Definitive surgical treatment of osteomalacia induced by skull base tumor and determination of the half-life of serum fibroblast growth factor 23.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome often associated with fibroblast growth factor 23 (FGF23)-producing tumors such as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) affecting the bone and soft tissue. We experienced a patient with progressive bone and muscle pain due to FGF23-related TIO. Venous sampling had strongly suggested the anterior skull base as a source of FGF23, which led to the discovery of a small tumor in the ethmoid sinus extending intracranially. Radical surgical resection confirmed the histological diagnosis of PMTMCT with FGF23 immunopositivity and achieved durable tumor control with complete resolution of symptoms. We serially measured serum FGF23 level before, during and after surgery and analyzed the data to determine the half-life of FGF23. Serum FGF23 level sharply declined as early as 20 minutes after en bloc tumor resection and completely normalized after surgery. The half-life of FGF23 was calculated to be approximately 18.5 minutes using single phase exponential decay model as well as semilog transformation formula. Serial measurements of serum FGF23 level can potentially declare "complete" resection of a FGF23-producing tumor and total cure of TIO; in this regard, development of its intraoperative measurement would be helpful in the management of this endocrine tumor.

Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma.

BACKGROUND: Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. METHODS: We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed an intraoperative hypertensive crisis. RESULTS: A patient with a history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Workup revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade before the second stage. Serum catecholamine levels after this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. CONCLUSION: Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma.

A comparison of cell-cycle markers in skull base and sacral chordomas.

OBJECTIVE: Despite refinement of surgical techniques and adjuvant radiotherapy, the prognosis for patients with a chordoma remains poor. Identification of prognostic factors related to tumor biology might improve this assessment and result in molecular markers for targeted therapy. Limited studies have been performed to unravel the impact of cell-cycle markers in chordoma, and those performed have shown inconclusive results. In the current study, we aimed to discover the impact of cyclin-dependent kinase 4 (CDK4) expression and its relation to prognosis and other cell-cycle markers in chordoma. METHODS: Twenty-five human formalin-fixed, paraffin-embedded chordoma specimens were examined by immunohistochemistry for the expression of CDK4, protein 53 (p53), and murine double minute 2 (MDM2). The MIB-1 labeling index and mitotic index were used for the examination of proliferation. We collected detailed demographic and clinical data. RESULTS: Overexpression of CDK4, p53, and MDM2 was found in five (20%), seven (28%), and 14 (56%) of the cases, respectively. All three cell-cycle markers showed a significant correlation with MIB1 labeling index. Expression of CDK4 (P = 0.02) and p53 (P < 0.01) were both significantly correlated with poor overall survival. Also, histologically observed necrosis (P < 0.05) and a dedifferentiated tumor subtype (P < 0.01) were related to adverse patient outcome. CONCLUSION: Our results show that the expression of CDK4 and p53 are related to cell proliferation capacity and worse outcome in patients with chordoma.

[Comparative analysis of surgical and medical treatment of macroprolactinoma of different localization].

The authors performed comparative analysis of results of primary surgical and medical treatment of 306 patients with macroprolactinoma. The series included 178 male and 128 female patients. The tumor was endosellar in 48 cases, endosuprasellar in 94, invaded skull base in 164. The paper demonstrates that according to dynamics of visual function, neurological and hypopituitary symptoms, and probability of prolactin level normalization, treatment with cabergoline has significant advantages in comparison to surgery. Only surgical treatment of endosellar prolactinomas can compete with conservative treatment. After these operations no postoperative complications were observed, normalization of prolactin level was present in 67% of cases, and these results did not differ from results of medical treatment (71%). In case of extrasellar grown of macroprolactinoma, especially invading skull base, primary medical therapy is preferred.

Falsely low serum prolactin in two cases of invasive macroprolactinoma.

The differential diagnosis of tumors at the base of the skull comprises meningiomas, neurinomas, gliomas, metastatic carcinomas, chordomas, epidermoids, and pituitary adenomas. About half of the pituitary adenomas are prolactinomas which are unique in a sense that medical therapy causes rapid tumor shrinkage and symptomatic improvement. We report on two patients in which the diagnosis of an invasive macroprolactinoma was masked by apparently low prolactin levels caused by a high-dose hook effect in the chemiluminometric assay. The first case a 49 year old male with impairment of hearing on the left side was presented in the Department of Otorhinolaryngology. A massive invasively growing tumor was demonstrated on a cranial MRI. Endocrine tests revealed normal pituitary function and normoprolactinemia. The patient underwent debulking surgery, occipitocervical fusion because of destruction of the first cervical vertebra and subsequent irradiation. The histopathological diagnosis was invasive prolactinoma. A repeat prolactin (PRL) sample, which was assayed using serial dilutions, revealed a real PRL level of 89,700 ng/ml. Dopamine agonist therapy was initiated under which PRL levels declined in parallel with tumor size. The second case a 40 year old male was presented with acute visual loss. Cranial MRI showed a large tumor at the base of the skull. Based on a transnasal biopsy, the preliminary diagnosis was a poorly differentiated carcinoma for which emergency irradiation was performed. Endocrine tests demonstrated partial hypopituitarism and moderate hyperprolactinemia. Hydrocortisone was substituted and dopamine agonist therapy was started because of moderate hyperprolactinemia. The final histopathological diagnosis was invasive prolactinoma. A repeat PRL sample assayed in serial dilution demonstrated an apparent rise in PRL with a maximum value of 6,460 ng/ml. Under dopamine agonist therapy, PRL declined to normal values, tumor size decreased and cranial nerve palsies disappeared. The apparently falsely low prolactin levels in the initial work-up of both patients were caused by a high-dose hook effect in the PRL assay. Serial dilutions of serum PRL samples is, therefore, mandatory in the diagnostic work-up of patients with large invasive tumors at the base of the skull. This avoids unnecessary aggressive and dangerous treatment like surgery or radiotherapy in cases where pharmacological treatment may be the choice.

Renal cell carcinoma with skull base metastasis preceded by paraneoplastic signs in a chronic hemodialysis patient.

A 59-year-old man who had received chronic hemodialysis developed left occipital pain and hypoglossal nerve palsy. He was diagnosed as having skull base metastasis from renal cell carcinoma related to acquired cystic kidney. Retrospective analysis revealed the patient had had elevated serum C-reactive protein and alkaline phosphatase levels before the symptoms appeared. Radiotherapy to the skull base relieved the pain. Finally he died with generalized metastases. Serum interleukin-6 levels measured during admission had been elevated, and interleukin-6 mRNA was detected in the autopsy specimen of renal cell carcinoma. Interleukin-6 might be involved in the etiology of paraneoplastic signs.