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https://www.readbyqxmd.com/read/27892929/a-review-of-kinase-fusions-in-melanocytic-tumors
#1
Sara C Shalin
Translocations resulting in a kinase fusion are well reported in many tumor types and indeed can be defining, particularly in the case of hematopoietic malignancies. The recent reports of multiple protein kinase fusions within melanocytic neoplasms, particularly in those with spitzoid morphology, have heralded a new era of classification of these melanocytic tumors. Seen within approximately half of all spitzoid neoplasms and present within the full spectrum of benign, atypical, and malignant lesions, kinase fusions likely represent an early oncogenic event contributing to cell proliferation and growth...
November 28, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27874206/spitz-nevi-and-other-spitzoid-neoplasms-in-children-overview-of-incidence-data-and-diagnostic-criteria
#2
REVIEW
Emi Dika, Giulia Maria Ravaioli, Pier Alessandro Fanti, Iria Neri, Annalisa Patrizi
Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or spindle melanocytes or both. In some rare cases their presentation overlaps with the clinical and histopathologic features of malignant melanoma, so a differential diagnosis can be difficult to make. Intermediate forms between Spitz nevi and malignant melanoma, with unpredictable behavior, have been called atypical Spitz tumors. A literature search was performed to review the clinical, dermoscopic, genetic, and histopathologic aspects of spitzoid tumors...
November 22, 2016: Pediatric Dermatology
https://www.readbyqxmd.com/read/27862191/significance-of-epidermal-mitoses-in-challenging-melanocytic-proliferations
#3
Eugen C Minca, Steven D Billings, Paul Elson, Michael T Tetzlaff, Aleodor A Andea, Jennifer S Ko
BACKGROUND: Accurate diagnosis of melanoma remains histologically challenging. Dermal mitoses support malignancy, but are only occasionally seen in melanomas. Since melanomagenesis is thought to begin at the dermal-epidermal junction, we investigated the significance of epidermal melanocytic mitoses (EM) in a spectrum of lesions with molecular characterization. METHODS: EM density (EMD) was evaluated in 46 straightforward lesions (24 benign, 22 malignant) and 30 challenging lesions with expert interpretation, fluorescence-in-situ-hybridization, and myPath-score characterization (12 favor-benign, 9 favor-malignant, 9 ambiguous)...
November 15, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27860221/spitz-nevi-diverse-clinical-dermatoscopic-and-histopathological-features-in-childhood
#4
Emi Dika, Iria Neri, Pier Alessandro Fanti, Alessia Barisani, Giulia Maria Ravaioli, Annalisa Patrizi
BACKGROUND AND OBJECTIVES: The characterization of clinical features and biological potential of Spitz nevi has attracted a lot of interest in past decades. The aim of our paper was to describe the clinical, dermatoscopic features as well as the clinical outcome of surgically excised Spitz nevi in three different pediatric age groups. PATIENTS AND METHODS: A retrospective study analyzing clinical features, videodermatoscopic images, histopathological diagnosis and patient outcome...
November 10, 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27776007/a-comparison-of-morphologic-and-molecular-features-of-braf-alk-and-ntrk1-fusion-spitzoid-neoplasms
#5
Sapna M Amin, Alexandra M Haugh, Christina Y Lee, Bin Zhang, Jeffrey A Bubley, Emily A Merkel, Anna Elisa Verzì, Pedram Gerami
Recent studies have identified translocations involving the kinase domains of ALK, NTRK1, BRAF, RET, and ROS in spitzoid neoplasms. Subsequent studies have also characterized morphologic features corresponding to ALK and NTRK1 translocations. In this study, we sought to further compare morphologic features across a range of 49 genetically defined spitzoid neoplasms with ALK, NTRK1, BRAF, or RET fusions to determine discriminating features. We also compared them with a group of 22 spitzoid neoplasms, which were confirmed to be negative for fusions in ALK, NTRK1, BRAF, and RET...
October 21, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27686456/the-utilization-of-spitz-related-nomenclature-in-the-histological-interpretation-of-cutaneous-melanocytic-lesions-by-practicing-pathologists-results-from-the-m-path-study
#6
Ge Zhao, Kachiu C Lee, Sue Peacock, Lisa M Reisch, Stevan R Knezevich, David E Elder, Michael W Piepkorn, Joann G Elmore, Raymond L Barnhill
BACKGROUND: Spitz nevi, atypical Spitz tumors and spitzoid melanomas ('spitzoid lesions') represent controversial and poorly understood cutaneous melanocytic lesions that are difficult to diagnose histologically. It is unknown how these terms are used by pathologists. METHODS: We describe use of Spitz-related terminology using data from the Melanoma Pathology (M-Path) study database comprising pathologists' interpretations of biopsy slides, a nation-wide study evaluating practicing US pathologists' (N = 187) diagnoses of melanocytic lesions (8976 independent diagnostic assessments on 240 total test cases, with 1 slide per case)...
