M.L. Del Basso De Caro

Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: Tumour progression or radionecrosis?

OBJECTIVES This study investigates the diagnosis and management of patients with resected brain glioblastomas who presented early clinical and neuroradiological worsening after the completion of the Stupp protocol. Its aim is to discuss the occurrence of early radionecrosis. METHODS Fifty patients with brain glioblastoma treated by surgical resection and Stupp protocol were reviewed; 15 among them (30%) had early clinical and neuroradiological worsening at the 6-month follow-up. The MR spectroscopy and surgical findings of these patients are reviewed. RESULTS MR spectroscopy was in favour of tumour recurrence in 14 among 15 patients and showed radionecrosis in one. Among 10 patients who were reoperated on, 7 had histologically verified tumour recurrence or regrowth, whereas in 3 histopathology showed necrosis without evidence of tumour. The 7 patients with tumour progression had prevalence of focal neuroradiological signs (6/7) and a survival of 7.5-12 months (median survival 10 months). The 4 patients with early radionecrosis (including one patient who was not reoperated on) had clinical worsening with mental deterioration, confusion and ataxia, and MR spectroscopy positive for tumour recurrence in 3. Three were alive 24-30 months after the end of the radiotherapy, whereas one died at 40 months. CONCLUSION Early radionecrosis after the Stupp protocol is not a rare event due to the radiosensitization effect of temozolomide. This phenomenon may predict a durable response to radiotherapy. MR spectroscopy may simulate tumour recurrence. A correct diagnosis is necessary to avoid useless reoperations and incorrect withdrawal of temozolomide.

Expression and Function of Somatostatin Receptor Subtype 1 in Human Growth Hormone Secreting Pituitary Tumors Deriving from Patients Partially Responsive or Resistant to Long-Term Treatment with Somatostatin Analogs

The role of somatostatin (SS) receptor subtype 1 (SSTR1) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR1 agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR1 mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR1 receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR1, BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR1 subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR1 may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo.

The biological characterization of neuroendocrine tumors: The role of neuroendocrine markers

Neuroendocrine tumors (NET) may originate in different organs, from cells embriologically different but expressing common phenotypic characteristics, such as: the immuno-re-activity for markers of neuroendocrine differentiation (defined as “pan-neuroendocrine”), the capacity to secrete specific or aspecific peptide and hormones and the expression of some receptors, that are at the basis of the current diagnostic and therapeutical approach, peculiar to these tumors. NET have been conventionally distinguished in functioning, when associated with a recognized clinical endocrine syndrome, and non-functioning. However, this terminology may be misleading, since the great majority of NET may secrete neuroendocrine peptides, which can be employed as clinical markers for both diagnosis and follow-up. On the other hand, tissue immuno-reactivity for specific hormones does not always reflect secretory activity of the tumor cells. Finally, receptors and genetic markers are acquiring a relevant role in the characterization of NET, both improving knowledge of biology and physiopathology of NET, as well as in developing specific strategies to establish an early diagnosis and targeted therapies, to adopt prophylactic strategies in familial forms, and to identify more efficacious targets for therapy in the future.

Paravertebral High Cervical Chordoma A Case Report

Spinal chordomas are more often located on the midline and are associated with marked destruction of the vertebral bodies. We report a rare case of large cervical (C2-C3) right lateral paravertebral chordoma extending into the spinal canal through a very enlarged intervertebral foramen. The tumor was initially diagnosed as a mucous adenocarcinoma on a percutaneous needle biopsy. However, the neuroradiological features, including the well-defined tumor margins, the regular and sclerosing lytic bone changes with regular enlargement of the intervertebral C2-C3 foramen, were in favor of a more slowly growing lesion, such as schwannoma or neurofibroma. At surgery a well-demarcated capsulated tumor involving the nerve root was partially resected. Histology was in favor of a low-grade chordoma (Ki-67/MIB-1<1%). Postoperative proton beam therapy was also performed. The differential neuroradiological diagnosis is discussed.

Primary cerebellar germinomas of the posterior fossa.

Primary cerebellar germinomas, in the absence of germ-cell tumours outside the nervous system or elsewhere in the cranial cavity and CSF pathways, are exceptional; only two previous cases have been reported in the literature. Two personal observations are described from our 20-year records of intra-axial posterior fossa tumours. The patients were a 32-year-old man and a 17-year-old woman with a clinical history of posterior fossa tumour, studied by computed tomography. The first patient with slight cerebellar signs had a small right hemispheric cerebellar tumour, and the other had a left cerebellar mass with hydrocephalus and progressive intracranial hypertension. Both were treated by tumour removal and irradiation to the whole posterior fossa. The survival times were 58 and 49 months, respectively. The diagnosis of primary cerebellar germinoma cannot be suspected before pathological confirmation. The clinical, neuroradiological and surgical findings are non-specific and quite similar to those of other malignant cerebellar tumours, such as anaplastic gliomas or metastases. Surgery and radiotherapy ensure adequate tumour control in the early stages; cases of recurrence or disseminated disease may be treated by irradiation and chemotherapy.

