SP09 | LYMPH NODES INVOLVEMENT BY ACUTE MYELOID LEUKEMIA IN MYELODISPLASTIC SYNDROME/MYELOPROLIFERATIVE NEOPLASMS: MORPHOLOGIC DISCORDANCE WITH BONE MARROW DISEASE, CLINICAL AND BIOLOGICAL FEATURES AND THERAPY IMPLICATIONS. A SINGLE CENTRE EXPERIENCE

Extramedullary involvement (EMI) refers to myeloid leukemic cells found outside the blood or bone marrow, more frequently in skin, bone, and lymph nodes; in the literature occurring in 2–9% of AML. EMI have to be confirmed by histopathology, morphology, cytogenetics, molecular biology, flow cytometry, IIC and NGS. A 75-year-old woman presented to our hospital in 2021 for leukocytosis. Blood count showed WBC 47680×109/L (89,6% N). Bone marrow biopsy (BMB) was suggestive for a MDS/MPN with neutrophilia. Molecular biology is negative for BCR/ABL JAK2, MPL and CALR. NGS demonstrated CSF3R, SETBP1, SRSF2 mutations and Cytogenetic 46 XX [20] karyotype. Ultrasound revealed normal spleen size. Cytoreductive treatment was started with hydroxyurea. In 2023 for leukocitosis, anemia and thrombocytopenia we repeated a BMB that was compatible with MPN. NGS demonstrated CSF3R, SETBP1, SRSF2 , AXL1 mutations. TC revealed splenomegaly (23 cm) and abdominal lymph nodes; excisional adenopathy biopsy showed massive infiltration of blasts CD34/CD117+ indicative of AML. Due to the patient's age and PS we started a treatment with Azacitidine, but she died post-cycle 1. A 73-year-old man with a Chronic myelomonocytic leukemia (CMML) was treated with hydroxyurea since 2018. In 2024 for leukocitosis and thrombocytopenia we repeated a BMB confirming CMML. NGS demonstrated TET2, SETBP1, SRSF2, AXL1 mutations and Cytogenetic 46 XY[20] karyotype. TC revealed normal spleen size and mediastinal, cervical and axillary lymph nodes. Excisional axillary adenopathy biopsy showed diffuse proliferation of cells MPO, CD303, CD123+, CD56-indicative of AML and Plasmocitoid dendritic cells proliferation. We started a therapy with Venetoclax+ Azacitidine but patient died from infection post-cycle 1. The mechanism for EMI is not fully understood: homing to extramedullary tissues may be due to the blast expression e.g. CD56 (neural adhesion molecule), to deregulation of CBF in inv(16), to the lack of CD117 as possible causes of leukemic cell migrations. Associated factors are leukocytosis, myelomonocytic/monocitoyd differentiation, mutations of NPM1, FLT3, MLL, chromosomal anomalies such us t(8,21), inv(16), +4, +8,+,- 7, deletions of 5q, 20q,complex karyotype. The clinical presentation of EMI depends on the site involved. The treatment paradigm is the same as AML and depends on comorbidities and patient’s age, on the biological and cytogenetic characteristics and should be started early.