Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.
Biomarkers, Tumor/genetics* ; Child ; Chordoma/genetics* ; Diagnosis, Differential ; Female ; Humans ; Male ; Prognosis ; Rhabdoid Tumor/diagnosis* ; SMARCB1 Protein/genetics* ; Skull Base

OBJECTIVETo present an established human chordoma cell line for chordoma research.

METHODSThe specimens pathologically identified as chordoma were cultured, using primary tissue culture in vitro. The surviving cells were analyzed by morphology, histochemical stain, cell cycling analysis, karyotype analysis, electron microscopic observation, heterotransplantation and study of invasive capacity in vitro.

RESULTSThe newly established cell line CM-319 has been maintained in continual cultures for over 100 generations in two years. Its morphological observation, histochemical staining properties, electron microscopic observation and heterotransplantation showed the common characteristics of chordoma. The doubling time of cells was about 33 hours. Cell cycle analysis showed: G(1) 55.6%, G(2) 21.9% and S 22.5%, G(2)/G(1) = 1.90. Chromosome analysis showed a hypotriploid feature and the success rate of heterotransplantation was 100%. It is capable of invasion in vitro.

CONCLUSIONCM-319, as a cell line derived from human chordoma cells, may serve for further studies of chordoma.

Animals ; Cell Line, Tumor ; Cell Proliferation ; Chordoma ; genetics ; pathology ; Humans ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness