Mediastinal Myeloid Sarcoma with TP53 Mutation Preceding Acute Myeloid Leukemia with a PICALM-MLLT10 Fusion Gene

Abstract

Introduction: Myeloid sarcoma (MS), previously known as granulocytic sarcoma or chloroma, is a rare neoplastic condition defined as a tumor mass consisting of myeloblasts or immature myeloid cells occurring at an extramedullary site. Clinical presentation is diverse and determined by a tumor mass effect or local organ dysfunction. Case Report: We report the case of a 25-year-old previously healthy male with rapidly progressive shortness of breath. A chest CT scan demonstrated a heterogenous anterosuperior mediastinal mass with pleural and pericardial invasion. A diagnosis of MS with both myeloid and lymphoid characteristics was made by pathologic, morphologic, and immunophenotypic investigation. Next generation analysis revealed a pathogenic TP53 mutation (c.1035_1036insCT, p.Glu346Leufs*25). After 4 cycles of chemotherapy only a partial metabolic response and tumor size reduction was obtained. A pretransplant bone marrow biopsy revealed the progression of disease to acute myeloid leukemia. Cytogenetic analysis demonstrated a t(10; 11)(p12;q21). Fluorescence in situ hybridization confirmed the presence of a PICALM-MLLT10 fusion gene. Conclusion: MS with a mediastinal localization is rare and often misdiagnosed as malignant lymphoma. Acute leukemia harboring a PICALM-MLLT10 fusion gene is characterized by a mixed T cell and myeloid phenotype. The rearrangement is a rare recurrent translocation associated with specific clinical features, as illustrated in this case report.

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“…20,21 Another common fusion gene is phosphatidylinositol-binding clathrin assembly lymphoid-myeloid (PICALM, previously called as CALM), with the translocation t(10;11)(p13;q21). 22 In addition, NAP1L1-MLLT10 recombination was found in pediatric T-acute lymphoblastic leukemia. 23 MLLT10/IL3 rearrangement was also found in acute lymphoblastic leukemia.…”

MLLT10 rearranged acute leukemia: Incidence, prognosis, and possible therapeutic strategies

“…The MLLT10 (Mixed lineage leukemia or myeloid/lymphoid leukemia, translocated to, 10, formerly known as AF10 ) gene was first described as a fusion partner of KMT2A ( Histone‐lysine N‐methyltransferase 2A , also known as MLL, MLL1 , or acute lymphoblastic leukemia [ ALL1 ]) in acute myeloid leukemia (AML) 1 . Chimeric fusion genes involving MLLT10 arise from chromosomal rearrangements occurring at the MLLT10 locus on chromosome 10p12, and are recurrent events in ALL 2 and AML 3 , and also in isolated cases of acute leukemia of ambiguous lineage, 4 lymphoblastic lymphoma 5 and myeloid sarcoma 6 . While there is no published evidence for MLLT10 ITDs, point mutations involving MLLT10 are reported across a range of malignancies 7 .…”

Extramedullary Myeloid Leukemia in the Setting of a Myeloproliferative Neoplasm

“…TP53 mutations have also been found in secondary AML associated with polycythemia vera (PV) and ET [ 25 , 28 ]. We identified five cases of MS associated with TP53 mutations published in literature [ 29 ]. One of these cases reported a mediastinal MS preceding AML with a PICALM-MLLT10 fusion gene mutation in addition to the TP53 mutation [ 29 ].…”

“…We identified five cases of MS associated with TP53 mutations published in literature [ 29 ]. One of these cases reported a mediastinal MS preceding AML with a PICALM-MLLT10 fusion gene mutation in addition to the TP53 mutation [ 29 ]. Two other cases reported de novo MS and two additional cases had underlying MDS before developing MS [ 1 , 11 ].…”