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(Cutaneous metastasis) pathogenesis

Christina Drusio, Jürgen C Becker, Dirk Schadendorf, Selma Ugurel
Merkel cell carcinoma is a rare, highly aggressive skin tumor with neuroendocrine features found in older people. The pathogenesis is associated with immunosuppression, chronic UV light exposure and the Merkel cell polyomavirus. Clinically, Merkel cell carcinoma presents as a solitary, cutaneous or subcutaneous, red to bluish node. Due to early lymphogenic metastasis, locoregional metastases are already present in approximately 30% of cases at the time of diagnosis. The frequent local recurrences as well as the regional and distant metastases usually appear within the first 2-3 years after the initial diagnosis...
January 30, 2019: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Zacharie Segaoula, Aline Primot, Frederic Lepretre, Benoit Hedan, Emmanuel Bouchaert, Kevin Minier, Laurent Marescaux, François Serres, Sylvie Galiègue-Zouitina, Catherine André, Bruno Quesnel, Xavier Thuru, Dominique Tierny
BACKGROUND: Metastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging...
December 4, 2018: BMC Cancer
Ciro Dantas Soares, Thayná Melo de Lima Morais, Roman Carlos, Oslei Paes de Almeida, Fernanda Viviane Mariano Brum Corrêa, Albina Messias de Almeida Milani Altemani, Maria Goretti Freire de Carvalho, Marcelo Brum Corrêa, Rodrigo Ribas Dias Dos Reis, Luciana Schultz Amorim, Jacks Jorge
Mitochondrial dysfunction is caused by an imbalance in the fission and fusion processes, and it has been implicated in the pathogenesis of several human cancers. However, the role of mitochondrial markers in melanomas still remain poorly understood. In this study, the authors assessed the expression of three mitochondrial markers [antimitochondrial (AMT), fission protein 1 (FIS1) and mitofusin 2 (MFN2)] in a series of head and neck mucosal and cutaneous melanomas. Patients with cutaneous (n=56), and mucosal [oral - n=30 and sinonasal - n=26] melanomas of the head and neck region were enrolled in this study...
November 20, 2018: Human Pathology
Lubna Suaiti, Oluwakemi Onajin, Omar Sangueza
The coexistence of Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) in the same cutaneous lesion is well known. The pathogenesis is believed to be distinct from conventional polyomavirus-related MCC, and it has a more aggressive course. Metastasis of MCC and SCC to the same lymph node is exceedingly rare with only one previously reported case in the English literature. To the best of our knowledge, this is the second case of MCC and SCC with metastasis to the same lymph node. Our case demonstrates the aggressive nature of the combined MCC and SCC in the setting of immunosuppression...
November 15, 2018: American Journal of Dermatopathology
Patrick Armstrong, Meghan M Woody, Jason S Reichenberg, Alde Cp Gavino
Acral cutaneous metastasis from internal malignancy is rare, and the pathogenesis is not completely understood. We present the case of a 54-year-old black woman with a history of breast cancer diagnosed 2 years prior who developed multiple cutaneous metastases to acral sites involving the palmar and plantar surfaces of the hands and feet. This case represents an unusual metastatic pattern of breast carcinoma that arose after treatment with bevacizumab, an angiogenesis inhibitor that binds vascular endothelial growth factor A...
September 2018: Cutis; Cutaneous Medicine for the Practitioner
Miho Ikeuchi, Ryota Asahina, Hidetaka Nishida, Hiroaki Kamishina, Katsuya Kitoh, Hiroki Sakai, Sadatoshi Maeda
BACKGROUND: In canine epitheliotropic cutaneous T-cell lymphoma (ECTCL), neoplastic cells cause skin lesions and potentially metastasize to lymph nodes, blood and other organs. Murine models are potentially valuable for elucidating the molecular mechanisms responsible for regulation of ECTCL cell migration. HYPOTHESIS/OBJECTIVES: To describe a phenotype of mice xenografted with canine ECTCL cells (EO-1 cells). ANIMALS: Four NOD.CB17-Prkdcscid /J (NOD SCID) mice were used...
