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.

Intracranial dural metastasis from uterine leiomyosarcoma with orbital extension.

Intracranial metastases from uterine leiomyosarcoma are very rare and have been found mainly in the brain (17 cases); on the other hand, metastases to the skull, dura and orbit are really exceptional. The authors report the case of a 57-year-old woman who presented with a 6-week history of right proptosis, left hemiparesis, intracranial hypertension and torpor 8 months after surgery for uterine leiomyosarcoma. CT scan showed a very large right frontal tumor with both intracranial and intraorbital extension. At operation the tumor was found to arise from the dura of the right anterior cranial fossa; complete removal of the intracranial tumor mass and partial removal of the intraorbital component were performed. However, early tumor regrowth was observed 45 days after operation and death occurred 2 months later. Pathologic examination showed a high-grade sarcoma with smooth muscle differentiation and high mitotic activity. Immunohistochemical staining revealed positivity for actin and vimentin and negativity for S-100 protein, cytocheratin and desmin. This is the first reported case of uterine leiomyosarcoma metastatic to the dura of the anterior cranial fossa with intracranial and intraorbital extension. An aggressive surgical resection is the best treatment of intracranial metastatic leiomyosarcoma, because of the scarce response to radiotherapy and chemotherapy. However, the outcome is poor, with early recurrence.

Symptomatic spinal cord metastasis from cerebral oligodendroglioma.

Spinal subarachnoid spread is not uncommon in brain oligodendrogliomas; on the other hand, symptomatic involvement of the spinal cord and cauda is very rare, with only 16 reported cases. We report the case of a 41-year-old man who underwent resection of a low-grade frontal oligodendroglioma 4 years previously. He was again observed because of bilateral sciatic pain followed by left leg paresis. A spine MRI showed an intramedullary T12-L1 tumor with root enhancement. At operation, an intramedullary anaplastic oligodendroglioma with left exophytic component was found and partially resected. Two weeks later, a large left frontoparietal anaplastic oligodendroglioma was diagnosed and completely resected. The patient was neurologically stable for 8 months and died 1 year after the spinal surgery because of diffuse brain and spinal leptomeningeal spread. The review of the reported cases shows that spinal symptomatic metastases can occur in both low-grade and anaplastic oligodendrogliomas, even many years after surgery of the primary tumor; however, they exceptionally occur as first clinical manifestation or as anaplastic progression. The spinal seeding represents a negative event leading to a short survival.

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.

Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog.

The Silent Corticotroph Adenoma (SCA) is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH) and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well.

Intracranial extension of salivary gland tumors.

OBJECTIVE: The aim of this report is to describe 3 cases of salivary gland tumors with intracranial extension associated to an extracerebral mass lesion, and to discuss the frequence, pathology and treatment of these very rare localizations. CLINICAL MATERIAL: The 3 patients were 1 woman and 2 men, aged 44, 53 and 74 years, respectively. The primary tumors were an adenocarcinoma and a malignant oncocytoma of the parotid gland and an adenoid cystic carcinoma of the submandibular gland. The location of the intradural extra-axial tumor was the middle fossa and temporal region in 2 cases and the cerebellopontine angle in 1. Surgical treatment consisted in the seemingly complete removal of 2 tumors with middle fossa localization and partial removal of the cerebellopontine angle lesion. Radiotherapy was administered in all 3 cases and chemotherapy in 2. RESULTS: 1 patient is alive and free of recurrence 32 months after removal of the intracranial tumor; 2 other patients died 28 months and 12 months postoperatively. CONCLUSIONS: The intracranial extension of salivary gland tumors is a very rare event. An aggressive surgical resection followed by radiotherapy is justified in cases with significant intracranial mass lesions and scarce bone and dural involvement.

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.

Diagnostic and prognostic implications of the World Health Organization classification of neuroendocrine tumors.

BACKGROUND: Neuroendocrine differentiation of tumors is often difficult to establish. In the same manner, the evaluation of the prognostic role of neuroendocrine differentiation may constitute a relevant clinical problem. Although different classifications are used for neuroendocrine tumors (NET) of different origin, the last World Health Organization (WHO) classification of NET, originally proposed for gastroenteropancreatic tumors, has proved to be a practical tool to allow pathologists to uniform the diagnoses and re-classify these tumors into 3 main categories. AIM: The present study was carried out in order to evaluate diagnostic and prognostic implications of NET reclassification according to the last WHO classification of NET. MATERIALS AND METHODS: Thirty-one tumors with an initial diagnosis referable to a NET achieved before 1999 were independently evaluated by 3 pathologists on the basis of the 2000 WHO classification of NET. Immunohistochemistry for panneuroendocrine markers and Ki-67 was also performed in all cases. RESULTS: Twelve, 14, and 4 tumors were respectively reclassified as well-differentiated NET, well-differentiated neuroendocrine carcinoma and poorly differentiated neuroendocrine carcinoma; 1 tumor was reclassified as mixed endocrine-exocrine tumor. Two or more neuroendocrine markers were expressed in all NET regardless of histotype, differentiation degree, and site of primary tumor. After revision, 10 of the 31 tumors under study (32%) changed histo-prognostic category when compared to the initial diagnosis. Ki-67 score was the best predictor of survival at the multivariate analysis. CONCLUSION: The WHO classification is suitable to accurately reclassify tumors with an initial diagnosis referable to a NET and to separate these tumors in 3 well-distinct histo-prognostic categories with relevant clinical implications. Ki-67 score seems to be a better predictor of survival than the degree of differentiation.

