Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion

Abstract

Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features of both entities are considered hybrid LGFMS-SEF lesions. While the majority of LGFMS cases are characterized by FUS-CREB3L2 gene fusions, most cases of pure SEF show EWSR1 gene rearrangements. In the largest study of hybrid LGFMS-SEF tumors to date, all cases exhibited FUS rearrangements, a similar genetic profile to LGFMS. We herein describe the clinicopathological features and genetic findings of a case of primary renal hybrid LGFMS-SEF occurring in a 10-year-old child, with disseminated metastases. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was performed on both the primary renal tumor that showed the morphology of a LGFMS, and a cervical metastasis that showed the morphology of SEF. An EWSR1-CREB3L1 gene fusion occurring between exon 11 of EWSR1 and exon 6 of CREB3L1 was present in both the LGFMS and SEF components. This unusual case provides evidence that a subset of hybrid LGFMS-SEF harbor EWSR1-CREB3L1 gene fusions. In this case, these features were associated with an aggressive clinical course, with disease-associated mortality occurring within 12 months of diagnosis.

Sclerosing Epithelioid Fibrosarcoma of the Kidney: First Reported Case in a Young Child

“…Of note, a hybrid LGFMS-SEF of the kidney was previously reported in a 10-year-old female. 16 Unlike our case, it showed LGFMS morphology in the primary lesion, and features of SEF were only apparent in metastases. Interestingly, it harbored an EWSR1-CREB3L1 fusion (similar to pure SEF) rather than an FUS fusion expected in LGFMS and hybrid LGFMS-SEF.…”

EWSR1—The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review

“…Most often, these tumors occur in the deep soft tissue of the lower extremities, particularly thigh and limb girdles and the trunk. However, a wide variety of involved anatomic sites are reported, including intraabdominal, kidney, and bone [5,[141][142][143][144][149][150][151][152][153].…”

Detecting disease‐defining gene fusions in unclassified round cell sarcomas using anchored multiplex PCR/targeted RNA next‐generation sequencing—Molecular and clinicopathological characterization of 16 cases

“…More recently, testing gene panels based on anchored multiplex PCR followed by targeted RNA next generation sequencing (AMP/RNA‐seq) have been developed, allowing for simultaneous examination of multiple fusion transcripts and characterization of their partners with accurate breakpoints . This technique has been used successfully to characterize therapeutically relevant and prognostically significant fusions in other types of cancer, such as ALK and ROS1 rearrangements in lung adenocarcinoma, as well as to better classify challenging cases of sarcoma, including those currently considered within the Ewing family of tumors, and other round cell neoplasms, such as lymphomas …”

“…5 More recently, testing gene panels based on anchored multiplex PCR followed by targeted RNA next generation sequencing (AMP/RNA-seq) have been developed, allowing for simultaneous examination of multiple fusion transcripts and characterization of their partners with accurate breakpoints. 6 This technique has been used successfully to characterize therapeutically relevant and prognostically significant fusions in other types of cancer, such as ALK and ROS1 rearrangements in lung adenocarcinoma, 7 as well as to better classify challenging cases of sarcoma, 8,9 including those currently considered within the Ewing family of tumors, 10 and other round cell neoplasms, such as lymphomas. 11 In this study, we evaluate the utility of a FusionPlex Sarcoma panel using AMP/RNA-seq (ArcherDx, Boulder, CO) as an ancillary tool in the diagnosis of bone and soft tissue tumors, with emphasis on the diagnosis of sarcomas with round cell morphology, for which FISH studies were insufficient to arrive to a final diagnosis.…”