Functional skin barrier requires sphingolipid homeostasis; 3-ketodihydrosphingosine reductase or KDSR is a key enzyme of sphingolipid anabolism catalyzing the reduction of 3-ketodihydrosphingosine to sphinganine. Biallelic mutations in the KDSR gene may cause erythrokeratoderma variabilis et progressive-4, later specified as PERIOPTER syndrome, emphasizing a characteristic periorifical and ptychotropic erythrokeratoderma. We report another patient with compound heterozygous mutations in KDSR, born with generalized harlequin ichthyosis, which progressed into palmoplantar keratoderma. To determine whether patient-associated KDSR mutations lead to KDSR substrate accumulation and/or unrecognized sphingolipid downstream products in stratum corneum (SC), we analyzed lipids of this and previously published patients with non-identical biallelic mutations in KDSR. In SC of both patients, we identified 'hitherto' unobserved skin ceramides with an unusual keto-type sphingoid base in lesional and non-lesional areas, which accounted for up to 10% of the measured ceramide species. Furthermore, an overall shorter mean chain length of free and bound sphingoid bases was observed-shorter mean chain length of free sphingoid bases was also observed in lesional psoriasis vulgaris SC, but not generally in lesional atopic dermatitis SC. Formation of keto-type ceramides is probably due to a bottle neck in metabolic flux through KDSR and a bypass by ceramide synthases, which highlights the importance of tight intermediate regulation during sphingolipid anabolism and reveals substrate deprivation as potential therapy.

• MeSH
• atopická dermatitida * MeSH
• ceramidy metabolismus   MeSH
• epidermis metabolismus   MeSH
• ichtyóza * MeSH
• lidé MeSH
• mutace MeSH
• oxidoreduktasy metabolismus   MeSH
• palmoplantární hyperkeratóza * genetika   MeSH
• sfingolipidy genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ceramidy MeSH
• oxidoreduktasy MeSH
• sfingolipidy MeSH

We present the case of a 35-year-old man who developed a follicular differentiated cutaneous carcinoma with an eosinophil-rich infiltrate and an aggressive clinical behavior. After an in-depth histopathological investigation the diagnosis of trichoblastic carcinoma was made. Over the course of the disease the patient developed a cutaneous in-transit metastasis as well as an axillary lymph node metastasis 18 months after the excision of the primary tumor on his back. Based on a literature review we discuss the different concepts behind the term "trichoblastic carcinoma" and we summarize the clinical and histological details of previously reported cases. Furthermore, we focus on the phenomenon of tumor-associated eosinophilia.

• Klíčová slova
• eosinophil-rich infiltrate, follicular neoplasm, trichoblastic carcinoma,
• MeSH
• dospělí MeSH
• karcinom patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• nádory kůže patologie   MeSH
• nemoci vlasů patologie   MeSH
• vlasový folikul patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH