A 55-year-old male presents to his primary care physician complaining of right hip pain for the past eight months. He also reports progressive loss of hearing over the same time period. Radiographic imaging reveals multiple areas of expanded bony cortices and coarsened trabeculae in his right hip and skull. Laboratory analysis reveals an isolated elevation in alkaline phosphatase with normal levels of serum calcium and phosphate. Which of the following histologic findings is most likely to be seen if one of the lesions were biopsied?
Q2
An investigator is studying DNA repair processes in an experimental animal. The investigator inactivates a gene encoding a protein that physiologically excises nucleotides from damaged, bulky, helix-distorting DNA strands. A patient with a similar defect in this gene is most likely to present with which of the following findings?
Q3
A 12-year-old Caucasian male presents with his mother to the pediatrician’s office complaining of right thigh pain. He reports that he has noticed slowly progressive pain and swelling over the distal aspect of his right thigh over the past two months. He denies any recent trauma to the area and his temperature is 100.9°F (38.3°C). On exam, there is swelling and tenderness overlying the distal right femoral diaphysis. Laboratory evaluation is notable for an elevated white blood cell (WBC) count and elevated erythrocyte sedimentation rate (ESR). A radiograph of the patient’s right leg is shown. Biopsy of the lesion demonstrates sheets of monotonous small round blue cells with minimal cytoplasm. Which of the following genetic mutations is most likely associated with this patient’s condition?
Q4
A 5-year-old boy is brought to the pediatric clinic for evaluation of fever, pain, swelling in the left leg, and limping. Review of systems and history is otherwise unremarkable. The vital signs include: pulse 110/min, temperature 38.1°C (100.6°F), and blood pressure 100/70 mm Hg. On examination, there is a tender swelling over the lower part of his left leg. Which 1 of the following X-ray findings is most suggestive of Ewing’s sarcoma?
Q5
An 18-month-old boy is brought to the doctor’s office for evaluation of abdominal pain. The boy looks emaciated and he is now significantly below his growth chart predicted weight. The family history is non-contributory. The vital signs are unremarkable. On physical examination, a non-tender mass is felt in the upper part of the abdomen. A magnetic resonance image (MRI) scan of his abdomen demonstrates a mass in his right adrenal gland. Biopsy of the mass demonstrates an abundance of small round blue cells. With this biopsy result, which 1 of the following findings would confirm the diagnosis?
Q6
A 4-year-old boy with Down syndrome presents with fatigue and recurrent infections. CBC shows WBC 150,000/μL with 90% myeloblasts, hemoglobin 6.5 g/dL, platelets 15,000/μL. Flow cytometry confirms acute myeloid leukemia with megakaryoblastic features (AMKL). The parents are concerned about treatment intensity given their child's baseline developmental delays and increased treatment-related toxicity risk in Down syndrome. Evaluate the treatment approach considering the unique biology and competing risks.
Q7
A 15-year-old boy presents with right distal femur pain and a palpable mass. X-ray shows a mixed lytic-sclerotic lesion with periosteal elevation creating a Codman triangle and sunburst pattern. Biopsy confirms osteosarcoma. Staging shows pulmonary micrometastases. Alkaline phosphatase is markedly elevated. The family requests consideration of alternative therapies and limb salvage options. Synthesize the treatment plan addressing oncologic outcomes and functional preservation.
Q8
A 2-year-old girl presents with a large abdominal mass, aniridia, and developmental delay. Family history reveals a sibling who died of Wilms tumor at age 3. Genetic testing shows a germline WT1 mutation. Ultrasound reveals bilateral renal masses. The parents are concerned about treatment options that preserve renal function. Evaluate the optimal management strategy considering long-term outcomes.
Q9
A 6-year-old girl presents with acute onset left leg pain and refusal to bear weight. X-ray shows a lytic lesion with periosteal reaction in the femoral diaphysis demonstrating an 'onion-skin' pattern. MRI reveals a large soft tissue mass. Biopsy shows small round blue cells that are CD99 positive. Molecular studies show EWSR1-FLI1 fusion. Staging shows no metastases. Analyze the pathophysiology and treatment rationale.
Q10
A 9-year-old boy presents with painless cervical lymphadenopathy and fever. Biopsy shows Reed-Sternberg cells in a background of inflammatory cells. Staging workup reveals disease in cervical and mediastinal lymph nodes above the diaphragm without B symptoms. PET-CT shows no extranodal involvement. Analyze the stage and optimal treatment approach.
