Perioperative chemotherapy with pemetrexed and cisplatin for pulmonary large-cell neuroendocrine carcinoma: a case report and literature review

Hong Tang, Hongyan Wang, Shaoyan Xi, Chunyu He, Yuxi Chang, Qiming Wang, Yufeng Wu, Hong Tang, Hongyan Wang, Shaoyan Xi, Chunyu He, Yuxi Chang, Qiming Wang, Yufeng Wu

Abstract

Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is associated with poor prognosis, and its treatment strategy is still controversial, especially regarding chemotherapy regimens.

Case report: We present the case of a 49-year-old Chinese male with primary pulmonary LCNEC treated with neoadjuvant and adjuvant chemotherapy with cisplatin plus pemetrexed. A suspected quasi-circular mass in the left lower pulmonary lobe and an enlarged mediastinal lymph node were found. The patient was diagnosed with adenocarcinoma with neuroendocrine differentiation based on computerized tomography-guided percutaneous lung biopsy. An EGFR gene mutation test showed negative results. Cisplatin and pemetrexed were administered as the neoadjuvant chemotherapy regimen. The primary lesion had reduced markedly, and the enlarged mediastinal lymph node had disappeared after two cycles of neoadjuvant chemotherapy. A left lower lobectomy and mediastinal lymph node dissection were performed. The lesion was confirmed as LCNEC based on postoperative histopathological analysis and immunohistochemical results. The patient underwent four cycles of adjuvant chemotherapy with cisplatin and pemetrexed for a month postoperatively, followed by postoperative adjuvant radiotherapy. The patient was still alive after a follow-up of 24 months, with no evidence of tumor recurrence.

Conclusion: Cisplatin combined with pemetrexed is effective and safe for patients with pulmonary LCNEC.

Keywords: cisplatin; large-cell neuroendocrine carcinoma; pemetrexed; pulmonary tumor.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Prior to neoadjuvant chemotherapy, computerized tomography images of chest in March 2015 indicated a quasi-circular mass in the left lower pulmonary lobe, together with an enlarged mediastinal lymph node.
Figure 2
Figure 2
Histopathological examination of the biopsy specimen revealed a poorly differentiated adenocarcinoma with neuroendocrine differentiation (A, ×100), immunohistochemical staining for CK (B, ×200), CK7 (C, ×200), Ki-67 (D, ×200), P63 (E, ×200), and transcription factor-1 (F, ×200). Abbreviation: CK, cytokeratin.
Figure 3
Figure 3
After two cycles of pemetrexed with cisplatin neoadjuvant chemotherapy, computerized tomography images of chest in May 2015 indicated that the left lower lobe tumor shrank significantly than before and the enlarged mediastinal lymph node almost disappeared.
Figure 4
Figure 4
Histopathological examination of surgical specimens revealed LCNEC. Notes: H&E staining for specimens (A, ×200) and immunohistochemical staining for CD56 (B, ×200), synaptophysin (C, ×200), chromogranin-A (D, ×200), neuron-specific enolase (E, ×200), and NapsinA (F, ×200). Abbreviations: CD56, cluster of differentiation 56; LCNEC, large-cell neuroendocrine carcinoma.
Figure 5
Figure 5
Computerized tomography images of chest indicated that no evidence of recurrence has been detected during the 24-month follow-up. (A and B) Images in June 2015; (C and D) Images in March 2017. (A and C) Images of vertical window; (B and D): images of lung window.

