Clinicopathologic characteristics of poorly differentiated chordoma

Abstract

Chordoma is a rare malignant tumor of bone with high morbidity and mortality. Recently, aggressive pediatric poorly differentiated chordoma with SMARCB1 loss has been described. This study summarizes the clinicopathologic features of poorly differentiated chordoma with SMARCB1 loss in the largest series to date. A search of records between 1990-2017 at MGH identified 19 patients with poorly differentiated chordoma. Immunohistochemical stains were evaluated. Kaplan-Meier survival statistics and log-rank (Mantel Cox) tests compared survival with other subtypes. The patients (n = 19) were diagnosed at a median age of 11 years (range: 1-29). Tumors arose in the skull base and clivus (n = 10/19; 53%); cervical spine (n = 6/19; 32%); and sacrum or coccyx (n = 3/19; 16%). The clinical stage of these patients (AJCC 7e) was stage 2A (n = 7/16; 44%); stage 2B (n = 6/16; 38%); stage 4A (n = 1/16; 6%); and stage 4B (n = 2/16; 13%). The tumors were composed of sheets of epithelioid cells with nuclear pleomorphism, abundant eosinophilic cytoplasm, and increased mitoses. Tumors were positive for cytokeratin (n = 18/18; 100%) and brachyury (n = 18/18; 100%). Patients were treated with a combination of excision, radiation therapy, and chemotherapy. No difference in overall survival, progression free survival, local control time, and metastasis free survival was identified between poorly differentiated chordoma of the skull base and of the spine. Compared to other chordoma subtypes, poorly differentiated chordoma has a significantly decreased mean overall survival after stratification by site (p = 0.037). Pediatric poorly differentiated chordoma has a distinct clinical and immunohistochemical profile, with characteristic SMARCB1 loss and decreased survival compared to conventional/chondroid chordoma. Recognition of this subtype is important because these malignancies should be treated aggressively with multimodality therapy.

An update of molecular pathology of bone tumors. Lessons learned from investigating samples by next generation sequencing

“…This subtype of chordoma is most commonly seen in patients under the age of 30 occurring most commonly at the skull base or high cervical vertebra, although more recently a small number have been reported in the sacral region. These tumors typically show an inferior prognosis compared to conventional chordoma …”

“…These tumors typically show an inferior prognosis compared to conventional chordoma. 62,63 In a recent study, we reviewed 359 chordoma cases, all of which were immunoreactive for TBXT and cytokeratins, for the expression of SMARCB1. Ninety two (25.6%) of these occurred at the skull base Notably five chordomas considered to represent conventional chordomas have been reported to show loss of INI-1 expression.…”

Molecular characteristics of poorly differentiated chordoma

“…3 Conventional chordoma can be recognized morphologically with classic "physaliphorous cells" in a myxoid background, and the chondroid type contains matrix that mimics hyaline cartilage. 9 Although poorly differentiated chordoma has immunohistochemical evidence of abnormalities in the SWI/SNF chromatin remodeling complex (specifically, SMARCB1), only a few small series investigating the genetics of poorly differentiated chordoma have identified deletion of SMARCB1 by fluorescent in-situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) assays. All subtypes (except the dedifferentiated component in dedifferentiated chordoma) typically show positive immunohistochemical staining for keratins, T brachyury, S100, and epithelial membrane antigen, which together are suggestive of notochordal differentiation.…”

“…Although rare, these tumors occur in a pediatric population and tend to involve the skull base, with a significant decrease in mean overall survival compared to conventional and chondroid chordoma. 9 Although poorly differentiated chordoma has immunohistochemical evidence of abnormalities in the SWI/SNF chromatin remodeling complex (specifically, SMARCB1), only a few small series investigating the genetics of poorly differentiated chordoma have identified deletion of SMARCB1 by fluorescent in-situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) assays. 6,8,10 More recently, a small number of pediatric chordomas with SMARCB1 loss by immunohistochemistry have also been identified to have point mutations in SMARCB1.…”

Poorly differentiated chordoma: review of 53 cases

“…Inclusion criteria in this review included involvement of axial skeleton (vertebra and clivus, which are common locations for classical chordoma), INI1 loss (either with the aid of immunohistochemistry or various molecular techniques), and immunohistochemical brachyury expression. According to these qualifications, we came up with 53 cases reported up to March 2018, from different institutions (2)(3)(4)(5)(8)(9)(10)(11)(12)(13)(14)(15). The clinical, imaging, histopathological features, and immunohistochemical and molecular findings of those 53 cases were given in Table 1 and summarized in Table 2.…”