Differences in dermoscopic findings between early and mature clear cell acanthoma.

Clear cell acanthoma (CCA) is a rare benign epidermal tumor that is difficult to diagnose by visual inspection. Conversely, its diagnosis by dermoscopy is relatively easy owing to the characteristic serpiginous arrangement of coiled vessels, sometimes described as the "string-of-pearls" formation. However, in few published reports, the dermoscopic diagnosis of mature CCA has been reported. Here, we report the histopathological and detailed dermoscopic findings of two CCA cases. Between these, one case was of early (~6 months) CCA exhibiting the characteristic vascular string-of-pearls formation, whereas the other was of a more mature (~10 years) CCA; although the latter case showed combined thick and thin white intersecting lines with large coiled vessels and/or red clods, it had the string-of-pearls formation. Thus, regardless of CCA maturity, the string-of-pearls formation was present. We propose that the combination of combined thick and thin white intersecting lines along with the vascular string-of-pearls formation reflecting large coiled vessels and/or red clods on dermoscopy is a diagnostic clue to mature CCA.

Glucagonoma With Necrolytic Migratory Erythema: Metabolic Profile and Detection of Biallelic Inactivation of DAXX Gene.

Context: Necrolytic migratory erythema (NME) occurs in approximately 70% of patients with glucagonoma syndrome. Excessive stimulation of metabolic pathways by hyperglucagonemia, which leads to hypoaminoacidemia, contributes to NME pathogenesis. However, the molecular pathogenesis of glucagonoma and relationships between metabolic abnormalities and clinical symptoms remain unclear. Patient: A 53-year-old woman was referred to our hospital with a generalized rash and weight loss. NME was diagnosed by histopathological examination of skin biopsy tissue. Laboratory tests revealed diabetes, hyperglucagonemia, marked insulin resistance, severe hypoaminoacidemia, ketosis, and anemia. Enhanced computed tomography scans detected a 29-mm pancreatic hypervascular tumor, which was eventually diagnosed as glucagonoma. Preoperative treatment with octreotide long-acting release reduced the glucagon level, improved the amino acid profile, and produced NME remission. Surgical tumor excision normalized the metabolic status and led to remission of symptoms, including NME. Interventions: Whole-exome sequencing (WES) and subsequent targeted capture sequencing, followed by Sanger sequencing and pyrosequencing, identified biallelic alteration of death-domain associated protein (DAXX) with a combination of loss of heterozygosity and frameshift mutations (c.553_554del:p.R185fs and c.1884dupC:p.C629fs) in the glucagonoma. Consistently, immunohistochemistry confirmed near-absence of DAXX staining in the tumor cells. Tumor expression of glucagon and somatostatin receptor subtype 2 and 3 messenger RNA was markedly upregulated. Conclusions: This is a report of glucagonoma with biallelic inactivation of DAXX determined by WES. The tumor manifested as glucagonoma syndrome with generalized NME. This case showed the relationship between hypoaminoacidemia and NME status. Further investigations are required to elucidate the underlying mechanisms of NME onset and glucagonoma tumorigenesis.