Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy
Introduction
Pulmonary neuroendocrine tumors include a spectrum of four clinicopathological entities classified on the basis of the morphological and biological features: typical carcionoid and atypical carcinoid, which are tumors of low to intermediate grade malignancy, and large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC), which are high-grade malignant tumors. Travis et al. proposed the term LCNEC in 1991 [1], for classifying a type of poorly differentiated high-grade carcinoma characterized by a neuroendocrine appearance under light microscopy. LCNEC exhibits more prominent cellular pleomorphism and higher mitotic activity than the atypical carcinoid (AC), and is distinguished from SCLC by the tumor cell size and chromatin morphology. Although several different terminologies and classifications have been proposed previously, and even the present classification of pulmonary neuroendocrine tumors lacks uniform definition criteria, this class of tumors could become widely accepted and included in the updated histological classification of the World Health Organization [2].
The clinical features of LCNEC have not yet been completely clarified. The prognosis of patients with surgically resected LCNEC is reported to be intermediate between that of AC and SCLC [3], [4], [5], and the same as that of resected NSCLC, except that stage I LCNEC has a poorer prognosis than stage I non-small cell lung cancer (NSCLC) [6]. To the best of our knowledge, however, there are no studies that have examined the role of chemotherapy for LCNEC and the prognosis of patients with unresectable LCNEC, even though several reports have been published on the association between response to chemotherapy and the neuroendocrine differentiation of NSCLC [7], [8], [9]. The appropriate treatment of unresectable LCNEC, therefore, remains unclear. In the present study, we attempted to investigate the effectiveness of chemotherapy with cisplatin-based regimens for LCNEC in patients with unresectable and recurrent LCNEC.
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Materials and methods
Eighty-seven of 2790 patients with primary lung cancer who underwent tumor resection from 1982 to 1999 at the National Cancer Center Hospital were found to have tumors with the histological characteristics of LCNEC [6]. Of these, five had received cisplatin-based chemotherapy at the time of recurrence, and were enrolled as subjects of this study. In addition, 303 of 567 patients who were autopsied from 1983 to 1997 at the National Cancer Center Hospital who had the following histological
Results
Overall, 22 cases were recognized as having tumors with histological characteristics consistent with LCNEC among the autopsied and surgically resected cases of primary lung cancer that had received cisplatin-based chemotherapy and had evaluable lesions; of these 17 were autopsied cases and five were surgically resected cases. Two of the autopsied cases were excluded, because no pretreatment pathological or cytological samples were available. The typical microscopic appearance of the tumor
Discussion
In this extensive review of over 3000 lung cancer patients, we found considerable difficulty in evaluating the response of LCNEC to systemic chemotherapy. The pathological diagnosis of LCNEC was established in 87 (3.1%) of 2790 patients treated by surgical resection. This low incidence of LCNEC in surgically treated lung cancer patients is comparable to that in other previously published reports: 2.4% (50/2070), 2.9% (22/766), and 3.6% (53/1530) [16], [17], [18]. Of the 87 patients, only five
Acknowledgment
We thank Ms. Yuko Yabe for kindly preparing this manuscript.
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