images and diagnosis Faggot cells in a non-promyelocytic acute myeloid leukemia Tushar Sehgal, Prashant Sharma *, Neelam Varma Department of Hematology, Postgraduate Institute of Medical Education and Research, Level 5, Research Block A, Sector 12, Chandigarh 160012, India * Corresponding author. Tel.: +91 88 72016123; fax: +91 172 2744401 Æ [email protected] (T.shegal) Æ [email protected] (P.Sharma) Æ [email protected] (N.Varma) Æ Accepted for publication 18 April 2014 Hematol Oncol Stem Cell Ther 2014; xx(xx): xxx–xxx ª 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved. DOI: http://dx.doi.org/10.1016/j.hemonc.2014.04.003
KEYWORDS: Acute promyelocytic leukemia, Bone marrow, Hematopathology, Immunophenotyping, Molecular diagnosis, Morphology
A
28-year-old female presented with fever, cough, and sore throat over a period of eight days. Examination revealed pallor, bilateral tonsillomegaly and hepatomegaly 2 cm below the right costal margin without palpable lymphadenopathy or splenomegaly. Hemoglobin was 82 grams/liter, total leukocyte count was 323.6 · 109/liter and platelets 38 · 109/liter. A blood film showed 40% blasts. Bone marrow examination revealed 96% myeloperoxidasepositive blasts (Figures 1 and 2). Also seen were occasional faggot cells with multiple Auer rods and blasts with lobulated nuclei, raising an initial suspicion of the microgranular variant of acute promyelocytic leukemia (APL) (Figure 2).
However, flow cytometric immunophenotyping revealed a large blast cluster with low side-scatter expressing granulocytic (CD13, CD33 and MPO) and monocytic (CD4, CD11c, CD14 and CD64) markers. Blasts were negative for CD34 but positive for HLA-DR (Figure 3). Reverse transcriptase-polymerase chain reaction for PML-RARa, t(8;21) and inv(16), and immunofluorescence test for PMLbodies were negative. The final diagnosis was acute myelomonocytic leukemia [French-American-British classification subtype AML-M4]. Faggot cells (named for the resemblance of the multiple Auer rods to a bundle of sticks) are often considered virtually pathognomic for APL. However,
Figure 1. Bone marrow showed 96% blasts that were 2–4 times the size of mature lymphocytes with opened up chromatin, 1–4 prominent nucleoli, round to indented nuclei, and a moderate amount of finely granular basophilic cytoplasm. A few faggot cells were seen (arrow). MayGrnwald Giemsa 1000·.
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images and diagnosis
FAGGOT CELLS IN MYELOID LEUKEMIA
Figure 2. The blasts were positive for myeloperoxidase on cytochemistry. Diaminobenzidine-based myeloperoxidase stain, hematoxylin counterstain 1000·.
Figure 3. Flow cytometric immunophenotyping revealed a single large blast region population with dim CD45 and low side scatter. The blasts were positive for CD4, CD11c, CD13, CD14, and CD33.
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images and diagnosis
FAGGOT CELLS IN MYELOID LEUKEMIA
as our patient demonstrates, this is not always the case – they have been reported in non-promyelocytic leukemias as well.1,2 Current laboratory approaches to leukemia diagnosis are multi-modal in nature: morphology, cytochemistry, immunophenotype, and genetics. Pathologists in resource-constrained settings may consider omitting immunophenotyping in obviously myeloid acute leukemias,3 and genetic analyses
are often unavailable. Our case, however, highlights the importance of immunophenotyping and genetic analysis in avoiding misdiagnosis and inappropriate therapy.
CONFLICT OF INTEREST None declared.
REFERENCES 1. Ohnishi H, Yoshino H, Yoneyama R, Ishii M, Watanabe T, Bessho F. Faggot formation in mature neutrophils and metamyelocytes in acute myeloid leukemia without maturation. Pediatr Hematol Oncol 2008;25(3):165–70.
Hematol Oncol Stem Cell Ther xx(xx)
2. Jerez A, del Mar Osma M, Amigo M, OrtuÇo FJ. Faggot cells in an HIV-positive patient with inv(16)/ therapy-related acute myeloid leukaemia. Br J Haematol 2010;150(6):646. 3. Sharma P, Kumar M, Lall M, Kumar L, Bhargava M. Therapy-related MDS: the importance of repeat-
xxx Quarter 2014
hemoncstem.edmgr.com
ing cytogenetics and immunophenotyping in ``relapsed'' AML. J Hematopathol 2013;6(4):207–11.