September 30, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27569296/loss-of-p16-expression-and-copy-number-changes-of-cdkn2a-in-a-spectrum-of-spitzoid-melanocytic-lesions
#7
Paul W Harms, Thomas L Hocker, Lili Zhao, May P Chan, Aleodor A Andea, Min Wang, Kelly L Harms, Michael L Wang, Shannon Carskadon, Nallasivam Palanisamy, Douglas R Fullen
Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status...
August 25, 2016: Human Pathology
https://www.readbyqxmd.com/read/27502312/imaging-mass-spectrometry-assists-in-the-classification-of-diagnostically-challenging-atypical-spitzoid-neoplasms
#8
Rossitza Lazova, Erin H Seeley, Heinz Kutzner, Richard A Scolyer, Glynis Scott, Lorenzo Cerroni, Isabella Fried, Milena E Kozovska, Arlene S Rosenberg, Victor G Prieto, Bahig M Shehata, Megan M Durham, Gina Henry, Jose L Rodriguez-Peralto, Erica Riveiro-Falkenbach, Jochen T Schaefer, Richard Danialan, Sylvie Fraitag, Sonja Vollenweider-Roten, Alireza Sepehr, Martin Sangueza, Nouf Hijazi, Yamile Corredoira, Rachel Kowal, Olga M Harris, Francisco Bravo, Alan S Boyd, Ralitza Gueorguieva, Richard M Caprioli
BACKGROUND: Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas. OBJECTIVE: We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior. METHODS: We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS...
December 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27469124/classification-of-indeterminate-melanocytic-lesions-by-microrna-profiling
#9
Nicholas Latchana, Sara E Martin Del Campo, Valerie P Grignol, Jennifer R Clark, Scott P Albert, Jie Zhang, Lai Wei, Jennifer H Aldrink, Kathleen K Nicol, Mark A Ranalli, Sara B Peters, Alejandro Gru, Prashant Trihka, Philip R O Payne, J Harrison Howard, William E Carson
PURPOSE: Identification of indeterminate melanocytic skin lesions capable of neoplastic progression is suboptimal and may potentially result in unnecessary morbidity from surgery. MicroRNAs (miRs) may be useful in classifying indeterminate Spitz tumors as having high or low risk for malignant behavior. METHODS: RNA was extracted from paraffin-embedded tissues of benign nevi, benign Spitz tumors, indeterminate Spitz tumors, and Spitzoid melanomas in adults (n = 62) and children (n = 28)...
July 28, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27391457/atypical-spitzoid-neoplasms-in-childhood-a-molecular-and-outcome-study
#10
Christina Y Lee, Lauren M Sholl, Bin Zhang, Emily A Merkel, Sapna M Amin, Joan Guitart, Pedram Gerami
The natural history of atypical Spitz neoplasms remains poorly understood, resulting in significant patient and clinician anxiety. We sought to better characterize outcomes that correlated with molecular features by performing a prospective cohort study of pediatric atypical spitzoid neoplasms in which fluorescence in situ hybridization studies were obtained for diagnosis. Cases with sufficient tissue underwent additional retrospective assessment for translocations in ALK, NTRK1, BRAF, RET, and ROS1. Among 246 total patients assessed, 13% had a positive fluorescence in situ hybridization result...
July 7, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27348579/cutaneous-malignant-melanoma-in-children-and-adolescents-treated-in-pediatric-oncology-units
#11
Yves Réguerre, Marie Vittaz, Daniel Orbach, Caroline Robert, Christine Bodemer, Christina Mateus, Dominique Plantaz, Emmanuel Plouvier, Patrick Lutz, Josue Rakotonjanahary, Sylvie Fraitag, Ludovic Martin
OBJECTIVES: Recent progress in the understanding of tumor biology and new targeted therapies has led to improved survival in adults with malignant melanoma (MM). MM is rare in children, especially before puberty. We report here our experience with pediatric patients with MM, describe the clinical presentation, treatment and evolution, and compare prepubescent and postpubescent disease. METHODS: A retrospective, descriptive, national multicenter study was undertaken of 52 cases of MM in children and adolescents...
November 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27256160/ros1-fusions-in-cancer-a-review
#12
Arnaud Uguen, Marc De Braekeleer
The ROS1 gene belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. A literature review identified a ROS1 fusion in 2.54% of the patients with lung adenocarcinoma and even higher frequencies in spitzoid neoplasms and inflammatory myofibroblastic tumors. At present, 26 genes were found to fuse with ROS1, some of them already known to fuse with RET and ALK. All the fusion proteins retain the ROS1 kinase domain, but rarely its transmembrane domain. Most of the partners have dimerization domains that are retained in the fusion, presumably leading to constitutive ROS1 tyrosine kinase activation...
August 2016: Future Oncology
https://www.readbyqxmd.com/read/27222771/time-to-reconsider-spitzoid-neoplasms
#13
REVIEW
Carmelo Urso
BACKGROUND: Spitzoid neoplasms may pose significant diagnostic problems because in a fraction of them it is quite difficult or impossible to establish if they are benign or malignant lesions. An extraordinarily large number of studies have been made in attempts to solve this problem; regrettably, the histological criteria proposed and the various special sophisticated techniques employed have proven to be ineffective in making this distinction with confidence. OBJECTIVES: To explore the possible causes for this diagnostic failure and an attempt to identify the source of this problem...
