Aim-To investigate whether immunohistochemical staining for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) is useful in distinguishing Merkel cell carcinomas (MCCs) from metastatic small cell carcinomas (SCCs). Methods-Eleven cases of MCC and 10 of lung SCC were stained for CK20 and TTF-1. Results-Ten of 11 MCCs stained with the antibody to CK20. None was positive for TTF-1. No SCC stained with anti-CK20 and all stained strongly with anti-TTF-1. Conclusions-The use of both anti-CK20 and anti-TTF-1 can reliably distinguish between MCC and metastatic SCC, thus avoiding the need for a detailed clinical investigation of patients with MCC in whom metastatic SCC must be excluded. (J Clin Pathol 2001;54:727-729)
Summary
Background
The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high‐risk stage I tumour subsets.
Objectives
To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma.
Methods
Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas.
Results
Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7‐year disease‐free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi‐quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low‐risk group (n = 239) vs. 85·4% in the AMLo high‐risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69–9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93–9·56; P = 0·068) in stage IB patients.
Conclusions
Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high‐risk tumour subsets independently of Breslow depth.
What's already known about this topic?
There is an unmet clinical need for biomarkers of early‐stage melanoma.
Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor.
Loricrin is a marker of epidermal terminal differentiation.
What does this study add?
AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation.
The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth.
What is the translational message?
The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow‐up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.
Introduction Gallstone disease is treated commonly with cholecystectomy. Malignant disease of the gallbladder may present similarly and has a poor prognosis. It is common for cholecystectomy specimens to be sent for histological examination to exclude malignancy. However, the incidence of incidental gallbladder carcinoma (IGBC) is low and it has therefore been suggested that macroscopic inspection of the gallbladder by the surgeon, followed by selective histological examination of abnormal specimens, may be safe and cost saving. Methods All cholecystectomies performed between 1 May 2003 and 1 September 2009 were identified from clinical coding. Pathology records were used to identify gallbladder malignancies; these were searched manually to identify IGBC. Pathology reports and case notes were cross-referenced to determine whether there were macroscopic abnormalities present. Annual cost savings were estimated by comparing the number of gallbladder specimens over one year (May 2013 – April 2014) with the total number of cholecystectomies performed in that time. Results Of 4,776 cholecystectomies identified, 12 (0.25%) were cases of IGBC. These cases had a higher median age (68 vs 54 years, p<0.001) and a higher proportion were emergency operations (50% vs 12%, p<0.001). All cases had some form of macroscopic abnormality, most commonly wall thickening (n=6, 50%). Only two cases (17%) had a visible tumour present. Conclusions All cases of IGBC in this study had a macroscopically abnormal gallbladder. Our findings suggest it is safe to adopt a selective approach to histological examination. Savings of almost £20,500 per annum have been achieved.
The aim of this study was to assess bone heating caused by the passage of fine (<2 mm) K-wires of different types. Stainless steel K-wires of trocar and diamond point configurations (0.8-2.0 mm) were drilled into the metatarsal bones from a freshly amputated lower limb at a constant force. Temperature measurements were made by miniature thermocouples inserted into the bones, at 3 second intervals over a period of 3 minutes while each K-wire was drilled three times. The temperature reached varied with the tip configurations and the diameter of the K-wires. Regardless of point configuration, thinner wires generated more heat than thicker ones.
Background. We conducted a re-audit of the surgical practice of UK dermatologists for the treatment of nonmelanoma skin cancer and examined changes with reference to our previous audit in 2014. The audit was supplemented by a detailed assessment of completeness of the histopathology reports for each tumour. Methods. UK dermatologists collected data on 10 consecutive nonmicrographic excisions for basal cell carcinoma (BCC) and 5 for squamous cell carcinoma (SCC). Data were collected on site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins. Results. In total, 222 responses were received from 135 centres, reporting on 3290 excisions. Excisions from the head and neck accounted for 56.7% of cases. Tumour diameter (mean AE SD) was 11.4 AE SD 7.1 mm (maximum size 100 mm) and 97% of cases were primary excisions. BCCs and SCCs respectively accounted for 65.7% and 26.8% of total cases. Of the suspected BCCs and SCCs, 95.8% and 80.4%, respectively, were confirmed histologically. All margins for any tumour were clear in 97.0% of cases, and complication rate in the audit was < 1%. Of the 2864 histology reports evaluated, only 706 (24.6%) contained all core data items; 95% of these were structure (synoptic) reports. Commonly omitted items were level of invasion, risk and T stage, which were absent from 35.7%, 64.2% and 44.1% of reports, respectively. Conclusions. Diagnostic accuracy and complete excision rates remain high. Complication rates may be under-reported owing to lack of follow-up. Histopathology reporting has a greater chance of being complete if reports are generated on a fieldbased platform (synoptic reporting).
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