Intra-Articular and Juxta-Articular Lipomas of the Knee

True lipomas involving the joints are rare. In this study, we investigated 18 intra-articular and juxta-articular lipomas of the knee. The tumor occurred in middle-aged or older patients (median age: 63 years) with a strong female predilection (3 males and 15 females), and most presented with palpable masses without associated pain. Four tumors were entirely intra-articular, whereas 11 involved both intra-articular and extra-articular compartments, consistent with herniation from the joint. The herniation commonly occurred through the space between the patellar tendon and either the lateral or medial patellar retinaculum, with the extra-articular masses being located anterolaterally or anteromedially to the joint. All tumors analyzed at least focally involved or abutted the infrapatellar fat pad. The relationship with the joint was not recognized at diagnosis in most of the herniated cases. The remaining 3 were juxta-articular lipomas that were firmly fixed to the joint. All 18 lipomas revealed distinct histology, and included fine lobulation, fibrosis with spindle cells, conspicuous presence of medium-caliber vessels and slivers of dense, tendon-like fibrous tissue. Myxoid changes, chondro-osseous metaplasia, and fat necrosis were commonly observed. These findings led to a suspicion of atypical lipomatous tumors, other benign lipomatous tumors, malformation, or hamartoma, and originally prevented a definitive diagnosis in the majority of cases. HMGA2 immunoreactivity was observed in all 18 tumors, whereas all were negative for MDM2 expression and RB1 loss. RNA sequencing revealed HMGA2 fusions in 8 of the 12 tumors tested. Intra-articular and juxta-articular lipomas of the knee, particularly the herniated intra-articular subset, are likely under-recognized and can be a source of diagnostic concern because of peculiar histology and unawareness of the relationship with the joint.