Mark D. Murphey, MD, FACR

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Fundamental Concepts of Musculoskeletal Neoplasm: CT and MRI Mark D.

of primary skeletal neoplasms is best determined by radiographs But.

Soft Tissue Neoplasm Radiographs only occasionally helpful CT and more often MRI can be tissue specific But.

Causes of Tissue-Specific Diagnosis on CT/MRI in Evaluating Soft Tissue Masses 20% 50% cases (My opinion will rise to 70% 90%) Contrast resolution, MRI>CT Multiplanar imaging, MRI>CT Location

1 Fundamental Concepts of Musculoskeletal Neoplasm: CT and MRI Mark D. Murphey, MD, FACR Important Features in Evaluation of Musculoskeletal Masses Differential diagnosis Preoperative assessment and staging Osseous Neoplasm [Figures 1 & 2] Differential diagnosis of primary skeletal neoplasms is best determined by radiographs But... MRI and/or CT are vital for delineating and staging osseous neoplasms prior to surgery Figure 1 Enchondroma vs chondrosarcoma on radiograph due to chondroid mineralization (arrow). Soft Tissue Neoplasm Radiographs only occasionally helpful CT and more often MRI can be tissue specific But.. MRI and/or CT are again vital for defining extent, staging, and preoperative evaluation. Clinical and radiologic characteristic often limit differential diagnosis. Causes of Tissue-Specific Diagnosis on CT/MRI in Evaluating Soft Tissue Masses 20% 50% cases (My opinion will rise to 70% 90%) Contrast resolution, MRI>CT Multiplanar imaging, MRI>CT Location of mass Growth pattern and history Soft Tissue Masses Diagnosed with Imaging Alone [Figures 3 & 4] Lipomatous lesions Angiomatous lesions Neurogenic tumors Elastofibroma and fibromatosis Pigmented villonodular synovitis (PVNS) and ganglion Figure 2 A, B & C Chondrosarcoma (same patient as previous radiograph) on MR and gross specimen due to associated cortical destruction and soft tissue mass (arrows). Figure 3 A & B Lipoma (coronal T1- and T2-weighted images) isointense to fat on all pulse sequences (*) with single thin septation (arrows). 947

Enneking Staging of Musculoskeletal Tumors: Malignant [Figures 6-8] Stage 1 (G 1 ): low-grade, welldifferentiated, few mitoses; tend to recur

many mitoses; high incidence of metastases [Figure 7] 2A intraosseous/intracompartmental 2B extraosseous/extracompartmental Stage 3:

patient with neurofibromatosis type 1 (note second small subcutaneous neurofibroma - curved arrow).

clinical course Stage 2 active growth; symptomatic, remains intracapsular but may be deforming Stage 3 aggressive local growth; may penetrate

2 Enneking Staging of Musculoskeletal Tumors: Malignant [Figures 6-8] Stage 1 (G 1 ): low-grade, welldifferentiated, few mitoses; tend to recur locally [Figure 6] 1A intraosseous/intracompartmental 1B extraosseous/extracompartmental Stage 2 (G 2 ): high grade, poorly differentiated, many mitoses; high incidence of metastases [Figure 7] 2A intraosseous/intracompartmental 2B extraosseous/extracompartmental Stage 3: metastases; regional or remote (visceral, lymphatic, or osseous) [Figure 8] Figure 4 A & B Malignant peripheral nerve sheath tumor (arrow) in patient with neurofibromatosis type 1 (note second small subcutaneous neurofibroma - curved arrow). Enneking Staging of Musculoskeletal Tumors: Benign (G 0 ) [Figure 5] Stage 1 unchanged or healing lesion; well-encapsulated; indolent clinical course Stage 2 active growth; symptomatic, remains intracapsular but may be deforming Stage 3 aggressive local growth; may penetrate cortex or compartment; higher recurrence rate Figure 6 A, B, C & D Enneking staging system. Figure 5 A to F Enneking staging system (benign). Figure 7 A, B, C & D Enneking staging system (malignant). 948

