A 33-year-old woman comes to the physician 1 week after noticing a lump in her right breast. Fifteen years ago, she was diagnosed with osteosarcoma of her left distal femur. Her father died of an adrenocortical carcinoma at the age of 41 years. Examination shows a 2-cm, firm, immobile mass in the lower outer quadrant of the right breast. A core needle biopsy of the mass shows adenocarcinoma. Genetic analysis in this patient is most likely to show a defect in which of the following genes?
Q2
An investigator studying the molecular characteristics of various malignant cell lines collects tissue samples from several families with a known mutation in the TP53 tumor suppressor gene. Immunohistochemical testing performed on one of the cell samples stains positive for desmin. This sample was most likely obtained from which of the following neoplasms?
Q3
A 19-month-old girl is brought by her mother to the local walk-in clinic after noticing a mass protruding from her vagina. The mass had the appearance of "a bunch of grapes". She also says that she has been having a vaginal discharge for the past 6 months. Her family and personal history are not significant for malignancies or inherited disorders. The physical examination is unremarkable except for the presence of soft nodules protruding from the vaginal canal. A tissue sample is obtained for histologic evaluation. Several weeks later the patient returns to the walk-in clinic for a scheduled follow-up visit. The pathology report describes a polypoid mass beneath an epithelial surface with atypical stromal cells positive for polyclonal desmin. What is the most likely diagnosis in this patient?
Q4
An 8-year-old boy is brought to the physician by his mother because of a 3-week history of irritability and frequent bed wetting. She also reports that he has been unable to look upward without tilting his head back for the past 2 months. He is at the 50th percentile for height and weight. His vital signs are within normal limits. Ophthalmological examination shows dilated pupils that are not reactive to light and bilateral optic disc swelling. Pubic hair development is Tanner stage 2. The most likely cause of this patient's condition is a tumor in which of the following locations?
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 1-month-old boy is brought to the physician because of a 5-day history of generalized fatigue and multiple episodes of vomiting which is most pronounced after formula feeding. His vomiting progressed from 2–3 episodes on the first day to 6–8 episodes at present. The vomitus is whitish in color. The mother reports that he has been very hungry after each episode of vomiting. The patient was born at 38 weeks' gestation and weighed 3100 g (6 lb 13 oz); he currently weighs 3500 g (7 lb 11 oz). He appears irritable. His temperature is 37.1°C (98.8°F), pulse is 130/min, respirations are 43/min, and blood pressure is 74/36 mm Hg. Examination shows dry mucous membranes. The abdomen is soft and not distended. There is a round mass palpable in the epigastric region. The liver is palpated 1 cm below the right costal margin. Laboratory studies show:
Hemoglobin 15.3 g/dL
Leukocyte count 6300/mm3
Platelet count 230,000/mm3
Serum
Na+ 133 mEq/L
K+ 3.4 mEq/L
Cl- 92 mEq/L
Glucose 77 mg/dL
Creatinine 1.0 mg/dL
A urinalysis shows a decreased pH. Which of the following is the most appropriate next step in the management of this patient?
Q7
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.
Q8
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.
Q9
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.
Q10
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.
Rhabdomyosarcoma US Medical PG Practice Questions and MCQs
Question 1: A 33-year-old woman comes to the physician 1 week after noticing a lump in her right breast. Fifteen years ago, she was diagnosed with osteosarcoma of her left distal femur. Her father died of an adrenocortical carcinoma at the age of 41 years. Examination shows a 2-cm, firm, immobile mass in the lower outer quadrant of the right breast. A core needle biopsy of the mass shows adenocarcinoma. Genetic analysis in this patient is most likely to show a defect in which of the following genes?
A. BRCA1
B. KRAS
C. TP53 (Correct Answer)
D. Rb
E. PTEN
Explanation: ***TP53***
- This patient's presentation with **early-onset breast cancer**, a history of **osteosarcoma** at a young age, and a father's death from **adrenocortical carcinoma** at 41 years strongly suggests **Li-Fraumeni syndrome**.
