Musculoskeletal Oncology and Pathology

2


Musculoskeletal Oncology and Pathology


Amanda Fantry, Alan Schiller, Robin N. Kamal, and Richard M. Terek


I. Workup and Staging


A. Workup for Bone Lesion (Fig. 2.1)


1. Biopsy should be performed by treating surgeon at a sarcoma center.


2. Common reason for referral to orthopaedic oncologist is incomplete excision of an unknown sarcoma. Always refer suspicious lesions to surgeon at a sarcoma center.


3. Regardless of a known primary, a new lesion without a previous diagnosis of metastatic bone disease should be biopsied.


B. Workup for Soft Tissue Sarcoma


See Soft Tissue Tumors section, below.


C. Staging



Stage is the most important prognostic factor for survival.


1. Enneking staging for malignant bone tumors (Table 2.1)


2. Enneking staging for benign bone tumors


• Stage 1: latent [nonossifying fibroma (NOF), enchondroma]


• Stage 2: active [aneurysmal bone cyst (ABC)/unicameral bone cyst (UBC), chondroblastoma]


• Stage 3: aggressive (giant cell tumor of bone)


3. American Joint Committee on Cancer (AJCC) staging for malignant bone tumors (Table 2.2)


• Stage is most important prognostic factor for survival.


• Presence or absence of metastatic disease has most significant impact on long-term survival of a primary bone sarcoma.


4. AJCC staging for soft tissue sarcomas (Table 2.3)


D. Treatment


1. Goal is to remove lesion with minimal risk of recurrence.



Table 2.1 Enneking System for Staging Malignant Bone Tumors

























Stage


Description


IA


Low grade, intracompartmental (no soft tissue involvement)


IB


Low grade, extracompartmental (penetration of cortex)


IIA


High grade, intracompartmental


IIB


High grade, extracompartmental


IIIA


Metastasis, intracompartmental


III B


Metastasis, extracompartmental


Note: Low grade: well or moderately differentiated. High grade: poorly differentiated.


• Local control versus amputation: must be equal in outcomes and remaining limb must be functional


• Criteria for amputation:


a. Cannot obtain adequate surgical margin


b. Unacceptably high morbidity


c. Nonfunctional resulting limb


d. Continued tumor growth


e. Tumor encases major neurovascular bundles (relative)


Sciatic nerve involvement does not necessitate amputation, as balanced palsy can be managed with orthoses.


2. Surgical margins (Fig. 2.2)


• Intralesional: within tumor


• Marginal: through reactive zone around tumor


• Wide: cuff of normal tissue surrounding


• Radical: removal of entire compartment


3. Adjuvant therapy


• Chemotherapy: multiagent chemotherapy for osteogenic sarcoma and Ewing’s sarcoma with improved survival and limb salvage


a. Mechanism of chemotherapy: induction of apoptosis


b. For both osteogenic sarcoma and Ewing’s sarcoma, preoperative chemotherapy followed by restaging, surgery, and then additional chemotherapy


c. Chemotherapy controversial for soft tissue sarcomas


d. Common chemotherapy agents (Table 2.4)


• Radiation: used for Ewing’s sarcoma, lymphoma, myeloma, metastatic bone disease, soft tissue sarcoma


a. Preoperative versus postoperative radiation risks and benefits for sarcoma


Table 2.2 American Joint Committee on Cancer (AJCC) System for Staging Malignant Bone Tumors




























Stage


Description


IA


Low grade, < 8 cm


IB


Low grade, > 8 cm


IIA


High grade, < 8 cm


IIB


High grade, > 8 cm


III


Discontinuous tumor; skip lesions (any grade)


IVA


Metastasis to lungs (any grade)


IVB


Metastasis to regional lymph nodes, or another distant site (any grade)


Note: Low grade: well or moderately differentiated. High grade: poorly differentiated.


