Pediatric Annals

Pitfalls in Diagnosis: Pediatric Musculoskeletal Tumors

Ernest U Conrad, III, MD

Abstract

The diagnosis of pediatric musculoskeletal tumors is challenging, not because of the subtlety of symptoms, but because of the subtle difference between their symptoms and those of the more common traumatic or inflammatory conditions seen in children. Although great advances have been made in the treatment of musculoskeletal malignancies, early diagnosis remains the key to success. ' A delayed diagnosis may result in pulmonary metastases, cutting patient survival by 50%. An understanding of the incidence and basic clinical and radiographic characteristics of these tumors will enhance the pediatrician's ability to make an appropriate initial evaluation.

Figure IA shows the x-ray of a 13-year-old female who presented with knee pain that was diagnosed at different times as a horseback riding injury, patellofemoral joint pain, and then as a torn meniscus. She was seen in follow-up 3 months later with a repeat x-ray (Figure IB) and subsequent bone scan (Figure IC) demonstrating a metaphyseal osteosarcoma. A more careful history and physical examination would have allowed the physician to make the diagnosis at the initial clinic visit. The initial management of this particular patient typifies the usual presentation of a musculoskeletal tumor.

INCIDENCE

The most common malignancies in children are leukemia (20%), central nervous system tumors (15%), lymphoma (10%), neuroblastoma (7%), soft tissue tumors (5%). Wilms' tumors (4%). and bony tumors (3.4%).2 Primary malignancies of soft tissue, bone, and cartilage are referred to as sarcomas, a term coined in the late 19th century to describe tumors with a "fish flesh" consistency. Soft tissue sarcomas of the extremities in children most commonly originate in skeletal muscle (rhabdomyosarcoma), interfascial planes (undifferentiated sarcomas) or adjacent to joints (synovial sarcoma). The two common primary bone tumors in children are osteosarcoma (osteogenic sarcoma) and Ewing's sarcoma. Other pediatric malignancies such as lymphoma or neuroblastoma also may present as "bone" tumors and need to be distinguished appropriately, as the treatment varies significantly according to the diagnosis.

Osteosarcoma is the most common pediatric bone malignancy with approximately 2,000 new cases in the United States per year. However, the typical orthopedic surgeon will see only one osteosarcoma in a lifetime, and a school-aged child is several hundred times more likely to have a fracture rather than an osteosarcoma. The majority of sarcomas in children occur in adolescence (12-18 years) with an incidence (3-4/100,000) several times higher than that of the younger children. Benign bone tumors (osteoid osteoma, chondroblastoma, osteochondroma) also occur commonly in adolescence. The predisposition for neoplasms in this age group may be explained by the growth spurt between the ages of 12 to 14 years. Similarly, the rapid growth in the distal femur also may explain the high incidence of tumors in the metaphysis of the distal femur, where 37% of the growth of the lower extremity occurs.

SUMMARY

In general, the 5 -year survival for patients with most types of sarcomas has doubled since the 1970s; improved chemotherapy, surgery, radiographic, and pathologic techniques all have contributed to this accomplishment. The 5-year survival for patients with osteosarcoma, like most sarcomas, is approximately 60% when the disease is treated with appropriate chemotherapy, l surgery5 or radiation therapy. ' The details of treatment are complex and many controversies remain. The initial workup, biopsy, chemotherapy, and surgery should be delivered by a center with experience in the treatment of sarcomas.

1. Simun MA: Current concepts review. Causes of increased surviv-.il of patients with osteosarcoma: Current controversies. J Bone; Joint Surg 1984: 66A:306-310.

2. Putnam It, Cohen A), Constine LS: Pediatric solid tumors, in Rubin P (ed): Clinica Oncologyt ed 6, American Cancer Society, 1983, p 393.

3. Huvos AG: Osteogenic sarcomi, in…

The diagnosis of pediatric musculoskeletal tumors is challenging, not because of the subtlety of symptoms, but because of the subtle difference between their symptoms and those of the more common traumatic or inflammatory conditions seen in children. Although great advances have been made in the treatment of musculoskeletal malignancies, early diagnosis remains the key to success. ' A delayed diagnosis may result in pulmonary metastases, cutting patient survival by 50%. An understanding of the incidence and basic clinical and radiographic characteristics of these tumors will enhance the pediatrician's ability to make an appropriate initial evaluation.

