AAOS musculoskeletal tumors and diseses 2017.pdf

Musculoskeletal Tumors and Diseases  Figure 1a Figure 1b Figure 1c Figure 1d CLINICAL SITUATION FOR QUESTIONS 1 THROUGH 4 Figures 1a through 1d are the MR images and biopsy specimen of a 68-year-old man...

Musculoskeletal Tumors and Diseases  Figure 1a Figure 1b Figure 1c Figure 1d CLINICAL SITUATION FOR QUESTIONS 1 THROUGH 4 Figures 1a through 1d are the MR images and biopsy specimen of a 68-year-old man who has a painless mass in his leg. He believes the mass may have been present for several years, and it is more apparent now because he recently lost weight after changing his diet and exercise patterns. He also recently experienced modest trauma to his leg while moving furniture. Question 1 of 100 What is the diagnosis? 1- Dedifferentiated liposarcoma 2- Intramuscular lipoma 3- Atypical lipomatous tumor 4- Myositis ossificans PREFERRED RESPONSE: 1- Dedifferentiated liposarcoma Question 2 of 100 The role of surgery in this condition is best described as 1- marginal resection is performed with a low likelihood of recurrence. 2- best performed after the lesion becomes “cold” on a bone scan. 3- wide resection as an indication for curative treatment. 4- not indicated. PREFERRED RESPONSE: 3- wide resection as an indication for curative treatment. Question 3 of 100 The role of radiation treatment for this lesion is 1- proven to decrease local recurrence. 2- associated with a high rate of post-radiation sarcoma development. 3- contra-indicated for benign pathology. 4- associated with a higher risk of wound complications if given post-operatively. PREFERRED RESPONSE: 1- proven to decrease local recurrence. Question 4 of 100 Chemotherapy for this condition is 1- contraindicated when pathology is benign. 2- associated with a high risk for subsequent myelodysplastic syndrome. 3- provides dramatic survival benefits. 4- provides modest survival benefits. PREFERRED RESPONSE: 4- provides modest survival benefits. DISCUSSION This patient has a dedifferentiated liposarcoma within a preexisting atypical lipomatous tumor. The imaging demonstrates a large fatty mass with increased internal septations proximally (the atypical lipomatous tumor) and a solid enhancing mass distally (the dedifferentiated portion). A biopsy reveals a high-grade liposarcoma. The other diagnostic responses do not reflect sarcomatous transformation of the lesion. Surgical treatment of a high-grade sarcoma involves wide surgical resection. Radiation decreases local recurrence but does not clearly influence overall survival. The role of chemotherapy in high-grade soft-tissue sarcomas remains investigational; there is a modest (8%-15%) associated improvement in overall survival. Intramuscular lipomas and atypical lipomatous tumors are treated with marginal resection alone. Radiation therapy for soft-tissue sarcomas may be given before or after surgery. When administered before surgery, patients have a higher wound complication rate but better long-term function attributable to lower rates of lymphedema, fibrosis, and contractures. Figure 5a Figure 5b Question 5 of 100 Figures 5a and 5b are the radiographs of a 74-year-old man with poorly differentiated squamous cell carcinoma of the lung. He has had an uneventful recovery after undergoing a wedge resection of his left upper lobe 6 months ago. He is experiencing left lateral knee pain, and a whole-body positron emission tomography/CT scan shows no avid area other than the lateral left distal femur. This patient has needed to use a wheelchair for 3 weeks because of his pain. You discuss these treatment options: aggressive curettage, local adjuvant treatment, cementation, and prophylactic fixation vs distal femoral resection and megaprosthesis total knee arthroplasty reconstruction. You should tell him that 1- his overall disease-free survival will be no different with either procedure. 2- fixation failure may occur with cementation and prophylactic fixation but not with megaprosthesis reconstruction. 3- infection rates with megaprosthesis reconstruction are lower than with cementation after aggressive curettage. 4- radiation will not be necessary after undergoing either procedure. PREFERRED RESPONSE: 1- his overall disease-free survival will be no different with either procedure. DISCUSSION Distal femoral megaprosthetic reconstruction after tumor resection is a reliable oncologic procedure, but 5-year implant survival is as low as 74% with an approximate 8% deep infection rate. The amputation rate is as high as 8% because of infection or recurrence, and there is an overall 18% revision rate. More than 10% of distal femoral megaprosthetic reconstructions are performed to address metastatic disease. Fixation failure and infection may occur with either procedure. Radiation may not be recommended after a megaprosthesis reconstruction unless margins are not free of tumor. Either operation may be equally successful in returning patients to functional activities. Overall disease-free survival is related to the aggressiveness of the tumor and not the type of reconstruction performed. Figure 6a Figure 6b  Figure 6c Figure 6d Figure 6e Figure 6f Question 6 of 100 Figures 6a through 6d are the radiographs and T1-weighted sagittal and fat-saturated axial MR images of an otherwise healthy 56-year-old man who has anterior knee pain and intermittent swelling after sustaining a noncontact twisting injury. Low-power and high-power hematoxylin and eosin stained histologic specimens are shown in Figures 6e and 6f. Based on the history, radiographs, CT scan, MR imaging, and histologic findings, what is the most likely diagnosis? 1- Localized pigmented villonodular synovitis (PVNS) 2- Synovial hemangioma 3- Synovial chondromatosis 4- Biphasic synovial sarcoma PREFERRED RESPONSE: 2- Synovial hemangioma DISCUSSION The lesion in the posterior intercondylar knee notch is a benign synovial hemangioma. Intralesional calcifications, classically associated with hemangiomas, are frequently not identified on plain radiographs. The MR imaging reveals a hypervascular lesion with multiple filling defects, with hyperintensity on T2-weighted images and low-to- intermediate signal intensity on T1-weighted images. Histologically, vascular lakes within fine capillaries with a synovium on the surface of the lesion are characteristic of this condition. Many patients with synovial hemangioma have pain, swelling, stiffness, or mechanical symptoms. The correlation of symptoms with the hemangioma for this patient is unclear because there was recent trauma and a concurrent meniscus tear. Simultaneous treatment of both potential sources of pain is typically recommended. As with PVNS, the disease can be localized or diffuse. Surgical excision, either open or arthroscopic, is the recommended treatment. PVNS is the most common intra-articular tumor, but hypointensity in either the diffuse or localized type is characteristic in both T1- and T2-weighted images. Synovial sarcoma, although often found close to a joint, is not characteristically found within a joint. Figure 7a Figure 7b  Figure 7c Figure 7d Question 7 of 100 Figures 7a through 7d are the radiograph, MR images, and biopsy specimen of a 35-year-old man who has a painful, slowly enlarging knee mass. Which chromosomal translocation is characteristic of this pathology? 1- t(11;22) 2- t(9;22) 3- t(x;18) 4- t(12;16) PREFERRED RESPONSE: 3- t(x;18) DISCUSSION Synovial sarcoma is a soft-tissue sarcoma that usually occurs in young adults. Synovial sarcoma often causes pain, unlike most soft-tissue sarcomas, which generally do not cause pain. Imaging characteristics include soft-tissue calcifications on plain radiographs and a heterogeneous mass that is generally isointense to muscle on T1-weighted images and hyperintense to muscle on T2-weighted images. There are biphasic and monophasic types of synovial sarcoma. The biphasic type, which is depicted here, has both spindle cell and epithelial components and will stain for both vimentin and cytokeratin. More than 90% of patients with synovial sarcoma have a characteristic genetic translocation of t(X;18), which results in the fusion protein SS18-SSX. This translocation can be stained for use of florescence in situ hybridization technology. t(11;12) is seen in Ewing sarcoma. T(9;22) is seen in extraskeletal myxoid chondrosarcoma. t(12;16) is seen in myxoid liposarcoma. Question 8 of 100 A 45-year-old woman has a painless thigh mass that is larger than 5 cm. What is the best next step? 1- Percutaneous biopsy 2- Positron emission tomography (PET)/CT scan 3- Excisional biopsy 4- MRI of the thigh with gadolinium PREFERRED RESPONSE: 4- MRI of the thigh with gadolinium DISCUSSION Masses exceeding 5 cm in size and any deep mass should be evaluated with MRI prior to biopsy or excision to ensure the most viable tissue is sampled and to minimize morbidity and complications from an improperly placed biopsy site. Examinations are unreliable when attempting to determine if a mass is a simple lipoma, and any large or deep mass should be considered a sarcoma until proven otherwise. PET/CT is a staging examination to evaluate for metastatic or multifocal disease. These are expensive tests that should not be ordered prior to MR imaging of the primary lesion. For patients that are unable to obtain an MRI, CT of the mass is the preferred imaging modality. Figure 9a Figure 9b  Figure 9c Figure 9d CLINICAL SITUATION FOR QUESTIONS 9 THROUGH 11 Figures 9a through 9d are the anteroposterior and lateral radiographs, CT scan, and technetium bone scan of a 12- year-old boy who has experienced 7 months of pain in his lower leg. The pain limits his ability to participate in sports and he is having difficulty sleeping. He is afebrile, and laboratory study findings including an erythrocyte sedimentation rate, C-reactive protein, and complete blood count are within normal limits. Question 9 of 100 What is the most likely diagnosis? 1- Osteomyelitis 2- Osteoid osteoma 3- Stress fracture 4- Adamantinoma PREFERRED RESPONSE: 2- Osteoid osteoma Question 10 of 100 The most appropriate treatment of this lesion involves 1- radiofrequency ablation (RFA). 2- wide resection and hemicortical allograft reconstruction. 3- prophylactic internal fixation followed by radiation. 4- local debridement and an infectious disease consultation. PREFERRED RESPONSE: 1- radiofrequency ablation (RFA). Question 11 of 100 If this lesion occurred in the spine, which features would most likely be present? 1- Syrinx and paralysis 2- Spondylolisthesis and radiculopathy 3- Epidural abscess and fever 4- Scoliosis and paraspinal pain PREFERRED RESPONSE: 4- Scoliosis and paraspinal pain DISCUSSION The images and clinical history support a diagnosis of osteoid osteoma, which most commonly occurs in adolescence. Although these lesions can be seen in any bone, they are usually located in the femur and tibia. The significant inflammatory response to this tumor is secondary to high levels of prostaglandin production. Characteristic night pain is relieved with nonsteroidal anti-inflammatory drugs (NSAIDs) or by aspirin. Radiographic images show thickened bone and a small central nidus. Thin-cut CT scan is the imaging of choice to visualize the nidus. A bone scan is associated with uptake but is not specific. Treatment options include expectant management with NSAIDs and observation under the premise that these lesions eventually burn out. Contemporary treatment involves RFA. Historically, these lesions were treated with en bloc resection; however, this technique has largely fallen out of favor because of the high efficacy and comparative low morbidity associated with RFA. When an osteoid osteoma occurs in the spine, it is located in the posterior elements, and paraspinal pain and scoliosis often are present.  