Case 377

Submitting Author: Song, Joo Young, MD
Institution: Department of Pathology and Laboratory Medicine, University of California, Davis
Session: Therapy-related myeloid neoplasms

HISTORY

The patient is a 63 year-old male with a history of CLL (treated with FCR and Rituxan), prostate cancer, and autoimmune hemolytic anemia who presented with fevers (102) and watery stools. He was noted to be hypotensive with tachycardia.

After diagnosis, patient received induction chemo but showed residual disease. He was enrolled in a clinical trial (high dose lenolidomide for refractory AML) but had refractory disease, with relatively rapid progress to septic shock and demise.

DETAILS

Peripheral Blood: The peripheral blood showed normocytic normochromic anemia. There were numerous dysplastic granulocytes showing toxic granulation and Pelgeroid forms. Occasional circulating blasts were noted that were medium in size with moderate agranular basophilic cytoplasm, round nuclear contours, fine chromatin, and prominent nucleoli. Thrombocytopenia was present.

WBC 15.8, RBC 3.15, Hgb 9.2, MCV 85.1, Plt 55, Diff: 71% neutrophils, 13% lymphocytes, 10% monocytes, 3% blasts.

Bone marrow aspirate/touch prep: The aspirate was hypercellular with left shifted myeloid and increased blasts (25%) with the same morphology as above. There was also dysplastic granulocytes and marked decrease in erythroid precursors and megakaryocytes (hypolobated and small).

Bone marrow core biopsy: Markedly hypercellular marrow (>90%) with increased myeloid cells and blasts that were clustering (30-40% of the elements). Rare megakaryocytes were seen and erythroid precursors were markedly decreased.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Immunohistochemical stains showed the blasts were positive for CD117.

By flow cytometry, the blast population was positive for CD34, CD117, CD5 (partial), CD13, CD33 (partial), HLA-DR (dim), MPO (partial), and negative for TdT, cCD15, CD11b, and CD64.

No evidence of CLL by flow with only rare B-cells.

CYTOGENETIC FINDINGS

47~48,XY,-4,der(5)del(5)(p15.1p15.3)t(5;17)(q35;q21),+8, add(12)(p13),del(13)(q12q14),add(16)(p13.3),-17,add(21)(p10),+r,+3mar[cp18]

FISH results showed a complex karyotype, with approximately 90% of nuclei having trisomy 8, deletion 5p (not 5q), 13q, and 17p deletion, and monosomy 20.

MOLECULAR FINDINGS

KIT mutation not detected.

CEBPA mutation not detected.

FLT3 ITD and D835 variant not detected.

No RAR alpha-APL t(15;17) translocation was detected.

INTERESTING FEATURES

This case is interesting in that there was marked granulocytic dysplasia and a complex cytogenetics consistent with an acute myeloid leukemia with myelodysplasia related changes. However, a t(5;17)(q35;q21) that is seen with acute promyelocytic leukemia that may not have Auer rods or APL morphology, was detected by karyotypic analysis (NPM/RARA). This translocation is rare and seen predominately in children and has been reported to be sensitive to ATRA. NPM IHC staining typically shows a microspeckled pattern throughout the nucleus; however this stain was unavailable to us. Overall, based on the information, we favored a diagnosis of AML with myelodysplasia related changes. The patient was treated with 7+3 induction chemotherapy with residual disease.

Reference: Zelent A, Guidez F, Melnick A, Waxman S, Licht JD. Translocations of the RARalpha gene in acute promyelocytic leukemia. Oncogene. 2001;20(49):7186-7203.

PROPOSED DIAGNOSIS

Acute myeloid leukemia with myelodysplasia related changes.

CONSENSUS DIAGNOSIS

Therapy-related myeloid neoplasm, acute myeloid leukemia