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

Abstract

Translocations involving PLAG1 occur in several tumors, most commonly pleomorphic adenoma and lipoblastoma. Recently, a distinctive soft tissue tumor with a PLAG1 fusion has been reported in the pediatric age group. These are low grade tumors with a fibroblastic or mixed fibroblastic and myxoid morphology but no other lines of differentiation. They are typically immunopositive for desmin and CD34. The partner genes for these tumors have included YWHAZ, EEF1A1, ZFHX4l, CHCHD7, and PCMTD1. We report another case of this fibromyxoid tumor with a PLAG1 fusion, this time with COL3A1 as the partner gene. The fusion placed expression of a full‐length PLAG1 protein under the control of the constitutively active COL3A1 promoter. Overexpression of PLAG1 was confirmed by diffusely positive immunostaining for PLAG1. The most novel aspect of this tumor is the intracranial location. Opinion has been divided over whether these tumors are a specific entity, or related to lipoblastoma, since that tumor also typically occurs in soft tissue in the pediatric age group and shows many of the same gene fusions. However, lipoblastoma has never been reported in an intracranial location and, thus, our case provides compelling evidence that this fibromyxoid tumor is indeed a distinct entity.

Calcifying Spindle Cell Soft Tissue Tumor With SOX10::PLAG1 Fusion: A Case Report of a Morphologically Distinctive and Potentially Novel Soft Tissue Tumor

“…However, clinicopathological features of eccrine-type cutaneous mixed tumors, such as predominant dermal location in head and neck areas and the presence of prominent epithelial differentiation and keratin expression, are quite distinct from our case. Although the presented tumor has neither clinical nor morphological similarity with lipoblastoma, it may morphologically slightly resemble a more recently described pediatric fibromyxoid soft tissue tumor with PLAG1 fusions [4,14]. The latter tumors have somewhat overlapping morphological and molecular features with lipoblastomas but lack the lipomatous component, leading some authors to label them "fibroblastic lipoblastomas" [2].…”

Pediatric dermatofibrosarcoma protuberans: A clinicopathologic and genetic analysis of 66 cases in the largest institution in Southwest China

“…Genetically important, NGS revealed the GCF containing a novel COL3A1-PDGFB fusion that was first presented in DFSP. COL3A1, located in 2q32.2, belongs to the collagen genes together with COL1A1 and COL1A2, and encodes a structural protein of type III collagen, which is found in abundance in extensible connective tissues, such as skin, blood vessels, gastrointestinal tract, and the developing brain (38)(39)(40)(41). The translocation of COL3A1 had been reported as a rare partner fusing to PLAG1-rearranged neoplasms (including lipoblastoma and (40,(42)(43)(44)(45)(46).…”

“…COL3A1, located in 2q32.2, belongs to the collagen genes together with COL1A1 and COL1A2, and encodes a structural protein of type III collagen, which is found in abundance in extensible connective tissues, such as skin, blood vessels, gastrointestinal tract, and the developing brain (38)(39)(40)(41). The translocation of COL3A1 had been reported as a rare partner fusing to PLAG1-rearranged neoplasms (including lipoblastoma and (40,(42)(43)(44)(45)(46). In addition, atypical variants of COL3A1 were associated with Ehlers-Danlos syndrome (EDS) involving connective tissue disorders (39,47).…”

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.…”

“…The result was high expression of PLAG1 and reduced expression of CTNNB1 (1). Subsequently, numerous chimeras in which PLAG1 is the 3'-end partner gene have been described in various tumors (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). As a consequence, the PLAG1 gene becomes either overexpressed or activated resulting in deregulation of the genes it targets, ultimately leading to tumor development (12)(13)(14)(15)(16).…”