title: Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis.
abstract: OBJECTIVE
  To report the presence of microscopic neoplasms of the testis in men with anti-Ma2-associated encephalitis (Ma2-encephalitis) and to discuss the clinical implications.
  
  
  METHODS
  Orchiectomy specimens were examined using immunohistochemistry with Ma2 and Oct4 antibodies.
  
  
  RESULTS
  Among 25 patients with Ma2-encephalitis younger than 50 years, 19 had germ-cell tumors, and 6 had no evidence of cancer. These 6 patients underwent orchiectomy because they fulfilled five criteria: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits, 3) age < 50 years, 4) absence of other tumors, and 5) new testicular enlargement or risk factors for germ-cell tumors, mainly cryptorchidism or ultrasound evidence of testicular microcalcifications. All orchiectomy specimens showed intratubular-germ cell neoplasms unclassified type (IGCNU) and other abnormalities including microcalcifications, atrophy, fibrosis, inflammatory infiltrates, or hypospermatogenesis. Ma2 was expressed by neoplastic cells in three of three patients examined. Even though most patients had severe neurologic deficits at the time of orchiectomy (median progression of symptoms, 10 months), 4 had partial improvement and prolonged stabilization (8 to 84 months, median 22.5 months) and two did not improve after the procedure.
  
  
  CONCLUSIONS
  In young men with Ma2-encephalitis, 1) the disorder should be attributed to a germ-cell neoplasm of the testis unless another Ma2-expressing tumor is found, 2) negative tumor markers, ultrasound, body CT, or PET do not exclude an intratubular germ-cell neoplasm of the testis, and 3) if no tumor is found, the presence of the five indicated criteria should prompt consideration of orchiectomy.
authors.affiliation: Department of Neurology, Division Neuro-oncology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Mathew
authors.forename: R
authors.initials: R
authors.lastname: Vandenberghe
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Merino
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: J C
authors.initials: JC
authors.lastname: Landolfi
authors.forename: M R
authors.initials: MR
authors.lastname: Rosenfeld
authors.forename: J E
authors.initials: JE
authors.lastname: Rossi
authors.forename: B
authors.initials: B
authors.lastname: Thiessen
authors.forename: E J
authors.initials: EJ
authors.lastname: Dropcho
authors.forename: J
authors.initials: J
authors.lastname: Dalmau
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis / Q000097:blood / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D006801:Humans; D020363:Limbic Encephalitis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009434:Neural Pathways / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009919:Orchiectomy / Q000592:standards; D011237:Predictive Value of Tests; D013736:Testicular Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; C119249:Ma2 antigen; D009419:Nerve Tissue Proteins