Distinguishing epithelioid blue nevus from blue nevus-like cutaneous melanoma metastasis using fluorescence in situ hybridization
ABSTRACT Blue nevus (BN)-like cutaneous melanoma metastasis is a well-recognized variant of melanoma metastasis. These lesions may clinically and histologically simulate benign blue nevi. The histologic changes may be indistinguishable from conventional blue nevi or epithelioid blue nevi (EBN), a benign dermal-based melanocytic neoplasm with epithelioid morphology and heavily pigmented cytoplasm. Distinguishing BN-like cutaneous melanoma metastasis from benign conventional or EBN is important for staging and treatment. We evaluated a fluorescence in situ hybridization (FISH) assay using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1), and centromere 6 (Cep6) with previously determined criteria, to distinguish EBN and BN-like melanoma metastasis. Ten BN-like cutaneous melanoma metastatic lesions and 10 EBN were blindly evaluated with the above mentioned FISH probes. FISH enumeration and criteria for diagnosis of melanoma was as previously described. Nine of 10 BN-like cutaneous metastatic lesions showed significant aberrations and met previously established criteria for melanoma. None of the EBN cases showed evidence of significant copy number changes or met FISH criteria for a diagnosis of melanoma. FISH is an important diagnostic adjunct for melanocytic neoplasms. In this study, we show that a FISH assay targeting 6p25, 6q23, 11q13, and centromere 6 can distinguish EBN from BN-like metastatic melanoma with high accuracy. The test and the parameters previously established can perform with high sensitivity and specificity when dealing with this differential diagnosis.
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- "2010) A (100% 6/6) (Busam et al. 2010) A (54% 6/11) (Speicher et al. 1994) B (18% 13/74) (Kilic et al. 2006) E 6q- (6% 1/17) (Dalton et al. 2010) A (25% 6/24) (Dalton et al. 2010) A (0% 0/15) (Gerami et al. 2011) A (0% 0/15) (Gerami et al. 2011) A (0% 0/10) (Pouryazdanparast et al. 2009) A (0% 0/12) (Gammon et al. 2011) A (70% 7/10) (Pouryazdanparast et al. 2009) A (60% 3/5) (Gammon et al. 2011) A (0% 0/6) (Busam et al. 2010) A (83% 5/6) (Busam et al. 2010) A (46% 5/11) (Speicher et al. 1994) B (28% 21/74) (Kilic et al. 2006) E (22% 10/44) (Mensink et al. 2008) B +7 (6% 1/17) (Bastian et al. 1999) B (12% 1/8) (Ali et al. 2010) B +9 (9% 1/11) (Speicher et al. 1994) B 9p- (27% 3/11) (Speicher et al. 1994) B (9% 7/74) (Kilic et al. 2006) E +11p (18 % 3/17) (Bastian et al. 1999) B (12% 1/8) (Ali et al. 2010) B +11q13 (6% 1/17) (Dalton et al. 2010) A (42% 10/24) (Dalton et al. 2010) A (0% 0/15) (Gerami et al. 2011) A (33% 5/15) (Gerami et al. 2011) A (0% 0/10) (Pouryazdanparast et al. 2009) A (0% 0/12) (Gammon et al. 2011) A (80% 8/10) (Pouryazdanparast et al. 2009 "
Article: Cytogenetics of Melanoma: A Review[Show abstract] [Hide abstract]
ABSTRACT: Malignant melanoma is an aggressive cutaneous neoplasm whose incidence has continued to increase worldwide. Currently, histopathologic examination of specimens is the gold standard for the diagnosis and categorization of melanoma. Cytogenetic analysis represents a powerful, and currently underused, adjunct to traditional histologic examination in distinguishing nevi and melanomas. Chromosomal studies have shown that malignant melanomas often contain multiple chromosomal alterations, most commonly of chromosomes 1, 6, 7, 9, 10 and 11. These chromosomes often include genes within the MAPK molecular pathway, which is involved in the development and progression of melanoma. Fluorescence in situ hybridization (FISH) can detect a number of recurrent anomalies, and commercially available kits for melanoma detection have been devised. The utility of cytogenetics in melanocytic lesions at certain anatomic sites has been evaluated, including acral lesions, uveal lesions, and lymph node metastases. Recurring cytogenetic anomalies have been defined in various challenging histologic subtypes, such as desmoplastic melanomas and Spitzoid lesions. Cytogenetic analysis may also be used to provide supplementary information in prognostication, particularly in uveal melanomas. We provide a brief review of the molecular pathways found in melanoma and a summary of what is known and remains unknown regarding cytogenetic aberrations associated with malignant melanoma. Keywords: nevus, nodal nevus, blue nevus, cutaneous melanoma, desmoplastic melanoma, uveal melanoma, blue nevus-like melanoma, cytogenetics, FISH, fluorescence in situ hybridizationJournal of the Association of Genetic Technologists 10/2014; 40(4):209-218.
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ABSTRACT: With the advent of genetic and epigenetic research, molecular techniques could someday be used to discriminate nevus from melanoma so that ambiguous melanocytic lesions could be more accurately classified or that prognostication could be improved in melanoma patients. That promised day might be closer than realized. The last 20 years of research in cytogenetic and genetic alterations in melanoma have culminated in defined chromosomal lesions discriminating benign from malignant melanocytic tumors. Exploiting these differences, fluorescence in situ hybridization (FISH) can reproducibly discriminate unequivocal melanomas from melanocytic nevi with high sensitivity and specificity. The discriminating power of FISH in melanocytic tumors with ambiguous histopathology is questionable, however, because there is no standard definition of "malignancy." Additional FISH studies on ambiguous cases are needed through international collaborations where large collections of such cases are shared and the "proof of malignancy" is established by adequate clinical follow-up. This contribution reviews the diagnostic utility of DNA-based FISH technology as it compares the diagnostic accuracy in melanocytic tumors with unambiguous vs ambiguous histopathology. The melanoma epigenome is further characterized through research into various activities of small interfering RNAs, such as microRNAs, providing the pathway for the application of microRNA-based strategies that could be the basis for future diagnostic biomarkers and molecular therapies in melanoma.Clinics in dermatology 05/2013; 31(3):317-23. DOI:10.1016/j.clindermatol.2012.08.007 · 1.93 Impact Factor
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ABSTRACT: This frequency synthesis PLL contains a pulse width detection (PWD) mechanism to measure and compare from cycle to cycle the width of up and down error pulses from a phase and frequency detector (PFD). Correction signals are sent to a digitally controlled oscillator (DCO) only if the phase error is small and increasing or large and not getting smaller. The advantages provided by the PWD and DCO are tolerance to process variations, ease of design and analysis, low bandwidth-to-operating frequency ratio (< 0.005), and deterministic error correction. An on-chip decoupling capacitor in the DCO (1OOpF) filters the supply and substrate noise to minimize jitterSolid-State Circuits Conference, 1997. Digest of Technical Papers. 43rd ISSCC., 1997 IEEE International; 03/1997