Article
Medicine, General & Internal
Georgina Long, Susan M. Swetter, Alexander M. Menzies, Jeffrey E. Gershenwald, Richard A. Scolyer
Summary: Cutaneous melanoma is a malignancy derived from skin melanocytes, primarily caused by ultraviolet radiation. Diagnosis is based on clinical and histopathological findings, and treatment options vary depending on disease stage and characteristics. Multidisciplinary care, including systemic drug therapies, has significantly improved melanoma survival rates.
Article
Medicine, General & Internal
Ken Kudura, Florentia Dimitriou, Daniela Mihic-Probst, Urs J. Muehlematter, Tim Kutzker, Lucas Basler, Robert Forster, Reinhard Dummer, Joanna Mangana, Lars Husmann, Irene A. Burger, Michael Christoph Kreissl
Summary: The use of FDG-PET/CT in metastatic melanoma patients has increased significantly due to improved survival rates. Indeterminate findings on FDG-PET/CT in these patients should be further investigated, as almost half of them are malignant with the majority being melanoma metastases. Other primary malignancies are also found in a significant proportion of cases, impacting clinical management in the majority of malignant findings.
Editorial Material
Oncology
Jeffrey E. Gershenwald
Summary: The prognostic significance of primary cutaneous melanoma tumor mitotic rate (TMR) has been of interest in the clinical field worldwide for many years. Is there a way to utilize the findings from Patuzzo et al. and other studies to enhance the classification and staging of melanoma, as well as develop clinical tools that incorporate TMR for improved risk and prognostic assessment?
Article
Health Care Sciences & Services
Hyo Jae Shin, Kyung Jin Lee, Minchan Gil
Summary: The study found that CRBN mRNA expression was downregulated in various cancer types, and in some cancer types, CRBN expression was significantly positively correlated with overall survival. Additionally, CRBN expression was downregulated regardless of clinicopathological characteristics in lung adenocarcinoma and kidney renal clear cell carcinoma.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Julie My Van Nguyen, Danielle Vicus, Sharon Nofech-Mozes, Lilian T. Gien, Marcus Q. Bernardini, Marjan Rouzbahman, Liat Hogen
Summary: Patients with ovarian clear cell carcinoma are at increased risk of developing second primary malignancies, with the most common being breast, skin, and gastrointestinal tract cancers. Smoking and radiation therapy are associated with an increased risk of second primary malignancy. However, radiation therapy is not a significant risk factor for those developing second primary malignancies after ovarian clear cell carcinoma.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2021)
Article
Oncology
Xinxin Zhou, Jiayuan He, Qingyuan Wang, Teng Ma
Summary: The study revealed that miR-128-3p acts as a tumor suppressor in malignant melanoma cells by inhibiting proliferation, migration, invasion, and inducing apoptosis. The oncogene neurotrophin receptor 3 (NTRK3) was found to be up-regulated in MM cells, enhancing their malignant behaviors. The interaction between miR-128-3p and NTRK3 genes modulate the malignant behavior of MM, suggesting potential new therapeutic targets.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Ramon Yarza, Mateo Bover, Mercedes Herrera-Juarez, Macarena Rey-Cardenas, Luis Paz-Ares, Jose A. Lopez-Martin, John Haanen
Summary: TCR-based ACT has shown promising results in treating metastatic cutaneous melanoma, with a notable antitumor activity and survival benefit.
Article
Oncology
Ramon Yarza, Mateo Bover, Mercedes Herrera-Juarez, Macarena Rey-Cardenas, Luis Paz-Ares, Jose A. Lopez-Martin, John Haanen
Summary: This study conducted a systematic review and meta-analysis to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma. The results showed promising antitumor activity and survival for TCR-T therapy, with a significantly higher benefit for cancer/testis antigen targeting cells.
