Imaging Features with Histopathologic Correlation of CNS High-Grade Neuroepithelial Tumors with a BCOR Internal Tandem Duplication

Abstract Casestudy: High-grade uterine sarcomas are rare mesenchymal tumors in which the underlying genetics of many have been recently elucidated. BCOR internal tandem duplications are present in a subset of high-grade uterine sarcomas. We report a diagnostically challenging case of a high-grade uterine sarcoma with a BCOR internal tandem duplication presenting with total uterine inversion. The case is that of a 24 year old G0P0 female with a four month history of intermittent diffuse abdominal pain and abnormal uterine bleeding. Pelvic examination revealed a mass protruding to the hymenal ring. The patient was suspected of having a prolapsed fibroid through the cervix, and a myomectomy was planned. During the procedure, total uterine inversion was noted as a result of a submucosal mass emanating from the uterine apex. The mass was removed off a broad base using sharp dissection, and the uterus was reverted in a subsequent procedure. Grossly, the mass was polypoid, rubbery, and measured 7 cm in greatest dimension. It was grey-white to red-brown, variegated, and fibrotic with focal hemorrhagic areas. Histologically, the neoplasm had variable cellularity with spindle cells and a myxoid background. There was diffuse mild to moderate cytologic atypia and areas of increased mitotic activity. Tongue-like growth was present at the interface of the tumor with the normal myometrium. The neoplastic cells showed strong immunoreactivity for cyclin D1, BCOR, and TRK. There was focal immunoreactivity for CD10, and ALK was negative. Next-generation sequencing was performed and demonstrated an insertion into the BCOR gene, consistent with a diagnosis of high- grade uterine sarcoma with BCOR internal tandem duplication. In conclusion, we report an interesting presentation of a high-grade uterine sarcoma with BCOR internal tandem duplication causing total uterine inversion. The morphologic features and immunohistochemical profile suggested the possibility of the entity, and next generation sequencing confirmed the diagnosis.

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A Rare Case Of CNS High-Grade Neuroepithelial Tumor With BCOR Alteration (HGNET-BCOR)

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.064 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S31-S32

Author(s):

A Al-Habib ◽

M Bhattacharjee

Keyword(s):

Tumor Cells ◽

Tandem Duplication ◽

S100 Protein ◽

Tumor Resection ◽

Hematologic Malignancies ◽

Solid Organ ◽

High Grade ◽

Internal Tandem Duplication ◽

Tumor Entity ◽

New Treatment

Abstract Introduction/Objective HGNET-BCOR is a distinct molecular CNS tumor entity that was first identified by DNA methylation analysis in 2016. It is defined by an in-frame internal tandem duplication in exon 15 of the BCOR gene. The BCOR mutation is not unique to this tumor entity and can be seen in other CNS tumors, as well as solid organ and hematologic malignancies. In this report, we describe the pathology in a 2-year-old girl with a posterior fossa brain tumor initially diagnosed as high-grade neuropeithelial tumor at an outside facility. Methods She underwent resection and adjuvant chemotherapy at the same institution. She presented later to our hospital complaining of fatigue and vomiting, and tumor recurrence on MRI. Microscopic examination of the recurrent tumor showed a relatively circumscribed lesion with atrophic cerebellar folia associated with some of the tumor fragments. Tumor cells were arranged in papillary, pseudopapillary, and rosetted patterns in a myxoid (Alcian-blue positive) background. The tumor showed regional necrosis and frequent mitoses (mitotic index ~14–15 /10 HPFs). An extensive panel of immunostains was performed. Results The tumor was diffusely and strongly positive only for vimentin and EGFR, with diffuse moderate staining for BCL-2, and patchy weak staining for S100 protein. There were rare, focal tumor cells with GFAP and neurofilament staining. The Ki67 labeling index was 80–90%. All other tested markers were negative. The primary tumor resection was later found to be positive for BCOR by IHC. Sequencing for exon 15 of the BCOR gene showed an in-frame internal tandem duplication. Conclusion These features are consistent with the diagnosis of HGNET-BCOR. The pathologic and clinical features for this rare tumor entity are not widely known. Further studies with additional patients are needed to expand our understanding of these rare tumors to develop new treatment approaches.

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ETMR-01. TREATMENT OUTCOME OF TWO CASES WITH HIGH-GRADE NEUROEPITHELIAL TUMOR WITH BCOR ALTERATION

Neuro-Oncology ◽

10.1093/neuonc/noaa222.205 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii322-iii322

Author(s):

Ines Kristensen ◽

Louise Lindholt Hansen ◽

Torben Stamm Mikkelsen ◽

Louise Tram Henriksen ◽

Benedicte Parm Uldhøi ◽

...

Keyword(s):

Tandem Duplication ◽

Primary Tumour ◽

Radical Resection ◽

Liver Lesion ◽

Residual Tumour ◽

High Grade ◽

Internal Tandem Duplication ◽

The Central Nervous System ◽

Tumor Entity ◽

Primary Tumour Site

Abstract INTRODUCTION High grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication (HGNET BCOR) is a recently described tumor entity of the central nervous system (CNS) with a distinct methylation profile and characteristic genetic alteration. We report the outcome of two cases after 1st line multimodality therapy. MATERIAL AND METHOD A 7 year old girl with a ventricular tumour and a 6 year old boy with a tumour in the occipital region with infiltration of the transverse and sigmoid sinus were both diagnosed based on histology and methylation with HGNET-BCOR. No spinal or liquor dissemination were found at diagnosis in both cases. Treatment consisted of radical resection of the tumour. In the case of the lesion with sinus infiltration residual tumour in the vessel could not be removed. Both children were postoperatively treated with radiotherapy (craniospinal 36 Gy and boost to 54 Gy), concomitant Vincristin and adjuvant Cisplatin, Lomustine and Vincristine. RESULTS The girl developed a local recurrence at the primary tumour site 18 months after diagnosis. Reoperation showed the same histology. Start of 2nd line chemotherapy with Temozolomid and Irinotecan is being discussed. The boy with sinus infiltration developed seven months after diagnosis multiple liver, lung and bone metastasis. Biopsy of a liver lesion showed HGNET-BCOR. He was treated with Temozolomid, Irinotecan and died nine months after diagnosis. CONCLUSION We report two cases with failure after 1st line treatment for HGNET-BCOR. To our knowledge HGNET-BCOR with development of hematological disease dissemination is a rare finding.

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