Diagnostic review of neurofibromatosis type 1

Vineeta V. Batra, Michael Mines, Fausto J. Rodriguez

Research output: Contribution to journalReview article


ABSTRACT: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic syndrome associated with numerous neoplastic and nonneoplastic manifestations affecting a variety of organ systems, including skin, eye, nervous system, skeleton, and endocrine and gastrointestinal tract. The syndrome results from heterozygous germline mutations in the NF1 gene encoding for neurofibromin. Somatic inactivation of the remaining NF1 gene is a near-universal feature in tumors developing in these patients. Tumors of the nervous system are an important cause of morbidity and mortality in NF1 patients. These include low-grade neoplasms with little malignant potential (eg, pilocytic astrocytomas and localized neurofibromas), premalignant tumors (eg, plexiform neurofibromas), and high-grade malignant tumors (eg, malignant peripheral nerve sheath tumors and high-grade astrocytomas). It is important for pathologists to accurately classify these tumors and to separate atypical from frank malignant changes in surgical specimens. Ancillary techniques may be helpful in the diagnosis of malignant tumors in NF1 patients, including immunohistochemistry for p53 and p16 protein, as well molecular testing for CDKN2A loss. A subset of tumors occurring in NF1 patients is difficult to classify or may contain hybrid features preventing unequivocal assignment to a single diagnostic category. Occurrence of specific peripheral nerve sheath tumor types, such as deep/large plexiform neurofibromas and massive soft-tissue neurofibromas, is essentially limited to NF1 patients. Therefore, appropriate recognition of neoplasms occurring in the context of NF1 has important ramifications for clinical management in this unique patient population.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalPathology Case Reviews
Issue number2
StatePublished - Jan 1 2014


  • astrocytoma
  • glioma
  • malignant peripheral nerve sheath tumor
  • neurofibroma
  • neurofibromatosis
  • pilocytic astrocytoma
  • plexiform neurofibroma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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