Skin lesions in neurofibromatosis type 2: diagnostic and prognostic significance of cutaneous (plexiform) schwannomas

Abstract

Background: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied.

Objectives: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity.

Methods: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved.

Results: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque-like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque-like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype-based classes.

Conclusions and relevance: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis.

Figure 1

(a) Deep schwannoma, located on the wrist of a patient with NF2. (b and c) Plaque‐like plexiform schwannoma, defined as soft, slightly raised, roughened lesions with hypertrichosis and a darker colour than the surrounding skin, in a patient with NF2. (d) Plexiform schwannoma characterized by bundles of spindle cells surrounded by a thin fibrous capsule in the superficial dermis. The cells are positive for s‐100. (e) Superficial schwannoma in a patient with NF2. [Colour figure can be viewed at wileyonlinelibrary.com]