Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Unlabelled: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery.

Bortezomib-based therapy is effective and well tolerated in frontline and multiply pre-treated Waldenström macroglobulinaemia including BTKi failures: A real-world analysis.

Waldenström macroglobulinemia (WM) is a rare, incurable low grade lymphoma following a relapsing trajectory. Management strategies have evolved with the introduction of targeted therapy including new classes of Bruton tyrosine kinase inhibitor (BTKi). Treatment may however be limited particularly at relapse by a lack of drug availability and tolerability.

IgG4-related hypophysitis: a retrospective cohort study.

Purpose: IgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for patients with histologically proven IgG4-related hypophysitis.

Methods: A prospectively maintained electronic database was searched over a 14-year period from 1 January 2007 to 31 December 2020 at a single academic centre to identify all patients with a histological diagnosis of IgG4-RH.

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity.

Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma.

Background: Medullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor.

Patients And Methods: A retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC.

Anaplastic Transformation of Differentiated Papillary Thyroid Carcinoma Presenting as Cauda Equina Syndrome.

BACKGROUND Papillary thyroid carcinoma is usually an indolent disease, with an almost 80% 5-year survival rate for metastatic disease. Conversely, anaplastic thyroid cancer is much more aggressive, with median overall survival rates of 4 months. CASE REPORT A 67-year-old woman presented with metastatic papillary thyroid cancer with bone metastasis, including an unstable L4 pathological fracture.

Spindle cell tumour with thymus-like differentiation (SETTLE) on fine needle aspiration cytology: A case report highlighting diagnostic pitfalls.

A 7-year-old girl presented with a painless neck swelling localised near the left lobe of the thyroid gland, which was initially investigated by fine needle aspiration cytology. This raised a differential diagnosis of medullary thyroid carcinoma and small round blue cell tumour. Only after several additional clinical investigations and a total thyroidectomy was a definitive diagnosis of spindle cell tumour with thymus-like differentiation (SETTLE) reached.

Treating papillary and follicular thyroid cancer in children and young people: Single UK-center experience between 2003 and 2018.

Aim: Differentiated thyroid cancer (DTC) in children and adolescents is rare and data about its presentation and management are not well known. The aim of this study was to provide evidence of the current practice in the United Kingdom before the launch of the Rare National Paediatric Endocrine Tumours Guidelines (to be published in 2020).

Methods: Seventy-two children and adolescents with DTC (<18 years) who were treated at our institution between 2003 and 2018 were identified and their presentation, treatment and outcomes were reviewed.

Papillary thyroid microcarcinoma presenting as a metastasis to the brain.

The brain is a particularly rare site of metastasis from papillary microcarcinoma, with only few cases described in the literature. We present a case of 59-year-old man who presented with seizures and dysphasia due to left frontal lobe cystic mass, which was excised and turned out on histopathology to be of thyroid origin. Total thyroidectomy was performed and histology showed multifocal papillary microcarcinoma with the largest focus of 3mm with no other adverse features.

Novel markers in pediatric-type follicular lymphoma.

The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance.

Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.

Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint.

Purpose: Cdc7 is a serine/threonine kinase which is responsible for the 'firing' of replication origins leading to initiation of DNA replication. Inhibition or depletion of Cdc7 in normal cells triggers a DNA origin activation checkpoint causing a reversible G1 arrest. Here we investigate Cdc7 as a novel therapeutic target in pancreatic cancer.

Do Cell-Cycle Phase-Specific Markers Predict Disease Grade, Stage, and Outcome in Cervical Carcinoma?

Aims: Multiparameter analysis of cell cycle markers has shown a strong relationship between cell cycle progression and tumor grade, stage, and clinical outcome in penile, renal, ovarian, and breast cancers. We sought to link expression of cell cycle phase-specific markers in cervical cancer to tumor grade, stage, and clinical outcome to investigate their potential use as prognostic and predictive markers.

Methods: Pretreatment biopsy material was obtained from 35 patients with cervical cancer (stage IB2-IVA) and 12 normal cervix control cases.

Primary mucoepidermoid carcinoma of the thymus presenting with myasthenia gravis.

Mucoepidermoid carcinoma (MEC) of the thymus is a rare malignant neoplasm of the anterior mediastinum. There are less than 30 cases described in the English literature. We report a case of a 47-year-old lady who presented with myasthenia gravis and was found to have a well-circumscribed anterior mediastinal mass in her medical work-up.