Table 2.3 American Joint Committee on Cancer (AJCC) System for Staging Soft Tissue Sarcomas

























Stage


Description


IA


Low grade, < 5 cm


IB


Low grade, > 5 cm


IIA


High grade, < 5 cm


IIB


High grade, > 5 cm


III


Metastasis to regional lymph nodes (any grade)


IV


Distant metastasis (any grade)


Note: Tumors are staged as T1 (< 5 cm in greatest dimension) or T2 (> 5 cm in greatest dimension). Tumor further qualified as T1a/T2a (superficial tumor) or T1b/T2b (subfascial tumor).


Preoperative radiation


♦ Benefits: requires lower dose than postoperative (50 Gy), decreased surrounding edema, capsule formation around tumor


♦ Risks: delayed wound healing, wound complication (30%), infection


Postoperative radiation


♦ Risks: fibrosis, fractures, joint stiffness, wound healing complications, higher dose of radiation required (66 Gy) to larger treatment field


b. Risk factors for pathologic fracture postradiotherapy: female, higher dose of radiation (> 60 Gy), age > 60 years, periosteal stripping during tumor excision




c. Radiation-associated sarcoma usually occurs > 5 years after therapy in the field of radiation treatment, with different histology than the initial lesion.


E. Chromosomal Translocations (Table 2.5)


Table 2.5 Common Tumor Chromosomal Translocations

























Tumor


Translocation/gene


Ewing’s sarcoma


t (11;22). EWS, FLI1


Clear cell sarcoma


t (12;22). EWS, ATF1.


Myxoid liposarcoma


t (12;16). CHOP, TLS


Alveolar rhabdomyosarcoma


t (2;13). PAX3


Synovial sarcoma


t (X;18). SYT, SSX


Aneurysmal bone cyst


USP6


II. Bone


A. Benign Bone Producing Tumors


1. Osteoid osteoma (Figs. 2.3, 2.4, 2.5)





• Demographic: young patients (ages 5–30 years), male-to-female ratio = 2:1


• Presentation: increasing pain, worse at night


• Relieved by nonsteroidal anti-inflammatory drugs (NSAIDs)/aspirin



• Tumor releases prostaglandins, so NSAIDs uniquely relieve pain in this tumor.


• Locations: proximal femur, tibial diaphysis, posterior elements of spine


a. Can cause scoliosis: lesion at center of concavity of curve


• Imaging: computed tomography (CT) superior to magnetic resonance imaging (MRI); nidus of bone surrounded by reactive bone


a. Hot on bone scan


b. Nidus always < 1–1.5 cm


• Histology: thin osteoid seams, immature trabeculae; fibrovascular rim surrounding nidus


• Treatment: radiofrequency ablation (RFA), observation/NSAIDs, or open excision


a. RFA contraindicated for lesions in digits secondary to risk of thermal necrosis and damage to neurovascular bundles.


• Prognosis: usually self limited to 3–5 years


2. Osteoblastoma (Figs. 2.6, 2.7, 2.8, 2.9)


• Demographic: young (ages 10–30 years), male-to-female ratio = 2:1


• > 2 cm



• “Big brother” lesion to osteoid osteoma


• Presentation: dull, aching pain not relieved by NSAIDs


• Locations: posterior elements of spine, proximal humerus, femur, tibia, hip, mandible


a. May be blastic or lytic






• Imaging: radiolucent lesion, > 2 cm in size, typically two thirds are cortically based, well marginated; hot on bone scan


• Differential: osteosarcoma, ABC, osteoid osteoma, osteomyelitis


• Histology: similar to osteoid osteoma but less organized: irregular osteoid with fibrovascular stroma and giant cells



• Presence of normal osteoblasts producing osteoid differentiates osteoblastoma from osteosarcoma where malignant cells produce osteoid.



• Treatment: curettage and bone grafting


3. Myositis ossificans (Figs. 2.10, 2.11, 2.12)


• Reactive process typically caused by trauma, characterized by proliferation of fibroblasts, cartilage, bone within muscle.


