Submitting Author: Swamy, Vinushree, MD
Institution: Henry Ford Hospital
Additional authors:Juan Gomez-Gelvez, MD, Kristin Karner-Hunt, MD, Kedar Inamdar, MD, PhD
Session: AML with myelodysplasia-related changes

An 86 year old female presented to the ER with the sudden onset of severe respiratory distress. Her past medical history is negative for other comorbidities, smoking, and alcohol or drug abuse. Her labs revealed anemia and Neutropenia. Lowest absolute neutrophil recorded 0.94 (1.80 -7.70 k/ml) and Hb was 7.5g/dl. Bone marrow was performed to evaluate for causes of anemia and neutropenia. She was given a single dose of Neupogen (300 ug/dl subcutaneous) one week prior to bone marrow biopsy procedure was done.

Disease course: Bone marrow showed up to 30% Myeloblasts and there was high degree of suspicion for making the diagnosis of myelodysplastic syndrome versus acute leukemia but the diagnosis remained unclear due to the effects of recent administration of Neupogen. Two months later, she presented with respiratory distress and full blown pancytopenia. No follow up bone marrow biopsy was done. Clinically they suspected myelodysplastic syndrome in the background of pancytopenias and considered her for chemotherapy and Neupogen. Her cytopenias remained resistant to chemotheraphy or future doses of Neupogen. Her hemoglobin, WBC count; platelet count trended low until she expired due to clostridium difficile toxic megacolon and severe ARDS

Details and Pathology: Bone marrow biopsy from left iliac crest. Fixed in Bouin’s and decalcified with hydrogen chloride solution.

Overall cellularity of marrow accounted for about 40%. Myeloid series is increased with a left shifted maturation, and dysgranulopoiesis including hypo lobated and hypogranular forms as well as nuclear-cytoplasmic dyssynchronous maturation. Blasts were increased up to 30% of total cells in a 500-cell differential count of aspirate smears. Erythroid series was slightly decreased in number with evidence of dyserythropoiesis including nuclear irregularities and budding. Iron stain of aspirate smear revealed up to 35% ring sideroblasts.

IHC: A CD34 immunostain with appropriately reacting controls reveals increased number of positive blasts.

Flow cytometry analysis revealed a population of myeloblasts with the following immunoprofile: HLA-DR+, CD13+, CD117+, CD34+ and CD33+ (dim to moderate); The blasts were negative for CD19, CD10, CD5, CD7, CD56, CD61, CD235a, CD14, CD11b, CD15, CD79a and CD3. The majority are negative for MPO

Normal female karyotype 46, XX

FISH cytogenetics for MDS and AML were negative for all loci studied.

JAK2 Mutational analysis on blood was performed and no activating JAK2 mutation was detected

This case highlights the diagnostic challenge posed by effect of G-CSF (Neupogen) administration in arriving at a diagnosis of MDS and determining whether the blast counts in this setting would truly allow consideration of acute myeloid leukemia. The administration of Neupogen just 1-week prior to the marrow biopsy resulted in peak effects on accentuating the marrow features resulting in an overestimation of the blast counts. This is a well recognized effect as reported by Meyerson HJ et al. Am J Clin Pathol 1998, 109(6):375, in which they report the elevations of baseline blast count after the administration of G-CSF ranging from 10 to 40%. Counts returned to their pretherapy level within 3-5 weeks, suggesting that the peaking of blasts are due to stimulation/ regeneration phenomenon rather than being leukemic in origin.

In our case, administration of Neupogen 1 week prior to the bone marrow biopsy caused a diagnostic challenge in distinguishing the effects of Neupogen from MDS or AML. The frequent trilineage dysplasia with the patient's symptoms of bicytopenia allowed consideration of MDS as the likely diagnosis. The presence of 30% blasts however made it difficult to determine as to how much of the blast increase was truly secondary to underlying myelodysplasia. Cytogenetic studies in our case did not reveal MDS or AML related cytogenetic abnormalities.

Myeloid malignancy in the setting of recent Neupogen administration - high grade MDS versus Acute myeloid leukemia. Repeat biopsy after the holding Neupogen was advised.

Myelodysplastic syndrome, status post recent Neupogen administration

Case 315