Figure IA shows the x-ray of a 13-year-old female who presented with knee pain that was diagnosed at different times as a horseback riding injury, patellofemoral joint pain, and then as a torn meniscus. She was seen in follow-up 3 months later with a repeat x-ray (Figure IB) and subsequent bone scan (Figure IC) demonstrating a metaphyseal osteosarcoma. A more careful history and physical examination would have allowed the physician to make the diagnosis at the initial clinic visit. The initial management of this particular patient typifies the usual presentation of a musculoskeletal tumor.

INCIDENCE

The most common malignancies in children are leukemia (20%), central nervous system tumors (15%), lymphoma (10%), neuroblastoma (7%), soft tissue tumors (5%). Wilms' tumors (4%). and bony tumors (3.4%).2 Primary malignancies of soft tissue, bone, and cartilage are referred to as sarcomas, a term coined in the late 19th century to describe tumors with a "fish flesh" consistency. Soft tissue sarcomas of the extremities in children most commonly originate in skeletal muscle (rhabdomyosarcoma), interfascial planes (undifferentiated sarcomas) or adjacent to joints (synovial sarcoma). The two common primary bone tumors in children are osteosarcoma (osteogenic sarcoma) and Ewing's sarcoma. Other pediatric malignancies such as lymphoma or neuroblastoma also may present as "bone" tumors and need to be distinguished appropriately, as the treatment varies significantly according to the diagnosis.

Osteosarcoma is the most common pediatric bone malignancy with approximately 2,000 new cases in the United States per year. However, the typical orthopedic surgeon will see only one osteosarcoma in a lifetime, and a school-aged child is several hundred times more likely to have a fracture rather than an osteosarcoma. The majority of sarcomas in children occur in adolescence (12-18 years) with an incidence (3-4/100,000) several times higher than that of the younger children. Benign bone tumors (osteoid osteoma, chondroblastoma, osteochondroma) also occur commonly in adolescence. The predisposition for neoplasms in this age group may be explained by the growth spurt between the ages of 12 to 14 years. Similarly, the rapid growth in the distal femur also may explain the high incidence of tumors in the metaphysis of the distal femur, where 37% of the growth of the lower extremity occurs.

Figure IA. Presenting radiograph in a 13-year-old female with a "horseback riding injury" was diagnosed as a torn meniscus. IB. Repeat radiograph of patient in Figure IA taken 3 months later with a lesion (osteosarcoma) in the medial metaphysis.IC. Bone scan of the same patient that is typical of an aggressive metaphyseal malignancy

Figure IA. Presenting radiograph in a 13-year-old female with a "horseback riding injury" was diagnosed as a torn meniscus. IB. Repeat radiograph of patient in Figure IA taken 3 months later with a lesion (osteosarcoma) in the medial metaphysis.

IC. Bone scan of the same patient that is typical of an aggressive metaphyseal malignancy

CLINICAL PRESENTATION

Osteosarcoma, the most common pediatric primary malignancy of bone, represents the typical intraosseous malignancy. It occurs most commonly in the distal femur of a teenager, and shows a slight male tendency (1.5:1, male:female ratio). J The typical patient has a 3-month history of knee pain that is worse at night and unrelated to activity. Although trauma is reported in 25% to 30% of patients presenting with osteosarcoma, it has not been found to be a causative factor, but rather represents an incidental finding. The most helpful characteristics of the history in considering bone malignancy are a child's age and the true nature of the pain. Teenagers in particular should be evaluated carefully, especially when their pain has persisted without an obvious etiology.

Night pain in a teenager is a symptom that should raise a red flag in the initial evaluation, as it frequently signals the intraosseous pain of a bone tumor. Acute hematogenous osteomyelitis also may produce intraosseous pain, but is far more likely to occur in a child younger than 10 years of age. Fractures may also result in bone pain, but are usually associated with an obvious injury and radiographic findings. "Growing pains" are a poorly defined problem that may occur around the knee with prominent pain at night, but typically affect children younger than 10 years. Awareness of the age tendencies of these different diagnoses is helpful in the clinical assessment of musculoskeletal pain (Figures 2 and 3).

