Poorly differentiated chordoma with whole‐genome doubling evolving from a <scp><i>SMARCB1</i></scp>‐deficient conventional chordoma: A case report

Curcio, Christian; Cimera, Robert; Aryeequaye, Ruth; Rao, Mamta; Fabbri, Nicola; Zhang, Yanming; Hameed, Meera

doi:10.1002/gcc.22895

Cited by 10 publications

(12 citation statements)

References 23 publications

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“…In our case number 6 with both conventional and poorly differentiated chordoma components, we found heterozygous deletion of SMARCB1 in the conventional chordoma component without additional genetic alterations. Similar to our previous case report of axial poorly differentiated chordoma, 39 the extra‐axial poorly differentiated chordomas (two cases) demonstrated a complex hyperdiploid genomic profile with gain of multiple chromosomes and a homozygous deletion of SMARCB1 . No mutations or structural variants were identified in all three extra‐axial chordomas with available NGS‐targeted sequencing analysis (MSK‐IMPACT).…”

Section: Discussionsupporting

confidence: 87%

“…Poorly differentiated variant of chordoma is a tumor of pediatric and young adult age group, commonly occurring at clivus/cervical vertebral location and is pathologically characterized by sheets of epithelioid cells with eosinophilic cytoplasm, nuclear atypia and loss of INI‐1 expression due to inactivating mutations and/or recurrent isolated copy number losses involving SMARCB1 at 22q11.23 5–7 . In a prior case report of a conventional chordoma from the sacrum with transformation to poorly differentiated chordoma, we showed that SMARCB1 loss (homozygous) may be an early event in rare cases of axial conventional chordoma and a poorly differentiated chordoma can evolve through additional genomic aberrations such as doubling of the genome 39 . Extra‐axial poorly differentiated chordoma is exceptionally rare with a single published case report of a 67‐year‐old female who presented with a knee mass with destruction of the medial cortex of metadiaphysis of distal femur and a large extraosseous soft tissue mass 21 …”

Section: Discussionmentioning

confidence: 79%

“…[5][6][7] In a prior case report of a conventional chordoma from the sacrum with transformation to poorly differentiated chordoma, we showed that SMARCB1 loss (homozygous) may be an early event in rare cases of axial conventional chordoma and a poorly differentiated chordoma can evolve through additional genomic aberrations such as doubling of the genome. 39 Extra-axial poorly differentiated chordoma is exceptionally rare with a single published case report of a 67-year-old female who presented with a knee mass with destruction of the medial cortex of metadiaphysis of distal femur and a large extraosseous soft tissue mass. 21 As chordomas in general belong to the C-class group, we utilized This was a biopsy material and the partial loss of INI1 could be related to the decalcification.…”

Section: Clinical Datamentioning

confidence: 99%

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Recurrent loss of chromosome 22 and SMARCB1 deletion in extra‐axial chordoma: A clinicopathological and molecular analysis

Wen

Cimera

Aryeequaye

et al. 2021

Genes Chromosomes & Cancer

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Extra-axial chordoma is a rare neoplasm of extra-axial skeleton and soft tissue that shares identical histomorphologic and immunophenotypic features with midline chordoma. While genetic changes in conventional chordoma have been well-studied, the genomic alterations of extra-axial chordoma have not been reported. It is well known that conventional chordoma is a tumor with predominantly non-random copy number alterations and low mutational burden. Herein we describe the clinicopathologic and genomic characteristics of six cases of extra-axial chordoma, with genomewide high-resolution single nucleotide polymorphism array, fluorescence in situ hybridization and targeted next-generation sequencing (NGS) analysis. The patients presented at a mean age of 33 years (range: 21-54) with a female to male ratio of 5:1. Four cases were histologically conventional type, presented with bone lesions and three of them had local recurrence. Two cases were poorly differentiated chordomas, presented with intra-articular soft tissue masses and both developed distant metastases. All cases showed brachyury positivity and the two poorly differentiated chordomas showed in addition loss of INI-1 expression by immunohistochemical analysis. Three of four extra-axial conventional chordomas showed simple genome with loss of chromosome 22 or a heterozygous deletion of SMARCB1. Both poorly differentiated chordomas demonstrated a complex hyperdiploid genomic profile with gain of multiple chromosomes and homozygous deletion of SMARCB1. Our findings show that heterozygous deletion of SMARCB1 or the loss of chromosome 22 is a consistent abnormality in extra-axial chordoma and transformation to poorly differentiated chordoma is characterized by homozygous loss of SMARCB1 associated with genomic complexity and instability such as hyperdiploidy. K E Y W O R D Sextra-axial chordoma, extra-axial poorly differentiated chordoma, INI1, SMARCB1

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 79%

Section: Clinical Datamentioning

confidence: 99%

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Recurrent loss of chromosome 22 and SMARCB1 deletion in extra‐axial chordoma: A clinicopathological and molecular analysis