References

    1. Travis WD, Linnoila RI, Tsokos MG, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol. 1991;15(6):529–553.
    1. Dresler CM, Ritter JH, Patterson GA, Ross E, Bailey MS, Wick MR. Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg. 1997;63(1):180–185.
    1. Takei H, Asamura H, Maeshima A, et al. Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg. 2002;124(2):285–292.
    1. Paci M, Cavazza A, Annessi V, et al. Large cell neuroendocrine carcinoma of the lung: a 10-year clinicopathologic retrospective study. Ann Thorac Surg. 2004;77(4):1163–1167.
    1. Veronesi G, Morandi U, Alloisio M, et al. Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer. 2006;53(1):111–115.
    1. Iyoda A, Hiroshima K, Toyozaki T, Haga Y, Fujisawa T, Ohwada H. Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology. Cancer. 2001;91(11):1992–2000.
    1. Zacharias J, Nicholson AG, Ladas GP, Goldstraw P. Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection. Ann Thorac Surg. 2003;75(2):348–352.
    1. Asamura H, Kameya T, Matsuno Y, et al. Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol. 2006;24(1):70–76.
    1. Isaka M, Nakagawa K, Ohde Y, et al. A clinicopathological study of peripheral, small-sized high-grade neuroendocrine tumours of the lung: differences between small-cell lung carcinoma and large-cell neuroendocrine carcinoma. Eur J Cardiothorac Surg. 2012;41(4):841–846.
    1. Travis WD, Rush W, Flieder DB, et al. Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol. 1998;22(8):934–944.
    1. Iyoda A, Hiroshima K, Baba M, Saitoh Y, Ohwada H, Fujisawa T. Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors. Ann Thorac Surg. 2002;73(4):1049–1054.
    1. Peng WX, Sano T, Oyama T, Kawashima O, Nakajima T. Large cell neuroendocrine carcinoma of the lung: a comparison with large cell carcinoma with neuroendocrine morphology and small cell carcinoma. Lung Cancer. 2005;47(2):225–233.
    1. Jones MH, Virtanen C, Honjoh D, et al. Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles. Lancet. 2004;363(9411):775–781.
    1. Iyoda A, Hiroshima K, Nakatani Y, Fujisawa T. Pulmonary large cell neuroendocrine carcinoma: its place in the spectrum of pulmonary carcinoma. Ann Thorac Surg. 2007;84(2):702–707.
    1. Rossi G, Cavazza A, Marchioni A, et al. Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol. 2005;23(34):8774–8785.
    1. Kozuki T, Fujimoto N, Ueoka H, et al. Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol. 2005;131(3):147–151.
    1. Yamazaki S, Sekine I, Matsuno Y, et al. Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer. 2005;49(2):217–223.
    1. Embry JR, Kelly MG, Post MD, Spillman MA. Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy. Gynecol Oncol. 2011;120(3):444–448.
    1. Le Treut J, Sault MC, Lena H, et al. Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study. Ann Oncol. 2013;24(6):1548–1552.
    1. Gilligan D, Nicolson M, Smith I, et al. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet. 2007;369(9577):1929–1937.
    1. Thomas M, Rube C, Hoffknecht P, et al. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol. 2008;9(7):636–648.
    1. Rekhtman N. Neuroendocrine tumors of the lung: an update. Arch Pathol Lab Med. 2010;134(11):1628–1638.
    1. Varlotto JM, Medford-Davis LN, Recht A, et al. Should large cell neuroendocrine lung carcinoma be classified and treated as a small cell lung cancer or with other large cell carcinomas? J Thorac Oncol. 2011;6(6):1050–1058.
    1. Younossian AB, Brundler MA, Totsch M. Feasibility of the new WHO classification of pulmonary neuroendocrine tumours. Swiss Med Wkly. 2002;132(37–38):535–540.
    1. Gibbs AR, Thunnissen FB. Histological typing of lung and pleural tumours: third edition. J Clin Pathol. 2001;54(7):498–499.
    1. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–1260.
