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- W2952665418 abstract "Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Ferris et al., 2018Ferris L. Moy R. Gerami P. Sligh J.E. Jansen B. Yao Z. et al.Non-invasive analysis of high-risk driver mutations and gene expression profiles in primary cutaneous melanoma.J Invest Dermatol. 2018; (pii: S0022-202X:32894)https://doi.org/10.1016/ j.jid.2018.10.041Google Scholar (https://doi.org/10.1016/j.jid.2018.10.041). Detailed answers and a list of relevant references are available following the Quiz Questions below. 1.What is your diagnosis?a.Seborrheic Keratosesb.Dermatofibromac.Melanomad.Nevus Spiluse.Pigmented Basal Cell Carcinoma2.How were the performance metrics of the pigmented lesion assay (PLA) validated in the study?a.The PLA measured the expression of hotspot somatic mutations TERT, NRAS, and BRAF non-V600E and correlated the results to histopathological findingsb.The PLA measured expression of TERT promoter mutations and validated the results against patients with known BRAFV600E mutationsc.The PLA determined expression of LINC and PRAME and correlated the results to histological examination in cohort 2d.The PLA correlated expression of 2 genes, LINC and PRAME, with histology and presence of hotspot somatic mutationse.The PLA correlated expression of TERT, NRAS, and BRAFV600E with hotspot somatic mutations, LINC and PRAME3.As proposed by the authors, which of the following is NOT a way the pigmented lesion assay (PLA) may improve the diagnosis and treatment of primary cutaneous melanoma?a.Histopathological examination is subjective as seen from significant variation in classification of melanocytic lesions, whereas PLA can provide an objective measureb.The PLA has been shown to have high sensitivity in the diagnosis of melanomasc.The PLA can be used as marker for tumors with BRAFV600E mutations and used to guide targeted systemic treatmentsd.The PLA may identify tumors with high malignant potential and aggressive behaviore.The PLA may reduce the number of surgical biopsies performed on benign or low-risk lesions See following pages for detailed answers. 1.What is your diagnosis?CORRECT ANSWER: C. MelanomaMelanomas typically appear as a macule or nodule with asymmetric borders, color variegation, and a large diameter. The ABCDE criteria (asymmetry, border irregularity, color variegation, diameter greater than 6 mm, evolving) may be used to assist in diagnosis, although sensitivity and specificity can vary (Friedman et al., 1985Friedman R.J. Rigel D.S. Kopf A.W. Early detection of malignant melanoma: the role of physician examination and self-examination of the skin.CA Cancer J Clin. 1985; 35: 130-151Crossref PubMed Scopus (648) Google Scholar). The “ugly duckling” sign may also be used to assist in the diagnosis of melanoma where one pigmented lesion is distinctly different from others and should be considered suspicious even if it does not fulfill ABCDE criteria (Grob and Bonerandi, 1998Grob J.J. Bonerandi J.J. The 'ugly duckling' sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening.Arch Dermatol. 1998; 134: 103-104Crossref PubMed Google Scholar). Adjuncts to clinical diagnosis include dermoscopy and other non-invasive tissue analysis techniques. Dermoscopic features include atypical pigment networks, peripheral streaks, and blue-black globules. Other non-invasive tools that aid in diagnosis include reflectance confocal microscopy (RCM) and multispectral imaging. RCM uses a low power laser that reflects off epidermal structures to create a 3D image. Melanin granules are known to have a high refractive index, and areas with an increased concentration of melanin will appear brighter with confocal microscopy (Ferris and Harris, 2012Ferris L.K. Harris R.J. New diagnostic aids for melanoma.Dermatol Clin. 2012; 30: 535-545https://doi.org/10.1016/j.det.2012.04.012Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar). Multispectral imaging can use varying wavelengths of spectral radiation to generate an image for analysis, which can potentially strengthen indications for biopsy (March et al., 2015March J. Hand M. Grossman D. Practical application of new technologies for melanoma diagnosis: part I. Noninvasive approaches.J Am Acad Dermatol. 2015; 72 (quiz 941–22): 929-941https://doi.org/10.1016/j.jaad.2015.02.1138Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar).Discussion of Incorrect Answers:a.Seborrheic Keratoses: Seborrheic keratoses are benign pigmented lesions, which typically appear in the elderly on almost any part of the body. They present as light brown macules that can progress to papules or plaques with a velvety nature that are well-demarcated with a greasy surface. They are often described as having a “stuck on” appearance. Examination with a dermatoscope reveals multiple milia cysts, comedo openings, and fissures in a cerebriform pattern. However, there are often a wide variety of dermoscopic presentations and other non-invasive diagnostic tools, may be beneficial in aiding in diagnosis. RCM allows for noninvasive differentiation of seborrheic keratoses at the cellular level and often shows a regular honeycomb pattern of epidermis that is densely packed into well circumscribed dermal papillae at the dermoepidermal junction (Ahlgrimm-Siess et al., 2013Ahlgrimm-Siess V. Cao T. Oliviero M. Laimer M. Hofmann-Wellenhof R. Rabinovitz H.S. et al.Seborrheic keratosis: reflectance confocal microscopy features and correlation with dermoscopy.J Am Acad Dermatol. 