Case Report

Megakaryocytic Sarcoma Transformed from a LongStanding Essential Thrombocythemia: An Extremely Rare Clinical Scenario

by Ahmed Arfa1, Ling Zhang2*

1Department of Pathology, Augusta University, Augusta, GA, USA

2Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

*Corresponding author: Ling Zhang, Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

Received Date: 08 August 2023

Accepted Date: 12 August 2023

Published Date: 15 August 2023

Citation: Arfa A, Zhang L (2023) Megakaryocytic Sarcoma Transformed from a Long-Standing Essential Thrombocythemia: An Extremely Rare Clinical Scenario. Ann Case Report 8: 1403.


Essential thrombocythemia is a myeloproliferative neoplasm. Leukemic transformation occurs among 1% to 4% of patients with a median follow-up of 7 to 10 years. Few patients manifest with acute megakaryocytic leukemia or, rarely, with megakaryocytic sarcoma. The clinical outcomes of megakaryocytic transformation are dismal, with a median overall survival of <2.2 months. Herein, we report on a 55-year-old patient with a CALRmut ET who remained stable over 20 years while receiving hydroxyurea and anagrelide therapy, then rapidly progressed to megakaryocytic sarcoma after an acquired TP53 mutation. Laboratory studies at the time of transformation showed normal white blood cells, anemia (hemoglobin of 10 g/dL), and thrombocytopenia (platelet count of 77 × 109/L). A computed tomography/positron emission tomography scan revealed generalized lymphadenopathy, splenomegaly (6.5 × 17 × 19 cm), and a bone lesion with increased bone-marrow metabolic activity. Despite receiving immediate chemotherapy, the patient died 3.5 months after the leukemic transformation. To our knowledge, this is the first report of a CALRmut and TP53mut megakaryocytic sarcoma, derived from essential thrombocythemia. We believe that the acquired somatic TP53mut played a critical role in disease transformation. Advanced molecular diagnosis during follow-ups would be beneficial not only for early diagnoses but also to enable targeted therapy, thereby improving overall survival.

Keywords: Megakaryocytic Sarcoma; Leukemia; CALR; TP53; Essential Thrombocythemia; Case Report


Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) that primarily affects the megakaryocytic lineage and is commonly associated with JAK2, CALR, or MPL gene mutations. Unlike other MPNs, transformation of ET into acute myeloid leukemia (AML) or myeloid sarcoma rarely occurs except among approximately <1% to 6.5% of patients who have a median follow-up of 7 to 10 years [1]. The transformation from ET into AML is typically attributed to advanced age, disease duration, platelet levels, white blood cell (WBC) count, myelofibrotic transformation, or cytoreduction therapy (eg, melphalan). The relationship between hydroxyurea or busulfan and ET transformation is currently being debated [2]. ET transformation to acute megakaryocytic leukemia is rare, and transformation to megakaryocytic sarcoma is even rarer, presenting a diagnostic challenge. Clinically, megakaryocytic transformation has a dismal clinical outcome with a median overall survival (OS) of <2.2 months, which prompts an earlier diagnosis and immediate treatment. Additionally, molecular mechanism of this transformation is poorly understood.

Case Presentation

Herein, we present an extremely rare case of a 55-year-old man with a 20-year history of ET on hydroxyurea and anagrelide therapy who ultimately progressed to secondary myelofibrosis and concurrent AML with megakaryocytic differentiation and extramedullary megakaryocytic sarcoma with retained CALRmut and acquired TP53mut.


For the past 20 years, the patient had moderate thrombocytosis, and his platelet count ranged from 460 × 109/L to 899 × 109/L with accompanying with anemia leukocytosis, organomegaly, or thrombotic episodes. Since diagnosis, he received hydroxyurea, low-dose aspirin, and intermittent anagrelide. Within the last 12 months, he experienced a progressive decrease in platelets. Recent complete blood count data showed anemia (hemoglobin level of 10 g/dL) and thrombocytopenia (platelet count of 78 × 109/L). He complained of chronic fatigue, low back pain, and a palpable enlarged axillary lymph node. A bone marrow biopsy was performed at an outside hospital and reported increased CD34positive blasts (80%) and diffuse severe reticulin fibrosis (marrow fibrosis [MF] 3/3) consistent with a blastic-phase MPN.

