Large-cell neuroendocrine carcinoma of the lung: an aggressive neuroendocrine lung cancer

Large cell neuroendocrine carcinoma (LCNEC) is part of the neuroendocrine spectrum of pulmonary tumors. This increasingly recognized tumor has been reported to have 5-year actuarial survival rates following resection that are worse than those described for other variants of non-small cell lung cancer (NSCLC). Therefore, debate has emerged regarding whether the tumors should be classified and treated as NSCLC or small-cell lung cancer. This article reviews the tumor characterization, biology, presentation and diagnosis, surgical therapy, results of therapy, and long term prognosis of patients with LCNEC.     

Large cell neuroendocrine carcinoma of the lung: an aggressive disease potentially treatable with surgery

BACKGROUND: Assessment of clinical and pathologic features of large cell neuroendocrine carcinoma to confirm its specificity in the setting of high grade neuroendocrine pulmonary tumors. METHODS: From 1989 to 2001, 123 patients with a neuroendocrine carcinoma were surgically treated in a curative intent at a single institution. According to the 1999 World Health Organization classification, 20 patients were reviewed as having a large cell neuroendocrine carcinoma. Clinical data as well as detailed pathologic analysis and survival were collected. RESULTS: There were 18 men and 2 women. The median age was 62 years. Four patients had a preoperative diagnosis of large cell neuroendocrine carcinoma. The resections consisted of 14 lobectomies and 6 pneumonectomies. There was no operative death. Complications occurred in 7 patients (35%). Four patients had a stage I of the disease, 4 had stage II, 9 had stage III, and 3 had stage IV. At follow-up (median, 46 months), 13 patients died from general recurrence and 7 patients were still alive. Median time to progression was 9 months (range, 1 to 54 months). The 5-year survival rate was 36% (median, 49 months) and it seemed to be negatively influenced by the disease stage (54% for stage I-II vs 25% for stage III-IV; p = 0.07), the presence of metastatic lymph node (45% for N0/N1 vs 17% for N2; p = 0.12), or vessel invasion (66 vs 25%; p = 0.18). CONCLUSIONS: Large cell neuroendocrine carcinoma predominantly occurred in men. An accurate tissue diagnosis was rarely obtained preoperatively. Although overall survival after resection was substantial, large cell neuroendocrine carcinoma frequently showed pathologic features of occult metastatic disease, such as lymph node or vessel invasion, or both.     

Large cell neuroendocrine carcinoma: an unusual presentation

Primary lung cancer presenting as a pulmonary artery mass is unusual. We describe such a presentation in a patient with a large cell neuroendocrine carcinoma of the lung, its evaluation, and its treatment.     

Large cell carcinoma with neuroendocrine morphology of the lung

We experienced a surgical case of large cell carcinoma with neuroendocrine morphology (LCCNM) of the lung. A 76-year-old man was admitted to our hospital because a routine chest X-ray examination had revealed a nodular shadow in the left lung field. 18F-fluorodeoxyglucose positron emission tomography showed accumulation of fluorodeoxyglucose in an area corresponding to the shadow. Transbronchial lung biopsy failed to give a definitive diagnosis, therefore, open lung biopsy was performed because of suspected lung cancer. Needle biopsy was performed, and the tumor was diagnosed as large cell neuroendocrine carcinoma by rapid intraoperative pathological examination. As sampling of hilar lymph nodes revealed no metastasis, left upper segmentectomy was performed for severe obstructive pulmonary disease. Immunohistochemical examination finally diagnosed the tumor as LCCNM. The patient is doing well without recurrence at ten months after surgery.     

Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer

OBJECTIVE: Although visceral pleural invasion by non-small cell lung cancer is considered a poor-prognostic factor, further information is lacking, especially in relation to other clinicopathologic prognostic factors. We assessed the relationship between visceral pleural invasion and other clinicopathologic characteristics and evaluated its significance as a prognostic factor. METHODS: We reviewed 1074 patients with surgically resected T1/2 non-small cell lung cancer for their clinicopathologic characteristics and prognoses. The patients were divided into 2 groups according to visceral pleural invasion status (visceral pleural invasion group and non-visceral pleural invasion group). Both groups were compared with regard to age, sex, histology, tumor size, tumor differentiation, lymph node involvement, lymphatic invasion, vascular invasion, scar grade, nuclear atypia, mitotic index, serum carcinoembryonic antigen level, and survival. Univariate and multivariate analyses were conducted. RESULTS: Visceral pleural invasion was identified in 288 (26.8%) of the resected specimens. Survival was 76.0% at 5 years and 53.2% at 10 years in the non-visceral pleural invasion group and was 49.8% at 5 years and 37.0% at 10 years in the visceral pleural invasion group. The difference between groups was highly significant ( P < .0001). Visceral pleural invasion was also significantly associated with a higher frequency of lymph node involvement. However, regardless of N status (N0 or N1/2), there was a significant difference in survival when the visceral pleura was invaded. Visceral pleural invasion was observed significantly more frequently in tumors with factors indicative of tumor aggressiveness/invasiveness: moderate/poor differentiation, lymphatic invasion, vascular invasion, high scar grade, high nuclear atypia grade, high mitotic index, and high serum carcinoembryonic antigen level. By multivariate analysis, visceral pleural invasion proved to be a significant independent predictor of poor prognosis in non-small-cell lung cancer patients with or without lymph node involvement. CONCLUSIONS: Visceral pleural invasion is a significant poor-prognostic factor, regardless of N status. Our analyses indicated that visceral pleural invasion is an independent indicator of non-small cell lung cancer invasiveness and aggressiveness.     

