The assessment of B-raf proto-oncogene, serine/threonine kinase (
) gene status is now standard practice in patients diagnosed with metastatic melanoma with its presence predicting a clinical ...response to treatment with BRAF inhibitors. The gold standard in determining BRAF status is currently by DNA-based methods. More recently, a BRAF V600E antibody has been developed. We aim to investigate whether immunohistochemical detection of BRAF mutation is a suitable alternative to molecular testing by polymerase chain reaction (PCR).
We assessed the incidence of BRAF mutation in our cohort of 132 patients, as determined by PCR, as well as examining clinical and histopathological features. We investigated the sensitivity and specificity of the anti-BRAF V600E VE1 clone antibody in detecting the presence of the BRAF V600E mutation in 122 cases deemed suitable for testing.
The incidence of BRAF mutation in our cohort was 28.8% (38/132). Patients with the BRAF mutation were found to be significantly younger at age of diagnosis. BRAF-mutated melanomas tended to be thinner and more mitotically active. The antibody showed a sensitivity of 86.1% with a specificity of 96.9%. The positive predictive value was 96.9%; the negative predictive value was 94.4%. The concordance rate between PCR and immunohistochemical BRAF status was 95.1% (116/122).
The rate of BRAF mutation in our cohort (28.8%) was lower than international published rates of 40%-60%. This may reflect ethnic or geographic differences within population cohorts. The high concordance rate of PCR and immunohistochemical methods in determining BRAF status suggests that immunohistochemistry is potentially a viable, cost-effective alternative to PCR testing and suitable as a screening test for the BRAF mutation.
Background
Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these ...tumors. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites.
Methods
Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these cases, paired primary and metastatic specimens were available for polymerase chain reaction (PCR) and immunohistochemical evaluation.
Results
Fifty‐two out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by immunohistochemistry (IHC). In one case, a metastasis and its matched primary were positive by IHC, but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary, and repeat PCR in the metastasis was positive, following macrodissection.
Conclusions
Our results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, IHC provided strong evidence that initial PCR testing had provided a false‐negative result due to low tumor volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumor can be used with confidence.
Measurements and predictions of ambient ozone (O3), planetary boundary layer (PBL) height, the surface energy budget, wind speed, and other meteorological parameters were made near downtown Houston, ...Texas, and were used to investigate meteorological controls on elevated levels of ground‐level O3. Days during the study period (1 April 2009 to 31 December 2010 for measurements and 15 April 2009 to 17 October 2009 for modeled) were classified into low (LO3) and high ozone (HO3) days. The majority of observed high HO3 days occurred in a postfrontal environment. Observations showed there is not a significant difference in daily maximum PBL heights on HO3 and LO3 days. Modeling results showed large differences between maximum PBL heights on HO3 and LO3 days. Nighttime and early morning observed and modeled PBL heights are consistently lower on HO3 days than on LO3 days. The observed spring LO3 days had the most rapid early morning PBL growth (~350 m h−1) while the fall HO3 group had the slowest (~200 m h−1). The predicted maximum average hourly morning PBL growth rates were greater on HO3 (624 m h−1) days than LO3 days (361 m h−1). Observed turbulent mixing parameters were up to 2–3 times weaker on HO3 days, which indicate large‐scale subsidence associated with high‐pressure systems (leading to clear skies and weak winds) substantially suppresses mixing. Lower surface layer ventilation coefficients were present in the morning on HO3 days in the spring and fall, which promotes the accumulation of O3 precursors near the surface.
Key Points
Observed/modeled PBLHs are lower during nighttime/morning on high ozone days
Observed PBL growth rates are lower during early morning on high ozone days
Observed mixing parameters are 2‐3 times weaker on high ozone days
A solitary chest nodule McCarthy, S.; McMenamin, M. E.; Heffron, C. C. B. B. ...
Clinical and experimental dermatology,
August 2019, 2019-Aug, 2019-08-00, 20190801, Letnik:
44, Številka:
6
Journal Article
Recenzirano
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Background
The lupus band test (LBT) is a direct immunofluorescence (DIF) technique which shows a band of localised immunoglobulins at the dermo‐epidermal junction in lesional, non‐sun‐exposed skin ...of patients with both systemic and cutaneous lupus erythematosus (LE), and in perilesional skin of patients with systemic LE. However, low sensitivity and poor concordance between histological and clinical diagnoses warrant a review of the application of the LBT in the diagnosis of LE.
Objectives
To assess the sensitivity and specificity of the LBT in diagnosing LE following clinico‐pathological correlation (CPC).
