Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5\') and centromeric (3\') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5\'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5\'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5\'-predominant amplification, can be reclassified out of the UPS category.

Microdeletions (12q13.13-q13.2) involving the HOXC gene cluster are rare. Only three patients with this contiguous deletion have been reported, all resulting in phenotypic features that include skeletal anomalies, facial dysmorphism, and intellectual disability. The deletion of the HOXC gene cluster is thought to result in skeletal anomalies in these patients. We report on siblings with a 969 kb deletion in the 12q13.13-q13.2 region detected by array comparative genomic hybridization (aCGH). This deletion spans seven of nine HOXC cluster genes. FISH analysis confirmed the siblings and mother were carriers of the 12q13.13-q13.2 deletion. Although minor facial dysmorphic features were present in both siblings, no skeletal anomalies were present in the siblings or the mother. The proband had autistic-like features and mild developmental delay, while the sibling and mother are of normal intelligence. The absence of skeletal anomalies in our family suggests that deletion of the entire HOXC gene cluster may be required to result in an abnormal skeletal phenotype, or those skeletal anomalies in previously reported patients may be attributed to other genes within the deletion interval.