Two Cases of Insulin-Derived Amyloidosis With Acanthosis Nigricans-Like Changes.

ABSTRACT: Insulin-derived amyloidosis (AIns) is a rare iatrogenic subtype of cutaneous amyloidosis occurring at frequent insulin injection sites. Here, we describe 2 cases of AIns accompanied by acanthosis nigricans (AN)-like changes, a rare finding which has been reported fewer than 5 times in the literature. We also report the first case of an AIns nodule being misdiagnosed as a keloid. Both of our patients presented with asymptomatic, hyperkeratotic, pigmented plaques at frequent insulin injection sites, and histopathologic examination showed (1) nodular aggregates of amyloid demonstrating apple-green birefringence with Congo red staining and (2) AN-like features, such as epidermal papillomatosis, hyperkeratosis, and hyperpigmentation. Accurate diagnosis of AIns is crucial, because repeated insulin injection into a nodule can impair glycemic control. However, misdiagnosis is common, as observed with our second patient, whose AIns nodule was misdiagnosed by an outside provider as a keloid, perhaps because of the presence of AN-like features. Our case report adds to the limited but growing body of literature on AIns and significantly increases the number of reported cases of AIns with AN-like features, an even rarer phenomenon.

Lichen striatus colocalized with a Spitz nevus.

A 7-year-old healthy girl presented with an 11-month history of an asymptomatic red, dome-shaped papule on her right medial elbow and 6-month history of linearly distributed, few millimeter, flesh-colored papules extending from and including the red papule. Histopathology demonstrated features of both a Spitz nevus and lichen striatus. The Spitz nevus was removed with a punch biopsy and the lichen striatus subsequently resolved. To our knowledge, co-localization of a Spitz nevus with lichen striatus has not been previously reported and highlights the potential association between the immunogenicity of Spitz nevi and the development of lichen striatus.

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function.

A growing number of gene-centric studies have highlighted the emerging significance of lncRNAs in cancer. However, these studies primarily focus on a single cancer type. Therefore, we conducted a pan-cancer analysis of lncRNAs comparing tumor and matched normal expression levels using RNA-Seq data from ∼ 3,000 patients in 8 solid tumor types. While the majority of differentially expressed lncRNAs display tissue-specific expression we discovered 229 lncRNAs with outlier or differential expression across multiple cancers, which we refer to as 'onco-lncRNAs'. Due to their consistent altered expression, we hypothesize that these onco-lncRNAs may have conserved oncogenic and tumor suppressive functions across cancers. To address this, we associated the onco-lncRNAs in biological processes based on their co-expressed protein coding genes. To validate our predictions, we experimentally confirmed cell growth dependence of 2 novel oncogenic lncRNAs, onco-lncRNA-3 and onco-lncRNA-12, and a previously identified lncRNA CCAT1. Overall, we discovered lncRNAs that may have broad oncogenic and tumor suppressor roles that could significantly advance our understanding of cancer lncRNA biology.

Endothelin-1 and α-melanocortin have redundant effects on global genome repair in UV-irradiated human melanocytes despite distinct signaling pathways.

Human melanocyte homeostasis is sustained by paracrine factors that reduce the genotoxic effects of ultraviolet radiation (UV), the major etiological factor for melanoma. The keratinocyte-derived endothelin-1 (End-1) and α-melanocyte-stimulating hormone (α-MSH) regulate human melanocyte function, proliferation and survival, and enhance repair of UV-induced DNA photoproducts by binding to the Gq - and Gi -protein-coupled endothelin B receptor (EDNRB), and the Gs -protein-coupled melanocortin 1 receptor (MC1R), respectively. We hereby report that End-1 and α-MSH regulate common effectors of the DNA damage response to UV, despite distinct signaling pathways. Both factors activate the two DNA damage sensors ataxia telangiectasia and Rad3-related and ataxia telangiectasia mutated, enhance DNA damage recognition by reducing soluble nuclear and chromatin-bound DNA damage binding protein 2, and increase total and chromatin-bound xeroderma pigmentosum (XP) C. Additionally, α-MSH and End-1 increase total levels and chromatin localization of the damage verification protein XPA, and the levels of γH2AX, which facilitates recruitment of DNA repair proteins to DNA lesions. Activation of EDNRB compensates for MC1R loss of function, thereby reducing the risk of malignant transformation of these vulnerable melanocytes. Therefore, MC1R and EDNRB signaling pathways represent redundant mechanisms that inhibit the genotoxic effects of UV and melanomagenesis.

Partial Rescue of Ocular Pigment Cells and Structure by Inducible Ectopic Expression of Mitf-M in MITF-Deficient Mice.

Purpose: Complete deficiency of microphthalmia transcription factor (MITF) in Mitfmi-vga9/mi-vga9 mice is associated with microphthalmia, retinal dysplasia, and albinism. We investigated the ability of dopachrome tautomerase (DCT) promoter-mediated inducible ectopic expression of Mitf-M to rescue these phenotypic abnormalities. Methods: A new mouse line was created with doxycycline-inducible ectopic Mitf-M expression on an Mitf-deficient Mitfmi-vga9 background (DMV mouse). Adult DMV mice were phenotypically characterized and tissues were collected for histology, immunohistochemistry, and evaluation of Mitf, pigmentary genes, and retinal pigment epithelium (RPE) gene expression. Results: Ectopic Mitf-M expression was specifically induced in the eyes, but was not detected in the skin of DMV mice. Inducible expression of Mitf-M partially rescued the microphthalmia, RPE structure, and pigmentation as well as a subset of the choroidal and iris melanocytes but not cutaneous melanocytes. RPE function and vision were not restored in the DMV mice. Conclusions: Ectopic expression of Mitf-M during development of Mitf-deficient mice is capable of partially rescuing ocular and retinal structures and uveal melanocytes. These findings provide novel information about the roles of Mitf isoforms in the development of mouse eyes.