Wen

Cimera

Aryeequaye

et al. 2021

Genes Chromosomes & Cancer

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“…The PDC, a tumor that often occurs in children, prefers the base of the skull and appears nuclear TBXT positivity along with INI-1 loss [ 34 , 35 ]. Case analysis findings suggest that a SMARCB1 deletion is an early event in the rare traditional chordoma that may transform into PDC through supernumerary genome variation [ 36 ]. SMARCB1/INI1-negative PDC is a unique subset of chordomas with clinical, histopathological, and molecular specificity, rapid progression, and poor prognosis, and should not be confused with traditional chordomas [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020

et al. 2022

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Introduction Chordoma is formed from embryonic residues or ectopic chordae and locally aggressive or malignant tumors. We visually analyzed the research tendency and hotspot of chordoma. Methods The bibliometric analysis was conducted from the Web of Science Core Collection database over the past two decades. The term and strategies were as follows: “TS = (chordoma) OR TS = (chordoblastoma) OR TS = (chordocarcinoma) OR TS = (chordoepithelioma) OR TS = (chordosarcoma) OR TS = (notochordoma). AND Language: English. AND Reference Type: Article OR Review”. A total of 2,118 references were retrieved and used to make a visual analysis by VOSviewer 1.6.15. Results The chordoma was on a steady rise and chordoma but remained the focus of scholars and organizations over the last two decades. The Chinese institutions and scholars lacked cooperation with their counterparts in other countries. The citations of documents and co-citation analysis of cited references suggested that M.L. McMaster, B.P. Walcott, P. Bergh, and S. Stacchiotti were leading researchers in this field of chordoma and their papers had been widely accepted and inspired recent researches. Keywords associated with recent chemotherapy, PD-1-related immunotherapy, and SMARCB1/integrase interactor 1 (INI1) in chordoma were a shortage of research and there may be more research ideas in the future by scholars. The research of chordoma will continue to be the hotspot. Conclusions Thus, explaining the molecular mechanism and potential role of transcriptional inhibition and immunologic responses to SMARCB1/INI1-negative poorly differentiated chordoma will be available for preclinical experiments and clinical trials and lead to new therapeutic opportunities for chordoma patients.

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“…Brachyury is a transcription factor in the T-box group and is highly specific for chordoma 19,20 ; it is diffusely positive in this condition. [21][22][23] Poorly differentiated chordoma (PC) also shows diffuse positivity for brachyury, [24][25][26] with complete loss of 24 One extra-axial PC case has been described, but showed diffuse positivity for brachyury, 27 in contrast to METC. In addition, PC shows mild to moderate nuclear pleomorphism, abundant eosinophilic cytoplasm, and geographical necrosis.…”

Section: Discussionmentioning

confidence: 99%

Myxoepithelioid tumour with chordoid features: a clinicopathological, immunohistochemical and genetic study of 14 cases of SMARCB1/INI1‐deficient soft‐tissue neoplasm

Kinoshita¹,

Kohashi²,

Yamamoto³

et al. 2021

Histopathology

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Myxoepithelioid tumour with chordoid features: a clinicopathological, immunohistochemical and genetic study of 14 cases of SMARCB1/INI1-deficient soft-tissue neoplasm Aims: Complete loss of SMARCB1/INI1 in soft-tissue tumours such as malignant rhabdoid tumour, epithelioid sarcoma, myoepithelial tumour of soft tissue and extraskeletal myxoid chondrosarcoma is often associated with high-grade malignancy and poor prognosis. The diagnosis is sometimes challenging, owing to histological similarities, so careful differential diagnosis is required. Therefore, soft-tissue tumours with complete SMARCB1/ INI1 loss could potentially include an unknown entity. Methods and results: We analysed 160 cases of SMARCB1/INI1-deficient soft-tissue tumour, and found 14 cases that were not classifiable into already existing categories and had common clinical and histological features. These involved two male and 12 female patients, ranging in age from 20 years to 61 years. The tumours were located in the the puboinguinal region (n = 13) and pelvic cavity (n = 1). Histologically, the tumours showed relatively uniform epithelioid to spindle-shaped cells with myxoid stroma. All tumours showed immunoreactivity for brachyury, epithelial membrane antigen, and progesterone receptor, and 12 of 14 cases did so for oestrogen receptor. Variable positive staining for a-smooth muscle actin, S100 and glial fibrillary acidic protein (GFAP) was seen. NR4A3 and EWSR1 gene rearrangements were not detected in 13 and 11 examined cases, respectively. Clinical follow-up data for the 14 patients showed that 13 were alive without disease and one had been lost to follow-up; four patients developed local recurrence and/or metastases. Conclusion:The designation 'myxoepithelioid tumour with choroid features' (METC) was proposed as a tumour with intermediate malignancy controllable with appropriate treatment, including the entity of myoepithelioma-like tumour of the vulvar region. METC represents a novel and independent subset that is histologically, biologically and clinically distinct from already existing SMARCB1/INI1-deficient soft-tissue tumours.

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Poorly differentiated chordoma with whole‐genome doubling evolving from a SMARCB1‐deficient conventional chordoma: A case report

Cited by 10 publications

References 23 publications

Recurrent loss of chromosome 22 and SMARCB1 deletion in extra‐axial chordoma: A clinicopathological and molecular analysis

Recurrent loss of chromosome 22 and SMARCB1 deletion in extra‐axial chordoma: A clinicopathological and molecular analysis

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020

Myxoepithelioid tumour with chordoid features: a clinicopathological, immunohistochemical and genetic study of 14 cases of SMARCB1/INI1‐deficient soft‐tissue neoplasm

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