Contributed by R. Abeygunaratne*, G. Roberts*, L. Gunawardena#, J. Joseph^ and T. Dawson^
Departments of Neuropathology(^), Neuroradiology(#) and Neurosurgery(*),
Lancashire Teaching Hospital NHS Trust, Preston PR2 9HT, United Kingdom.
A 50 year old lady presented to the clinic with mild occipital headaches, vomiting, swallowing difficulties and ataxia which had developed over a period of 3 months and were progressively worsening in severity. No significant past medical history was noted and she was not on any regular medication. The social and family histories were unremarkable. Examination demonstrated a GCS 15/15, horizontal nystagmus, intention tremor and disdiadokokinesis. Fundoscopy revealed bilateral papilloedema. No cranial nerve dysfunction was identified. MR imaging revealed a 4th ventricular enhancing mass with significant obstructive hydrocephalus and a degree of tonsillar herniation (Fig 1).
She underwent a posterior fossa craniectomy with splitting of the cerebellar vermis to expose a well-demarcated mass in the fourth ventricle. This had a dark grey/black appearance of soft consistency and complete excision was attempted. The tissue was submitted for histopathological examination. Postoperatively the patient was found to have bilateral seventh nerve palsies and dysarthria but made a good recovery.
Nine months after the initial surgery she presented to the clinic again with worsening bilateral facial nerve palsies and complete blindness in her right eye. Repeat MR imaging revealed widespread discrete lesions, some of which appeared dural based, mainly in the posterior fossa while others were clustered around the basal forebrain (Fig 2, T-1 weighted). Recurrent tumor was also evident in the 4th ventricle with associated non-communicating hydrocephalus. A ventricular peritoneal shunt was inserted and biopsies of several lesions were carried out at the same time. Macroscopically on this occasion the lesional tissue appeared both pigmented and unpigmented and samples of both were submitted for histopathological examination. Unfortunately she continued to deteriorate and died 3 weeks following surgery. Permission for post mortem was obtained.
Paraffin sections of the original fourth ventricular tumor showed uniform sheets of epithelioid cells with regular nuclear profiles exhibiting prominent nucleoli (Figure 3). Mitotic activity was inconspicuous and necrosis was absent but dusty pigmentation could be seen throughout the lesion. Tumor cells were negative with epithelial markers (CAM5.2, CK7, CK20, EMA). Cytoplasmic staining was evident with melanocyte marker MelA but HMB45 only showed focal membrane staining. The neuroectodermal lineage marker, S100, showed diffuse cytoplasmic positivity. The MIB-1 immuno-proliferation index was around 1%.
In contrast, the majority of the recurrent tumor (Figure 4) comprised highly anaplastic, mitotically active epithelioid cells with pleomorphic nuclei containing prominent nucleoli. Dusty pigmentation was scant but geographic necrosis was prominent and vascular invasion identified. The MIB-1 proliferation index was in excess of 8%. Tumor cells still demonstrated positive MelA and diffuse S100 staining but the HMB45 was negative. In one part of the recurrent biopsy though, the bland cytonuclear features of the original tumor could still be seen suggesting an element of clonal progression. CSF cytology also showed disseminated tumor cells.
On opening the cranium and reflection of the dura there were extensive pigmented and nonpigmented tumor nodules adherent to the dura particularly in the posterior fossa. The leptomeninges at the base of the brain showed extensive pigmented tumor involvement particularly in the pre-pontine area and in the sellar region (Figure 5). The right optic nerve was completely ensheathed by dark tumor tissue which extended into the optic canal. The lateral ventricles were dilated with tumor involvement of the ependymal lining. There was residual dark pigmented tumor in the fourth ventricle and the vermis of the cerebellum. No tumor was present in the cerebral parenchyma.
Histology of the above lesions showed an aggressive tumor with cellular anaplasia, frequent mitoses, focal melanin pigmentation and necrosis similar to that seen in the recurrent biopsies. There was no evidence of any primary melanotic lesion elsewhere in the body or any evidence of extracranial metastasis.