P10.01PARANEOPLASTIC BRAINSTEM ENCEPHALITIS AS PRESENTING SYMPTOM OF MERKEL CELL CARCINOMA (MCC) FOLLOWED BY INTRACRANIAL AND LEPTOMENINGEAL DIFFUSION

CASE REPORT: A 52 years-old man was hospitalized for dizziness and dysarthria, followed by sleepiness, ataxia and dysphagia with forced rest in bed and need of parenteral nutrition. Neurological examination revealed bilateral lateral nystagmus, positive Romberg's sign, gait ataxia. Magnetic resonance imaging (MRI) of the brain was negative. Cerebrospinal fluid examination showed increased protein and normal count cells; PCR for neurotropic viruses was negative. Neoplastic markers and onconeuronal antibodies resulted negative. Findings on computed tomography of the chest and abdomen were normal. PET scan showed high metabolic activity in axillary and inguinocrural right lymph nodes. Excisional biopsy of the inguinal lymph node documented metastasis from a malignant neuroendocrine cutaneous neoplasia cromogranina A, CK 20 EMA and Synaptophysin positive. This profile was consistent with metastatic MCC. No skin lesions were detected. A diagnosis of paraneoplastic brainstem encephalitis was formulated: the patient was treated with intravenous infusion of immunoglobulins with partial benefit. The primitive neoplasm was treated with a combination therapy of Etoposide 100 mg/mq administered for three days and Cisplatin 75 mg/mq for one day in a 21-day-cycle. One month after the first cycle the patient recovered autonomous deambulation and normal feeding. About five months later the patient complained of dysarthria, dysphagia and ataxia. A brain MRI revealed a pineal lesion with contrast enhancement. Cerebrospinal fluid examination revealed 50 mononucleate cells per field, protein level of 47 mg/dl. Cytofluorimetric study of CSF showed 7% of CD45 negative cells, EMA (epithelial membrane antigen) positive cells consistent with leptomeningeal invasion. The patient deteriorated rapidly: he presented an epileptic seizure followed by coma and a few days after he deceased. Discussion and conclusion Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neurondocrine tumor. Literature reports few cases of paraneoplastic complications and also CNS metastasis are rare. In this case report, the onset of neurological symptoms lead to a diagnosis of a MCC. A paraneoplastic disease was supposed because of normal neuroradiological and laboratory findings although onconeuronal antibodies were absent. The rapid clinical response to treatment (both intravenous immunoglobulins and chemotherapy) seemed to confirm that view. The relapse of symtoms was caused by intracranial and leptomeningeal localization with poor prognosis. In the case described the MCC reveals a high affinity for CNS, both indirectly (an immune response against neuronal proteins expressed by the tumor cells is supposed to be the cause of the paraneoplastic syndrome) and directly with neurometastatic progression. In our knowledge this is the first case described of MCC with this high tropism for CNS.