Case 1: a 10-year-old girl, with a history of distal radius fracture 3 years earlier, presented with a firm, nontender swelling in the same right distal forearm. Her wrist function was unimpaired. As shown in Fig. 1, X-ray examination revealed a large lobulated, compartmentalized, osteolytic, expansive tumor mass in the metadiaphysis of the distal radius. On MRI, the tumor measured 35 x 46 x 47 mm and had a well-defined boundary, but no sclerotic margin. Starting from the distal radius, there was cortical destruction, an extensive soft tissue component, and impression and bowing of the distal ulna. There were no imaging signs of invasive growth, necrosis or fluid-liquid mirrors. Bone scintigraphy did not show increased uptake at the location of the lesion. These imaging features were consistent with a destructive tumor that originated from the distal radius, grew slowly, and then broke through the cortex of the radius into the adjacent soft tissue. The tumor was excised intralesionally. Grossly, the largest tumor fragment measured 6 x 5 x 3 cm. On cut surface the tumor tissue was pale and fibrous. 
Tumor histology was reminiscent of desmoid fibromatosis and consistent with desmoplastic fibroma, as it showed a lesion composed of bundles of moderately cellular, collagenous tumor tissue with fibroblastic spindle cells with oval, monomorphic nuclei with bland, finely granular chromatin, small nucleoli and ample cytoplasm. Mitoses were not found (Fig. 2a). 
Cytogenetic analysis revealed a normal female karyotype in 18 cells, with trisomy 8 detected in 2 cells (Fig. 2b).
The cancer hotspot NGS analysis revealed a CTNNB1 hotspot class 5 pathogenic variant in exon 3: p.Ser45Phe and, using IHC, the fibroblastic tumor cells showed more than focal nuclear staining for beta-catenin (Fig. 2c), in support of a diagnosis of desmoplastic fibroma.
Case 2: a 24-year-old woman presented with progressive pain in the right hip region that had existed for 1 year. X-ray images showed an osteolytic tumor in the metadiaphysis of the right distal femur with cortical bone destruction on the dorsolateral side. The central part of the tumor had no matrix calcification. On MRI, the tumor destroyed the cortex and extended to the surrounding soft tissues. There was strong tumor enhancement after administration of intravenous gadolinium (Fig. 3a). A resection of the right distal femur was performed. The tumor in the distal femur measured 12 x 4 cm. On cut surface the tumor was pale and fibrous. There was extension to surrounding soft tissue (Fig. 3b). 
Tumor histology strongly resembled the desmoplastic fibroma diagnosed in case 1, however, with some differences. As shown in Fig. 4a, this tumor also consisted of bundles of moderate cellular tissue, with fibroblast-like, spindle cells in abundant collagenous stroma. However, there was evidence of invasive growth in trabecular bone and surrounding skeletal muscle tissue. Although nuclear chromatin was bland, few normal mitoses were found. Osteoid or trabecular bone was absent. 
As depicted in Fig. 4b, cytogenetic analysis showed an abnormal karyotype: 47~49,XX,del(13) (q12q32),+ 1~2r,+1~2mar,1dmin [cp17]/46,XX [2]. This encompasses an interstitial deletion of the long arm of chromosome 13 (q12q32), consistent with heterozygous loss of the RB1 tumor suppressor gene. With cancer hotspot NGS analysis we found amplification of CDK4 (NM_000075.3) and an imbalance of the RB1 gene on chromosome 13.
With IHC, tumor cells exhibited strong nuclear staining for CDK4 (Fig. 4c) and moderate nuclear staining for SATB2. RB1 expression was heterogeneous, not completely lost.
In this case a conclusive diagnosis of DF-LGOS could be made, based on histologic features (an invasive fibroblastic tumor with mitotic activity), karyotyping (heterozygous loss of RB1) and molecular genetics/IHC (CDK4 amplification).