This report highlights the importance of screening for DICER1 mutations in the presence of the early-onset features of this syndrome and extends the spectrum of DICER1-related tumors by showing the mutation in a case of ERMS of the uterine corpus.
We present the case of a germline heterozygous NRAS mutation producing a severe phenotype involving embryonal rhabdomyosarcoma, severe intellectual disability, and numerous melanocytic nevi in addition to more typical manifestations of Noonan syndrome.
These results indicate that berberine derivatives have the potential of anti-tumor drugs for RMS therapy.<b>Abbreviations</b>: ARMS: alveolar rhabdomyosarcoma; ERMS: embryonal rhabdomyosarcoma; RMS: rhabdomyosarcoma.
For instance, an upregulation of the Hpo downstream effector Yes-Associated Protein 1 (YAP) leads to the development of embryonal rhabdomyosarcoma (eRMS) in murine activated muscle satellite cells.
For instance, an upregulation of the Hpo downstream effector Yes-Associated Protein 1 (YAP) leads to the development of embryonal rhabdomyosarcoma (eRMS) in murine activated muscle satellite cells.
IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL).
This is the first report of embryonal rhabdomyosarcoma in association with a germline CBL pathogenic variant, further broadening the CBL cancer predisposition spectrum.
The identified combination of genetic events indicates a relationship between the intracranial tumors analyzed and DICER1 predisposition syndrome-associated sarcomas such as embryonal rhabdomyosarcoma or the recently described group of anaplastic sarcomas of the kidney.
Conclusively, the high expression of EZH2 is a promising marker in distinguishing well-differentiated LMS from cellular leiomyoma, or well-differentiated ERMS from fetal rhabdomyoma, and the upregulation of EZH2 protein expression may occur at transcriptional level.
The immunohistochemical analysis was positive for the antigens: MyoD1, myogenin, desmin, and Ki67 (100% positivity in neoplastic cells), allowing the identification of the tumour as an eRMS.
Immunohistochemical stains were positive for vimentin, CD99, myogenin, and MyoD1 consistent with a diagnosis of embryonal rhabdomyosarcoma, botryoid subtype.
The metachronous occurrence of two unrelated tumor entities (eRMS and CBME) in a very young child within a short timeframe should have raised the suspicion of an underlying cancer susceptibility syndrome and should be prompt tested for DICER1.