Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes

Abstract

CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity.

Sensitivity of HOXB13 as a Diagnostic Immunohistochemical Marker of Prostatic Origin in Prostate Cancer Metastases: Comparison to PSA, Prostein, Androgen Receptor, ERG, NKX3.1, PSAP, and PSMA

“…It is less well known that even though the genomic translocation is highly specific for prostate cancer, ERG protein expression is seen in a variety of other tumors, too. This includes, apart from vascular tumors, round cell sarcomas and leukemias, the more common differential diagnosis of urothelial carcinoma and, according to the human protein atlas (), also melanoma, testicular, and gastrointestinal tumors [22,23,24]. …”

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

“…However, heterologous cartilaginous differentiation in these neoplasms, as seen in one of the cases in our study, has not been previously reported. From an immunophenotypic standpoint, the majority of sarcomas with BCOR fusions demonstrate nuclear expression of TLE‐1, SATB2, and BCOR . Expression of these three markers, however, is not entirely specific, since they can also be seen in a proportion of clear cell sarcomas of the kidney.…”

“…Expression of these three markers, however, is not entirely specific, since they can also be seen in a proportion of clear cell sarcomas of the kidney. In addition, synovial sarcomas are typically positive for TLE‐1 and can express BCOR in up to 50% of cases . Larger studies evaluating the prognostic features of these neoplasms have shown a relatively favorable clinical behavior when compared to CIC ‐rearranged sarcomas, with mortality and metastatic rates that somewhat mirror those of synovial sarcoma, and favorable response to Ewing sarcoma chemotherapy .…”

Epigenetic Alterations in Bone and Soft Tissue Tumors

“…Similarly, the morphologic spectrum of BCOR-CCNB3 fusion sarcomas is broad, containing round, spindled, myxoid and, in rare cases, even pleomorphic tumors, though this latter morphology may be due in part to therapy. 70–73 …”