A Unique Pattern of Dyskeratosis Characterizes Epidermolytic Hyperkeratosis and Epidermolytic Palmoplantar Keratoderma

Abstract

Hereditary skin diseases that are characterized ultrastructurally by intracellular clumpings of keratin tonofilaments, such as Darier disease and Ichthyosis Hystrix of Curth-Macklin, display epidermal dyskeratosis also histologically. Epidermolytic hyperkeratosis (EHK) and epidermolytic palmoplantar keratoderma (Voerner type) (EPPK) are 2 types of autosomal dominant keratodermas, which are also characterized ultrastructurally by intracellular clumpings of tonofilaments but usually without a clear description of histological dyskeratosis. The main aim of the present study was to characterize the histologic signs of keratin aggregation and clumping in the involved epidermis of EHK and EPPK. Two cases of EHK caused by KRT1 mutations and 4 cases of EPPK caused by KRT9 mutations were studied. The biopsies were obtained mostly from the involved skin of the palm. All 6 biopsies were studied histologically, and 4 biopsies (2 EHKs and 2 EPPKs) were also studied ultrastructurally. All 6 cases displayed the characteristic histological epidermolytic changes. In addition, intracytoplasmic and perinuclear eosinophilic homogenizations and round to oval eosinophilic inclusions were identified with varying frequencies in the involved epidermis of all 6 cases. These findings, which were more prominent in the EHK cases, corresponded most likely to the intracytoplasmic aggregates of tonofilaments and to the large round to oval dense clumps of tonofilaments, which were observed ultrastructurally. In conclusion, varying degrees of dyskeratosis are frequently present in EHK and EPPK and should be considered to be a histological characteristic of these disorders.

Disadhesion of epidermal keratinocytes: A histologic clue to palmoplantar keratodermas caused by DSG1 mutations

“…The eosinophilic condensations might represent perinuclear clumpings of keratin tonofilaments as a result of a dominantnegative effect of the altered keratin 16 and 17 filaments. This phenomenon has been observed in inherited autosomal keratin disorders such as epidermolysis bullosa Dowling-Meara and epidermolytic hyperkeratosis, 3,25 in which the mutated keratin filament is believed to form an abnormal complex with the wild-type keratin filament. Ultrastructural examination of a family with pachyonychia type I associated with a KRT16 mutation revealed keratin filaments that were greatly condensed but did not form the dense amorphous aggregates seen in a number of other keratin disorders.…”

“…There are a few exceptions such as epidermolytic PPK caused by mutations in KRT9 encoding keratin 9, in which the characteristic epidermolytic changes in the malpighian cell layer are prominent and may lead to a specific diagnosis. [1][2][3] Recent developments in molecular genetics have enabled regrouping of various entities and syndromes leading to more precise histopathologic classifications. 4 Keratosis palmoplantaris striata (KPS) is a rare autosomal-dominant form of PPK characterized by linear hyperkeratotic streaks along the volar surface of the fingers, and focal keratoderma of the soles.…”

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…In combination with characteristic features, routine histology can give an important clue for IV 213,214 or EI. 52,61,62,215,216 However, one should consider that a reduced or absent SG suggestive for IV can also be seen in acquired ichthyosis, NS, Refsum syndrome, TTDs, or Conradi-Hünermann-Happle syndrome. Hair mounts can demonstrate bamboo hairs (trichorrhexis invaginata) in NS 123 ; although not invariably present, bamboo hairs are pathognomonic of this disorder.…”

Dermatopathology and molecular genetics

“…Dyskeratosis in the form of intracytoplasmic eosinophilic inclusions and homogenizations as a result of intracellular keratin aggregation and clumping have been also demonstrated in epidermolytic hyperkeratosis and epidermolytic palmoplantar keratoderma (EPPK). 9 Epidermolytic hyperkeratosis is caused by KRT1 and KRT10 mutations and EPPK by KRT9 mutations. Hence, dyskeratosis may be a valuable clue to KRT mutations, which lead to keratin destabilization and clumpings.…”