Primitive neuroectodermal tumour

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Primitive neuroectodermal tumour
Diagnosis in short

CNS primitive neuroectodermal tumour H&E stain.

Synonyms CNS-PNET
LM DDx small round blue cell tumours
IHC S-100 +ve, Syn +/-ve
Site brain, spinal cord

Prevalence rare - typically in young adults
Prognosis poor (WHO Grade IV)


CNS Primitive neuroectodermal tumour, abbreviated CNS-PNET, is an abandoned neuropathology tumour description within in the group of embryonal tumours. The terminology was introduced in 1973 [1] and used in the WHO 2007 classification of CNS tumors. Since 2016 this category has been replaced by the designation other CNS embryonal tumors.

General

  • Should not be confused with peripheral primitive neuroectodermal tumour (abbreviated pPNET[2]), AKA Ewing sarcoma.
  • The former category contained a heterogenous group of poorly differentiated WHO grade IV tumours associated with following ICD-O codes:
    • 9473/3 CNS-PNET, NOS.
    • 9500/3 CNS neuroblastoma.
    • 9490/3 CNS ganglioneuroblastoma.
    • 9501/3 Medulloepithelioma.
    • 9392/3 Ependymoblastoma.
  • Mainly children and adolescents.
  • Cerebral hemisphere, brain stem or spinal cord.
  • Cerebrospinal dissemination found in up to 1/3 patients.[3]
  • Very poor prognosis[4]

Microscopic

Features:

  • Small round blue cell tumour.
    • Focal differentation into astrocytic, neuronal or ependymal phenotypes possible.
  • May have true rosettes (slit-like/oval).
  • Growth in streams or palisades possible ("spongioneuroblastoma").
  • Vascular endothelial proliferations.
  • Fibrillary background in tumours with advanced neuronal maturation (ganglioneuroblastomas).
  • Variable mitotic activity.

Supratentorial PNET

  • This category of small round- and blue cell tumor was used in the WHO 2007 CNS tumor classification to separate them from medulloblastomas.
  • Tumors are today classified as AT/RT, Pineoblastoma, ETMR, H3F3A-mutated glioblastoma or CNS embryonal tumor, NOS.

CNS neuroblastoma

  • Since WHO 2016 CNS classification this is now a subgroup of Other CNS embryonal tumours.
  • Many CNS neuroblastoma / CNS ganglioneuroblastoma cluster molecularly into a group designated as CNS NB-FOXR2.[5]
  • Usu Olig-2 +ve.
  • Synaptophysin +ve.

CNS ganglioneuroblastoma

Lipomatous medulloblastoma

Melanotic medulloblastoma

  • In WHO CNS 1997 still a distinct tumor.
  • These tumors are now considered a variant of medulloblastoma.

Medullomyoblastoma

  • Embryonal tumor with primitive neuronal cells and striated muscle component.
  • First description in 1933.[6]
  • Since WHO 2007 CNS tumor classification tumors were classified as medulloblastoma with myogenic differentiation.

Medulloepithelioma

  • Neuroepithelial tumor cells arranged papillary, tubular or trabecular.
  • Pseudostratified with PAS-positive membrane.
  • Medulloepithelioma are grouped with ependymoblastomas and ETANTR into embryonal tumors with multilayered rosettes (ETMR).[7]
  • Not the same tumour as the intraocular medulloepithelioma.[8]

Ependymoblastoma

  • Often supratentorial, well circumscribed.
  • Multilayered ("ependymoblastous") rosettes.
  • High mitotic and proliferative activity
  • Ependymoblastoma are grouped with medulloepithelioma and ETANTR into embryonal tumors with multilayered rosettes (ETMR).[7]

Immunohistochemistry

  • S-100 +ve.
  • INI1 +ve (loss defines tumour as ATRT).
  • LIN28+ve (in ETMR), otherwise -ve. [9]
  • Nestin +ve
  • MAP2 +ve/-ve
  • Vimentin +ve
  • IDH-1 -ve
  • No ATRX loss
  • MIB-1 between 20-80% (usu. 50%)

