Oncology | Ewing Sarcoma

0:00Hi everyone, welcome back to the Med Bullets Step 2 and 3 podcast. In today's episode, we covered the topic of Ewing Sarcoma found under the oncology section at medbullets.com. Let's begin with a clinical snapshot. A 12-year-old boy presents to the pediatric emergency department with pain in his right lower extremity. He was recently playing soccer, but he denies any trauma to the leg. Physical exam is notable for mild swelling in the right mid-tibia and tenderness to palpation. A radiograph of the leg demonstrates periosteolivation and onion skinning concerning for malignancy. Let's continue with an introduction to Ewing Sarcoma. As a general overview, remember that this is a neoplastic disease of the bone that most often arises in the long bones of the extremities and the pelvic bones. In terms of the incidence, remember that children and adolescents are most commonly affected with the median age of diagnosis being 15 years of age.

1:05In terms of the pathophysiology, there's a chromosomal translocation T1112 that leads to the production of an oncogenic fusion protein, EWS, FLI-1, that enhances cellular proliferation and malignant transformation. In terms of the genetics, there is a chromosomal translocation between the Ewing Sarcoma breakage region 1 or EWS and a rhithroblast transformation-specific family transcription factors, FLI-1, which results in the T1122 fusion protein. This leads to the production of the oncogenic fusion proteins. Moving on to the presentation, symptoms will include constitutional symptoms in 10 to 20% of cases. This may include fever, weight loss, and fatigue. There will also be pain at the site of involvement. On exam, one may note swelling and tenderness at the site of involvement. In terms of further imaging, radiography is indicated as the initial

2:08imaging study. Specific findings may include onion skin patterns of osteolytic lesions. This commonly affects the diaphysis of the bone, but can also involve the metaphysis. One may also note codmin's triangle, which is due to periosteolivation. MRI is indicated to evaluate for the extent of disease. This provides an image with higher definition than radiography. Radio nucleic bone scan is indicated to survey the entire skeleton for the presence of metastasis. In terms of further studies, invasive studies may include an open or coronetal biopsy. This is indicated to confirm the diagnosis and allows one to perform histology and molecular testing. Findings on histology may include small round blue cells that are poorly differentiated. These are of neuro-acted dermal origin and demonstrate a scant cytoplasm. Molecular testing will demonstrate chromosomal translocations of 1122.

3:10In terms of the differential, make sure to think about osteosarcoma, with differentiating factors being that this will present with malignant osteoblasts, and the lesions are most often found in the metaphysis, and they typically have a rim of bone formation, which is uncommon in uing sarcoma. In terms of treatment, medical options include chemotherapy. This is indicated typically as the initial treatment option in most cases. Another option is radiation therapy. This may be used if surgical resection is not indicated. Operative options include resection, which is indicated as a treatment option for local disease. And lastly, complications related to uing sarcoma include metastasis, which may occur to other bone sites, bone marrow, or the lungs. Now that we've discussed the major points relating to uing sarcoma, let's walk through a question to apply what we've learned and get a sense of how the topic might be tested. For this question, consider the following clinical scenario. A 15-year-old boy

4:16presents with a three-week history of right leg pain. He is an active soccer player, but his satout of practice due to increased pain for the last week, along with daily fevers and fatigue. His temperature is 101 degrees Fahrenheit, or 38.8 degrees Celsius. Blood pressure is 125 over 78. Pulse is 80 beats per minute, and respirations are 15 breaths per minute. On exam, his right leg demonstrates swelling and tenderness of the midcheft at the tibia. A radiograph of the right leg is obtained, which demonstrates onion skinning. Laboratory evaluation reveals a white blood cell count of 13,000, and an erythrocyte sedimentation rate of 30. A bone biopsy is performed, which demonstrates small, dark, round, and densely arranged undifferentiated cells. Which of the following is the most likely cause of this patient's disease? In the answer choices are choice one, T-1122 chromosomal translocation,

5:21choice two, receptor activator of nuclear factor capobata ligand overactivation, choice three, salmonella species, choice four, staflochoccus aureus, or choice five, tumor protein 53 mutation. The best answer to this question is choice one, T-1122 chromosomal translocation. This patient presents with progressive leg pain, fevers, fatigue, leukocytosis, elevated ESR, radiographic evidence of diaphyseopereostial reaction, and small blue and aplastic cells on bone biopsy, consistent with viewing sarcoma. A T-1122 chromosomal translocation drives the oncogenesis of viewing sarcoma. Ewing sarcoma is a malignant bone tumor that predominantly affects Caucasian males under 20 years of age. The T-1122 chromosomal translocation

6:24leads to a fusion of the Ewing sarcoma breakpoint region one protein and the friend leukemia integration one transcription factor to create the EWS FLI-1 oncogenic protein. Ewing sarcoma most often presents in the diaphysis of lower extremity long bones, but can arise in any bone and occasionally in the soft tissues. The tumor can be aggressive with early metastasis. Treatment involves a combination of local excision, chemotherapy, and radiation. Let's also discuss whether other choices are incorrect. Choice 2. Receptor activator nuclear factor capobata ligand overactivation drives the pathogenesis of giant cell tumors, which present as progressive bone pain primarily in individuals 20 to 40 years old. The rank ligand overactivation leads to local bone resorption at the epiphysis, causing the classic soap bubble appearance on plain radiographs. Choice 3. Salmonella species are the most common cause of bacterial osteomyelitis

7:28in patients with sickle cell disease, and it presents similarly to the patient with focal bone pain, overlying warmth, erythema, fever, and radiographic evidence of focal bony lysis with surrounding periosteal thickening. However, Salmonella osteomyelitis would not have small primitive cells on bone biopsy. Choice 4. Staphylococcus orius is the most common overall cause of bacterial osteomyelitis, and would also present similarly to this patient with fever, progressive bone pain, and reactive bone radiographic findings. However, small primitive cells on bone biopsy would be atypical. Choice 5. Tumor protein 53 mutation leads to many cancer syndromes, including osteosarcoma, which presents with progressive bone pain, and classically the conman triangle of reactive periosteolivation on plain radiograph. In contrast to ewing sarcoma,

8:29osteosarcoma occurs at the metaphysis and systemic symptoms such as fever and fatigue are less common. Finally, a bullet summary. Ewing sarcoma is a malignant, undifferentiated, predominantly pediatric bone tumor that presents with pain, fever, fatigue, and onion skin perioste reaction on plain radiograph, and it is driven by a T1122 chromosome transplantation. That's all for this review about Ewing sarcoma. We hope that was helpful. This is the Med Bullets Step 2 and 3 podcast, a daily audio review session for Med Bullets, the free learning and collaboration community for medical student education. As a reminder, you can follow along with these podcast episodes by reviewing the topics directly on medbullets.com. You can listen to these episodes on the Med Bullets website or phone app while reading through the topic. If the Med Bullets podcast has been valuable to you, we'd be thrilled if you consider leaving us a 5 star rating and writing

9:33us a review on Apple podcasts. It will help us spread the word and increase our discoverability tremendously. Thanks for tuning in. We'll see you all tomorrow, right here on the Med Bullets Step 2 and 3 podcast.