Ewing sarcoma US Medical PG Practice Questions and MCQs
Question 1: A 55-year-old male presents to his primary care physician complaining of right hip pain for the past eight months. He also reports progressive loss of hearing over the same time period. Radiographic imaging reveals multiple areas of expanded bony cortices and coarsened trabeculae in his right hip and skull. Laboratory analysis reveals an isolated elevation in alkaline phosphatase with normal levels of serum calcium and phosphate. Which of the following histologic findings is most likely to be seen if one of the lesions were biopsied?
A. Mature lamellar bone with collagen fibers arranged in lamellae
B. Immature woven bone with collagen fibers arranged irregularly (Correct Answer)
C. Chondroblasts and chondrocytes forming a cartilaginous matrix
D. Sheets of monotonous round blue cells
E. Large pleomorphic cells with numerous atypical mitotic figures and “lacey” osteoid formation
Explanation: ***Immature woven bone with collagen fibers arranged irregularly***
- The clinical presentation (hip pain, hearing loss, elevated **alkaline phosphatase**, and radiographic findings of expanded cortices and coarsened trabeculae) is highly suggestive of **Paget's disease of bone** (osteitis deformans).
- Biopsy of a Pagetic lesion classically shows a **mosaic pattern of woven and lamellar bone**, with prominent cement lines, reflecting the chaotic and rapid bone turnover. **Immature woven bone** is a hallmark.
*Mature lamellar bone with collagen fibers arranged in lamellae*
- This describes normal healthy adult bone and would not be seen in a condition characterized by **disordered bone remodeling** such as Paget's disease.
- **Lamellar bone** is the characteristic type of bone found in healthy adults, where collagen fibers are organized in parallel layers.
*Chondroblasts and chondrocytes forming a cartilaginous matrix*
- This describes **cartilage**, which is not the primary tissue affected in Paget's disease within bone lesions.
- This finding would be typical of cartilaginous tumors or normal epiphyseal plates, not a bone remodeling disorder.
*Sheets of monotonous round blue cells*
- This description is characteristic of certain **hematologic malignancies** or small round cell tumors, such as lymphomas, Ewing sarcoma, or neuroblastoma.
- These findings are not associated with Paget's disease, which is a disorder of bone remodeling.
*Large pleomorphic cells with numerous atypical mitotic figures and “lacey” osteoid formation*
- This describes **osteosarcoma**, a primary malignant bone tumor, which can be a rare complication of long-standing Paget's disease but is not the primary histological finding of Paget's disease itself.
- While the patient has Paget's, the question asks for the most likely finding of the lesion itself, not a potential malignant transformation.
Question 2: An investigator is studying DNA repair processes in an experimental animal. The investigator inactivates a gene encoding a protein that physiologically excises nucleotides from damaged, bulky, helix-distorting DNA strands. A patient with a similar defect in this gene is most likely to present with which of the following findings?
A. Ataxic gait and facial telangiectasias
B. Malignant breast and ovarian growths
C. Leukocoria and a painful bone mass
D. Colorectal and endometrial cancers
E. Dry skin and increased photosensitivity (Correct Answer)
Explanation: ***Dry skin and increased photosensitivity***
- The description of excising **nucleotides from damaged, bulky, helix-distorting DNA strands** points to a defect in **Nucleotide Excision Repair (NER)**.
- Patients with defects in NER, such as those with **xeroderma pigmentosum**, are highly susceptible to UV-induced DNA damage, leading to **dry skin, increased photosensitivity**, and a high risk of skin cancers.
*Ataxic gait and facial telangiectasias*
- This constellation of symptoms is characteristic of **ataxia-telangiectasia**, a disorder caused by mutations in the **ATM gene**, which is involved in **DNA double-strand break repair**.
- While a DNA repair defect, it's not primarily linked to the excision of bulky, helix-distorting DNA strands.
*Malignant breast and ovarian growths*
- These cancers are commonly associated with mutations in the **BRCA1 and BRCA2 genes**, which play crucial roles in **homologous recombination repair of DNA double-strand breaks**.
- This type of repair is distinct from the excision of bulky, helix-distorting DNA strands described in the question.
