Morphologic heterogeneity of acute promyelocytic leukemia (APL)

Abstract

6741 Background: Three morphological forms of APL recognized; hypergranular, hypogranular and hyperbasophilic forms. Other subtypes were rare, however, have been described. Methods: We describe a case of AML with PML-RARα fusion gene without above morphology. A 67-year-old caucasian male was hospitalized with diverticulits. He received radioactive seed-implants for prostate cancer 1.5 years ago. CBC showed WBC 9,000/cmm, Hemoglobin 12.4g/dl, platelet 25,000/cmm, neutrophil 5%, band 3%, lymphocyte 30%, monocyte 20%, metamyelocyte 2%, myelocyte 15%, promyelocyte 15%, myeloblast 10%. Clotting profile was normal except INR 1.6 and elevated D-dimers. Bone marrow biopsy was consistent with AML-M2. Induction chemotherapy was initiated resulting in worsening DIC. This raised the suspicion for morphologic variant of APL. The cytogenetic study revealed no diving cells. FISH and PCR studies were positive for PML-RARα fusion gene. He was then started on all-trans retinoic acid. Currently he has received 2 cycles of consolidation chemotherapy. The literature was reviewed for atypical morphologic presentations of APL on MEDLINE. Results: In a review of the literature of t(15:17) in AML subtypes other than M3, there have been 16 reported cases including our case. Male: Female:Unknown- 5:8:3; Subtypes: M1- 6, M2- 5, M4- 1, acute esosinophilic leukemia- 1, M7- 2, undifferentiated L2/M1- 1; DIC: Yes- 4, No-4, unknown- 8; Treatment with ATRA: Yes- 7, No- 6, unknown- 3; Outcomes: Complete hematologic remission - Yes- 7, Died - 3, unknown- 6. Molecular responses: Yes- 1, No- 6, unknown- 9. Conclusion: Patients with t(15;17) are amenable to treatment with ATRA making this most curable AML. The diagnosis of APL can be made from morphology and flow cytometry, but our case and the literature illustrate there are occasions where APL may present with atypical morphology. All efforts must be made rule out PML-RARα gene rearrangement in AML patients, especially with DIC. Summary of APL cases without typical M3 morphology Reference Age/Sex AML subtypes Disseminated Intravascular Coagulation (DIC) Use of All-trans Retinoic Acid (ATRA) Outcome Neame et al 60/F M1 No No Unknown 73F M1 Yes Yes Died 45M M2 Unknown No Unknown 53F M2 Unknown Yes Remission 54M M2 Unknown No Unknown Foley et al 45M L2/M1 Undifferentiated Yes Yes Remission Allford et al 15/F M1 No Yes Died 36/M M2 unknown No Died Head et al unknown M1 unknown unknown unknown unknown M1 unknown unknown unknown unknown M1 unknown unknown unknown Hast et al 22/F M4 Yes No Remission Aventin et al 22/F M7 No Yes Remission Morgan et al 18/F M7 No No Remission Yu et al 66/F Acute eosinophilic leukemia unknown Yes Remission This case 67/M M2 Yes Yes Remission No significant financial relationships to disclose.