A novel WWTR1::AFF2 fusion in an intra‐abdominal soft tissue sarcoma with associated endometriosis

Abstract

Application of molecular testing in clinical practice has led to significant advances in the classification of soft tissue sarcomas. Despite remarkable progress, there are still challenging cases that remain unclassified. In this study, we present an unusual spindle cell sarcoma arising in the abdominal cavity of a 37‐year‐old female. An extensive panel of immunostains was nonspecific for a line of differentiation and the tumor was subjected to targeted RNA sequencing for further classification. The findings showed a novel WWTR1::AFF2 fusion, which was further confirmed by break‐apart FISH analysis for WWTR1 gene rearrangement. The tumor was attached to the wall of sigmoid colon and showed a highly cellular proliferation of plump spindle to epithelioid cells arranged in intersecting fascicles. Areas of extensive endometriosis were identified adjacent to the tumor. The immunoprofile was significant for reactivity with desmin, calponin, WT‐1, ER, and PR, while negative for CD10, SMA, caldesmon, pan‐keratin, ALK, CD117, and S100. The patient is alive and well after 11 months of follow‐up. The exact histogenesis of this sarcoma remains unclear, however, the presence of adjacent endometriosis and coexpression of WT1/ER/PR raises the possibility of an unusual endometrioid stromal sarcoma, occurring outside the GYN tract. Additional cases are needed to establish the recurrent potential of this fusion event and to better define its pathogenesis and clinical behavior.

A Novel Cryptic t(2;3)(p21;q25) Translocation Fuses theWWTR1andPRKCEGenes in Uterine Leiomyoma With 3q- as the Sole Visible Chromosome Abnormality

“…The WWTR1 protein contains an N-terminal region which interacts with the TEAD family of transcription factors, a 14-3-3 binding site, a WW-domain, a transcription activation domain, and, at the Cterminal end, a conserved PDZ-domain (45)(46)(47). WWTR1 has been reported to fuse, as a 5'-end partner in various tumors (48)(49)(50)(51)(52)(53)(54). In epithelioid hemangioendothelioma, WWTR1 fuses with…”

“…Age of patients and abnormal karyotypes were obtained from Mitelman database of chromosome aberrations and gene fusions in cancer. intra-abdominal sarcoma associated with endometriosis it fuses with AF4/FMR2 family member 2 (AFF2 on Xq28) (54). PRKCE codes for a serine-and threonine-specific protein kinase which is a member of the protein kinase C (PKC) family (55,56).…”

DEK::AFF2 Fusion Carcinomas of Head and Neck

“…49 AFF2 rearrangements are associated with many malignant neoplasms, including DEK::AFF2 fusion carcinoma, a subset of pediatric peripheral T-cell lymphoma (STAG2::AFF2 fusion), 49 metastatic neuroendocrine tumor of unknown primary in the neck (CHD4::AFF2 fusion), 50 advanced stage lung adenocarcinoma (AFF2::RET fusion), 51 neuroepithelial tumor with PATZ1 fusion (LARGE1::AFF2 fusion), 52 and intra-abdominal spindle cell sarcoma associated with endometriosis (WWTR1::AFF2 fusion). 53 The oncogenic mechanism of DEK::AFF2 fusion still remains unknown and requires further investigation.…”