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CASE REPORT Table of Contents  
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Adult acute megakaryoblastic leukemia with persistent diarrhea and extreme thrombocytosis: A very unusual case

1 Department of Hematology, Pamukkale University Faculty of Medicine, Denizli, Turkey
2 Department of Pathology, Pamukkale University Faculty of Medicine, Denizli, Turkey

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Date of Submission09-Mar-2022
Date of Decision08-May-2022
Date of Acceptance09-May-2022
Date of Web Publication14-Apr-2023


Acute megakaryoblastic leukemia (AML-M7) is rarely seen in adult patients and patients usually present with cytopenias. Here we discuss diagnostic challenges and pathologic features in a patient with AML-M7 who presented with thrombocytosis and diarrhea. A 63-year-old male patient presented with persistent diarrhea lasting for 2 months, fatigue, and thrombocytosis. The diagnostic workup included a stool analysis, endoscopy colonoscopy, and imaging studies; however, these studies did not reveal any possible etiology. The hematologic evaluation included peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry, and cytogenetic analysis. Eventually, according to pathologic and flow cytometric findings, a diagnosis of AML-M7 was made. Diagnosis of AML-M7 may be challenging, especially in adult patients with atypical presentation. Patients with megakaryoblastic leukemia respond poorly to standard induction regimens and they should be advised to participate in a clinical trial.

Keywords: Diarrhea, leukemia, megakaryoblast, thrombocytosis

How to cite this URL:
Aslan NA, Gülten G. Adult acute megakaryoblastic leukemia with persistent diarrhea and extreme thrombocytosis: A very unusual case. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jun 1]. Available from:

   Introduction Top

Acute megakaryoblastic leukemia (AML-M7) is a rare type of acute myeloid leukemia (AML) in the adult population, and the prognosis is worse than other types of leukemia.[1]According to the diagnostic criteria set by the World Health Organization (WHO) in 2008 for the diagnosis of AML-M7, bone marrow blasts must be ≥20% of all nucleated cells and >50% of these blasts must be megakaryoblasts.[2] Cytopenias are prominent in patients with AML-M7; however, thrombocytosis is rare.[3] There are limited reports on cases of adult AML-M7 presenting with thrombocytosis in the literature.[4],[5],[6],[7] Herein we describe the case of an adult AML-M7 with extreme thrombocytosis and persistent diarrhea.

   Case Top

A 63-year-old male patient who presented with neutropenia, thrombocytosis, and intractable diarrhea was referred to our Department of Hematology in December 2020. According to his medical history, he had been admitted to the hospital with complaints of diarrhea and fatigue and had been diagnosed with iron deficiency anemia with mild thrombocytosis and mild neutropenia, 2 months ago. Endoscopic and colonoscopic examination revealed erosive gastritis; however, the etiology of diarrhea remained unclear. After parenteral iron therapy, the patient developed severe neutropenia and thrombocytosis was aggravated. There was no history of previous exposure to chemical toxins, radiotherapy, or cytotoxic agents.

His physical examination revealed pallor, the splenic edge was palpable 1 cm below the costal margin; however, any enlarged lymph node was not detected. Laboratory workup showed that a hemoglobin level of 11,9 g/dL, a white blood cell count of 2150/μL, an absolute neutrophil count of 30/μL, a thrombocyte count of 1548 × 109/L, a sedimentation rate of 43 mm/h, a C-reactive protein (CRP) level of 59 mg/L, and a lactate dehydrogenase level of 319 U/L. Examination of peripheral blood smear revealed abundant giant thrombocytes and nuclear fragmentation of megakaryocytes. There were 3% blasts with round-shaped nuclei and without Auer rods, resembling megakaryoblasts, 6% normoblasts, 8% neutrophils, 76% lymphocytes, 7% monocytes, and some teardrop cells [Figure 1].
Figure 1: (a) Giant thrombocytes (black arrow) and megakaryoblast (red arrow) in peripheral blood smear (hematoxylin and eosin staining, ×100). (b) Teardrop cells (black arrows) (×100). (c) Megakaryocyte secreting thrombocytes (red arrow) (×100)

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A diagnostic workup for diarrhea was done. No bacteria or parasites were detected in the microscopic and microbiologic examination of the stool and he tested negative for Clostridium difficile toxin. Contrast-enhanced computed tomography failed to show any intestinal pathology. Urinary catecholamine levels were measured to rule out any possible neuroendocrine tumor and these were found to be within the normal range, and thyroid function tests suggested euthyroid sick syndrome.

The examination of the bone marrow aspiration material showed that all particle areas were covered by platelets and megakaryocytes. Megakaryocytes were hypolobulated, 25% of the nucleated cells were blasts, and 70% of the blasts were evaluated as megakaryoblasts. Flow cytometry analysis demonstrated that there were 10% blasts, which were positive for CD117, HLA-DR, and CD34, and negative for MPO and TdT. Also, there were a 40% undetermined cell population and further analysis showed that it was positive for CD41 and CD34, and negative for MPO.

The examination of bone marrow biopsy showed that there were 30% megakaryoblasts, which were diffusely stained with CD61, positive for CD34, and focally positive for CD33, and bone marrow reticulin fibrosis was evaluated as grade 1–2 [Figure 2].
Figure 2: (a) Bone Marrow; diffuse infiltration with blasts and megakaryoblasts in dysplastic morphology (hematoxylin and eosin staining, ×200). (b) CD34 expression in blastic cells (×400). (c) CD61 expression in blastic cells (×400)

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Cytogenetic analysis of 20 metaphases obtained from bone marrow samples revealed a 46XY karyotype. No genetic abnormality was found in fluorescence in situ hybridization (FISH) analysis or in the molecular genetic examination of bone marrow cells.