Article
Multidisciplinary Sciences
Jing Xu, Dongping Wu, Bicheng Zhang, Chi Pan, Yinglu Guo, Qichun Wei
Summary: This study investigates the role of RIPK4 in cutaneous squamous cell carcinoma (SCC) and finds that the silencing of RIPK4 promotes tumor malignancy but does not affect radiosensitivity to radiation therapy.
Article
Cell Biology
Shuo Han, Xue Li, Ke Wang, Dingheng Zhu, Bingyao Meng, Jieyu Liu, Xiaoting Liang, Yi Jin, Xingyuan Liu, Qian Wen, Liang Zhou
Summary: The study identified a long noncoding RNA called PURPL as an oncogene in melanoma cells, promoting cell proliferation and migration while inhibiting autophagic cell death by modulating the activity of the autophagy initiation factor ULK1. This suggests that targeting PURPL could be a potential intervention strategy for melanoma therapy.
CELL DEATH & DISEASE
(2021)
Article
Medicine, General & Internal
Attila Mokanszki, Gabor Mehes, Szilvia Lilla Csoma, Sandor Kollar, Yi-Che Chang Chien
Summary: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy often associated with sun exposure, with Merkel cell polyomavirus (MCPyV) implicated in its pathogenesis. Genetic differences were identified between MCPyV-positive and -negative MCC cases, with more pathogenic variants found in virus-associated cases. Further research is needed to understand the clinical implications of these findings.
Article
Medicine, General & Internal
Lauren Banner, Daniel Joffe, Emily Lee, Pierluigi Porcu, Neda Nikbakht
Summary: The risk of developing cutaneous melanoma (CM) is increased in middle-aged white males within 5 years of diagnosis of primary cutaneous B-cell lymphoma (PCBCL), while the risk of Merkel cell carcinoma (MCC) is increased in elderly patients within 1 year of PCBCL diagnosis.
FRONTIERS IN MEDICINE
(2023)
Review
Oncology
Dimitri Kasakovski, Marina Skrygan, Thilo Gambichler, Laura Susok
Summary: Cutaneous Melanoma (CM) is an aggressive cancer originating from pigment-producing melanocytes in the skin, with high metastatic potential. Although it represents a small fraction of skin cancers, it accounts for most skin-cancer-related deaths globally. Immune checkpoint inhibition has been a significant therapeutic approach, but challenges such as the immunosuppressive tumor microenvironment and treatment resistance persist. Combining local and systemic treatments can enhance therapeutic response and overcome resistance, yet complex drug combinations may increase the risk of immune-related adverse events.
Review
Oncology
Yoshiaki Shoji, Matias A. Bustos, Rebecca Gross, Dave S. B. Hoon
Summary: In this article, we reviewed studies from the past 15 years on the assessment of circulating tumor cells (CTCs) in cutaneous melanoma patients in relation to different clinical outcomes. The most common method used was quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate multiple molecular melanoma-associated antigen (MAA) markers, which improved the sensitivity of the assay, addressed tumor heterogeneity, and predicted patient outcomes. Multicenter studies showed the utility of CTC assays in reducing bias observed in single-center trials. The recent development of CTC enrichment platforms provided reproducible methods for CTC assessment, enabling genomic profiling of both multiple mRNAs and DNAs. CTC assessment provided specific translational information on tumor progression, treatment response prediction, and survival outcomes for cutaneous melanoma patients.
Article
Oncology
Alyssa A. Wiener, Jessica R. Schumacher, Jennifer M. Racz, Sharon M. Weber, Yaohui G. Xu, Heather B. Neuman
Summary: This study utilized the SEER database to determine the 5- and 10-year incidences of second primary cutaneous melanomas in survivors of cutaneous melanoma. The results showed that older age, male sex, and regional disease were associated with an increased risk of a second primary melanoma diagnosis.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Review
Cell Biology
Jaclyn M. Plotzke, David J. Adams, Paul W. Harms
Summary: Recent discoveries have revealed diverse oncogenic drivers and tumour suppressor alterations in adnexal tumours, implicating various pathways and identifying novel markers.