• Demographic: ages 15–35 years, males > females


• Presentation: pain, swelling, decreased range of motion, increasing in size over several months


• Locations: muscles surrounding diaphysis of long bones (quadriceps, brachialis, gluteal muscles)


• Imaging: peripheral mineralization with central lucent area, not attached to bone; may initially be only periosteal reaction


a. Differential diagnosis: extraskeletal or parosteal osteosarcoma



• Myositis ossificans: mineralizes from outside in with mature bone initially at periphery of lesion; opposite of osteosarcoma, which mineralizes from inside out


• Myositis ossificans (MO): mature from outside inwards


• Histology: woven bone in zonal pattern with mature bone at periphery and immature fibrous tissue at center; may be confused with osteosarcoma





• Treatment: observation, repeat radiographs; may excise when lesion is mature (typically 6–12 months)


4. Melorheostosis (Fig. 2.13)


• Rare disorder of new periosteal bone formation on surface of multiple bones


• Demographic: discovered at age < 40 years


• Presentation: significant pain, decreased range of motion (ROM)


• Location: long bones, feet


• Imaging: “dripping candle wax” with wavy appearance, can involve joint


• Treatment: can excise hyperostotic areas to improve ROM or observe if asymptomatic


B. Benign Reactive Lesions of Bone


1. Aneurysmal bone cyst (Table 2.6, Figs. 2.14, 2.15, 2.16)


• Benign, locally aggressive lesion of bone


• May be primary or in association with other tumors [giant cell tumor (GCT), chondroblastoma, chondromyxoid fibroma, fibrous dysplasia (FD)]


• Genetics: upregulation of ubiquitin-specific protease (USP)-6


• Demographic: age < 20 years


• Presentation: pain, swelling


• Location: distal femur, proximal tibia, pelvis, posterior elements of spine (25%)


• Imaging: eccentric, lytic, expansile area of destruction in metaphysis, typically with rim of new bone surrounding lesion


a. Expands wider than physis


b. MRI: fluid–fluid levels


c. Differential: UBC, telangiectatic osteosarcoma


• Histology: cavernous blood-filled spaces, no endothelial lining, + giant cells, septations



• Must evaluate histology to differentiate from telangiectatic osteosarcoma


• Treatment: curettage, bone grafting


• Risk of recurrence


• Factors leading to increased risk of recurrence: young age, open physes, high stage, positive margin at time of excision


2. Unicameral bone cyst (Table 2.6, Figs. 2.17 and 2.18)


• Demographic: age < 20 years


• Presentation: pain, usually after fracture from minor trauma



Table 2.6 Aneurysmal Bone Cyst Versus Unicameral Bone Cyst
























 


Aneurysmal Bone Cyst


Unicameral Bone Cyst


Presentation


Pain, swelling


Pathologic fracture


Location


Distal femur, proximal tibia, pelvis, posterior elements of spine


Proximal humerus, proximal femur


Imaging


Metaphyseal lytic lesion, wider than physis
MRI: fluid–fluid levels


Metaphyseal, lytic lesion, less than width of physis
Falling leaf sign


Treatment


Curettage, bone graft


Methylprednisolone
Curettage/bone graft (proximal femur)






• UBC commonly discovered after proximal humerus fracture with throwing injury.


• Location: proximal humerus most common, then proximal femur, distal tibia, tarsal bones of feet


• Imaging: lytic lesion with symmetric cystic expansion, thinning of cortices, bone no wider than physis


a. Falling leaf sign: pathognomonic for UBC (scattered, horizontal bone wisps in cystic cavity)


b. Active (cyst abuts physeal plate) versus latent (normal bone intervenes)


• Histology: thin, fibrous lining (fibrous tissue, giants cells, hemosiderin)


• Treatment: observation, curettage/bone graft, aspiration and injection: methylprednisolone acetate, bone marrow, synthetic bone graft. Only aspirate and inject after pathologic fracture has healed. There is a risk of recurrence with any treatment.