April 2016: Dermatology Practical & Conceptual
https://www.readbyqxmd.com/read/27173829/differential-diagnosis-of-spitzoid-melanocytic-neoplasms
#14
REVIEW
C Stefanaki, K Stefanaki, L Chardalias, E Soura, A Stratigos
Atypical Spitzoid neoplasms represent a controversial and incompletely defined diagnostic category for lesions with intermediate architecture and cytomorphology between Spitz nevus and melanoma. The vast majority of these neoplasms have a good overall prognosis. Only a small proportion of patients will end up developing distant metastases and death. The distinction between Spitz tumours with atypical features and Spitzoid melanoma remains difficult on clinical and histological grounds and the prediction of the biological behaviour of those tumours even with sentinel lymph node biopsy is impossible...
August 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27152444/immunohistochemical-evaluation-of-p16-expression-in-cutaneous-histiocytic-fibrohistiocytic-and-undifferentiated-lesions
#15
Emily H Smith, Lori Lowe, Paul W Harms, Douglas R Fullen, May P Chan
BACKGROUND: Expression of p16 is frequently evaluated in melanocytic lesions. Expression of p16 in cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions has not been well characterized. METHODS: We evaluated p16 expression in a cohort of histiocytic (reticulohistiocytoma, Langerhans cell histiocytosis, xanthogranuloma, Rosai Dorfman disease and xanthoma), fibrohistiocytic (dermatofibroma, epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans) and undifferentiated (atypical fibroxanthoma and pleomorphic undifferentiated sarcoma) lesions...
August 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27102343/a-diagnostic-algorithm-for-atypical-spitzoid-tumors-guidelines-for-immunohistochemical-and-molecular-assessment
#16
Jeong Hee Cho-Vega
Atypical spitzoid tumors are a morphologically diverse group of rare melanocytic lesions most frequently seen in children and young adults. As atypical spitzoid tumors bear striking resemblance to Spitz nevus and spitzoid melanomas clinically and histopathologically, it is crucial to determine its malignant potential and predict its clinical behavior. To date, many researchers have attempted to differentiate atypical spitzoid tumors from unequivocal melanomas based on morphological, immonohistochemical, and molecular diagnostic differences...
July 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27062047/teledermoscopy-in-doubtful-melanocytic-lesions-is-it-really-useful
#17
Vincenzo de Giorgi, Alessia Gori, Imma Savarese, Antonietta D'Errico, Marta Grazzini, Federica Papi, Vincenza Maio, Piero Covarelli, Carmelo Urso, Daniela Massi
INTRODUCTION: The diagnosis of cutaneous pigmented lesions remains a challenge for both dermatologists and pathologists. Our aim was to determine the diagnostic concordance between the conventional face-to-face diagnosis and the telediagnosis of 10 dermatologists with expertise in dermato-oncology of 10 challenging pigmented lesions. METHODS: Using a store-and-forward teledermatology method, clinical and dermoscopic digital images of all selected lesions were transmitted via e-mail to 10 dermatologists...
October 2016: International Journal of Dermatology
https://www.readbyqxmd.com/read/27020388/paediatric-melanoma
#18
Benjamin A Wood
Cutaneous melanoma occurs only rarely in children under 10 years of age. Mimics of melanoma, including Spitz naevi and proliferative nodules in congenital melanocytic naevi are much more frequent in this age group. Melanoma arising in congenital melanocytic naevus is uncommon, but can show aggressive behaviour. Although spitzoid lesions constitute the majority of 'diagnostically challenging' cases, they are an uncommon cause of mortality in this age group. Among lesions with undoubted metastatic potential, there are biologically distinct tumours which differ significantly in behaviour from the common types of melanoma seen in adults...
February 2016: Pathology
https://www.readbyqxmd.com/read/27020384/genomic-aberrations-in-spitzoid-melanocytic-tumours-and-their-implications-for-diagnosis-prognosis-and-therapy
#19
Thomas Wiesner, Heinz Kutzner, Lorenzo Cerroni, Martin C Mihm, Klaus J Busam, Rajmohan Murali
Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas common acquired naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET...
February 2016: Pathology
https://www.readbyqxmd.com/read/26999339/clinical-follow-up-of-atypical-spitzoid-tumors-analyzed-by-fluorescence-in-situ-hybridization
#20
Genevieve L Egnatios, Tammie C Ferringer
Many neoplasms with spitzoid features remain enigmatic, especially those with intermediate grade features or "atypical spitzoid tumors" (ASTs). Fluorescence in situ hybridization (FISH) has emerged as a complementary technique to conventional microscopy, with certain chromosomal patterns conveying diagnostic information. In this study, we examined 36 ASTs analyzed by FISH for specific abnormalities in chromosomes 6, 9, and 11. Aberrations were detected in 11 cases, 7 of which met FISH criteria for spitzoid melanoma...
April 2016: American Journal of Dermatopathology
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