    1. Wick MR, Berg LC, Hertz MI. Large cell carcinoma of the lung with neuroendocrine differentiation. A comparison with large cell “undifferentiated” pulmonary tumors. Am J Clin Pathol. 1992;97(6):796–805.
    1. Jiang SX, Kameya T, Shoji M, Dobashi Y, Shinada J, Yoshimura H. Large cell neuroendocrine carcinoma of the lung: a histologic and immunohistochemical study of 22 cases. Am J Surg Pathol. 1998;22(5):526–537.
    1. Roesel C, Terjung S, Weinreich G, et al. A single-institution analysis of the surgical management of pulmonary large cell neuroendocrine carcinomas. Ann Thorac Surg. 2016;101(5):1909–1914.
    1. Albores-Saavedra J, Gersell D, Gilks CB, et al. Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute. Arch Pathol Lab Med. 1997;121(1):34–39.
    1. Gilks CB, Young RH, Gersell DJ, Clement PB. Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a clinicopathologic study of 12 cases. Am J Surg Pathol. 1997;21(8):905–914.
    1. Saji H, Tsuboi M, Matsubayashi J, et al. Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy. Anticancer Drugs. 2010;21(1):89–93.
    1. Iyoda A, Hiroshima K, Moriya Y, et al. Prospective study of adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma. Ann Thorac Surg. 2006;82(5):1802–1807.
    1. Sarkaria IS, Iyoda A, Roh MS, et al. Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience. Ann Thorac Surg. 2011;92(4):1180–1186. discussion 1186–1187.
    1. Malapelle U, Morra F, Ilardi G, et al. USP7 inhibitors, downregulating CCDC6, sensitize lung neuroendocrine cancer cells to PARP-inhibitor drugs. Lung Cancer. 2017;107:41–49.
    1. Iyoda A, Hiroshima K, Moriya Y, et al. Postoperative recurrence and the role of adjuvant chemotherapy in patients with pulmonary large-cell neuroendocrine carcinoma. J Thorac Cardiovasc Surg. 2009;138(2):446–453.
    1. Kenmotsu H, Niho S, Ito T, et al. A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for completely resected high-grade pulmonary neuroendocrine carcinoma (large cell neuroendocrine carcinoma and small cell lung cancer) Lung Cancer. 2014;84(3):254–258.
    1. Kenmotsu Y, Oshita F, Sugiura M, et al. Nedaplatin and irinotecan in patients with large-cell neuroendocrine carcinoma of the lung. Anticancer Res. 2012;32(4):1453–1456.
    1. Kim KW, Kim HK, Kim J, Shim YM, Ahn MJ, Choi YL. Outcomes of curative-intent surgery and adjuvant treatment for pulmonary large cell neuroendocrine carcinoma. World J Surg. 2017;41(7):1820–1827.
    1. Ahmad SI, Kirk SH, Eisenstark A. Thymine metabolism and thymineless death in prokaryotes and eukaryotes. Annu Rev Microbiol. 1998;52:591–625.
    1. Adjei AA. Pharmacology and mechanism of action of pemetrexed. Clin Lung Cancer. 2004;5(suppl 2):S51–S55.
    1. Heidelberger C, Chaudhuri NK, Danneberg P, et al. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 1957;179(4561):663–666.
    1. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589–1597.
    1. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543–3551.
    1. Scagliotti G, Hanna N, Fossella F, et al. The differential efficacy of pemetrexed according to NSCLC histology: a review of two phase III studies. Oncologist. 2009;14(3):253–263.
    1. Ceppi P, Volante M, Saviozzi S, et al. Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer. 2006;107(7):1589–1596.
    1. Ceppi P, Volante M, Ferrero A, et al. Thymidylate synthase expression in gastroenteropancreatic and pulmonary neuroendocrine tumors. Clin Cancer Res. 2008;14(4):1059–1064.
    1. Zheng Z, Li X, Schell MJ, et al. Thymidylate synthase in situ protein expression and survival in stage I nonsmall-cell lung cancer. Cancer. 2008;112(12):2765–2773.
    1. Ishihama H, Chida M, Araki O, et al. Comparison of 5-fluorouracil-related gene expression levels between adenocarcinomas and squamous cell carcinomas of the lung. Jpn J Clin Oncol. 2009;39(1):33–36.
    1. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–2644.

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