*Leukocoria and a painful bone mass*
- **Leukocoria** can indicate **retinoblastoma**, linked to mutations in the **RB1 tumor suppressor gene**, which regulates the cell cycle but isn't primarily a DNA repair gene.
- A painful bone mass could suggest **osteosarcoma**, which is sometimes seen in retinoblastoma patients but not directly related to the specific DNA repair defect described.
*Colorectal and endometrial cancers*
- These cancers are hallmarks of **Lynch syndrome (hereditary nonpolyposis colorectal cancer - HNPCC)**, which is caused by defects in **Mismatch Repair (MMR)** genes (e.g., MLH1, MSH2, MSH6, PMS2).
- Mismatch repair corrects errors that arise during DNA replication, which is different from excising bulky, helix-distorting DNA damage.
Question 3: A 12-year-old Caucasian male presents with his mother to the pediatrician’s office complaining of right thigh pain. He reports that he has noticed slowly progressive pain and swelling over the distal aspect of his right thigh over the past two months. He denies any recent trauma to the area and his temperature is 100.9°F (38.3°C). On exam, there is swelling and tenderness overlying the distal right femoral diaphysis. Laboratory evaluation is notable for an elevated white blood cell (WBC) count and elevated erythrocyte sedimentation rate (ESR). A radiograph of the patient’s right leg is shown. Biopsy of the lesion demonstrates sheets of monotonous small round blue cells with minimal cytoplasm. Which of the following genetic mutations is most likely associated with this patient’s condition?
A. t(11;22) (Correct Answer)
B. RB1 inactivation
C. TP53 inactivation
D. t(8;14)
E. t(X;18)
Explanation: ***t(11;22)***
- The clinical presentation of a **12-year-old male** with progressive **thigh pain and swelling**, fever, elevated WBC and ESR, a radiograph showing a bone lesion [1], and a biopsy revealing **small round blue cells with minimal cytoplasm**, is highly suggestive of **Ewing sarcoma** [2].
- **Ewing sarcoma** is characterized by the **t(11;22)(q24;q12) chromosomal translocation**, which fuses the *EWSR1* gene with the *FLI1* gene, leading to the formation of a chimeric transcription factor.
*t(X;18)*
- The **t(X;18) translocation** is the characteristic genetic abnormality of **synovial sarcoma**, another soft tissue malignancy.
- While synovial sarcoma can also present in young patients, it typically affects older adolescents and young adults, and the histology differs from the small round blue cell pattern seen in Ewing sarcoma [2].
*RB1 inactivation*
- **RB1 gene inactivation** is centrally involved in the pathogenesis of **retinoblastoma**, a childhood eye cancer.
- It also plays a role in various other cancers, such as **osteosarcoma** [3] and small cell lung cancer, but its primary association is not with Ewing sarcoma.
*TP53 inactivation*
- **TP53 gene inactivation** is a common event in a wide range of human cancers, as *TP53* is a critical **tumor suppressor gene**.
- While *TP53* mutations can be found in some sarcomas, it is not the defining or most likely specific genetic mutation for **Ewing sarcoma**.
*t(8;14)*
- The **t(8;14)(q24;q32) chromosomal translocation** is the characteristic genetic abnormality found in **Burkitt lymphoma**.
- This translocation leads to the **c-MYC proto-oncogene** being placed near the immunoglobulin heavy chain locus, promoting its overexpression, which is unrelated to Ewing sarcoma.
**References:**
[1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Osteoarticular And Connective Tissue Disease, pp. 671-672.
[2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1204-1205.
[3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1200-1202.
Question 4: A 5-year-old boy is brought to the pediatric clinic for evaluation of fever, pain, swelling in the left leg, and limping. Review of systems and history is otherwise unremarkable. The vital signs include: pulse 110/min, temperature 38.1°C (100.6°F), and blood pressure 100/70 mm Hg. On examination, there is a tender swelling over the lower part of his left leg. Which 1 of the following X-ray findings is most suggestive of Ewing’s sarcoma?
A. Mixed lytic and blastic appearance in the X-ray
B. X-ray showing broad-based projections from the surface of the bone
C. X-ray showing lytic bone lesion with periosteal reaction (Correct Answer)
D. X-ray showing a sharply marginated radiolucent area within the apophysis
E. X-ray showing deep muscle plane displacement from the metaphysis
Explanation: ***X-ray showing lytic bone lesion with periosteal reaction***
- **Ewing's sarcoma** typically presents as a **lytic bone lesion** with an **aggressive periosteal reaction**, often described as an **"onion-skin" appearance** due to layers of new bone formation.
