Multi-system manifestations of AML : A case of CNS involvement and leukemic synovitis

Associated predominantly with myeloid leukemias of monocytic origin, leukemic synovitis is an uncommon complication. It has been proposed that genetic factors in the setting of pre-existing joint arthritis, such as osteoarthritis (OA) or rheumatoid arthritis, promote synovitis, possibly due to monocyte-recruiting cytokines that are known to be prevalent in these diseases.

A 62-year-old gentleman with a medical history significant for OA and gout presented with two weeks of unintentional weight loss of 50 pounds, night sweats, and a few days of right ankle pain. On examination, his right knee was non-erythematous, tender to palpation, with decreased range of motion, and notably different from gout flares in the past. Synovial studies showed red, cloudy fluids with no crystals, 1843 total nucleated cells/μL with 57% blasts. Laboratory studies were significant for a white blood count of 105,000/μL (48% blasts), hemoglobin of 4.9 g/dL, and platelets of 73,000/μL. Bone marrow biopsy showed 49% blasts with atypical monocytosis, suggesting a component of antecedent chronic myelomonocytic neoplasm. Genetic testing was notable for mutations in DNMT3A, IDH2, and BCORL1. As he was not a candidate for intensive chemotherapy, he was started on azacitidine/venetoclax, which improved symptoms of right ankle pain. However, he was also found to have <1% blasts in cerebrospinal fluid (CSF) studies, necessitating intrathecal methotrexate. On follow-up, he was found to have controlled disease with negative CSF studies.

Leukemic synovitis must be considered in any patient with joint swelling and myeloid neoplasm and may even be the initial presentation of leukemia. Interestingly, monocytic differentiation is a risk factor related to both CNS involvement as well as synovitis. Treatment of leukemic synovitis primarily involves chemotherapy targeted at the underlying myeloid neoplasm, rather than intra-articular modalities.