Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature.

BACKGROUND: Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are easy to diagnose. However, borderline forms may occur and be, for the pathologists, very difficult to classify. In these cases, there is a strong need to identify factors that may aid. Official classification systems for endocrine neoplasms are based on the evaluation of proliferation and, in most cases, they rely on mitotic count. In support, the study of Ki67 is carried out which, however, has not yet been included in any official classification system, except for neuroendocrine neoplasms of the gastro-entero-pancreatic tract. PURPOSE: The aim of the present study was to investigate the proven or unproven role of Ki67 in endocrine neoplasms, in different districts, in order to bring to light the substantial differences, in terms of proliferation, existing between neoplasms so similar, but at the same time, so different. METHODS: A thorough search of English language literature was performed, looking for articles concerning Ki67 in five endocrine neoplasms (pituitary adenomas, thyroid neoplasms, adrenocortical neoplasms, pheochromocytomas and paragangliomas). RESULTS: From 2170, 236 articles were selected and it was seen that the endocrine neoplasm in which Ki67 was most studied was the pituitary, where it still shows a controversial role. In other neoplasms different roles were identified. CONCLUSION: The pathologist should be aware of the contribution that this proliferative marker can give to the diagnosis and, sometimes, to the therapy selection, for the clinician.

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.

Advances in trans-sphenoidal pituitary surgery.

Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, requiring precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. Actually, it could be considered the result of a close cooperation between different specialists, i.e. the ophthalmologist, the neuroradiologist, the endocrinologist, the neurosurgeon, the pathologist, etc. In this teamwork environment each member plays his own role, offering his contribute to the final result; every effort is performed to provide patients with the best possible procedure, individually measured. The endoscopic pituitary surgery performed by means of a transsphenoidal approach perfectly fits this scenario, being though advocated as the result of an evolutionary process rather than a revolutionary one. The "pure" endoscopic transsphenoidal surgery - consisting of a whole procedure performed with the endoscope alone and without the use of any transsphenoidal retractor - offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy, very important at the tumor/gland interface and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate are similar to those reported in the major microsurgical series but patient compliance is by far better.

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.

miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPµ.

Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 3' untranslated region of the protein tyrosine phosphatase µ (PTPµ). Previous studies indicated that PTPµ suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 overexpression induced a downregulation of PTPµ as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPµ gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPµ in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPµ protein expression.

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.

Expression of growth factors in brain tumors: correlation with tumor grade, recurrence and survival.

OBJECTIVE: The aim of this study is to evaluate the correlation between the expression of some growth factors (GFs) and the tumor grade, recurrence and survival of brain glial and ependymal tumors. MATERIAL AND METHODS: The expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), tenascine, transforming growth factor (TGFbeta), isomeres, platelet-derived growth factor (PDGF) and p53 was studied in 40 primary brain tumors, both low-grade and high-grade, including astrocytomas, oligodendrogliomas, glioblastomas and ependymomas. The same GFs were also studied in 46 specimens of recurrent tumors from the same patients. The positivity and intensity of the immunohistochemical expression were correlated with the tumor grade, the interval and type of recurrence, and the survival. RESULTS: The expression of all GFs, excepting TGFbeta1, TGFbetaRI and tenascine, was found to be correlated with the tumor grade in all tumors of both astroglial and oligodendroglial origin, whereas ependymomas showed significant differences only for EGFR. Low-grade (Grade II) tumors recurring as anaplastic (Grade III) forms showed GF expression rather similar to initially high-grade gliomas and significantly higher than that of low-grade (Grade II) tumors in both initial surgery and recurrence. Besides, low-grade (Grade II) tumors recurring as low-grade showed significantly longer median recurrence time (5.4 vs. 3.5 years) and better median survival (8.3 vs. 5.4 years) than those recurring as anaplastic forms (WHO III). CONCLUSION: The immunohistochemical study of expression of VEGF, EGFR, TGFbeta2, TGFbeta3, PDGF and p53 in all low-grade (Grade II) brain gliomas at the first operation may help to differentiate cases with slower evolution and longer survival from those with higher potential of anaplastic transformation.

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.

SOM230, a new somatostatin analogue, is highly effective in the therapy of growth hormone/prolactin-secreting pituitary adenomas.

PURPOSE: We have previously shown that transgenic mice ubiquitously overexpressing the HMGA2 gene develop growth hormone/prolactin-secreting pituitary adenomas. This animal model has been used to evaluate the therapeutic efficacy of SOM230, a somatostatin analogue with high affinity for the somatostatin receptor subtypes 1, 2, 3, and 5, on the growth of the pituitary adenomas. EXPERIMENTAL DESIGN: Four groups of 3- and 9-month-old HMGA2 transgenic mice were treated for 3 months with a continuous s.c. injection of two different dosages of SOM230 (5 or 50 microg/kg/h), one dose of octreotide, corresponding to that used in human therapy, and a placebo, respectively. The development of the tumor before and after therapy was monitored by magnetic resonance imaging of the pituitary region and evaluation of the serum prolactin levels. RESULTS: The highest dose of SOM230 induced a drastic regression of the tumor, whereas octreotide was not able to induce any significant tumor regression, although tumor progression was significantly slowed down. No significant differences were observed between the animals treated with the lowest dose of SOM230 and those receiving placebo. CONCLUSIONS: These results clearly support the efficacy of the SOM230 treatment in human pituitary adenomas secreting prolactin based on the dramatic tumor shrinkage and fall in prolactin levels. This beneficial effect could be of crucial clinical usefulness in patients bearing tumors resistant to dopaminergic drugs.

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.

Endoscopic endonasal transsphenoidal removal of an intra-suprasellar schwannoma mimicking a pituitary adenoma.

Intracranial schwannomas, accounting for 8 to 10 % of all primary brain neoplasms, are relatively frequent intracranial tumors, but a "pure" intrasellar localization is exceptional. We report the case of an intra-suprasellar schwannoma mimicking a non-functioning pituitary macroadenoma both radiographically and clinically. A 73-year-old man presented with an episode of lipothymia followed by episodes of mental confusion. The neurological investigations revealed a bitemporal hemianopia and a hypopituitaric status. The neuroradiological investigations showed an intra-suprasellar mass resembling a pituitary adenoma. The patient underwent surgery performed by means of an endoscopic endonasal transsphenoidal approach, with a subtotal excision of the tumor. The histopathological studies revealed a cellular schwannoma. The review of the literature disclosed another 8 cases of intrasellar schwannomas. The possibility of an intrasellar schwannoma has to be considered in the differential diagnoses of neoplastic and non-neoplastic lesions of the sellar area.

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.