Haematologica. 2001 Feb;86(2):216-7.

An unusual acute myeloid leukemia associated with hyper IgE: another case of AML-M5c?
Lima M, Orfão A, Coutinho J, Ferreira G, Freitas I, Silvestre F, Justiça B.

PMID: 11224498 [PubMed - indexed for MEDLINE

COUTINHO, J.

FERREIRA, G.

FREITAS, I.

JUSTICA, B.

LIMA, M.

ORFAO, A.

SILVESTRE, F

Haematologica

Repositório Científico da Unidade Local de Saúde de Santo António

216haematologica vol. 86(2):February 2001haematologica 2001; 86:216-217 [http://www.haematologica.it/2001_02/0217.htm]scientific correspondenceAn unusual acute myeloid leukemia associated with hyperIgE: another case of AML-M5c?Although a large number of histiocytic diseases have beendescribed, their classification remains controversial1,2 and onlya few cases of primary histiocytic disorders presenting withor evolving into an overt leukemic phase - AML-M5c – havebeen reported.3,9 We describe a leukemia with unusual clin-ical and laboratory features whose diagnosis is compatiblewith AML-M5c.A 50-year old white male was studied because of anemia andthrombocytopenia. Clinically, only anemia-related symptomswere found and the physical examination yielded negativeresults. Blood counts were: hemoglobin (Hb) 5.9 g/dL, platelets(PLT) 48×109/L, white blood cells (WBC) 6.8×109/L (neutrophils63%, eosinophils 1%, lymphocytes 27%, monocytes 9%). Bio-chemical tests were normal except for increased serum lacticdehydrogenase (744 U/L; normal range 225-450 U/L), ferritin(523 ng/mL; normal range 12-200 ng/mL) and lysozyme (15µg/mL; normal values <12 µg/mL). There was a polyclonal hyperIgE (2,198 IU × 2/mL, normal values < 100 IU × 2/mL), withoutany clinical or laboratory evidence of parasitosis or atopic con-ditions. The bone marrow (BM) film showed 24% blasts, 44%granulocytic cells, 2% monocytes, 16% lymphocytes, 3% plas-ma cells and 11% erythroid precursors. Blasts were markedlypolymorphic and hemophagocytosed other blood cells; a fewmature-looking histiocytes were also found (Figure 1A). The BMbiopsy showed a hypercellular and disorganized marrow withexcess of blasts (Figure 1B). The megakaryocytic and erythroidlineages showed dystrophic elements while granulocytic cellsmatured normally. Ultrastructural studies did not shown Birbeckgranules or ferritin deposits (Figure 1C). BM cells had a normalTable 1. Blast cell cytochemical, immunophenotypic andimmunohistochemical studies.Positive NegativeCytochemistry Acid phosphatase Naphthol AS-D chloroacetate esteraseα-naphthyl butyrate Myeloperoxidaseesterase* Sudan Blackα-naphthyl acetate esterase*Periodic acid schiffImmunophenotyping CD4 CD1a CD41CD11a CD2 CD45ROCD11c CD3 CD56CD13 CD5 CD57CD15 CD7 CD61CD16 CD8 CD64CD29 CD10 CDw65CD33 CD11b CD66bCD35 CD14 Glycophorin  ACD38 CD19 HLA-DRCD42 CD20 Ig heavy chainsCD45 CD22 Ig light chainsCD45RA CD25 TCRαβCD54 CD54 TCRγδCD117 CD34Immunohistochemistry CD68 CD20 CD61Lysozyme CD45RO VWFIg, Immunoglobulins; TCR, T-cell receptor; vWF, von Willebrand Factor; *Inhibited bysodium fluoride.Figure 1. Bone marrow film (Leishmann´sstain) showing polymorphic medium to largesized blast cells, one of which is hemophago-cytosing an erythroblast (panel A); blast cellshad a relatively abundant cytoplasm with mod-erate to strong basophilia, sometimes withscattered vacuoles and fine granules. Thenucleus was usually round, sometimes eccen-tric and had reticulated chromatin, usually withone or more well defined nucleoli. Somemature-looking histiocytes with hemophago-cytic features were also found. As shown inpanel B, bone marrow trephine biopsy revealeda hypercellular disorganized marrow withCD68+ blast cells. Ultrastructural microscopystudies illustrated in panel C showed blastcells with round or oval, sometimes irregularlyshaped nuclei, with a marked predominance ofeuchromatin and large nucleoli: the cytoplasmwas rich in cytoplasmic organelles. Birbeck´sgranules, azurophilic granules or other specif-ic granules were not found, neither were fer-ritin deposits. Occasionally, hemophagocyticfeatures were observed. Representative dotplots illustrating some of the immunopheno-typing features of the blast cells are displayedin panel D.217haematologica vol. 86(2):February 2001haematologica 2001; 86:216-217 [http://www.haematologica.it/2001_02/0217.htm]scientific correspondencechromosomal constitution. Blast cell cytochemical, immunophe-notypic and immunohistochemical features are illustrated inTable 1 and Figure 1D. Blasts expressed a low intensity of CD45and myeloid associated markers such as CD13, CD15, CD33 andCD117. In spite of the negativity for CD14 and CD11b, they werepositive for other markers that are usually found on monocyte-macrophage cells such as surface CD4, CD11c, CD16, CD29,CD35, CD38, CD54, cytoplasmic CD68 and lysozyme. However,the disease did not fulfill criteria for conventional AML-M4 andAML-M5 and AML-M5 with erythrophagocytosis was alsoexcluded due to the lack of t(8;16) in conventional cytogenet-ics, no cells being available for molecular studies. The diagnosisof an AML-M6 was excluded based on FAB criteria, negativityfor glycophorin A and absence of ferritin granules. The possibil-ity of an AML-M7 appeared very unlikely