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Katharina Wiedemeyer, Antonio Guadagno, Jonathan Davey, Thomas Brenn
Spitz nevi on acral sites are rare and poorly documented. The combination of Spitzoid cytomorphology and atypical architectural features of the junctional component may lead to an erroneous diagnosis of melanoma. To study the clinicopthologic and immunohistochemical features, 50 Spitz nevi localized on the distal extremities were retrieved from departmental files. Clinical data and follow-up were obtained and the histologic features were analyzed. P16 and P21 immunohistochemical staining of the dermal component was compared with that of 10 acral lentiginous melanomas and 10 acral nevi...
March 13, 2018: American Journal of Surgical Pathology
Masakazu Fujimoto, Yuki Togashi, Ibu Matsuzaki, Satoko Baba, Kengo Takeuchi, Yutaka Inaba, Masatoshi Jinnin, Shin-Ichi Murata
Frequent kinase fusions have been reported in spitzoid neoplasms, approximately 10% of which involve ALK rearrangements. Herein, we report a case of atypical Spitz tumour (AST) with a novel MLPH-ALK fusion, which has not been previously reported to contribute to cancer development. The tumour was detected in the right arm of a 40-year-old woman. The novel ALK fusion was identified by a 5'-rapid amplification of cDNA ends-based system optimised for formalin-fixed paraffin-embedded tissue. Initially, ALK expression was detected by immunohistochemistry (IHC) using 5A4 antibodies for both sensitive and conventional polymer detection method...
March 4, 2018: Human Pathology
Carolina Martinez Ciarpaglini, Jose Gonzalez, Beatriz Sanchez, Jaime Agusti, Lara Navarro, Gema Nieto, Carlos Monteagudo
AIMS: The risk assessment of spitzoid lesions is one of the most difficult challenges in dermatopathology practice. In this regard, the loss of p16 expression and the homozygous deletion of CDKN2A, have been pointed in the literature as reliable indicators of high risk. However, these findings are poorly reproducible, and the molecular bases underlying the loss of p16 expression remain unclear. We aimed to identify the underlying events causing loss of CDKN2A/p16 in spitzoid tumors. MATERIALS AND METHODS: We evaluated the immunohistochemical expression of p16, and the presence of CDKN2A genetic alterations detected through fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA), in a series of 130 Spitz nevi, 20 atypical spitzoid tumors, and 11 spitzoid melanoma...
February 27, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Lindsay McCORMACK, Elena B Hawryluk
Pediatric melanoma is a rare disease that affects approximately 6 out of every one million children and accounts for 1-4 percent of all melanomas. This article reviews the epidemiology, etiology, diagnosis, treatment and prognosis of pediatric melanoma - with particular attention to recent updates in the literature. While awareness of melanoma increases among the general population, recent data suggest stable and even declining incidence rates among certain pediatric populations. Studies have examined clinical features and presentations of melanoma among the pediatric population and the conventional ABCDE criteria used to diagnosis adult melanoma may not be entirely appropriate for pediatric melanoma; as such, additional pediatric-ABCD and CUP criteria have been proposed...
February 26, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Emilie Perron, Daniel Pissaloux, Angela Neub, Daniel Hohl, Marie Dominique Tartar, Laurent Mortier, Laurent Alberti, Arnaud de la Fouchardiere
The current classification of melanocytic tumors includes clinical, pathological, and molecular data. A subset of lesions remains difficult to classify according to these complex multilayer schemes. We report two cases of deeply infiltrating melanomas with a sclerosing background. The first case occurred on the back of a middle-aged man appearing clinically as a dermatofibroma. The architectural and cytological aspects resembled those of a desmoplastic melanoma but the strong expression of both melanA and HMB45, two stainings usually reported as negative in this entity, raised the question of an alternate diagnosis...
February 21, 2018: Virchows Archiv: An International Journal of Pathology
Marloes Sophia van Kester, Celine Eggen, Auke Beishuizen, Nicole Ariane Kukutsch
No abstract text is available yet for this article.
February 5, 2018: Australasian Journal of Dermatology
V Papageorgiou, Z Apalla, E Sotiriou, C Papageorgiou, E Lazaridou, S Vakirlis, D Ioannides, A Lallas
Dermoscopy has been documented to increase the diagnostic accuracy of clinicians evaluating skin tumors, improving their ability to detect skin cancer and better recognize benign moles. However, dermoscopically "false positive" and "false negative" tumors do exist. False positive diagnosis usually leads to unnecessary excisions. False negative diagnosis is much more dangerous, since it might result in overlooking a cancer, with severe undesirable consequences for the patient and the physician. Therefore, management strategies should mainly focus on addressing the risk of dermoscopically false negative tumors...
