Pathology Notes

Neurofibromatosis I   Updated: 03/29/2020 © Jun Wang, MD, PhD General features Also called von Recklinghausen disease, NF1 Either autosomal dominant or de novo mutation 5 - 13% develop malignant peripheral nerve sheath tumor 2 - 4 x increased risk of other tumors (childhood CML , ganglioneuroma, meningioma, pheochromocytoma, rhabdomyosarcoma ); acoustic neuroma (schwannoma) , astrocytoma, gastric carcinoid, GIST , glomus tumor , lipoma , optic nerve glioma, Wilm tumor Clinical presentations Multiple neurofibromas (plexiform, solitary) Plexiform neurofibromas relatively specific 6 or more cafe au lait spots over nerve trunks Lisch nodules (pigmented iris hamartomas, majority by age 6) Pathogenesis Neurofibromin defect Resulted in ineffective conversion of RAS to inactive form Genetic abnormality Mutation of NF1 (neurofibromin) at chromosome 17q11.2 Back to soft tissue tumors Back to syndromes Back to contents

Neurofibromatosis II Updated: 03/29/2020 © Jun Wang, MD, PhD General features Also known as NF2, acoustic neurofibromatosis Autosomal dominant Clinical presentations Bilateral acoustic neuromas ( schwannomas ) Multiple meningiomas Spinal cord ependymomas Schwannosis (ingrowth of Schwann cells into cord) Meningioangiomatosis Glial hamartia Café au lait NO Lisch nodules (unlike NF1 ) Pathogenesis Abnormal activation of PI3K, RAS and RAC by mutated merlin Genetic abnormality Loss of function mutation of merlin at 22q12 Back to soft tissue tumors Back to syndromes Back to contents

Schwannoma   Updated: 08/07/2020 © Jun Wang, MD, PhD General features Benign nerve sheath tumor arising from differentiated Schwann cells Most commonly 20 - 50 years old Majority are sporadic, may be associated with neurofibromatosis II (NF2) or Carney complex Clinical presentations Mass with abnormal sensation Commonly in limbs, especially upper limbs, head and neck Deep tumor commonly in posterior mediastinum or retroperitoneum Pathogenesis Abnormal activation of PI3K, RAS and RAC due to merlin inactivation Genetic abnormality Loss of function mutation of merlin at 22q12 Morphological features Encapsulated biphasic nerve sheath tumor Cellular component(Antoni A) that palisades (Verocay bodies), and myxoid component (Antoni B) Marker Positive for S100 Back to soft tissue tumors Back to contents

Neurofibroma Updated: 03/28/2020 © Jun Wang, MD, PhD General features Benign tumor with nerve sheath differentiation If multiple, likely associated with neurofibromatosis type 1 Malignant transformation rare Subtypes Plexiform: Irregularly expanded nerve bundles with nodular appearance, prominent myxoid matrix; associated with NF1 Diffuse cutaneous: Large plaque like elevation , typically NF1-associated Superficial cutaneous: Pedunculated nodules, solitary (sporadic) or multiple (likely NF1 associated) Clinical presentations Flesh-colored, soft nudule, solitary or multiple Slow growing, painless May have abnormal sensation (electric-like shock with light touch) Key morphological features Non-encapsulated spindle cell proliferation Thin slandering nuclei (coma like) Fibrillary background May be plexiform Markers Positive for S-100 May be focally positive for CD34 and Factor XIIIa Genetic abnormalities NF1 if neurofibromatosis Treatment

Malignant peripheral nerve sheath tumor Updated: 08/07/2020 © Jun Wang, MD, PhD General features AKA: Malignant schwannoma, neurofibrosarcoma Commonly associated with neurofibromatosis (NF) 1 May arise de novo More common in adults May have history of radiation exposure May recur, distant metastases common Clinical presentations Deep seated tumor associated with major nerves Commonly location: Neck, forearm, lower leg, buttock Key morphological features Hyperchromic spindle cells Markers Positive for S-100, CD56 Negative for EMA, keratin (different from synovial sarcoma) Treatment Excision Radiation Chemotherapy Back to soft tissue tumors Back to contents