Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation

Nadine Abdallah,1 Misako Nagasaka,2,3 Eman Abdulfatah,4 Dongping Shi,4 Antoinette J Wozniak,2 Ammar Sukari2 1Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA; 2Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, De...

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Autores principales:	Abdallah N, Nagasaka M, Abdulfatah E, Shi D, Wozniak AJ, Sukari A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Checkpoint inhibitor transformation of pathology second primary Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5ec7a9bbf8d14c17a509a9cc8032296a
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spelling	oai:doaj.org-article:5ec7a9bbf8d14c17a509a9cc8032296a2021-12-02T09:22:11ZNon-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation1179-2728https://doaj.org/article/5ec7a9bbf8d14c17a509a9cc8032296a2018-10-01T00:00:00Zhttps://www.dovepress.com/non-small-cell-to-small-cell-lung-cancer-on-pd-1-inhibitors-two-cases--peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Nadine Abdallah,1 Misako Nagasaka,2,3 Eman Abdulfatah,4 Dongping Shi,4 Antoinette J Wozniak,2 Ammar Sukari2 1Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA; 2Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; 3Department of Advanced Medical Innovation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan; 4Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA Introduction: Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in EGFR-mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors.Case presentations: Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology. He received six cycles of carboplatin and pemetrexed, then maintained on pemetrexed. He had disease progression after nine cycles of pemetrexed and was switched to nivolumab. He progressed after five cycles of nivolumab. Core biopsy of the lung mass revealed SCLC. Case 2, a 68-year-old man was diagnosed with two primary NSCLCs and underwent resection. He had recurrence after several months and was treated with four cycles of carboplatin, paclitaxel, and pembrolizumab on clinical trial, with partial response. He was continued on pembrolizumab and had disease progression after 30 cycles. Biopsy of the new lesions showed SCLC.Discussion: Histologic transformation from NSCLC to SCLC can be explained by the presence of a common cell precursor. Proposed molecular mechanisms include loss of RB1, TP53 mutations, and MYC amplification. The distinction between transformation and mixed histology tumors is challenging, especially when pathologic material used for the initial diagnosis is limited. The possibility of a second metachronous primary lung cancer cannot be excluded in our cases.Conclusion: Histologic transformation with PD-1 inhibitors could be under-recognized. Disease progression should prompt re-biopsy to uncover new histology and change in treatment. Future studies are needed to elucidate mechanisms and predictors of transformation. Keywords: transformation, small cell lung cancer, non-small cell lung cancer, PD-1 inhibitor, resistance, checkpoint inhibitor Abdallah NNagasaka MAbdulfatah EShi DWozniak AJSukari ADove Medical PressarticleCheckpoint inhibitortransformation of pathologysecond primaryNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 9, Pp 85-90 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Checkpoint inhibitor transformation of pathology second primary Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Checkpoint inhibitor transformation of pathology second primary Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Abdallah N Nagasaka M Abdulfatah E Shi D Wozniak AJ Sukari A Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
description	Nadine Abdallah,1 Misako Nagasaka,2,3 Eman Abdulfatah,4 Dongping Shi,4 Antoinette J Wozniak,2 Ammar Sukari2 1Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA; 2Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; 3Department of Advanced Medical Innovation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan; 4Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA Introduction: Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in EGFR-mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors.Case presentations: Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology. He received six cycles of carboplatin and pemetrexed, then maintained on pemetrexed. He had disease progression after nine cycles of pemetrexed and was switched to nivolumab. He progressed after five cycles of nivolumab. Core biopsy of the lung mass revealed SCLC. Case 2, a 68-year-old man was diagnosed with two primary NSCLCs and underwent resection. He had recurrence after several months and was treated with four cycles of carboplatin, paclitaxel, and pembrolizumab on clinical trial, with partial response. He was continued on pembrolizumab and had disease progression after 30 cycles. Biopsy of the new lesions showed SCLC.Discussion: Histologic transformation from NSCLC to SCLC can be explained by the presence of a common cell precursor. Proposed molecular mechanisms include loss of RB1, TP53 mutations, and MYC amplification. The distinction between transformation and mixed histology tumors is challenging, especially when pathologic material used for the initial diagnosis is limited. The possibility of a second metachronous primary lung cancer cannot be excluded in our cases.Conclusion: Histologic transformation with PD-1 inhibitors could be under-recognized. Disease progression should prompt re-biopsy to uncover new histology and change in treatment. Future studies are needed to elucidate mechanisms and predictors of transformation. Keywords: transformation, small cell lung cancer, non-small cell lung cancer, PD-1 inhibitor, resistance, checkpoint inhibitor
format	article
author	Abdallah N Nagasaka M Abdulfatah E Shi D Wozniak AJ Sukari A
author_facet	Abdallah N Nagasaka M Abdulfatah E Shi D Wozniak AJ Sukari A
author_sort	Abdallah N
title	Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
title_short	Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
title_full	Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
title_fullStr	Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
title_full_unstemmed	Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
title_sort	non-small cell to small cell lung cancer on pd-1 inhibitors: two cases on potential histologic transformation
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/5ec7a9bbf8d14c17a509a9cc8032296a
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Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation

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