A 56-year-old man from Southeast Asia comes to the physician because of fatigue, low grade fever, and left upper abdominal discomfort for the past 1 month. He denies bleeding, recent infections, or previous hospitalizations. His other medical problems include hypertension, for which he is taking hydrochlorothiazide and atenolol.
Vital signs are within normal limits. Examination shows massive splenomegaly and moderate hepatomegaly. There is no lymphadenopathy. Cardiopulmonary examination is normal. The remainder of the examination is within normal limits.
Laboratory results are as follows:

Peripheral blood smear is shown below:

Which of the following is the most likely diagnosis?

Question

A 56-year-old man from Southeast Asia comes to the physician because of fatigue, low grade fever, and left upper abdominal discomfort for the past 1 month.  He denies bleeding, recent infections, or previous hospitalizations.  His other medical problems include hypertension, for which he is taking hydrochlorothiazide and atenolol.
Vital signs are within normal limits.  Examination shows massive splenomegaly and moderate hepatomegaly.  There is no lymphadenopathy.  Cardiopulmonary examination is normal.  The remainder of the examination is within normal limits.
Laboratory results are as follows:

Peripheral blood smear is shown below:

Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec193a_982b_fd88_853d_af65bbca8f38_MD0002_00 This patient has normocytic anemia, massive splenomegaly, and teardrop cells on peripheral smear. These findings are consistent with primary myelofibrosis (PMF). Primary myelofibrosis is a chronic myeloproliferative disorder characterized by an overproduction of megakaryocytes and bone marrow stromal cells, which release fibrosis-promoting cytokines into the bone marrow. Most patients initially have leukocytosis and thrombocytosis due to marrow proliferation. However, patients then develop normocytic anemia, leukopenia, and thrombocytopenia as fibrosis replaces the marrow. The end result is extramedullary hematopoiesis manifesting as massive hepatosplenomegaly (hallmark of PMF). peripheral smear Peripheral smear usually shows characteristic dysmorphic erythrocytes (teardrop-shaped), early erythrocyte forms (nucleated erythrocytes), and immature granulocytes (myelocytes, metamyelocytes, and blasts). This patient needs a bone marrow biopsy to confirm marrow fibrosis and exclude malignant or granulomatous cells, since similar findings can occur with bone marrow infiltration (myelophthisis) by metastatic cancer or infectious granulomata. Frequently, the bone marrow is not easily aspirated in patients with myelofibrosis, often resulting in a dry tap. (Choice A) Chronic myeloid leukemia (CML) also presents with massive splenomegaly. However, the peripheral smear does not usually show teardrop cells in CML. Rather, it shows an increased number of immature granulocytes, mild anemia, thrombocytosis, and basophilia. (Choice B) Patients with malaria can have splenomegaly, thrombocytopenia, and hemolytic anemia with elevated LDH. However, peripheral smear shows intracytoplasmic parasitic inclusions rather than teardrop cells. (Choice C) Myelodysplastic syndrome commonly presents in the elderly with megaloblastic anemia and cytopenias. Hepatomegaly, splenomegaly, and teardrop cells on peripheral smear are not seen. (Choice E) Thalassemia intermedia usually presents later in life than thalassemia major with milder anemia (that does not require chronic transfusions) and extensive medullary and extramedullary hematopoiesis. However, this patient's symptom acuity, systemic symptoms, age, and absence of target cells make this diagnosis less likely. Educational objective: Myelofibrosis is characterized by bone marrow fibrosis, massive splenomegaly, normocytic anemia, and circulating immature myeloid cells, erythroblasts, and teardrop cells. Bone marrow aspirate usually results in a dry tap, and diagnosis requires bone marrow biopsy to confirm fibrosis and exclude other causes of marrow involvement. __________ References: Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. (http://www.ncbi.nlm.nih.gov/pubmed/17488875) Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. (http://www.ncbi.nlm.nih.gov/pubmed/22086865)

A 56-Year-Old Man from Southeast Asia Comes to the Physician