Pulmonary Large-Cell Neuroendocrine Carcinoma: From Epidemiology to Therapy

Abstract

Lung neuroendocrine tumors are a heterogeneous subtype of pulmonary cancers representing approximately 20% of all lung cancers, including small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). The frequency appears to be approximately 3% for LCNEC. Diagnosis of LCNEC requires attention to neuroendocrine features by light microscopy and confirmation by immunohistochemical staining for neuroendocrine markers. Both SCLC and pulmonary LCNEC are high-grade and poor-prognosis tumors, with higher incidence in males and smokers and peripheral localization. LCNEC is very rare, and the precise diagnosis on small specimens is very difficult, so we have still too few data to define a standard of treatment for pulmonary LCNECs. Data of literature, most based on retrospective analysis, indicated a poor 5-year overall survival, with a high incidence of recurrence after surgery, even in stage I disease. Primary surgery should be the first option in all operable patients because there is no validate therapeutic approach for LCNEC due to lack of clinical trials in this setting. Neoadjuvant platinum-based regimens remain only an option for potentially resectable tumors. In advanced stages, SCLC-like chemotherapy seems the best option of treatment, with a good response rate but a poor overall survival (from 8 to 16 months in different case series). New agents are under clinical investigation to improve LCNEC patients’ outcome. We reviewed all data on treatment options feasible for pulmonary LCNEC, both for localized and extensive disease.

Clinical significance of nestin and its association with survival in neuroendocrine lung tumours

“…However, some authors suggested that low and high-grade neuroendocrine tumours do not represent the continuum of the same lesion [32]. In our study, in LCNEC patients lymph node status, but not nestin expression, was associated with shorter survival.…”

What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms?

“…However, an increasing body of knowledge is accumulating in lung NET about biomarkers with predictive value, which could modify the therapy of these tumors in near future. This holds true especially for TC and AC where treatment, when non directly surgical (as mainly happens), relies on multimodality approaches or non-conventional drugs, whilst LCNEC and SCLC are generally cured by exclusive chemo-radiotherapy 87,88 .…”

Evaluation of the efficacy of cisplatin–etoposide and the role of thoracic radiotherapy and prophylactic cranial irradiation in LCNEC

“…PCI in patients with ES-SCLC reduces the incidence of brain metastasis, but the impact on overall survival is controversial [20, 21]. The role of TRT and PCI in local or advanced LCNEC remains undefined [6, 22, 23]. …”