Figure 12a Figure 12b Question 12 of 100 Figures 12a and 12b are a recent radiograph and a whole-body bone scan of an 81-year-old man who has hip pain and difficulty walking. His medical history is significant for obesity, hypertension, chronic kidney disease, and coronary artery disease. An examination demonstrates moderate tenderness with passive range of motion of the left hip and an inability to actively flex the left hip against gravity. What is the best next step? 1- Dynamic hip screw 2- Long cephalomedullary nail 3- Staging studies 4- Toe-touch weight-bearing activity for 6 weeks PREFERRED RESPONSE: 3- Staging studies DISCUSSION This patient has no known history of active malignancy. The radiograph shows a lesser trochanteric avulsion fracture (a fracture routinely associated with an underlying neoplasm). The bone scan reveals no other bone lesions. The femur fracture is statistically most likely to occur because of metastatic disease, but, without other evidence of metastasis, a primary bone sarcoma is possible, and biopsy is recommended before surgical fixation. Observation of this fracture, which is pathognomonic for neoplastic disease, is strongly discouraged. Figure 13a Figure 13b Question 13 of 100 Figures 13a and 13b are the radiographs of a 57-year-old man who is seen in the emergency department. He has been experiencing left thigh pain for 2 month. Four years ago he underwent laparoscopic nephrectomy and states that he has been disease free since the resection (although he has not seen a doctor in 2 years). The pathogenesis of osteolysis in renal cell carcinoma metastatic to bone includes secretion of parathyroid hormone-related peptide (PTHrP), transforming growth factor-B (TGF-B), and vascular endothelial growth factor (VEGF), which directly cause overexpression receptor activation of nuclear factor kB ligand (RANKL) on which cells? 1- Osteoblasts 2- Osteoclasts 3- Osteoclast precursors 4- Both osteoclast precursors and the mature osteoclast PREFERRED RESPONSE: 1- Osteoblasts DISCUSSION Tumor cells in renal cell carcinoma interact with the bone microenvironment to drive bone destruction and tumor growth by secreting factors such as PTHrP, TGF-B, and VEGF. These factors stimulate the host osteoblast, causing overexpression of RANKL, which in turn causes bone resorption through stimulation of osteoclasts. RANKL expression is upregulated in many types of metastatic cancer to bone, and blocking the RANK/RANKL interaction prevents progression of metastases. Other actions of RANKL include triggering the migration of human tumor cells that express RANK. RANK and RANKL are expressed in metastatic renal cell carcinoma, and their presence strongly signifies potential recurrence. The use of denosumab, which binds and inactivates RANKL, has its basis in these findings in renal cell carcinoma. Figure 14a Figure 14b Figure 14c Question 14 of 100 Figures 14a through 14c are the MR images of a 72-year-old man who has had a slow-growing asymptomatic mass in his thigh for more than 5 years. Cytogenetic testing on the mass reveals a ring chromosome and MDM2 expression with no 12;16 translocation. What is the most likely diagnosis? 1- Myxoid liposarcoma 2- High-grade pleomorphic liposarcoma 3- Atypical lipomatous tumor 4- Intramuscular lipoma PREFERRED RESPONSE: 3- Atypical lipomatous tumor DISCUSSION This slowly growing mass has lipomatous features on MRI with a fat signal noted on T1 and T2 fat-suppressed images. Some thin striations seen on MRI may suggest an atypical lipomatous tumor. The molecular changes confirm that this is not a simple lipoma. High-grade sarcomas are generally rapidly growing and typically do not have the significant amount of largely homogenous fat signal as seen on this MRI. The negative result of a 12;16 translocation makes the diagnosis of myxoid liposarcoma unlikely. Atypical lipomas typically have a ring chromosome and express MDM2 but do not have the 12;16 translocation, as demonstrated in this patient. Atypical lipomas are synonymous with well-differentiated liposarcomas and pose risk for local recurrence but do not pose significant risk for metastatic spread. Figure 15a Figure 15b Figure 15c Question 15 of 100 Figures 15a through 15c are the radiograph and MR images of a 16-year-old girl who experienced posterior knee pain after a dance recital 3 weeks ago; the pain resolved 1 week ago with ibuprofen use. What is the most appropriate treatment for this patient? 1- Image-guided core needle biopsy 2- Clinical observation and serial radiographs 3- Tc-99 whole-body bone scan 4- CT scan with sagittal and coronal reconstructions PREFERRED RESPONSE: 2- Clinical observation and serial radiographs DISCUSSION The images reveal a small reactive-type lesion in the posteromedial aspect of the distal femur consistent with an avulsive cortical irregularity. Also referred to as a cortical desmoid, periosteal desmoid, or “tug lesion,” this lesion is seen most commonly in young adolescents, with a slight preponderance in boys, with one-third occurring bilaterally. It is thought to be related to repeated microtrauma from pulling of the adductor magnus or medial gastrocnemius on their respective periosteal attachment sites. Proper treatment involves recognition of this benign disorder without further workup. Often best seen on an oblique radiograph, the lack of soft-tissue mass or bone destruction leads to the benign diagnosis. Serial radiographs typically show complete resolution by age 20. Figure 16a Figure 16b Figure 16c Question 16 of 100 Figures 16a through 16c are the radiograph, MR image, and biopsy specimen of a 12-year-old boy who injured his leg during a soccer game. Assuming other staging study findings are negative, what is the Musculoskeletal Tumor Society (MSTS) stage of this lesion? 1- IA 2- IIA 3- IB 4- IIB PREFERRED RESPONSE: 4- IIB DISCUSSION The MSTS staging system assigns progressively higher degrees of risk to neoplasms based on their surgical grade, anatomic location, and presence or absence of metastases. Lesions that are low grade are assigned a score of I, while high-grade lesions are assigned a score of II. Lesions contained in the bone or those that are intracompartmental are designated as A, and extracompartmental lesions are designated as B. Metastases elevates the score to III. The radiograph and biopsy specimen reveal a high-grade bone sarcoma with a soft-tissue component with no evidence of metastatic disease. Therefore, this is a stage IIB lesion. Figure 17a Figure 17b Question 17 of 100 A 57-year-old man has a bone lesion that was identified on radiograph and MR imaging (Figures 17a and 17b) that were taken to evaluate anterior knee pain. An examination reveals a positive patellar apprehension test finding. The patient brings his imaging findings to his appointment, and you learn that an image-guided core needle biopsy was performed based upon the radiologist’s interpretation of the imaging. The core needle biopsy pathology interpretation text reads, “a low-grade cartilage consistent with either enchondroma or low-grade chondrosarcoma. Clinical and imaging correlation is recommended.” What is the best next step? 1- Fluorescent in situ hybridization analysis of the biopsy sample for the t(9;22) translocation 2- Repeat core needle biopsy, sampling a different site within the tumor 3- Observation with serial radiographs or MR imaging 4- Intercalary resection and intramedullary fixation PREFERRED RESPONSE: 3- Observation with serial radiographs or MR imaging DISCUSSION Low-grade cartilage lesions are among the few diagnoses for which proceeding to definitive surgical treatment without a definitive histologic diagnosis is appropriate. Extended curettage with adjuvants is an acceptable treatment option for both enchondroma and low-grade chondrosarcoma of the extremities; as such, it is appropriate to proceed to definitive treatment when these are the only diagnoses in the differential. There is no consensus regarding the number and type of adjuvants used in intralesional curettage. There is also lack of consensus regarding how to reconstruct the resultant defect, with some favoring cement and others favoring bone grafting. A wide resection with intercalary resection is not indicated. Most commonly, serial radiologic studies are recommended to ensure no change occurs over time when the lesion is found incidentally, as in this patient. The t(9;22) translocation occurs in extraskeletal myxoid chondrosarcoma, which is not a consideration for this patient based upon location, imaging, and the biopsy interpretation. Repeat core needle biopsy is not indicated because the value of core needle biopsy in general for low-grade cartilage lesions is questionable in light of sampling error concerns and the inability of expert pathologists to reliably distinguish between enchondroma and low-grade chondrosarcoma. Many orthopaedic oncologists favor proceeding directly to curettage with adjuvants without any biopsy when the imaging is classic for a low-grade cartilage tumor without any evidence of dedifferentiation. Enchondromas are frequently positron emission tomography (PET) avid, and PET is not used to distinguish enchondroma from low-grade chondrosarcoma. Figure 18a Figure 18b Figure 18c CLINICAL SITUATION FOR QUESTIONS 18 THROUGH 21 Figures 18a through 18c are the radiographs and bone scan of a 23-year-old woman. Question 18 of 100 What is the most likely diagnosis? 1- Fibrous dysplasia 2- Metastatic carcinoma 3- Multiple hereditary exostosis 4- Multiple myeloma PREFERRED RESPONSE: 1- Fibrous dysplasia Question 19 of 100 Despite adequate medical management, the patient continues to experience leg pain that interferes with even the lowest demands of daily living. You recommend prophylactic intramedullary nailing of the tibia with interlocking screws. Prior to the surgery, you should recommend 1- an echocardiogram. 2- an endocrinology consultation. 3- a serum calcium level. 4- a repeat nuclear bone scan. PREFERRED RESPONSE: 2- an endocrinology consultation. Question 20 of 100 The most common extraskeletal manifestation of this disease is 1- café au lait macules. 2- urinary protein elevation. 3- a primary lung mass. 4- an arrhythmia. PREFERRED RESPONSE: 1- café au lait macules. Question 21 of 100 The underlying cause of the neoplasm is 1- ALK gene rearrangement. 2- a nongerm-cell mutation of the GNAS1 gene. 3- a germline alteration in EXT1 and EXT2. 4- an abnormality arising from the translocation t(11;14)(q13;q32). PREFERRED RESPONSE: 2- a nongerm-cell mutation of the GNAS1 gene. DISCUSSION The bone scan reveals multiple bone lesions, which does not rule out any of the responses. The radiographs reveal dysplastic bone with a “ground glass” appearance, suggesting fibrous dysplasia as the preferred response. Multiple myeloma typically demonstrates purely lytic, “punched out” lesions and would be highly unusual in a 23-year-old woman. Multiple hereditary exostosis would demonstrate more expansile lesions concentrated in the metaphysis. Metastatic carcinoma could have a lytic or blastic appearance but is less likely to occur in a 23-year-old woman. McCune-Albright syndrome in polyostotic fibrous dysplasia is present in as many as 50% of patients and should be evaluated for during an endocrine consultation. Adrenal, pituitary, parathyroid, and thyroid endocrinopathies may be present. Untreated hyperthyroidism can be life threatening during a surgical procedure. There is no indication to repeat the nuclear bone scan. Although phosphate wasting and, rarely, oncogenic osteomalacia have been reported in polyostotic fibrous dysplasia, an endocrinology consultation always should be sought. Café au lait macules are the most common extraskeletal manifestation of fibrous dysplasia, often referred to as “coast of Maine” in appearance because of their irregular borders (in comparison to the “Coast of California” with smooth borders as seen in neurofibromatosis). Multiple myeloma would not ordinarily appear with increased uptake on a bone scan unless a pathologic fracture of some duration were present. A long area of bone involvement would not appear in patients with metastatic lung adenocarcinoma. An ALK rearrangement occurs in nonsmall-cell lung cancer. The translocation t(11;14)(q13;q32) should be recognized as a poor prognosticator in multiple myeloma. The germline alteration in EXT1 and EXT2 occurs in multiple hereditary exostosis. All forms of fibrous dysplasia are caused by a nongerm-cell mutation that occurs during early embryogenesis. A missense mutation of the GNAS1 gene, which encodes the alpha subunit of the stimulatory G-protein-couple- receptor, Gs alpha, results in G-protein activation and the production of cyclic adenosine monophosphate affecting melanocytes, endocrine cells, and osteoprogenitor cells. Figure 22a Figure 22b Question 22 of 100 Figures 22a and 22b are the anteroposterior knee radiograph and an axial T2-weighted MR image of an 11-year-old boy who experienced knee pain following soccer practice. What is the best approach for biopsy? 