Submitting Author: Brooks, Sarah Ashley, MD
Institution: Medical University of South Carolina
Additional authors:Ana Maria Medina, MD, Robert Stuart, MD, Natalie Mason, MD, Nicole Miller, MD, John Lazarchick, MD
Session: AML with myelodysplasia-related changes

A 60 year old man with a medical history of polymalgia rheumatica, atrial fibrillation, diverticulosis, drug induced lupus, and anemia presented to the Emergency Department with fatigue, myalgias, and dyspnea on exertion. His symptoms had begun 5 months earlier with diffuse muscular pain, arthralgias, and fatigue. He denied fever, chills, night sweats, weight loss, nausea, vomiting, easy bruising or bleeding. No organomegaly or lymphadenopathy was appreciated on physical exam or by imaging studies. He was found to be pancytopenic (WBC = 1.48 K/CUMM with 5% blasts, Hemoglobin =7.2 gm/dL, Hematocrit =21.4%, and platelet count = 74K/CUMM). A bone marrow biopsy was performed; however an aspirate was not able to be obtained. Findings are described below. The patient was treated with induction chemotherapy, but continued to have prolonged cytopenias. He was then started on celecoxib with slight recovery in his counts. Unfortunately, a suitable donor has not been found for bone marrow transplantation and the patient is currently requiring intermittent transfusion support.

B + solution followed by 10% formalin fixation of iliac crest bone marrow biopsy

The peripheral smear shows moderate anisocytosis and poikilocytosis with occasional fragments, rare dacryocytes, and elliptocytes. Rare polychromatic forms are identified; no nucleated red cells are seen. There is a predominance of small mature appearing lymphocytes among the circulating white blood cell population. Hypolobated neutrophils are present, along morphologically unremarkable monocytes and eosinophils. Few large blasts with agranular cytoplasm are seen. The platelet count is decreased. A peripheral blood differential cell count by percentage reveals 12% segmented neutrophils, 1% monocytes, 78% lymphocytes, 2% basophils, and 5% blasts.

The bone marrow biopsy is approximately 15% cellular with marked fibrosis. The myeloid series is markedly decreased in number and left shifted. The erythroid series progresses through the full maturation sequence. Megakaryocytes are present with monolobed forms and occasional multinucleation. Many plasma cells and fibroblasts are also identified.

Flow cytometric analysis of the peripheral blood reveals approximately 3% blasts expressing HLA-DR, CD34, CD33, CD13, CD117, CD38, and dim CD4.

A Gordon and Sweet Reticulin stain shows Grade 2 reticulin fibrosis (2/3 MF). A Trichrome stain shows no significant collagen fibrosis. AE1/AE3 is negative. CD20 highlights few scattered B-lymphocytes while CD3 highlights scattered T-lymphocytes and a single small lymphoid aggregate. Glycophorin A shows many erythroid precursors and e-cadherin highlights few erythroid blasts. Myeloperoxidase highlights scattered and decreased numbers of maturing granulocytic precursors. Factor VIII shows dysplastic megakaryocytes in the form of monolobation and multinucleation. CD117 highlights occasional mast cells and rare blasts, while CD34 highlights scattered blasts.

46,XY,del(7)(q?11.2q23)[1]

Cytogenetic analysis reveals a deletion of 7q.

FISH confirms the deletion of 7q.

JAK2 mutational analysis is pending at this time.

This is an interesting case of myelodysplastic syndrome with myelofibrosis. Due to his presentation of extreme fatigue, myalgias and bone pain, acute myeloid leukemia-M7 was high in the clinical differential diagnosis, as well as hairy cell leukemia with his “dry tap” marrow aspirate. The marked reticular fibrosis, lack of organomegaly, lack of leukoerythroblastic peripheral blood smear with only rare teardrop red blood cells, and the monolobed megakaryocytes without significant clustering, support the proposed diagnosis. Approximately 10% of MDS cases can exhibit myelofibrosis according to the WHO, however, it is still unclear whether fibrosis represents an independent prognostic parameter.

Myelodysplastic syndrome with myelofibrosis: Refractory anemia with excess blasts -2 (RAEB-2-F)

Refractory anemia with excess blasts-2 with myelofibrosis (RAEB-2-F)

Case 375