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Transformation into large-cell neuroendocrine carcinoma associated with acquired resistance to erlotinib in nonsmall cell lung cancer.

Lim JU, Woo IS, Jung YH, Byeon JH, Park CK, Kim TJ, Kim HR - Korean J. Intern. Med. (2014)

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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To the Editor, The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib is active in patients with metastatic lung adenocarcinoma carrying mutations in the EGFR gene... Although erlotinib has been found to improve markedly progression-free survival and quality of life, most patients who show an initial response eventually develop disease progression... Possible mechanisms of acquired or secondary resistance to erlotinib include second mutations in the EGFR gene such as T790M, activation of an alternative pathway including Met or HER2 amplification, histological transformation to small cell lung cancer (SCLC) and epithelial to mesenchymal transition... After 1 month observation period, the patient visited our emergency room with fever and dyspnea... Chest CT showed enlarged mediastinal lymph nodes invading the trachea and superior vena cava (SVC), consistent with SVC syndrome... Palliative emergency radiation treatment of the mediastinal mass (3,000 cGy in 10 fractions) was started immediately... Follow-up chest CT showed that several parenchymal nodules in both lungs had increased in size, while others had decreased and the size of the mediastinal lymph nodes had decreased... Our patient presented with a combined tumor, consisting of adenocarcinoma and LCNEC components when he developed resistance to erlotinib... The pathological results were confirmed by the histological features of the tumor and with immunohistochemistry of neuroendocrine markers... Our findings suggest that, during treatment with the EGFR TKI erlotinib, the adenocarcinoma had partially transformed to LCNEC or was undergoing histological transformation... Moreover, rebiopsy of the paratracheal lymph node showed the tumor had a marked initial response to erlotinib but became enlarged again at the time of resistance to EGFR TKI... The mechanisms of the LCNEC transformation during treatment with EGFR TKI and the development of acquired resistance require further investigations... In conclusion, we described a patient with metastatic lung adenocarcinoma who experienced a histological transformation to combined LCNEC and adenocarcinoma of the lung during treatment with erlotinib.

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(A) Adenocarcinoma from brain tissue after craniotomy at the time of initial diagnosis (H&E, ×400). (B) Large-cell neuroendocrine carcinoma (LCNEC) from rebiopsied sample (H&E, ×400). (C) LCNEC from rebiopsied sample (chromogranin, ×400). (D) LCNEC from rebiopsied sample (neuron specific enolase, ×400).
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Figure 2: (A) Adenocarcinoma from brain tissue after craniotomy at the time of initial diagnosis (H&E, ×400). (B) Large-cell neuroendocrine carcinoma (LCNEC) from rebiopsied sample (H&E, ×400). (C) LCNEC from rebiopsied sample (chromogranin, ×400). (D) LCNEC from rebiopsied sample (neuron specific enolase, ×400).

Mentions: A left frontal craniotomy was performed to remove the mass in the left frontal lobe. The specimen was positive for cytokeratin-7 (CK-7), thyroid transcription factor-1 (TTF-1), leukocyte common antigen, CK-20, and vimentin, indicating a well-differentiated adenocarcinoma (Fig. 2). The patient was subsequently referred to the Department of Medical Oncology.


Transformation into large-cell neuroendocrine carcinoma associated with acquired resistance to erlotinib in nonsmall cell lung cancer.

Lim JU, Woo IS, Jung YH, Byeon JH, Park CK, Kim TJ, Kim HR - Korean J. Intern. Med. (2014)

(A) Adenocarcinoma from brain tissue after craniotomy at the time of initial diagnosis (H&E, ×400). (B) Large-cell neuroendocrine carcinoma (LCNEC) from rebiopsied sample (H&E, ×400). (C) LCNEC from rebiopsied sample (chromogranin, ×400). (D) LCNEC from rebiopsied sample (neuron specific enolase, ×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219976&req=5

Figure 2: (A) Adenocarcinoma from brain tissue after craniotomy at the time of initial diagnosis (H&E, ×400). (B) Large-cell neuroendocrine carcinoma (LCNEC) from rebiopsied sample (H&E, ×400). (C) LCNEC from rebiopsied sample (chromogranin, ×400). (D) LCNEC from rebiopsied sample (neuron specific enolase, ×400).
Mentions: A left frontal craniotomy was performed to remove the mass in the left frontal lobe. The specimen was positive for cytokeratin-7 (CK-7), thyroid transcription factor-1 (TTF-1), leukocyte common antigen, CK-20, and vimentin, indicating a well-differentiated adenocarcinoma (Fig. 2). The patient was subsequently referred to the Department of Medical Oncology.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

To the Editor, The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib is active in patients with metastatic lung adenocarcinoma carrying mutations in the EGFR gene... Although erlotinib has been found to improve markedly progression-free survival and quality of life, most patients who show an initial response eventually develop disease progression... Possible mechanisms of acquired or secondary resistance to erlotinib include second mutations in the EGFR gene such as T790M, activation of an alternative pathway including Met or HER2 amplification, histological transformation to small cell lung cancer (SCLC) and epithelial to mesenchymal transition... After 1 month observation period, the patient visited our emergency room with fever and dyspnea... Chest CT showed enlarged mediastinal lymph nodes invading the trachea and superior vena cava (SVC), consistent with SVC syndrome... Palliative emergency radiation treatment of the mediastinal mass (3,000 cGy in 10 fractions) was started immediately... Follow-up chest CT showed that several parenchymal nodules in both lungs had increased in size, while others had decreased and the size of the mediastinal lymph nodes had decreased... Our patient presented with a combined tumor, consisting of adenocarcinoma and LCNEC components when he developed resistance to erlotinib... The pathological results were confirmed by the histological features of the tumor and with immunohistochemistry of neuroendocrine markers... Our findings suggest that, during treatment with the EGFR TKI erlotinib, the adenocarcinoma had partially transformed to LCNEC or was undergoing histological transformation... Moreover, rebiopsy of the paratracheal lymph node showed the tumor had a marked initial response to erlotinib but became enlarged again at the time of resistance to EGFR TKI... The mechanisms of the LCNEC transformation during treatment with EGFR TKI and the development of acquired resistance require further investigations... In conclusion, we described a patient with metastatic lung adenocarcinoma who experienced a histological transformation to combined LCNEC and adenocarcinoma of the lung during treatment with erlotinib.

Show MeSH
Related in: MedlinePlus