1- Lateral parapatellar 2- Medial parapatellar 3- Directly medial 4- Directly anterior PREFERRED RESPONSE: 3- Directly medial DISCUSSION The biopsy should cross only 1 compartment if possible and proceed as directly as possible to the tumor. The lateral parapatellar and medial parapatellar approaches cross the knee joint, potentially visualizing tumor into the knee. A direct anterior approach will contaminate an extensive portion of the quadriceps muscle and potentially complicate limb salvage. Biopsy should be performed at the institution at which definitive resection is planned. Figure 23a Figure 23b Figure 23c Question 23 of 100 Figures 23a through 23c are the MR images of a 55-year-old woman who has experienced more than 10 years of right lower extremity pain that is radiating along the sciatic nerve distribution even though she has had multiple spine decompression procedures. She cannot sit comfortably in a chair and feels a fullness in the posterior aspect of her thigh. What is the most likely diagnosis? 1- Malignant peripheral nerve sheath tumor 2- Schwannoma 3- Myxoid liposarcoma 4- Desmoid fibromatosis PREFERRED RESPONSE: 2- Schwannoma DISCUSSION This patient has had long-standing radiating pain along the sciatic nerve distribution that has not been relieved with spine decompression procedures. Localized symptoms to her posterior thigh should elicit further evaluation with MR imaging. The chronicity of pain and homogeneous appearance of the lesion on MRI would speak against a malignant peripheral nerve sheath tumor. MR imaging reveals a large fusiform mass along the course of the sciatic nerve with a bright T2 signal that is consistent with a nerve sheath tumor. Neurofibroma is another viable option but is not listed as a response, and the patient does not have neurofibromatosis. Myxoid liposarcoma is an intermediate-grade malignancy and could cause long-standing symptoms, but this diagnosis is inconsistent with the imaging provided. Desmoid fibromatosis has features inconsistent with the imaging provided; it typically would involve a darker T2 signal than a myxoid liposarcoma or Schwannoma, and, while sometimes involving a major nerve, this condition typically does not grow along the course of the nerve like a benign nerve sheath tumor. Figure 24a Figure 24b Question 24 of 100 Figures 24a and 24b are the right femur radiograph and bone scan of a 71-year-old man with long-standing metastatic prostate cancer who has experienced increasing right thigh pain for 2 months. The pain is worse with activity and is alleviated with rest. He experienced similar pain in his left thigh 18 months ago and subsequently sustained a left subtrochanteric femur fracture after a low-energy twisting injury. He was successfully treated with an intramedullary nail. He had been receiving zoledronic acid for 4 years prior to the fracture. This patient’s history includes heavy steroid use. His current symptoms are most likely the result of 1- a prostaglandin-secreting prostate metastasis. 2- inhibition of osteoclastic function. 3- right L4 radiculopathy secondary to prostate metastasis. 4- direct inhibition of osteoclast prenylation. PREFERRED RESPONSE: 2- inhibition of osteoclastic function. DISCUSSION This patient’s history and imaging are most consistent with an atypical femoral fracture attributable to impaired bone remodeling. Both bisphosphonates and denosumab are associated with atypical femur fractures. Atypical fractures may occur in the diaphysis and the subtrochanteric region. The patient’s prior femur fracture was attributable to bisphosphonate (zoledronic acid) use. Bisphosphonates directly inhibit osteoclasts. He subsequently experienced a long symptom-free interval during which he took denosumab, which is an indirect osteoclast inhibitor. The imaging is not consistent with a symptomatic prostate metastasis. L4 radiculopathy may cause thigh pain, but there is no evidence (other than the mention of spine metastasis) supporting this diagnosis. Question 25 of 100 Denosumab, the human monoclonal antibody that specifically binds and inactivates receptor activator of nuclear factor-kB ligand (RANKL), is commonly used in the setting of metastatic disease. Its cell surface receptor is expressed by 1- mature osteoclasts only. 2- mature osteoblasts only. 3- both osteoclast precursors and mature osteoclasts. 4- both osteoblast precursors and mature osteoblasts. PREFERRED RESPONSE: 3- both osteoclast precursors and mature osteoclasts. DISCUSSION Bone remodeling involves both osteoblasts and osteoclasts. RANKL, a member of the tumor necrosis factor (TNF) family, is a key regulator of osteoclast formation and function. The receptor of RANKL, RANK, is expressed by both osteoclast precursors and mature osteoclasts. Denosumab inhibits the binding of RANKL to RANK, decreasing osteoclastogenesis and bone-resorption by mature osteoclasts. Osteoblasts produce osteoprotegerin, which stimulates osteoclasts to induce apoptosis by acting as a decoy for RANKL, preventing the binding of RANKL to RANK. Osteoprotegerin also binds to other TNF-related apoptosis- inducing ligands and other TNF members including TNF-a, TNF-B, and CD40 ligand. Denosumab does not bind to any other TNF members. Breast cancer metastases produce cytokines that induce osteoblasts to express elevated levels of RANKL, stimulating osteoclastogenesis via binding to RANK and activating downstream signaling pathways to osteoclast precursors, causing further bone resorption. Measurements of bone product turnover (including N-telopeptide) decrease during treatment with denosumab.  Figure 26 Figure 27 Figure 28 Figure 29 Figure 30 Figure 31 RESPONSES FOR QUESTIONS 26 THROUGH 31 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy For each clinical scenario or question below, select the most appropriate evaluation or treatment step listed above. Question 26 of 100 Figure 26 is the posteroranterior chest radiograph of a 76-year-old man with an atraumatic gradually enlarging mass overlying his left clavicle that has been present for 6 months. There are no changes in overlying skin. His only noteworthy medical history involves facial squamous cell carcinomas that have been successfully removed surgically. 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy PREFERRED RESPONSE: 2- MRI with and without contrast Question 27 of 100 A 63-year-old man with right hip pain was followed 8 years ago for an incidental intraosseous lesion in the right periacetabular and ischial region that was isointense with fat on all images. He was discharged from follow-up after 3 years when no change was documented. He began experiencing pain in his hip, and a bone scan showed grade 3 uptake. New MR imaging was obtained, and an axial image at the level of the hip is shown in Figure 27. A PET/CT scan shows dramatic activity in the lesion without any other area of activity. 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy PREFERRED RESPONSE: 10- Core needle biopsy Question 28 of 100 Figure 28 is the MR image of a 65-year-old man with an American Joint Committee on Cancer III anterior arm pleomorphic intermediate- to high-grade sarcoma. The patient is now considering treatment options. He underwent a wide excision at an outside hospital 2 years previously. The treating surgeon recommended an amputation, and the patient is now seeking a second opinion. Imaging studies reveal no other sites of disease. 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy PREFERRED RESPONSE: 5- Presurgical radiation therapy Question 29 of 100 Figure 29 is the MR image of a 44-year-old woman who elects surgical treatment of an intramuscular lipoma in her dominant right arm. 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy PREFERRED RESPONSE: 6- Marginal resection Question 30 of 100 Figure 30 is the MR image of a 29-year-old man with a large and enlarging thigh mass. Needle biopsy findings are inconclusive. 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy PREFERRED RESPONSE: 8- Incisional biopsy centered over the mass in line with the long axis of the limb Question 31 of 100 Figure 31 is the sagittal MR image of a 30-year-old man with a clear-cell sarcoma of the foot. There is no evidence of disease elsewhere after standard staging of a soft-tissue sarcoma. 1- Ultrasound 2- MRI with and without contrast 3- Chest CT scan and whole-body bone scan 4- Positron emission tomography (PET) 5- Presurgical radiation therapy 6- Marginal resection 7- Transverse incisional biopsy centered over the mass 8- Incisional biopsy centered over the mass in line with the long axis of the limb 9- Sentinel node biopsy 10- Core needle biopsy PREFERRED RESPONSE: 9- Sentinel node biopsy DISCUSSION For patients with rapidly enlarging painless masses, particularly those that are either large or deep, the diagnosis of a soft-tissue sarcoma should be entertained. Masses exceeding 5 cm in largest dimension that are subfascial and heterogenous on MRI are concerning. MRI with and without contrast is the preferred imaging modality for evaluation of soft-tissue sarcomas because it can delineate location of the lesion, involvement of neurovascular structures, intra-articular involvement, and underlying signal alteration in the osseous structures. Most patients can relate the onset of their symptoms to a traumatic event, and the interpretation of an MRI may include a hematoma. Ultrasound is more commonly used to confirm the clinical impression of a cyst and to distinguish cystic from solid masses. A core needle biopsy can easily be performed in an outpatient setting or with image guidance to aid in the diagnosis. Core needle biopsies preserve the architectural relationship of cells, which is important in the diagnosis of mesenchymal lesions. A core needle biopsy is appropriate for soft-tissue lesions and osseous lesions and should be performed in a multidisciplinary setting with a surgeon performing the resection so unnecessary compartmental contamination is not introduced into the needle tract. A fine-needle aspiration allows cytologic but not histologic analysis and generally is not favored for the diagnosis of a sarcoma. If an open biopsy is performed, the incision must be oriented in line with the long axis of the extremity to minimize contamination of surrounding structures. Meticulous hemostasis and closure of the tumor pseudocapsule must be achieved to minimize local tissue contamination. An open biopsy is commonly used if an initial needle biopsy is nondiagnostic. Transverse biopsy incisions should not be used. Presurgical radiation for sarcomas is advantageous to decrease the field of radiation and overall radiation dose, but a significant postsurgical wound-healing complication rate (up to 35%) is associated with presurgical radiation therapy. Staging of sarcomas is important to help predict prognosis. Not all sarcomas are reliably positive on a PET scan, so the preferred staging studies are CT scan of the chest and whole-body bone scan. Hematogenous spread of sarcomas is the most common route of metastatic disease, which speaks to the value of chest CT scans. Clear-cell sarcomas (in addition to synovial sarcoma, angiosarcoma, epithelioid sarcoma, and rhabdomyosarcoma) tend to involve lymphatic nodal metastatic disease, so sentinel node biopsy is considered when assessing these tumors. Evidence supports efficacy of sentinel node biopsy for clear-cell sarcomas in particular.  