Methods
All cases sent to our pathology department between 2011 and 2018 for DIF with a clinical query of LE were reviewed. Data collection included demographic details, pathology requests, histology and DIF reports, clinical reports and diagnoses, and serology.
Results
Of 256 histology requests, 9% (n = 23) had a positive LBT. This was discordant with the prevalence of LE diagnosis, as 46.3% were diagnosed with LE following CPC. The sensitivity and specificity of the LBT for LE was 17.6% and 98.8% respectively, with a positive predictive value of 92.9% and negative predictive value of 58.2%.
Conclusion
The LBT is not a sensitive diagnostic test for LE, but is highly specific, and should be considered as a supportive diagnostic tool for LE. This is the largest reported case series evaluating the efficacy of the LBT in the diagnosis of LE.
The lupus band test (LBT) is a direct immunofluorescence (DIF) technique which shows a band of localised immunoglobulins at the dermo‐epidermal junction in lesional, non‐sun‐exposed skin of patients with both systemic and cutaneous lupus erythematosus (LE). In this large review, the sensitivity and specificity of the LBT for LE was 17.6% and 98.8% respectively, with a positive predictive value of 92.9% and negative predictive value of 58.2%. The LBT is not a sensitive diagnostic test for LE, but is highly specific, and should be considered as a supportive diagnostic tool for LE.
Pathologic discordance affecting patient management may approach 20% in melanocytic cases following specialist review. The diagnostic utility of PRAME has been highlighted in several studies but ...interpretative challenges exist including its use in severely dysplastic compound nevi showing progression to melanoma in situ, nevoid melanoma, and coexisting nevi with melanoma. We examine the PRAME status of a broad spectrum of melanocytic lesions including challenging, dysplastic nevi with severe atypia from a large Irish patient cohort. Retrospective review of the dermatopathology database was conducted to evaluate the PRAME staining characteristics of two hundred and twenty-one melanocytic lesions using a commercially available PRAME antibody (EPR20330). The proportion of nuclear labeling and intensity of staining was recorded. The sensitivity and specificity of PRAME for in situ and malignant melanocytic lesions was 77% and 100%, respectively. Virtually all of our melanoma in situ from high-cumulative sun damaged (CSD) skin (22/23) and all acral lentiginous melanoma (5/5) were PRAME positive while 80% (8/10) of our lentigo maligna melanoma showed diffuse expression. None of our benign subgroup showed diffuse immunoexpression (0/82), including thirty-seven moderate or severely dysplastic nevi. In all cases of melanoma in situ arising in association with a dysplastic compound nevus (0/10), no immunoexpression was observed in the nevic component while in five cases of melanoma in situ with coexistent, intradermal nevus immunostaining was confined to the in situ component. A total of 100% (2/2) of desmoplastic melanomas and 50% (4/8) of nodular melanomas were PRAME positive. PRAME is a sensitive and highly specific immunostain in the diagnosis of in situ and invasive melanoma and we emphasize its application in the evaluation of high CSD and acral melanoma subtypes as well as in challenging threshold cases.
A facial nodule McCarthy, S.; Neville, G.; Clover, A. J. P. ...
Clinical and experimental dermatology,
April 2020, 2020-Apr, 2020-04-00, 20200401, Letnik:
45, Številka:
3
Journal Article
Recenzirano
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The density and phenotype of tumour-associated macrophages have been linked with prognosis in a range of solid tumours. While there is strong preclinical evidence that tumour-associated macrophages ...promote aspects of tumour progression, it can be challenging to infer clinical activity from surface markers and ex vivo behaviour. We investigated the association of macrophage infiltration with prognosis and functional changes in the tumour microenvironment in primary human melanoma.
Fifty-seven formalin-fixed, paraffin-embedded primary melanomas were analysed by immunohistochemical analysis of CD68, CD163, inducible nitric oxide synthase (iNOS) and arginase expression. RNA sequencing was performed on serial sections of 20 of the stained tumours to determine the influence of macrophage infiltration on gene expression.
CD68
cells are a functionally active subset of macrophages that are associated with increased iNOS and arginase staining and altered gene expression. In comparison, while there is a greater accumulation of CD163
macrophages in larger tumours, these cells are comparatively inactive, with no association with the level of iNOS or arginase staining, and no effect on gene expression within the tumour. The infiltration of either subset of macrophages did not correlate to overall survival.
Thus, melanomas contain distinct macrophage populations with diverse phenotypes, but with no observable prognostic role.
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