- The combination of fever, localized pain, swelling, and limping in a child, along with a lytic lesion and periosteal reaction on X-ray, is highly suggestive of this diagnosis.
*Mixed lytic and blastic appearance in the X-ray*
- A mixed lytic and blastic appearance is more characteristic of metastatic disease or certain other bone tumors like osteosarcoma in later stages, but less specific for primary Ewing's sarcoma.
- While some blastic components can occur, the primary hallmark of Ewing's is its lytic and destructive nature with typical periosteal reactions.
*X-ray showing broad-based projections from the surface of the bone*
- Broad-based projections from the bone surface are characteristic of **osteochondromas**, which are benign bone tumors.
- These are typically painless unless they impinge on nerves or blood vessels, and do not usually present with systemic symptoms like fever.
*X-ray showing a sharply marginated radiolucent area within the apophysis*
- A sharply marginated radiolucent area within the apophysis could suggest a benign lesion like a **fibrous cortical defect** or a **non-ossifying fibroma**, particularly if it is well-defined and non-aggressive.
- It does not indicate the aggressive, destructive nature seen with Ewing's sarcoma.
*X-ray showing deep muscle plane displacement from the metaphysis*
- Deep muscle plane displacement can indicate a significant soft tissue mass, but it is a **non-specific finding** and does not point directly to the bony destruction or characteristic periosteal reaction of Ewing's sarcoma.
- This finding could be associated with various soft tissue tumors, hematomas, or infections.
Question 5: An 18-month-old boy is brought to the doctor’s office for evaluation of abdominal pain. The boy looks emaciated and he is now significantly below his growth chart predicted weight. The family history is non-contributory. The vital signs are unremarkable. On physical examination, a non-tender mass is felt in the upper part of the abdomen. A magnetic resonance image (MRI) scan of his abdomen demonstrates a mass in his right adrenal gland. Biopsy of the mass demonstrates an abundance of small round blue cells. With this biopsy result, which 1 of the following findings would confirm the diagnosis?
A. Elevation of vanillylmandelic acid in the urine (Correct Answer)
B. MRI showing the intrarenal origin of the mass
C. Increased lactic dehydrogenase
D. Increased alpha-fetoprotein
E. Radiograph of the bone showing the presence of lytic bone lesion with periosteal reaction
Explanation: ***Elevation of vanillylmandelic acid in the urine***
- The clinical presentation (abdominal mass, emaciation, age) and biopsy finding of **small round blue cells** in the adrenal gland are highly suggestive of **neuroblastoma**.
- **Neuroblastomas** arise from neural crest cells and characteristically produce **catecholamines**, leading to elevated urinary levels of their metabolites like **vanillylmandelic acid (VMA)** and **homovanillic acid (HVA)**.
*MRI showing the intrarenal origin of the mass*
- An **intrarenal origin** of the mass would suggest a **Wilms tumor** (nephroblastoma), which is another common pediatric abdominal malignancy.
- However, the mass is described as being in the **adrenal gland**, and the biopsy shows small round blue cells, which are characteristic of neuroblastoma rather than Wilms tumor.
*Increased lactic dehydrogenase*
- Elevated **lactic dehydrogenase (LDH)** is a non-specific tumor marker often associated with a high tumor burden and rapid cell turnover in various malignancies, including neuroblastoma.
- While it can be elevated in neuroblastoma, it is not a specific diagnostic marker and would not confirm the diagnosis over other pediatric cancers.
*Increased alpha-fetoprotein*
- Elevated **alpha-fetoprotein (AFP)** is primarily associated with **hepatoblastoma** and **germ cell tumors**.
- It is not typically elevated in neuroblastoma and would therefore not confirm this diagnosis.
*Radiograph of the bone showing the presence of lytic bone lesion with periosteal reaction*
- While **neuroblastoma** can metastasize to bones, causing **lytic bone lesions** and a periosteal reaction, these findings indicate metastatic disease rather than confirming the primary diagnosis.
- A bone radiograph showing such lesions points to advanced disease but doesn't specifically confirm neuroblastoma as the primary tumor type.