August 30, 2018: Veterinary Dermatology
Teruki Yanagi, Shinya Kitamura, Hiroo Hata
Cutaneous squamous cell carcinoma (SCC) is one of the common cancers in Caucasians, accounting for 20-30% of cutaneous malignancies. The risk of metastasis is low in most patients; however, aggressive SCC is associated with very high mortality and morbidity. Although cutaneous SCC can be treated with surgical removal, radiation and chemotherapy singly or in combination, the prognosis of patients with metastatic SCC is poor. Recently, the usage of immune checkpoint blockades has come under consideration. To develop effective therapies that are less toxic than existing ones, it is crucial to achieve a detailed characterization of the molecular mechanisms that are involved in cutaneous SCC pathogenesis and to identify new drug targets...
2018: Frontiers in Oncology
Keitaro Fukuda, Takeru Funakoshi
Extramammary Paget's disease (EMPD) is a rare, slow-growing, cutaneous adenocarcinoma that usually originates in the anogenital area and axillae outside the mammary glands. EMPD mostly progresses slowly and is often diagnosed as carcinoma in situ ; however, upon becoming invasive, it promptly and frequently metastasizes to regional lymph nodes, leading to subsequent distant metastasis. To date, several chemotherapy regimens have been used to treat metastatic EMPD; however, they present limited effect and patients with distant metastasis exhibit a poor prognosis...
2018: Frontiers in Oncology
Miguel Zúñiga-Castillo, Naiura V Pereira, Mirian N Sotto
AIMS: Acral lentiginous melanoma (ALM) is the most common type of melanoma in people with darker skin phototypes. There is some evidence that the aetiology, pathogenesis, risk factors and natural history of ALM differ from those of superficial spreading melanoma (SSM). ALM behaves more aggressively than SSM, but the biological explanation for these differences remains unknown. The presence of one subtype of macrophages, termed M2-macrophage (M2-M), has been found to be related to local progression, metastasis and poor prognosis in several neoplasms...
June 2018: Histopathology
Kathleen Coggshall, Tiffany L Tello, Jeffrey P North, Siegrid S Yu
Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine cancer. It most commonly presents as an indurated plaque or nodule on sun-damaged skin in elderly patients and is characterized by high rates of local recurrence and nodal metastasis. Survival at 5 years is 51% for local disease and as low as 14% for distant disease, which underscores the aggressive nature of this tumor and challenges in management. Advances in immunology and molecular genetics have broadened our understanding of the pathophysiology of MCC and expanded our therapeutic arsenal...
March 2018: Journal of the American Academy of Dermatology
Marn Joon Park, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Yoon Se Lee
OBJECTIVE: De novo cancers of head and neck area in solid organ transplantation recipients show standardized incidence ratio (SIR) of 3.8. Immunosuppression following transplantation is suggested to play as a crucial factor in pathogenesis of secondary malignancy. Prognosis of head and neck cancer arising in solid organ transplantation recipients is proven to have poor prognosis. The incidence, risk, prognosis, and survival of de novo malignancy of head and neck area in solid organ transplantation recipients in single-tertiary medical center followed up for 20 years...
August 2018: Auris, Nasus, Larynx
Shayna Gordon, Caroline Fischer, Ann Martin, Ilana S Rosman, M Laurin Council
BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare, locally aggressive cutaneous neoplasm that commonly occurs on the face. OBJECTIVE: The purpose of this article is to comprehensively review the current literature on MAC pertaining to epidemiology, pathogenesis, clinical presentation, histology, immunohistochemistry, prognosis, follow-up, and treatment. MATERIALS AND METHODS: An extensive literature review was conducted using OVID MEDLINE and PubMed to identify articles relating to MAC...
August 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
Emmanuel Agosto-Arroyo, Marilin Rosa, Alec Chau, Laila Khazai
BACKGROUND: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies. PURPOSE/METHOD: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast...
