Harlequin ichthyosis: neonatal management and identification of a new ABCA12 mutation.

A case of harlequin ichthyosis with compound heterozygous mutations in ABCA12 was successfully managed with intensive neonatal care and endotracheal intubation and without oral retinoids. The individual's appearance improved dramatically during hospitalization and at discharge resembled congenital ichthyosiform erythroderma.

Deep learning-aided decision support for diagnosis of skin disease across skin tones.

Although advances in deep learning systems for image-based medical diagnosis demonstrate their potential to augment clinical decision-making, the effectiveness of physician-machine partnerships remains an open question, in part because physicians and algorithms are both susceptible to systematic errors, especially for diagnosis of underrepresented populations. Here we present results from a large-scale digital experiment involving board-certified dermatologists (n = 389) and primary-care physicians (n = 459) from 39 countries to evaluate the accuracy of diagnoses submitted by physicians in a store-and-forward teledermatology simulation. In this experiment, physicians were presented with 364 images spanning 46 skin diseases and asked to submit up to four differential diagnoses. Specialists and generalists achieved diagnostic accuracies of 38% and 19%, respectively, but both specialists and generalists were four percentage points less accurate for the diagnosis of images of dark skin as compared to light skin. Fair deep learning system decision support improved the diagnostic accuracy of both specialists and generalists by more than 33%, but exacerbated the gap in the diagnostic accuracy of generalists across skin tones. These results demonstrate that well-designed physician-machine partnerships can enhance the diagnostic accuracy of physicians, illustrating that success in improving overall diagnostic accuracy does not necessarily address bias.

Coexistence of patch stage mycosis fungoides and interstitial granuloma annulare in the same patient: a pitfall in the clinicopathologic diagnosis of mycosis fungoides.

Several clinical and histopathologic variants of mycosis fungoides (MF) have been well described, including the often elusive interstitial MF. Differentiation from other inflammatory disorders, such as interstitial granuloma annulare (GA) and inflammatory morphea, may be extremely difficult. We report a case of MF and GA coexisting in a 54-year-old woman who initially presented to clinic in 2000 with slightly scaly patches on the trunk and extremities, histopathologically diagnostic of MF. A second biopsy taken a few months later revealed an interstitial infiltrate that was initially interpreted as interstitial MF. Over the following 10 years, additional biopsies revealed features of conventional MF. In 2009, a new biopsy showed unequivocal features of interstitial GA. Reevaluation of the original biopsy, diagnostic of "interstitial MF," revealed that this, too, could be better classified as interstitial GA than interstitial MF. Our case illustrates that MF and interstitial GA may coexist simultaneously, thus representing a pitfall in the histopathologic diagnosis of MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret GA as interstitial MF.

Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers.

PURPOSE: CLIC4, a member of a family of intracellular chloride channels, is regulated by p53, c-Myc, and tumor necrosis factor-alpha. Regulation by factors involved in cancer pathogenesis, together with the previously shown proapoptotic activity of CLIC4, suggests that the protein may have a tumor suppressor function. To address this possibility, we characterized the expression profile, subcellular localization, and gene integrity of CLIC4 in human cancers and determined the functional consequences of CLIC4 expression in tumor epithelium and stromal cells. EXPERIMENTAL DESIGN: CLIC4 expression profiles were analyzed by genomics, proteomics, bioinformatics, and tissue microarrays. CLIC4 expression, as a consequence of crosstalk between stroma and epithelium, was tested in vitro by coculture of breast epithelial tumor cells and normal fibroblasts, and the functional consequences of CLIC4 expression was tested in vivo in xenografts of human breast tumor cell lines reconstituted with CLIC4 or mixed with fibroblasts that overexpress CLIC4 transgenically. RESULTS: In cDNA arrays of matched human normal and tumor tissues, CLIC4 expression was reduced in renal, ovarian, and breast cancers. However, CLIC4 protein levels were variable in tumor lysate arrays. Transcript sequences of CLIC4 from the human expressed sequence tag database and manual sequencing of cDNA from 60 human cancer cell lines (NCI60) failed to reveal deletion or mutations in the CLIC4 gene. On matched tissue arrays, CLIC4 was predominantly nuclear in normal human epithelial tissues but not cancers. With advancing malignant progression, CLIC4 staining became undetectable in tumor cells, but expression increased in stromal cells coincident with up-regulation of alpha-smooth muscle actin, suggesting that CLIC4 is up-regulated in myofibroblasts. Coculture of cancer cells and fibroblasts induced the expression of both CLIC4 and alpha-smooth muscle actin in fibroblasts adjacent to tumor nests. Introduction of CLIC4 or nuclear targeted CLIC4 via adenovirus into human breast cancer xenografts inhibited tumor growth, whereas overexpression of CLIC4 in stromal cells of xenografts enhanced tumor growth. CONCLUSION: Loss of CLIC4 in tumor cells and gain in tumor stroma is common to many human cancers and marks malignant progression. Up-regulation of CLIC4 in tumor stroma is coincident with myofibroblast conversion, generally a poor prognostic indicator. Reactivation and restoration of CLIC4 in tumor cells or the converse in tumor stromal cells could provide a novel approach to inhibit tumor growth.

Transvitreal optic neurotomy for nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To evaluate the role of transvitreal optic neurotomy in the treatment of nonarteritic anterior ischemic optic neuropathy, a scleral outlet compartment syndrome, in which neurovascular compression at the prelaminar and laminar regions of the optic nerve head may play a major role. METHODS: Seven eyes of seven selected patients with severe vision loss (<20/800) from nonarteritic anterior ischemic optic neuropathy underwent transvitreal nasal radial optic neurotomy. The study was not masked and not randomized. Visual acuity and visual fields, when possible, were measured, and fluorescein angiography was performed preoperatively and postoperatively. RESULTS: Four male and three female patients had a mean age of 52.4 years; five had bilateral disease. The mean follow-up was 13 +/- 7 weeks. Mean preoperative visual acuity was 20/2400; mean postoperative visual acuity was 20/250, with an average of 10 lines of improvement. Six of seven patients showed visual improvement. One patient had peripapillary choroidal neovascularization. In two patients with sufficient visual acuity, preoperative visual fields could be obtained; these patients showed significant improvement in postoperative perimetry. Five patients had some loss of vision, which made it impossible to obtain preoperative visual fields. CONCLUSION: Relaxation of the scleral ring of the prelaminar and laminar regions of the optic nerve head reduces constriction and may prevent necrosis of salvageable but underperfused nerve fibers. Despite improvement of visual acuity in our patients, transvitreal optic neurotomy should be considered experimental, requiring a randomized clinical trial.