Tumors and neoplastic lesions of undetermined differentiation

Clear cell sarcoma is a rare malignancy occurring in children of unknown origin in patients with a mean age of 36 months.The 2016 edition of the WHO guidelines updated its molecular genetic alterations, with approximately 13%-25% of tumors having a t(10;17)(q22;p13) translocation producing the YWHAE-FAM22 fusion gene, which is also present in a a subset of high-grade endometrial mesenchymal sarcomas. This gene activates the expression of cyclinD1, and therefore high expression of cyclinD1 in tumors can be used as a diagnostic marker.

Uterine mesenchymal tumors

should be used for high-grade endometrial mesenchymal sarcoma. The 2014 edition of the WHO classification combines data on the histologic features, clinical prognosis, and molecular genetics of ESTs to encompass four types of tumors: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), and high-grade endometrial stromal sarcoma (ETS). endometrial stromal sarcoma (HGESS) and UUS, reflecting the highest level of human knowledge of EST at this stage.

There are at least three known molecular genetic abnormalities of HGESS: (1) ESTs with the YWHAE-NUTM2 fusion gene; (2) ESTs with abnormalities in the BCOR gene; and (3) HGESS with the ZC3H7B-BCOR fusion gene.The 2014 WHO classification categorizes ESTs with YWHAE-NUTM2 fusion genes into HGESS.

YWHAE is a key protein in the regulation of cellular signaling, and NUTM2 has a high degree of homology to the gene sequence of NUT (NUTM1), which has an important role in NUT midline tumors. The fusion gene has not yet been detected in other benign and malignant lesions of the female reproductive system. Given the extremely low prevalence of HGESS, testing for the YWHAE-NUTM2 fusion gene is necessary to confirm the diagnosis.

When diagnosing HGESS with the YWHAE-NUTM2 fusion gene, it is first necessary to differentiate it from LGESS. Extensive sampling and searching for areas of high-grade round cells are key to the differential diagnosis.

UUS is an exclusionary diagnosis with no specificity for immunohistochemical and molecular alterations, and other types of uterine sarcoma must be excluded from the diagnosis.UUS does not contain genetic alterations specific to LGESS and HGESS, such as the JAZF1-SUZ12, ZC3H7B-BCOR fusion genes and YWHAE gene rearrangements.