2017: SAGE Open Medical Case Reports
Mohammed Dany
Melanoma is by far the most aggressive type of skin cancer with a poor prognosis in its advanced stages. Understanding the mechanisms involved in melanoma pathogenesis, response, and resistance to treatment has gained a lot of attention worldwide. Recently, the role of sphingolipid metabolism has been studied in cutaneous melanoma. Sphingolipids are bioactive lipid effector molecules involved in the regulation of various cellular signaling pathways such as inflammation, cancer cell proliferation, death, senescence, and metastasis...
July 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
Kelly L Harms, Lorena Lazo de la Vega, Daniel H Hovelson, Samantha Rahrig, Andi K Cani, Chia-Jen Liu, Douglas R Fullen, Min Wang, Aleodor A Andea, Christopher K Bichakjian, Timothy M Johnson, Scott A Tomlins, Paul W Harms
Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. In rare cases, the development of an additional cutaneous MCC tumor is clinically consistent with a second primary MCC tumor rather than a cutaneous metastasis, which has important treatment and prognostic implications. Objective: To evaluate genetic relatedness in 4 cases with the clinical diagnosis of multiple primary MCCs. Design, Setting, and Participants: In this case series, 7 cases of clinically designated multiple primary MCC were identified; 4 cases met inclusion criteria for next-generation sequencing (NGS) analysis...
June 1, 2017: JAMA Dermatology
Rebecca Kohnken, Karthik M Kodigepalli, Anjali Mishra, Pierluigi Porcu, Li Wu
Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that is characterized by aggressive spread of neoplastic CD4+ T-cells from the skin into the bloodstream with metastasis to visceral organs. The deoxynucleoside triphosphohydrolase SAMHD1 is highly expressed in normal CD4+ T-cells, while its expression is down-regulated in CD4+ T-cells from SS patients. MicroRNA (miR) dysregulation is an important epigenetic mechanism in the pathogenesis and progression of SS. MiR-181 has been shown to inhibit SAMHD1 expression in cell lines and was identified as an important prognostic biomarker in CTCL...
January 2017: Leukemia Research
Ann-Cathrine Larsen, Lauge H Mikkelsen, Rehannah Borup, Katalin Kiss, Peter B Toft, Christian von Buchwald, Sarah E Coupland, Jan U Prause, Steffen Heegaard
PURPOSE: Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and prognostic microRNA (miRNA) in CM and to compare the miRNA profile with that of MM. METHODS: Using microarray analysis (Affymetrix) we determined the miRNA expression profile in 40 CMs compared with 7 normal conjunctival samples...
August 1, 2016: Investigative Ophthalmology & Visual Science
Klaus G Griewank
Malignant melanoma remains the skin cancer with the highest number of mortalities worldwide. While early diagnosis and complete surgical excision remain the best possibility for curing disease, prognosis at the stage of metastasis is still poor. Recent years have brought about considerable advances in terms of understanding the pathogenesis of melanoma and treating advanced disease. The discovery of activating BRAF mutations in around 50% of tumors has led to the introduction of targeted therapies downregulating BRAF signaling output...
2016: Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum
Harvind S Chahal, Yuan Lin, Katherine J Ransohoff, David A Hinds, Wenting Wu, Hong-Ji Dai, Abrar A Qureshi, Wen-Qing Li, Peter Kraft, Jean Y Tang, Jiali Han, Kavita Y Sarin
Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7-11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10(-8)) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2...
July 18, 2016: Nature Communications
Junna Oba, Wei Wei, Jeffrey E Gershenwald, Marcella M Johnson, Cynthia M Wyatt, Julie A Ellerhorst, Elizabeth A Grimm
The metabolic hormone leptin has been implicated in the pathogenesis of various malignancies and may contribute to the high rate of cancer in obese individuals. We reported that leptin and its receptor are expressed by melanoma tumors and cell lines, and that leptin stimulates proliferation of cultured melanoma cells. Here, we tested the hypothesis that leptin contributes to early melanoma progression by assessing its association with sentinel node positivity in cutaneous melanoma patients. The study enrolled 72 patients who were scheduled to undergo lymphatic mapping and sentinel node biopsy...
March 2016: Medicine (Baltimore)
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