What to know about schwannomatosis: a literature review

Figures & data

Table 1. Diagnosis of schwannomatosis based on molecular and/or clinical diagnostic criteria according to Plotkin et al.⁶ and Pstrow et al.¹¹

Clinical diagnosis
≥2 non-intradermal schwannomas, 1 pathologically confirmed schwannoma and absence of bilateral vestibular schwannomas
or
1 pathologically confirmed schwannoma or intracranial meningioma and 1 affected first-degree relative
Combined molecular and clinical diagnosis
≥2 pathologically confirmed schwannomas or meningiomas	≥2 tumors with 22q LOH and 2 different somatic NF2 mutations
or
1 pathologically confirmed schwannoma or meningioma	Germline SMARCB1 or LZTR1 pathogenic mutation
Exclusion criteria
Germline pathogenic NF2 mutation
Diagnostic criteria for NF2 fulfilled
First-degree relative with NF2
Schwannomas occur exclusively in a region of previous radiation therapy

Figure 1. (A) Low power view of a schwannoma, showing an encapsulated spindle cell lesion and vessels with hyaline walls. (B) Presence of diffuse S-100 staining.

Figure 2. (A) T1-weighted MRI scan with contrast demonstrating the contrast enhanced schwannomas. (B) T1-weighted MRI scan without contrast.

Figure 3. Hyperintense lesions on T2-weighted MRI scan without contrast.

Figure 4. The four-hit, three-step model for tumorigenesis in schwannomatosis (here shown for SMARCB1): germline mutation in SMARCB1 (hit 1), loss of a region of chromosome 22 (hit 2 and 3) and pathogenic mutation in remaining WT NF2 allele (m = pathogenic mutation; + = WT). The same mechanism has also been demonstrated for germline LZTR1 mutations.

Plotkin SR, Blakeley JO, Evans DG, et al. Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria, in. Am J Med Genet 2013;161:405–16.

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Ostrow KL, Donaldson K, Blakeley J, Belzberg A, Hoke A. Immortalized human schwann cell lines derived from tumors of schwannomatosis patients. PLoS ONE 2015;10:e0144620.

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