N0 M0 G3 Any T N1 M0 Any G IV Any T Any N M1 Any G Staging for Sarcoma of Soft Tissue: TNM Definitions Primary tumor (T) TX: primary tumor cannot be assessed T0: no evidence of primary tumor T1:

3 Figure 8 Stage III: metastases; regional or remote (visceral, lymphatic, or osseous). CT chest PET/CT. American Joint Committee on Cancer Staging for Soft Tissue Sarcoma (2010) Stage T N M G IA T1a, T1b N0 M0 G1, GX IB T2a, T2b N0 M0 G1, GX IIA T1a, T1b N0 M0 G2, G3 IIB T2a, T2b N0 M0 G2 III T2a, T2b N0 M0 G3 Any T N1 M0 Any G IV Any T Any N M1 Any G Staging for Sarcoma of Soft Tissue: TNM Definitions Primary tumor (T) TX: primary tumor cannot be assessed T0: no evidence of primary tumor T1: tumor 5 cm or less in greatest dimension T1a: superficial tumor T1b: deep tumor T2: tumor more than 5 cm in greatest dimension T2a: superficial tumor T2b: deep tumor Regional lymph nodes (N) NX: regional lymph nodes cannot be assessed N0: no regional lymph node metastasis N1: regional lymph node metastasis Distant metastasis (M) M0: no distant metastasis M1: distant metastasis Histologic grade (G) GX: grade cannot be assessed G1: grade 1 (FNCLCC* score 2 or 3) G2: grade 2 (FNCLCC* score 4 or 5) G3: grade 3 (FNCLCC* score 6 8) *FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer). American Joint Committee on Cancer Staging for Primary Malignant Tumors of Bone (2010) Stage T N M G IA T1 N0 M0 G1, G2 (low grade), GX IB T2, T3 N0 M0 G1, G2 (low grade), GX IIA T1 N0 M0 G3, G4 (high grade) IIB T2 N0 M0 G3, G4 (high grade) III T3 N0 M0 G3, G4 IVA Any T N0 M1a Any G IVB Any T N1 Any M Any G Any T Any N M1b Any G Staging for Primary Malignant Tumors of Bone: Definitions of TNM Primary tumor (T) TX: primary tumor cannot be assessed T0: no evidence of primary tumor T1: tumor 8 cm or less in greatest dimension T2: tumor more than 8 cm in greatest dimension T3: discontinuous tumors in the primary bone site Regional lymph nodes (N) NX: regional lymph nodes cannot assessed N0: no regional lymph node metastasis N1: regional lymph node metastasis Distant metastasis (M) M0: no distant metastasis M1: distant metastasis M1a: lung M1b: other distant sites Histologic grade (G) GX: grade cannot be assessed G1: well-differentiated (low grade) G2: moderately differentiated (low grade) G3: poorly differentiated G4: undifferentiated Musculoskeletal Tumors: Surgical/ Pathological Zones [Figure 9] Figure 9 Staging of Musculoskeletal Neoplasm has Implication on Surgical Treatment [Figures 9 & 10] Intracapsular excision Marginal excision Wide excision Radical resection Amputation 949

involvement Neurovascular involvement Joint involvement Intramedullary/Soft Tissue Extent Musculoskeletal Neoplasm [Figures 11 & 12] MRI superior to CT Superior

Done in institution of definitive procedure Give orthopod anatomic landmarks Ewing sarcoma following chemotherapy with prominent reactive zone (*) around the

MRI May Overestimate Musculoskeletal Neoplasm Extent Because of Surrounding Edema (Reactive Zone) Musculoskeletal Neoplasm Lesion Matrix Evaluation I.