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

Neuroendocrine tumors (NET) may originate in different organs, from cells embryologically different but expressing common phenotypic characteristics, such as: the immuno-reactivity 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.

Local versus diffuse recurrences of meningiomas: factors correlated to the extent of the recurrence.

OBJECTIVE: The aim of this study is to evaluate the factors correlated with the different patterns (local, peripheral and diffuse) of meningioma recurrence. MATERIAL AND METHODS: 55 patients with benign (WHO I) meningiomas which recurred after seemingly complete removal were reviewed; 40 (Group I) had local or peripheral recurrences (< 3 cm from the initial dural attachment) and 15 (Group II) had distant and diffuse recurrences. Patient age and sex, tumor location, interval of recurrence, tumor shape, type of brain-tumor interface, histological subtype, mitotic index (MI) and progesterone receptor (PR) expression of the initial tumor, histological WHO Grade of the recurrent tumor and patient outcome were analyzed and correlated with the pattern of recurrence. RESULTS: Flat-shaped meningiomas with large dural attachment showed a significantly higher rate of diffuse recurrences than round tumors, whereas the brain-tumor interface and the tumor location were not relevant (excepting the lack of convexity meningiomas in the group of diffuse tumors). There were no significant differences of histology, MI and PR expression of the initial tumor and histological grade of the recurrent tumor between the two groups. CONCLUSIONS: The different patterns of meningioma recurrences (local, peripheral, diffuse) are not correlated with the tumor location and histology and do not represent a different biological tumor progression. We agree that most unexpected extensive recurrences result from a more extensive microscopic dural involvement.

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.

Prognostic and survival-related factors in patients with well-differentiated oligodendrogliomas.

Oligodendrogliomas are brain tumors with unpredictable biological and clinical behavior. Prognostic factors related to survival are still controversial. The present study reviews 50 patients with well-differentiated (WHO grade II) oligodendrogliomas, located in the cerebral hemispheres and operated upon between 1980 and 1998. Prognostic factors studied include patient's age and sex, tumor location and extent, preoperative KPS, and extent of the surgical resection. The Ki-67 and the proliferative cell nuclear antigen (PCNA) levels were studied in all patients and some growth factors (GFs), including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and tenascine were examined in 20 patients. The long-term outcome and survival are not significantly correlated with the patient's age and sex, tumor location and extent, preoperative KPS and procedure for resection. Patients with lower Ki-67 and PCNA showed a significantly longer survival time (p < 0.001 and p < 0.019, respectively). Between 45 and 70 % of the tumors stained positive for one or more growth factors. Interestingly, cases with late recurrences (more than 4 years after surgery) and longer survival are significantly associated to negative GF expression or slight positivity, as compared with the variable and more often moderate immunoreactivity of cases with early anaplastic recurrences and shorter survival time. The presented data suggest that low proliferation indices and negative GF expression are associated with longer survival in well-differentiated oligodendrogliomas.

Aggressive eosinophilic granuloma of the parietal bone. An immunohystochemical study of Ki-67 expression.

Solitary eosinophilic granuloma (EG) of the skull is a rare lesion, the natural history of which is still to be defined. We report a case of a 26-year-old female who presented with progressive headache and nausea accompanied by a painful firm mass in her left parietal region, which grew very rapidly during the last two weeks before admission. Computed tomography scan showed an osteolytic lesion, which on magnetic resonance imaging appeared hyperintense on both T1- and T2-weighted images, with marked and heterogeneous enhancement after gadolinium administration. Total surgical excision of the lesion was performed and histopathological diagnosis was compatible with eosinophilic granuloma. Immuno-histochemical study of Ki-67 antigen expression was also performed with a labelling index of 10%. In a review of the pertinent literature, we found one case report showing a Ki-67 labelling index of 6.2% in a patient harboring EG of the occipital bone. These two relatively high percentages of proliferative activity suggest a role of local Langerhans'cell proliferation, along with that of inflammatory response, in the aggressive clinical course and rapid expansion observed in some rare cases of solitary eosinophilic granuloma.

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 (SSTR(1)) 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 SSTR(1) 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 SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) 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 SSTR(1) 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.

Dural metastasis mimicking falx meningioma. Case report.

