A 60-year-old man comes to the office due to 3 months of progressive weakness and fatigue. The patient could previously walk 1-2 miles with no difficulty but now gets tired walking across his house. He has had no excessive daytime sleepiness and feels refreshed after a full night of sleep. The patient reports no fever, night sweats, dyspnea, cough, feelings of depression, or anhedonia but has lost 7 kg (15.4 lb) in the last 3 months. His appetite is unchanged, and he is eating the same food as usual but finds that he gets full more quickly than usual. The patient also reports vague abdominal discomfort but has had no dysphagia, melena, or changes in bowel habits. His medical problems include hypertension and hyperlipidemia. The patient is a former smoker with a 30-pack-year history, and he drinks alcohol occasionally. He has not recently traveled.
Vital signs are within normal limits. BMI is 26 kg/m². There is no scleral icterus, lymphadenopathy, rash, or extremity edema. The thyroid is normal to palpation. Cardiopulmonary examination shows no abnormalities. A firm, nontender mass is palpable in the left upper abdominal quadrant down to the level of the umbilicus. There is no hepatomegaly. Stool test for occult blood is negative.
Laboratory results are as follows:
The peripheral blood smear is shown in the exhibit.
Which of the following is the most appropriate next step in management of this patient?

Question

A 60-year-old man comes to the office due to 3 months of progressive weakness and fatigue. The patient could previously walk 1-2 miles with no difficulty but now gets tired walking across his house. He has had no excessive daytime sleepiness and feels refreshed after a full night of sleep. The patient reports no fever, night sweats, dyspnea, cough, feelings of depression, or anhedonia but has lost 7 kg (15.4 lb) in the last 3 months. His appetite is unchanged, and he is eating the same food as usual but finds that he gets full more quickly than usual. The patient also reports vague abdominal discomfort but has had no dysphagia, melena, or changes in bowel habits. His medical problems include hypertension and hyperlipidemia. The patient is a former smoker with a 30-pack-year history, and he drinks alcohol occasionally. He has not recently traveled.
Vital signs are within normal limits. BMI is 26 kg/m². There is no scleral icterus, lymphadenopathy, rash, or extremity edema. The thyroid is normal to palpation. Cardiopulmonary examination shows no abnormalities. A firm, nontender mass is palpable in the left upper abdominal quadrant down to the level of the umbilicus. There is no hepatomegaly. Stool test for occult blood is negative.
Laboratory results are as follows:

The peripheral blood smear is shown in the exhibit.

Which of the following is the most appropriate next step in management of this patient?

Quizplus · Accepted Answer

11ec193a_9846_6388_853d_117bd9d5738e_MD0002_00 This patient has findings consistent with hairy cell leukemia (HCL), a rare, mature B-cell lymphoproliferative neoplasm associated with BRAF V600E gene mutation. Most cases present with palpable splenomegaly (80%-90%) and complications related to pancytopenia (60%-80%), including fatigue, recurrent infections, and bleeding. Constitutional B symptoms and hepatomegaly/lymphadenopathy are uncommon but do occur in a minority (10%-20%) of patients. Peripheral blood smear usually reveals tumor cells that are 1-2 times the size of a normal lymphocyte and have an abundant, pale-blue cytoplasm with "hairy" projections. Diagnosis requires peripheral blood flow cytometry and trephine bone marrow biopsy to determine the extent of bone marrow involvement; bone marrow aspirate is frequently "dry" due to fibrosis. Patients with HCL are usually observed until symptoms develop and then are initiated on cytotoxic chemotherapy with a purine analogue (eg, cladribine), which induces remission in >96% of patients. Other common treatment modalities include interferon alfa and splenectomy. Most patients have a normal life expectancy but remain at high risk for infections. (Choice A) This patient likely has early satiety due to massive splenomegaly (left upper quadrant mass extending to the umbilicus). Given his negative fecal occult blood smear and the laboratory/peripheral blood smear findings, an evaluation for HCL, not gastrointestinal endoscopy, is the priority. (Choice B) Heterophile antibody is seen in Epstein-Barr virus infections such as infectious mononucleosis, which commonly causes splenomegaly and fatigue. However, lymphadenopathy is universal and most patients have fever and pharyngitis. (Choice C) JAK2 mutations are seen in 60%-80% of patients with primary myelofibrosis, which can cause massive splenomegaly and pancytopenia. However, the presence of hairy cells on peripheral smear makes HCL more likely. JAK2 mutation is also tightly linked to polycythemia vera. (Choice E) Serum protein electrophoresis is used in the evaluation of other plasma cell neoplasms, such as multiple myeloma and Waldenström macroglobulinemia, which generate circulating monoclonal immunoglobulins. Multiple myeloma is usually associated with bone pain, renal insufficiency, anemia, and hypercalcemia; splenomegaly is not a typical feature. Although Waldenström macroglobulinemia can cause splenomegaly (<20%) and, rarely, pancytopenia (<2%), the presence of hairy cells on this patient's peripheral blood smear makes HCL far more likely. Educational objective: Hairy cell leukemia (HCL) is a rare, mature B-cell lymphoproliferative disorder that typically causes splenomegaly and pancytopenia. HCL is usually suspected when a peripheral blood smear shows tumor cells that are 1-2 times the size of normal lymphocytes with "hairy" projections. Confirmation is made with peripheral blood flow cytometry and trephine bone marrow biopsy with immunohistochemical stains. __________ References: Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. (http://www.ncbi.nlm.nih.gov/pubmed/27903528)

A 60-Year-Old Man Comes to the Office Due to 3