MRI Features of Spinal Solitary Fibrous Tumors A Report of Two Cases and Literature Review

Spinal solitary fibrous tumors (SFT) are very rare neoplasms occurring in the spinal canal, with only 38 cases reported in ten years since the first description. We describe two cases of SFT of the spine and review 33 well-documented cases in the literature to define distinctive radiological and surgical features raising the suspicion of a spinal SFT before histological verification. A 67-year-old man with cervical myeloradiculopathy had a large extramedullary tumor of the cervical spinal canal extending from C4 to C7. On MRI the tumor was isointense on T1-sequences and hypointense on T2-sequences, and had marked contrast enhancement. At surgery, the tumor was intradural extramedullary, with no dural or root attachment, but it was adherent to the cord. Complete tumor removal was achieved with good outcome. A 75-year-old man with progressive thoracic myelopathy had an intramedullary tumor at C6 and C7 level, which was hypointense on T1- and T2-weighted images of MRI. At surgery, the tumor was intramedullary and strongly adherent to the cord; it was successfully removed. Both tumors were composed of elongated cells with a collagen-matrix background. Immunohistochemical staining was positive for vimentin, CD34, and bcl-2, and negative for EMA and S-100 protein. A careful analysis of our own and the other reported cases of spinal SFTs may disclose some peculiar features of this rare tumor. A spinal intramedullary or extramedullary tumor, hypointense on T2-weighted images of MRI, which intraoperatively shows hard consistency, scarce vascularization, no nerve root involvement, no or weak dural attachment, absence of arachnoidal interface, and adherence to the spinal cord may suggest the diagnosis of SFT.

Ectopic Suprasellar Pituitary Adenoma A Case Report

The occurrence of a pituitary adenoma located entirely outside the sella turcica, so-called ectopic adenoma, is extremely rare. We report a case of a non secreting-pituitary adenoma located above the diaphragma sellae, with no invasion into the sella turcica, confirmed at surgery. The tumor was initially treated unsuccessfully by operations via the transphenoidal route. After initial negative exploration by the transphenoidal route, the patient was successfully treated by an endoscopic endonasal transphenoidal approach extended to the tuberculum sellae and the posterior planum sphenoidale to access the suprasellar supraglandular region. A brief review of ectopic adenomas and a discussion of the preoperative diagnosis are presented.

Diabetes insipidus and increased serum levels of leptin and lactate-dehydrogenase (LDH) in an adolescent boy with a primary intracranial germinoma. Case Report and an endocrinological revaluation of literature

A 16-year-old boy presented with a four-month history of polyuria-polydipsia and a diplopia which had reverted after treatment. The neuroimaging studies performed had been strongly suggestive of an optic nerve glioma, while en-docrinological investigation (β-hCG 420 IU/L) has lead to the correct diagnosis later confirmed at the immunohystochemical analysis performed at biopsy. The high serum level of hCG was unaffected by bromocriptine nor octreotide, while the PRL level (80.0 μg/L) was reduced only by bromocriptine. Among the several tumor markers which may be secreted by such lesions, ours is the first reported case of an elevation of serum LDH for a primary intracranial germinoma. Moreover, the elevated value of serum leptin reported by us might be due to the insensitivity of the hypothalamic structures to endogenous leptin.

Un caso di Neurofibromatosi di tipo 1 “complicata” da processo espansivo cerebellare maligno con aspetti TC/RM atipici

A 13 year-old boy, previously diagnosed as having Neurofibromatosis Type 1 (NF1) but otherwise healthy, was referred to our Department for headache, vomiting, ataxia and VI-VII left cranial nerve palsy. Emergency head CT scan was performed, immediately followed by contrast-enhanced MR scan with Echo-Planar (EPI) water diffusibility study. A large ovalar mass lesion was evident in the left cerebellar hemisphere, hyperdense on CT, hypointense in T2-weighted images, isointense to grey matter in FLAIR and T1-weighted images, with clear mass effect on the surrounding structures, but only mild peripheral contrast-enhancement in the anterior part of the mass, these features resembling those of a desmoplastic medulloblastoma. However, the EPI Diffusion-weighted images (DWI) and corresponding Apparent Diffusion Coefficient (ADC) maps consistently showed increased water diffusivity, a pattern not compatible with the dense cell-packing typical of medulloblastomas. The pathological analysis of the surgical specimen indeed showed focal neoplastic cell clusters interspersed in a diffusely altered cerebellar cortex. Neoplastic cells exhibited large eosinophilic cytoplasma, hyperchromatic and multinucleolated nuclei, and frequent mitoses, a pattern indicative of anaplastic astrocytoma. The case presented supports the evidence that NF1 is associated with increased risk of developing several different neoplasms, beside the well-known pilocytic astrocytomas of the optic pathway. As these neoplasms may exhibit misleading imaging features at CT or “conventional” MRI study, the assessment of water diffusivity may provide useful data for reaching a correct pre-operative diagnosis, since it reflects the histological architecture of the neoplastic tissue.

Isolated Cervical Neurenteric Cyst: A Case Report

Neurenteric cysts are rare congenital intraspinal cysts of endodermal origin. Herewith reported is a case of a 17-year-old girl harbouring an isolated cervical (C1-C3) neurenteric cyst, with intradural extramedullary development and without mediastinal enterogenous cyst. Magnetic resonance imaging was diagnostic. Surgery by means of a cervical laminectomy resulted in total removal of the lesion compressing the spinal cord on its ventral aspect and in rapid relief of symptoms, that were cervicooccipital pain and lower limb weakness of 1-month duration.