Central Nervous System embryonal tumor



Central Nervous System (CNS) embryonal tumors represent a heterogeneous group of highly aggressive tumors occurring preferentially in children but also described in adolescents and adults. The World Health Organization Classification of Tumors of the Central Nervous System 2021, drastically changed the diagnosis of other CNS embryonal tumors including new histo-molecular tumor types.

Medulloblastoma

  Medulloblastomas, molecularly defined

   Medulloblastoma, WNT-activated

   Medulloblastoma, SHH-activated and TP53-wildtype

   Medulloblastoma, SHH-activated and TP53-mutant

   Medulloblastoma non-WNT/non-SSH

  Medulloblastomas, histologically defined

 Other CNS embryonal tumors

  Atypical teratoid/rhabdoid tumor

  Cribriform neuroepithelial tumor

  Embryonal tumor with multilayered rosettes

  CNS neuroblastoma, FOXR2-activated

  CNS tumor with BCOR internal tandem duplication

  CNS embryonal tumor


Initially, the term primitive neuroectodermal tumor (PNET) encompassed a wide variety of previously individually named tumors which all seemed to share certain pathologic features suggesting origin from a common progenitor cell in the subependymal matrix (primitive neuroectodermal cells) (although the actual cell of origin is unknown). They are histologically indistinguishable but genetically distinct 1).

Now, the recommendation is to call these “embryonal tumors”, 2) but the term PNET is entrenched. These tumors include: retinoblastoma, pineoblastoma, neuroblastoma, esthesioneuroblastoma.

Medulloblastoma (MB) is more than just a PNET of the posterior fossa, as alterations involved in evolution of MBs such as beta-catenin and APC mutations are absent in pineoblastomas and supratentorial PNETs (sPNETs). At least some MBs originate from the external granular layer (EGL) of the cerebellum.

Embryonal tumors most commonly arise in the cerebellar vermis (medulloblastoma), but also occur in cerebrum, pineal, brainstem or spinal cord. Primary spinal cord PNETs are extremely rare (approximately 30 cases reported by 2007 3)).

Dissemination: Embryonal tumors (ETs) may disseminate via the CSF spontaneously, 4) or iatrogenically (following surgery or shunting, the latter is a rare cause of tumor dissemination 5)). Thus, all patients with ETs require spinal axis evaluation (gadolinium enhanced MRI is about as sensitive as water-soluble myelography) and cytologic examination of CSF. Prophylactic craniospinal XRT is indicated following surgical removal, but cranial XRT is avoided if at all possible before 3 years of age to avoid intellectual impairment and growth retardation. Extraneural metastases can also occur.

Collin ’s law: AKA period of risk of recurren ce (PRR) is often applied to children who have been treated for embryonal tumors (especially medulloblastoma) but may also be used with any tumor thought to arise from a gestational event. It states that PRR is equal to the age at diagnosis plus 9 months 6). Patients that remain free of recurrence beyond the PRR have a much lower risk of recurrence, however recurrence beyond this time has been reported in a small number (≈ 1.4%) of cases, 7) and other tumors may occur e.g. as a result of induction by XRTused to treat the initial tumor.


A mass of rapidly growing cells that begins in embryonic (fetal) tissue. Embryonal tumors may be benign or malignant and include neuroblastomas and Wilms tumors. Also called embryoma.


1)
Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002; 415:436–442
2)
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Bosman FT, Ja e ES, Lakhani SR, Ohgaki H. WHO classification of tumors of the central nervous system. Lyon 2007
3)
Kumar R, Reddy SJ, Wani AA, Pal L. Primary spinal primitive neuroectodermal tumor: case series and review of the literature. Pediatr Neurosurg. 2007; 43:1–6
4)
Tomita T, McLone DG. Spontaneous Seeding of Medulloblastoma: Results of Cerebrospinal Fluid Cytology an d Arach noid Biopsy from th e Cistern a Magna. Neurosurgery. 1983; 12:265–267
5)
Berger MS, Baumeister B, Geyer JR, Milstein J, et al. The Risks of Metastases from Shunting in Children with Primary Central Nervous System Tumors. J Neurosurg. 1991; 74:872–877
6)
Collins VP, Loe er RK, Tivey H. Observations on growth rates of human tumors. Am J Roentgenol Radium Ther Nucl Med. 1956; 76:988–1000
7)
Sure U, Berghorn WJ, Bertalan y H. Collins' law. Prediction of recurrence or cure in childhood medulloblastoma? Clin Neurol Neurosurg. 1997; 99:113–116
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