Leprosy-an unusual cause of a suspicious nodule on mammography

A routine mammogram identified changes thought to be due to a lymph node, which was confirmed on biopsy. The lymph node was infiltrated with macrophages and showed fragmented acid-fast bacilli. The patient had been treated for leprosy some years before and was still taking thalidomide for erythema nodosum leprosum. Leprosy-associated lymphadenopathy may be identified on routine breast screening

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. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

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. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

Fatal cardiovascular instability secondary to hypercalcaemia and intracellular calcium deposition complicating T-cell leukaemia-lymphoma

Adult T-cell leukaemia-lymphoma is a rare haematological malignancy, which can cause severe hypercalcaemia and metastatic calcification resulting in life-threatening arrhythmias

The impact of brush cytology from endoscopic retrograde cholangiopancreatography (ERCP) on patient management at a UK teaching hospital

INTRODUCTION: Patients with suspected pancreaticobiliary cancers frequently undergo endoscopic retrograde cholangiopancreatography (ERCP) to obtain brush cytology for confirmatory diagnosis. The outcome of this often leads to the management of the patient and can avoid more invasive investigations. There is a wide range of sensitivities and specificities reported in the literature. AIMS: To determine the accuracy of the brush cytology obtained at ERCP by performing a retrospective audit of all patients admitted to Guy's and St. Thomas’ Hospital for ERCP during 2008–2013. Also, to evaluate the impact of cytology results on patient care following ERCP. METHOD: Data were collected from 4 January 2008 to 27 December 2013. This involved analysing EndoSoft (the in-house software for endoscopic data entry), Pathnet (the pathology database) and Electronic Patient Records. RESULTS: 162 patients underwent brush cytology during ERCP. 58 patients had positive cytology. With intention-to-treat analysis, sensitivity was 54.7%, specificity was 100.0% and negative predictive value was 53.9% with a positive predictive value of 100%. Patients with a positive brush cytology result required fewer investigations compared with patients with a negative cytology result. CONCLUSIONS: Our results compare favourably with previous studies in the field. Brush cytology has been ignored in recent times due to perceived poor results and efficacy. Our audit shows that it can reduce the number of investigations required to reach a diagnosis of malignancy and so is a valuable tool in the diagnosis of pancreaticobiliary malignancies. However, better guidance on preparation of samples for cytology is needed to reduce the number of insufficient samples