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. 2018 Mar 1;154(3):341-346.
doi: 10.1001/jamadermatol.2017.5464.

Early Genetic Diagnosis of Neurofibromatosis Type 2 From Skin Plaque Plexiform Schwannomas in Childhood

Elisabeth Castellanos  1 , Adrià Plana  2 , Cristina Carrato  3 , Meritxell Carrió  1 , Inma Rosas  1 , Emilio Amilibia  4 , Francesc Roca-Ribas  4 , Cristina Hostalot  5 , Alicia Castillo  6 , Andrea Ros  6 , Ariadna Quer  3 , Juan Luis Becerra  7 , Hector Salvador  8 , Conxi Lázaro  9 , Ignacio Blanco  6 , Eduard Serra  1 , Isabel Bielsa  2 ; for CSUR Phakomatoses Multidisciplinary Clinics HUGTiP-ICO-IGTP
Affiliations

Early Genetic Diagnosis of Neurofibromatosis Type 2 From Skin Plaque Plexiform Schwannomas in Childhood

Elisabeth Castellanos et al. JAMA Dermatol. .

Erratum in

  • Missing Affiliation.
    [No authors listed] [No authors listed] JAMA Dermatol. 2018 Jul 1;154(7):852. doi: 10.1001/jamadermatol.2018.2294. JAMA Dermatol. 2018. PMID: 29998308 Free PMC article. No abstract available.

Abstract

Importance: Neurofibromatosis type 2 (NF2) is a devastating genetic condition characterized by the development of multiple tumors of the nervous system. An early diagnosis of individuals with NF2 would facilitate treatment and reduction of disease impact because most severe effects of the disease do not usually develop before adolescence. Little attention has traditionally been paid to dermatological signs in NF2. However, skin plaques are commonly seen in patients with NF2, normally appearing either at birth or early childhood, providing an opportunity for early NF2 detection and testing.

Objective: To determine the clinical utility of skin plaque identification and characterization in children for reaching an early diagnosis of patients with NF2 and to evaluate their molecular pathogenesis and their use in the genetic diagnostics of NF2.

Design, setting, and participants: Diagnostic test study by the histological and genetic characterization of skin plaques from patients with NF2. Patients were 7 individuals with NF2 or clinical suspicion of NF2 treated at the Spanish Reference Center on Phakomatoses.

Main outcomes and measures: Histological evaluation of all skin plaques was performed. Fresh skin plaques were cultured to obtain Schwann cells and the NF2 gene was genetically analyzed. For all 7 patients, NF2 clinical history was reviewed.

Results: In all 7 patients (4 male and 3 female), all skin plaques analyzed were histologically characterized as plexiform schwannomas. Genetic analysis of primary Schwann cell cultures derived from them allowed the identification of a constitutional and a somatic NF2 mutation. Genetic testing allowed the early diagnosis of NF2 in a child only exhibiting the presence of skin plaques. Most of the patients with NF2 analyzed had an early presentation of skin plaques and a severe NF2 phenotype.

Conclusions and relevance: This work emphasizes the clinical utility of a careful dermatological inspection and the correct identification of skin plaques in children for an early diagnosis of NF2. We show for the first time that Schwann cells derived from skin plaque plexiform schwannomas bear the double inactivation of the NF2 gene and thus constitute an excellent source of tissue for genetic testing, especially in the context of mosaicism.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Clinical, Histopathological, and Cell Culture Characterization of Skin Plaques
A and B, Macroscopic appearance of a skin plaque from patient 139. C, Histological low-power field view of skin plaque plexiform schwannoma depicted in (A) showing multiple nodules interconnected with each other on hematoxylin-eosin (H&E) staining (original magnification ×40). D, Tumoral nodules within skin plaque showed strong and diffuse S100 positivity by immunostaining (original magnification ×40). E, Microscopic bright-field image of a cell culture from skin plaque plexiform schwannoma depicted in (A) showing fragments of skin plaque nodules (original magnification ×200). F, Microscopic fluorescence image showing S100 immunostaining of the cell culture in (E) exhibiting Schwann cell nature (original magnification ×200). G, Biopsy of skin plaque plexiform schwannoma of patient 403 (original magnification ×40). H, Biopsy of skin plaque plexiform schwannoma of patient 3 (original magnification ×20).
Figure 2.
Figure 2.. Algorithm Describing Clinical Guidelines After Skin Plaque Identification in Children
NF2 indicates neurofibromatosis type 2; NGS, next-generation sequencing.
See this image and copyright information in PMC

References

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