Tall cell variant: an aggressive form of papillary thyroid carcinoma.

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.     

Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases

OBJECTIVE: Large cell neuroendocrine carcinoma of the lung is a newly recognized clinicopathologic entity. The clinical characteristics and optimal treatment of patients with large cell carcinomas are not yet established. The aim of this study was to define the clinicopathologic characteristics of large cell neuroendocrine carcinoma. METHODS: The histologic characteristics of the patients receiving an initial diagnosis of poorly differentiated non-small cell lung carcinoma (n = 484), small cell carcinoma (n = 55), carcinoid (n = 31), and large cell neuroendocrine carcinoma (n = 12) were retrospectively reviewed according to World Health Organization criteria. Immunohistochemistry was performed to confirm the neuroendocrine phenotype. The outcomes and other clinical characteristics of those patients with large cell neuroendocrine carcinoma were retrospectively analyzed and compared with those of patients with poorly differentiated carcinoma of other histologic types. RESULTS: A total of 87 patients were given a diagnosis of large cell neuroendocrine carcinoma after the histologic review. These patients comprised 3.1% of all patients undergoing resection for primary lung cancer during the same period. The overall 5-year survival was 57%. The 5-year survivals of patients with stage I, II, III, and IV disease were 67%, 75%, 45%, and 0%, respectively. There was no statistically significant difference between the overall survival of patients with large cell neuroendocrine carcinoma and those with other non-small cell lung cancers. There was a significant difference between the survival of patients with stage I large cell neuroendocrine carcinoma and that of patients with the same stage of other non-small cell lung carcinomas. The site of the first documented recurrence was locoregional in 12 patients (34%), distant metastases in 20 patients (57%), and both simultaneously in 3 patients. Locoregional lymph node recurrences were observed frequently. More than 80% of recurrences were found within 1 year after the operation. CONCLUSION: In terms of prognosis, large cell neuroendocrine carcinoma is distinctly different from other non-small cell lung cancers. The prognosis of large cell neuroendocrine carcinoma was poor, even for early stage disease; the prognosis of the stage I disease of large cell neuroendocrine carcinoma was poorer than that of the same stage of other non-small cell lung cancers. Because of its aggressive clinical behavior and poor prognosis, large cell neuroendocrine carcinoma should be recognized as one of the poorest prognostic subgroups among primary lung cancers, and therefore novel therapeutic approaches should be established.     

Large cell neuroendocrine carcinoma of the lung; report of a case

Large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer and it has the least favorable prognosis. We describe our experience with a patient in whom LCNEC was diagnosed. A 65-year-old man who was pointed out abnormal shadow on a chest X-ray film in the health screening was admitted to the hospital. Chest X-ray film and computed tomography (CT) scan showed a 4 x 3 cm mass in the left-S2. Poorly differentiated adenocarcinoma of the left lung was suspected based on CT guided cytology. An upper lobectomy of the left lung and dessection of the mediastinal lymph nodes were performed. This tumor showed light microscopic and immunohistochemical evidences of neuroendocrine differentiation. Further it showed positive responses in neuronspecific enolase (NSE), synaptophysin, and chromogranin-A stainings. Pathological diagnosis was stage IB (pT2N0M0) LCNEC. There have been no findings of tumor recurrence 22 months after the operation.     

Large cell neuroendocrine carcinoma of the lung: a 10-year clinicopathologic retrospective study

BACKGROUND: Large cell neuroendocrine carcinoma is a recently recognized histologic entity whose clinical features and optimal treatment have not yet been well defined and are still being assessed. We report our retrospective assessment of cases of large cell neuroendocrine carcinoma observed from 1989 to 1999 in terms of survival. METHODS: Cases of large cell neuroendocrine carcinoma diagnosed between 1989 and 1999 were reassessed retrospectively according to the World Health Organization classification. The clinical outcome and pathologic features of all cases are described. Survival rates of patients with large cell neuroendocrine carcinoma are compared with those patients with small cell lung cancer treated in the same period. RESULTS: Patients were 41 men and 7 women with an average age of 63.7 years. Twenty-nine patients (60.4%) had pathologic stage I disease, 11 patients (22.9%) had pathologic stage II disease, and 7 patients (14.6%) had pathologic stage IIIA disease. One patient (2.1%) had pathologic stage IIIB disease. No patient underwent induction chemotherapy. Two patients underwent adjuvant chemotherapy and 2 underwent mediastinal radiotherapy for N2. No death was reported in the perioperative period. The median follow-up was 5 years. The actuarial survival for the entire group was 60.4% at 1 year, 27.5% at 3 years, and 21.2% at 5 years. The actuarial survival of accurately staged, stage I patients at 5 years was 27%. CONCLUSIONS: The findings suggest that treating large cell neuroendocrine carcinoma by means of applying treatment for nonsmall cell lung cancer leads to a prognosis that is worse than that for nonsmall cell lung cancer, even in terms of low pathologic stages.     

