title: Skin Biopsy in Netherton Syndrome: A Histological Review of a Large Series and New Findings.
abstract: Netherton syndrome (NS) is a severe genetic skin disorder, with often delayed or misleading clinical signs. The histological features of skin biopsies, usually described as a psoriasiform hyperplasia, have only been reported in isolated case reports or small case series. The aim of this study is to define, for the first time, the precise histological pattern of cutaneous lesions, in a large cohort of skin biopsies from confirmed NS patients. The study included 80 consecutive skin biopsies from 67 patients taken between January 1995 and June 2014. All were from confirmed NS patients with either a negative lympho-epithelial Kazal-type-related inhibitor (LEKTI) immunohistochemistry and/or molecular confirmation by identified mutation in SPINK5. In this cohort, the most frequent histological finding was also psoriasiform hyperplasia, but there were additional, less common, or previously unreported findings, including compact parakeratosis with large nuclei, subcorneum or intracorneum splitting, presence of clear cells in the upper epidermis or stratum corneum, dyskeratosis, dermal infiltrate with neutrophils and/or eosinophils, and dilated blood vessels in the superficial dermis. An early confirmation of the diagnosis of NS is essential for improved patient management. Thus, in the situation of a patient with an unknown skin disorder and non specific clinical presentation, the dermatopathologist may now be able to suggest the diagnosis of NS based on these newly reported characteristics. However, LEKTI immunohistochemistry remains the essential diagnostic investigation in cases with misleading or nonspecific histological features and is mandatory for the definitive diagnosis of NS in all patients.
authors.affiliation: *Dermatopathologist and Dermatologist, Department of Pathology, Hôpital Necker-Enfants Malades, APHP, Paris, France; Reference Center for Rare Cutaneous Diseases MAGEC, Hôpital Necker-Enfants Malades, APHP, Paris, France; Department of Dermatology, Hôpital Necker-Enfants Malades, APHP, Paris, France; †Head of the Department of Dermatology, Department of Pathology, Hôpital Necker-Enfants Malades, APHP, Paris, France; Reference Center for Rare Cutaneous Diseases MAGEC, Hôpital Necker-Enfants Malades, APHP, Paris, France; University Paris Descartes-Sorbonne Paris Cité, Paris, France; ‡Researcher, University Paris Descartes-Sorbonne Paris Cité, Paris, France; INSERM UMR 1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France; §Senior Consultant in Dermatology, Department of Pathology, Hôpital Necker-Enfants Malades, APHP, Paris, France; Reference Center for Rare Cutaneous Diseases MAGEC, Hôpital Necker-Enfants Malades, APHP, Paris, France; University Paris Descartes-Sorbonne Paris Cité, Paris, France; ¶Dermatologist, Department of Pathology, Hôpital Necker-Enfants Malades, APHP, Paris, France; Reference Center for Rare Cutaneous Diseases MAGEC, Hôpital Necker-Enfants Malades, APHP, Paris, France; ‖Head of the Department of Pediatric Dermatology, University Children's Hospital Zürich and University Hospital Zürich, Zürich, Switzerland; **Senior Dermatologist, Department of Dermatology, Hôpital Fournier, Nancy, France; ††Medical Doctor, Department of Dermatology, MAGEC, Hôpital Saint Louis, APHP, Paris, France; ‡‡Assistant Professor, Department of Pathology, Hôpital Henri Mondor, APHP, Paris, France; §§Head of the Department of Pathology, Hôpital Necker-Enfants Malades, APHP, Paris, France; University Paris Descartes-Sorbonne Paris Cité, Paris, France; ¶¶Professor of Genetics, University Paris Descartes-Sorbonne Paris Cité, Paris, France; Director of Genetic Skin Disease Laboratory, INSERM UMR 1163, Laboratory o
authors.forename: Stephanie
authors.initials: S
authors.lastname: Leclerc-Mercier
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.forename: Laetitia
authors.initials: L
authors.lastname: Furio
authors.forename: Smail
authors.initials: S
authors.lastname: Hadj-Rabia
authors.forename: Laetitia
authors.initials: L
authors.lastname: de Peufeilhoux
authors.forename: Lisa
authors.initials: L
authors.lastname: Weibel
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Bursztejn
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bourrat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Thierry Jo
authors.initials: TJ
authors.lastname: Molina
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009154:Mutation; D056770:Netherton Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D012867:Skin / Q000737:chemistry / Q000473:pathology*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5