Article
Dermatology
Paul W. Harms, Monique E. Verhaegen, Josh N. Vo, Jean C. Tien, Drew Pratt, Fengyun Su, Saravana M. Dhanasekaran, Xuhong Cao, Doris Mangelberger, Julia VanGoor, Jae Eun Choi, Vincent T. Ma, Andrzej A. Dlugosz, Arul M. Chinnaiyan
Summary: This study investigated DNA methylation in MCC and found similar patterns to other cancer types. The hypomethylating agent decitabine has therapeutic effects on antigen-presenting mechanisms and shows differential effects on MCC cells with different viral status.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Cell Biology
Aleodor A. Andea
Summary: The work-up of melanocytic tumors has evolved significantly in recent years due to the rapid development of molecular assays. This article provides an updated overview of the major ancillary tests used in clinical practice, which can help pathologists in the diagnosis and classification of melanocytic tumors, as well as in predicting prognosis and response to systemic therapy in melanoma.
Article
Pathology
Paul W. Harms, Monique E. Verhaegen, Kevin Hu, Steven M. Hrycaj, May P. Chan, Chia-Jen Liu, Marina Grachtchouk, Rajiv M. Patel, Aaron M. Udager, Andrzej A. Dlugosz
Summary: MCC and SCCIS show significant overlap in gene mutations, with no unique gene mutations found in all cases of MCC. Transcriptome analysis reveals large differences in gene expression between MCC and SCCIS, including epidermal markers and immune genes. Immunohistochemistry studies show increased expression of SOX2 in the MCC component.
Article
Dermatology
Jaclyn M. Plotzke, Nicholas A. Zoumberos, Steven M. Hrycaj, Paul W. Harms, Scott C. Bresler, May P. Chan
JOURNAL OF CUTANEOUS PATHOLOGY
(2022)
Article
Cell Biology
Steven M. Hrycaj, Julianne M. Szczepanski, Lili Zhao, Javed Siddiqui, Dafydd G. Thomas, David R. Lucas, Rajiv M. Patel, Paul W. Harms, Scott C. Bresler, May P. Chan
Summary: PRAME immunostain can aid in distinguishing spindle cell melanoma from other sarcomatoid neoplasms, but its use should be as part of an immunohistochemical panel rather than a standalone diagnostic marker.
Letter
Dermatology
Paul W. Harms, May P. Chan, Scott C. Bresler, Aleodor A. Andea, Alexandra C. Hristov, Douglas R. Fullen, Rajiv M. Patel, Lori Lowe
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Pathology
Aleodor A. Andea
Summary: The diagnostic work-up of melanocytic tumors has been revolutionized in recent years with the advent of molecular assays. This review gives an overview of the major molecular tests used in clinical practice, including predicting therapy response, prognosis, tumor classification, and differential diagnosis.
Article
Pathology
Julianne M. Szczepanski, Javed Siddiqui, Rajiv M. Patel, Paul W. Harms, Steven M. Hrycaj, May P. Chan
Summary: SATB2 can serve as an immunohistochemical marker for osteoblastic differentiation. The expression of SATB2 was evaluated in different cutaneous sarcomatoid neoplasms, and it was found to be common in these tumors except for atypical fibroxanthomas. Strong staining and a high-positive h-score can improve the specificity of SATB2 in differentiating these tumors from osteosarcoma.
Article
Dermatology
Olabisi Afolayan-Oloye, Lili Zhao, Trilokraj Tejasvi, May P. Chan, Paul W. Harms, Douglas R. Fullen, Ryan A. Wilcox, Alexandra C. Hristov
Summary: This study investigated the expression of CD30 in cutaneous B-cell lymphomas (CBCLs) and correlated it with clinicopathological features. The results showed that CD30 was expressed in 35% of CBCL cases, with varying intensity and extent. CD30 expression was most common in primary cutaneous follicle center lymphoma (PCFCL) and associated with favorable clinical features. In cases with strong and diffuse expression, CD30 could potentially be a therapeutic target.
