REVIEW

EVALUATION OF PEDIATRIC MUSCULOSKELETAL TUMORS Bülent Erol, Murat Bezer, Osman Güven Department of Orthopaedics and Traumatology,School of Medicine, Marmara University,Istanbul, Turkey

ABSTRACT A wide range of musculoskeletal tumors occurs in the pediatric population. Physicians should be aware of the clinical and radiographic manifestations of these tumors in order to provide timely specialist referrals so that early diagnosis and treatment can be achieved. Improvements in diagnosis and treatment have increased survival for many children with malignant musculoskeletal tumors.

Keywords: Pediatrics, Musculoskeletal tumors

PEDİATRİK MUSKÜLOSKELETAL TÜMÖRLER ÖZET Pediatrik popülasyonda geniş bir yelpazeyi içeren musküloskeletal tümörler görülebilir. Bu tümörlerin ilgili uzmanlara zamanında danışılabilmesi ve dolayısıyla erken tanı ve tedavinin sağlanabilmesi için, doktorların çocukluk çağı musküloskeletal tümörlerinin klinik ve radyografik bulguları hakkında bilgi sahibi olmaları gerekir. Tanı ve tedavideki ilerlemeler habis musküloskeletal tümörlü çocukların çoğunda sağkalım oranını arttırmıştır.

Anahtar Kelimeler: Pediatri, Musküloskeletal tümörler

INTRODUCTION and death, but also may allow for successful limb Pediatric musculoskeletal tumors are uncommon, salvage surgery rather than amputation of the and when they occur, are usually benign. Early limb. The primary bone and soft tissue tumors of detection of a malignant musculoskeletal tumor childhood can be classified based on their tissue may not only make the difference between life origin (Table I).

Table I: Classification of pediatric musculoskeletal tumors based on tissue of origin Bone tumors

Bone origin; osteoid osteoma, osteoblastoma, osteosarcoma Cartilaginous origin; osteochondroma, chondroblastoma, chondromyxoid fibroma, enchondroma, periosteal chondroma Fibrous origin; nonossifying fibroma, fibrous dysplasia, osteofibrous dysplasia, desmoplastic fibroma Miscellaneous; unicameral bone cyst, aneurysmal bone cyst, giant cell tumor Langerhans cell histiocytosis, Ewing sarcoma Musculoskeletal manifestations of leukemia Bone lymphomas Metastatic tumors; neuroblastoma, retinoblastoma, hepatoblastoma Soft tissue tumors Vascular tumors; hemangioma, vascular malformations Nerve origin; neurolemmoma, neurofibroma, malignant peripheral nerve sheath tumor Fibrous origin; fibromatosis, fibrosarcoma Muscular origin; rhabdomyosarcoma Miscellaneous; synovial sarcoma Primitive neuroectodermal tumors Ganglion and synovial cyst

Corresponding author: Bülent Erol Department of Orthopaedics and Traumatology Marmara Medical Journal 2004;17(3);140-145 The Hospital of University of Marmara Tophanelioglu Caddesi, No: 13/15 Altunizade/Istanbul E-mail: [email protected] Tel:+90 216 325 45 82 Fax: 216 325 45 82

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Marmara Medical Journal 2004;17(3);140-145 Bülent Erol, et al. Evaluation of Pediatric Musculoskeletal Tumors

EVALUATION Clinical evaluation

A thorough evaluation of the history of the patient and gait pattern of the patient. The size, and physical examination are the basis for consistency, and mobility of a mass should be determining the correct diagnosis and therapy. evaluated. For soft tissue masses, small (< 5cm), Children with a musculoskeletal tumor usually superficial, soft, and movable masses are usually, present with pain, mass, pathologic fracture, or but not always, benign. On the other hand, large incidental findings on radiographs (Table II). The (> 5cm), deep, firm, fixed, and tender masses raise physical examination should include suspicion of malignancy and are less commonly neurovascular examination of the affected benign. extremity, range of motion of the adjacent joint,

Table II: Clinical presentations of pediatric musculoskeletal tumors

1) Pain ▪Duration ▪ Localization ▪ Severity ▪ Character ▪ Relief and how obtained 2) Mass ▪ Duration ▪ Size ▪ Consistency ▪ Mobility 3) Pathologic fracture spectrum from microfractures to displaced fractures ▪ Prior symptoms and signs ▪ Mechanism of fracture ▪ Characteristics of fracture 4) Incidental radiographic findings ▪ Prior symptoms and signs ▪ Why radiograph obtained

Most musculoskeletal tumors occur more shows a race association; it is very prevalent in commonly in boys than in girls. The gender of the whites and is rarely seen in African-Americans. patient, however, usually does not play a The age of the patient is important in establishing significant role in formulating the differential a differential diagnosis, because certain tumors diagnosis. Ewing sarcoma is unusual because it tend to occur in certain age groups (Table III).