Figure 32a Figure 32b Figure 32c Figure 32d Question 32 of 100 Figures 32a through 32d are the radiographs and MR images of a 13-year-old girl with new posterolateral knee pain following a fall. What is the best next step? 1- Percutaneous biopsy 2- Open curettage and grafting 3- Referral to a musculoskeletal oncologist 4- Observation with follow-up radiographs PREFERRED RESPONSE: 4- Observation with follow-up radiographs DISCUSSION This patient has an incidentally noted benign-appearing fibro-osseous lesion of her proximal tibia. The lesion does not correspond to her area of pain, and there is no indication she experienced pain from the lesion prior to the fall. Radiographs and MR imaging findings are consistent with a fibrous cortical defect or nonossifying fibroma. There is no surrounding edema in the bone or soft tissue and no soft-tissue mass, and the lesion has a sclerotic rim around it. These are common lesions in children, and there is no need for a biopsy, curettage, or referral to a tumor specialist. This patient should not be at high risk for pathologic fracture from this lesion. Observation with follow- up radiographs in 3 to 6 months is the treatment of choice. Figure 33a Figure 33b  Figure 33c Figure 33d Question 33 of 100 Figures 33a through 33d are the radiograph, MR images, and biopsy specimen of a 66-year-old woman with a several-month history of an enlarging thigh mass after “pulling a muscle” while playing softball. Several weeks ago her physician aspirated the cyst, but the result is no change. Treatment of this lesion should include 1- embolization. 2- reaspiration and observation. 3- radiation therapy alone. 4- radiation therapy and surgery. PREFERRED RESPONSE: 4- radiation therapy and surgery. DISCUSSION This patient’s imaging and biopsy specimen are consistent with a high-grade undifferentiated pleomorphic sarcoma (UPS). Histologically, UPS is characterized by high cellularity, marked nuclear pleomorphism, abundant mitotic activity (including atypical mitoses), and a spindle cell morphology. Necrosis is common and characteristic of high- grade lesions. Treatment consists of wide surgical excision and, in almost all cases, radiation. Radiation eliminates the need for limb amputation, and there is level I evidence to show that it leads to equivalent rates of survival. Radiation may be delivered either before or after surgery depending on the surgeon’s and multidisciplinary tumor board’s recommendations. There may be a role for presurgical embolization in some cases of high-grade soft-tissue sarcoma, but this is not appropriate as a standalone treatment. Chemotherapy provides limited survival improvement in adults with high-grade soft-tissue sarcomas. Question 34 of 100 A 79-year-old woman is seen for follow-up of a right arm posterior compartment high-grade soft-tissue sarcoma after undergoing wide resection of the tumor with preservation of the radial nerve and minimal stripping of the posterior humeral periosteum. She then received 70 Gy of postsurgical radiation. Local recurrence occurred 4 years later, and she was treated with re-resection and adjuvant doxorubicin and ifosfamide chemotherapy. At that time, she learned she had osteoporosis and was treated with alendronate. She experienced an atraumatic fracture 2 years later without evidence of local recurrence. Which treatment poses highest risk for fracture in this scenario? 1- Chronic oral bisphosphonate use 2- Doxorubicin and ifosfamide chemotherapy 3- Timing and dose of radiation 4- Surgical periosteal stripping PREFERRED RESPONSE: 3- Timing and dose of radiation DISCUSSION Although postsurgical radiation is associated with lower rates of wound complication, radiation that is administered after surgery necessitates higher radiation doses and a larger tissue field than radiation administered before surgery. Risk for radiation-associated fracture increases with larger fields and higher doses. Retrospective studies have demonstrated increased fracture risk with postsurgical radiation doses of at least 60 Gy compared with presurgical radiation doses of 50 Gy. The influence of periosteal stripping on fracture risk is controversial. In a series of patients receiving primarily postsurgical radiation, extensive stripping was an accepted risk factor, but it was not found to be a significant risk factor in a more recent analysis of patients receiving lower-dose presurgical radiation. Cytotoxic chemotherapy is detrimental to healing of established fractures but does not correlate with risk for fracture in soft-tissue sarcoma. Chronic bisphosphonate use is associated with atypical fractures, but the location, timing, and radiographic appearance in this scenario are not consistent with this etiology. Figure 35 CLINICAL SITUATION FOR QUESTIONS 35 THROUGH 37 Figure 35 is the intraoperative finding of a 28-year-old man with a recurrent nontraumatic effusion who undergoes arthroscopy. Question 35 of 100 A neoplasm that involves rearrangements of 1p13 involving the colony-stimulating factor 1 (CSF1) gene which, when expressed, causes proliferation of neoplastic cells and the recruitment of monocyte-macrophage non- neoplastic cells is 1- a tenosynovial giant-cell tumor. 2- a nodular fasciitis. 3- an infantile fibrosarcoma. 4- an inflammatory myofibroblastic tumor. PREFERRED RESPONSE: 1- a tenosynovial giant-cell tumor. Question 36 of 100 This tumor has been recently treated in phase 1 trials with molecularly targeted therapies including a conformation- specific inhibitor of CSF1 receptor (CSF1R), resulting in at least a 50% reduction of tumor volume in some patients. This type of inhibitor is further defined as 1- a tyrosine kinase inhibitor. 2- a substrate binding synthetic molecule. 3- an anti-CSF1R antibody. 4- an anti-CSF1 antibody. PREFERRED RESPONSE: 2- a substrate binding synthetic molecule. Question 37 of 100 What is the neoplastic cell of origin for this tumor? 1- Lymphocyte 2- Monocyte 3- Macrophage 4- Mononuclear phagocyte PREFERRED RESPONSE: 4- Mononuclear phagocyte DISCUSSION Tenosynovial giant-cell tumors are widely known as pigmented villonodular synovitis (PVNS), although this term is misleading because this tumor type is a clonal neoplasm and does not involve an inflammatory process. It often is shown to have a t(1:2)(p13q37) karyotype resulting in CSF1-COL6A3 gene fusion. There are various amounts of mononuclear cells, osteoclastlike giant cells, foamy histiocytes, hemosiderophages, and chronic inflammatory cells. Local recurrences are common, but CSF1R inhibitors are being investigated in studies involving local control improvement and disease regression. Targeted therapy trials to assist in control of the diffuse-type tenosynovial giant-cell tumor (formerly called PVNS) involve the use of monoclonal antibodies that inhibit CSF1R activation. CSF1R-expressing mononuclear phagocytes are affected by these monoclonal antibodies. Infantile fibrosarcoma is associated with the t(12;15)(p13;q25) karyotype and ETV6-NTRK3 gene fusion product. Nodular fasciitis is associated with the t(17;22)(p13;q13.1) karyotype and MYH9-USP6 gene fusion product. Inflammatory myofibroblastic tumor is associated with translocations involving 2p23 resulting in multiple fusion products of ALK with TPM4 (19p13.1), TPM3 (1q21), CLTC (17q23), RANBP2 (2q13), ATIC (2q35), SEC31A (4q21), and CARS (11p15). No nonpreferred response has a histologic appearance that includes hemosiderin, foamy histiocytes, and osteoclastlike giant cells. A conformation-specific inhibitor of the juxtamembrane region of CSF1R is a synthetic molecule that is designed to access the autoinhibited state of the receptor through direct interactions with the juxtamembrane residues embedded in the adenosine 5’-triphosphate-binding pocket. It is designed to bind in the regulatory a-helix of the N- terminal lobe of the kinase domain in neoplastic cells of tenosynovial giant-cell tumor that have expression of the CSF1 gene. There is a structural plasticity of the domain of the CSF1R that allows the molecule to directly bind the autoinhibited state of CSF1R. Another approach involves the development of the anti-CSF1R antibody, emactuzumab, which targets tumor- associated macrophages. A lower percentage of volume reduction has been reported with imatinib, a tyrosine kinase inhibitor. Alkylating agents have not been used in this benign neoplasm. Tenosynovial giant-cell tumor is characterized by an overexpression of CSF1. CSF1R activation leads to recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage. Figure 38a Figure 38b Question 38 of 100 Figures 38a and 38b are the radiographs of a 12-year-old girl with a slowly enlarging mass on her posterior elbow. She has an unremarkable medical history. The mass is nontender, soft, and mobile with respect to the underlying bone. Her elbow motion is supple and unrestricted. What is the most likely cause of this condition? 1- Inherited abnormality of phosphate metabolism 2- Inherited abnormality of calcium metabolism 3- Renal disease with chronic renal insufficiency 4- Chronic hyperparathyroidism PREFERRED RESPONSE: 1- Inherited abnormality of phosphate metabolism DISCUSSION The history, examination, and radiographs strongly suggest tumoral calcinosis. Inherited forms of tumoral calcinosis are often attributable to a genetic disorder involving phosphate homeostasis. Acquired tumoral calcinosis is usually secondary to chronic renal disease and dialysis with secondary hyperparathyroidism. Figure 39a Figure 39b Figure 39c Question 39 of 100 Figures 39a through 39c are the radiographs and MR image of a 14-year-old boy who has intermittent knee swelling and pain exacerbated by activity. What is the most likely diagnosis? 1- Vascular malformation 2- Synovial chondromatosis 3- Diffuse pigmented villonodular synovitis (PVNS) 4- Lipoma arborescens PREFERRED RESPONSE: 1- Vascular malformation DISCUSSION This patient’s history does not rule out any of these diagnoses. Imaging shows multifocal areas of ropey vascular malformations with signal voids in the thigh. The MR image shows intra-articular involvement that is often the most symptomatic area in these patients. The radiographs do not show the classic phleboliths seen with venous malformations or the typical calcifications of synovial chondromatosis. Lipoma arborescens would involve an overabundance of fat throughout the joint noted on MRI, and PVNS will typically involve an effusion, diffuse synovial hyperplasia, and multiple focal nodules of disease. The appropriate treatment for intra-articular vascular malformations has not been established. Compression garments should be considered initially, with persistent symptoms warranting arthroscopic or open excision of the vascular malformations with synovectomy. Question 40 of 100 A 21-year-old man learned he had Ewing sarcoma of the right distal femur at age 13. He underwent treatment with neoadjuvant chemotherapy, surgical resection with distal femoral replacement, and adjuvant chemotherapy. He completed treatment at age 14, and subsequent surveillance imaging has shown no evidence of recurrence. He has noted increasing fatigue during the last 3 months, however, and bleeding when he brushes his teeth. An examination is unremarkable with the exception of bilateral pretibial bruising for which the patient does not recall trauma. Which tests will aid in diagnosis? 1- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 2- Serum protein electrophoresis 3- Complete blood count (CBC) with a peripheral smear 4- Platelet aggregation testing and bleeding time PREFERRED RESPONSE: 3- Complete blood count (CBC) with a peripheral smear DISCUSSION This patient most likely has therapy-associated leukemia, which occurs in approximately 2% of patients who have Ewing sarcoma within 5 years of receiving treatment. Most cases are myelodysplasia or acute myeloid leukemia. Most patients with therapy-associated leukemia respond poorly to conventional chemotherapies and require allogenic stem cell transplant for cure. Fatigue, gum bleeding, and bruising should raise concern for leukemia in light of his clinical history. A CBC with a peripheral smear will likely reveal an elevated leukocyte count with an abnormal percentage of myeloblasts. ESR and CRP are required to assess for infection of a prosthesis. Fatigue may be associated with chronic infection, but bleeding would be atypical. Platelet aggregation test results may be abnormal for this patient, but this testing is unlikely to reveal a specific diagnosis because drugs and genetic disorders may cause platelet aggregation dysfunction. Serum protein electrophoresis is diagnostic for multiple myeloma, but this patient is the wrong age for this condition and does not have appropriate signs and symptoms. A CBC can demonstrate early findings for leukemia with anemia and platelet suppression despite no blast presence. Of note, 25% of long-term survivors of Ewing sarcoma have findings of cardiotoxicity.  Figure 41a Figure 41b Figure 41c Figure 41d Question 41 of 100 Figures 41a through 41d are the radiograph, MR images, and biopsy specimen of a 35-year-old woman with pain and progressive paresthesias in her left arm. Staging shows no other lesions. Appropriate local control for this condition requires 1- forequarter amputation. 2- Tikhoff-Linberg limb salvage resection. 3- contaminated wide resection with a postsurgical radiotherapy boost. 4- chemotherapy and radiotherapy alone. PREFERRED RESPONSE: 1- forequarter amputation. DISCUSSION This patient has a pathologic fracture from a high-grade chondrosarcoma with encasement of the axillary contents. Meaningful wide resection necessitates amputation. Radiotherapy and chemotherapy do not have a defined role in the treatment of conventional chondrosarcoma. The resection of the axillary, musculocutaneous, or radial nerve or all 3 nerves is not an indication for a forequarter amputation. If the median or the ulnar nerve is expected to be resected, forequarter amputation should be seriously considered. An absolute indication of a forequarter amputation is encasement of the vascular bundle. Another strong indication is a pathologic fracture. In 1 study that included both chondrosarcoma and dedifferentiated chondrosarcoma with pathologic fractures involving the proximal femur, the overall 5-year survival rates were 57% and 0%, respectively. In another study, local recurrence was a prelude to distant metastasis, and tumor grade and size and adequacy of the resection trended toward predictors of outcome. Figure 42a Figure 42b Figure 42c Figure 42d Question 42 of 100 Figures 42a through 42d are the radiograph, CT scans, and biopsy specimen of a 38-year-old man who arrived at the emergency department with urinary retention. He has no other symptoms. What is the most appropriate treatment for this lesion? 1- Surgery alone 2- Surgery and radiation therapy 3- Surgery, radiation therapy, and chemotherapy 4- Radiation therapy alone PREFERRED RESPONSE: 1- Surgery alone DISCUSSION These images reveal a chondrosarcoma. On radiograph, chondrosarcoma is a fusiform, lucent defect with scalloping of the inner cortex and periosteal reaction. Extension into the soft tissue may be present, as well as punctate or stippled calcification of the cartilage matrix. Histologically, chondrosarcoma is differentiated from benign cartilage tumors by enlarged plump nuclei, multiple cells per lacunae, binucleated cells, and hyperchromic nuclear pleomorphism. Treatment of most chondrosarcomas is surgery only because adjuvant treatments are not effective. Question 43 of 100 Which treatment regimen for Ewing sarcoma most effectively controls disease? 1- Chemotherapy alone 2- Chemotherapy plus wide surgical resection 3- Chemotherapy plus radiation therapy 4- Surgery plus radiation therapy PREFERRED RESPONSE: 2- Chemotherapy plus wide surgical resection DISCUSSION Patients with Ewing sarcoma need chemotherapy to treat micrometastatic disease. Historical outcomes of patients who receive local control alone without chemotherapy are dismal. Chemotherapy alone, however, is not adequate to control local bulky disease. Local control options include radiation therapy or wide surgical resection. Historically, it was believed that surgery should be recommended for expendable bones to minimize morbidity. More recent data support improved outcomes (vs outcomes associated with radiation alone to the primary site of disease) for patients who undergo wide surgical resection; consequently, chemotherapy plus wide surgical resection is the most effective regimen. Figure 44a Figure 44b Figure 44c Figure 44d Figure 44e Figure 44f  Figure 44g Question 44 of 100 Figures 44a through 44c are the clinical photograph and radiographs of a 59-year-old man who has a 4-year history of metastatic renal cell carcinoma to the brain, lungs, and bones. He has been referred for a painful left proximal femur metastasis. Axial MR images are shown in Figures 44d and 44e. Presurgical embolization, en bloc resection, and proximal femur replacement are performed. The resection specimen and a postsurgical radiograph are shown in Figures 44f and 44g. Compared with intramedullary nail fixation, this treatment strategy 1- entails a higher perioperative mortality risk. 2- improves overall survival. 3- poses lower risk for local treatment failure. 4- is associated with less complete pain relief. PREFERRED RESPONSE: 3- poses lower risk for local treatment failure. DISCUSSION Both a retrospective study and retrospective review of the prospectively collected Scandinavian Sarcoma Group database have shown lower rates of revision surgery and local control failure with en bloc resection than with intralesional procedures. Multiple retrospective studies of solitary renal cell metastases have demonstrated an overall survival benefit with en bloc resection; however, these data are not applicable because this patient has multisystem disease. A perioperative mortality difference between resection and nailing procedures has not been demonstrated. Although surgical intervention to treat pathologic fractures improves pain, studies comparing the adequacy of different interventions are limited. In this patient, a nail procedure would necessitate less surgical dissection and shorter surgical time. However, a nail would not address the large soft-tissue mass that likely was a major contributor to this patient’s pain.  Figure 45a Figure 45b Question 45 of 100 Figures 45a and 45b are the radiographs of a previously asymptomatic 10-year-old girl who fell off of her bike. Treatment of this lesion should consist of 1- observation. 2- MRI with and without contrast. 3- curettage and bone grafting. 4- open biopsy. PREFERRED RESPONSE: 1- observation. DISCUSSION Nonossifying fibroma of bone is a common entity and consists of a solitary eccentric, lytic expanded lesion in the metaphysis of a long bone. Clinically, nonossifying fibromas are asymptomatic and are usually an incidental finding on radiograph. These lesions normally regress spontaneously.  Figure 46a Figure 46b Figure 46c Figure 46d Figure 46e Figure 46f Question 46 of 100 Figure 46a is the lateral radiograph of a 54-year-old man who has had a painless soft-tissue mass on his right foot that has been growing slowly for about 1 year. MR sequences are shown in Figures 46b through 46e. A biopsy is performed, and a low-power hematoxylin and eosin photomicrograph is seen in Figure 46f. The most appropriate treatment for this lesion is 1- a diet that reduces uric acid production. 2- wide local resection followed by radiotherapy. 3- marginal excision. 4- excision and radiotherapy after the mineralization matures. PREFERRED RESPONSE: 3- marginal excision. DISCUSSION This is a giant-cell tumor of the tendon sheath. A solid lesion larger than 1.5 cm in the hand or foot warrants biopsy to rule out malignancy. The 3 most common benign tumors of the foot are ganglion cysts, giant-cell tumors of tendon sheath, and hemangiomas. Radiographs are nonspecific but may reveal extrinsic erosions of bone by a giant-cell tumor of the tendon sheath. MR findings of prominent low-signal intensity (seen with T2 weighting) and “blooming” artifact from the hemosiderin (seen with gradient-echo sequences) are nearly pathognomonic of this diagnosis, as seen here. Pathology shows hemosiderin-laden macrophages and giant cells as seen in the histology. Uric acid reduction would be indicated for gout and wide local excision for a soft-tissue sarcoma. Observation awaiting mature mineralization would apply to heterotopic ossification.  Figure 47a Figure 47b Question 47 of 100 Figures 47a and 47b are the radiograph and axial CT section of a 73-year-old woman with metastatic lung cancer who has a painful left periacetabular lesion. She is a high-risk surgical candidate because of a prior pneumonectomy and progressive metastatic disease of her remaining lung. Palliative radiation is recommended. Two regimens are being considered: a single fraction of 8 Gy or 15 fractions of a 30-Gy cumulative dose over 3 weeks. Compared to the multifraction regimen, the 8-Gy single fraction is associated with 1- inferior pain relief. 2- higher cost. 3- superior pain relief. 4- equivalent pain relief. PREFERRED RESPONSE: 4- equivalent pain relief. DISCUSSION Multiple prospective randomized controlled trials have evaluated single vs multifraction radiation regimens for the treatment of painful bone metastases. All studies have demonstrated equivalent pain relief. Retreatment rates are higher with single-fraction dosing, but it is unknown if this is because of higher rates of recurrent pain with single fractions or reluctance of radiation oncologists to give additional radiation when multifraction regimens with higher cumulative doses have failed. Single-fraction radiation is less expensive and more convenient for patients. The American Board of Internal Medicine Foundation’s Choosing Wisely® campaign to encourage physician leadership in reducing harmful or inappropriate resource use selected “Don’t recommend more than a single fraction of palliative radiation for an uncomplicated painful bone metastasis” as 1 of the “5 things physicians and patients should question in hospice and palliative medicine.”  Figure 48a Figure 48b Figure 48c Figure 48d Figure 48e Question 48 of 100 Figures 48a through 48e are the MR image, radiograph, CT scan, and biopsy specimens of a 14-year-old boy with right shoulder pain without antecedent trauma. What is the most likely diagnosis? 