January 5, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Anna Eisenstein, Izabela P Panova, Hye J Chung, Lynne J Goldberg, Qing Zhang, Rossitza Lazova, Jag Bhawan, Klaus J Busam, James T Symanowski, Rhoda M Alani, Byungwoo Ryu
There is a significant need for the development of diagnostic tools that can precisely distinguish Spitz nevi and spitzoid melanomas. Here, we report the development of a PCR-based quantitative diagnostic assay for spitzoid melanocytic lesions utilizing the expression ratio of neuropilin-2 and melan-A genes in primary tumor specimens. We find that the expression ratio of neuropilin-2/melan-A is significantly increased in spitzoid melanomas compared with Spitz nevi. The diagnostic potential of this quantitative assay was validated in two independent sets of patient samples as demonstrated in a receiver operating characteristic curve analysis showing an area under the curve value of 91...
February 2018: Melanoma Research
Amin A Hedayat, Konstantinos Linos, Hou-Sung Jung, Laura J Tafe, Shaofeng Yan, Robert E LeBlanc, Joel A Lefferts
Histopathology is the gold standard for diagnosing melanocytic lesions; however, distinguishing benign versus malignant is not always clear histologically. Single nucleotide polymorphism (SNP) microarray analysis may help in making a definitive diagnosis. Here, we share our experience with the Oncoscan FFPE Assay and demonstrate its diagnostic utility in the context of ambiguous melanocytic lesions. Eleven archival melanocytic lesions, including three benign nevi, four melanomas, three BAP1-deficient Spitzoid nevi and one nevoid melanoma were selected for validation...
December 2017: Experimental and Molecular Pathology
Andrew J Rand, Wendy L Flejter, Christopher A Dowling, Linda M Brooke, Genevieve M Boland, Daniela Kroshinsky, Isaac R Rosenblum, Marier Hernandez-Perez, Julie D R Reimann
ALK rearrangements occur in up to 10% of spitzoid melanocytic neoplasms. No reported cases have shown homozygous deletion of 9p21 (CDKN2A) or gains of 6p25 (RREB1) or 11q13 (CCND1), which have been associated with aggressive clinical behavior. Here we report 2 unique cases. Case 1 occurred in a 9-year-old male with a 14-mm nodule on the anterior left thigh. Biopsy revealed an ALK-positive Spitz tumor containing an irregular nodule of densely packed melanocytes with increased mitoses and loss of p16 immunoreactivity...
February 2018: Journal of Cutaneous Pathology
Cristina Carrera, Alon Scope, Stephen W Dusza, Giuseppe Argenziano, Gianluca Nazzaro, Alice Phan, Isabelle Tromme, Pietro Rubegni, Josep Malvehy, Susana Puig, Ashfaq A Marghoob
BACKGROUND: Knowledge regarding the morphologic spectrum of pediatric melanoma (PM) is sparse, and this may in part contribute to delay in detection and thicker tumors. OBJECTIVE: To analyze the clinicodermoscopic characteristics of PM. METHODS: Retrospective study of 52 melanomas diagnosed in patients before the age of 20 years. RESULTS: On the basis of its clinical, dermoscopic, and histopathologic characteristics, PM can be classified as spitzoid or nonspitzoid...
February 2018: Journal of the American Academy of Dermatology
Sonja Offenmueller, Ulrike Leiter, Benedikt Bernbeck, Claus Garbe, Thomas Eigentler, Arndt Borkhardt, Carl Friedrich Classen, Selim Corbacioglu, Uta Dirksen, Georg Ebetsberger-Dachs, Lucie Heinzerling, Norbert Jorch, Michaela Kuhlen, Jennifer Lawlor, Felix Niggli, Monika Streiter, Dominik T Schneider, Ines Brecht
Background Malignant melanoma (MM) is a common malignancy in adults while it is rare in children. Thus, information on clinical behavior of pediatric MM is incomplete. Patients The German Pediatric Rare Tumor Registry (STEP) presents a prospective analysis of 60 childhood MM cases diagnosed between June 2006 and December 2014. Method Patients' ages ranged between 0 and 17 years at initial diagnosis (median age 9.6 years). Information on patient's and tumor characteristics was obtained by standardized documentation...
November 2017: Klinische Pädiatrie
Prodipto Pal, Zanobia Khan
ROS1 is a receptor tyrosine kinase that has recently been shown to undergo gene rearrangements in~1%-2% of non-small cell lung carcinoma (NSCLC) and in a variety of other tumours including cholangiocarcinoma, gastric carcinoma, colorectal carcinoma and in spitzoid neoplasms, glioblastoma and inflammatory myofibroblastic tumours. The ROS1 gene fusion undergoes constitutive activation, regulates cellular proliferation and is implicated in carcinogenesis. ROS1 fusions can be detected by fluorescence in situ hybridisation, real-time PCR, sequencing-based techniques and immunohistochemistry-based methods in clinical laboratories...