Table III: Peak age of common pediatric musculoskeletal tumors Age (years) Benign Malignant 0-5 Langerhans cell histiocytosis Fibrosarcoma Osteomyelitis Metastatic tumors Leukemia Ewing sarcoma ------5-10 Unicameral bone cyst Osteosarcoma Aneurysmal bone cyst Rhabdomyosarcoma Nonossifying fibroma Fibrous dysplasia Osteoid osteoma Langerhans cell histiocytosis ------10-20 Fibrous dysplasia Osteosarcoma Osteoid osteoma Ewing sarcoma Fibroma Chondrosarcoma Aneurysmal bone cyst Rhabdomyosarcoma Chondroblastoma Synovial cell sarcoma Osteofibrous dysplasia

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Marmara Medical Journal 2004;17(3);140-145 Bülent Erol, et al. Evaluation of Pediatric Musculoskeletal Tumors

Radiographic evaluation

After careful history and physical examination, typifies slow-growing, benign lesions, whereas looking at the imaging studies of the lesion is the moth-eaten (i.e., characterized by multiple, small, next step in the evaluation. Plain radiographs give often clustered lytic areas) and permeative (i.e., the most detailed information about skeletal characterized by ill-defined, very small oval lesions. Plain radiographs, at least in two views radiolucencies or lucent streaks) types of bone (anteroposterior and lateral), showing the entire destruction mark rapidly growing, infiltrating lesion are necessary. Thirty to 40% of a bone must tumors 2. The response of the bone to the be destroyed before changes can be seen in plain neoplastic process involves the response of the radiographs. It is often difficult to see soft tissue adjacent cortex and periosteum 3. The lesion may tumors and soft tissue extension from bony be contained by the cortex or “walled off” by neoplasms with plain radiographs. It is useful to dense sclerotic bone, implying a very slow- ask some questions when evaluating plain growing or static lesion, or it may destroy the radiographs of bony lesions: Where is the lesion cortex and form a soft tissue mass, mostly located in the bone? What is the lesion doing to indicating an aggressive neoplastic process. Like the bone? What is the bone doing to the lesion? the pattern of bone destruction, the pattern of What is the periosteal response 1 ? periosteal reaction is an indicator of the biologic activity of a lesion. Although no single periosteal The anatomic location of bony lesions should be response is unique for a given lesion, a continuous identified as epiphyseal, metaphyseal, or periosteal reaction indicates a long-standing diaphyseal, and central or eccentric (Table IV). (slow-growing) benign process. An interrupted The lesion may be destroying or replacing the periosteal reaction, on the other hand, is existing bone. Bone destruction can be described commonly seen in malignant tumors; in these as geographic, moth-eaten, and permeative (Fig. tumors, the periosteal reaction may appear in a 1). sunburst (“hair-on-end”) or onion-skin Although none of these features are (lamellated) pattern. A reactive periosteal cuff at pathognomonic for any specific neoplasm, the the periphery of the tumor, a Codman’s triangle, type of destruction may suggest a benign or a also may form (Fig. 2). malignant process. Geographic bone destruction

Fig 1: Different patterns of bone destruction Fig 2: Different patterns of periosteal reaction

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Marmara Medical Journal 2004;17(3);140-145 Bülent Erol, et al. Evaluation of Pediatric Musculoskeletal Tumors

Table IV: Common locations of pediatric bone tumors Epiphysis Pelvis Chondroblastoma Ewing sarcoma Brodie’s abscess of the epiphyses Osteosarcoma Giant cell tumor Osteochondroma Fibrous dysplasia Metastasis Metaphysis Fibrous dysplasia Any tumor Anterior elements of spine Diaphysis (FAHEL) Langerhans cell histiocytosis Fibrous dysplasia Leukemia Osteofibrous dysplasia Metastatic Langerhans cell histiocytosis Giant cell tumor Ewing sarcoma Posterior elements of spine Leukemia, lymphoma Aneurysmal bone cyst Occasional diaphyseal Osteoblastoma Osteoid osteoma Osteoid osteoma Unicameral bone cyst Rib Multiple Fibrous dysplasia Leukemia (metastasis) Langerhans cell histiocytosis Multiple hereditary exostoses Ewing sarcoma Langerhans cell histiocytosis Metastasis Polyostotic fibrous dysplasia Enchondromatosis

If the radiographs reveal a lesion that has a response to preoperative chemotherapy, and for potential for malignancy or do not confirm a long-term followup of most bone and soft tissue specific diagnosis, further staging studies are sarcomas. CT can demonstrate bone destruction indicated. A magnetic resonance imaging (MRI) and mineralization (calcifications or bone and a computed tomography (CT) scan will serve formation within the tumor), and is particularly as the best imaging to further evaluate the lesion. helpful for bone tumors involving axial skeleton MRI best demonstrates the soft tissue anatomy (i.e., pelvis, spine) (Fig.4). A total body and intramedullary extension of the tumor. The radionuclide bone scan will evaluate the biologic ability of MRI to produce images of the body in activity of the primary bone lesion and search for three planes (axial, sagittal, coronal) provides a other lesions within the skeletal system. It may be significant advantage in defining the extent of indicated to locate obscure lesions such as osteoid many tumors (Fig.3A-B) 4. MRI remains the osteoma or stress fracture. modality of choice for staging, for evaluating

