Dedifferentiated melanoma with MDM2 gene amplification mimicking dedifferentiated liposarcoma

Abstract

Please cite this article as: Yousef S et al., Dedifferentiated melanoma with MDM2 gene amplification mimicking dedifferentiated liposarcoma, Pathology,

Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications

“…CDK4 gene amplification in sarcomas has been observed in both bone and soft tissue tumors, while MDM2 gene amplification predominates in soft tissue tumors, often without coamplification of other genes in the 12q13-q15 region [77,[91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108].…”

“…The presence of amplification in one or both of these genes can strongly suggest diagnoses such as well-differentiated liposarcoma, dedifferentiated liposarcoma, intimal sarcoma, or low-grade central or parosteal osteosarcoma [92][93][94][95][96][97]. However, it is important to note that these genes can also be amplified in other tumor types, such as carcinomas or melanomas [98][99][100]. Therefore, gene amplification alone is not entirely specific for making a definitive diagnosis and requires the integration of clinical, radiological, morphological, and immunohistochemical findings.…”

“…Lastly, it is worth noting that MDM2 or CDK4 amplification is not exclusive to mesenchymal neoplasms; this genetic alteration has also been observed in other epithelial neoplasms or melanomas [98][99][100]. This suggests the potential use of MDM2 or CDK4 inhibitors in neoplasms where alterations in these genes do not aid the pathological diagnosis but may help identify potential therapeutic targets.…”

“…This suggests the potential use of MDM2 or CDK4 inhibitors in neoplasms where alterations in these genes do not aid the pathological diagnosis but may help identify potential therapeutic targets. Despite the diagnostic implications that the overlap of genetic alterations in neoplasms with changes in genes within the 12q13-15 region could create, the discovery of coamplifications of MDM2 with CDK4 and GLI1 offers new therapeutic targets in neoplasms with MDM2/CDK4 amplification [92][93][94][95][96][97][98][99][104][105][106][107][108]. This particularly applies to well-differentiated or dedifferentiated liposarcomas, which might not only benefit from MDM2 or CDK4 inhibitors, but also from anti-GLI1 therapies.…”

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment

“…These tumors are usually present as biphasic neoplasms with conventional melanoma components and heterologous components resembling other malignancies [ 2 ]. Divergent differentiation is a well-described phenomenon in metastatic settings [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Phenotype switching in metastatic melanomas is a form of cancer cell plasticity and is considered an adaptative mechanism for promoting invasion and resistance to therapy [ 10 , 11 , 12 , 13 ].…”