Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases (original) (raw)
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The American Journal of Surgical Pathology, 2012
The diagnosis of certain melanocytic proliferations remains one of the most challenging areas in pathology. In recent times, fluorescence in situ hybridization (FISH) has emerged as a promising diagnostic aid to conventional microscopy. We previously showed that a 4-probe FISH assay targeting 6p25 (RREB1), 6q23 (MYB), Cep6 (centromere 6), and 11q13 (CCND1) could discriminate between histologically unequivocal melanomas and benign nevi with a sensitivity of 86.7% and specificity of 95.4%. However, the sensitivity of the assay is approximately 70% in melanomas with spitzoid morphology. Furthermore, differentiating true gains from tetraploidy may cause difficulties in interpretation by inexperienced examiners. Here we refine the current probe set to better target spitzoid melanomas and more easily distinguish cells with imbalanced copy number aberrations from tetraploid cells. Using FISH data from 3 training sets of 322 tumors, including 152 melanomas and 170 nevi, we identified 9p21, 6p25, 11q13, and 8q24 as a probe set with improved discriminatory power in differentiating melanomas from nevi. In a validation set of 51 melanomas and 51 nevi this probe set had a sensitivity of 94% and specificity of 98%, compared with the original probe set that had a sensitivity of 75% and specificity of 96% in the same validation cohort. We propose that by incorporating 9p21 into the 4-probe FISH assay, with a new diagnostic algorithm, this new probe set would have improved discriminatory power in melanocytic neoplasms and improved sensitivity for detecting spitzoid melanomas, as demonstrated by our previous studies.
FISH as an effective diagnostic tool for the management of challenging melanocytic lesions
Diagnostic pathology, 2011
The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions. A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens. Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9...
The American Journal of Surgical Pathology, 2010
With the increase in sentinel lymph node biopsies in melanoma patients, pathologists are frequently confronted with small deposits of morphologically bland melanocytes in the node, which occasionally cannot be readily classified as benign nodal nevi or melanoma. As most melanomas harbor characteristic chromosomal aberrations which can be used to distinguish it from benign nevi, we used fluorescence in-situ hybridization (FISH) with markers for three regions on chromosome 6 and one on chromosome 11 to determine the presence of chromosomal aberrations in sentinel lymph node specimens with small foci of melanocytes that had been diagnosed as metastatic melanoma or nodal nevi by histopathology. 59 tissue samples from 41 patients (24 lymph node metastases, 17 with nodal nevi, and 18 of the available corresponding primary melanomas) were analyzed by FISH. 20 of 24 (83%) cases diagnosed as metastatic melanoma showed aberrations by FISH. Of the four negative cases, three were unequivocal melanoma metastases, while one on re-review was histopathologically equivocal. Of the 17 nodal nevi one (6%) also showed aberrations by FISH, while the remainder were negative. Multiple aberrations were present in the positive case, some of which were also found in the corresponding primary tumor, identifying this case as a deceptively bland melanoma metastasis that had been misclassified by histomorphology. Our data indicate that FISH is a useful adjunct tool to traditional methods in the diagnostic workup of deposits of melanocytes in the lymph node that are histopathologically ambiguous.
Modern Pathology, 2010
Recently, initial studies describing the use of multicolor fluorescence in situ hybridization (FISH) for classifying melanocytic skin lesions have been published demonstrating a high sensitivity and specificity in discriminating melanomas from nevi. However, the majority of these studies included neither histologically ambiguous lesions nor a clinical long-term follow up. This study was undertaken to validate a special multicolor FISH test in histologically ambiguous melanocytic skin lesions with known clinical long-term follow up. FISH was scored by three independent pathologists in a series of 22 melanocytic skin lesions, including 12 ambiguous cases using four probes targeting chromosome 6p25, centromere 6, 6q23, and 11q13. The FISH results were compared with array comparative genomic hybridization data and correlated to the clinical long-term follow up (mean: 65 months). Pair-wise comparison between the interpretations of the observers showed a moderate to substantial agreement (j 0.47-0.61). Comparing the FISH results with the clinical behavior reached an overall sensitivity of 60% and a specificity of 50% (v 2 ¼ 0.25; P ¼ 0.61) for later development of metastases. Comparison of array comparative genomic hybridization data with FISH analyses did not yield significant results but array comparative genomic hybridization data demonstrated that melanocytic skin lesions with the development of metastases showed significantly more chromosomal aberrations (Po0.01) compared with melanocytic skin lesions without the development of metastases. The FISH technique with its present composition of locus-specific probes for RREB1/MYB and CCND1 did not achieve a clinically useful sensitivity and specificity. However, a reassessment of the probes and better standardization of the method may lead to a valuable diagnostic tool.
