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Arq. Neuro-Psiquiatr. vol.66 no.3b São Paulo 2008
Unusual presentation of central nervous system metastases: mechanisms of spread and radiological findings
Metástases incomuns do sistema nervoso central: mecanismos de disseminação e achados radiológicos
Marcus André AciolyI; Carlos Henrique CarvalhoI; João L. Pinheiro-FrancoI; Jens SchittenhelmII; Ulrike ErnemannIII; Michael WellerIV; Jürgen HoneggerI
IDepartment of Neurosurgery - University Hospital, Tübingen, Germany
IIDepartment of Neuropathology/Brain Research Institute - University Hospital, Tübingen, Germany
IIIDepartment of Neuroradiology - University Hospital, Tübingen, Germany
IVDepartment of Neurology - University Hospital, Tübingen, Germany
Brain metastases are a well-known complication of systemic cancer, occurring in 2040% of the patients suffering from cancer1. In adults, the lungs represent the most common source of brain metastases comprising 3664% of the cases1. The cerebral hemispheres, cerebellum, brainstem1, pituitary (sellar region)2-4, cerebellopontine angle (CPA)/ internal auditory canal (IAC)2,5, and leptomeningeal metastases (LM)1,2,6,7 are potential locations of dissemination.
We report an unusual case, in which solely the association of pituitary metastases (PM), bilateral CPA metastases and LM was found in a patient affected of a large cell neuroendocrine carcinoma (LCNEC) of the lung.
A 63-year-old woman presented with a 4-month history of emesis, anorexia, weight loss, and increasing thirst. After three months, the patient suddenly developed bilateral hearing loss, tinnitus and increased dizziness. Fluid intake and urine output were consistent with diabetes insipidus. The neurological examination revealed bilateral hearing loss, incomplete right peripheral facial palsy and unstable gait. Other motor or sensory deficits were not noted. The tendon reflexes were brisk.
Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar space-occupying lesion isointense in T1-weighted precontrast study with strong enhancement in contrast images infiltrating the pituitary gland, the pituitary stalk and the hypothalamus (Fig 1A and 1B), as well as bilateral CPA lesions. There was also loss of high-signal intensity of the pituitary posterior lobe.
A spinal tap showed a nonspecific lymphocytic pleocytosis. The patient underwent a transsphenoidal biopsy revealing a high-grade pleomorphic epithelial tumour, like a large-cell carcinoma. Besides, malignant cells were encountered on CSF cytology, confirming the diagnosis of LM (Fig 2A).
MRI also revealed the typical small nodular depot along the cauda, L4L5 on the right side and L5S1 on the left side, and ventral of conus medullaris with strong enhancement in contrast images consistent with the diagnosis of LM (Fig 2B). Thoracic computed tomography (CT) scans showed a mass (measuring 1.4 × 1.1 cm) on the right side located within the retrotracheal space and a single increased lymph node (0.7 × 1.0 cm) near the right hilus. The bone scintigraphy revealed metastases exclusively to the skull base. A bronchoscopy was performed showing few nonspecific inflammatory cells.
The immunohistochemical profile of the tumour cells revealed a large-cell neuroendocrine carcinoma (LCNEC) with expression of cytokeratin 7 (CK7), thyroid transcription factor-1 (TTF-1) and synaptophysin with probable origin in the lung. The treatment was conducted with whole brain palliative radiotherapy and chemotherapy.
This publication was authorized by the ethical committee at our institution.
Morita and colleagues reported on a patient with PM who developed LM after a transsphenoidal procedure4. In another study, Lee and colleagues2 described a case with bilateral CPA lesions and a suprasellar mass, nonetheless without evidence of intrasellar or spinal involvement. Several combinations of PM and CPA metastases are encountered in literature3,5 including postmortem studies3. We described a unique case of metastases of LCNEC of the lung solely to the pituitary, LM and CPA at the time of diagnosis. This is an unusual presentation of central nervous system metastases in a patient affected of LCNEC lung cancer.