Fig 3A-B: (A) The coronal T2-weighted image of the proximal leg shows an expansile lesion in the proximal fibula, replacing the bone marrow. Increased signal, representing edema is also seen in the muscles surrounding the mass (arrow). (B) The axial T2- weighted image demonstrates complete replacement of the marrow with a large soft tissue component surrounded by a thin layer of new bone formation. In addition, soft nodules (arrows) are seen outside the margin of bone formation. The diagnosis of this lesion is osteosarcoma.

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Fig 4: The axial computed tomography image of the pelvis demonstrates destructive lesions in the right sacral alae and a lytic lesion in the right ilium. The diagnosis of this lesion is Non-Hodgkin’s lymphoma of bone.

Staging and biopsy Staging of lesions that appear to be malignant is sarcoma and should be performed following required prior to biopsy. Staging includes a total completion of the radiographic staging and body bone scan, a CT scan of the chest, and a preoperative consultation with the oncologist, MRI of the primary lesion (Table V). Based on radiologist, pathologist, and surgeon. After these studies, a biopsy can be planned to confirm staging studies are completed, a differential the diagnosis. Biopsy should be the last step in the diagnosis can be formulated. evaluation of a patient with a bone or soft tissue

Table V: Current treatment principles of malignant bone tumors of childhood Staging of primary lesion and search for other lesions Magnetic resonance imaging of the primary site including the joint above and below Total body radionuclide bone scan; to search for bone metastases and skip lesions Computed tomography of the chest; to search for lung metastases Pediatric oncology consultation Incisional biopsy Intraoperative frozen section Bone marrow aspiration/biopsy for Ewing sarcoma Broviac placement for chemotherapy Preoperative neoadjuvant chemotherapy (usually multiagent chemotherapy) Repeat magnetic resonance imaging after chemotherapy and prior to definitive surgery Radiographic evaluation of the tumor response to chemotherapy (change in size of tumor, change in amount of tumor edema, involvement of neurovascular structures) Surgical planning Surgery; excision of the tumor with wide surgical margins Limb-salvage surgery; resection of the tumor with wide surgical margins and reconstruction. Currently, possible in most patients with extremity sarcoma Amputation Histologic examination of resection specimen Histologic evaluation of the tumor response to chemotherapy (> 90% tumor necrosis demonstrates good response) Verification of wide surgical margins Continued chemotherapy (adjuvant chemotherapy) after local control surgery Usually same protocol with neoadjuvant chemotherapy if tumor response to chemotherapy is good Followup Every 3 months first year, then 6 to 12 months intervals

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The best biopsy method for a musculoskeletal REFERENCES neoplasm depends on the differential diagnosis, the location of the neoplasm, and the ability of the 1. Enneking WF: Musculoskeletal tumor surgery. New York, Churchill Livingstone, 1983. pathologist to make a diagnosis on a sample of 2. Madewell JE, Ragsdale BD, Sweet DE: Radiologic and tissue. A well-planned biopsy provides an pathologic analysis of solitary bone lesions. Part I: accurate diagnosis and facilitates treatment. On Internal margins. Radiol Clin North Am 1981; 19: 715- the other hand, a poorly performed biopsy may 48. fail to provide a diagnosis and more importantly, 3. Ragsdale BD, Madewell JE, Sweet DE. Radiologic and pathologic analysis of solitary bone lesions. Part II: may have a negative impact on treatment options Periosteal reactions. Radiol Clin North Am 1981; 19: and/or survival. Needle aspiration may provide 749-83. adequate tissue for a histologic diagnosis; 4. Gillespy T III, Manfrini M, Ruggieri P, Spanier SS, however, many oncologic surgeons prefer an open Petterson H, Springfield DS. Staging of intraosseous extent of osteosarcoma: Correlation of preoperative CT incisional technique, which also provides and MR imaging with pathologic macroslides. sufficient tissue for the multiple studies often Radiology 1988; 167: 765-67. needed, including newer molecular diagnostics. 5. Simon MA, Biermann JS. Biopsy of bone and soft tissue Incisional biopsy involves removing only a lesions. J Bone Joint Surg 1993; 75A: 616-21. portion of the tumor without contaminating the 6. Erol B, Dormans JP, States L, Pawel B. Tumors. In: Cramer KE, ed. Orthopaedic Surgery Essentials- surrounding soft tissue structures. A biopsy is best Pediatrics. Philadelphia: Lippincott Williams & Wilkins, accomplished at the institution that would perform 2004: 250-270. the definitive surgery if it becomes necessary 5,6.

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