Faculty Bibliography

An 82-year-old Japanese nonsmoking man presented with persistent dry cough and small left apical pneumothorax. High resolution CT scan of the chest demonstrated bilateral upper lobe pleuroparenchymal thickening and architectural distortion. Serial imaging revealed mild progression and development of small bilateral pneumothoraces, and pneumomediastinum. A surgical lung biopsy was required to confirm the diagnosis.

The tumor microenvironment (TME) represents a milieu that enables tumor cells to acquire the hallmarks of cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. Concerted interactions between genetically altered tumor cells and genetically stable intratumoral stromal cells result in an "activated/reprogramed" stroma that promotes carcinogenesis by contributing to inflammation, immune suppression, therapeutic resistance, and generating premetastatic niches that support the initiation and establishment of distant metastasis. The lungs present a unique milieu in which tumors progress in collusion with the TME, as evidenced by regions of aberrant angiogenesis, acidosis and hypoxia. Inflammation plays an important role in the pathogenesis of lung cancer, and pulmonary disorders in lung cancer patients such as chronic obstructive pulmonary disease (COPD) and emphysema, constitute comorbid conditions and are independent risk factors for lung cancer. The TME also contributes to immune suppression, induces epithelial-to-mesenchymal transition (EMT) and diminishes efficacy of chemotherapies. Thus, the TME has begun to emerge as the "Achilles heel" of the disease, and constitutes an attractive target for anti-cancer therapy. Drugs targeting the components of the TME are making their way into clinical trials. Here, we will focus on recent advances and emerging concepts regarding the intriguing role of the TME in lung cancer progression, and discuss future directions in the context of novel diagnostic and therapeutic opportunities.

OBJECTIVES: The distinction between metastatic breast carcinomas (BCs) and primary lung carcinomas (PLCs) can be difficult. This study tested the utility of trefoil factor 1 (TFF1) for this purpose and compared it with mammaglobin and GATA protein binding 3 (GATA-3). METHODS: Tissue microarrays containing 365 BCs and 338 PLCs were stained with TFF1, mammaglobin, and GATA-3, and an H-score was calculated. Sensitivity, specificity, and accuracy were calculated, and logistical regression analysis was performed. RESULTS: Accuracy of correctly classifying the tumor type was 81.9%, 71.3%, and 64.0% for GATA-3, mammaglobin, and TFF1, respectively. Odds ratios for selecting BCs were 25.69, 93.15, and 4.17, respectively, with P values less than .001. With a single exception, the best immunopanel included GATA-3 and mammaglobin in all comparisons. CONCLUSIONS: TFF1 demonstrated breast specificity but was inferior to mammaglobin and GATA-3. Therefore, its routine clinical use may not be justified. TFF1 showed little benefit when added to an immunopanel.

A 78-year-old woman with metastatic low-grade serous ovarian cancer presented with rapidly progressive exertional dyspnoea and hypoxia, and was found to have new-onset severe pulmonary hypertension (PH) by right heart catheterisation. A diagnosis of pulmonary tumour thrombotic microangiopathy (PTTM) was made at autopsy. PTTM is a rare complication of advanced cancer that often presents as rapidly progressive PH or acute hypoxic respiratory failure. Widespread tumour cell emboli in the pulmonary arteries and arterioles are hypothesised to induce fibrocellular subintimal proliferation and microthrombi, leading to increased pulmonary vascular resistance and PH. PTTM arising from serous ovarian cancer is exceedingly rare, with only two previously reported cases. A discussion of the pathophysiology, diagnosis and management of PTTM is presented.