Subungual Exostosis Presenting as a Pyogenic Granuloma-like Lesion with Reactive Myofibroblastic Proliferation in Two Young Women.

Subungual exostosis (SE) is a well-recognised benign proliferation of the distal phalanx most often seen in young adults and affecting the big toe. Possible triggers include previous trauma and chronic irritation or infection. We describe two atypical cases of SE in two young women presenting with pyogenic granuloma-like lesions clinically. Diagnostic biopsies were performed to confirm the diagnosis and excluded amelanotic melanoma. However, histology unexpectedly revealed reactive myofibroblastic proliferations mimicking nodular fasciitis overlying the SE. Given the atypical clinical presentation, the diagnosis was initially missed or not considered in both patients. They highlight two important points; the first is that SEs may present with pyogenic granuloma-like lesions clinically and that histological analysis is then required to exclude malignancy, particularly amelanotic melanoma. Secondly, that the histology will show a reactive myofibroblastic proliferation and if the sample is relatively superficial and pathologists are not aware of this potential reaction pattern, the underlying diagnosis of SE may be missed.

Genome-Wide Analysis of Circulating Cell-Free DNA Copy Number Detects Active Melanoma and Predicts Survival.

BACKGROUND: A substantial number of melanoma patients develop local or metastatic recurrence, and early detection of these is vital to maximise benefit from new therapies such as inhibitors of BRAF and MEK, or immune checkpoints. This study explored the use of novel DNA copy-number profiles in circulating cell-free DNA (cfDNA) as a potential biomarker of active disease and survival. PATIENTS AND METHODS: Melanoma patients were recruited from oncology and dermatology clinics in Sheffield, UK, and cfDNA was isolated from stored blood plasma. Using low-coverage whole-genome sequencing, we created copy-number profiles from cfDNA from 83 melanoma patients, 44 of whom had active disease. We used scoring algorithms to summarize copy-number aberrations and investigated their utility in multivariable logistic and Cox regression analyses. RESULTS: The copy-number aberration score (CNAS) was a good discriminator of active disease (odds ratio, 3.1; 95% CI, 1.5-6.2; P = 0.002), and CNAS above or below the 75th percentile remained a significant discriminator in multivariable analysis for active disease (P = 0.019, with area under ROC curve of 0.90). Additionally, mortality was higher in those with CNASs above the 75th percentile than in those with lower scores (HR, 3.4; 95% CI, 1.5-7.9; P = 0.005), adjusting for stage of disease, disease status (active or resected), BRAF status, and cfDNA concentration. CONCLUSIONS: This study demonstrates the potential of a de novo approach utilizing copy-number profiling of cfDNA as a biomarker of active disease and survival in melanoma. Longitudinal analysis of copy-number profiles as an early marker of relapsed disease is warranted.

WITHDRAWN: Defining In Vivo Mucosal Inflammatory Activity Using Laser Scanning Confocal Endomicroscopy in Human Ulcerative Colitis.

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Chromoscopic endomicroscopy: in vivo cellular resolution imaging of the colorectum.

Advances in imaging technology and engineering have now permitted functional integration of a confocal endomicroscope into the distal tip of a conventional video colonoscope enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. For the first time, the endoscopist is now able to resolve the surface and subsurface mucosa at cellular resolution in vivo and in real time. A new era in endoscopic imaging has therefore begun - histoendoscopy. In addition to providing a high-accuracy in vivo optical biopsy tool for the differentiation between benign hyperplasia, intra-epithelial neoplasia and carcinoma in sporadic cohorts, endomicroscopy with targeted biopsies has now been shown to increase the yield of intra-epithelial neoplasia complicating ulcerative colitis. Furthermore, recent data examining endomicroscopic molecular ex vivo imaging using anti-CD44v6 antibody has identified aberrant crypt foci based on their surface molecular expression. Receptor overexpression in vivo in humans may, in the near future, be exploited for the diagnosis of inflammation, neoplasia and in predicting targeted molecular therapy. Endomicroscopy will be key to this immuno-imaging interface. Within the present review, we discuss the current clinical evidence in support of confocal endomicroscopy and explore the new diagnostic possibilities for this technology.

Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.

BACKGROUND: Resection of an adenoma-like mass (ALM) in chronic ulcerative colitis (CUC) complicated by mucosal fibrosis has historically not been technically feasible. Endoscopic submucosal dissection techniques may now provide a therapeutic tool enabling the division of submucosal fibrotic scarring, hence enabling endoluminal resection for the first time in this select patient group. The aim was prospective evaluation of endoscopic submucosal dissection-assisted (ESD) resection of flat, sessile, and lateral spreading tumors in CUC complicated by submucosal desmoplasis. Clinical endpoints were postresection recurrence rates, R0 resection status, and complications. METHODS: ESD-assisted endoscopic mucosal resection (EMR) using the Olympus KD-630L insulation-tipped knife was performed on selected lesions. RESULTS: Sixty-nine patients met inclusion criteria, of which 2 were excluded due to follow-up default. En bloc resection was performed in 52/67 (78%) cases with 15/67 (7%) requiring a piecemeal approach. R0 resection was achieved in 49/52 (94%) of lesions undergoing en bloc resection (perforation rate 2/67 [3%]). Bleeding complications occurred in 7/67 (10%) of cases. No metachronous circumscribed intraepithelial neoplastic lesions or cancer was detected at follow-up. At a median of 18 months follow-up, overall cure rates for the ESD-assisted EMR cohort was 66/67 (98%). CONCLUSIONS: We have shown for the first time that endoscopic resection of ALM even in the presence of complicating mucosal fibrosis is technically achievable using a combined ESD-assisted EMR technique. In an appropriately selected cohort, this technique may provide a technically feasible and clinically acceptable therapy where otherwise colectomy would be required.

Confocal endomicroscopy in ulcerative colitis: differentiating dysplasia-associated lesional mass and adenoma-like mass.

BACKGROUND & AIMS: The management of dysplasia-associated lesional mass (DALM) and adenoma-like mass (ALM) in chronic ulcerative colitis (CUC) differs radically, involving total pan-proctocolectomy vs endoscopic resection and surveillance. Such lesions cannot be reliably differentiated using conventional colonoscopy. Confocal laser scanning imaging enables in vivo surface and subsurface cellular resolution imaging during ongoing video endoscopy. The aim of this study was to prospectively assess the clinical applicability and predictive power of the Pentax EC3870K endomicroscope for the in vivo differentiation of ALM and DALM in CUC during ongoing videocolonoscopy. METHODS: Patients were recruited who had a diagnosis of ALM or DALM within the previous 16 weeks. Confocal laser endomicroscopic (CLE) imaging of the circumscribed lesion and 4 adjacent mucosal segments was performed. Targeted biopsy with and without tissue sampling with endoscopic mucosal resection was performed and compared with conventional histopathology as the gold standard. RESULTS: Thirty-six patients with 36 lesions fulfilled the study entry criteria. Using modified Mainz criteria for the in vivo diagnosis of ALM and DALM, the kappa coefficient of agreement between CLE and histopathologic evaluation was 0.91, and accuracy was 97% (95% confidence interval = 86%-99%). CONCLUSIONS: This is the first study addressing the novel application of the Pentax EC3870K endomicroscopy system for the in vivo differentiation of ALM and DALM during ongoing video colonoscopy in CUC. We have shown that ALM and DALM can be differentiated with a high overall accuracy, enabling the safe selection of patients suitable for endoluminal resection versus immediate referral for pan-proctocolectomy.