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H.J. Kwon
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-018 - Osteosarcomatous Differentiation in the Rebiopsy Specimens of Patients Harboring Pulmonary Adenocarcinoma with EGFR-TKI Resistance (ID 4539)
14:30 - 14:30 | Author(s): H.J. Kwon
- Abstract
Background:
Histological transformation including small cell carcinoma and epithelial to mesenchymal transition (EMT) is one of the discovered mechanisms of the acquired resistance to EGFR-TKI. We report two cases of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor(EGFR-TKI) resistant pulmonary adenocarcinoma associated with EMT features that showed osteosarcomatous differentiation in rebiopsy specimens.
Methods:
We identified two patients with primary lung adenocarcinoma that showed osteosarcomatous transformation on second biopsy (n = 60) between 2010 and 2016. Histomorphologic features and EGFR mutation results were compared between initial and second biopsy samples.
Results:
Case 1 A 55-year-old female, non-smoker presenting chronic cough was found to have pulmonary adenocarcinoma harboring EGFR exon 19 deletion mutation with disseminated intrapulmonary metastasis. After 1 year of gefinitib treatment, radiologic evaluation showed left iliac metastases with extraosseous ossification. Case 2 A 58-year-old man who had undergone right upper lobectomy of the lung was diagnosed as adenocarcinoma with pT1N0M0 harboring an EGFR exon 19 deletion mutation. Three years after surgery, metastatic lesions developed in the right lower lobe and pleura. After 15 months of conventional chemotherapy, 2nd biopsy for the pulmonary lesion confirmed T790M mutation and additional metastatic lesions found in T2 and T5 vertebral bodies were removed by surgical curettage. Rebiopsy of the metastatic bone lesions of these two patients showed metastatic adenocarcinoma merging with poorly differentiated sarcomatous components. Remarkably, the spindle shaped sarcomatous tumor cells produced ill-defined eosinophilic lace-like osteoid. These osteoid components were closely associated with the tumor cells and deposited as disorganized features. The sarcomatous neoplastic cells intermingled with osteoid demonstrate unequivocal features of malignancy, which is different from reactive osteoid or callus formation. EGFR mutation status were same from that of primary lung specimen and IHC showed vimentin expression and decreased E-cadherin (EMT feature).
Conclusion:
To the best of our knowledge, this is the first report to describe pulmonary adenocarcinoma with osteosarcomatous differentiation in rebiopsy specimens of EGFR-TKI resistant patients. As the evaluation of metastatic sites for rebiopsy were bone lesions in both patients, the role of the tumor microenvironment may support the transformation from adenocarcinoma to osteosarcomatous phenotype. A few previous studies suggested that a bone environment is essential for osteosarcoma development from transformed mesenchymal stem cells. Our findings suggest that the differences of the intrinsic nature between epithelial and osteosarcomatous mesenchymal cancers may be the cause of the acquired resistance of EGFR-TKI.
