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NF1-associated atypical neurofibroma

Tuesday 25 January 2011

Digital slides

- Case 56 (HPC:56) : Atypical neurofibroma in neurofibromatosis type 1


Patients suffering from neurofibromatosis type 1 and 2 (NF1 and NF2) are the main risk groups to develop peripheral nerve sheath tumours (PNSTs).

Neurofibromatosis type 1 (NF1) patients have a 13% risk of developing a malignant peripheral nerve sheath tumor (MPNST).

Many MPNSTs are histopathologically complex, with regions exhibiting features of the original benign plexiform neurofibroma (PNF), of an atypical plexiform neurofibroma, or of MPNST showing varying degrees of de-differentiation.


- podoplanin (D2-40) (20821344)

  • Podoplanin shows an inverse expression pattern to CD34 labelling mainly the compact parts of schwannoma and atypical neurofibroma.
  • MPNSTs are characterized by strong podoplanin staining at the invasive front.
  • NF1-patients who suffered from atypical neurofibromas did not develop MPNST at a higher frequency than other NF1-patients, although these tumours expressed podoplanin.
  • Podoplanin expression in schwannoma and atypical neurofibroma adds to other phenotypic and genotypic similarities between these tumours, like nuclear atypia, regressive changes and euploid polyploidisation.
  • Podoplanin expression in atypical neurofibroma was not associated with tumour progression towards MPNST.

- Ki-67

  • Ki-67 proliferation indices did not differ significantly between neurofibromas, atypical neurofibromas and schwannomas. (20821344)

- CD34

  • In accordance with other studies, CD34 was found to be of limited value for classification and grading of PNST due to its ubiquitous expression. (20821344)

- CD10 (19661328)

  • CD10 immunopositivity is absent or very weak and focal in neurofibromas.
  • CD10 is strongly expressed in all the MPNST and most atypical neurofibromas.
  • CD10 is useful in the assessment of peripheral sheath tumors.
  • CD10 could give evidence that atypical myxoid and/or diffuse neurofibromas, sometimes histologically difficult to distinguish from low-grade MPNST.
  • CD10 represent not only a histological but also an immunohistochemical continuum with MPNST.

Molecular biology

- Chromosome 17p deletions and p53 gene mutations are associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. (2142531)

- In one patient with a germline NF1 splice-site mutation, the NF1-associated LOH analysis found that LOH increased in the three tumor areas, with 9, 42, and 97% LOH evident in different regions. Additional genetic changes, including losses of TP53, RB1, CDKN2A, and of several oncogenes and cell-cycle genes, were found only in the malignant MPNST. Array CGH also identified genomic gains and losses in DNA in one tumoral region. (20229272)


- Podoplanin and CD34 in peripheral nerve sheath tumours: focus on neurofibromatosis 1-associated atypical neurofibroma. Naber U, Friedrich RE, Glatzel M, Mautner VF, Hagel C. J Neurooncol. 2010 Sep 7. PMID: 20821344

- Molecular evolution of a neurofibroma to malignant peripheral nerve sheath tumor (MPNST) in an NF1 patient: correlation between histopathological, clinical and molecular findings. Spurlock G, Knight SJ, Thomas N, Kiehl TR, Guha A, Upadhyaya M. J Cancer Res Clin Oncol. 2010 Dec;136(12):1869-80. PMID: 20229272

- Diagnostic and prognostic value of CD10 in peripheral nerve sheath tumors. Cabibi D, Zerilli M, Caradonna G, Schillaci L, Belmonte B, Rodolico V. Anticancer Res. 2009 Aug;29(8):3149-55. PMID: 19661328

- Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Menon AG, Anderson KM, Riccardi VM, Chung RY, Whaley JM, Yandell DW, Farmer GE, Freiman RN, Lee JK, Li FP, et al. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5435-9. PMID: 2142531