Question 6: A 4-year-old boy with Down syndrome presents with fatigue and recurrent infections. CBC shows WBC 150,000/μL with 90% myeloblasts, hemoglobin 6.5 g/dL, platelets 15,000/μL. Flow cytometry confirms acute myeloid leukemia with megakaryoblastic features (AMKL). The parents are concerned about treatment intensity given their child's baseline developmental delays and increased treatment-related toxicity risk in Down syndrome. Evaluate the treatment approach considering the unique biology and competing risks.
A. Modified chemotherapy protocol with dose reductions of cytarabine but standard anthracyclines, given Down syndrome-associated AML excellent prognosis (Correct Answer)
B. Bone marrow transplantation as first-line therapy
C. Palliative care approach given poor baseline function and high treatment toxicity
D. Reduced-intensity chemotherapy due to Down syndrome and baseline developmental concerns
E. Standard AML chemotherapy protocol without modification
Explanation: ***Modified chemotherapy protocol with dose reductions of cytarabine but standard anthracyclines, given Down syndrome-associated AML excellent prognosis***
- Children with **Down syndrome-associated AML (DS-AML)**, specifically the **megakaryoblastic (AMKL)** subtype, exhibit hyper-sensitivity to **cytarabine** due to lower levels of the enzyme cytidine deaminase.
- While they have an **excellent prognosis** (cure rates >80%), they face a high risk of **treatment-related toxicity**, necessitating dose modifications to improve safety without sacrificing efficacy.
*Bone marrow transplantation as first-line therapy*
- **Hematopoietic stem cell transplant** is not indicated as first-line therapy because DS-AML responds exceptionally well to **chemotherapy** alone.
- Transplant carries a high risk of **morbidity and mortality**, which is unnecessary given the high survival rates with modified chemo regimens.
*Palliative care approach given poor baseline function and high treatment toxicity*
- Palliative care is inappropriate as the primary strategy because DS-AML is a **highly curable** malignancy in pediatric patients.
- Developmental delays and baseline status do not preclude aggressive **curative intent** therapy, as long as protocols are adjusted for toxicity.
*Reduced-intensity chemotherapy due to Down syndrome and baseline developmental concerns*
- While toxicity is a concern, broad "reduced-intensity" therapy may lead to **under-treatment** and increased risk of **relapse**.
- Specific modifications, rather than blanket reductions, are required to maintain the **high cure rate** associated with the **GATA1 mutation** characteristic of this disease.
*Standard AML chemotherapy protocol without modification*
- Using standard AML protocols in children with Down syndrome leads to **excessive toxicity**, particularly severe **mucositis** and life-threatening infections.
- The unique **pharmacogenomics** of Down syndrome patients requires dedicated protocols like the **Children's Oncology Group (COG) AAML0431** to manage treatment risks.
Question 7: A 15-year-old boy presents with right distal femur pain and a palpable mass. X-ray shows a mixed lytic-sclerotic lesion with periosteal elevation creating a Codman triangle and sunburst pattern. Biopsy confirms osteosarcoma. Staging shows pulmonary micrometastases. Alkaline phosphatase is markedly elevated. The family requests consideration of alternative therapies and limb salvage options. Synthesize the treatment plan addressing oncologic outcomes and functional preservation.
A. Limb salvage surgery without chemotherapy followed by observation
B. Radiation therapy alone as primary treatment
C. Palliative care focus given metastatic disease at presentation
D. Immediate amputation without chemotherapy due to metastatic disease
E. Neoadjuvant chemotherapy, tumor necrosis assessment, limb salvage with endoprosthesis, and adjuvant chemotherapy with potential pulmonary metastasectomy (Correct Answer)
Explanation: ***Neoadjuvant chemotherapy, tumor necrosis assessment, limb salvage with endoprosthesis, and adjuvant chemotherapy with potential pulmonary metastasectomy***
- This comprehensive approach is the standard of care; **neoadjuvant chemotherapy** treats micrometastases and allows for **tumor necrosis assessment**, a critical prognostic factor (>90% necrosis).
- **Limb salvage** is oncologically equivalent to amputation when **wide margins** are achievable, and aggressive resection of **pulmonary metastases** can still lead to long-term survival in up to 40% of patients.
*Limb salvage surgery without chemotherapy followed by observation*
- Surgery alone is insufficient because **osteosarcoma** is considered a systemic disease at diagnosis, with **pulmonary micrometastases** present in nearly all patients.
- Omitting **adjuvant chemotherapy** results in high recurrence rates and significantly lower survival outcomes.
