<i><scp>BCOR</scp>–<scp>CCNB</scp>3</i>‐positive soft tissue sarcoma with round‐cell and spindle‐cell histology: a series of four cases highlighting the pitfall of mimicking poorly differentiated synovial sarcoma

Li, Wan Shan; Liao, I‐Chuang; Wen, Mei‐Chin; Lan, Howard Haw Chang; Yu, Shih Chen; Huang, Hsuan Ying

doi:10.1111/his.13001

Cited by 46 publications

(54 citation statements)

References 28 publications

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“…13 BCOR rearrangements have also been identified in soft tissue small blue round cell sarcomas and clear cell sarcoma of the kidney, albeit involving the 5' end in contrast to the 3' end that is seen in tumors harboring ZC3H7B-BCOR fusion. [44][45][46][47] We also recently identified BCOR internal tandem duplications in highgrade endometrial stromal sarcoma, the same genetic aberration detected in soft tissue small blue round cell sarcomas and clear cell sarcoma of the kidney. 9 Our clinical data are limited because of the rarity of ZC3H7B-BCOR endometrial stromal sarcomas.…”

Section: Discussionmentioning

confidence: 83%

ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity

et al. 2018

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High-grade endometrial stromal sarcoma likely encompasses underrecognized tumors harboring genetic abnormalities besides YWHAE-NUTM2 fusion. Triggered by three initial endometrial stromal sarcomas with ZC3H7B-BCOR fusion characterized by high-grade morphology and aggressive clinical behavior, we herein investigate the clinicopathologic features of this genetic subset by expanding the analysis to 17 such tumors. All of them occurred in adult women with a median age of 54 (range, 28-71) years. They were predominantly based in the endomyometrium and demonstrated tongue-like and/or pushing myometrial invasion. Most were uniformly cellular and displayed haphazard fascicles of spindle cells with mild to moderate nuclear atypia. Myxoid matrix was seen in 14 of 17 (82%) tumors, and collagen plaques were seen in 8 (47%). The mitotic index was ≥10 mitotic figures/10 high-power fields (HPFs) in 14 of 17 (82%) tumors with a median of 14.5 mitotic figures/10 HPFs. No foci of conventional or variant low-grade endometrial stromal sarcoma were seen. All tumors expressed CD10 with only limited or absent desmin, SMA and/or h-caldesmon staining. ER and PR expression in >5% of cells was seen in 4 of 12 (33%) tumors. Diffuse cyclin D1 and BCOR immunoreactivity was present in 7 of 8 (88%) and 7 of 14 (50%) tumors, respectively. Fluorescence in situ hybridization or targeted RNA sequencing confirmed ZC3H7B-BCOR fusion in all tumors, including four and two previously diagnosed as myxoid leiomyosarcoma and undifferentiated uterine sarcoma, respectively. Limited clinical data suggest that patients present at higher stage and have worse prognosis compared with published outcomes in low-grade endometrial stromal sarcoma. Tumors with ZC3H7B-BCOR fusion constitute a distinct group of endometrial stromal sarcomas with high-grade morphology that should be distinguished from other uterine mesenchymal neoplasms that may demonstrate myxoid morphology.

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Section: Discussionmentioning

confidence: 83%

ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity

et al. 2018

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“…Morphologic and immunohistochemical overlap of BCOR-CCNB3 soft tissue sarcomas with synovial sarcoma has been reported 27 , as has overlap between CCSK and renal synovial sarcoma 28 . Along these lines, BCOR overexpression has been demonstrated in approximately half (49%) of soft tissue synovial sarcomas 5 , though BCOR expression had not been addressed in primary renal synovial sarcomas until now.…”