2013; 69: 120-126https://doi.org/10.1016/j.jaad.2012.12.969Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). These findings can be correlated to en face high definition–optical coherent tomography (HD-OCT) findings, which include honeycomb and enlarge interpapillary spaces with edged papillae (Oliveira et al., 2017Oliveira A. Zalaudek I. Arzberger E. Hofmann-Wellenhof R. Seborrhoeic keratosis imaging in high-definition optical coherence tomography, with dermoscopic and reflectance confocal microscopic correlation.J Eur Acad Dermatol Venereol. 2017; 31: e125-e127https://doi.org/10.1111/jdv.13874Google Scholar).b.Dermatofibroma: Dermatofibroma or benign fibrous histiocytoma are mesenchymal tumors. They occur most commonly in women and are often located on the lower extremities. Although they are mostly asymptomatic, they can present with exquisite tenderness and/or itching. Dermatofibromas appear as slow growing solitary nodules with an overlying red-brown hue. A central dimple with lateral compression has been a useful clinical feature for diagnosis (Requena et al., 1994Requena L. Fariña M.C. Fuente C. Piqué E. Olivares M. Martín L. et al.Giant dermatofibroma. A little-known clinical variant of dermatofibroma.J Am Acad Dermatol. 1994; 30: 714-718Abstract Full Text PDF PubMed Scopus (54) Google Scholar). Dermoscopic features include a peripheral delicate pigment network with central scar-like area. Diagnosis of dermatofibromas remains largely based on clinical appearance, but other non-invasive diagnostic tools can be used, including ultrasound imaging and HD-OCT. Ultrasound imaging shows a hypoechoic solid nodule, whereas the most common features with HD-OCT are bright hyper-reflective dermal structures arranged in thick bundles (Picard et al., 2016Picard A. Long-Mira E. Chuah S.Y. Passeron T. Lacour J.P. Bahadoran P. Interest of high-definition optical coherent tomography (HD-OCT) for non-invasive imaging of dermatofibroma: a pilot study.J Eur Acad Dermatol Venereol. 2016; 30: 485-487https://doi.org/10.1111/jdv.12868Google Scholar, Wortsman and Wortsman, 2010Wortsman X. Wortsman J. Clinical usefulness of variable-frequency ultrasound in localized lesions of the skin.J Am Acad Dermatol. 2010; 62: 247-256https://doi.org/10.1016/j.jaad.2009.06.016Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar).d.Nevus Spilus: Nevus spilus or speckled lentiginous nevus is an area of multiple hyperpigmented macules or papules superimposed on a lighter brown patch. Often described as a café-au-lait–like background, they are typically noticed at birth with darker, hyperpigmented spots appearing over time. Nevus spilus can range from lentigines to junctional, compound, and intradermal nevi. On dermoscopy, homogenous brown pigment patterns with focal gray-blue areas, black dots, and black blotches may be observed. Whereas malignant transformation is unlikely, follow up may be warranted. Non-invasive diagnosis using RCM demonstrates dermal papillae demarcated by a rim of bright monomorphous cells corresponding to pigmented keratinocytes and melanocytes (Prodinger et al., 2013Prodinger C. Tatarski R. Laimer M. Ahlgrimm-Siess V. Large congenital nevus spilus-improved follow-up through the use of in vivo reflectance confocal microscopy.Dermatol Pract Concept. 2013; 3: 55-58https://doi.org/10.5826/dpc.0302a08Google Scholar).e.Pigmented Basal Cell Carcinoma: Basal cell carcinoma (BCC) is the most common cancer. Dermoscopic evaluation of pigmented BCCs reveals melanoma-like features including brown-black globules, blue veil-like structures, and nonarborizing telangiectacic vessels. While definitive diagnosis relies on histopathological evaluation, RCM can demonstrate aggregations of tightly packed cells with palisading, cordlike structures (Agero et al., 2006Agero A.L. Busam K.J. Benvenuto-Andrade C. Scope A. Gill M. Marghoob A.A. et al.Reflectance confocal microscopy of pigmented basal cell carcinoma.J Am Acad Dermatol. 