*Radiation therapy alone as primary treatment*
- Osteosarcoma is traditionally considered a **radioresistant** tumor, making radiation therapy ineffective as a primary or sole curative modality.
- Surgical resection with **clear margins** is mandatory for local control and achieving a cure.
*Palliative care focus given metastatic disease at presentation*
- Unlike many other adult cancers, **pediatric osteosarcoma** with limited metastatic disease (especially to the lungs) is potentially curable with aggressive therapy.
- A shift to purely **palliative care** would be premature and denies the patient a significant chance at long-term survival.
*Immediate amputation without chemotherapy due to metastatic disease*
- **Immediate amputation** does not address systemic micrometastases and provides no clinical benefit over **limb salvage** if negative margins can be obtained.
- Bypassing **neoadjuvant chemotherapy** loses the opportunity to assess **chemosensitivity**, which is vital for tailoring postoperative treatment.
Question 8: A 2-year-old girl presents with a large abdominal mass, aniridia, and developmental delay. Family history reveals a sibling who died of Wilms tumor at age 3. Genetic testing shows a germline WT1 mutation. Ultrasound reveals bilateral renal masses. The parents are concerned about treatment options that preserve renal function. Evaluate the optimal management strategy considering long-term outcomes.
A. Chemotherapy followed by bilateral nephrectomy and immediate transplantation
B. Bilateral renal biopsy followed by neoadjuvant chemotherapy and bilateral nephron-sparing surgery (Correct Answer)
C. Close surveillance with delayed intervention until symptoms develop
D. Immediate bilateral nephrectomy with dialysis and future transplantation
E. Unilateral nephrectomy of the larger tumor followed by observation of contralateral kidney
Explanation: ***Bilateral renal biopsy followed by neoadjuvant chemotherapy and bilateral nephron-sparing surgery***
- The patient presents with **WAGR syndrome** (Wilms tumor, Aniridia, Genitourinary anomalies, and Range of developmental delays), which is associated with a high risk of **bilateral Wilms tumors** and subsequent chronic renal failure.
- **Neoadjuvant chemotherapy** is used to reduce tumor volume, facilitating **nephron-sparing surgery** (partial nephrectomy) to preserve as much renal parenchyma as possible and avoid the need for dialysis.
*Chemotherapy followed by bilateral nephrectomy and immediate transplantation*
- Complete **bilateral nephrectomy** results in permanent renal failure, requiring lifelong dialysis which is associated with high morbidity in very young children.
- **Kidney transplantation** is typically deferred for 1–2 years after completion of chemotherapy to ensure there is no tumor recurrence.
*Close surveillance with delayed intervention until symptoms develop*
- **Wilms tumors** are aggressive malignancies that require timely intervention to prevent local progression and **distant metastasis** (commonly to the lungs).
- Delaying treatment in a patient with a known **germline WT1 mutation** and visible masses is unethical and significantly worsens the oncologic prognosis.
*Immediate bilateral nephrectomy with dialysis and future transplantation*
- Proceeding directly to surgery without **neoadjuvant chemotherapy** misses the opportunity to shrink the tumors and increase the success rate of **nephron preservation**.
- Managing a 2-year-old on **long-term dialysis** is technically challenging and carries a significant risk of developmental delay and cardiovascular complications.
*Unilateral nephrectomy of the larger tumor followed by observation of contralateral kidney*
- Leaving a confirmed malignant tumor in the contralateral kidney without treatment allows for **metastatic spread** and continued tumor growth.
- The standard of care for bilateral disease involves treating both sides simultaneously or in a planned sequence to achieve **complete oncologic clearance**.
Question 9: A 6-year-old girl presents with acute onset left leg pain and refusal to bear weight. X-ray shows a lytic lesion with periosteal reaction in the femoral diaphysis demonstrating an 'onion-skin' pattern. MRI reveals a large soft tissue mass. Biopsy shows small round blue cells that are CD99 positive. Molecular studies show EWSR1-FLI1 fusion. Staging shows no metastases. Analyze the pathophysiology and treatment rationale.
