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Mihm melanoma

Soheil S Dadras, Jun Lu, Artur Zembowicz, Thomas J Flotte, Martin C Mihm
The presence of enlarged epithelioid/spindled nests located deep in the reticular dermis of a biphasic melanocytic neoplasm can mimic melanoma arising in a preexisting nevus, causing over-interpretation of malignancy. We aimed to define the clinicopathologic significance of epithelioid/spindled nests in melanocytic nevi. Retrospectively using clinical and histologic information, we characterized 121 patients with a single lesion showing epithelioid/spindled melanocytes in the reticular dermis or subcutaneous fat, surrounded by melanophages, sometimes blending in with the adnexa...
January 17, 2018: Journal of Cutaneous Pathology
C Clemente
This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas...
June 2017: Pathologica
Martin G Cook, Daniela Massi, Willeke A M Blokx, Joost Van den Oord, Senada Koljenović, Vincenzo De Giorgi, Eleanor Kissin, Megan Grant, Amit Mandal, Gabriela Gremel, Caroline Gaudy, Amaya Viros, Nathalie Dhomen, Kiarash Khosrotehrani, Richard Marais, Adele C Green, Martin C Mihm
AIMS: Because the term 'naevoid melanoma' has variable clinical and pathological interpretations, we aimed to clarify the features of melanomas referred to as naevoid. METHODS AND RESULTS: A review was undertaken of 102 melanomas diagnosed histopathologically as naevoid melanomas and ascertained by European Organization for Research and Treatment of Cancer Melanoma Group Subcommittee pathologists from their records. We found these could be classified morphologically into three groups...
December 2017: Histopathology
Aaron Muhlbauer, Shabnam Momtahen, Martin C Mihm, James Wang, Cynthia M Magro
BACKGROUND: FISH has recently emerged as a technique to better assess the malignant potential of histologically ambiguous melanocytic lesions. However, the usefulness of FISH has not been conclusively established. The purpose of this study was to further explore the diagnostic value of FISH in distinguishing the borderline melanocytic tumor (BMT) from melanoma. METHOD: 73 cases with BMT were analyzed retrospectively from a dermatopathology database between 2010-2015...
June 2017: Annals of Diagnostic Pathology
Jonathan J Lee, Ricardo E Vilain, Scott R Granter, Nina R Hu, Scott C Bresler, Shuyun Xu, Alexander H Frank, Martin C Mihm, Robyn P M Saw, Christopher D Fletcher, Richard A Scolyer, George F Murphy, Christine G Lian
BACKGROUND: 5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker detectable through immunohistochemistry (IHC) that has been shown to distinguish benign nevi from melanoma with high sensitivity and specificity. The purpose of the study was to explore its diagnostic utility in a subset of histologically challenging, heavily pigmented cutaneous melanocytic neoplasms. METHODS: 5-hmC IHC was performed on 54 heavily pigmented melanocytic tumors. Semi-quantitative analysis of immunoreactivity was correlated with clinical, pathologic and follow-up data...
March 2017: Journal of Cutaneous Pathology
Carlos N Prieto-Granada, Cecilia Lezcano, Richard A Scolyer, Martin C Mihm, Adriano Piris
Melanoma in children is rare, representing 3% of paediatric malignancies and <1% of all melanomas. Very few detailed descriptions of bona fide lethal childhood melanomas exist in the literature. We performed a retrospective clinicopathological review of 12 paediatric (≤16 years) melanoma patients who died of metastatic disease, including detailed assessment of architectural and cytomorphological features. There were nine prepubertal patients (median age 7 years old) and three postpubertal cases (median age 15 years old)...
December 2016: Pathology
B Pérez Tato, Á Juarranz, L Nájera, M C Mihm, P Fernández, Y Gilaberte, S González
BACKGROUND: Neuropeptide Y (NPY) is involved in the carcinogenesis of different tumours, especially neural crest-derived tumours. OBJECTIVE: The aim of our study is to investigate the expression of NPY on melanoma and its relation with prognostic histological parameters and survival. METHODS: This is a retrospective observational study of two independent series, with a total of 79 primary melanomas, diagnosed in two independent University Hospitals in Spain, from January 2000 to December 2004...
March 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
Jason P Lott, Joann G Elmore, Ge A Zhao, Stevan R Knezevich, Paul D Frederick, Lisa M Reisch, Emily Y Chu, Martin G Cook, Lyn M Duncan, Rosalie Elenitsas, Pedram Gerami, Gilles Landman, Lori Lowe, Jane L Messina, Martin C Mihm, Joost J van den Oord, Michael S Rabkin, Birgitta Schmidt, Christopher R Shea, Sook Jung Yun, George X Xu, Michael W Piepkorn, David E Elder, Raymond L Barnhill
BACKGROUND: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. OBJECTIVE: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. METHODS: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions...
August 2016: Journal of the American Academy of Dermatology
Nayoung Lee, Labib R Zakka, Martin C Mihm, Tobias Schatton
The field of systemic cancer therapy for metastatic disease has entered an exciting era with the advent of novel immunomodulatory strategies targeting immune checkpoints. At the heart of these promising efforts are the tumour-infiltrating lymphocytes (TILs). As the reports demonstrating efficacy of modulating TIL effector function in patients with advanced stage cancer continue to accrue, it has become essential to better understand TIL immunobiology in order to further improve clinical outcome. In addition to providing an overview of the current immunotherapies available for metastatic melanoma, this review will briefly introduce the history and classification of TILs...
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
Richard A Scolyer, Ricardo E Vilain, Martin C Mihm
No abstract text is available yet for this article.
