Takahiko Naka

Chordomas of the skull base: surgical management and outcome.

OBJECT The goal of this study was to report on the surgical management of skull base chordomas and to evaluate both the short- and long-term treatment outcomes. METHODS The authors retrospectively studied data from 49 patients who had undergone consecutive surgeries at a single institution. They also analyzed patterns of chordoma extension. Complications and surgery-related morbidity were recorded. A Kaplan-Meier analysis was performed to determine survival rates in patients 5 and 10 years after their first surgery. Operative approaches were selected on the basis of the predominant tumor extension. RESULTS The approach used most frequently was the transethmoidal in 36.3%, followed by the pterional in 23.4% and the retrosigmoid in 23.4%. The tumor was totally removed in 49.4% and subtotally in 50.6%. The rate of total removal was highest at initial surgery (78%) and progressively declined thereafter. In 11.8% of cases a new neurological deficit developed, while the preoperative deficit remained unchanged. In 20% of cases the preoperative deficits improved, but new deficits also appeared. The 5- and 10-year survival rates are 65 and 39%, respectively. CONCLUSIONS With an individually tailored surgical approach, total tumor removal in 78% of the cases was achieved at the initial surgery. Radical surgery appears to increase slightly the surgical morbidity, but at the same time prolongs the recurrence-free interval. Chordomas cannot be regarded as surgically curable tumors given the 5- and 10-year survival rates in patients harboring such lesions.

Overexpression of bcl-2 protein in synovial sarcoma: A comparative study of other soft tissue spindle cell sarcomas and an additional analysis by fluorescence in situ hybridization

The expression of bcl-2 protein was analyzed in 19 synovial sarcomas and 29 additional soft tissue spindle cell sarcomas as controls by the immunohistologic staining of paraffin-embedded specimens; 15 of 19 (79%) synovial sarcoma cases were positive, but all other spindle cell sarcomas were negative including 20 leiomyosarcomas, 4 malignant peripheral nerve sheath tumors, and 4 fibrosarcomas. In 4 cases of bcl-2-positive synovial sarcoma (3 biphasic and 1 focally glandular type), bcl-2 protein staining was much stronger in the spindle cells than in the epithelial cells. A fluorescence in situ hybridization (FISH) analysis with centromeric and whole chromosome painting probes for chromosome 18 and X was performed on 7 synovial sarcomas. The six cases of bcl-2-positive synovial sarcoma consisted of five cases with the t(X; 18) and one case with tetrasomy of chromosome 18 and X. It has been speculated that bcl-2 protein expression is caused by the 14; 18 translocation and other abnormalities of chromosome 18. This study thus showed the feasibility of such a correlation between bcl-2 protein expression and the characteristic cytogenetic abnormality in the synovial sarcoma-X; 18 translocation. In addition, bcl-2 protein also appears to be a characteristic marker of synovial sarcoma and is thus considered to be potentially useful in distinguishing synovial sarcoma from other spindle cell sarcomas.

Proliferative activities in conventional chordoma: A Clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia

Chordoma shows various degrees of atypia histologically, however, the relationship between the histological features and the biological behavior still remains controversial. The authors subclassified 17 specimens with chordoma into two groups (ie, trabecular type showing a trabecular patterns and solid type mainly consisting of a diffuse proliferation of tumor cells). The histological grading was performed according to the degree of nuclear atypia on a scale of 1 to 3. Using DNA flow cytometric and immunohistochemical techniques, both the proliferative index (% S + G2 + M phase) and the MIB-1 labeling index (LI) of the tumor cells were estimated regarding their proliferative activities. In addition, p53 overexpression was also investigated using immunohistochemical techniques. There were eight (47.1%) specimens of trabecular type and nine (52.9%) of solid type. In nine specimens of solid type, those with higher nuclear atypia (grade 2 or 3) were significantly more frequent (five specimens, 55.6%) than in trabecular type in which all of the eight specimens were grade 1 (P = 0.44). The proliferative index was significantly higher in grade 2 or 3 lesions than in grade 1 lesions (P = .014), and the MIB-1 LI tended to be higher in solid type than in trabecular (P = .088). p53 overexpression was detected in two specimens of solid type, and the MIB-1 LI in these two specimens was significantly higher (P = .037) than that in the specimens without p53 overexpression. It was considered that the preceding anaplastic histological features, including either diffuse proliferation or high grade nuclear atypia, together with p53 overexpression, were thus closely related to the proliferative activities in chordomas.