C. Malignant Bone Producing Tumors


1. High-grade intramedullary osteosarcoma (Figs. 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25)


• High-grade, intermediate-grade, low-grade variants


a. High-grade variants: osteoblastic, fibroblastic [differentiate from malignant fibrous histiocytoma (MFH)], chondroblastic (differentiate from chondrosarcoma), telangiectatic (differentiate from ABC), small cell (differentiate from Ewing’s sarcoma), giant cell rich (differentiate from giant cell tumor of bone)


b. No difference in prognosis between high-grade variants


c. All grades may be intramedullary or surface lesions.




• Demographic: bimodal; affects young patients (10–20 years) and older patients (Paget’s osteosarcoma); male-to-female ratio = 1.5:1


• Genetics: associated with retinoblastoma (Rb) and p53 mutations (Li-Fraumeni syndrome)


• Risks: prior radiation, Paget’s disease


• Presentation: pain, mass


• Location: distal femur > proximal tibia > proximal humerus


• Staging: most common stage: IIB (75%): high grade, extracompartmental


a. 10–20% with metastases (stage III)


• Imaging: mixed appearance (both lytic and blastic) originating in medullary canal or classic “sunburst” appearance, Codman triangle


a. MRI: extension into soft tissue, skip metastases (2–3%)


b. Differential: osteomyelitis, Ewing’s sarcoma


• Histology: malignant spindle cells forming osteoid in existing trabeculae with mitotic figures, pleomorphism; may have giant cells or cartilage


• Workup: plain films (lytic or blastic), CT chest, MRI of entire bone (skip metastases), laboratories


• Treatment: Neoadjuvant chemotherapy (Adriamycin/doxorubicin, methotrexate, cis-platinum, Ifofsamide), wide surgical resection, adjuvant chemo



• Chemotherapy drugs induce apoptosis between G1 and S phases of cell cycle.


• Survival: 60–70%


a. Poor prognostic factors: age < 14 years, high alkaline phosphatase, tumor volume > 200 mL, two-drug chemotherapy, inadequate margins, poor histological response to radiation, +p-glycoprotein


b. Metastasis: lungs most commonly, then bone


c. Presence of distant bone metastasis has poor prognosis, equivalent to lung metastasis








2. Telangiectatic osteosarcoma (Figs. 2.26 and 2.27)


• Rare variant of osteosarcoma containing cavernous blood-filled spaces


• Demographics: ages 10–30 years


• Location: knee, proximal femur, proximal humerus—same as ABC


• Imaging: destructive, lytic lesion; MRI demonstrates fluid–fluid lesions


a. Differential: ABC





• Histology: few cellular elements, blood filled (“bag of blood”); septa with high-grade sarcoma, pleomorphic cells, and multiple mitoses


• Treatment: neoadjuvant chemotherapy, wide resection, adjuvant chemotherapy


3. Parosteal osteosarcoma


• Low-grade surface osteosarcoma; can rarely transform to dedifferentiated high-grade lesion


• Genetics: may have supernumerary ring chromosomes


• Demographic: ages 20–30 years, more common in females


• Presentation: painless or dull, chronic pain and swelling


• Location: metaphysis of posterior distal femur (80%), proximal tibia, proximal humerus


• Imaging: ossified, lobulated mass arising from cortex with no cortical or medullary invasion (75%) and central density, “stuck-on appearance”; 25% with intramedullary invasion




• On imaging, parosteal osteosarcoma appears to be a bony mass stuck on the femur.


a. “String sign”: cleavage plane between portions tumor and cortex of bone


b. Hot on bone scan


c. Differential: myositis ossificans, osteochondroma


• Histology: regularly arranged trabeculae with atypical spindle cells and bland stroma invading skeletal muscle at periphery of tumor


a. Dedifferentiated high-grade parosteal osteosarcoma seen with area of highly cellular spindle cells



• Treatment: wide resection, no chemotherapy if low grade (low-grade parosteal osteosarcoma does not require chemotherapy)


a. If high grade, neoadjuvant chemotherapy, wide surgical excision, adjuvant chemotherapy






4. Periosteal osteosarcoma (Figs. 2.28, 2.29, 2.30)


• Demographic: ages 10–20 years


• Presentation: pain


• Location: diaphysis of long bones (femur/tibia)


