Estudio clínico, microscópico y genético de las manifestaciones cutáneas de la neurofibromatosis tipo 2

Abstract

Background: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple benign tumors in the nervous system. NF2 is associated with high morbidity. It is very important to diagnose the disease early in life, specially, in the most serious cases because an early diagnosis favors a better management and improves survival. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied. The main objective in our study is to characterize cutaneous lesions both clinically and histologically, in a cohort of patients with NF2. Secondary objectives of this study are to investigate whether these skin lesions have prognostic value and whether they can be useful in the genetic diagnosis of the disease. Method: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analyzed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset and age at diagnosis, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved. Besides we genetically analyzed material obtained from skin lesions from 7 patients with NF2 searching a constitutional and a somatic mutation NF2 mutation. Results: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analyzed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form they were distributed as follow: 24 patients (48%) had deep schwannomas, 21 (42%) had plaque-like lesions, and 3 patients (6%) had superficial tumors. Histologic examination from 27 lesions analyzed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumors biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumors analyzed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumors. In our cohort, 100% of the patients with plaque-like lesions and superficial tumors 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. Besides, genetic analysis of primary Schwann cell cultures derived from 7 skin plaques (100%) allowed the identification of a constitutional mutation in all of them. Conclusions: Cutaneous lesions, especially plexiform schwannomas, are common in NF2, they usually appear at an early age and their presence is associated with a worst prognosis. Besides, these lesions can be used to genetically diagnose the disease.