Myeloid Sarcoma of the Testis in Children: Clinicopathologic and Immunohistochemical Characteristics With KMT2A (MLL) Gene Rearrangement Correlation

Abstract

Myeloid sarcoma (MS) is defined as an extramedullary mass-forming lesion composed of immature myeloid cells. It is a rare but well-known manifestation of acute myeloid leukemia. Pediatrics testicular MS may pose a possible diagnostic challenge, an issue that is underscored in the few testicular pediatric MS cases reported in the literature. Herein, we report a series of 5 cases of pediatric testicular MS that are evaluated at the morphologic and immunohistochemical levels with correlation with the KMT2A (MLL) rearrangement status. Three patients presented with no prior history of acute myeloid leukemia. All 5 cases showed monoblastic morphology; positive for CD33, CD43, CD68, CD163, CD4 (dim), and lysozyme; and negative for CD10, CD34, CD117, and myeloperoxidase. KMT2A (MLL) rearrangement was detected in 4 of the 5 cases. In the literature, 8 more cases of pediatric testicular lymphoma were reported. Most of them showed monocytic differentiation and KMT2A (MLL) rearrangement was reported in 3 of the cases. In conclusions, testicular MS in pediatric patients shows monoblastic differentiation which may be attributed to the KMT2A (MLL) rearrangement. We also highlight the importance of using an extended immunohistochemistry panel in the diagnosis of MS.

Myeloid Sarcoma Involving the Testis in Adults: Clonal Evolution of Acute Myeloid Leukemia

“…Meta-analysis of the literature published before this study indicates that MS at this site has a better prognosis than at other anatomic sites 9. In children, testicular MS is associated with KMT2A gene rearrangement 11…”

“…Testicular MS is a rare manifestation of myeloid neoplasia, and the body of literature surrounding this entity continues to be limited 10. Notably, previously to this study, only 2 case series were published: a recent one focusing on children and comprising 5 patients11 and a relatively old 1 of 4 adult cases 8. An interesting finding of the first study was the monocytic differentiation of the neoplastic cells and the apparent association of pediatric testicular MS with translocations involving KMT2A .…”

Adult Acute Myeloid Leukemia with the <b><i>KMT2A-</i></b>Mixed Lineage Leukemia <b><i>T10</i></b> Fusion: An Analysis of 10 Cases Showed Common Features and Frequent Mutations in the RAS Signaling Pathway

“…Similarly, a study with 118 AML patients showed that the most common concomitant cytogenetic alterations were +8 (38%) and +21 (18%) but none of cytogenetic aberrations associated with clinical parameters or with the OS were observed [14] [9,20]. AMLs with KMT2A (MLL) rearrangements usually show monocytic differentiation and immunophenotypical features [17]. Accordingly, immunophenotypic analysis of the 10 patients showed that all of them presented CD33, which is positive on myeloid cells, and CD117, CD13, and majority of them expressed CD64, which is specified on the monocytic cells, M4, or M5.…”

“…Unlikely, another case showed lower numbers of leukocyte probably because of C-terminal KMT2A gene deletion [16]. Further, KMT2A rearrangements in AML mostly were present in M4 or M5 [2, 14, 17]. KMT2A-MLLT3 and KMT2A-MLLT10 most frequently occurred in M5 [2, 18].…”

“…t (9;11)(p21;q23.3)/ KMT2A-MLLT3 translocation is included in the intermediate-risk group, while t (10;11)(p12;q23.3)/ KMT2A-MLLT10 generally is associated with a poor prognosis [9, 20]. AMLs with KMT2A (MLL) rearrangements usually show monocytic differentiation and immunophenotypical features [17]. Accordingly, immunophenotypic analysis of the 10 patients showed that all of them presented CD33, which is positive on myeloid cells, and CD117, CD13, and majority of them expressed CD64, which is specified on the monocytic cells, M4, or M5.…”