A 58-year-old woman was diagnosed with peritoneal epithelioid mesothelioma, postdebulking surgery. Peripheral blood showed neutrophilic leukocytosis with left-shifted granulopoiesis, anemia, and mild thrombocytosis (white blood cells [WBCs], 89 × 109/L; hemogloblin [Hb], 6.0 g/dL; platelets, 617 × 109/L). Four months later, she presented to our institution with liver metastasis, progressive marked left-shifted neutrophilic leukocytosis, and anemia (WBCs, 284 × 109/L; absolute neutrophil count, 272 × 109/L; Hb, 7.4 g/dL; platelets, 145 × 109/L) (panels A-B; Wright-Giemsa stain), concerning for myeloid neoplasm (MN) including myeloproliferative neoplasms (MPNs; chronic myeloid leukemia [CML], chronic neutrophilic leukemia [CNL]) or myelodysplastic syndrome/MPN. Bone marrow examination showed hypercellularity (95%) with left-shifted granulocytic hyperplasia without basophilia, eosinophilia, or morphologic dysplasia (panels C-D; hematoxylin & eosin stain [C], Wright-Giemsa stain [D]). No metastatic mesothelioma was identified. Serum granulocyte colony-stimulating factor (G-CSF) was normal. Myeloid precursors showed unremarkable immunophenotype by flow cytometry. Cytogenetic analysis showed diploid female karyotype. Fluorescence in situ hybridization was negative for BCR-ABL1. Next-generation sequencing (81-gene panel) including CSF3R/JAK2/CALR/MPL and SETBP1 showed no mutations. Thus, overall findings were in keeping with a marked paraneoplastic leukemoid reaction (LR) in response to metastatic mesothelioma.
LR is reactive/paraneoplastic left-shifted neutrophilic leukocytosis (WBCs, >50 × 109/L), and can mimic MN. Marked LR in the setting of mesothelioma is exceedingly rare and can be idiopathic or attributed to cytokine production (G-CSF/granulocyte macrophage colony-stimulating factor/interleukin-6) by tumor cells. This case highlights the comprehensive approach of correlating clinical presentation with morphology (no dysplasia, atypical megakaryocytes or abnormal monocytes, presence of Döhle bodies), flow cytometry (no aberrant myeloblasts/abnormal myeloid maturation), and absence of clonality by cytogenetic and molecular studies, helping to distinguish reactive marked LR from MNs.
A 58-year-old woman was diagnosed with peritoneal epithelioid mesothelioma, postdebulking surgery. Peripheral blood showed neutrophilic leukocytosis with left-shifted granulopoiesis, anemia, and mild thrombocytosis (white blood cells [WBCs], 89 × 109/L; hemogloblin [Hb], 6.0 g/dL; platelets, 617 × 109/L). Four months later, she presented to our institution with liver metastasis, progressive marked left-shifted neutrophilic leukocytosis, and anemia (WBCs, 284 × 109/L; absolute neutrophil count, 272 × 109/L; Hb, 7.4 g/dL; platelets, 145 × 109/L) (panels A-B; Wright-Giemsa stain), concerning for myeloid neoplasm (MN) including myeloproliferative neoplasms (MPNs; chronic myeloid leukemia [CML], chronic neutrophilic leukemia [CNL]) or myelodysplastic syndrome/MPN. Bone marrow examination showed hypercellularity (95%) with left-shifted granulocytic hyperplasia without basophilia, eosinophilia, or morphologic dysplasia (panels C-D; hematoxylin & eosin stain [C], Wright-Giemsa stain [D]). No metastatic mesothelioma was identified. Serum granulocyte colony-stimulating factor (G-CSF) was normal. Myeloid precursors showed unremarkable immunophenotype by flow cytometry. Cytogenetic analysis showed diploid female karyotype. Fluorescence in situ hybridization was negative for BCR-ABL1. Next-generation sequencing (81-gene panel) including CSF3R/JAK2/CALR/MPL and SETBP1 showed no mutations. Thus, overall findings were in keeping with a marked paraneoplastic leukemoid reaction (LR) in response to metastatic mesothelioma.
LR is reactive/paraneoplastic left-shifted neutrophilic leukocytosis (WBCs, >50 × 109/L), and can mimic MN. Marked LR in the setting of mesothelioma is exceedingly rare and can be idiopathic or attributed to cytokine production (G-CSF/granulocyte macrophage colony-stimulating factor/interleukin-6) by tumor cells. This case highlights the comprehensive approach of correlating clinical presentation with morphology (no dysplasia, atypical megakaryocytes or abnormal monocytes, presence of Döhle bodies), flow cytometry (no aberrant myeloblasts/abnormal myeloid maturation), and absence of clonality by cytogenetic and molecular studies, helping to distinguish reactive marked LR from MNs.