• Imaging: sunburst lesion overlying cortical depression


• Histology: typically high grade, chondroblastic matrix, osteoid


• Treatment: neoadjuvant chemotherapy, wide resection, adjuvant chemotherapy


D. Benign Cartilage Producing Lesions


1. Periosteal chondroma


• Benign cartilage tumor on surface of bone


• Location: 50% proximal humerus, femur


• Imaging: eccentric, cortically based lesion eroding the underlying cortex, producing a saucer-like defect


a. Differential diagnosis: osteochondroma (but without stalk) or myositis ossificans


• Histology: chondroid matrix and lacunae with multiple chondrocytes


• Treatment: marginal excision including underlying cortex


2. Enchondroma (Figs. 2.31, 2.32, 2.33, 2.34)


• Benign cartilage lesion in medullary cavity





• Demographic: age > 20 years


• Presentation: incidental, painless; may present as pathologic fracture, such as in the metacarpal/phalanx


• Location: diaphysis and metaphysis in hand, metaphyseal proximal humerus, distal femur



• Most common benign skeletal lesion in hand


• Imaging: well-defined, lucent, medullary lesions with stippled/mottled calcified appearance, popcorn calcification


a. Can expand and thin cortex (common)


b. Differential: low-grade chondrosarcoma, bone infarct (“smoke up chimney”)


c. Present in 3% of knee MRIs



• Histology: mature hyaline cartilage lobules separated by normal marrow, hypocellular


• Treatment: observation with serial radiographs (most common)


a. Curettage and graft only after pathologic fracture has healed or prior to a fracture occurring if noted incidentally on X-ray (in the hand)


b. Enchondromas of the hand generally treated surgically after fracture to prevent repeat fractures (Fig. 2.35)


• Syndromes


a. Ollier’s: multiple enchondromas, particularly unilateral, 30% lifetime risk of malignancy


b. Maffucci’s: multiple enchondromas, associated soft tissue hemangiomas, increased risk of visceral malignancies, 100% risk of transformation to chondrosarcoma


3. Osteochondroma (Figs. 2.36, 2.37, 2.38)


• Benign surface lesions (35% benign lesions), typically associated with tendon insertions


• May be single or multiple (multiple hereditary exostosis)


• Demographic: ages 10–30 years


• Presentation: incidental or painful (if overlying bursae, irritating tendon, joint capsule)


• Location: metaphyseal—knee, proximal femur, proximal humerus


• Imaging: surface lesion with cortex of the lesion and underlying cortex continuous with medullary cavity


a. Sessile versus pedunculated


b. Cartilage cap grows away from physis


c. Stops growing with skeletal maturity


d. Obtain MRI or CT to evaluate thickness of cartilaginous cap and presence of soft tissue mass if suspicious for chondrosarcoma in an adult with an enlarging lesion.



CT scan will demonstrate that the lesion is in continuity with the medullary cavity.


• Histology: similar to that of enchondroma


a. If cartilage cap > 2 cm, raise concern about conversion to chondrosarcoma


b. Hyaline cartilage cap with cortical and trabecular bone comprising stalk, endochondral ossification


• Treatment: observation (asymptomatic) versus excision (soft tissue irritation)


a. New change in pain should be worked up to address concern about conversion to chondrosarcoma (order an MRI).






• Syndrome


a. Multiple hereditary exostosis (Fig. 2.39)


Gene: EXT1, EXT2, EXT3, autosomal dominant


♦ Mutation affects prehypertrophic chondrocytes of the growth plate


5–10% develop secondary chondrosarcoma, EXT1 > EXT2


Primarily sessile lesions large in size


May cause progressive skeletal deformities including short stature, limb-length discrepancies, valgus deformity or knee and ankle, asymmetry of pectoral and pelvic girdle, bowing of radius with ulnar deviation, subluxation of radiocapitellar joint


Jun 28, 2018 | Posted by in ORTHOPEDIC | Comments Off on Musculoskeletal Oncology and Pathology
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