Rajendra Sharma and Abha Sharma
Background: The development of pulmonary metastases is a critical step in oncology management as it is a major determinant of survival for patients with cancer. Primaries that commonly metastasize to the lung arise from breast, head/neck, and the gastrointestinal tract. The aim of this study was to review the pathobiogenesis of pulmonary metastases and the evolution of curative pulmonary metastasectomy as reported in the literature in addition to analyzing in detail uncommon pulmonary metastatic lesions received over a period of 14 years.
Design: The indexed uncommon pulmonary metastases were reviewed and analyzed in detail. A 14-year (1996-2010) computer-based review using the Laboratory-Information-System was conducted in our laboratory. Results were categorized based on age, sex, and primary sites of origin with special emphasis to study unusual pulmonary metastases.
Results: 230 cases of pulmonary metastases were retrieved on review. 129 females (56%) and 101 males (44%) ranging in age from 19 months to 91 years (median 65 years) were identified with their primary sites of origin being: breast (28.3%), gastrointestinal tract (27.8%), kidney (8.7%), and melanoma (7.0%). Three uncommon diagnoses were identified and studied in detail: 1) an index case of metastatic benign pleomorphic adenoma, case series of 2) endometrial stromal sarcoma and 3) osteosarcoma.
Conclusion: Due to the poor prognosis of metastatic lung cancer, early recognition with accurate diagnosis is an important step for optimal patient management. In this context, pathologic awareness of uncommon metastases remains a challenging task. Pulmonary metastasectomy is a curative option for an increasing number of patients due to recent advances in chemotherapy that achieve locoregional control of the primary tumours. With this increased number of pulmonary metastasectomy, recognition of not only ‘common’ pulmonary malignancies but also more rare entities becomes central to best practices in surgical pathology.
The Japanese apricot “Prunus mume,” which is also known as the Ume fruit in Japan, is a centuries-old traditional Japanese medicine, and it is a commonly consumed food. MK615, a compound extract from Ume fruits, has been shown to have anti-tumor and anti-inflammatory effects. In this study, we assessed the effects of MK615 on the in vitro growth of nine non-small cell lung cancer (NSCLC) cell lines and the HBEC4 immortalized bronchial epithelial cell line. While MK615 inhibited the in vitro cell growth of the majority of the NSCLC cell lines, the growthinhibitory effects varied among the cell lines, and some cell lines exhibited MK615 resistance. In the H1299 and H157 NSCLC cell lines that are highly sensitive to MK615, the induction of autophagy was observed after MK615 treatment. In addition, cell-cycle analysis showed that MK615 increased the proportion of cells in the G0-G1 phase in H1299 and H157 cells. In H1792 cells that overexpress IL-8, MK615 down-regulated IL-8 expression at the mRNA and protein levels in a dose-dependent manner. These results suggest that MK615 has multiple anti-tumor activities including the inhibition of cell proliferation, autophagy induction, G0-G1 cell cycle arrest and the downregulation of IL-8 expression in NSCLC cells.
During the past decade, a number of novel agents developed for the treatment of advanced NSCLC had, by coincidence, shown survival benefit predominantly among patients with nonsquamous histology, namely pemetrexed (anti-folate), bevacizumab (VEGF pathway inhibition), erlotinib/gefitinib (EGFR receptor tyrosine kinase inhibitors) and crizotinib (ALK receptor tyrosine kinase inhibitor. This has sparked a heightened interest in discovering key molecular aberrations that may be relevant for the treatment of squamous cell carcinoma (SCC) of the lung, a histologic subtype that represents approximately 25% of lung cancer cases diagnosed globally. This article highlights the most promising recent discoveries and targeted agents in development that may be relevant for the treatment of SCC of the lung.
Filipe Moreira de Andrade, Luiz Felippe Judice, Paulo de Biasi and Robert Cerfolio
Lung cancer incidence has dramatically risen in the past century. It is now the leading cause of cancer death in the world, both among men and women. Accurate staging is important because treatment options and prognosis differ significantly by stage. If there are no distant metastases, the status of mediastinal lymph nodes is the critical point to distinct between patients who will benefit from surgical therapy, neoadjuvant therapy or clinical treatment. Noninvasive imaging studies including chest computed tomography and positron emission tomography scanning should be performed in all patients who are potentially candidates to pulmonary resection. The findings of these noninvasive studies are critical, and the invasive mediastinal staging must be performed according to the medical examination and the results of noninvasive tests. In patients with extensive mediastinal infiltration by lung cancer, the disease is considered advanced and invasive staging is not needed. In patients with mediastinal lymph node enlargement seen at computed tomography, a sample tissue of these nodes is necessary. In these cases there are several methods to invasive staging the mediastinum, but mediastinoscopy is the gold standard. In patients with clinical T2 or with central tumors, invasive staging of the mediastinal nodes is necessary. Patients with a peripheral clinical T1 lung cancer do not usually need invasive confirmation of mediastinal nodes unless there is an abnormal standard uptake value in the nodes, found on positron emission tomography scanning. The staging of patients with left upper lobe tumors should include an assessment of the preaortic and aortopulmonary window lymph nodes. Pancoast tumors always need invasive mediastinal staging if they are considered for surgical resection.