Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Kozuki, Toshiyuki; Fujimoto, Nobukazu; Ueoka, Hiroshi; Kiura, Katsuyuki; Shiomi, Katsuhiko; Mizobuchi, Koichi; Tabata, Masahiro; Hamazaki, Shuji; Tanimoto, Mitsune

doi:10.1007/s00432-004-0626-z

Cited by 32 publications

(26 citation statements)

References 24 publications

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“…The two patients received chemotherapy in an induction setting followed by complete surgical resection. However, because of the difficulty of making a preoperative pathological diagnosis of LCNEC, most previous reports have focused on the postoperative diagnosis of surgical specimens 2, 9. Even when complete surgical resection is achieved, recurrence is frequently observed in patients with LCNEC.…”

Section: Discussionmentioning

confidence: 99%

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Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound‐guided transbronchial needle aspiration

et al. 2017

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BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) is a relatively rare subtype of lung malignancy. According to revised 2015 World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry. In this study, we reevaluated endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) samples of patients previously diagnosed with LCNEC using the revised WHO criteria.MethodsClinical tissue samples that had been obtained by EBUS‐TBNA between January 2004 and December 2011, and that had been pathologically diagnosed as LCNEC according to the previous criteria, were reevaluated according to the revised WHO criteria.ResultsThe records of 471 lung cancer patients with mediastinal or hilar lymph node metastasis diagnosed by EBUS‐TBNA were analyzed. Thirteen patients were diagnosed with LCNEC; one of which was diagnosed based on cytology alone because the histological material was insufficient for a histological examination. Among the 12 cases in which a histological examination was performed, nine were diagnosed with possible LCNEC based on neuroendocrine marker positivity, while three were diagnosed with suspected LCNEC because they did not meet the immunostaining criteria. The patient who was cytologically diagnosed was found to have non‐small cell carcinoma with neuroendocrine morphology.ConclusionLCNEC could be pathologically diagnosed based on 2015 WHO criteria using EBUS‐TBNA samples.

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Section: Discussionmentioning

confidence: 99%

“…The prognosis of patients with LCNEC is reported to be poor, with five‐year survival rates of 15–57% 2. According to the revised World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry (IHC).…”

Section: Introductionmentioning

confidence: 99%

Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound‐guided transbronchial needle aspiration

et al. 2017

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“…This finding suggests that it inappropriate to classify LCNEC into LCC according to the miRNA marker method. LCNEC is actually known to be genetically and immunohistochemically more similar to SCLC than NSCLC (25,26).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma

Hamamoto

Soejima

Yoda

et al. 2013

Molecular Medicine Reports

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Abstract. Recent advances in the treatment of non-small cell lung cancer (NSCLC) with new agents require accurate histological subtyping at diagnosis to avoid the higher risk of an adverse response and to obtain the maximum therapeutic response. However, interobserver variability, tumor hetero geneity and the degree of differentiation may affect the decision concerning a pathological diagnosis of NSCLC. Therefore, the aim of this study was to identify specific microRNAs (miRNAs) as standardized biomarkers with high sensitivity and specificity in order to distinguish between squamous cell carcinoma (SCC) and adenocarcinoma (AC). Quantitative polymerase chain reaction (qPCR)-based miRNA array analysis was performed to identify microRNAs differentially expressed between SCC and AC using 86 resected NSCLC samples in addition to adjacent normal tissues. The results were confirmed by independent qRT-PCR assays with the same test samples and 88 additional validation samples, and from this we evaluated the usefulness of the identified miRNAs as biomarkers to distinguish between SCC and AC. Three miRNAs (hsa-miR-196b, hsa-miR-205 and hsa-miR-375) were identified. Discriminant analysis combining the three miRNAs appeared to distinguish SCC from AC accurately in the test and validation samples, demonstrating a sensitivity and specificity of 76 and 80%, and 85 and 83%, respectively. hsa-miR-196b, hsa-miR-205 and hsa-miR-375 were identified as biomarkers capable of distinguishing between lung SCC and lung AC. These newly identified miRNAs may prove to be highly valuable molecular markers for the classification of NSCLC histological subtypes and may contribute to the pathogenesis of each subtype of NSCLC.

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“…The type and efficacy of salvage chemotherapeutic regimens differed considerably between the two groups: salvage regimens including irinotecan, platinum, or taxanes, commonly used in the SCLC-regimen group, provided relatively high objective response rates; whereas the frequently used salvage agents in the NSCLC-regimen group, such as pemetrexed, gefitinib, and erlotinib, failed to induce objective responses. A small retrospective review of 12 patients with LCNEC [13] provided support for the therapeutic approach used in SCLC, i.e. cisplatin-etoposide chemotherapy with or without radiotherapy, which produced partial or complete responses.…”

Section: Discussionmentioning

confidence: 99%

Multicentre phase II study of cisplatin–etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study

Treut¹,

Sault²,

Léna³

et al. 2013

Annals of Oncology

146

114

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17. Herder GJ, van Tinterent TH, Golding RP et al. Clinical prediction Background: The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear.Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives.Patients and methods: Prospective, multicentre, single-arm, phase II study with a centralised review of treatmentresponse and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days. Results: Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients. Conclusions:The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC). Key words: carcinoma, clinical trial phase II, large cell neuroendocrine tumours, small-cell lung cancer introduction Large-cell neuroendocrine carcinoma (LCNEC) of the lung accounts for no more than 1% of all lung cancers. The typical histological features, first described in 1991 [1, 2], include large cells with abundant cytoplasm, a high mitotic rate, extensive necrosis, and a neuroendocrine growth pattern. The World Health Organisation currently classifies LCNEC as a distinct subtype of pulmonary large-cell carcinoma [3] and, therefore, as a subtype of non-small-cell lung carcinoma (NSCLC). However, LCNEC lacks the specific histologic features of NSCLC such as glandular or squamous differentiation, but instead displays evidence of neuroendocrine differentiation reminiscent of small-cell lung carcinoma (SCLC), although the malignant cells in SCLC are smaller, with scant cytoplasm, and invade the tissues in sheets. LCNECLCNEC shares genetic alterations with SCLC [4]. The higher mitotic rates and more extensive necrosis seen in LCNEC and SCLC are in contrast to the lower-grade neuroendocrine tumours, i.e. typical and atypical carcinoids. LCNEC and SCLC also share clinical characteristics including a preponderance of males and smokers and an aggressive clinical course [5][6][7][8][9]. The clinical outcome of LCNEC patients is poor, with overall 5-year survival rates ranging from 15% to 57%. Studies have demonstrated signifi...

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Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Cited by 32 publications

References 24 publications

Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound‐guided transbronchial needle aspiration

Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound‐guided transbronchial needle aspiration

Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma

Multicentre phase II study of cisplatin–etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study

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