According to an outside report, karyotyping revealed a normal male karyotype of 46,XY[20], and next-generation sequencing (NGS) demonstrated a CALR p.L367fs mutation (VAF, 77%). The patient was prescribed decitabine and venetoclax for 2 cycles for management of his leukemia. He demonstrated a transient response after the first cycle but developed persistent severe pancytopenia that necessitated intermittent transfusions.

The patient was transferred to Moffitt Cancer Center for consideration of other therapeutic options. Upon admission,  his labs showed a WBC count of 0.3 × 109/L, a hemoglobin level of 6.9 g/dL, and thrombocytopenia (11 × 109/L). His absolute neutrophil count was only 0.009 × 109/L (3% of WBCs). A computed tomography/ positron emission tomography scan revealed numerous multilevel metabolically active left neck, supraclavicular, subclavian, and axillary lymph nodes with a maximum standardized uptake value (SUVmax) of 10.1; splenomegaly (6.5 × 16.9 × 19 cm); a left inferior scapula lytic lesion with an SUVmax of 10.8; and a heterogeneous increased metabolic activity throughout the bone marrow.

A bone marrow biopsy was conducted at Moffitt Cancer Center approximately 4 months after his initial leukemic transformation and after he received induction chemotherapy. The received aspirate appeared acellular and markedly hemodiluted. Touch imprint showed 7% myeloblasts. The core biopsy exhibited normocellularity (50%) with partial histomorphology of myeloid preponderance and atypical megakaryopoiesis as well as a focal collection of blasts (Figure 1A-D). The blasts showed overlapping CD34 and CD61 staining (Figure 1E, F). An additional biopsy from axillary masses revealed diffuse effacement of normal lymph-node architecture, with sheets of intermediate-to-large immature cells associated with active mitosis (Figure 2) and moderate-to-marked reticulin fibrosis (score of MF 2-3/3). These immature precursors were positive for CD34, megakaryocytic markers (CD61, CD31, factor VIIIa), and p53 protein, with a high proliferation index highlighted by its Ki67 score (70%-80%) (Figure 2); the immature precursors were negative for myeloperoxidase, spectrin, lysozyme, CD68, CD163, CD3, CD20, PAX-5, CD138, MUM1, and CD30.


Figure 1: A. Peripheral circulating blasts (Wright, 1000×). B. Bone marrow aspirate/touch imprint shows megakaryoblasts (Wright-Giemsa, 1000×). C, D. Low-power view of H&E section of the bone marrow core biopsy shows atypical megakaryopoiesis associated with mild myeloid preponderance, dilated sinusoid space, and increased vasculatures (C) and focal increase in immature precursors/blasts in sheets (D) (H&E, 200×). E. Higher-power view reveals atypical megakaryocytes with hyperchromatic nuclei, and focally, sheets of immature precursors with dispersed-to-open chromatin, visible nucleoli, and scant cytoplasm associated with brisk mitosis associated with a couple of abnormal multilobate megakaryocytes (H&E, 600×). F. Reticulin stain highlights reticulin fibrosis (MF 2-3/3) (reticulin, 200×). G-I. The immature precursors/blasts are partially positive for CD34 (a stem cell marker) (G) and diffusely express megakaryocytic marker CD61 (H) consistent with megakaryoblasts, and they are negative for CD117 (I) (immunoperoxidase, 600×). Abbreviation: H&E, hematoxylin and eosin.

Karyotyping at this time still revealed a normal male karyotype 46,XY[20]. A fluorescence in situ hybridization study panel, including del(5q)/−5, del(7q)/−7, +8, del(17p), and del(20q) probe sets, did not reveal any abnormalities. NGS performed on the bone marrow specimen showed only a CALR frameshift mutation (VAF, 41.4%). The paraffin-embedded biopsy tissue from the axillary lymph node was submitted for Foundation One Heme genomic profiling (Beverly, MA, USA), which identified commutations of TP53 p. Y163C and CALR L367fs46.


The overall findings were consistent with AML with megakaryocytic differentiation and megakaryocytic sarcoma that had transformed from a long-standing ET.