- Li-Fraumeni syndrome is an autosomal dominant disorder caused by a germline mutation in the **tumor suppressor gene TP53**, increasing the risk for multiple primary cancers at a young age.
*BRCA1*
- While **BRCA1 mutations** are associated with an increased risk of breast and ovarian cancer, they are not typically linked to osteosarcoma or adrenocortical carcinoma.
- The constellation of cancers in this patient is more indicative of Li-Fraumeni syndrome than solely a BRCA1-related cancer syndrome.
*KRAS*
- **KRAS** is an oncogene commonly mutated in several cancers, including pancreatic, colorectal, and lung cancer, but is not primarily associated with either Li-Fraumeni syndrome or the specific tumors seen in this family history.
- Mutations in KRAS are typically somatic mutations acquired during a person's lifetime, not germline mutations causing inherited cancer syndromes like the one suggested here.
*Rb*
- Mutations in the **retinoblastoma (Rb) gene** are associated with retinoblastoma and an increased risk of osteosarcoma, but not typically with adrenocortical carcinoma or breast cancer as part of a classic inherited syndrome.
- The combination of breast cancer, osteosarcoma, and adrenocortical carcinoma points more specifically to TP53.
*PTEN*
- **PTEN mutations** are associated with Cowden syndrome, which increases the risk for breast cancer, thyroid cancer, and endometrial cancer, along with benign growths.
- However, Cowden syndrome does not typically include osteosarcoma or adrenocortical carcinoma as prominent features, making PTEN less likely than TP53 for this specific family history.
Question 2: An investigator studying the molecular characteristics of various malignant cell lines collects tissue samples from several families with a known mutation in the TP53 tumor suppressor gene. Immunohistochemical testing performed on one of the cell samples stains positive for desmin. This sample was most likely obtained from which of the following neoplasms?
A. Squamous cell carcinoma
B. Rhabdomyosarcoma (Correct Answer)
C. Prostate cancer
D. Endometrial carcinoma
E. Melanoma
Explanation: ***Rhabdomyosarcoma***
- **Desmin** is an intermediate filament present in **muscle cells**, and its positive staining is a definitive marker for tumors of muscle origin
- A **rhabdomyosarcoma** is a malignant tumor of **skeletal muscle** differentiation, thus explaining the positive desmin staining.
*Squamous cell carcinoma*
- **Squamous cell carcinomas** are epithelial tumors that typically stain positive for **cytokeratin**, not desmin, as they originate from epithelial cells.
- They are characterized by features such as **intercellular bridges** and **keratinization**.
*Prostate cancer*
- **Prostate cancer** is an adenocarcinoma, meaning it's derived from glandular epithelial cells, and would stain positive for markers like **PSA (prostate-specific antigen)**, not desmin.
- This tumor type is characterized by glandular differentiation.
*Endometrial carcinoma*
- **Endometrial carcinomas** are adenocarcinomas of the uterine lining, derived from glandular epithelial cells, and would express **cytokeratins**, not desmin.
- Histologically, they show glandular structures and atypical endometrial cells.
*Melanoma*
- **Melanomas** are malignant tumors of melanocytes and would stain positive for markers such as **S-100**, **HMB-45**, and **Mart-1**, not desmin.
- These tumors originate from neural crest cells and are not muscle-derived.
Question 3: A 19-month-old girl is brought by her mother to the local walk-in clinic after noticing a mass protruding from her vagina. The mass had the appearance of "a bunch of grapes". She also says that she has been having a vaginal discharge for the past 6 months. Her family and personal history are not significant for malignancies or inherited disorders. The physical examination is unremarkable except for the presence of soft nodules protruding from the vaginal canal. A tissue sample is obtained for histologic evaluation. Several weeks later the patient returns to the walk-in clinic for a scheduled follow-up visit. The pathology report describes a polypoid mass beneath an epithelial surface with atypical stromal cells positive for polyclonal desmin. What is the most likely diagnosis in this patient?
