A 19-year-old Caucasian male presents to the clinic and has had lower right knee pain for the last three weeks. He plays soccer and has a long history of bilateral knee injury. However, he recently missed soccer practice due to pain that occurs with walking. He says the pain has become much worse in the past week despite the use of icing and non-steroidal antiinflammatory drugs (NSAIDs). The pain does not change character with motion and becomes worse at night.
       The patient’s past medical history is significant for multiple episodes of infected acne that has been treated and resolved with the last episode occurring two months ago. He denies using alcohol, tobacco or illegal drugs. His mother has osteoarthritis (OA).
       The physical exam reveals a well-developed, well-nourished adolescent man in mild distress. His blood pressure is 118/66. He has a heart rate of 64 beats per minute and 14 breaths per minute. The patient weighs 160 pounds with clothes and is 5’12” shoes. With the anterior inspection, the patient’s right distal thigh looks swollen. There are no changes in skin color or temperature.
       The bulge sign is negative. There are no abnormalities with the medial and lateral collateral ligaments and the Lachman test reveals no abnormalities. Upon palpation, the medial and lateral condyles are non-tender. However, on the distal femur, we palpate a bony enlargement. The patient’s range of motion in the right knee is limited due to the pain, especially upon knee extension. He shifts weight to his left leg when walking. Deep tendon reflexes and the sensory exam are normal bilaterally. Radiography of the right knee reveals a mixed lytic and sclerotic lesion on the metaphyseal region of the right, distal femur.

Which of the following is the most likely diagnosis?