Molecular genetics

Divergent molecular subgroups are emerging:

  • Loss of 9q / CDKN2A deletions in CNS neuroblastoma[10]
  • Amplification 19q13.42 in ETMR[11]


DDx:

Images

www:

See also

References

  1. Hart, MN.; Earle, KM. (Oct 1973). "Primitive neuroectodermal tumors of the brain in children.". Cancer 32 (4): 890-7. PMID 4751919.
  2. PST. 14 February 2011.
  3. Horten, BC.; Rubinstein, LJ. (Dec 1976). "Primary cerebral neuroblastoma. A clinicopathological study of 35 cases.". Brain 99 (4): 735-56. PMID 1030655.
  4. Tulla, M.; Berthold, F.; Graf, N.; Rutkowski, S.; von Schweinitz, D.; Spix, C.; Kaatsch, P. (Sep 2015). "Incidence, Trends, and Survival of Children With Embryonal Tumors.". Pediatrics 136 (3): e623-32. doi:10.1542/peds.2015-0224. PMID 26304823.
  5. Sturm, D.; Orr, BA.; Toprak, UH.; Hovestadt, V.; Jones, DTW.; Capper, D.; Sill, M.; Buchhalter, I. et al. (Feb 2016). "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.". Cell 164 (5): 1060-1072. doi:10.1016/j.cell.2016.01.015. PMID 26919435.
  6. Brody, BS.; German, WJ. (Oct 1933). "Medulloblastoma of the Cerebellum: A Report of 15 Cases.". Yale J Biol Med 6 (1): 19-29. PMID 21433586.
  7. 7.0 7.1 Horwitz, M.; Dufour, C.; Leblond, P.; Bourdeaut, F.; Faure-Conter, C.; Bertozzi, AI.; Delisle, MB.; Palenzuela, G. et al. (Oct 2015). "Embryonal tumors with multilayered rosettes in children: the SFCE experience.". Childs Nerv Syst. doi:10.1007/s00381-015-2920-2. PMID 26438544.
  8. Korshunov, A.; Jakobiec, FA.; Eberhart, CG.; Hovestadt, V.; Capper, D.; Jones, DT.; Sturm, D.; Stagner, AM. et al. (Jul 2015). "Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.". Neuropathology. doi:10.1111/neup.12227. PMID 26183384.
  9. Korshunov, A.; Ryzhova, M.; Jones, DT.; Northcott, PA.; van Sluis, P.; Volckmann, R.; Koster, J.; Versteeg, R. et al. (Dec 2012). "LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR).". Acta Neuropathol 124 (6): 875-81. doi:10.1007/s00401-012-1068-3. PMID 23161096.
  10. Pfister, S.; Remke, M.; Toedt, G.; Werft, W.; Benner, A.; Mendrzyk, F.; Wittmann, A.; Devens, F. et al. (Sep 2007). "Supratentorial primitive neuroectodermal tumors of the central nervous system frequently harbor deletions of the CDKN2A locus and other genomic aberrations distinct from medulloblastomas.". Genes Chromosomes Cancer 46 (9): 839-51. doi:10.1002/gcc.20471. PMID 17592618.
  11. Korshunov, A.; Remke, M.; Gessi, M.; Ryzhova, M.; Hielscher, T.; Witt, H.; Tobias, V.; Buccoliero, AM. et al. (Aug 2010). "Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes.". Acta Neuropathol 120 (2): 253-60. doi:10.1007/s00401-010-0688-8. PMID 20407781.
  12. Buccoliero AM, Castiglione F, Degl'Innocenti DR, et al. (February 2010). "Embryonal tumor with abundant neuropil and true rosettes: morphological, immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation". Neuropathology 30 (1): 84–91. doi:10.1111/j.1440-1789.2009.01040.x. PMID 19563506.