1. Case Study MICR 410 - Hematology Spring, 2011 Case # 6 Monique Quiroz Mike Pehl Andrew Ho

2. Case Summary John, a 52-year-old man with hyperuricemia, was seen at the clinic for follow-up evaluation for splenomegaly. His palpable spleen, noted 18 months earlier, had been gradually enlarging. Originally he denied fatigue, fever, and discomfort. He was examined and a CBC was ordered. The results revealed leukocytosis, thrombocytosis, and anemia. Physical examination revealed a slightly enlarged liver and palpable spleen. Blood counts showed: Hb:11.6 g/dLMCV = 97 fl Normocytic Hct:35%MCHC = 33 Normochromic RBC:3.6 x10 12 /LLow WBC:26.2 x10 9 /LHigh Platlets:853 x10 6 /LHigh The blood cell differential showed marked anisocytosis, poikilocytosis with many teardrops, and numerous nucleated RBCs. Immature myeloid cells were found and large platelets. The blood cell differential showed marked anisocytosis, poikilocytosis with many teardrops, and numerous nucleated RBCs. Immature myeloid cells were found and large platelets. During subsequent visits John complained of fatigue, bone pain, abdominal pain and discomfort. During subsequent visits John complained of fatigue, bone pain, abdominal pain and discomfort.

3. Diagnostic Tests Bone marrow biopsy Bone marrow biopsy - moderate to marked hyperplasia, clusters of platelets, abnormal megakaryocyte morphology, and fibrotic marrow spaces -dry tap Cytogenetic analysis Cytogenetic analysis -trisomy 8

4. Key Information Pointing to Diagnosis Physical Examination Splenomegaly Splenomegaly Bone Pain Bone Pain Weakness/fatigue Weakness/fatigue Peripheral blood smear Immature myeloid cells Immature myeloid cells Large platelets Large platelets Anisocytosis Anisocytosis Poikilocytosis with many teardrops Poikilocytosis with many teardrops Nucleated RBCs Nucleated RBCs Bone marrow biopsy Dry tap Fibrotic marrow spaces Marked hyperplasia Clusters of platelets Abnormal megakaryocyte morphology Cytogenetic Testing Trisomy 8

5. What caused the splenomegaly? Extramedullary hematopoiesis Extramedullary hematopoiesis Culling of the teardrop RBC and immature cells Culling of the teardrop RBC and immature cells Note: His abdominal pain is most likely a result of both the extramedullary hematopoiesis occuring in the kidneys, liver, and spleen, as well as thrombosis of the vasculature associated with the gastroinstestinal tract.

6. The Diagnosis Myelofibrosis with myeloid metaplasia = MMM Middle aged Middle aged Anemia Anemia Hepatosplenomegaly Hepatosplenomegaly Leukocytosis Leukocytosis Thrombocytosis Thrombocytosis Bizarre, functional platelets Bizarre, functional platelets Hypercellular bone marrow Hypercellular bone marrow Fibrotic marrow spaces Fibrotic marrow spaces Hyperplasia Hyperplasia Clusters of platlets Clusters of platlets Abnormal megakaryocytes Abnormal megakaryocytes

7. Pathophysiology of Disease MMM Change in hematopoeitic precursor cells Increased hematopoesis Teardrop RBC as they squeeze out of the bone marrow Hypercellularity of bone marrow Associated bone pain and osteosclerosis Extramedullary hematopoesis Splenomegaly Fibrosis of bone marrow Anemia

8. Therapy and Prognosis for Disease MMM Therapy Immunosupressive therapy Slow down rapidly dividing hematopoetic cells Surgery for splenomegaly Blood transfusions Oral chemotherapy or low dose radiation Attack rapidly dividing hematopoetic cells Bone Marrow Transplant Prognosis Can terminate in acute mylocytic leukemia = AML

9. Prevention of Disease MMM Disease is idiopathic, so it is difficult to determine how to prevent it Disease is idiopathic, so it is difficult to determine how to prevent it Unfortunately patient shows genetic predisposition, so only preventative measures would be to avoid known carcinogens and have frequent blood analysis Unfortunately patient shows genetic predisposition, so only preventative measures would be to avoid known carcinogens and have frequent blood analysis

10. Take Home Message The diagnosis is myelofibrosis with myeloid metaplasia (extramedullary hematopoiesis) The diagnosis is myelofibrosis with myeloid metaplasia (extramedullary hematopoiesis) Typical symptoms are hepatosplenomegaly, anemia, bone pain. Typical symptoms are hepatosplenomegaly, anemia, bone pain. The cause of the disease is idiopathic. The cause of the disease is idiopathic. Diagnostic tests include bone marrow biopsy and cytogenetics. Diagnostic tests include bone marrow biopsy and cytogenetics. Treatment is supportive care, immunosuppressive therapy, and eventually a bone marrow transplant. Treatment is supportive care, immunosuppressive therapy, and eventually a bone marrow transplant. Prognosis is eventual progression to lethal AML. Prognosis is eventual progression to lethal AML. Prevention is nonexistant. Prevention is nonexistant.

11. References Mayo Clinic : Myelofibrosis Resource. http://www.mayoclinic.org/myelofibrosis/ Mayo Clinic : Myelofibrosis Resource. http://www.mayoclinic.org/myelofibrosis/ Harmening, D.M. Clinical Hematology and Fundamentals of Hemostasis. 5 th Edition. Philadelphia, PA. F.A. Davis Company. 2009. Harmening, D.M. Clinical Hematology and Fundamentals of Hemostasis. 5 th Edition. Philadelphia, PA. F.A. Davis Company. 2009. McQueen, N. (2011, May). Lecture 13. Neoplastic Disorders of the Bone Marrow. Micr 410. CSULA. McQueen, N. (2011, May). Lecture 13. Neoplastic Disorders of the Bone Marrow. Micr 410. CSULA.