Complete Bone Marrow Necrosis with Charcot-Leyden Crystals Caused by Myeloid Neoplasm with Mutated <i>NPM1</i> and <i>TET2</i>

Abstract

Bone marrow necrosis (BMN) has various underlying diseases. In hematological malignancies, both lymphoid and myeloid neoplasms have been shown to cause BMN. Charcot-Leyden crystals (CLCs) are bipyramidal crystals that have been found in patients with immune system diseases, tumors, skin diseases, asthma, infections, and intestinal diseases. Because the combination of CLCs and acute myeloid leukemia (AML) is rare, the relationship between BMN, CLCs, and AML remains largely unexplored. We herein report a suspected case of AML that was difficult to diagnose morphologically because of complete BMN with CLCs but achieved complete hematologic remission with treatment similar to that for AML.

NPM1‐mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions

“…Immunohistochemical detection of cytoplasmic NPM1 41 may help in defining myeloid sarcoma (Figure 2) which is difficult to diagnose by molecular assays because of the small size of the bioptic sample. Immunohistochemistry may also help to identify multilineage dysplasia 34 and to diagnose cases with aplastic or necrotic BM resulting in dry tap 42,43 . Moreover, immunohistochemistry can predict NPM1 mutations occurring at exons other than 12 (e.g., exons 9, 11, and 5) 18,19,44,45 that may be missed by standard molecular assays.…”

“…Immunohistochemistry may also help to identify multilineage dysplasia 34 and to diagnose cases with aplastic or necrotic BM resulting in dry tap. 42,43 Moreover, immunohistochemistry can predict NPM1 mutations occurring at exons other than 12 (e.g., exons 9, 11, and 5) 18,19,44,45 that may be missed by standard molecular assays. However, in NPM1 exon 5 mutations, cytoplasmic NPM1 is detected only by anti-N terminal NPM1 antibodies but not by the antibody specific for the mutant A.…”

Rare presence of Charcot–Leyden crystals in acute myeloid leukemia

“…Rarely, CLCs have been identified in patients with acute myeloid leukemia (AML).The finding of CLC in the setting of AML is unusual, particularly without concurrent presence of serum or bone marrow eosinophilia.Interestingly, this has been the case in majority of published case studies (Table 1). [3][4][5][6][7][8][9][10][11][12][13] Further, CLCs have been frequently identified in AML patients with massive bone marrow necrosis (BMN). Given the ambiguous molecular function of CLCs, its presence and possible pathophysiology in AML remain largely unknown.…”

“…Interestingly, this has been the case in majority of published case studies (Table 1). [3][4][5][6][7][8][9][10][11][12][13] Further, CLCs have been frequently identified in AML patients with massive bone marrow necrosis (BMN). Given the ambiguous molecular function of CLCs, its presence and possible pathophysiology in AML remain largely unknown.…”