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.

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 .…”

“…One view is that these tumors lie within the morphologic spectrum of lipoblastoma 11,12 given that lipoblastoma shows PLAG1 fusions with similar partner genes, including YWHAZ and EEF1A1 . The term “fibroblastic” lipoblastoma has been proposed for cases showing “a predominance of fibrous stroma, largely obscuring the adipocytic nature of the tumor.” 11 COL3A1 is one of the many genes known to partner with PLAG1 in lipoblastoma 4,9,11,15,16 . Thus, our case could be viewed as conforming to this model.…”

“…It is true that we cannot rule out a pathogenetic relationship of our case to lipoblastoma. Nevertheless, we do not feel there is convincing evidence that our case is related to lipoblastoma or any other adipocytic tumor and, instead, we feel it is another example of a distinct tumor phenotype, similar to the six tumors recently documented in soft tissue 8–11 . The term “PLAG1 mesenchymal tumors” has been suggested 10 .…”

“…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 .…”