Question

A patient with a known mutation in the Rb gene is disease free from retinoblastoma. The patient is at highest risk of developing which of the following malignancies?

• A. Renal cell carcinoma
• B. Osteosarcoma
• C. Pinealoblastoma
• D. Chondrosarcoma

Hint:

RB1 carriers face lifelong second cancers, and the commonest one arises in bone.

Answer 1

The Correct Option is B

Step 1: The RB1 gene is a tumour suppressor on chromosome 13q14. In hereditary (germline) retinoblastoma every cell carries one mutated copy, so a second hit anywhere in the body can start a new cancer. These patients carry a lifelong risk of second primary tumours.
Step 2: The single most common second malignancy in survivors of hereditary retinoblastoma is osteosarcoma. The risk is highest in bone, both inside and outside any radiation field, and is further raised by prior radiotherapy.
Step 3: So option B is the highest risk and is the answer. Soft tissue sarcomas and melanoma also occur but osteosarcoma leads the list of second tumours.
Step 4: Option C, pinealoblastoma, occurs as part of trilateral retinoblastoma. However it presents in early childhood alongside the eye tumour, not as a long-term second malignancy in a disease-free survivor, and is much less common than osteosarcoma.
Step 5: Renal cell carcinoma (A) is linked to VHL, not RB1. Chondrosarcoma (D) is not a characteristic RB1-associated second tumour.
Hence the answer is Option B: Osteosarcoma.