A 67-year-old man comes to the physician because of vague abdominal discomfort over the last several months. He also complains of fatigue but denies constipation, diarrhea, and dysphagia. His other medical problems include hypercholesterolemia, hypertension, and vitamin D deficiency. The patient underwent cholecystectomy at the age of 42 for gallstones. His daily medications include aspirin, simvastatin, valsartan, and vitamin D. The patient is a plumber and specializes in replacing old pipes. He has a sister who was diagnosed with sarcoidosis. He does not use tobacco, alcohol, or drugs.
His temperature is 37.8 C (100 F) , blood pressure is 150/80 mm Hg, pulse is 82/min, and respirations are 14/min. His BMI is 24 kg/m². Cardiopulmonary examination is unremarkable. The liver span is 16 cm and the liver edge feels firm on palpation. The tip of the spleen is palpated on deep inspiration.
Laboratory studies reveal:

No inclusion bodies are seen in the red or white cells on the peripheral smear.
Which of the following is most likely to establish this patient's diagnosis?

Question

A 67-year-old man comes to the physician because of vague abdominal discomfort over the last several months. He also complains of fatigue but denies constipation, diarrhea, and dysphagia. His other medical problems include hypercholesterolemia, hypertension, and vitamin D deficiency. The patient underwent cholecystectomy at the age of 42 for gallstones. His daily medications include aspirin, simvastatin, valsartan, and vitamin D. The patient is a plumber and specializes in replacing old pipes. He has a sister who was diagnosed with sarcoidosis. He does not use tobacco, alcohol, or drugs.
His temperature is 37.8 C (100 F) , blood pressure is 150/80 mm Hg, pulse is 82/min, and respirations are 14/min. His BMI is 24 kg/m². Cardiopulmonary examination is unremarkable. The liver span is 16 cm and the liver edge feels firm on palpation. The tip of the spleen is palpated on deep inspiration.
Laboratory studies reveal:

No inclusion bodies are seen in the red or white cells on the peripheral smear.
Which of the following is most likely to establish this patient's diagnosis?

Quizplus · Accepted Answer

This patient presents with vague abdominal pain, fatigue, and hepatosplenomegaly. Laboratory analysis shows leukocytosis with basophilia (defined as > 200 cells/µL). Basophilic leukocytosis (as seen in this patient) is very characteristic for basophilic variants of acute or chronic leukemia. This patient's clinical presentation and laboratory workup is most suggestive of chronic myelogenous leukemia (CML), a myeloproliferative disorder that causes 15-20% of all adult leukemias. Chronic myelogenous leukemia occurs more commonly in older men. Patients can be asymptomatic or present with nonspecific systemic symptoms (e.g., fatigue), hepatosplenomegaly, and peripheral eosinophilia and basophilia. Nearly 90-95% of CML patients have a reciprocal translocation that fuses the ABL1 gene found on chromosome 9 to the BCR gene on chromosome 22. The abnormal chromosome 22 (Philadelphia chromosome) with the BCR-ABL fusion gene results in the BCR-ABL fusion protein, which can be detected in the peripheral blood to confirm diagnosis. (Choice B) Lead can inhibit heme synthesis and RNA breakdown, resulting in denatured RNA in the red cells on peripheral smear (basophilic stippling). However, it is not usually associated with absolute basophilia, and this patient's smear showed no inclusion bodies. (Choice C) The HFE mutation helps differentiate hereditary hemochromatosis from other forms of hepatic iron overload. This patient has elevated ferritin but normal liver function tests, indicating that the ferritin may be elevated due to an acute phase response. (Choice D) JAK2 (Janus kinase 2) mutations are found in polycythemia vera, essential thrombocytosis, and primary myelofibrosis. However, these mutations are not usually seen in CML. (Choice E) Sarcoidosis can cause hepatosplenomegaly and elevated alkaline phosphatase due to biliary obstruction by granulomas. This patient's elevated alkaline phosphatase is most likely due to vitamin D deficiency. His other liver tests are normal, and his hepatosplenomegaly is most likely due to extramedullary hematopoiesis from CML. As a result, liver biopsy is not indicated in this patient. Educational objective: Absolute basophilia and eosinophilia in the peripheral blood are very suspicious for underlying myeloproliferative disorders, especially CML. Nearly 90-95% of patients with CML have the Philadelphia translocation. The resulting BCR-ABL fusion protein can be detected in the peripheral blood to confirm the diagnosis. __________ References: Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics. (http://www.ncbi.nlm.nih.gov/pubmed/19806146)

A 67-Year-Old Man Comes to the Physician Because of Vague