A. Osteosarcoma requiring neoadjuvant chemotherapy and limb salvage surgery
B. Ewing sarcoma requiring neoadjuvant chemotherapy, local control with surgery or radiation, and adjuvant chemotherapy (Correct Answer)
C. Neuroblastoma requiring MIBG therapy and immunotherapy
D. Benign reactive process requiring symptomatic treatment only
E. Osteomyelitis requiring prolonged antibiotics and possible debridement
Explanation: ***Ewing sarcoma requiring neoadjuvant chemotherapy, local control with surgery or radiation, and adjuvant chemotherapy***
- The presence of **small round blue cells**, **CD99 positivity**, and the **EWSR1-FLI1 fusion** (t(11;22)) is pathognomonic for **Ewing Sarcoma**.
- Radiographic findings of an **'onion-skin' periosteal reaction** in the **diaphysis** of a long bone confirm the need for multimodal therapy including chemotherapy and local control.
*Osteosarcoma requiring neoadjuvant chemotherapy and limb salvage surgery*
- **Osteosarcoma** typically presents with a **'sunburst' pattern** or **Codman triangle** on X-ray and occurs in the **metaphysis**, not the diaphysis.
- Histology would show **malignant osteoid** production rather than concentrated small round blue cells with CD99 expression.
*Neuroblastoma requiring MIBG therapy and immunotherapy*
- While **neuroblastoma** is a small round blue cell tumor, it usually presents as an **abdominal mass** and lacks the specific **EWSR1-FLI1** translocation.
- **MIBG therapy** is specific to sympathoadrenal tumors and is not the primary treatment for primary bone malignancies like Ewing sarcoma.
*Benign reactive process requiring symptomatic treatment only*
- The presence of a **large soft tissue mass**, **lytic bone destruction**, and specific **molecular fusions** definitively rule out a benign process.
- Reactive processes do not exhibit the **malignant cellular morphology** or the high-grade clinical progression described.
*Osteomyelitis requiring prolonged antibiotics and possible debridement*
- Although osteomyelitis can cause a periosteal reaction and pain, it would typically present with **fever**, elevated **inflammatory markers**, and lack a soft tissue mass with **atypical fusions**.
- Biopsy in osteomyelitis would reveal **neutrophils** and necrotic debris (sequestrum) rather than a uniform population of **CD99-positive blue cells**.
Question 10: A 9-year-old boy presents with painless cervical lymphadenopathy and fever. Biopsy shows Reed-Sternberg cells in a background of inflammatory cells. Staging workup reveals disease in cervical and mediastinal lymph nodes above the diaphragm without B symptoms. PET-CT shows no extranodal involvement. Analyze the stage and optimal treatment approach.
A. Stage IV disease requiring bone marrow transplantation
B. Stage III disease requiring intensive chemotherapy without radiation
C. Limited stage disease requiring observation only
D. Stage I disease requiring involved-field radiation therapy alone
E. Stage II disease requiring combined modality therapy with chemotherapy and involved-field radiation (Correct Answer)
Explanation: ***Stage II disease requiring combined modality therapy with chemotherapy and involved-field radiation***
- This patient has **Stage II disease** because there are two or more lymph node regions involved (cervical and mediastinal) localized on the same side of the **diaphragm**.
- In pediatric **Hodgkin lymphoma**, the gold standard is **combined modality therapy** (risk-adapted chemotherapy plus low-dose radiation) to achieve high cure rates while limiting long-term toxicity.
*Stage IV disease requiring bone marrow transplantation*
- **Stage IV** involves diffuse or disseminated involvement of one or more **extralymphatic organs**, which is not present in this localized case.
- **Bone marrow transplantation** is generally reserved for relapsed or refractory cases, not as a primary treatment for Stage II disease.
*Stage III disease requiring intensive chemotherapy without radiation*
- **Stage III** requires involvement of lymph node regions on **both sides** of the diaphragm, whereas this patient's involvement is limited to above the diaphragm.
- **Chemotherapy alone** is sometimes studied to reduce radiation side effects, but it is not the standard for Stage III, nor does the patient meet the staging criteria.
*Limited stage disease requiring observation only*
- While this is technically a "limited stage," **Hodgkin lymphoma** is a malignant process that is never managed with **observation only**.
- Without active treatment like **ABVE-PC chemotherapy**, the disease would be progressive and fatal.
*Stage I disease requiring involved-field radiation therapy alone*
- **Stage I** involves only a single lymph node region, but this patient has both **cervical** and **mediastinal** involvement.
- **Radiation therapy alone** is historically associated with higher recurrence rates and significant long-term **late effects** in growing children.
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