A. Squamous cell carcinoma (SCC)
B. Verrucous carcinoma
C. Sarcoma (Correct Answer)
D. Adenocarcinoma
E. Melanoma
Explanation: ***Sarcoma***
- The description of a **"bunch of grapes"** mass in a young girl, along with **atypical stromal cells** positive for **polyclonal desmin**, is highly characteristic of **embryonal rhabdomyosarcoma** (a type of sarcoma botryoides).
- **Desmin positivity** indicates a muscle cell origin, and the **polypoid mass** is consistent with the gross appearance of this aggressive childhood tumor.
*Squamous cell carcinoma (SCC)*
- SCC of the vagina is extremely rare in a **19-month-old girl** and typically affects older women.
- Histologically, SCC would show **dysplastic squamous epithelial cells** with **keratinization** or intercellular bridges, not atypical stromal cells positive for desmin.
*Verrucous carcinoma*
- This is a rare, well-differentiated variant of SCC, also typically occurring in **older individuals** and associated with HPV infection.
- It presents as a **warty, exophytic lesion** with minimal cellular atypia, distinct from a "bunch of grapes" mass and desmin positivity.
*Adenocarcinoma*
- Vaginal adenocarcinoma can occur in young girls, particularly **clear cell adenocarcinoma** associated with **diethylstilbestrol (DES) exposure**; however, this patient has no such history.
- Histology would show glandular differentiation and mucin production, not atypical stromal cells expressing desmin.
*Melanoma*
- Vaginal melanoma is very rare, typically presenting as a **pigmented lesion** in postmenopausal women.
- Histopathology would reveal malignant melanocytes with **positive S-100 and HMB-45 staining**, not atypical stromal cells positive for desmin.
Question 4: An 8-year-old boy is brought to the physician by his mother because of a 3-week history of irritability and frequent bed wetting. She also reports that he has been unable to look upward without tilting his head back for the past 2 months. He is at the 50th percentile for height and weight. His vital signs are within normal limits. Ophthalmological examination shows dilated pupils that are not reactive to light and bilateral optic disc swelling. Pubic hair development is Tanner stage 2. The most likely cause of this patient's condition is a tumor in which of the following locations?
A. Fourth ventricle
B. Sella turcica
C. Cerebellar vermis
D. Cerebral falx
E. Dorsal midbrain (Correct Answer)
Explanation: ***Dorsal midbrain***
- The inability to look upward (**Parinaud's syndrome**), dilated pupils with poor light reflex, and **optic disc swelling** (indicating increased intracranial pressure) are classic signs of a mass lesion compressing the **dorsal midbrain**, specifically the **tectal plate**.
- **Irritability and bedwetting** are nonspecific symptoms, but in this context, they could be related to **hydrocephalus** due to **aqueductal compression** by the tumor.
*Fourth ventricle*
- Tumors of the fourth ventricle typically present with symptoms related to **hydrocephalus** (headache, nausea, vomiting, papilledema) and **ataxia** due to cerebellar involvement, but not specifically with **Parinaud's syndrome**.
- **Truncal ataxia** and **gait instability** are common with posterior fossa tumors affecting the cerebellum.
*Sella turcica*
- Tumors in the sella turcica primarily affect the **pituitary gland** and **optic chiasm**, leading to **endocrine dysfunction** (e.g., growth retardation, precocious puberty, hypogonadism) and **bitemporal hemianopsia**.
- **Parinaud's syndrome** and **dilated, unreactive pupils** are not typical presentations for sellar tumors.
*Cerebral falx*
- Tumors associated with the cerebral falx (e.g., meningiomas) are often located **supratentorially** and can cause focal neurological deficits like **seizures** or **hemiparesis**, depending on their location and size.
- They do not typically cause the specific eye movement disorders or pupillary abnormalities seen in this patient.
*Cerebellar vermis*
- Cerebellar vermis tumors often lead to **truncal ataxia**, **gait disturbance**, and **hydrocephalus** due to compression of the aqueduct or fourth ventricle outflow.
- While they can cause increased intracranial pressure, they do not directly cause **Parinaud's syndrome** or isolated deficits of upward gaze.