February 2016: Pathology
Richard L Lin, Thomas J Wang, Cara J Joyce, Martin C Mihm, George F Murphy, Christine G Lian, Jennifer Y Lin
Melanoma causes over 9000 deaths annually in the USA. Among its subtypes, nodular melanoma leads to a disproportionate number of fatalities compared with superficial spreading melanoma, the most common subtype. Recent breakthroughs in melanoma research have indicated a strong connection between melanoma virulence and the immune system. We hypothesize that the aggression of nodular melanoma may, in part, be because of decreased recognition by the immune system, as represented by a decreased presence of tumor-infiltrating lymphocytes (TILs), compared with its superficial spreading counterpart...
October 2016: Melanoma Research
Paolo A Ascierto, Michael Atkins, Carlo Bifulco, Gerardo Botti, Alistair Cochran, Michael Davies, Sandra Demaria, Reinhard Dummer, Soldano Ferrone, Silvia Formenti, Thomas F Gajewski, Claus Garbe, Samir Khleif, Rolf Kiessling, Roger Lo, Paul Lorigan, Grant Mc Arthur, Giuseppe Masucci, Ignacio Melero, Martin Mihm, Giuseppe Palmieri, Giorgio Parmiani, Igor Puzanov, Pedro Romero, Bastian Schilling, Barbara Seliger, David Stroncek, Janis Taube, Sara Tomei, Hassane M Zarour, Alessandro Testori, Ena Wang, Jérôme Galon, Gennaro Ciliberto, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS)...
November 30, 2015: Journal of Translational Medicine
Jonathan J Lee, Martin Cook, Martin C Mihm, Shuyun Xu, Qian Zhan, Thomas J Wang, George F Murphy, Christine G Lian
Melanomas in the vertical growth phase (VGP) not infrequently demonstrate cellular heterogeneity. One commonly encountered subpopulation displays small cell/nevoid morphology. Although its significance remains unknown, such subpopulations may pose diagnostic issues when faced with differentiating such changes from associated nevus or mistaking such regions for nevic maturation (pseudomaturation). That 'loss' of the epigenetic biomarker, 5-hydroxymethylcytosine (5-hmC), is a hallmark for melanoma and correlates with virulence prompted us to explore the diagnostic utility and biological implications of 5-hmC immunohistochemistry (IHC) in melanomas with small cell/nevoid subpopulations...
November 10, 2015: Oncotarget
Sonja Kleffel, Christian Posch, Steven R Barthel, Hansgeorg Mueller, Christoph Schlapbach, Emmanuella Guenova, Christopher P Elco, Nayoung Lee, Vikram R Juneja, Qian Zhan, Christine G Lian, Rahel Thomi, Wolfram Hoetzenecker, Antonio Cozzio, Reinhard Dummer, Martin C Mihm, Keith T Flaherty, Markus H Frank, George F Murphy, Arlene H Sharpe, Thomas S Kupper, Tobias Schatton
Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice...
September 10, 2015: Cell
Martin C Mihm, James J Mulé
In the past five decades, the role for lymphocytes in host immune response to tumors has been shown, at least in some patients, to be a critical component in disease prognosis. Also, the heterogeneity of lymphocytes has been documented, including the existence of regulatory T cells that suppress the immune response. As the functions of lymphocytes have become better defined in terms of antitumor immunity, specific targets on lymphocytes have been uncovered. The appreciation of the role of immune checkpoints has also led to therapeutic approaches that illustrate the effectiveness of blocking negative regulators of the antitumor immune response...
August 2015: Cancer Immunology Research
Jonathan J Lee, Lynette M Sholl, Neal I Lindeman, Scott R Granter, Alvaro C Laga, Priyanka Shivdasani, Gary Chin, Jason J Luke, Patrick A Ott, F Stephen Hodi, Martin C Mihm, Jennifer Y Lin, Andrew E Werchniak, Harley A Haynes, Nancy Bailey, Robert Liu, George F Murphy, Christine G Lian
BACKGROUND: Recent developments in genomic sequencing have advanced our understanding of the mutations underlying human malignancy. Melanoma is a prototype of an aggressive, genetically heterogeneous cancer notorious for its biologic plasticity and predilection towards developing resistance to targeted therapies. Evidence is rapidly accumulating that dysregulated epigenetic mechanisms (DNA methylation/demethylation, histone modification, non-coding RNAs) may play a central role in the pathogenesis of melanoma...
2015: Clinical Epigenetics
John M Goldberg, David E Fisher, George D Demetri, Donna Neuberg, Stephen A Allsop, Catia Fonseca, Yukoh Nakazaki, David Nemer, Chandrajit P Raut, Suzanne George, Jeffrey A Morgan, Andrew J Wagner, Gordon J Freeman, Jerome Ritz, Cecilia Lezcano, Martin Mihm, Christine Canning, F Stephen Hodi, Glenn Dranoff
PURPOSE: Alveolar soft-part sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral-mediated gene transfer to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF)...
July 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Erika M Yazawa, Jenna E Geddes-Sweeney, Filiberto Cedeno-Laurent, Kempland C Walley, Steven R Barthel, Matthew J Opperman, Jennifer Liang, Jennifer Y Lin, Tobias Schatton, Alvaro C Laga, Martin C Mihm, Abrar A Qureshi, Hans R Widlund, George F Murphy, Charles J Dimitroff
Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening antitumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity, and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely dysplastic nevi, as well as in primary and metastatic melanomas...
July 2015: Journal of Investigative Dermatology
Adriano Piris, Martin C Mihm, Mai P Hoang
BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation...
February 2015: Human Pathology
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