JOURNAL OF CUTANEOUS PATHOLOGY
(2023)
Article
Multidisciplinary Sciences
Feiyang Ma, Olesya Plazyo, Allison C. C. Billi, Lam C. C. Tsoi, Xianying Xing, Rachael Wasikowski, Mehrnaz Gharaee-Kermani, Grace Hile, Yanyun Jiang, Paul W. W. Harms, Enze Xing, Joseph Kirma, Jingyue Xi, Jer-En Hsu, Mrinal K. K. Sarkar, Yutein Chung, Jeremy Di Domizio, Michel Gilliet, Nicole L. L. Ward, Emanual Maverakis, Eynav Klechevsky, John J. J. Voorhees, James T. T. Elder, Jun Hee Lee, J. Michelle Kahlenberg, Matteo Pellegrini, Robert L. L. Modlin, Johann E. E. Gudjonsson
Summary: Single cell and spatial transcriptomics can be used to investigate changes in Psoriasis and other inflammatory skin diseases during severity stages. The authors compared different inflammatory skin diseases and found differences in immune cells and inflammatory markers, with a particular focus on keratinocytes and fibroblasts. The study revealed IL-36 dependent amplification of IL-17A and TNF inflammatory responses in psoriasis, occurring within the supraspinous layer of the skin. They also identified a subset of SFRP2(+) fibroblasts in psoriasis that contribute to immune network amplification through a pro-inflammatory state transition.
NATURE COMMUNICATIONS
(2023)
Article
Dermatology
Ahmed K. Alomari, Paul W. Harms, Aleodor A. Andea, Simon J. Warren
Summary: This study investigates the characteristics and features of melanocytic tumors driven by MAP2K1 in-frame deletions. The findings suggest that these tumors share similarities with Spitz tumors but are better classified along the conventional pathway. Furthermore, they have a high mutational burden and show ultraviolet radiation features, similar to tumors with BRAF V600E mutations.
JOURNAL OF CUTANEOUS PATHOLOGY
(2023)
Review
Pathology
Paul W. Harms, Timothy L. Frankel, Myrto Moutafi, Arvind Rao, David L. Rimm, Janis M. Taube, Dafydd Thomas, May P. Chan, Liron Pantanowitz
Summary: Our understanding of human disease has evolved greatly in recent decades, particularly in the areas of immunology and cancer treatment. Advances in digital pathology have opened new avenues for studying the tumor microenvironment. Traditional tissue-based evaluations are limited in their ability to analyze complex quantitative data and multiple biomarkers, making multiplex staining techniques a promising alternative.
Article
Medicine, Research & Experimental
Monique E. Verhaegen, Paul W. Harms, Julia J. Van Goor, Jacob Arche, Matthew T. Patrick, Dawn Wilbert, Haley Zabawa, Marina Grachtchouk, Chia-Jen Liu, Kevin Hu, Michael C. Kelly, Ping Chen, Thomas L. Saunders, Stephan Weidinger, Li-Jyun Syu, John S. Runge, Johann E. Gudjonsson, Sunny Y. Wong, Isaac Brownell, Marcin Cieslik, Aaron M. Udager, Arul M. Chinnaiyan, Lam C. Tsoi, Andrzej A. Dlugosz
Summary: Merkel cell carcinoma (MCC) is an aggressive skin cancer that expresses specific genes similar to skin-resident Merkel cells. Researchers have used ATOH1 to induce MCC development in mice by cellular reprogramming. By conditionally expressing MCPyV TAgs and ATOH1 in mouse epidermal cells, they were able to generate MCC-like tumor cells from hair follicles. The study confirmed the similarity between mouse and human MCCs and revealed that loss of p53 is necessary for the progression of MCC in this mouse model.
JOURNAL OF CLINICAL INVESTIGATION
(2022)