3
KEYWORDS: Acute promyelocytic leukemia, Bone marrow, Hematopathology, Immunophenotyping, Molecular diagnosis, Morphology
A
28-year-old female presented with fever, cough, and sore throat over a period of eight days. Examination revealed pallor, bilateral tonsillomegaly and hepatomegaly 2 cm below the right costal margin without palpable lymphadenopathy or splenomegaly. Hemoglobin was 82 grams/liter, total leukocyte count was 323.6 · 109/liter and platelets 38 · 109/liter. A blood film showed 40% blasts. Bone marrow examination revealed 96% myeloperoxidasepositive blasts (Figures 1 and 2). Also seen were occasional faggot cells with multiple Auer rods and blasts with lobulated nuclei, raising an initial suspicion of the microgranular variant of acute promyelocytic leukemia (APL) (Figure 2).
However, flow cytometric immunophenotyping revealed a large blast cluster with low side-scatter expressing granulocytic (CD13, CD33 and MPO) and monocytic (CD4, CD11c, CD14 and CD64) markers. Blasts were negative for CD34 but positive for HLA-DR (Figure 3). Reverse transcriptase-polymerase chain reaction for PML-RARa, t(8;21) and inv(16), and immunofluorescence test for PMLbodies were negative. The final diagnosis was acute myelomonocytic leukemia [French-American-British classification subtype AML-M4]. Faggot cells (named for the resemblance of the multiple Auer rods to a bundle of sticks) are often considered virtually pathognomic for APL. However,
Figure 1. Bone marrow showed 96% blasts that were 2–4 times the size of mature lymphocytes with opened up chromatin, 1–4 prominent nucleoli, round to indented nuclei, and a moderate amount of finely granular basophilic cytoplasm. A few faggot cells were seen (arrow). MayGrnwald Giemsa 1000·.
Hematol Oncol Stem Cell Ther xx(xx)
xxx Quarter 2014
hemoncstem.edmgr.com
1
images and diagnosis
FAGGOT CELLS IN MYELOID LEUKEMIA
Figure 2. The blasts were positive for myeloperoxidase on cytochemistry. Diaminobenzidine-based myeloperoxidase stain, hematoxylin counterstain 1000·.
Figure 3. Flow cytometric immunophenotyping revealed a single large blast region population with dim CD45 and low side scatter. The blasts were positive for CD4, CD11c, CD13, CD14, and CD33.
2
Hematol Oncol Stem Cell Ther xx(xx)
xxx Quarter 2014
hemoncstem.edmgr.com
images and diagnosis
FAGGOT CELLS IN MYELOID LEUKEMIA
as our patient demonstrates, this is not always the case – they have been reported in non-promyelocytic leukemias as well.1,2 Current laboratory approaches to leukemia diagnosis are multi-modal in nature: morphology, cytochemistry, immunophenotype, and genetics. Pathologists in resource-constrained settings may consider omitting immunophenotyping in obviously myeloid acute leukemias,3 and genetic analyses
are often unavailable. Our case, however, highlights the importance of immunophenotyping and genetic analysis in avoiding misdiagnosis and inappropriate therapy.
CONFLICT OF INTEREST None declared.
REFERENCES 1. Ohnishi H, Yoshino H, Yoneyama R, Ishii M, Watanabe T, Bessho F. Faggot formation in mature neutrophils and metamyelocytes in acute myeloid leukemia without maturation. Pediatr Hematol Oncol 2008;25(3):165–70.
Hematol Oncol Stem Cell Ther xx(xx)
2. Jerez A, del Mar Osma M, Amigo M, OrtuÇo FJ. Faggot cells in an HIV-positive patient with inv(16)/ therapy-related acute myeloid leukaemia. Br J Haematol 2010;150(6):646. 3. Sharma P, Kumar M, Lall M, Kumar L, Bhargava M. Therapy-related MDS: the importance of repeat-
xxx Quarter 2014
hemoncstem.edmgr.com
ing cytogenetics and immunophenotyping in ``relapsed'' AML. J Hematopathol 2013;6(4):207–11.
3
