Pediatric fibromyxoid soft tissue tumor with PLAG1 fusion: A novel entity?

Abstract

The classification of undifferentiated soft tissue tumors continues to evolve with the expanded application of molecular analysis in clinical practice. We report three cases of a unique soft tissue tumor in young children (5 months to 2 years old) displaying a purely fibromyxoid histology, with positive staining for desmin and CD34. In two cases, RNA sequencing detected a YWHAZ‐PLAG1 gene fusion, while in the third case, a previously unreported EEF1A1‐PLAG1 fusion was identified. PLAG1 fusions have been reported in several pathologic entities including pleomorphic adenoma, myoepithelial tumors of skin and soft tissue, and lipoblastoma, the latter occurring preferentially in young children. In these tumors, expression of a full length PLAG1 protein comes under the control of the constitutively active promoter of the partner gene in the fusion, and the current cases conform to that model. Overexpression of PLAG1 was confirmed by diffusely positive immunostaining for PLAG1 in all three cases. Our findings raise the possibility of a novel fibromyxoid neoplasm in childhood associated with these rare PLAG1 fusion variants. The only other report of a PLAG1‐YWHAZ fusion occurred in a pediatric tumor diagnosed as a “fibroblastic lipoblastoma.” This finding raises the possibility of a relationship with our three cases, even though our cases lacked any fat component. Further studies with regard to a shared pathogenesis are required.

Novel morphologic findings in PLAG1‐rearranged soft tissue tumors

“…The neoplasm from Patient 1 displays histologic features very similar to two recently reported fibromyxoid soft tissue tumors with YWHAZ‐PLAG1 fusions, 8 particularly the focal myxoid nodules, bland fibroblastic cytomorphology, and the fibrous stroma with fascicular and nodular architecture. These recently reported cases also showed CD34 and desmin co‐expression, and lacked an adipocytic component.…”

“…For example, pleomorphic adenoma and its soft tissue counterpart, soft tissue, or cutaneous myoepithelioma (so‐called chondroid syringoma or benign mixed tumor), 6,7 demonstrate distinctive morphology from lipoblastoma. Recent reports of other PLAG1‐ rearranged tumors have added to this diversity 8 . We report two soft tissue tumors harboring PLAG1 rearrangements, further expanding the histologic spectrum of neoplasms with this molecular driver.…”

Recurrent 8q11-13 Aberrations Leading toPLAG1Rearrangements, Including Novel ChimerasHNRNPA2B1::PLAG1andSDCBP::PLAG1, in Lipomatous Tumors

“…Apart from pleomorphic adenomas and lipoblastomas, PLAG1-chimeras have also been reported in neoplasms, such as uterine myxoid leiomyosarcoma (6,53), chondroid syringoma (8), pediatric fibromyxoid tumor (11,54), carcinoma ex pleomorphic adenoma (55), acute myeloid leukemia (56,57), myoepithelioma/myoepithelial carcinoma/mixed tumors (58,59), and other soft tissue tumors (10,60). Correspondingly, identical PLAG1-fusion genes were found in different tumor types.…”

“…Correspondingly, identical PLAG1-fusion genes were found in different tumor types. For example, TRPS1::PLAG1 was reported in soft tissue myoepithelial tumor, uterine myxoid leiomyosarcoma, and chondroid syringoma (6,8,59), YWHAZ::PLAG1 was found in lipoblastoma and pediatric fibromyxoid tumor (17,54), and so on. All this indicates that the PLAG1 rearrangements/fusion genes hit a stem cell capable of both transformation and differentiation in several directions.…”

A unique epithelioid vascular neoplasm of bone characterized by EWSR1/FUS‐NFATC1/2 fusions

“…The above gene panels include 507 and 85 cancer‐related genes, respectively, with EWSR1 , FUS , and NFATC2 genes being included in both panels. The detailed methods for both platforms have been described previously 12,13 …”