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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 U...
September 30, 2016: Journal of Cutaneous Pathology
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
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...
August 5, 2016: Journal of the American Academy of Dermatology
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
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
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
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
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
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
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
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
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
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
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
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
Gerardo Ferrara, Anna Chiara De Vanna
Although conventional histopathological examination is the undisputable mainstay for the diagnosis of melanocytic skin neoplasms, fluorescence in situ hybridization (FISH) has the potential to provide important information to morphologically challenging cases. The standard melanoma FISH test targeting RREB1 (6p25), MYB (6q23), CCND1 (11q13), and centromere 6 is an effective compromise between cost, technical complexity, and sensitivity. The authors use the standard FISH-positivity as a tie-breaker for challenging melanocytic neoplasms mainly in a non-Spitzoid morphologic context because the currently available test leaves several unresolved issues: namely, a relatively low diagnostic accuracy in morphologically ambiguous melanocytic neoplasms; a relatively low sensitivity and specificity in Spitzoid neoplasms; and the occurrence of false positives due to tetraploidy in Spitz nevi and in nevi with an atypical epithelioid component...
April 2016: American Journal of Dermatopathology
Elena Ardini, Maria Menichincheri, Patrizia Banfi, Roberta Bosotti, Cristina De Ponti, Romana Pulci, Dario Ballinari, Marina Ciomei, Gemma Texido, Anna Degrassi, Nilla Avanzi, Nadia Amboldi, Maria Beatrice Saccardo, Daniele Casero, Paolo Orsini, Tiziano Bandiera, Luca Mologni, David Anderson, Ge Wei, Jason Harris, Jean-Michel Vernier, Gang Li, Eduard Felder, Daniele Donati, Antonella Isacchi, Enrico Pesenti, Paola Magnaghi, Arturo Galvani
Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib. More recently, low-frequency rearrangements of TRK kinases have been described in NSCLC, colorectal carcinoma, glioblastoma, and Spitzoid melanoma. Entrectinib, whose discovery and preclinical characterization are reported herein, is a novel, potent inhibitor of ALK, ROS1, and, importantly, of TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins...
April 2016: Molecular Cancer Therapeutics
Gang Wu, Raymond L Barnhill, Seungjae Lee, Yongjin Li, Ying Shao, John Easton, James Dalton, Jinghui Zhang, Alberto Pappo, Armita Bahrami
Kinase activation by chromosomal translocations is a common mechanism that drives tumorigenesis in spitzoid neoplasms. To explore the landscape of fusion transcripts in these tumors, we performed whole-transcriptome sequencing using formalin-fixed, paraffin-embedded (FFPE) tissues in malignant or biologically indeterminate spitzoid tumors from 7 patients (age 2-14 years). RNA sequence libraries enriched for coding regions were prepared and the sequencing was analyzed by a novel assembly-based algorithm designed for detecting complex fusions...
April 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Klaus J Busam, Ricardo E Vilain, Trina Lum, Jonathan A Busam, Travis J Hollmann, Robyn P M Saw, Daniel C Coit, Richard A Scolyer, Thomas Wiesner
A number of common driver mutations have been identified in melanoma, but other genetic or epigenetic aberrations are also likely to play a role in the pathogenesis of melanoma and present potential therapeutic targets. Translocations of the anaplastic lymphoma kinase (ALK), for example, have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK expression. In this study, we sought to determine whether ALK was also expressed in nonspitzoid primary and metastatic cutaneous melanomas...
June 2016: American Journal of Surgical Pathology
Valeria Coco, Francesca Farnetani, Anna Maria Cesinaro, Silvana Ciardo, Giuseppe Argenziano, Ketty Peris, Giovanni Pellacani, Caterina Longo
BACKGROUND: Confocal microscopy is a second-level examination for dermoscopically equivocal melanocytic lesions. However, the number of false-negative cases on confocal microscopy and the scenarios in which confocal microscopy may fail have not been fully elucidated. OBJECTIVE: To calculate the percentage of false-negative melanomas upon reflectance confocal microscopy examination in a large series of cases. METHODS: A retrospective analysis on 201 melanomas, evaluated for dermoscopic/confocal criteria of melanoma, was carried out...
2016: Dermatology: International Journal for Clinical and Investigative Dermatology
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