Skull base chordomas: correlation of tumour doubling time with age, mitosis and Ki67 proliferation index

Abstract

The aim of the study was to assess the relationship between the rate of clinical tumour growth and various histological features, including Ki67 labelling index, in skull base chordoma. Cases of skull base chordoma from 19 patients (six female, 13 male; age range 8-63 years) were reviewed and the diagnosis confirmed based on histological and immunohistochemical features. In each biopsy cellularity, pleomorphism, mitotic activity, apoptotic bodies, necrosis and inflammatory cell infiltrate were graded and Ki67 labelling index (LI) calculated as a measure of proliferation. Tumour doubling time was assessed by quantitative analysis of tumour volumes in post-operative magnetic resonance images and correlated with age, sex, histological parameters and Ki67 LI. It was shown that increasing patient age, the presence of mitotic figures or a Ki67 LI in excess of 6% were associated with faster growing tumours.

Skull base chordomas: clinical outcome in a consecutive series of 45 patients with long-term follow-up and evaluation of clinical and biological prognostic factors

“…2,18,23,39,52,56 To the best of our knowledge, only 19 surgical series with at least 15 patients have been reported in the literature (Table 4). 13 In the present study we considered a consecutive series of 45 patients treated at our institution in the period from 1990 to 2011 for a histological diagnosis of chordoma, completely fulfilling the pathological criteria described by Holton et al 21 Although a better long-term outcome in patients harboring chondroid chordoma has been reported, 19,47,59 in our analysis the histological type did not influence prognosis. Since the 1990s, other authors have denied the prognostic significance of histological type.…”

“…21,44 The LOH analysis was performed on available histological specimens from 27 patients using 33 microsatellite markers included in the 1p36.33-1p36.12 genomic interval, 5 microsatellites (D1S2841, D1S1172, D1S2868, D1S2726, and D1S2696) mapped at 1p, and 6 microsatellites (D1S498, D1S400, D1S238, D1S413, D1S1175, and D1S2800) mapped at 1q, according to the University of California Santa Cruz Database (http://www.ucsc.com). Tumor DNA was obtained from 27 fresh or frozen SBCs using Trizol reagent (Life Technologies).…”

“…28 Tumor doubling time correlated with age, sex, histological parameters, and Ki 67 labeling index. 21 Nevertheless, today we know very little about the oncogenesis of chordomas, although it is well established that not all chordomas behave the same. There are at least 2 subsets of SBCs with distinct clinical behavior: one group with a benign course and another with an aggressive and rapidly progressive course.…”

Expression of matrix metalloproteinases-1, -2, and -9; tissue inhibitors of matrix metalloproteinases-1 and -2; cathepsin B; urokinase plasminogen activator; and plasminogen activator inhibitor, type I in skull base chordoma

“…We did not calculate mitotic or apoptotic indices because mitosis and apoptosis were scarce as previously reported [6][7][8][9]. Tumor invasion of adjacent bone trabeculae in the periphery of the lesion and/or entrapment of residual bone fragments of various sizes within the lesion were recorded as tumor infiltration of host bone tissue.…”

A multidisciplinary team approach to skull base chondrosarcomas

“…Diagnosis of chondrosarcoma was made in tumors demonstrating morphological features of chondroid differentiation, in which immunohistochemical findings proved to be positive for S-100 protein, but negative for the epithelial markers cytokeratin and epithelial membrane antigen, which are positive in samples of chordoma. 13 Examples of mesenchymal chondrosarcoma exhibited biphasic differentiation with areas of apparently well-differentiated cartilage accompanied by poorly differentiated tumor composed of sheets of small spindle cells with pleomorphic, hyperchromatic nuclei. Immunohistochemical staining for S-100 protein was positive in well-differentiated chondrocytes and in a proportion of the poorly differentiated cells.…”