Paraneoplastic anti-Ma2 Encephalitis Associated with Bilateral Intratubular Germ Cell Neoplasia. A Case Report and Review of the literature
Paraneoplastic (PNS) neurological syndromes are a group of neurologic disorders caused by an immune response (onconeural immunity) to an underlying malignancy. In young men this disorder associates with testicular tumors. The well-characterised onconeural antibody, anti-Ta, reacts with the paraneoplastic protein PNMA2 (former antibody name: anti-Ma2). Among all PNS, the anti-Ma2 immune response is the most specific for limbic encephalitis. Testicular germ cell tumors (TGCTs) represent the vast majority (90-95%) of malignant tumors of the testis.Intratubular germ cell neoplasia, unclassified (IGCNU) is the precursor of invasive germ-cell tumors and is found in essentially every case of TGCTs. Anti-Ta PNS with occult testicular IGCNU have been well-documented in 11 cases. Four were bilateral. We describe a patient who presented paraneoplastic anti-Ma2 encephalitis associated with bilateral IGCNU. Literature review was carried out to date.
Materiales y métodos
A 41-year-old man had episodes of amnesia, depression, headache, paresthesia and ophtalmoplegia.On admission, the voluntary eye movements were limited in horizontal directions. Cytology was negative for malignant cells in the Cerebrospinal fluid. The presence of paraneoplastic antibody anti-Ma2 was revealed in serum and CSF. Brain MRI showed hyperintense abnormalities in hipoccampus and medial temporal lobes. Ultrasonography of the scrotum showed right scrotal cacifications. Left orchyectomy was performed.
Macroscopic study demonstrated a cut surface that showed a well-circumscribed scar area. The histological evaluation revealed a fibrotic area and sclerotic seminiferous tubules with reduced spermatogenesis. Located immediately above a thickened basement membrane, atypical large germ cells were identified. The cells had clear cytoplasm, irregular nuclear contours, enlarged nucleoli and coarse chromatin. Mitoses were scarce. The dysplastic cells were positive with periodic acid-Schiff staining and expressed placental-like alkaline phosphatase and CD117. After surgery, the patient recovered from the neurological instabilities.After a few months the neurological symptoms recurred and right orchiectomy was performed. Histopathological findings were similar to those decribed in the left testicle.
Limbic encephalitis in young males can be a paraneoplastic manifestation of testicular cancer. Although the radiological images may not display solid tumors, it is necessary to perform pathological examination of tissue samples to rule out testicular precursor lesions of TGCTs.