Determining whether a patient has intraarticular or intraosseous symptoms is a challenge, and the history and physical exam should focus on that distinction. Distinguishing real joint pain from referred joint pain produced by a tumor proximal to the knee joint is a common problem that needs to be kept in mind in the evaluation of knee pain. Osteosarcoma, like most sarcomas, rarely involves the knee joint. Thus, true joint pain or tenderness is far more consistent with an intraarticular problem (eg, synovitis, tendonitis, ligament or meniscal injury, osteochondritis) and not a malignancy. In addition, joint problems, unlike intraosseous lesions, usually worsen with joint motion and sports activities, whereas intraosseous tumors are less sensitive to joint motion. Often such overuse or activity related symptoms will improve with the restriction of activity. An intraarticular injury usually presents with a bloody joint effusion and strongly suggests either an osteochondral fracture or other joint injury.

Figure 2. Pediatric musculoskeletal tumors versus age.

Figure 2. Pediatric musculoskeletal tumors versus age.

The physical examination of the knee should evalu' ate joint swelling or soft tissue masses, joint motion and stability, the exact location of pain and tenderness, and neurovascular status and strength. The patients gait also should be evaluated for weakness, stiffness, or a limp.

Although a true knee effusion rarely indicates a neoplasm, a soft tissue mass frequently does. The mass of a soft tissue sarcoma is typically non tender, firm, larger than 5 cm, and located deep in the muscle below the subcutaneous and superficial fascia. Tender soft tissue masses usually reflect an inflammatory or nonmalignant soft tissue process. In contrast, tender intraosseous tumors may well indicate a malignancy, and thus both a clinical and radiographic distinction between bone and soft tissue processes needs to be made. Most soft tissue sarcomas have the consistency of a firm or fibrous lesion, firmer than fat or normal muscle. Cystic or fluid filled masses around the knee joint usually represent a ganglion type of cyst, a meniscal cyst that communicates with the knee joint and meniscus, or a soft tissue abscess. Aspiration of a cyst in the clinic, yielding fluid for culture and cytology, can avoid the need for further anxiety and workup. Care should be taken on the physical exam to determine whether a lesion is truly cystic prior to any attempt at aspiration.

Intraosseous tumors, such as osteosarcoma, almost always present with bony tenderness and rarely extend into the adjacent joint. The exact location of tenderness is a critical finding and care should be taken to differentiate between bony tenderness in the metaphysis versus joint line or intraarticular tenderness (Figure 4). Musculoskeletal tumors may present with mild joint stiffness because of muscle involvement, but rarely demonstrate instability. The neurovascular exam is usually normal with bony or soft tissue tumors. If a patient presents with nerve or vascular changes, they usually have a lesion intrinsic to that structure. The secondary involvement of a nerve or vessel is usually a very late finding.

Laboratory studies are of limited value in the diagnosis of most sarcomas, however, serum alkaline phosphatase levels frequently are elevated with osteosarcoma and should be obtained if that is the possible diagnosis. Erythrocyte sedimentation rates are elevated with both tumors and infections and although the test is sensitive, the results are nonspecific in distinguishing tumors from infection. Sarcomas rarely metastasize to the liver and hepatic enzymes are of limited use in the initial evaluation for sarcomas, but may reflect other tumors or diseases. In general, the initial evaluation of children with a possible bone tumor should include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), and alkaline phosphatase levels. The CBC and ESR are helpful in screening for possible infections or bone marrow neoplasms.

RADIOGRAPHIC STUDIES

All patients with significant musculoskeletal symptoms should have an appropriate radiograph of the extremity involved. Although the subtleties of the radiographic differential diagonsis for various intraosseous tumors is challenging, distinguishing a benign from a malignant lesion is usually relatively straightforward. Most radiographs can be interpreted by evaluating the lesion's location, peripheral margin, and density. The most important characteristic of an intraosseous malignancy is its "margin" or interrace with normal bone. Intraosseous malignancies usually have a growth rate that is much greater than that of normal bone; thus, the surrounding normal bone does not have the opportunity to develop a relative sclerotic margin.