4 Figure 10 Limb salvage procedures. Figure 12 A & B Important Factors on Imaging for Staging Musculoskeletal Neoplasm Intramedullary extent Extent of soft tissue component Lesion matrix Cortical involvement Neurovascular involvement Joint involvement Intramedullary/Soft Tissue Extent Musculoskeletal Neoplasm [Figures 11 & 12] MRI superior to CT Superior contrast resolution Multiplanar imaging capability Regional metastases-osseous/lymph node Can be helpful to direct biopsy Always perform in consultation with orthopod Done in institution of definitive procedure Give orthopod anatomic landmarks Ewing sarcoma following chemotherapy with prominent reactive zone (*) around the low-signal intensity pseudocapsule (arrows). MRI May Overestimate Musculoskeletal Neoplasm Extent Because of Surrounding Edema (Reactive Zone) Musculoskeletal Neoplasm Lesion Matrix Evaluation I. Mineralized: CT>MRI A. Chondroid - rings and arcs [Figure 13] B. Osteoid cloud-like, ivory-like C. Other calcification - phlebolith, synovial sarcoma II. Nonmineralized: MRI>CT A. Fluid, necrosis, hemorrhage [Figure 14] B. Fat C. Soft tissue nonspecific Figure 11 A, B & C Osteosarcoma with spread across physeal plate (arrows) not seen on radiograph. 950 Figure 13 A & B Chondrosarcoma with chondroid matrix mineralization not seen on radiographs or MRI.

Figure 14 A & B Aneurysmal bone cyst with fluid levels on T2-weighted MRI (left image) reflecting cystic spaces on gross specimen (right image).

Improved contrast resolution Multiplanar MR images and MRA findings of stenosis 9% in soft tissue sarcomas; 3.

Soft tissue mass encase vessels definite involvement Musculoskeletal Neoplasm: Cortical Involvement [Figure 15] CT>MRI (my opinion) MRI=CT

& B Osteosarcoma with displaced but nonencased neurovascular bundle (arrows).

5 Figure 14 A & B Aneurysmal bone cyst with fluid levels on T2-weighted MRI (left image) reflecting cystic spaces on gross specimen (right image). Musculoskeletal Neoplasm: Neurovascular Involvement [Figures 16 to 20] Vital information for surgical resection MRI>CT (postcontrast if use CT-CTA) Improved contrast resolution Multiplanar MR images and MRA findings of stenosis 9% in soft tissue sarcomas; 3.3% of primary bone tumors Axial plane usually best Look for intact fat plane Best on T1-weighted images If fat plane lost cannot exclude involvement Soft tissue mass encase vessels definite involvement Musculoskeletal Neoplasm: Cortical Involvement [Figure 15] CT>MRI (my opinion) MRI=CT (literature) CT better spatial resolution Important in differential diagnosis of osseous lesions Important for surgical resection/staging Figure 16 A & B Osteosarcoma with displaced but nonencased neurovascular bundle (arrows). Figure 17 Pictorial representation without neurovascular encasement by Figure 15 A & B Osteoid osteoma (arrow) and lesion was difficult to detect on MRI (right image) compared to CT (left image). Figure 18 Pictorial representation with possible neurovascular encasement by 951

Figure 19 Pictorial representation with neurovascular encasement by Figure 21 Pictorial representation without joint involvement by Figure 20 A & B

(left image) and gross specimen (right image).

intensity vs tumor high signal On CT tendon/ligament similar to tumor attenuation Also multiplanar imaging of MR helpful Musculoskeletal Neoplasm: Joint

superior to CT multiplanar imaging Coronal or sagittal plane best Three routes of spread into joint Through bone/cartilage (transarticular) Around joint

6 Figure 19 Pictorial representation with neurovascular encasement by Figure 21 Pictorial representation without joint involvement by Figure 20 A & B Osteosarcoma with encased neurovascular bundle (arrows) illustrated by the tumor replacing normal fat seen about vessels on proton density MR images (left image) and gross specimen (right image). Musculoskeletal Neoplasm: Ligament and Tendon Involvement Important for surgical reconstruction MRI>CT; best on T2-weighted image Tendons/ligaments low intensity vs tumor high signal On CT tendon/ligament similar to tumor attenuation Also multiplanar imaging of MR helpful Musculoskeletal Neoplasm: Joint Involvement [Figures 21 to 24] Dramatically changes surgery from: Limb salvage; intraarticular resection Extraarticular limb salvage/amputation MRI superior to CT multiplanar imaging Coronal or sagittal plane best Three routes of spread into joint Through bone/cartilage (transarticular) Around joint margin (periarticular) Along ligaments/tendons, or hematogenous Presence of joint effusion suggestive Absence of joint effusion excludes Figure 22 A & B Pictorial representation with joint involvement by Figure 23 A & B Pictorial representation with joint involvement by 952

