Evaluation of Crizotinib Treatment in a Patient With Unresectable GOPC-ROS1 Fusion Agminated Spitz Nevi
Abstract Importance: Spitz nevi are benign melanocytic neoplasms that classically present in childhood. Isolated Spitz nevi have been associated with oncogenic gene fusions in approximately 50% of cases. The rare agminated variant of Spitz nevi, thought to arise from cutaneous genetic mosaicism, is characterized by development of clusters of multiple lesions in a segmental distribution, which can complicate surgical removal. Somatic single-nucleotide variants in the HRAS oncogene have been described in agminated Spitz nevi, most of which were associated with an underlying nevus spilus. The use of targeted medical therapy for agminated Spitz nevi is not well understood. Observations: A girl [...]
Counting mitoses: SI(ze) matters!
Abstract Mitoses are often assessed by pathologists to assist the diagnosis of cancer, and to grade malignancy, informing prognosis. Historically, this has been done by expressing the number of mitoses per n high power fields (HPFs), ignoring the fact that microscope fields may differ substantially, even at the same high power (×400) magnification. Despite a requirement to define HPF size in scientific papers, many authors fail to address this issue adequately. The problem is compounded by the switch to digital pathology systems, where ×400 equivalent fields are rectangular and also vary in the area displayed. The potential for error [...]
Melanoma with osseous or chondroid differentiation: a report of eight cases including SATB2 expression and mutation analysis.
Abstract Melanoma can present with osteocartilaginous differentiation, however few reports exist on this rare subtype. We present eight cases of melanoma with osteocartilaginous differentiation to highlight its clinical, pathological and molecular features. The cases showed no association with gender (5 males and 3 females) or age (range 23-84 years). Cases included both primary melanomas and distant metastases (6 and 2, respectively), with the majority arising from cutaneous sites (7/8) and the remaining case from a mucosal site. Tumour-infiltrating lymphocyte (TIL) score ranged from 0 to 3 (median 1), and 2/8 lesions had evidence of inflammatory changes or antecedent trauma. [...]
Predicting recurrence in patients with sentinel node-negative melanoma: validation of the EORTC nomogram using population-based data.
Abstract Background: Identifying patients with sentinel node (SN)-negative melanoma who are at greatest risk of recurrence is important. The European Organization for Research and Treatment of Cancer (EORTC) Melanoma Group proposed a prognostic model that has not been validated in population-based data. The EORTC nomogram includes Breslow thickness, ulceration status and anatomical location as parameters. The aim of this study was to validate the EORTC model externally using a large national data set. Methods: Adults with histologically proven, invasive cutaneous melanoma with a negative SN biopsy in the Netherlands between 2000 and 2014 were identified from the Dutch Pathology Registry, and [...]
Can patient-led surveillance detect subsequent new primary or recurrent melanomas and reduce the need for routinely scheduled follow-up? A protocol for the MEL-SELF randomised controlled trial.
Abstract Background: Most subsequent new primary or recurrent melanomas might be self-detected if patients are trained to systematically self-examine their skin and have access to timely medical review (patient-led surveillance). Routinely scheduled clinic visits (clinician-led surveillance) is resource-intensive and has not been shown to improve health outcomes; fewer visits may be possible if patient-led surveillance is shown to be safe and effective. The MEL-SELF trial is a randomised controlled trial comparing patient-led surveillance with clinician-led surveillance in people who have been previously treated for localised melanoma. Methods: Stage 0/I/II melanoma patients (n = 600) from dermatology, surgical, or general practice clinics [...]
Lentigo maligna: defining margins and predictors of recurrence utilising clinical, dermoscopic, confocal microscopy and histopathology features
Abstract Background: Lentigo maligna (LM) is a subtype of melanoma in situ with poorly defined margins and a high recurrence rate. The biological behaviour of LM appears to differ widely between cases, from biologically indolent to biologically active variants, with some patients experiencing multiple recurrences. It is not known whether this is secondary to inadequate margins, field cancerization or the innate biology of the lesion itself. Objectives: (a) Describe the margins of LM in detail by analysing LM in three zones, that is centre, edge and surround using reflectance confocal microscopy (RCM) and histopathology; (b) ascertain association of histological distance of [...]
Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis
Abstract Background: High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms. Methods: Using the Chromium 10X platform, we sequenced a [...]
The deacylase SIRT5 supports melanoma viability by influencing chromatin dynamics.
Abstract Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieve a durable remission. Sirtuin 5 (SIRT5) is a member of the sirtuin family of protein deacylases that regulates metabolism and other biological processes. Germline Sirt5 deficiency is associated with mild phenotypes in mice. Here we showed that SIRT5 was required for proliferation and survival across all cutaneous melanoma genotypes tested, as well as uveal melanoma, a genetically distinct melanoma [...]
Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial
Abstract Background: Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival. Methods: In this double-blind, randomised, placebo-controlled phase 3 study, involving 160 academic medical centres and hospitals in 16 countries (Australia, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Poland, South Africa, Spain, Switzerland, the UK, and the USA), patients aged 12 years or older with newly diagnosed, completely [...]
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