because blasts werepositive only for CD42b, a marker that may also be expressed onmonocytes and macrophages. Taken together, these results sug-gest that the proliferating cell was an immature cell potential-ly committed to the monocyte-macrophage lineage. Putativecauses for a secondary histiocytic proliferation were exhaus-tively ruled out, as was the possibility of a histiocytic lymphoma.In fact, there was no clinical or laboratory evidence of infectiousdiseases or other neoplasms, no organomegaly, adenomegaly,cutaneous lesions or bone alterations. The diagnosis of a diseaseof Langerhans-dendritic cells was excluded based on the nega-tivity for CD1a and the absence of Birbeck granules. The patientbecame dependent on blood transfusions for 4 months. By thattime he had fever and petechiae, Hb 8.6 g/dL, PLT 16×109/L, WBC7×109/L with 16% of circulating blasts and LDH 4,505 U/L.Chemotherapy was then proposed but the patient died beforetreatment due to a cerebral hemorrhage. Although at diagnosisthe disease was reminiscent of a myelodysplastic syndrome withexcess of blasts it rapidly evolved into an overt acute leukemiaand the data support the hypothesis that this was one of the veryuncommon cases of histiocytic leukemia previously referred toas AML-M5c. The significance of the associated hyper IgEremains an open question. As IgE synthesis is selectively pro-moted by interleukin 4, which is produced by T-cells and stim-ulates various macrophage functions,10 we speculate that hyperIgE is related to the immune disturbance associated with themalignant histiocytic proliferation.Margarida Lima,* Alberto Orfão,° Jorge Coutinho,* Glória Ferreira,# Inês Freitas,@ Frederico Silvestre,^ Benvindo Justiça**Service of Clinical Hematology, Hospital Santo António,Porto, Portugal, °Service of Cytometry, Hospital Universitario deSalamanca, Salamanca, Spain. #Service of Medicine,  @Serviceof Laboratory Hematology and ^Service of Pathology, HospitalSanto António, Porto, PortugalAcknowledgments: the authors are grateful to Dr. Maria dos AnjosTeixeira (Service of Clinical Hematology, Unit of Cytometry, Hos-pital Santo António, Porto, Portugal), Dr. Augustin Martinez (Ser-vice of Flow Cytometry, Hospital Universitario de Salamanca,Salamanca, Spain), Dr. Luis Escribano (Department of Hematol-ogy, Hospital Ramon y Cajal, Madrid, Spain), Dr. Júlia Vasconce-los (Service of Immunology, Hospital Santo António, Porto, Por-tugal) for contributing to the study of this case, Dr. Luísa Bernar-do (Service of Medicine, Hospital Santo António, Porto, Portugal)and Dr. Manuel Cunha (Service of Clinical Hematology, HospitalSanto António, Porto, Portugal) for clinical help and to Ana Hele-na Santos (Service of Clinical Hematology, Unit of Cytometry,Hospital Santo António, Porto, Portugal)  for technical assistance.Key words: AML, IgE, histiocytes, monocytes, leukemia.Correspondence: Margarida Lima, M.D., Serviço de HematologiaClínica Unidade de Citometria, Hospital Geral de Santo António,Rua D Manuel II 4050 Porto, Portugal. Phone: international +351-22-6004808 - Fax: international +351-22-6004808 – E-mail:mmc.lima@clix.pt; m.lima@ip.ptReferences1. Cline MJ. Histiocytes and histiocytosis. Blood 1994; 84:2840-53.2. Favara BE, Feller AC, Pauli M, et al. Contemporary classifi-cation of histiocytic disorders. The WHO Committee OnHistiocytic/Reticulum Cell Proliferations. ReclassificationWorking Group of the Histiocyte Society. Med Pediatr Oncol1997; 29:157-66.3. Miano C, Bosman C, Boldrini R, et al. Disseminated histio-cytosis with undetermined Langerhans´ cells simulating anacute non lymphoid leukemia. Haematologica 1991; 76:240-2.4. Sanchez Fayos J, Perez Saenz MA, Benitez J, et al. Sub-leukemic acute monophagocytic leukemia. A biologicalphenotype close to malignant histiocytosis. Sangre 1991;36:427-30.5. Hirose Y, Takiguchi T, Konda S, Konishi F, Sanada A, Naka-gawa T. Enzyme histochemical, immunohistochemical andelectron microscopic studies of two cases of leukemicmalignant histiocytosis. Int J Hematol 1991; 54:125-35.6. Laurencet FM, Chapuis B, Roux-Lombard P, Dayer JM, BerisP. Malignant histiocytosis in the leukemic phase: a newentity (M5c-AML) in the FAB classification? Leukemia1994; 8:502-6.7. Lauritzen AF, Delsol G, Hansen NE, et al. Histiocytic sarco-mas and monoblastic leukemias. A clinical, histological andimmunophenotypical study. Am J Clin Pathol 1994; 102:45-54.8. Esteve J, Rozman M, Campo E, Munoz F, Urbano-Ispizua A,Rozman C. Leukemia after true histiocytic lymphoma:another type of acute monocytic leukemia with histiocyt-ic differentiation (AML-M5c)? Leukemia 1995; 9:1389-91.9. Piccinini L, Bonacorsi G, Artusi T. Blast crisis of Ph1-CMLwith prevalent features of malignant histiocytosis. Haema-tologica 1998; 83:187-8.10. Snapper CM, Finkelman FD, Paul WE. Differential regulationof IgG1 and IgE synthesis by interleukin 4 and 5. ImmunolRev 1988; 102:189-99.

An unusual acute myeloid leukemia associated with hyper IgE: another case of AML‐M5c?

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An unusual acute myeloid leukemia associated with hyper IgE: another case of AML‐M5c?

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