A case of a 66-year-old woman with anterior-3(rd) falx metastasis from mammary carcinoma is reported. Radiological and therapeutic aspects are reported. The clinical presentation was headache and confusion together with gait disturbance. MRI showed a frontobasal mass with dural attachment suggestive of meningioma. Surgical resection was decided. Histology confirmed the diagnosis of breast cancer dural metastasis. Dural metastases are not frequent. Two radiological aspects are described: subdural hemorrhage and dural mass. No definitive theory exists about etiopathogenesis. As radiological findings are not specific, we emphasize the importance of suspecting dural metastasis in patients with tumor mass involving dura mater.

Neurocysticercosis. Case report.

In the present review we report a case of a 53-year-old woman affected with a cyst solitary cerebral hemispheric lesion causing acute generalized seizure. Clinical and neuroradiologic diagnosis of cystic astrocytoma was performed and the patient was operated. Microscopic analysis of the surgical specimen led to a diagnosis of parasitic infection, consistent with neurocysticercosis (NCC). NCC is the most frequent parasitosis of the central nervous system (CNS) in the world. The infective agent is taenia solium larvae. It is endemic in Latin America, Africa and some Asiatic countries, such as India. In Europe, many cases have been reported in Portugal, Spain, Poland and Romania. In Italy NCC is a rare disease. In recent years no cases have been described, but with high rate of immigration from endemic areas (Africa and East Europe) this parasitosis will be found in our country too, particularly affecting communities where hygienic conditions are poor. In conclusion we briefly analyze the relationship between pathogenesis of this parasitosis and its clinical symptoms.

In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2 receptor scintigraphy.

OBJECTIVE: GH and PRL cosecretion frequently occurs in acromegaly and the sensitivity of both hormones to somatostatin analogs (SA) and dopamine agonists (DA) alone or in combination, is still debated. This study was designed to evaluate the in vivo and in vitro sensitivity to SA and/or DA and correlate the response in terms of hormone suppression to the results of in vivo somatostatin and dopamine receptor scintigraphy and to the immunohistochemical findings. DESIGN AND PATIENTS: Scintigraphy using 111In-DTPA-D-Phe(1)-OCT (111In-OCT) and 123I-methoxybenzamide (123I-IBZM) was performed in four patients with acromegaly and high circulating GH, PRL and IGF-I levels. The results were correlated with the response to long-term treatment with octreotide (OCT), quinagolide (QN) and/or cabergoline (CAB), to the in vitro hormone suppression by OCT and DA in primary cultures from the pituitary tumors and to the immunohistochemical findings. RESULTS: The first patient showed high tumour uptake of 111In-OCT and 123I-IBZM, the second high uptake of only 111In-OCT, while the third one showed faint tumour uptake of only 123I-IBZM, and the fourth a faint uptake of 111In-OCT. In the first and in the fourth patients OCT or CAB administered alone failed to normalize hormone levels while the combined treatment induced circulating GH, IGF-I and PRL normalization. In the second patient OCT administered alone normalized hormone levels while QN reduced PRL levels only. In the third patient both OCT and QN, alone or in combination, failed to normalize hormone levels. However, in this patient GH and PRL suppression was significantly greater after QN than OCT treatment. After medical therapy, all the patients were operated on. Immunohistochemistry showed diffuse GH and focal PRL staining in the first patient, while diffuse GH and PRL staining in the remaining three. In vitro, OCT significantly suppressed GH secretion in the four primary pituitary tumor cultures, while PRL secretion was significantly suppressed only in the second and the fourth cases. Dopamine agonists (DA) significantly suppressed PRL release in all the cultures, while GH secretion was significantly suppressed in three out of four. CONCLUSIONS: These four acromegalics, presenting similar clinical findings and comparable peripheral hormone levels, showed different responsiveness to SA and DA. Moreover, during the in vitro study on primary tumor cell cultures, OCT and DA displayed an inhibiting activity on GH and PRL secretion positively correlated with the response observed in vivo. This evidence together with the in vivo receptor imaging study suggest the existence of somatostatin and/or dopamine D2 receptor heterogeneity in this class of pituitary tumors. The new potent DA might be primarily considered in the medical treatment of hyperprolactinemic acromegalics, while SA alone or in combination with DA in case of ineffective hormone suppression.

An unusual case of lipoblastic meningioma of the falx cerebri.

The clinicopathological features of a lipomatous meningioma of the falx cerebri with an unusual histological pattern 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 endocrinological investigation (beta-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 microg/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.

Intrasellar paraganglioma with suprasellar extension: case report.

Paragangliomas are usually benign tumors which can be found in many sites of the body, from the base of the skull down to the pelvic floor. In the central nervous system the sellar region is very rarely involved; only three well studied cases have been reported to date. We present the cytological, histological, histochemical, immunocytochemical and ultrastructural features of an intrasellar and suprasellar paraganglioma in an 84-year-old man.