Immunophenotypic features of dedifferentiated skull base chordoma: An insight into the intratumoural heterogeneity

Abstract

Chordomas are rare and low-grade malignant solid tumours, despite their histologically benign appearance, that arise in the bone from embryonic notochordal vestiges of the axial skeleton, a mesoderm-derived structure that is involved in the process of neurulation and embryonic development. Chordomas occurring in the skull base tend to arise in the basiocciput along the clivus. Three major morphological variants have been described (classical, chondroid, and atypical/dedifferentiated). The pathogenesis and molecular mechanisms involved in chordoma development remain uncertain. From a pathological standpoint, the microenvironment of a chordoma is heterogeneous, showing a dual epithelial-mesenchymal differentiation. These tumours are characterised by slow modality of biologic growth, local recurrence, low incidence of metastasis rates, and cancer stem cell (CSC) phenotype. The main molecular findings are connected with brachyury immunoexpression and activation of the downstream Akt and mTOR signalling pathways. The differentiation between typical and atypical chordomas is relevant because the tumoural microenvironment and prognosis are partially different. This review provides an insight into the recent and relevant concepts and histochemical markers expressed in chordomas, with special emphasis on dedifferentiated chordomas and their prognostic implications.

Clival Chondroid Chordoma: A Case Report and Review of the Literature

“…The most common locations involve the head and neck, specifically the clivus, spinal-occipital synchondrosis of the clivus, and sella turcica. Per histopathology and immunohistochemistry techniques, they can be further classified into classic, chondroid, and undifferentiated chordomas [ 3 , 5 , 13 ]. Clinical manifestations depend on the area of localization of the tumor mass.…”

“…Chordomas are characterized by lobulated arrangements of cells with a tendency to form bands or pseudoacinar structures [ 6 , 9 ]. Immunohistochemistry is positive for cytokeratin and EMA, S100, and vimetine [ 1 - 2 , 13 ].…”

Giant cranionasal epithelioid haemangioendothelioma with invasive growth pattern mimicking a skull base chondrosarcoma

“…Histologically, definitive diagnosis of these tumours may be a challenge, and histological examination and immunohistochemical markers is needed to distinguish EHE from poorly differentiated carcinomas [ 1 , 3 , 8 , 11 ]. The differential diagnosis thus includes angiosarcoma, chordoid meningioma [ 8 , 16 ], epithelioid haemangioma (EH), chordoma [ 17 ], and chondrosarcoma [ 18 ]. In this case, however, the results of immunohistochemical study excluded all of these tumours.…”

“…Chondrosarcomas represent the third most common malignant tumours of the bone and can be misdiagnosed as skull-base chordomas, being challenging lesions even for pathologists because of their strikingly similar morphology. Chondrosarcomas are composed of nested tumour cells with occasional vacuolisation embedded in a fibrous matrix [ 8 , 17 , 20 ]. Chordoma stains for EMA and cytokeratin.…”

MTNR1B loss promotes chordoma recurrence by abrogating melatonin‐mediated β‐catenin signaling repression

“…Chordoma is an extremely rare malignant bone tumor with an incidence of about 1/1 000 000/year . Chordoma arises from the remnants of embryonic notochord tissue and is usually located in the sacrum (50%) and the skull base region (35%) . Chordoma is characterized by a slow growth rate and a locally invasive capacity with low metastatic potential, and the median overall survival time is 140.5 months .…”