1- Unicameral bone cyst 2- Eosinophilic granuloma 3- Chondrosarcoma 4- Chondroblastoma PREFERRED RESPONSE: 4- Chondroblastoma DISCUSSION Imaging reveals a destructive mineralized lesion of the epiphysis and metaphysis in a skeletally immature patient. Epiphyseal lesions include chondroblastoma in skeletally immature patients and giant-cell tumors in skeletally mature patients. The histology confirms the diagnosis with the presence of multinucleated giant cells, “chicken- wire” calcifications, and chondroid islands. Chondrosarcoma would look histologically more aggressive than this and is unusual in children. Unicameral bone cysts do not have mineralization and are typically confined to the metaphysis radiologically. Eosinophilic granuloma can mimic many different lesions radiographically and can occasionally be found in the epiphysis of children, but the histology does not demonstrate classic Langerhans cells.  Figure 49 CLINICAL SITUATION FOR QUESTIONS 49 AND 50 Figure 49 is the radiograph of a 22-year-old woman with pain and snapping about the knee. Her husband does not have this condition. Question 49 of 100 What is the likelihood of this patient’s children having a similar condition? 1- No different than the likelihood among the general population 2- 25% only if her partner is similarly affected; if not, no different than the population average 3- 50% 4- 100% PREFERRED RESPONSE: 3- 50% Question 50 of 100 Germline alterations associated with this condition 1- affect proteins exostosin-1 (EXT1) and exostosin-2 (EXT2). 2- encode the alpha subunit of the stimulatory G-protein-coupled receptor, Gsa. 3- cause neoplastic cells to express vimentin, CD99, and FLI-1. 4- produce the WWTR1-CAMTA1 fusion. PREFERRED RESPONSE: 1- affect proteins exostosin-1 (EXT1) and exostosin-2 (EXT2). DISCUSSION The radiograph reveals multiple osteochondromas consistent with multiple hereditary exostoses (also termed osteochondromatosis). This is inherited in an autosomal-dominant fashion through the EXT1 and EXT2 genes. Thus, the likelihood of this patient’s children being affected is 50% for each child. An autosomal dominant manner with germiline alterations in EXT1 located at 8q24 and EXT2 located at 11p11-p12 occurs in approximately 1 in 50,000 people. Multiple hereditary exostoses is a disease in a spectrum of diseases caused by alterations in either EXT1 or EXT2. The gene products of EXT1 and EXT2 genes are considered essential for the function of fibroblast growth factor and Indian hedgehog signaling in the normal growth plate and catalyze heparin sulphate polymerization. The G- protein-couple receptor is involved in fibrous dysplasia, the expression of vimentin, and CD99. FLI-1 is associated with Ewing sarcoma, and WWTR1-CAMTA1 fusion is associated with epithelioid hemangioma, which is not related to multiple hereditary exostoses. Figure 51a Figure 51b Figure 52a Figure 52b Figure 52c CLINICAL SITUATION FOR QUESTIONS 51 THROUGH 54 Figures 51a and 51b are the radiographs of an 83-year-old active, independent, and healthy woman who has experienced 2 months of right lower thigh and knee pain. Her arthroplasty was previously well functioning, but her pain has increased progressively for several weeks. While exiting a car she “bumped” her knee against the door, felt a “crack,” and developed excruciating pain. She can no longer ambulate and was brought to the hospital. Question 51 of 100 Based on imaging alone, what does this bone lesion most closely resemble? 1- Multiple myeloma 2- Implant-associated osteolysis 3- Metastatic renal cell carcinoma 4- Enchondroma PREFERRED RESPONSE: 4- Enchondroma Question 52 of 100 Figures 52a through 52c show the biopsy of this lesion. Based on the clinical history, radiograph, and biopsy, which diagnosis is most likely? 1- Enchondroma 2- High-grade osteosarcoma 3- Metastatic renal cell carcinoma 4- Dedifferentiated chondrosarcoma PREFERRED RESPONSE: 4- Dedifferentiated chondrosarcoma Question 53 of 100 Staging for patients with this diagnosis necessitates which study or studies? 1- CT scan of the chest and a bone scan 2- Skeletal survey 3- Bone marrow aspirate 4- Bone marrow biopsy PREFERRED RESPONSE: 1- CT scan of the chest and a bone scan Question 54 of 100 Which local treatment option is most appropriate? 1- Radiation and wide surgical resection 2- Extended curettage with adjuvants 3- Wide surgical resection 4- Revision knee arthroplasty PREFERRED RESPONSE: 3- Wide surgical resection DISCUSSION This patient has a pathologic femur fracture. Her history of antecedent pain in the context of a previously well- functioning implant suggests that a new process such as dedifferentiation of a long-standing lesion may have occurred. The initial radiograph reveals a well-mineralized lesion within the intramedullary canal with punctate calcifications. This by itself suggests an enchondroma or low-grade chondrosarcoma. It is important to note that enchondromas in the long bones rarely cause pathologic fractures. This is not the case when they are present in the hands and feet, where enchondromas frequently have a more aggressive radiologic appearance and pose higher risk. Radiographic findings concerning for malignant dedifferentiation of an enchondroma include cortical thinning or breach, a soft-tissue mass, or periosteal elevation. The pathologic fracture obscures the ability to identify these hallmarks of malignant degeneration. Multiple myeloma, renal cell carcinoma, and osteolysis are all typically radiolucent. Implant-associated osteolysis lesions are commonly multiple and periarticular. The histopathology reveals a cartilage tumor. The chondroid tissue appears to be low grade. However, in an adjacent region there is a high-grade component seen both on the low-power view and the second higher-power sample that does not resemble cartilage. This is highly suggestive of a dedifferentiated chondrosarcoma. This component signifies that a portion of the original tumor (low-grade chondrosarcoma), which resembled the tissue of origin, converted into a different cell lineage with more aggressive properties (nearly any type of high-grade sarcoma). Dedifferentiated chondrosarcoma is a highly aggressive malignancy, with average 5-year survivals of less than 50%. As with most sarcomas, the most likely site of metastatic dissemination of chondrosarcoma is pulmonary. Consequently, standard staging entails a high-resolution CT scan of the lungs. Serum protein electrophoresis and a skeletal survey are used for diagnosis of multiple myeloma. Positron emission tomography/CT fusion scans are used at many centers in the staging of osteosarcoma, but their role in chondrosarcoma staging is an emerging modality that is being investigated. Radiation is not typically used for local treatment of extremity chondrosarcoma. Extended curettage is not appropriate for a high-grade lesion such as this. Revision arthroplasty alone does not address the tumor. Wide resection is the local treatment of choice for high- grade chondrosarcoma; because of the fracture, this patient may require an amputation to achieve wide margins.  Figure 55a Figure 55b Figure 55c Figure 55d Question 55 of 100 Figures 55a through 55d are the MR images, intraoperative photograph, and biopsy specimen of a 33-year-old man with progressive knee pain and recurrent effusions. What is the most likely diagnosis? 1- Lipoma arborescens 2- Synovial osteochondromatosis 3- Pigmented villonodular synovitis (PVNS) 4- Intra-articular hemangioma PREFERRED RESPONSE: 3- Pigmented villonodular synovitis (PVNS) DISCUSSION MR imaging and gross and microscopic specimens are consistent with PVNS. PVNS is a locally aggressive synovial tumor with 2 forms: diffuse and nodular. Nodular PVNS occurs most commonly in the hands, and diffuse is most common in the knee. Upon gross examination, the diffuse form of PVNS is a tan mass of villi and folds of synovium. Microscopically, PVNS is characterized by synovial cell hyperplasia on the surface and below the synovium. Lipoma arborescens would have imaging consistent with fat. Synovial chondromatosis would show synovium laden with cartilage tissue, and intra-articular hemangioma would show predominant vascular channels. Question 56 of 100 A disadvantage associated with presurgical (vs postsurgical) radiation therapy for soft-tissue sarcoma is a 1- larger radiation field. 2- lack of formation of a “pseudocapsule” to facilitate resection. 3- higher local recurrence rate. 4- higher wound complication rate. PREFERRED RESPONSE: 4- higher wound complication rate. DISCUSSION Radiation therapy is used for soft-tissue sarcoma treatment to facilitate resection of tumors that are close to adjacent structures and to diminish risk for local recurrence. The disadvantages of radiation therapy for soft-tissue sarcoma include patient inconvenience, risk for secondary malignancy, and higher wound complication rates. The advantages of presurgical (neoadjuvant) radiation therapy include a smaller radiation field, formation of a “pseudocapsule” to facilitate a planned close-margin resection, tumor shrinkage, and lower local recurrence rates. The main disadvantage of presurgical radiation therapy is the much higher risk for wound healing complications (as demonstrated in numerous studies).  Figure 57a Figure 57b Question 57 of 100 Figures 57a and 57b are the close-up femur radiographs of a 73-year-old man with nonsmall-cell carcinoma of the lung with visceral metastases. He has localized thigh pain at rest and with any range of motion of the ipsilateral hip or knee. A bone scan shows multiple areas of increased uptake. Other femur images in 2 views show no other lesions. The medical oncologist predicts a survival of 3 months. What is the best next step? 1- Needle biopsy of the femur to confirm the diagnosis 2- Cephalomedullary femur nailing 3- Palliative radiation only 4- Curettage and cementation with plate fixation of the involved femur PREFERRED RESPONSE: 2- Cephalomedullary femur nailing DISCUSSION A needle biopsy is not needed to confirm a diagnosis of metastatic disease when other sites of disease are present. Cephalomedullary nailing offers a percutaneous option to prophylactically stabilize the impending fracture and to assist in nursing and palliative care. Palliative radiation can be added, but risk for fracture (even with complete bedrest) is nearly 100% according to Mirels’ criteria. An open procedure offers no benefit to intramedullary nail placement. Recently, CT-based structural rigidity analysis has proven more accurate than Mirels’ scoring for metastatic femoral lesion fracture prediction, but this analysis is unnecessary when the likelihood of progression to fracture is so marked.  Figure 58a Figure 58b Figure 58c Question 58 of 100 Figures 58a through 58c are the radiograph, MR image, and sagittal CT scan of a 13-year-old boy with a 5-month history of a left hip injury. He has no current pain, but substantial, progressive limitations in hip flexion are present. What is the most likely diagnosis? 1- Extraskeletal osteosarcoma 2- Myositis ossificans 3- Chondrosarcoma 4- Pelvic osteosarcoma PREFERRED RESPONSE: 2- Myositis ossificans DISCUSSION This patient has a mineralized mass in the soft tissues in the rectus femoris origin. The clinical history favors an avulsion injury with subsequent myositis ossificans, and the imaging is consistent with an ossified soft-tissue mass. Extraskeletal osteosarcoma is a rare soft-tissue sarcoma and is generally seen in adults. Chondrosarcoma is also generally seen in adults and would have a more chondroid matrix as opposed to mature-looking bone on a CT scan. Pelvic osteosarcoma could have this appearance on radiograph, but the CT scan and MR image confirm this is a soft-tissue process with mature mineralization.  Figure 59a Figure 59b Figure 59c Figure 59d CLINICAL SITUATION FOR QUESTIONS 59 THROUGH 61 Figures 59a through 59d are the CT scans and biopsy specimen of a 68-year-old man with progressive radicular symptoms in his left lower extremity. Four years previously he underwent treatment of colorectal cancer with surgery, chemotherapy, and radiotherapy. Question 59 of 100 What is the diagnosis? 1- Radiation-associated insufficiency fracture 2- Postradiation osteosarcoma 3- Postradiation sclerosis 4- Metastatic colorectal cancer PREFERRED RESPONSE: 2- Postradiation osteosarcoma Question 60 of 100 The best treatment is 1- chemotherapy and wide surgical resection. 2- bisphosphonate treatment with or without sacroplasty. 3- gabapentin or similar pharmacologic therapy. 4- radiation therapy. PREFERRED RESPONSE: 1- chemotherapy and wide surgical resection. Question 61 of 100 The prognosis for this condition is 1- influenced by the latent time to presentation. 2- generally favorable. 3- variable, with periodic flares and remissions. 4- relatively poor. PREFERRED RESPONSE: 4- relatively poor. DISCUSSION This patient has postradiation osteosarcoma of the sacrum after undergoing treatment for pelvic cancer. Examinees should discern that this is a postradiation sarcoma by the imaging findings of an osteoblastic tumor with extraosseous extension arising in the expected radiation field for a patient who was treated with radiation for colorectal cancer 5 years earlier. The histology demonstrates a high-grade sarcoma. Postradiation sarcomas are treated with chemotherapy and margin-negative surgical resection, but they are associated with a relatively poor prognosis likely attributable to the advanced age of most affected patients and the frequent axial location of these tumors, which can delay diagnosis and make it difficult to obtain an appropriate margin of resection. The imaging reveals a tumor, not an insufficiency fracture or postradiation changes, and the histology shows a sarcoma, not colorectal cancer.  Figure 62a Figure 62b Question 62 of 100 Figures 62a and 62b are the radiographs of a 69-year-old woman who is seen for follow-up of a right arm posterior compartment high-grade soft-tissue sarcoma. She previously underwent wide resection of the tumor with preservation of the radial. She experienced an atraumatic fracture 2 years after completion of all treatment. There is no evidence of recurrence on MR imaging. The patient desires treatment because of pain and instability at the fracture site. What is the most reliable treatment option? 1- Injection of platelet-rich plasma and transcutaneous electrical stimulation 2- Debridement of the nonunion site, plate fixation of the fracture, and autologous bone grafting 3- Cemented long-stem proximal humerus replacement 4- Intramedullary humeral nail with bone morphogenetic protein-2 application PREFERRED RESPONSE: 3- Cemented long-stem proximal humerus replacement DISCUSSION Cemented long-stem proximal humerus replacement is not dependent upon bone healing and will protect the remaining humeral diaphysis against subsequent fracture. Multiple studies have demonstrated high failure rates with attempted fixation of radiation-associated fractures. The radiated bone has low capacity for healing regardless of the fixation technique. Although bone graft, platelet-rich plasma, growth factors, and electrical stimulation may have efficacy for other delayed unions and nonunions, their efficacy has not been reliably demonstrated for radiation-associated fractures.  Figure 63a Figure 63b Figure 63c Figure 63d Question 63 of 100 Figures 63a through 63d are the radiograph, CT scan, MR image, and biopsy specimen of a 20-year-old rower who has a several-month history of low-back pain. He has lost 10 pounds, but has no other constitutional symptoms. There is no bowel or bladder incontinence, and he does not have neurologic symptoms. Which medication can be used to treat this condition? 1- Methotrexate 2- Nonsteroidal anti-inflammatory drugs (NSAIDs) 3- Denosumab 4- Adriamycin PREFERRED RESPONSE: 3- Denosumab DISCUSSION Giant-cell tumor of bone (GCTB) is characterized by numerous multinucleated osteoclast-type giant cells. Giant cells are known to express receptor activator of nuclear factor ?B ligand (RANKL) and are responsible for the aggressive osteolytic nature of tumors. Denosumab is a human monoclonal antibody that targets and binds with high specificity to RANKL. Although generally benign, GCTB may be associated with multiple local recurrences, multicentricity, pulmonary metastases, or lesions that cannot be removed surgically without causing substantial morbidity. In a recent phase 2 study, denosumab administered to patients with surgically salvageable and unsalvageable GCTB was well tolerated and associated with inhibited disease progression (99%) and a reduced requirement for surgery. Methotrexate and adriamycin are common chemotherapeutic drugs used in the treatment of osteosarcoma of bone, but they have shown no efficacy in the treatment of GCTB. NSAIDs are useful for treating pain associated with osteoid osteomas, but they have no effect on GCTB. Question 64 of 100 Which blastic metastases to bone are most common? 1- Breast and prostate carcinomas 2- Renal cell and thyroid carcinomas 3- Cervical and bladder carcinomas 4- Lung and liver carcinomas PREFERRED RESPONSE: 1- Breast and prostate carcinomas DISCUSSION Breast and prostate bone metastases are often blastic but may be lucent or mixed. The other responses are predominantly lucent. Algorithms to detect spinal metastases have been developed because the spine and pelvis are the most common locations for metastases.  Figure 65a Figure 65b Question 65 of 100 Figures 65a and 65b are the axial and coronal MR images of a 72-year-old woman who underwent a right knee arthroplasty 14 years ago. She has been referred by her primary care provider for evaluation and management of a right medial knee mass. What is the next best step? 1- Open surgical biopsy 2- Bone scan 3- Right knee radiographs 4- Staging CT scan of chest PREFERRED RESPONSE: 3- Right knee radiographs DISCUSSION The MR images reveal metal artifact from the knee arthroplasty and a large mass medial to the joint line that has a relatively dark signal. Because this patient had knee arthroplasty 14 years ago, a large amount of polyethylene debris may have caused a pseudotumor mass. A radiograph would reveal evidence of radiographic wear/failure and is the best next step. If the patient needs revision knee arthroplasty, a biopsy with frozen section could be performed at the same time. Open biopsy might be appropriate, but further information for pathologists regarding potential polyethylene wear would be helpful. Embarking upon a staging workup at this point is unnecessary and is not cost effective.  Figure 66a Figure 66b Question 66 of 100 Figures 66a and 66b are the clinical photographs of an 86-year-old man with a high-grade undifferentiated pleomorphic sarcoma of the right thigh. He is pictured during preparations for wide surgical excision. What is a favorable prognostic factor? 1- Superficial location with ulceration 2- Appendicular, lower extremity location 3- Histological evidence of extensive necrosis 4- Local inflammatory reaction to tumor PREFERRED RESPONSE: 2- Appendicular, lower extremity location DISCUSSION Improved survival is found in patients with soft-tissue sarcoma involving the extremities (appendicular) rather than the torso (axial) or head and neck. Although the superficial location above the fascia is associated with improved survival, malignant ulceration or fungation is an independent risk factor for poor outcome. Areas of extensive necrosis are routinely found in high-grade undifferentiated pleomorphic sarcomas and do not suggest a favorable prognosis. Local inflammatory reactions to malignant ulceration do not improve survival. Figure 67a Figure 67b Figure 67c Question 67 of 100 Figures 67a and 67b are the fused positron emission tomography/CT scans of a calf lesion at groin level in a 36- year-old woman with a soft-tissue mass. Her biopsy specimen is shown in Figure 67c. Staging studies reveal no other lesions. Using the American Joint Committee on Cancer (AJCC) staging system, the stage is most likely 1- IA (G1 T2b N0 M0). 2- IIB (G1 T2b N0 M0). 3- III (G3 T2b N1 M0). 4- IV (G3 T2b N1 M1). PREFERRED RESPONSE: 3- III (G3 T2b N1 M0). DISCUSSION This patient has a high-grade subcutaneous angiosarcoma (G3 lesion) with subfascial extension as seen in Figure 67a and nodal metastases as seen in Figure 67b (N1 [1 regional lymph node]). Because there are no other lesions identified, there are no distant metastases. Tumor size is difficult to determine without a full imaging study, but all responses are T2b (tumors >5 cm with deep extension). This is a stage III tumor according to the AJCC system. Figure 68a Figure 68b Figure 68c  Figure 68d Figure 68e Figure 68f Figure 68g Question 68 of 100 Figure 68a is the clinical photograph of a 59-year-old woman who has had a long-standing fungating ulcer on her left lower leg. She states that the ulcer began as a small reddened area and gradually enlarged during the last 4 years. Anteroposterior (AP) and lateral radiographs of her left leg are shown in Figures 68b and 68c. A whole-body bone scan is shown in Figure 68d. An axial T1-weighted MR image is shown in Figure 68e. A CT scan of the pelvis at the level of the groin is shown in Figure 68f. A histologic specimen is shown in Figure 68g. Based on the clinical, radiographic, and histologic information, the diagnosis is 1- poorly differentiated squamous carcinoma. 2- dermatofibrosarcoma protuberans. 3- melanoma. 4- locally advanced osteomyelitis. PREFERRED RESPONSE: 1- poorly differentiated squamous carcinoma. DISCUSSION The clinical photograph reveals a large ulcerated lesion of the anterior leg. The AP and lateral radiographs reveal the soft-tissue abnormality, and the bone scan reveals increased metabolic activity of the underlying tibia. T1- weighted MR imaging reveals the lesion wrapping around the anterior tibia with loss of subcutaneous tissue. A CT scan of the pelvis reveals an inguinal lymph node. The histology reveals nests of polyhedral cells surrounded by reactive fibrosis. The diagnosis is poorly differentiated squamous cell carcinoma, and the patient has the characteristic findings of a long-standing squamous cell carcinoma with poor differentiation and likely regional lymph node metastasis. The history of a small reddened area does not suggest any of the other diagnoses. Although keratin pearls are not shown in this histologic field, nests of polyhedral cells indicate squamous cell carcinoma. A small subset of patients with squamous cell carcinoma will have advanced disease. Size and differentiation, as well as type of surgical procedure and margins of resection, are of prognostic significance. Sentinel node evaluation for patients at high risk has been suggested, including evaluations for lesions that are larger in size and with poor differentiation, perineural invasion, or compromised immunologic states. The nonpreferred responses are not associated with the clinical presentation of squamous cell carcinoma. Squamous cell carcinomas are keratin positive on immunohistochemistry. Figure 69a Figure 69b Figure 69c CLINICAL SITUATION FOR QUESTIONS 69 AND 70 Figure 69a is the radiograph of a 39-year-old woman with metastatic lung cancer who underwent a prophylactic right intramedullary nail procedure. There were no intraoperative or immediate postsurgical problems. Ten hours after surgery, the patient became increasingly confused and agitated. An examination was notable for altered mentation, tachycardia, and new-onset hypoxemia. Chest radiographs were obtained before surgery (Figure 69b) and immediately after symptom onset (Figure 69c). Question 69 of 100 Which treatment will most likely improve this patient’s condition? 