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![A 58-year-old woman was diagnosed with peritoneal epithelioid mesothelioma, postdebulking surgery. Peripheral blood showed neutrophilic leukocytosis with left-shifted granulopoiesis, anemia, and mild thrombocytosis (white blood cells [WBCs], 89 × 109/L; hemogloblin [Hb], 6.0 g/dL; platelets, 617 × 109/L). Four months later, she presented to our institution with liver metastasis, progressive marked left-shifted neutrophilic leukocytosis, and anemia (WBCs, 284 × 109/L; absolute neutrophil count, 272 × 109/L; Hb, 7.4 g/dL; platelets, 145 × 109/L) (panels A-B; Wright-Giemsa stain), concerning for myeloid neoplasm (MN) including myeloproliferative neoplasms (MPNs; chronic myeloid leukemia [CML], chronic neutrophilic leukemia [CNL]) or myelodysplastic syndrome/MPN. Bone marrow examination showed hypercellularity (95%) with left-shifted granulocytic hyperplasia without basophilia, eosinophilia, or morphologic dysplasia (panels C-D; hematoxylin & eosin stain [C], Wright-Giemsa stain [D]). No metastatic mesothelioma was identified. Serum granulocyte colony-stimulating factor (G-CSF) was normal. Myeloid precursors showed unremarkable immunophenotype by flow cytometry. Cytogenetic analysis showed diploid female karyotype. Fluorescence in situ hybridization was negative for BCR-ABL1. Next-generation sequencing (81-gene panel) including CSF3R/JAK2/CALR/MPL and SETBP1 showed no mutations. Thus, overall findings were in keeping with a marked paraneoplastic leukemoid reaction (LR) in response to metastatic mesothelioma.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/135/6/10.1182_blood.2019003936/2/m_bloodbld2019003936f1.png?Expires=1765972813&Signature=xEn~KdBqE757y1jVjE4PeQVW5g54HKjQNQWhrw3GV5T769CHwinRiXcE9EWcJCRylQbjgbmWUptWFd1~vqKQDF2uwCkFTEUVKAVE0Dve8HuZVLt3m~oW9ZBbhFXiUeSof7xaUC5n7r29i9Bxr4S0FkUjCsNXuoOkC1GOrd22N27VbWq04xP07BJHaW19KmDjq9d1t1QXmhrNCvjK9Q7xKSQFBAelfHlGsKEn4fWVSVqUpnxskH1~Uki1zelanT3wdnj54o33Toc7gOBpW5qKf8~GPTfJK2OUQXcmDSqgI4G2hQAv2nKxrM7tvNn0v0ySAdXjF1lRRyE1wo85tTa3JA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
![A 58-year-old woman was diagnosed with peritoneal epithelioid mesothelioma, postdebulking surgery. Peripheral blood showed neutrophilic leukocytosis with left-shifted granulopoiesis, anemia, and mild thrombocytosis (white blood cells [WBCs], 89 × 109/L; hemogloblin [Hb], 6.0 g/dL; platelets, 617 × 109/L). Four months later, she presented to our institution with liver metastasis, progressive marked left-shifted neutrophilic leukocytosis, and anemia (WBCs, 284 × 109/L; absolute neutrophil count, 272 × 109/L; Hb, 7.4 g/dL; platelets, 145 × 109/L) (panels A-B; Wright-Giemsa stain), concerning for myeloid neoplasm (MN) including myeloproliferative neoplasms (MPNs; chronic myeloid leukemia [CML], chronic neutrophilic leukemia [CNL]) or myelodysplastic syndrome/MPN. Bone marrow examination showed hypercellularity (95%) with left-shifted granulocytic hyperplasia without basophilia, eosinophilia, or morphologic dysplasia (panels C-D; hematoxylin & eosin stain [C], Wright-Giemsa stain [D]). No metastatic mesothelioma was identified. Serum granulocyte colony-stimulating factor (G-CSF) was normal. Myeloid precursors showed unremarkable immunophenotype by flow cytometry. Cytogenetic analysis showed diploid female karyotype. Fluorescence in situ hybridization was negative for BCR-ABL1. Next-generation sequencing (81-gene panel) including CSF3R/JAK2/CALR/MPL and SETBP1 showed no mutations. Thus, overall findings were in keeping with a marked paraneoplastic leukemoid reaction (LR) in response to metastatic mesothelioma.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/135/6/10.1182_blood.2019003936/2/m_bloodbld2019003936f1.png?Expires=1765972814&Signature=CzmKTbOUoBSTgqsHAKIF3CiV-NSiifC~oiS0XtBDcRXld7-cYDRjUN2MOspzLig2grOiRp7GC9dS2qrnH3I6CDSnKcAXjWUKNabhiT6-FG40mRg5utSOSqJNvGTKbHYybXzmRmxHIVMv1Q~WHv30meIEBC8SiJaDzldG1JDIAW6G3ZSEE1baN6SFPBM5c9VF4ptxxb8SLD~YuuH4jb7wtI-66Bhgsow9lGAFGTrB7nyvgYjbphwMPL~xja6dyDjZVTa1KG7vD4kql7m721IRZ13kquRzVT4iWjHLHMMQ42EAyEaNM7LKx22FRJwOhLVzrXCyv-ZuYsUWoxgKLoQhrA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)