Imaging Characteristics Suggesting Benign Soft Tissue Mass Small size Well marginated Homogeneous signal intensity No neurovascular encasement Enhancement pattern dynamic MRI (late, slow,

dynamic MRI (early, rapid, peripheral) Figure 24 A & B Osteosarcoma invading the knee joint with effusion (arrows) and tumor (*) along ACL (arrowheads) on sagittal T2-weighted MR and gross specimen.

matrix 0% 92% Cortical involvement 7% 72% Neurovascular involv.

7 Imaging Characteristics Suggesting Benign Soft Tissue Mass Small size Well marginated Homogeneous signal intensity No neurovascular encasement Enhancement pattern dynamic MRI (late, slow, diffuse/none) Imaging Characteristics Suggesting Malignant Soft Tissue Mass Large size Poor margin definition with edema Heterogeneous signal intensity Neurovascular encasement Enhancement pattern dynamic MRI (early, rapid, peripheral) Figure 24 A & B Osteosarcoma invading the knee joint with effusion (arrows) and tumor (*) along ACL (arrowheads) on sagittal T2-weighted MR and gross specimen. Overall Delineation of Musculoskeletal Masses: All Features (56 Cases, N=189) MRI>CT 60% MRI=CT 16% CT>MRI 24% MRI (N=56) CT (N=56) Intramedullary extent 81% 5% Soft tissue mass 89% 0% Mineralized matrix 0% 92% Cortical involvement 7% 72% Neurovascular involv. 78% 0% Joint involvement 73% 3% CT Indications Cannot perform MRI Matrix producing neoplasm not adequately evaluated on radiographs Unusual location Ribs, sternoclavicular region, scapula Abdominal/chest wall Fibula Distinction of Benign vs Malignant Soft Tissue by MRI Totty Radiology. 1986;160: (n=32) Sundaram MRI. 1988;6: (n=53) Kransdorf AJR. 1989;153: (n=112) Berquist AJR. 1990;155: (n=95) Crim Radiology. 1992;185: (n=83) Soft Tissue Masses Misinterpreted on MRI: Benign vs Malignant [Figures 25 to 27] Diabetic muscle ischemia Hematoma Fibromatosis Reactive lymph node, abscess, bursitis Myositis ossificans Synovial sarcoma Myxoid liposarcoma Figure 25 Myositis ossificans with aggressive appearance on coronal T2-weighted MRI image. 953

Figure 26 Myositis ossificans with early rim of ossification (arrow) on CT image (same patient as previous MRI).

Fluid collections: subfascial, lymphocele/seroma Postoperative Imaging MRI/CT: Abnormal [Figures 28 & 29] New bone destruction/marrow replacement Any recurrent or residual nodular region Tumor until

Figure 27 A & B Synovial sarcoma with homogeneous appearance and defined margins suggesting an indolent lesion. Intrinsically the lesion has nonspecific features of a solid mass.