Osmangazi Journal of Medicine, 2021
Melanocytic nevus (MN) may on occasion be difficult to distinguish from malignant melanoma (MM) histopathologically. Fluorescent in situ hybridization (FISH) has been demonstrated to be of use for the diagnosis of melanocytic neoplasms of the skin. In this study, the effectiveness of the standart melanoma FISH test (4-way probe targeting RREB1, CCND1, MYB genes and centro-mere 6) and additionally probes, targetting EGFR, TP53, MDM2 and P16 genes, in differentiating melanomas from melanocytic nevi were investigated. Standard FISH test was performed on 24 MM and 24 MN samples, but EGFR, TP53, MDM2 and TP53 gene copy numbers were investigated in 16 of 24 MM and 24 MN using FISH method. The incidence of FISH-detected positive genomic copy aberrations (4-way probe, and others) was determined as 83,3% in 24 MM cases, and 5,2% in 24 MN. Statistically significant differences were found between the MM and MN groups in terms of CCND1, RREB1, EGFR amplifications (p<0.001, p<0.05, p<0.05), but there was no association between histopathological features and detected abnormalities (p>0,05). In additionally , all 5 acral lentiginous melanomas, could be analysed, had EGFR amplifications. In conclusion, CCND1, RREB1, and EGFR amplifications have diagnostic significance for MM. The FISH test is very effective in terms of its use as an adjunct to histopatho-logical methods. But centromere controlled probes should be used to avoid false positive results.
Limitations of Histopathologic Analysis in the Recognition of Melanoma
Archives of Dermatology, 2005
A Plea for a Combined Diagnostic Approach of Histopathologic and Dermoscopic Evaluation T HE ARTICLE PUBLISHED BY SKVARA ET AL 1 IN this issue of the ARCHIVES focuses on the limitations of dermoscopy in the diagnosis of very early and mainly featureless melanomas. The authors report that baseline dermoscopic patterns of 262 melanocytic nevi did not differ from those of 63 melanomas observed by digital dermoscopy and finally excised because of changes overtime. The authors wisely foresee that this basically featureless or "feature-poor" group of melanomas will be used by both sides in the digital dermoscopy controversy: proponents will cite them as evidence that follow-up with digital dermoscopy is necessary; opponents point to them as evidence that dermoscopy is unnecessary and that every clinically suspicious lesion must be excised. The authors acknowledge the strengths and limitations of both views, but the question remains whether dermoscopically featureless or feature-poor lesions warrant excision.
Histopathology, 2012
Fluorescence in situ hybridization for the differential diagnosis between Spitz naevus and spitzoid melanoma Aims: The differential diagnosis between Spitz naevus and spitzoid melanoma can be extremely difficult, or even impossible. In recent years, many attempts have been made to find specific histopathological or immunohistochemical markers, although none has proved successful. Because the prognosis and treatment of each are very different, it is important to distinguish between these entities. We evaluated the ability of the fluorescence in situ hybridization (FISH) assay-designed to detect the copy number of the RREB1 (6p25), MYB (6q23) and CCND1 (11q13) genes and of centromere 6 (Cep 6)-in order to distinguish between Spitz naevus and spitzoid melanoma.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016
Melanoma accounts for most skin cancer-related deaths and has an increasing incidence. Accurate diagnosis and distinction from atypical nevi can be at times difficult using light microscopy alone. Fluorescence in situ hybridization (FISH) and melanoma gene expression score (myPath, Myriad Genetics) have emerged as ancillary tools to further aid in this differential diagnosis. Our aim in this study was to correlate FISH results, gene expression score, consensus histopathologic impression and clinical outcome on a series of 117 challenging melanocytic lesions collected from three separate institutions. The lesions were separated into two groups: 39 histopathologically unequivocal lesions (15 malignant, 24 benign) and 78 challenging lesions interpreted by expert consensus (27 favor malignant, 30 favor benign, and 21 ambiguous). Melanoma-FISH was performed using probes for 6p25, 11q13, 8q24, and 9p21/CEP9 and scored according to established criteria. Analysis by myPath gene expression s...