Expression of Matrix Metalloproteinase (MMP)-1, MMP-2, MMP-9, Cathepsin B, and Urokinase Plasminogen Activator in Non–Skull Base Chordoma

We analyzed the expression of proteases and the clinicopathologic significance in non-skull base chordoma (NSBC). By using immunohistochemical techniques, we studied the expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, cathepsin B (CatB), and urokinase plasminogen activator (uPA) in 29 NSBCs and compared these data with clinicopathologic parameters and the expression of cell differentiation markers. Expression of MMP-1 (P = .092), MMP-2 (P = .041), and CatB (P = .058) was associated with nuclear pleomorphism, a previously described adverse prognostic indicator. Expression of cytokeratin 8 correlated with that of MMP-1 (P = .005), MMP-2 (P = .002), and uPA (P = .032). Patients with higher MMP-2 expression had a poorer prognosis than those with lower MMP-2 expression (P = .013). We believe that NSBCs with nuclear pleomorphism or stronger epithelial character have a higher invasive ability than those without. In addition, high MMP-2 expression was an indicator of an unfavorable clinical outcome in NSBC.

Intralesional Fibrous Septum in Chordoma A Clinicopathologic and Immunohistochemical Study of 122 Lesions

Intralesional fibrous septum (IFS) generally is considered a reactive tissue in chordoma; however, little is known about its significance. We studied 122 chordomas for IFS using immunohistochemical techniques and compared IFS and lobular growth patterns (LGPs) formed by IFS with clinicopathologic parameters. Seventy-nine tumors (64.8%) revealed IFS. However, IFS frequently was infiltrated and interrupted by tumor cells with increased expression of proteases; only 33 (42%) of 79 tumors had LGP. In non-skull base chordomas, IFS and LGP were associated with nuclear pleomorphism, a previously described prognostic indicator, mitosis, and the MIB-1 labeling index, indicating a role of IFS and LGP in tumor growth or progression. Paradoxically, patients without LGP tended to have a worse prognosis than those with LGP. We believe that IFS exerts diverse influences on chordoma; however, invasion of IFS leading to loss of the LGP indicates advanced stages of tumor development, possibly predicting an unfavorable prognosis in chordoma.

Expression of c-MET, low-molecular-weight cytokeratin, matrix metalloproteinases-1 and -2 in spinal chordoma

Aims:  In skull base chordoma, c‐MET expression has been reported to correlate with younger patient age and favourable prognosis; however, it also contributes to tumour invasiveness, especially in recurrent lesions, suggesting variable roles for c‐MET according to clinical status. The aim of this study was to investigate the significance of c‐MET expression in spinal chordoma, which affects patients who are 10–20 years older than those with skull base chordoma.

Clivus Chordoma in Continuity with a Large Pontine Cyst

Chordomas are tumors commonly of extradural origin associated with bone destruction; their central nervous system invasion has rarely been reported. The authors describe a rare case of a 37-year-old man presenting with a clivial chordoma invading the brainstem with a large pontine cyst. A median suboccipital approach was selected to remove the tumor.

p53 Accumulation in Malignant Bone Tumors: An Immunohistochemical Analysis of 217 Cases

Using formalin-fixed paraffin-embedded tissue specimens, the authors studied the accumulation of p53 protein in various malignant bone tumors. p53 accumulation was detected in osteosarcoma (16.7%), malignant fibrous histiocytoma (MFH) of bone (30.4%), and chordoma (16.7%). In osteosarcoma, no difference was seen in the incidence of p53 accumulation according to the histologic grade of malignancy and any clinical factors including prognosis, but the incidence was significantly higher in conventional osteosarcoma than in other subtypes of osteosarcoma. In MFH of bone, the p53-positive group had a significantly worse prognosis compared with the p53-negative group. p53 accumulation is thus considered to be related to the prognosis of MFH of bone although it did not demonstrate any prognostic value for osteosarcoma in the current study.

Operative Management of Soft Tissue Sarcomas Adherent to Major Vessels

Eleven cases of soft tissue sarcomas arising in the thigh, particularly in the frontal or popliteal area, were estimated to be adherent to major large vessels by angiogram, CT, and/or MRI. Eight cases were tightly adherent to femoral vessels, and two to popliteal ones. Of these cases, seven underwent combined resection of tumor and affected vessels, followed by reconstruction with artificial vessels in five, and autogeneous saphenous vein graft in one. One case with femoral vein resection had no reconstruction.The popliteal fossa and femoral triangles are anatomicd spaces, but it is not feasible to resect large tumors safely or curatively without combined resection of these vessels. Therefore, in these areas, we recommend combined resection fo tumor and major vessels as the preferred management, at least in high grade lesions.