In contrast, benign tumors will demonstrate a reactive, sclerotic margin because their growth is slow enough to allow the surrounding bone to react to it. Consequently, the most important characteristic of an intraosseous tumor is its peripheral margin with normal bone. An example of a benign tumor is a nonossifying fibroma, which has a typical sclerotic scalloped border. Ewing's sarcoma and other "round cell" or small "blue cell" malignant tumors invade bone so quickly that they appear to percolate through the bone with what is sometimes called a permeative pattern (Figure 5). Ewing's sarcoma is the only tumor that combines this permeative diaphyseal pattern with a large soft tissue mass. Other permeati ve round cell or small blue cell tumots of bone in children include neuroblastoma, lymphoma, leukemia, and histiocytosis, (eosinophilic granuloma), which can closely mimic one another.

Figure 3. Pediatric musculoskeletal diagnoses versus age.

Figure 3. Pediatric musculoskeletal diagnoses versus age.

The initial radiographic workup of musculoskeletal tumors should include a radiograph of the extremity. If concern persists after the initial workup and radiographs, the patient should eithet be followed closely with repeat radiographs or evaluated further with a bone scan (bony lesions) or magnetic resonance imagery (MRl) (soft tissue lesions). Once there is strong evidence for a sarcoma, the patient should be evaluated for possible pulmonary metastases with a radiograph of the chest (anterior- posterior/lateral) and computerized tomography (CT) scan of the lung. The complete evaluation of an extremity sarcoma includes a total body bone scan with close up views of the involved extremity. A total body bone scan is essential for ruling out multiple skeletal lesions and is an excellent screening study in patients with difficult or worrisome initial radiographs. The workup for the primary lesion should include an MRI or CT scan of the involved extremity.4 The information from the radiographic studies may alter the biopsy technique or demonstrate the need for additional studies (bone matrow aspirate or biopsy) at the time of the biopsy. These studies should be carried out prior to the biopsy and are repeated during treatment to evaluate the response to chemotherapy before and after definitive surgery.

Figure 4. Diagramatic demonstration of the typical metaphyseal location of an osteosarcoma.

Figure 4. Diagramatic demonstration of the typical metaphyseal location of an osteosarcoma.

Figure 8. Radiograph of a "permeative" lesion of the distai the a that is poorty marginated and associated with periosteal reaction. These are typical findings of a small "blue cell" tumor. This is a 5year-old boy with an intraosseous lymphoma.

Figure 8. Radiograph of a "permeative" lesion of the distai the a that is poorty marginated and associated with periosteal reaction. These are typical findings of a small "blue cell" tumor. This is a 5year-old boy with an intraosseous lymphoma.

SUMMARY

In general, the 5 -year survival for patients with most types of sarcomas has doubled since the 1970s; improved chemotherapy, surgery, radiographic, and pathologic techniques all have contributed to this accomplishment. The 5-year survival for patients with osteosarcoma, like most sarcomas, is approximately 60% when the disease is treated with appropriate chemotherapy, l surgery5 or radiation therapy. ' The details of treatment are complex and many controversies remain. The initial workup, biopsy, chemotherapy, and surgery should be delivered by a center with experience in the treatment of sarcomas.

REFERENCES

1. Simun MA: Current concepts review. Causes of increased surviv-.il of patients with osteosarcoma: Current controversies. J Bone; Joint Surg 1984: 66A:306-310.

2. Putnam It, Cohen A), Constine LS: Pediatric solid tumors, in Rubin P (ed): Clinica Oncologyt ed 6, American Cancer Society, 1983, p 393.

3. Huvos AG: Osteogenic sarcomi, in Huvoe AG (ed): Bone Tumors. Philadelphia. WB Saunders. 1979. PP 47-93.

4. Ennelirq: WF: MusciduskeSeud Tiomir Surgtrx. Osseous Liskms Originating in Bone. NewYork. Churchill-Livingstone. 1983. pp 1021-112).

5. Simon MA, Aschliman MS, Thomas N, et al: Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg 1986; 68A:1331-1337.

10.3928/0090-4481-19890101-08

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