Kaplan USMLE Step 1 prep: What disorder is the boy at risk for?

If you’re preparing for the United States Medical Licensing Examination® (USMLE®) Step 1 exam, you might want to know which questions are most often missed by test-prep takers. Check out this example from Kaplan Medical, and read an expert explanation of the answer. Also check out all posts in this series.  

This month’s stumper

A 3-year-old boy is found to have an abnormal red reflex in his left eye on routine examination. Funduscopic examination shows a proliferative retinal mass. After surgical removal of the specimen, pathologic examination reveals small, round cells with hyperchromatic nuclei, some rosette arrangement and isolated regions of necrosis. There is no involvement of the optic nerve or tumor extension into adjacent brain tissue. The patient undergoes eye enucleation without surgical complications.

As the child ages, which of the following disorders is the patient also at risk for developing?

A. Acoustic neuroma.

B. Colon cancer.

C. Neurofibroma.

D. Osteosarcoma.

E. Wilms tumor.















The correct answer is D.

Kaplan Medical explains why

This patient presents with a classic presentation of retinoblastoma, a rapidly progressive cancer arising from immature retinal cells. It occurs almost entirely in young children and symptoms include visual impairment and strabismus. However, many cases are discovered incidentally on family photographs or physical exam with an absent red reflex (leukocoria). Leukocoria can also be found in a number of other conditions including congenital cataracts, but should always prompt a work-up for retinoblastoma.

Retinoblastoma can either be inherited or sporadic. The disease is associated with a mutation in the Rb tumor suppressor gene located at chromosome 13q14. Rb protein regulates cell-cycle progression from G1 (growth phase) to S (synthesis) during replication. Loss of function causes unregulated cell division. Other diseases caused by germline mutations in the Rb gene include osteosarcoma. So, as part of patient management, the child should be monitored for the risk of osteosarcoma development in future years. Somatic mutations at this site are also seen in some cases of breast, lung, prostate and bladder cancer.

Why the other answers are wrong

Choice A: Bilateral acoustic neuromas are associated with neurofibromatosis type 2, an inherited autosomal dominant condition resulting from mutation of NF2 tumor suppressor gene at chromosome 22q. Other features of this disease include juvenile cataracts and meningioma. Though patients with cataracts may have leukocoria, the pathologic findings in our patient are consistent with malignancy.

Choice B: Increased risk of colon cancer is classically seen in familial adenomatous polyposis coli (FAP). This inherited disease results in hundreds of adenomas along the colon and is associated with mutation in the APC tumor suppressor gene located at chromosome 5q. Normal APC protein is a negative regulator of beta catenin. In FAP, mutant APC protein cannot suppress cellular overgrowth, which leads to polyp formation.

Choice C: Neurofibromas are small benign, subcutaneous tumors arising from peripheral nerves and are associated with neurofibromatosis type 1, an autosomal dominant condition resulting from mutation of the NF1 tumor suppressor gene at chromosome 17q. Other findings in this disease can be encompassed with the mnemonic CAFE SPOT: cafe-au-lait spots, axillary freckling, eye "Lisch" nodules (iris hamartomas), scoliosis, pheochromocytoma, and optic tumors (gliomas).

Choice E: Wilms tumor is a childhood solid tumor arising from nephroblasts in the kidney. It usually presents as an abdominal mass (not crossing the midline) with possible hematuria and hypertension. The condition results from mutation of the WT1 tumor suppressor gene located at chromosome 11p. Wilms tumor may occur as part of the WAGR complex: Wilms tumor, aniridia (absent iris), genitourinary malformation, and retardation.

Tips to remember

  • Retinoblastoma is a highly aggressive cancer of early childhood derived from immature retinal cells.
  • Patients with retinoblastoma may have an absent red reflex (leukocoria).
  • It is associated with inherited mutation of the Rb tumor suppressor gene located at chromosome 13q14.
  • Germline mutation in Rb increases risk for both retinoblastoma and osteosarcoma.

For more prep questions on USMLE Steps 1, 2 and 3, view other posts in this series.

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