Novel morphologic findings in PLAG1‐rearranged soft tissue tumors

Abstract

Oncogenesis in PLAG1‐rearranged tumors often results from PLAG1 transcription factor overexpression driven by promoter‐swapping between constitutively expressed fusion partners. PLAG1‐rearranged tumors demonstrate diverse morphologies. This study adds to this morphologic heterogeneity by introducing two tumors with PLAG1 rearrangements that display distinct histologic features. The first arose in the inguinal region of a 3‐year‐old, appeared well‐circumscribed with a multinodular pattern, and harbored two fusions: ZFHX4‐PLAG1 and CHCHD7‐PLAG1. The second arose in the pelvic cavity of a 15‐year‐old girl, was extensively infiltrative and vascularized with an adipocytic component, and demonstrated a COL3A1‐PLAG1 fusion. Both showed low‐grade cytomorphology, scarce mitoses, no necrosis, and expression of CD34 and desmin. The ZFHX4‐/CHCHD7‐PLAG1‐rearranged tumor showed no evidence of recurrence after 5 months. By contrast, the COL3A1‐PLAG1‐rearranged tumor quickly recurred following primary excision with positive margins; subsequent re‐excision with adjuvant chemotherapy resulted in no evidence of recurrence after 2 years. While both tumors show overlap with benign and malignant fibroblastic and fibrovascular neoplasms, they also display divergent features. These cases highlight the importance of appropriate characterization in soft tissue tumors with unusual clinical and histologic characteristics.

Development and validation of an RNA sequencing panel for gene fusions in soft tissue sarcoma

“…The MEG3 gene transcribes a 1.6 kb lncRNA that acts as an antitumor component in different cancer cells such as breast, liver, glioma, colorectal, cervical, gastric, lung, ovarian, and osteosarcoma 36 . Tumorigenesis in PLAG1 fusion tumors often results from PLAG1 overexpression driven by constitutively expressed fusion partners 37,38 . The PLAG1 ‐rearranged STS displays a purely fibromyxoid histology, with high expression of CD34 and Desmin 25 .…”

“… 36 Tumorigenesis in PLAG1 fusion tumors often results from PLAG1 overexpression driven by constitutively expressed fusion partners. 37 , 38 The PLAG1 ‐rearranged STS displays a purely fibromyxoid histology, with high expression of CD34 and Desmin. 25 In addition, RPSAP52 is a pseudogene‐transcribed RNA that runs antisense to the oncofetal gene HMGA2 and positively regulates HMGA2 expression through the formation of an R loop structure.…”

Pediatric fibromyxoid tumor with PLAG1 fusion: An emerging entity with a novel intracranial location

“…Gene fusions involving COL3A1 are uncommon. Reports of fusion to PLAG1 , as detected in our case, are limited to lipoblastoma 4,9,11,15,16 . The only other gene fusion reported is to USP6 in myofibroblastic tumors, including cranial fasciitis, cellular fibroma of tendon sheath and a deep soft tissue myofibroblastic tumor 17–19 .…”

“…None of these tumors involve COL3A1 as the 5′ partner gene. COL3A1 is just one of the genes that may partner with PLAG1 in lipoblastoma; others include HAS2 , RAB2A , COL1A2 , BOC , RAD51L1 , CHCHD7 , HNRNPC , PI15 , ZEB , RUNX1T1 , VCAN , SRSF3 DDX6 , KLF10 , KANSL1L CTDSP2 , PCMTD1 , PPP2R2A , YWHAZ , ZFXH4 , and EEF1A1 4,9,11,12,15,26–28 …”

“…but no other lines of differentiation. They are typically immunopositive for desmin and CD34 8–10 . The partner genes for these tumors have included YWHAZ , EEF1A1 , ZFHX4l , CHCHD7 , and PCMTD1 .…”