8 Figure 26 Myositis ossificans with early rim of ossification (arrow) on CT image (same patient as previous MRI). Postoperative Imaging MRI/CT: Normal MRI>CT: improved contrast resolution Comparison to baseline study (first 2 3 months) Recognize normal changes Postop edema/myositis Radiation necrosis Muscle flap Fluid collections: subfascial, lymphocele/seroma Postoperative Imaging MRI/CT: Abnormal [Figures 28 & 29] New bone destruction/marrow replacement Any recurrent or residual nodular region Tumor until proven otherwise Texture sign Regardless of signal characteristics unless low all sequences representing fibrosis or fluid collection (homogeneous low T1/high T2) Contrast studies can be helpful Figure 27 A & B Synovial sarcoma with homogeneous appearance and defined margins suggesting an indolent lesion. Intrinsically the lesion has nonspecific features of a solid mass. The general consensus is that in an individual case, MRI is not accurate enough to predict whether a nonspecific solid soft tissue mass is benign or malignant. Musculoskeletal Neoplasm Follow-Up Preoperative: post-therapy Postoperative: recurrence MRI superior to CT Posttherapy Imaging Increasing ossification osteosarcoma, Ewing sarcoma radiographs/ct Change in size and extent MRI Increasing peritumoral edema Tumor necrosis and hemorrhage >90% required for pathologic good response Dynamic MR, US, PET/CT Figure 28 A, B, C & D Postoperative lymphocele/seroma (*) in patient with previous malignant fibrous histiocytoma resection with homogeneous low- (T1) and high- (T2) signal intensity as expected for a fluid collection. Postoperative Imaging: Radiographs Comparison to previous studies Findings of recurrence New bone destruction New areas matrix formation 954

Figure 29 A to E Recurrent malignant fibrous histiocytoma (arrows) adjacent to residual lymphocele/seroma (*) (same patient as previous MRI but 2 years later).

Figure 30 A, B & C Myxoid malignant fibrous histiocytoma with enhancing peripheral solid nodular tissue (arrows).

Musculoskeletal Neoplasm Use of MRI with Gadolinium [Figure 30] Increase lesion conspicuity (usually not needed) Tumor, edema, inflammation, and fibrosis all enhance Help differentiate

9 Figure 29 A to E Recurrent malignant fibrous histiocytoma (arrows) adjacent to residual lymphocele/seroma (*) (same patient as previous MRI but 2 years later). Note the tumor staining on angiogram (right image - arrowhead) versus vessels draped about fluid collection (curved arrow). Figure 30 A, B & C Myxoid malignant fibrous histiocytoma with enhancing peripheral solid nodular tissue (arrows). These enhancing areas represent viable tumor regions and biopsy should be directed toward these regions as they harbor diagnostic tissue and were only detected after contrast administration. Musculoskeletal Neoplasm Use of MRI with Gadolinium [Figure 30] Increase lesion conspicuity (usually not needed) Tumor, edema, inflammation, and fibrosis all enhance Help differentiate cyst/hemorrhage Helpful in postop cases to show nodular enhancement with recurrence Vanel/Bloem: dynamic subtraction MRI early enhancement of recurrent tumor and response to therapy Musculoskeletal Masses Imaging Goals Delineate precise extent of lesion Diagnosis/exclude metastases Give most likely tissue type and differential diagnosis References 1. Berquist TH. Magnetic resonance imaging of musculoskeletal neoplasms. Clin Orthop Relat Res. 1989;244: Review. 2. Sundaram M, McGuire MH. Computed tomography or magnetic resonance for evaluating the solitary tumor or tumor-like lesion of bone? Skeletal Radiol. 1988;17: Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res. 1986;204: Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980;153: Stacy SG, Mahal RS, Peabody TD. Staging of bone tumors: a review with illustrative examples. Am J Roentgenol. 2006;186: Murphy WA Jr. Imaging bone tumors in the 1990s. Cancer. 1991:15;67: Review. 7. Tateishi U, Yamaguchi U, Seki K, et al. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology. 2007;245: Gartner L, Pearce CJ, Saifuddin A. The role of the plain radiograph in the characterization of soft tissue tumours. Skeletal Radiol. 2009;38: Wu JS, Hochman MG. Soft-tissue tumors and tumorlike lesions: A systematic imaging approach. Radiology. 2009;253:

Introduction to Musculoskeletal Tumors. James C. Wittig, MD Orthopedic Oncologist Sarcoma Surgeon

Introduction to Musculoskeletal Tumors James C. Wittig, MD Orthopedic Oncologist Sarcoma Surgeon www.tumorsurgery.org Definitions Primary Bone / Soft tissue tumors Mesenchymally derived tumors (Mesodermal)