December 2017: Journal of Clinical Pathology
Severine Cao, Vinod E Nambudiri
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been implicated in the pathogenesis of a variety of neoplasms. As suggested by its name, ALK was first described as part of a translocation product in cases of anaplastic large-cell lymphoma, with other genetic and cytogenetic ALK mutations subsequently coming to attention in the development of many other hematologic and solid organ malignancies. ALK has now been shown to play a role in the pathogenesis of several cutaneous malignancies, including secondary cutaneous systemic anaplastic large-cell lymphoma (ALCL) and primary cutaneous ALCL, melanoma, spitzoid tumors, epithelioid fibrous histiocytoma, Merkel cell carcinoma, and basal cell carcinoma...
September 12, 2017: Cancers
Rossitza Lazova, Erin H Seeley
Mass spectrometry imaging can be successfully used for skin cancer diagnosis, particularly for the diagnosis of challenging melanocytic lesions. This method analyzes proteins within benign and malignant melanocytic tumor cells and, based on their differences, which constitute a unique molecular signature of 5 to 20 proteins, can render a diagnosis of benign nevus versus malignant melanoma. Mass spectrometry imaging may assist in the differentiation between metastases and nevi as well as between proliferative nodules in nevi and melanoma arising in a nevus...
October 2017: Dermatologic Clinics
R Jurakić Tončić, M Bradamante, G Ferrara, D Štulhofer-Buzina, M Petković, G Argenziano
Clinicopathological classification, diagnosis and management of spitzoid melanocytic lesion presents one of the most intriguing issues in dermatopathology (1,2). No single clinicopathological feature can offer reliable differentiation of Spitz nevus and melanoma. Although not all the experts agree with the concept of Spitzoid neoplasms as a morpho-biological spectrum, there is a four-tiered classification system proposed by Da Forno et al. and encompassing: 1) Spitz nevus; 2) atypical Spitz nevus; 3) (atypical) Spitz tumor; 4) Spitzoid melanoma (1,3)...
September 1, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
Berta M Geller, Paul D Frederick, Stevan R Knezevich, Jason P Lott, Heidi D Nelson, Linda J Titus, Patricia A Carney, Anna N A Tosteson, Tracy L Onega, Raymond L Barnhill, Martin A Weinstock, David E Elder, Michael W Piepkorn, Joann G Elmore
BACKGROUND: Research examining the role of second opinions in pathology for diagnosis of melanocytic lesions is limited. OBJECTIVE: To assess current laboratory policies, clinical use of second opinions, and pathologists' perceptions of second opinions for melanocytic lesions. MATERIALS AND METHODS: Cross-sectional data collected from 207 pathologists in 10 US states who diagnose melanocytic lesions. The web-based survey ascertained pathologists' professional information, laboratory second opinion policy, use of second opinions, and perceptions of second opinion value for melanocytic lesions...
August 29, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
Michael T Tetzlaff, Alexandre Reuben, Steven D Billings, Victor G Prieto, Jonathan L Curry
The histopathologic spectrum of Spitzoid neoplasms includes Spitz nevi, atypical Spitz tumors, and Spitzoid melanomas. Advances in molecular genetics have evolved to the point that Spitzoid lesions can now be reasonably classified according to their distinctive molecular-genetic alterations: Spitzoid lesions with (1) 11p amplification and/or HRAS mutations; (2) isolated loss of 6q23 by fluorescence in situ hybridization (FISH); (3) homozygous deletion of 9p21 by FISH; (4) BAP1 loss and BRAFV600 E mutation; (5) translocations involving any of a number of different oncogenic kinase drivers, including ROS1, ALK, NTRK1, NTRK3, MET, BRAF, and RET; and (6) TERT promoter mutations...
September 2017: Clinics in Laboratory Medicine
Paolo Broganelli, Simone Ribero, Ilaria Castagno, Fulvio Ricceri, Tommaso Deboli, Elena Marra, Carlo Tomasini, Carlotta Sacerdote, Simona Osella-Abate, Martina Sanlorenzo, Pietro Quaglino, Maria T Fierro
BACKGROUND: There is no universally-accepted classification of spitzoid tumours. This makes difficult to assign a correct diagnosis and select a treatment that minimises the risk of overestimating, or worse, underestimating, the malignant potential of these tumours. To describe the clinical-pathological and epidemiological features of spitzoid tumours, as well as to assess mortality in these patients. METHODS: This retrospective cohort study looked at data on spitzoid tumours excised in 1999-2012 at the Dermatologic Clinic of the Turin University Hospital...
July 11, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Stefan Kraft, Johanna B Moore, Alona Muzikansky, Kenneth L Scott, Lyn M Duncan
BACKGROUND: Recent molecular advances suggest that Spitz nevi and other spitzoid neoplasms are biologically distinct from melanoma and conventional nevi. The ubiquitin ligase UBE2C and the homeobox transcription factor HOXA1 are candidate oncogenes in melanoma. METHODS: Using RNA expression analysis and immunohistochemistry, we evaluated these biomarkers in Spitz nevi (n = 20), melanoma (n = 20), and by immunohistochemistry in conventional nevi (n = 20)...
June 28, 2017: Journal of Cutaneous Pathology
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