2006; 54: 638-643https://doi.org/10.1016/j.jaad.2005.11.1096Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar).2.How were the performance metrics of the pigmented lesion assay (PLA) validated in the study?CORRECT ANSWER: d. The PLA correlated expression of 2 genes (LINC and PRAME) with histology and the presence of hotspot somatic mutationsThe PLA is a noninvasive tool that has been validated against histopathology to rule out melanoma and reduce the need for surgical biopsies of atypical pigmented skin lesions. DNA and RNA are collected using adhesive patches placed on the skin, specifically for the expression of 2 genes, LINC and PRAME. To further validate the PLA, somatic hotspot mutations in genes that are known drivers of melanoma progression (BRAF-nonV600E, NRAS, and TERT) were also analyzed and correlated with PLA results.Discussion of Incorrect Answers:a.The PLA measured the expression of hotspot somatic mutations TERT, NRAS, and BRAF non-V600E and correlated the results to histopathological findings: False. In the study, the PLA measured the expression of LINC and PRAME and correlated the results to histopathological findings and hotspot somatic mutations to validate the non-invasive instrument.b.The PLA measured expression of TERT promoter mutations and validated the results against patients with known BRAFV600E mutations: False. In the study, the PLA measured the expression of LINC and PRAME and correlated the results to histopathological findings and hotspot somatic mutations to validate the non-invasive instrument.c.The PLA determined expression of LINC and PRAME and correlated the results to histological examination in cohort 2: False. Whereas the PLA did determine the expression of LINC and PRAME and correlated the results to histopathological examination in cohort 1, surgical biopsy data from cohort 2 was not available for comparison and therefore, not used in the validation of the PLA.e.The PLA correlated expression of TERT, NRAS, BRAFV600E with hotspot somatic mutations LINC and PRAME: False. In the study, the PLA measured the expression of LINC and PRAME and correlated the results to histopathological findings and hotspot somatic mutations to validate the non-invasive instrument.3.As proposed by the authors, which of the following is NOT a way the pigmented lesion assay (PLA) may improve the diagnosis and treatment of primary cutaneous melanoma?CORRECT ANSWER: c. The PLA can be used as marker for tumors BRAFV600E mutations and used to guide targeted systemic treatmentsIn the study, the PLA was correlated with somatic hotspot mutations including BRAF-nonV600E, NRAS, and TERT. As BRAFV600E mutations are common in benign nevi (Roh et al., 2015Roh M.R. Eliades P. Gupta S. Tsao H. Genetics of melanocytic nevi.Pigment Cell Melanoma Res. 2015; 28: 661-672https://doi.org/10.1111/pcmr.12412Crossref PubMed Scopus (97) Google Scholar), tumors were not interrogated for this specific mutation. To this point, BRAFV600E mutations were present in equal frequencies in melanomas and non-melanoma samples, and thus were not discriminatory. Interestingly, however, BRAFV600K mutations do occur in melanoma, and tumors with this mutation may be responsive to BRAF-inhibitor therapy (Ascierto et al., 2012Ascierto P.A. Kirkwood J.M. Grob J.J. Simeone E. Grimaldi A.M. Maio M. et al.The role of BRAF V600 mutation in melanoma.J Transl Med. 2012; 10: 85https://doi.org/10.1186/1479-5876-10-85Crossref PubMed Scopus (440) Google Scholar).Discussion of Incorrect Answers:a.Histopathological examination is subjective as seen from significant variation in classification of melanocytic lesions, whereas the PLA can provide an objective measure: True. Histological examination has been shown to be subjective and consensus agreement between pathologists is lower than expected (Elmore et al., 2017Elmore J.G. Barnhill R.L. Elder D.E. Longton G.M. Pepe M.S. Reisch L.M. et al.Pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study.BMJ. 2017; 357: j2813https://doi.org/10.1136/bmj.j2813Crossref PubMed Scopus (222) Google Scholar). The PLA may provide an objective measure to assist in diagnosis of melanoma.b.The PLA has been shown to have high sensitivity in the diagnosis of melanomas: True. The PLA, when compared with current standard of histopathological examination, has a lower false negative rate of 9% vs 16%, which translates to a higher sensitivity.d.The PLA may identify tumors with high malignant potential and aggressive behavior: True. In the study, the PLA measurements were correlated to hotspot driver mutations in BRAF-nonV600E, NRAS, and TERT, which have been known to be associated with aggressive tumor behavior, metastasis, and poor prognosis.e.The PLA may reduce the number of surgical biopsies performed on benign or low-risk lesions: True. The PLA has been demonstrated to have a high sensitivity for cutaneous melanoma and may assist in ruling out the diagnosis and thus the need for surgical biopsies of atypical pigmented skin lesions. Jeremy R. Etzkorn is supported by a Career Development Award in Dermatologic Surgery from the Dermatology Foundation." @default.
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- W2952665418 title "Cells to Surgery Quiz: July 2019" @default.
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