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 1-month-old boy is brought to the physician because of a 5-day history of generalized fatigue and multiple episodes of vomiting which is most pronounced after formula feeding. His vomiting progressed from 2–3 episodes on the first day to 6–8 episodes at present. The vomitus is whitish in color. The mother reports that he has been very hungry after each episode of vomiting. The patient was born at 38 weeks' gestation and weighed 3100 g (6 lb 13 oz); he currently weighs 3500 g (7 lb 11 oz). He appears irritable. His temperature is 37.1°C (98.8°F), pulse is 130/min, respirations are 43/min, and blood pressure is 74/36 mm Hg. Examination shows dry mucous membranes. The abdomen is soft and not distended. There is a round mass palpable in the epigastric region. The liver is palpated 1 cm below the right costal margin. Laboratory studies show:
Hemoglobin 15.3 g/dL
Leukocyte count 6300/mm3
Platelet count 230,000/mm3
Serum
Na+ 133 mEq/L
K+ 3.4 mEq/L
Cl- 92 mEq/L
Glucose 77 mg/dL
Creatinine 1.0 mg/dL
A urinalysis shows a decreased pH. Which of the following is the most appropriate next step in the management of this patient?
A. Measure serum cortisol levels
B. Perform upper GI endoscopy
C. Administer IV 0.9% NaCl and replace electrolytes (Correct Answer)
D. Perform emergency pyloromyotomy
E. Obtain CT scan of the abdomen with contrast
Explanation: ***Administer IV 0.9% NaCl and replace electrolytes***
- The patient exhibits signs of **dehydration** (dry mucous membranes, irritability) and **hypochloremic metabolic alkalosis** (low Na+ 133, K+ 3.4, Cl- 92) secondary to persistent vomiting.
- The clinical presentation strongly suggests **pyloric stenosis** (progressive non-bilious vomiting, palpable epigastric mass, hungry after vomiting), but the patient's **electrolyte imbalances and dehydration must be corrected before any surgical intervention** to minimize operative risks.
- The paradoxical aciduria (decreased urine pH) occurs because severe volume depletion triggers aldosterone secretion, leading to preferential H+ excretion over HCO3- despite metabolic alkalosis.
*Measure serum cortisol levels*
- While adrenal insufficiency can cause vomiting and electrolyte abnormalities, the specific presentation of **non-bilious vomiting** with an **epigastric mass** and **hunger after vomiting** strongly points to **pyloric stenosis**.
- There are no other clear signs of adrenal insufficiency such as **hyperpigmentation**, **significant hypoglycemia**, or **hyperkalemia** that would make this the immediate priority over correcting dehydration and electrolytes.
*Perform upper GI endoscopy*
- Upper GI endoscopy is primarily used to visualize the upper digestive tract for conditions like **esophagitis**, **gastritis**, or **ulcers**.
- It is not the initial diagnostic test for **pyloric stenosis**; an **abdominal ultrasound** is preferred for confirming the diagnosis (showing pyloric wall thickness >3mm and channel length >15mm).
- Correcting the patient's severe dehydration and electrolyte imbalances takes precedence over diagnostic procedures.
*Perform emergency pyloromyotomy*
- Although pyloric stenosis is strongly suspected and **pyloromyotomy** is the definitive treatment, it is an elective surgical procedure.
- The patient is currently **dehydrated** with **electrolyte abnormalities** (hypochloremic, hypokalemic metabolic alkalosis), which must be corrected *before* surgery to minimize anesthetic and surgical risks and improve outcomes.
- Pyloric stenosis is **not a surgical emergency**; stabilization always precedes surgery.
*Obtain CT scan of the abdomen with contrast*
- A CT scan uses **ionizing radiation** and **contrast agents**, which are generally avoided in infants unless absolutely necessary.
- An **abdominal ultrasound** is the diagnostic study of choice for **pyloric stenosis** due to its non-invasiveness, lack of radiation exposure, and effectiveness in identifying the characteristic hypertrophied pylorus ("olive" or "target sign").
Question 7: 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 8: 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 9: 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 10: 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**.
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