1- Broad-spectrum intravenous antibiotics 2- High-dose corticosteroids 3- Resuscitation and oxygen 4- Anticoagulation with heparin PREFERRED RESPONSE: 3- Resuscitation and oxygen Question 70 of 100 Which prophylactic measures may decrease risk for this postsurgical complication? 1- Distal femoral venting, perioperative hydration, and oxygenation 2- Presurgical antibiotics and antibiotic redosing 3- Perioperative normothermia with a forced-air warming device 4- Neuraxial or regional anesthesia PREFERRED RESPONSE: 1- Distal femoral venting, perioperative hydration, and oxygenation DISCUSSION This patient’s history, examination, and imaging findings are most consistent with fat embolism syndrome (FES). Classic findings of FES are mental status changes, hypoxemia, and petechial rash developing after intramedullary instrumentation procedures. FES is more common after closed femoral nailing for cancer treatment than after traumatic fractures. Patients with preexisting cardiopulmonary dysfunction are at increased risk. FES remains a clinical diagnosis, although a high-resolution CT scan may distinguish fat emboli from thrombi, and diffusion- weighted brain MRI may demonstrate fat emboli. Aggressive supportive care including as-needed mechanical ventilation and fluid resuscitation remains the primary treatment. A 2009 meta-analysis suggested that prophylactic steroids reduce the incidence and severity of FES, but evidence supporting the use of corticosteroids for established FES is anecdotal. FES prophylaxis generally consists of intraoperative hydration and oxygenation. Some authors suggest that distal femoral venting is beneficial to decrease intramedullary pressure and subsequent fat embolism. Broad-spectrum antibiotics would be an appropriate treatment for aspiration pneumonia. This patient has diffuse bilateral infiltrates as opposed to a focal infiltrate. Furthermore, the mental status changes are more consistent with FES than pneumonia. Anticoagulation would be the treatment of choice for pulmonary embolism. The timing after surgery is more consistent with FES, as are the changes in mental status.  Figure 71a Figure 71b Figure 71c Figure 71d Question 71 of 100 Figures 71a through 71d are the radiographs, MR images, and biopsy specimen of a 15-year-old boy with a several- month history of right hip pain with no history of injury. This condition is associated with increased activity of which gene product? 1- FGFR3 2- Ga stimulatory protein 3- COMP 4- EXT-1 PREFERRED RESPONSE: 2- Ga stimulatory protein DISCUSSION Fibrous dysplasia is a common benign skeletal lesion that may involve 1 bone (monostotic) or multiple bones (polyostotic) and occurs throughout the skeleton with a predilection for the long bones. The radiographic features of fibrous dysplasia typically illustrate a grayish “ground-glass” pattern that is similar to the density of cancellous bone. The key histologic features of fibrous dysplasia are trabeculae of immature bone, with no osteoblastic rimming, contained within a bland fibrous stroma of dysplastic spindle-shaped cells without any cellular features of malignancy. The etiology of fibrous dysplasia has been linked to an activating mutation in the gene that encodes the a subunit of stimulatory G protein located at 20q13.2-13.3. This leads to a constitutive activation of adenylate cyclase and increased cyclic adenosine monophosphate formation. FGFR3 mutations are associated with achondroplasia. COMP mutations are associated with pseudoachondroplasia and multiple-epiphyseal dysplasia. EXT-1 mutations are associated with multiple hereditary exostosis. Question 72 of 100 Figures 72a through 72d are the radiograph, MR images, and biopsy specimen of a 42-year-old man with an insidious onset of left hip pain. Further imaging reveals no other lesions. What is the most appropriate initial treatment? 1- Bisphosphonate or denosumab and observation with cementoplasty for refractory pain 2- Chemotherapy and wide surgical resection 3- Wide surgical resection alone 4- Extended intralesional curettage and grafting PREFERRED RESPONSE: 3- Wide surgical resection alone DISCUSSION This patient has a localized pelvic chondrosarcoma. Treatment is wide surgical resection. There is no defined role for chemotherapy or radiotherapy in the setting of conventional chondrosarcoma. Additionally, while intralesional treatment may be used for select low-grade extremity chondrosarcomas, it is not indicated for axial lesions. Treatment involving less than a wide surgical margin correlates with local recurrence.  Figure 73a Figure 73b Figure 73c Question 73 of 100 Figures 73a through 73c are the radiographs of a 68-year-old woman with a pathologic left femur fracture. A clinical examination demonstrates a large soft-tissue mass at the fracture site. CT scans of the chest, abdomen, and pelvis reveal numerous enlarged lymph nodes. Frozen section analysis at open biopsy reveals relapsed lymphoma. What is the most appropriate treatment? 1- Antegrade reconstruction nail 2- Antegrade reconstruction nail and distal femur plate fixation 3- Retrograde femoral nail 4- Retrograde femoral nail and proximal femur plate fixation PREFERRED RESPONSE: 3- Retrograde femoral nail DISCUSSION Retrograde femoral nail fixation is mechanically advantageous for this fracture because it permits fixation distal to that which can be achieved with an antegrade nail. Most modern retrograde nail systems permit placement of multiple distal interlock screws that can be locked in a fixed-angle construct. Lytic bone destruction extends to the femoral condyles, making antegrade femoral nail fixation comparatively unsuitable. Classic orthopaedic oncology principles advise fixation of the entire bone whenever feasible. Evidence indicates that new distant metastasis within a fixated femur is a rare event, and efforts to protect the “whole bone” may not be warranted, especially if they entail additional risk. This argument is stronger regarding lymphoma-associated fractures (vs the more common carcinoma-associated fractures) because chemotherapy and radiation may be used to treat lymphoma with curative rather than palliative intent. Combined plate and nail fixation is not preferred in this scenario. Plate fixation alone or augmented with cement is a viable option for this this fracture; however, the presence of a large soft tissue would likely necessitate extensive tumor debulking to appropriately place the plate. Question 74 of 100 Survival estimation in guiding surgical decision-making in metastatic spine disease includes scores that include 1- visceral metastases, multiple bone metastases, and tumor types with poorer prognosis. 2- body mass index, lower hemoglobin levels, older age, and visceral metastases. 3- peripheral vascular disease, diabetes, and visceral metastases. 4- disease confined to only adjacent vertebrae. PREFERRED RESPONSE: 1- visceral metastases, multiple bone metastases, and tumor types with poorer prognosis. DISCUSSION The modified Bauer and 6 other scoring systems have been used as accurate measures with which to establish the prognosis of metastatic spine disease. The modified Bauer scoring system assigns 1 point for no visceral metastases; 1 point if the diagnosis is not lung cancer; 1 point if the primary tumor is breast, kidney, lymphoma, or multiple myeloma; and 1 point if the tumor is a solitary skeletal metastasis. If the score totals 0 to 1, the recommendation is supportive care and no surgery. If the prognostic score is 2, short-term palliative surgery with a dorsal approach is performed. If the score is 3 to 4, middle-term local control with both ventral and dorsal approaches is suggested. The decision for or against surgery should not be based alone on any prognostic score but should take symptoms and neurological compromise into account. Figure 75a Figure 75b Question 75 of 100 A 52-year-old woman with a medical history that includes type 1 diabetes mellitus and rheumatoid arthritis has a painless right thigh mass that increased in size during the preceding year. Ultrasound was “consistent with lipoma,” and the patient underwent uneventful resection. Final pathology revealed high-grade undifferentiated sarcoma. Figures 75a and 75b are the clinical photograph and postresection MR image. The treatment rendered prior to referral to a sarcoma center most likely will result in increased 1- likelihood for amputation. 2- likelihood for flap coverage. 3- overall mortality. 4- need for radiation therapy. PREFERRED RESPONSE: 2- likelihood for flap coverage. DISCUSSION This patient had an unplanned resection of a high-grade soft-tissue sarcoma. The MR image shows that the unplanned resection extended deep to the fascia. Errors in this case include failure to obtain cross-sectional imaging of a tumor deep to the fascia prior to resection and use of a transverse incision. Flap coverage for unplanned soft- tissue sarcoma resection can increase the complexity of soft-tissue reconstruction. Radiation therapy would have been indicated for a high-grade soft-tissue sarcoma deep to the fascia regardless of the biopsy technique. Overall, mortality does not correlate with errors in biopsy technique. Although many studies demonstrate increased local recurrence risk is associated with unplanned resection, amputation is not indicated in most cases. Radiation therapy and wide re-resection with salvage of the involved limb is the treatment of choice. Figure 76a Figure 76b Question 76 of 100 A 16-year-old boy with a high-grade conventional osteosarcoma of the right proximal tibia has completed neoadjuvant chemotherapy. A restaging radiograph and MR image are shown in Figures 76a and 76b. Wide resection with limb salvage is planned. Which muscle will provide the primary protective margin for the tibial nerve and popliteal vessels? 1- Soleus 2- Popliteus 3- Medial gastrocnemius 4- Lateral gastrocnemius PREFERRED RESPONSE: 2- Popliteus DISCUSSION The popliteus muscle originates from the posterior aspect of the proximal tibia and serves as the primary barrier to tumor encroachment upon the tibial nerve and popliteal vessels. The medial and lateral heads of the gastrocnemius lie superficial to the neurovascular bundle. A portion of the soleus originates from the lateral proximal tibia, forming part of the soleal arch through which the neurovascular bundle passes; however, the majority of the soleus is superficial to the neurovascular structures. Figure 77a Figure 77b Question 77 of 100 Figures 77a and 77b are the recent knee radiographs of a 53-year-old man whose history includes tobacco use and secondary polycythemia. He is now experiencing bilateral knee pain, knee swelling, and increasing discomfort with ambulation. All efforts at nonsurgical treatment have failed. What is the most reasonable next treatment option? 1- Core biopsy 2- Knee arthroplasty with postsurgical radiation therapy 3- Knee arthroplasty 4- Debridement with intravenous antibiotics PREFERRED RESPONSE: 3- Knee arthroplasty DISCUSSION The radiographs reveal bilateral bone infarcts with subchondral collapse. The images are diagnostic for bone infarct. Other hematological conditions are associated with multiple bone infarcts, including sickle-cell disease, hemophilia, aplastic anemia, thalassemia, and acute lymphoblastic leukemia. Postsurgical radiation therapy is considered for Paget disease, but the radiographic appearance is not consistent with that diagnosis. Figure 78a Figure 78b Figure 78c Figure 78d CLINICAL SITUATION FOR QUESTIONS 78 AND 79 Figures 78a through 78d are the radiograph, CT scans, and biopsy specimen of a 45-year-old man with a history of treatment for localized low-grade pelvic chondrosarcoma with limb salvage. He now has recurrent pain about his hip. Question 78 of 100 This patient should be told that 1- he has developed a prosthetic joint i