WBR0930

Author	PageAuthor::William J Gibson (Reviewed by Serge Korjian)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology, MainCategory::Pharmacology
Sub Category	SubCategory::Hematology
Prompt	Prompt::A 35-year-old man is treated for acute promyelocytic leukemia with a sustained course of arsenic trioxide and All-trans-retinoic acid (ATRA). If he develops a secondary malignancy due to this therapy, which of the following is most probable?
Answer A	AnswerA::Gastric cancer
Answer A Explanation	AnswerAExp::Gastric cancer can occur as a result of nistrosamine exposure. Nitrosamines are carcinogenic chemical compounds present in various foods, notably smoked meats.
Answer B	AnswerB::Leukemia
Answer B Explanation	AnswerBExp::Leukemia can occur as a result of previous genotoxic chemotherapy, such as alkylating agents.
Answer C	AnswerC::Transitional cell carcinoma of the bladder
Answer C Explanation	AnswerCExp::Transitional cell carcinoma of the bladder is associated with previous exposure to napthylamine compounds (used in the manufacture of aniline synthetic dyes).
Answer D	AnswerD::Hepatocellular carcinoma
Answer D Explanation	AnswerDExp::Hepatocellular carcinoma is caused by exposure to aflatoxin.
Answer E	AnswerE::Angiosarcoma
Answer E Explanation	AnswerEExp::Angiosarcoma is a potential late complication of exposure to arsenic.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Acute promyelocytic leukemia (APML) is a rare subset of acute myeloid leukemia (AML). APML is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (RARA). APML cells undergo a differentiation arrest, which can be reversed with all-trans retinoic acid. Arsenic is thought to act by inhibiting the enzyme thioredoxin reductase, an enzyme that is essential for cell growth and survival and that is upregulated in APML cells. Histologically, APML is notable for leukemic cells containing rod-like cytoplasmic inclusions called “Auer rods”. Treatment of APML can precipitate release of these inclusions causing disseminated intravascular coagulopathy (DIC). Prolonged therapy with arsenic trioxide, a known carcinogenic agent, increases the risk of certain cancer particularly squamous cell carcinoma of the skin as well as angiosarcoma of the liver. Educational Objective: Angiosarcoma is a potential late complication of exposure to arsenic. References: Watts JM, Tallman MS. Acute promyelocytic leukemia: what is the new standard of care?. Blood Rev. 2014;28(5):205-12. Pershagen G. The carcinogenicity of arsenic. Environ Health Perspect. 1981;40:93-100.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Cancer, WBRKeyword::Chemotherapy, WBRKeyword::Side effect, WBRKeyword::Leukemia, WBRKeyword::Acute promyelocytic leukemia, WBRKeyword::Toxin
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