Based on these findings, the patient was diagnosed with AML-M7 and received induction therapy with idarubicin 12 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days. Because of severe neutropenia, cytoreduction with hydroxyurea was not appropriate. There were no signs of bleeding and thrombosis, therefore thrombocyte apheresis was not done. Cytopenia was aggravated on the 15th day of the treatment, the patient developed thrombocytopenia on the 9th day and recovered from diarrhea on the 20th day. Unfortunately, the evaluation of the response to induction therapy revealed a bone marrow blast ratio of 15%. A full-matched unrelated donor was available, so the reinduction therapy was started to obtain remission before performing an allogeneic bone marrow transplantation. However, the bone marrow response to reinduction therapy was consistent with stable disease. In accordance with the patient preference, the treatment was continued with a regimen including azacitidine and venetoclax. The patient tolerated well the first cycle and followed up in the outpatient clinic without a transfusion requirement. However, he could not receive the second cycle as he was reported to die of a heart attack at home in May 2021.

   Discussion Top

AML-M7 accounts for only 1% of all cases of AML in adults; therefore, clinical experience is limited. Most patients present with cytopenias, especially thrombocytopenia.[1],[8],[9] According to the GIMEMA study, the mean platelet count in AML-M7 patients was 66 × 109/L and the maximum platelet count was 572 × 109. Furthermore, M.D. Anderson Cancer Center's (MDACC) experience with 37 adult AML-M7 patients showed that the mean platelet count was 36 × 109/L and the maximum platelet count was 2292 × 109. AML-M7 is mostly associated with genetic abnormalities including Philadelphia chromosome (9;22) (q34;q11), chromosome 3 aberrations, del5q and del7q.[8],[9] Thrombocytosis is particularly associated with chromosome 3 aberrations and Ph chromosome in AML M7.[9] The patient we presented here had severe (1548 × 109/L) thrombocytosis without chromosomal abnormality.

The prognosis of AML-M7 is poor compared to other forms of AML. In a previous study of MDACC, the median disease-free survival of AML-M7 patients was 6–10 months and the median overall survival was 4–10 months.[9] Consistence with this study, our patient did not respond to the induction regimen and died 6 months after diagnosis because of acute myocardial infarction.

The patient in this report had also intractable diarrhea, which was resolved with treatment for leukemia. A detailed workup was performed; however, these efforts failed to identify the underlying etiology of diarrhea. Serotonin is an important neurotransmitter and has a role in intestinal motor and secretory function.[10] Serotonin released from platelets might enhance intestinal motility in our case. Diarrhea was resolved once the platelet count decreased and this provided further support for this theory.

   Conclusion Top

AML-M7 is a rare subtype of AML and may be difficult to diagnose. Moreover, in our case, the diagnosis became complicated by the presence of thrombocytosis and diarrhea. A detailed evaluation of patients for differential diagnosis is important. Standard treatment regimens are associated with a decreased disease-free survival in patients with AML-M7; therefore, further clinical trials are needed to improve prognosis.


I would like to thank Prof. Nil Güler for giving inspiration to me and supporting me in the evaluation of the patient.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Pagano L, Pulsoni A, Vignetti M, Mele L, Fianchi L, Petti MC, et al. Acute megakaryoblastic leukemia: Experience of GIMEMA trials. Leukemia 2002;16:1622-6.  Back to cited text no. 1
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Blood 2009;114:937-51.  Back to cited text no. 2
Zhao G, Wu W, Wang X, Gu J. Clinical diagnosis of adult patients with acute megakaryocytic leukemia. Oncol Lett 2018;16:6988-97.  Back to cited text no. 3
Balatzenko G, Guenova M, Zechev J, Toshkov S. Acute megakaryoblastic leukaemia with extreme thrombocytosis and p190(bcr/abl) rearrangement. Ann Hematol 2004;83:381-5.  Back to cited text no. 4
Hu R, Li J, Hu Y, Zhang J, Miao M, Zhu K, et al. Acute mono-megakaryoblastic leukemia associated with extreme thrombocytosis and complex karyotype abnormalities. Am J Case Rep 2013;14:157-60.  Back to cited text no. 5
Gupta N, Mittal A, Dadu T, Handoo A. Loss of normal polyploid spectrum as marker of clonality in acute megakaryoblastic leukemia evolving from pre-existing primary myelofibrosis. Indian J Hematol Blood Transfus 2021;37:193-6.  Back to cited text no. 6
Sasaki H, Mitani S, Kusumoto S, Marumo Y, Asano A, Yoshida T, et al. Pre- and post-transplant ponatinib for a patient with acute megakaryoblastic blast phase chronic myeloid leukemia with T315I mutation who underwent allogeneic hematopoietic stem cell transplantation. Int J Hematol 2019;110:119-23.  Back to cited text no. 7
Xu DM, Yu WJ, Xie L, Zhang ZW, Qiu JF, Xu CW, et al. The diagnostic profile of rare acute myelomegakaryoblastic leukemia. Leuk Lymphoma 2021;62:3204-11.  Back to cited text no. 8
Oki Y, Kantarjian HM, Zhou X, Cortes J, Faderl S, Verstovsek S, et al. Adult acute megakaryocytic leukemia: An analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood 2006;107:880-4.  Back to cited text no. 9
Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol 2004;141:1285-93.  Back to cited text no. 10

Correspondence Address:
Nevin Alayvaz Aslan,
Department of Hematology, Pamukkale University Faculty of Medicine, Pamukkale - 20070
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_233_22


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