Perineural and Meningothelial Neoplasms Flashcards
Spindle cell meningioma
Sheets or lobules of oval cells with intervening dense collagenous tissue. A syncytial growth pattern is present, where cytologic borders are indistinct. Whorls and psammomas bodies are characteristic features, as well as nuclear clearing and **nuclear pseudoinclusions. **
Meningiomas are immunoreactive to vimentin and epithelial membrane antigen (EMA).
More common in females.
IHC:
EMA positive
Vimentin positive
S100 negative
HMB-45 negative
desmin negative
Molecular:
Variety of causal mutations, however merlin/NF2 is an imporant one to know.
Meningioma grading
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986967/
Schwannoma
Biphasic: compact hypercellular Antoni A areas and myxoid hypocellular Antoni B areas
Nuclear palisading around fibrillary process (Verocay bodies) is often seen in cellular areas
Cells are narrow, elongated and wavy with tapered ends interspersed with collagen fibers. Chromatin is dense and cytoplasmic borders are ill-defined. May display ancient change, similar to benign nevi.
There should be no intratumorial axons.
IHC:
S100 positive (strong, diffuse)
SOX10 positive
Calretinin positive
Vimentin positive
EMA negative
SMA negative
Desmin negative
Molecular:
Can be associated with NF2 (merlin/NF2 mutations), Carney complex (PRKAR1A mutations), or schwannomatosis (SMARCB1 or LZTR1 mutations).
Plexiform schwannoma
Rare variant of schwannoma that is usually associated with merlin/NF2 mutations or schwannomatosis (SMARCB1 or LZTR1 mutations).
May involve multiple nerve fascicles, making resection difficult.
Microcystic/reticular schwannoma
Rare schwannoma variant, most commonly arising in the GI tract. Has no Antoni A or B areas and no Verocay bodies, but instead consists of strands of bland spindle cells in a myxoid background, with various proportions of microcystic structures.
Neurofibroma
Presents as a well circumscribed nonencapsulated proliferation of hypocellular spindle cells. Cells are bland, serpentine spindle cells and shredded carrot collagen. Mast cells are frequently recruited.
If you have a ddx of atypical neurofibroma vs MPNST, p16 can be helpful (MPNST are uniformly p16 null, neurofibromas are p16 retained).
IHC:
S100 positive (strong, diffuse)
SOX10 positive (strong)
Vimentin positive (strong)
Factor XIIIa positive (used to differentiate from neuratized nevus)
CD34 positive (“fingerprint” pattern)
EMA weak to negative
SMA negative
Desmin negative
Molecular:
CDKN2A retained
MPNST
Malignant spindle cell neoplasm with a “marbled” low power apperance (shown) and fascicular growth. On high power, there is a high N:C ratio and cells may appear as plump spindle cells, epithelioid, or have rhabdoid features.
A precursor neurofibroma may also be present.
50% sporadic, 40% in the setting of neurofibromin/NF1 mutations, 10% in the setting of radiation therapy (13.5 +/- 7.5 years following radiation).
IHC:
S100 focally positive to negative
SOX10 focally positive to negative
In NF1-independent tumors (sporadic, radiation assocaited), loss of nuclear H3K27me3 is characteristic.
Loss of INI-1 is present in ~50% of epithelioid MPNST.
Desmin, myogenin, MyoD1 positive (focally) when rhabdoid features are present.
Differentiating neurofibroma and MPNST
Table here: https://www.pathologyoutlines.com/topic/softtissueneurofibroma.html
Neurothekeoma
Benign, multinodular fibrous tumor of the dermis or subcutis of the head and neck with a myxoid matrix and peripheral fibrosis. Composed of whorled or focally fascicular patterns of spindled and epithelioid mononuclear cells with abundant cytoplasm and indistinct cell borders. Variable nuclear atypia is present. Often some mitoses will be present.
IHC:
Vimentin positive
CD10 positive
MITF positive
NKI-C3/CD63 positive
SMA focally positive
S100 negative
GFAP negative
MelanA negative
In patients with neurofibromin/NF1 pathogenic mutations, _ represents a precursor lesion to MPNST.
Plexiform neurofibroma
Classification of atypical neurofibroma-MPNST spectrum in NF1 patients
Atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP): At least 2 of the following features:
* Cytologic atypia
* Loss of neurofibroma architecture
* Hypercellularity
* > 1/50 mitoses per HPF and < 3/10 mitoses per HPF
MPNST, low grade: Features of ANNUBP but with mitotic index of 3 - 9/10 HPF and no necrosis
MPNST, high grade: MPNST with at least 10 mits/10 HPF or 3 - 9 mits/10 HPF combined with necrosis
Plexiform neurofibroma
Variant of a neurofibroma with a plexiform architecture.
These are congenital tumors that take time to grow slowly.
Strongly associated with germline NF-1. Can also be seen with germline GNAZ and LZTR1 variants.
IHC:
Scattered S100 positivity.
EMA highlights perineural cells (in plexixform but NOT normal neurofibromas)
CD34 frequently positive.
p16 retained
Desmin negative
SMA negative
Calretinin negative