Section: Discussionmentioning

confidence: 99%

Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion

Argani¹,

Kao

Zhang

et al. 2017

American Journal of Surgical Pathology

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We report two primary renal sarcomas demonstrating BCOR-CCNB3 gene fusions that have recently been identified in undifferentiated round cell sarcomas of bone and soft tissue. These neoplasms occurred in male children aged 11 and 12, and both were cystic as a result of entrapment and dilatation of native renal tubules. Both cases were composed of variably cellular bland spindle cells with fine chromatin set in myxoid stroma and separated by a branching capillary vasculature. Both neoplasms demonstrated immunoreactivity for BCOR, cyclin D1, TLE1 and SATB2 in the spindle neoplastic cells and negativity in the prominent capillary vasculature. One case was extensively cystic and had hypocellular areas that simulated cystic nephroma; this neoplasm recurred 3 years later as a solid, highly cellular spindle cell sarcoma in the abdominal cavity. The morphology and immunoprofile of these renal neoplasms was compared to a control group of other sarcomas with BCOR genetic abnormalities, including clear cell sarcoma of the kidney (CCSK), infantile undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy (URCS/PMMTI), and bone/soft tissue sarcomas with BCOR-CCNB3 gene fusion; along with primary renal synovial sarcoma. Our findings show that the renal sarcomas with BCOR-CCNB3 gene fusion overlap with CCSK. They are in keeping with a “BCOR-alteration family” of renal and extra-renal neoplasms which includes CCSK and URCS/PMMTI (which typically harbor BCOR internal tandem duplication), and BCOR-CCNB3 sarcomas, all of which are primarily driven by BCOR overexpression and have overlapping (but not identical) clinicopathologic features.

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“…Although BCOR immunohistochemistry has been recently shown as a highly sensitive marker for URCS with various BCOR genetic alterations, showing strong and diffuse reactivity, it is also positive in about half of SS cases tested (Kao et al, 2016b). Further immuno overlap between these two entities has been reported, including TLE1 positivity stain in a subset (3 out of 4 cases) of BCOR-CCNB3 fused tumors (Li et al, 2016) and SATB2 immunoreactivity in most (71%) BCOR-CCNB3 fused tumors and a small subset of SS (12%; Kao et al, 2016b).…”

Section: Discussionmentioning

confidence: 99%

BCOR upregulation in a poorly differentiated synovial sarcoma with SS18L1‐SSX1 fusion—A pathologic and molecular pitfall

Kao

Sung

Zhang

et al. 2017

Genes Chromosomes & Cancer

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The diagnosis of poorly differentiated synovial sarcoma (PD-SS) may be challenging due to overlapping morphologic features with other undifferentiated round cell sarcomas (URCS). Particularly relevant is the histologic overlap and shared BCOR overexpression between a subset of SS and URCS with various BCOR genetic abnormalities. Here we report a case of PD-SS lacking the canonical SS18-SSX gene fusion, but showing strong BCOR immunoreactivity and BCOR gene abnormalities by FISH which were misinterpreted as a URCS with BCOR gene rearrangements. The tumor had an unusual clinical presentation arising as an intraneural tumor in the ankle of a 29-year-old female. The tumor displayed a mixture of fascicular spindle cells and undifferentiated round cell components. FISH studies showed no SS18 gene abnormality; however, RNA sequencing identified a fusion transcript involving SS18L1 (a paralog gene of SS18 at 20q13.33) and SSX1. Further FISH testing validated rearrangements in SSX1 and SS18L1 genes, in addition to complex structural abnormalities of the Xp11.22-4 region. This is the second reported SS case harboring an SS18L1-SSX1 alternative fusion variant, similarly occurring in association with a large nerve. The lack of SS18 gene rearrangements by FISH corroborated with the BCOR overexpression at both mRNA and protein level may result in diagnostic pitfalls with URCS with BCOR gene abnormalities. Our results further suggest that BCOR upregulation is emerging as a common downstream pathway for SS with either typical SS18-SSX transcript or with rare fusion variants, such as SS18L1-SSX.

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BCOR–CCNB3‐positive soft tissue sarcoma with round‐cell and spindle‐cell histology: a series of four cases highlighting the pitfall of mimicking poorly differentiated synovial sarcoma

Abstract: BCOR-CCNB3-positive sarcomas may primarily occur in soft tissues of adults and show PDSS-mimicking round-cell and spindle-cell histology with aggressive behaviour. Cyclin B3 is useful for selecting candidates for BCOR-CCNB3 molecular testing.

Cited by 46 publications

References 28 publications

ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity

ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity

Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion

BCOR upregulation in a poorly differentiated synovial sarcoma with SS18L1‐SSX1 fusion—A pathologic and molecular pitfall

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