Neurosurgery notes/Tumours/Germ cell tumours/Germinoma

Germinoma

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Germ cell tumours

General

  • Highly malignant
  • + suprasellar
  • Large nuclei, clear cytoplasm
  • Giant syncitiotrophoblastic cells

Definition

  • A malignant germ cell tumour histologically characterized by the presence of large primordial germ cells with prominent nucleoli and variable cytoplasmic clearing.

Frequency

  • Most common in young male
  • 41.1%

Localisation

  • Germinomas
    • Suprasellar compartment
    • Basal ganglionic / thalamic regions

Histopathology

  • Macroscopic
    • Soft and friable tan white tissue
    • Mainly Solid but can have cystic changes
    • Rare haemorrhage and necrosis
  • Microscopic
      • Large undifferentiated cells
        • Resemble premodial cells, which arise as precursors of gametes sperms and eggs
      • Arranged in sheets, lobule, regimented cords and trabeculae
      • High proliferation rate
      • Prominent nucleoli; discrete cell membranes; and relatively abundant clear cytoplasm (glycogen)
      • Delicate fibrovascular septa (variably infiltrated by small lymphocytes) are a typical feature
      • Germinomas that provoke an intense granulomatous response can resemble sarcoidosis or tuberculosis
      Germinoma. (A) Tumour cells with abundant clear cytoplasm, round nuclei, and prominent nucleoli; note the lymphocytic infiltrates along fibrovascular septa. (B) Large tumour cells with round vesicular nuclei, prominent nucleoli, and clear cytoplasm. (C) Syncytiotrophoblastic giant cell in an otherwise typical germinoma. (D) Immunostaining for hCG.
      Germinoma.
      (A) Tumour cells with abundant clear cytoplasm, round nuclei, and prominent nucleoli; note the lymphocytic infiltrates along fibrovascular septa.
      (B) Large tumour cells with round vesicular nuclei, prominent nucleoli, and clear cytoplasm.
      (C) Syncytiotrophoblastic giant cell in an otherwise typical germinoma.
      (D) Immunostaining for hCG.

Immunophenotype

  • +
    • Consistent
      • Cell membrane and Golgi region immunoreactivity for KIT
      • Membranous D2-40
        • Distinguish germinomas from solid variants of embryonal carcinoma and yolk sac tumour,
      • RNA-binding LIN28A protein
      • Nuclear expression of the transcription factors (NANOG, OCT4, ESRG, UTF1, and SALL4)
    • Less consistent (and non-specific)
      • Cytoplasmic/membranous PLAP
      • Cytoplasmic CAM5.2
      • AE1/AE3 cytokeratin antibodies
      • Pure germinomas may harbour syncytiotrophoblastic elements that expresses beta-hCG and human placental lactogen
        • Seeing these one should not think it is choriocarcinoma
      • Reactive lymphoid elements within germinomas
        • Dominated by T cells, including both CD4-expressing helper/inducer cytotoxic/suppressor elements
        • Rare to see CD20-labelling B cells and CD138-labelling plasma cells and CD8-expressing
  • -
    • CD30
    • Alpha-fetoprotein

Blood markers

  • 50% might have beta-HCG
    • Elevations that are typically less than in non-germinomatous tumours.
  • PLAP

Radiological

  • May seed to the neuroaxis
Bifocal (synchronous) germinoma
Bifocal (synchronous) germinoma

Treatment

  • Pure germinomas can be cured with radiotherapy alone.
    • Sensitive to radio → high cure rates
    • Craniospinal irradiation (CSI) achieves 5-year progression-free survival (PFS) and overall survival (OS) rates more than 90%
  • Germinomas with high β-HCG (usually >50 IU/litre, due to presence of STGCs) have been distinguished as a subset of germinomas that may require more aggressive treatment.
  • A mixed non-germinomatous tumour with a germinoma component:
    • Surgery may be needed.
    • Better outcome for germinoma patients with less than 1.5 cm3 residual disease (recurrence rates after mean 6-years follow-up, 65% vs. 38%) (Souweidane 2010).
      • However, this data requires validation as it is contrary to the SIOP trials.
  • Chemotherapy:
    • The international CNS GCT studies showed that due to dismal survival rates (5-year PFS <50%) chemotherapy cannot be used on its own
    • Induction chemotherapy is still being evaluated.
      • The International Society of Paediatric Oncology (SIOP) regimen of ifosfamide, carboplatin (cisplatin due to reduced chemotoxicity), and etoposide (‘ICE’)