Extrapulmonary Small Cell Carcinoma Presenting as an Orbital Mass: A Case Report.

Extrapulmonary small cell carcinomas (ESCCs) are poorly differentiated neuroendocrine tumors that are characterized by an aggressive course and poor survival rates. While these tumors can be found anywhere in the body, presentations of lesions in the orbit are exceedingly rare. We present the case of a 47-year-old man who presented with blurry vision, lacrimation, and tenderness of his right eye, as well as a small but palpable temporal mass. Upon workup, he was diagnosed with ESCC in the orbit as well as lesions in the liver and spine. He received systemic chemotherapy but unfortunately proceeded to have rapid spread of his disease and succumbed to this cancer only a year after presentation. This patient illustrates the importance of developing optimal treatment strategies, which have yet to be delineated, and especially the impact of newer immunotherapy agents remains to be seen.

Solitary Primary Intracranial Extramedullary Plasmacytoma With Lymph Node Metastasis.

Multiple myeloma is a neoplastic disease of plasma cells. Plasma cell disorders can present as a single lesion (solitary plasmacytoma) or as multiple lesions (multiple myeloma). Solitary plasmacytomas can occur in bone (plasmacytoma of bone) or in soft tissues (extramedullary plasmacytoma), and both can serve as a precursor lesion to multiple myeloma. These lesions may occur anywhere, however, intracranial presentations are rare. Here, we present a rare case of solitary intracranial extramedullary plasmacytoma in a patient complaining of headaches and vision changes. Despite radiation treatment, intracranial progression and rare lymph node involvement were seen soon after, prompting myeloma-directed therapy followed by autologous stem cell transplant, which have resulted in remission to date.

The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner.

A variety of cancer entities are driven by KRAS mutations, which remain difficult to target clinically. Survival pathways, such as resistance to cell death, may represent a promising treatment approach in KRAS mutated cancers. Based on the frequently observed genomic deletions of BCL-2-related ovarian killer (BOK) in cancer patients, we explored the function of BOK in a mutant KrasG12D-driven murine model of lung cancer. Using KrasG12D/+ Bok-/- mice, we observed an overall tumor-promoting function of BOK in vivo. Specifically, loss of BOK reduced proliferation both in cell lines in vitro as well as in KrasG12D-driven tumor lesions in vivo. During tumor development in vivo, loss of BOK resulted in a lower tumor burden, with fewer, smaller, and less advanced tumors. Using KrasG12D/+ Tp53Δ/Δ Bok-/- mice, we identified that this phenotype was entirely dependent on the presence of functional p53. Furthermore, analysis of a human dataset of untreated early-stage lung tumors did not identify any common deletion of the BOK locus, independently of the TP53 status or the histopathological classification. Taken together our data indicate that BOK supports tumor progression in Kras-driven lung cancer.

MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

A step towards valid detection and quantification of lung cancer volume in experimental mice with contrast agent-based X-ray microtomography.

Tumor volume is a parameter used to evaluate the performance of new therapies in lung cancer research. Conventional methods that are used to estimate tumor size in mouse models fail to provide fast and reliable volumetric data for tumors grown non-subcutaneously. Here, we evaluated the use of iodine-staining combined with micro-computed tomography (micro-CT) to estimate the tumor volume of ex vivo tumor-burdened lungs. We obtained fast high spatial resolution three-dimensional information of the lungs, and we demonstrated that iodine-staining highlights tumors and unhealthy tissue. We processed iodine-stained lungs for histopathological analysis with routine hematoxylin and eosin (H&E) staining. We compared the traditional tumor burden estimation performed manually with H&E histological slices with a semi-automated method using micro-CT datasets. In mouse models that develop lung tumors with well precise boundaries, the method that we describe here enables to perform a quick estimation of tumorous tissue volume in micro-CT images. Our method overestimates the tumor burden in tumors surrounded by abnormal tissue, while traditional histopathological analysis underestimates tumor volume. We propose to embed micro-CT imaging to the traditional workflow of tumorous lung analyses in preclinical cancer research as a strategy to obtain a more accurate estimation of the total lung tumor burden.