A. Ewing’s sarcoma
B. Chondroblastoma
C. Osteochondroma
D. Osteosarcoma
E. Osteomyelitis

Keys To The Differential Diagnosis

A. Ewing’s sarcoma is not the correct answer. Ewing’s sarcoma is the second most common malignant bone tumor after osteosarcoma. Ewing’s sarcoma is common among Caucasian males ranging from five to 25 years in age. Eighty percent of cases occur within the first two decades of life. The most common sites are the diaphyses of the femur, tibia, humerus and fibula respectively. Pain is the most common presenting symptom of Ewing’s sarcoma. The disorder is often associated with systemic manifestations such as fever and weight loss in addition to malaise that is usually mistaken for osteomyelitis.
       Radiographs should reveal a permeative pattern of destruction in the diaphysis or metaphyseal portion of bone. The typical image is similar to onion skinning and results from the appearance of a primary lytic lesion surrounded by a periosteal reaction. One may also observe thinning and erosion of the cortex.
       Patients who have a favorable prognosis may have the following characteristics: age less than 10 years old, a distal extremity tumor, a tumor volume of less than 100 ml and a chemotherapy response prior to resection of less than 10 percent of the viable tumor. Unfavorable prognosis characteristics include a pelvis tumor, a tumor larger than 8 cm, an elevated white blood cell (WBC) count and erythrocyte sedimentation rate (ESR), a microscopic filigree pattern and a chemotherapy response prior to resection of greater than ten percent of the viable tumor. Treatment includes preoperative chemotherapy and subsequent surgical resection. The survival rate is approximately 60 percent for patients without metastases.
       B. Chondroblastoma is not the correct answer. Chondroblastoma is an uncommon benign tumor which arises in the epiphysis of a long bone. It occurs in children and represents one percent of all primary bone tumors. Chondroblastomas are commonly found in the distal femur, proximal tibia, proximal humerus and proximal femur.
       The clinical presentation is nonspecific and includes local pain, swelling and muscle wasting. Joint effusion occurs in 30 percent of patients. Symptom duration may vary from months to years before diagnosis. Preferred evaluation modalities include standard radiography and either computed tomography scanning or magnetic resonance imaging (MRI). Treatment includes curettage and bone grafting.
       C. Osteochondroma is not the correct answer. Osteochondroma (exostosis) is the most common benign tumor and is frequently asymptomatic. Most osteochondromas occur at the metaphyseal portions of long bones, particularly the distal femur, proximal tibia humerus and femur. However, lesions also occur in the scapulae and pelvis. Osteochondroma is more common in males than females. It is an aberrant cartilage nonneoplastic growth which results in a bony mass. The tumor develops during childhood. It grows until skeletal maturity is complete and arises in areas of growth plates of the long bones, pelvis and spine.
       Patients are generally diagnosed between the ages of 10 and 30, and seek medical advice because of a bony, non-tender mass. Activity-related pain occurs because the mass irritates surrounding muscle. Compression of an adjacent nerve causes radicular pain or paresthesia.
       Radiographs demonstrate a lesion with a peripheral rim of calcification and “stippled” calcification with the lesion. A CT scan is helpful in distinguishing benign versus malignant indicators. When it comes to a prepubertal presentation, one may observe it but pursue resection immediately upon growth of the lesion or the development of pain. In regard to an adult presentation of an osteochondroma, one may observe it if it is on the extremity and pursue resection if the pelvis is involved. Otherwise, one may pursue resection only if it is symptomatic or if growth occurs.
       D. Osteomyelitis is not the correct answer. Osteomyelitis is a bone marrow infection by bloodborne pathogens. It may be classified as acute, subacute or chronic, and is commonly caused by Staphylococcus aureus. Bone marrow infection may be triggered by trauma. Hematogenous spread of infection from a boil or sore throat is common in children.
       Diagnostic features of acute osteomyelitis include: a recent history of soft tissue abscess in patients with a fever above 100°F; limited movement of the adjacent joint (although not as severe as in septic arthritis); and limping or refusal to walk for approximately two weeks. Osteomyelitis is twice as common in males than females, most often only affects one bone and usually involves the lower extremity.
       Radiographic changes may include soft tissue swelling followed by periosteal elevation, demineralization ten to fourteen days later, sequestra or dead bone surrounding granulation tissue and subsequent periosteal growth. Bone scans will show increased focal activity.
       Magnetic resonance imaging is the most sensitive modality for detecting changes in bone and bone marrow consistent with osteomyelitis. Additionally, there will be an elevated WBC count and ESR. Positive blood cultures are evident in 50 to 60 percent of cases.
       Management includes identifying the organism(s) and utilizing intravenous antibiotics. One would follow this with a course of oral antibiotics and immobilization of the affected limb. Indications for surgery include drainage of abscess, debridement of tissue and refractory patients.
       E. Osteosarcoma is the correct answer. While osteosarcoma represents only 0.2 percent of all malignancies, it is the most common primary malignant bone tumor. Osteosarcoma usually develops during adolescence and early adulthood, and affects more males than females. Approximately 80 percent of cases occur in patients who are less than 20 years old. However, there is a secondary peak incidence among patients 50 to 60 years old with a history of radiation therapy.
       The etiology of osteosarcoma is unknown. Predisposing conditions are Li-Fraumeni syndrome, retinoblastoma and radiotherapy. However, Paget’s disease is the most common condition leading to osteosarcoma. Osteosarcoma may arise anywhere on the body but 70 percent of lesions develop in the metaphysic of the distal femur, proximal tibia or proximal humerus.
       Osteosarcoma may present as a pathologic fracture. The most common presenting symptom is pain. It may be initially mild and intermittent but rapidly progresses in severity and duration, and is worse at night. Later symptoms may include swelling, a palpable mass and decreased range of motion.
       Since symptoms are vague, imaging is necessary for diagnosis. Radiographs typically demonstrate an extensive, poorly defined destructive bony lesion in a “sunburst” pattern, usually with an extraosseous component. Radionuclide bone scanning identifies the extent of the primary lesion and metastases (80 percent pulmonary, followed by bone). Complete blood count and chemistry panel are usually normal. Alkaline phosphotase and lactate dehydrogenase may be elevated. Magnetic resonance imaging of the lesion and bone biopsy of a mixed lytic and blastic lesion will help the staging diagnosis.
       Standard treatment includes preoperative chemotherapy for 11 weeks. Physicians use this to increase limb salvaging excisions by decreasing the soft tissue involvement. Surgeons may utilize limb sparing resection for patients with extremity sarcomas and no neurovascular involvement. Several weeks of postoperative chemotherapy may be necessary and one should tailor this to the patient’s response to preoperative chemotherapy and the histologic determination from biopsy. The five-year, disease-free survival rate is approximately 70 percent for patients with stage II osteosarcoma who undergo standard treatment.

       Dr. Livingston is an Instructor for the Hahnemann Physician Assistant Program in the College of Nursing and Health Professions at Drexel University in Philadelphia.

       Dr. Auth is the Program Director for the Hahnemann Physician Assistant Program in the College of Nursing and Health Professions at Drexel University in Philadelphia.