Metastases can reach the sella via several routes3,4: 1) direct hematogenous spread to the pituitary parenchyma or diaphragma sellae; 2) spread from a hypothalamo-hypophyseal or stalk metastases through the portal vessels; 3) direct extension from the skull base or juxtasellar metastases; and 4) meningeal spread through the suprasellar cistern.
The most common route of spread for LM is hematogenously to cerebrospinal fluid (CSF) via small meningeal vessels2. Furthermore, direct extension, transport through valveless venous plexus, escape from subependymal tumours or iatrogenic (postoperative) are also reported8. Once in the CSF, tumour cells can also lodge in the sulci, the brain surface or on nerve roots growing into a thin diffuse coating of the meninges or focal nodules that are centered on the pia2,8, frequently involving regions in the basilar cisterns and cauda equina, where the slow CSF flow and gravity promote deposition of cells8. This direct leptomeningeal involvement and/or dissemination through the CSF are the likely mechanism for metastatic CPA lesions5. In the presented case, no single mechanism could explain such an unusual presentation. Thus, we could assume that a combination of hematogenous route and CSF spreading is the potential mechanism of dissemination. Due to clinical presentation of pituitary involvement followed by cranial nerve impairment, it is possible that malignant cells reached pituitary hematogenously and spread through CSF to CPA and LM.
Concerning the radiological findings, high-resolution cranial CT and MRI are sensitive for the diagnosis of PM9. Rapid growth of a sellar tumour with invasion of the infundibular recess remits to the diagnosis of PM. MRI is the technique of choice for LM6. Cranial nerve enhancement on cranial imaging and spinal intradural extramedullary (most frequently seen in cauda equina) enhancing nodules may be considered diagnostic of LM in cancer patients6. Infundibular invasion, loss of high-signal intensity of the pituitary posterior lobe, along with cranial nerve and spinal enhancing nodules suggested metastatic disease in the presented case.
Of relevance is the concept of loculated intracranial LM well studied by Lee and colleagues2 in MRI, a pattern that was also found in our patient imaging. Occasionally, collections of tumour cells can lodge in some portions of the intracranial arachnoidal space, including the ventricles, forming a rather distinct extra-axial lesion. When it occurs without diffuse pattern, it may cause a diagnostic dilemma and delay proper management2. The most frequent locations are the suprasellar cistern, the lateral ventricles, the lateral recess of the fourth ventricle, the CPA cistern and the fourth ventricle, where there are abundant CSF collections. Initially the tumour cells infiltrate the leptomeninges as a single layer or as thicker multilayered aggregates2,8 that are not detectable by radiological imaging. When a mass of tumour accumulates within the subarachnoid spaces cited above, a subarachnoidal extra-axial mass develops (Type A). Further tumour growth can lead to parenchymal infiltration. When the main tumour mass remains extra-axial and without edema, it is classified as type B. Once the tumour extends beyond the pial surface with vasogenic edema, it is considered type C. The tumour can also grow along the cranial nerves, in a dumbbell fashion, mimicking schwannomas in type D. The loculated LM is observed in 80% of the patients and may present in an associated fashion2.
In conclusion, the association of PM, bilateral CPA/IAC metastases and LM is a rare clinical presentation of central nervous system metastases. The hypothesis of metastatic disease should be remembered in patients with sudden development of cranial nerve palsies, and CPA or sellar region lesions, alone or in combination. Besides, investigation of CSF in such patients should be done routinely to evaluate the presence of concomitant LM.
ACKNOWLEDGEMENTS We are grateful to Mr. Gerd Pfister for his assistance with figure production.
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Received 22 January 2008, received in final form 9 June 2008. Accepted 7 July 2008.
Dr. Marcus Andre Acioly Department of Neurosurgery, University Hospital, Hoppe-Seyler-Strasse 3.D - 72076 Tübingen, Germany. E-mail: firstname.lastname@example.org