periosteal reaction, and matrix composition, while magnetic resonance imaging helps define the intraosseous and extraosseous extent of the tumor.1,20,23 On MRI scans, classic osteosarcoma is observed to be low signal on T1-weighted images. Marrow involvement by the tumor is consequently seen as areas of diminished signal intensity because the neoplasm has replaced the normal marrow fat.1,20 Use of MRI scans to evaluate the tumor extent within the marrow is indispensable, allowing for the evaluation of the presence of skip lesions, and enabling the surgeon to precisely plan the surgical resection.17,20 The T1-weighted MRI scan of the entire involved bone in the sagittal and/or coronal plane before chemotherapy is the most valuable study to determine the intramedullary extent of the tumor. A similar study after chemotherapy then is evaluated to help determine the level of tumor resection.

Other bone lesions that may present with a similar clinical history, examination, and radiographic evaluation, would include primary malignant bone tumors (Ewing’s and lymphoma), benign bone-forming tumors (osteoblastoma), and infection. The histologic evaluation helps differentiate between these when it is correlated with the clinical and radiographic interpretation.

Ewing’s sarcoma is a malignant, small, round-cell tumor, and is the second most common bone tumor in children.11 The radiographic appearance is more permeative than that seen with osteosarcoma, and frequently there is a soft tissue mass out of proportion to the findings seen on plain radiographs. It occurs in the same age range as primary intramedullary osteosarcoma and also presents with pain, swelling, and a mass.30 There is no second age peak as seek with secondary osteosarcomas. Histologically, Ewing’s sarcoma is composed of sheets of monotonous small, round blue cells and is easily distinguished from conventional osteosarcoma. Characteristic cytogenetics [t(11;22)(q24;q12)] and immunohistochemistry (CD-99 immunoreactivity) help confirm the diagnosis.

Another small round blue cell malignancy that can be seen in children and confused with Ewing’s sarcoma is lymphoma. Primary bone lymphoma is rare and accounts for less than 5% of primary bone tumors.6 The median age of 24 patients in a series with long-term followup was 38.5 years. The radiographic findings are variable, but typically suggest an aggressive malignant process. Immunohistochemistry and flow cytometry play a major role in identifying and classifying lymphoma.

Osteoblastoma is a rare, benign, bone-forming tumor, most commonly seen in the posterior elements of the spine. A majority of osteoblastomas show radiographic, pathologic, and clinical features distinct from those seen in osteosarcoma. Generally, the lesions are well-circumscribed radiodense lesions with nonaggressive radiographic features. However, there is a spectrum of disease and radiographic appearance which can be aggressive. Histologically, the lesion is composed of osteoblast-lined osteoid with a benign fibrovascular stroma between the bony trabeculae.9,10 A lack of cellular atypia, mitoses, and necrosis in a majority of osteoblastomas allow them to be distinguished from osteosarcoma.

Osteomyelitis can afflict people of all ages and involve any bone. Radiographic findings are varied, from indolent, focal bone lesions to areas with aggressive osteolysis, cortical destruction and soft tissue extension. In chronic cases or cases involving more virulent organisms, the radiographic changes suggest an aggressive process. A mixed population of acute and chronic inflammatory cells on histologic sections and positive cultures help distinguish the bone destruction attributable to infection from malignancy.23

After complete staging and confirmatory biopsy,21 the current standard of treatment for osteosarcoma includes neoadjuvant chemotherapy (multiagent preoperative chemotherapy) combined with wide surgical resection (limb sparing or ablative), followed by postoperative chemotherapy.7,11,13,14,16,18,22 With multidisciplinary treatment, the current overall survival rate is between 70 and 80% in patients with nonmetastatic osteosarcoma. In the period before chemotherapy, the overall survival was 20%. The administration of chemotherapy in patients with osteosarcoma has led to a dramatic increase in the 5-year survival rate and the rate of limb-salvage surgery.2,15,22,24,25,27,28 Poor prognostic factors include metastatic disease at presentation, poor response to preoperative chemotherapy, and large tumor size.3,4,5,11

Our patient was treated with four cycles of preoperative chemotherapy (ifosfamide, doxorubicin, cisplatinum) followed by wide surgical resection of the distal femur and previous biopsy tract. Coronal-plane sections showed a densely ossified mass that extended from the subchondral plate proximally into the femoral diaphysis, and filled the entire medullary cavity (Fig 7A). No viable tumor cells were identified in any of the histologic sections, indicating a 100% response to neoadjuvant chemotherapy (Fig 7B). An osteoarticular allograft was used to reconstruct the skeletal defect and she maintains excellent, pain-free knee function more than 5 years postoperatively (Fig 8).

Fig 7.

Fig 7.

Fig 8.

Fig 8.

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