Tumors arising from the meninges and ear canal

Question 1

Steps to examining a meningioma

Answer 1

1. Make sure it is really a meningioma (SSTR2 if necessary)
2. Grade the meningioma based on histology
3. Update grade based on additional features
   * If grade 1, order a Ki67, which can upgrade to grade 2
   * If grade 2, order H3K27me3 IHC/CDKN2A FISH/TERT promoter PCR
   * If rhabdoid features, order BAP1

Question 2

Grading a meningioma

Answer 2

Automatically grade 2 histologic patterns: Clear cell, chordoid, “atypical”
Automatically grade 3 patterns: papillary, rhabdoid, “anaplastic”

Question 3

Answer 3

Hemangioblastoma

IHC: Inhibin+, CD34 highlights rich vascular network.
Oil red O positive at frozens.

Question 4

Answer 4

Intracranial mesenchymal tumor, FET::CREB fusion positive

Morphology: Tumors have a wide morphologic spectrum, usually with collagenous stroma with dense intercellular matric highlighted by reticulin. Architecture may be syncytial or sheet-like to reticular and cord-like. Myxoid stroma is not always present. Cytology varies from epithelioid/rhabdoid to stellate/spindled, and rarely tumors of monotonous round cells are seen. Mitotic activity is generally low (less than 5 per mm2). Dense lymphoplasmacytic cuffing at the tumor periphery or along fibrous septa is often present, as is hematoidin or hemosiderin.

IHC: CD99+, desmin+, myogenin negative, MYOD1 negative, SSTR2 negative, OLIG2 negative, GFAP negative. There is no good, specific marker which stains positively in this tumor. So, rule out lookalikes and send it for FISH.

Question 5

Answer 5

Primary intracranial sarcoma, DICER1 mutant

Primary intracranial sarcoma composed of spindled or pleomorphic tumour cells typically displaying eosinophilic cytoplasmic globules, immunophenotypic evidence of myogenic differentiation, and occasionally foci of chondroid differentiation. Frequently contain cells with prominent eosinophilic cytoplasmic globules.

Molecular: Loss of DICER1 is key, but tumors usually also have mutated TP53, loss of ATRX, and a MAPK activating mutation.

Question 6

Answer 6

Endolymphatic sac tumor

Arises from the endolymphatic sac at the posterior medial petrous ridge of temporal bone

Usually associated with Von Hippel Lindau (11% of VHL patients), but can also be sporadic with somatic VHL mutation.

Can arise in late childhood through late adulthood - wide age range, average age 30.

IHC: CAIX+, PAX8+, VEGF+, keratin +. Variably S100 and EMA expression.
Iron stain is positive in these tumors, as is PAS+diastase for glycogen.

Main DDx is often with choroid plexus papilloma.

Question 7

Answer 7

Choroid plexus papilloma (without atypia)

CNS WHO grade 1

Arise from the choroid plexus associated with any ventricle OR may present as a cerebellopontine angle tumor. Without atypia, these tumors are benign, but may recur if incompletely resected.

IHC: Keratin +, transthyretin +, synaptophysin +, variable S100, EMA, and GFAP. Negative for CAIX and PAX8.

Question 8

Answer 8

Atypical choroid plexus papilloma

CNS WHO Grade 2

Defined by its mitotic rate: >2 mitoses per 10 hpf

Question 9

Answer 9

Choroid plexus carcinoma

CNS WHO grade 3

About 40% of cases are Li-Fraumeni associated. This is primarily a pediatric tumor, usually occuring in patients less than 4 years of age.

Usually have a papillary architecture and variable pleomorphism. Cytoplasmic clearing and hyaline globules can sometimes be seen. The mitotic rate should exceed that of an atypical papilloma, generally >5 per 10 hpf.

There is not a distinct cut-off, but this provisional one is suggested:

>5 mitoses per 10 hpf in presence of solid areas, hypercellularity, and necrosis