Brain Pathology Case of the Month - August 2007

DIAGNOSIS: DIFFUSELY INFILTRATING GERMINOMA

ADDITIONAL TREATMENT AND CLINICAL PROGRESS:

After the lesion was diagnosed as a germinoma, the patient was treated with whole brain irradiation in fractions of 1.6 Gy, to a total dose of 44.8 Gy. Follow-up MRI showed disappearance of the enhancement and her condition improved, although focal deficits remained present. Three years after treatment she had a relapse which was treated with chemotherapy (bleomycin-etoposide-cisplatin) with good respons. One year later a second relapse occurred.

DISCUSSION:

Germinomas are tumors of germ cell origin and represent the brain counterpart of testicular seminoma. They are relatively rare and represent 0.4-3.4% of all primary intracranial tumors, although in Northeast Asia this is significantly higher, up to 9% (4). Like other extragonadal germ cell tumors, germinomas occur primarily in the midline, with the region of the pineal gland being the most common site, followed by the suprasellar compartment (8). They occur predominantly in children with a peak incidence around 12 years of age (4).

Depending on anatomical localization, patients with a germinoma may present with a range of neurological, endocrine and psychiatric symptoms. Pineal region tumors often compress the cerebral aqueduct, resulting in progressive hydrocephalus, and invade the tectal plate, producing a paralysis of upward gaze and convergence known as Parinaud syndrome. Suprasellar germ cell tumors compress the optic chiasm, resulting in visual loss, and present with endocrinopathy due to pituitary failure with diabetes insipidus, retarded growth and sexual maturation (8). Cure rates for this tumor exceed 90% at 10 years, and limitation of treatment-related late morbidity is therefore essential (7).

In this case, the characteristic radiological features of a germinoma were absent (3, 5). There was no mass effect, i.e. compression of pre-existent anatomical structures by growth of a solid tumor, and no enhancement after gadolinium administration. Instead, the tumor was diffusely infiltrating the surrounding tissue and followed the contours of the ventricular system. In addition, the marker placental alkaline phosphatase (PLAP) usually present in germinomas (2) was negative and diagnosis was made on nuclear OCT3/4 staining, which has proven to be a valuable marker in diagnosis of germ cell tumors (6, 1).

REFERENCES:

  1. De Jong J, Stoop H, Dohle GR, Bangma CH, Kliffen M, Van Esser JWJ, Van den Bent M, Kros JM, Oosterhuis JW, Looijenga LHJ (2005) Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. J Pathol 206:242-249.
  2. Felix I, Becker LE (1990) Intracranial germ cell tumors in children: an immunohistochemical and electron microscopic study. Pediatr Neurosurg 16:156-162.
  3. Fujimaki T, Matsutani M, Funada N, Kirino T, Takakura K, Nakamura O, Tamura A, Sano K (1994) CT and MRI features of intracranial germ cell tumors. J Neurooncol 19:217-226.
  4. Jennings MT, Gelman R, Hochberg F (1985) Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg 63:155-167.
  5. Kanagaki M, Miki Y, Takahashi JA, Shibamoto Y, Takahashi T, Ueba T, Hashimoto N, Konishi J (2004) MRI and CT findings of neurohypophyseal germinoma. Eur J Radiol 49:204-211.
  6. Looijenga LHJ, Stoop H, De Leeuw HPJC, De Gouveia Brazao CA, Gillis AJM, Van Roozendaal KEP, Van Zoelen EJJ, Weber RFA, Wolffenbuttel KP, Van Dekken H, Honecker F, Bokemeyer C, Perlman EJ, Schneider DT, Kononen J, Sauter G, Oosterhuis JW (2003) POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res 63:2244-2250.
  7. Rogers SJ, Mosleh-Shirazi MA, Saran FH (2005) Radiotherapy of localised intracranial germinoma: time to sever historical ties? Lancet Oncol 6:509-519.
  8. Rosenblum MK, Matsutani M, Van Meir EG (2000) CNS germ cell tumours. In: World Health Organization Classification of Tumours. Pathology and genetics of the tumours of the nervous system, Kleihues P, Cavenee WK (eds.), pp. 208-214, IARC Press: Lyon.

Contributed by Jeroen de Jong, MD, Hans Stoop, Martin van den Bent, MD, Johan M. Kros, MD, PhD, Prof. J. Wolter Oosterhuis, MD, PhD, Prof. Leendert H.J. Looijenga, PhD

International Society of Neuropathology