Large cell carcinoma of the lung: a highly aggressive tumor with dismal prognosis

A retrospective review was made of 96 consecutive patients with large cell carcinoma of the lung admitted to Emory University Hospital over 10 years. Only 10 patients were seen with stage I lesions favorable for resection. The remainder were treated primarily with irradiation or chemotherapy. Mean survival for clinical stage I patients was 15.9 months; stage IIIA patients, 7.9 months; stage IIIB patients, 7.1 months; and stage IV patients, 5.8 months. Only 1 patient survived for 5 years. This distinct and highly aggressive form of lung cancer most commonly is seen at an advanced stage and is associated with an unusually dismal prognosis regardless of the method of treatment employed.     

Large cell neuroendocrine carcinoma of the lung metastatic to the cauda equina

Background ContextLarge cell neuroendocrine carcinoma of the lung is an aggressive tumor with unique histopathological features. It is not known to metastasize to the spine.PurposeTo report a metastatic case of this rare tumor to the cauda equina.Study DesignCase report.MethodsRetrospective case review and review of the literature.ResultsThe authors report a rare case of a large cell neuroendocrine lung metastasis to the lumbar spine, causing right foot drop. Magnetic resonance imaging revealed a heterogeneously enhancing intradural extramedullary mass at L2/L3 level compressing the surrounding nerve roots. During surgery, the identified nerve roots were encased by the tumor, and the dissection was tedious. Postoperatively, the patient reported significantly improved back pain and he had severe foot weakness. The functional outcome was poor because the patient lost entirely his foot function; however, his back pain improved significantly after surgery.ConclusionsThis is the first published study in which the authors described a metastasis of a rather uncommon lung cancer to the cauda equina. When a lesion of the cauda equina presents with a rapid progressive neurological deficit, leptomeningeal metastasis should be in the differential diagnosis.     

Stage I non-small cell lung carcinoma: really an early stage?

OBJECTIVE: We review our results on surgical treatment of patients with stage I non-small cell lung carcinoma and we attempted to clarify the prognostic significance of some surgical--pathologic variables. METHODS: From 1993 to 1999, 667 patients received curative lung resection and complete hilar and mediastinal lymphadenectomy for non-small cell lung cancer. Of these, there were 436 Stage I disease (65%), of whom 144 T1N0 and 292 T2N0. No patients had pre- or postoperative radio- or chemotherapy. Prognostic significance of the following independent variables was tested using univariate (log-rank) and multivariate (Cox proportional-hazards) analysis: type of resection (sublobar vs lobectomy vs pneumonectomy), histology (squamous cell vs adenocarcinoma), tumour size (3cm), histologic vascular invasion, visceral pleura involvement, positive bronchial resection margin, general T status. RESULTS: Overall 5-year survival was 63%. In both univariate and multivariate survival analysis, significant prognostic factors were histology (adenocarcinoma 65% vs squamous cell carcinoma 51%), tumour size (3cm 46%), and the presence of negative resection margin. Five-year survival by general T status was 66% in T1N0 vs 55% in T2N0 disease (P=0.19). CONCLUSIONS: Despite advances in early diagnosis and surgical technique, 5-year survival of stage I non-small cell lung carcinoma remains low as compared to survival of other solid organ neoplasm. Tumour size 相似文献   

Progress in lung cancer: Non-oat cell (non-small cell lung cancer)

Lung cancer remains the greatest killing cancer in the United States with 149,000 new cases expected in 1987. The present expected mortality rate is 87 per cent. More women in the United States died of lung cancer than breast cancer in 1986. Asymptomatic, early and curable lung cancer in high risk individuals is usually found by routine chest X-ray. So-called Stage I lung cancer was reported to have a 83 per cent survival rate at three years by Martini and Beattie in 1977 and 70 per cent five year survival rate subsequently. When the more than 30,000 volunteer males were enrolled in the National Cancer Institute, national lung program for screening, 223 unsuspected lung cancers were found. 47 per cent were Stage I with a survival rate at five years of over 76 per cent. The PMI-Strang/Memorial Sloan Kettering Cancer Center study found 53 cancers in its first screen and 235 lung cancers over the next eight years of the study. Forty per cent were Stage I with a five year survival rate of 70 per cent. Sputum cytology as compared to chest X-ray was of little additional value. Studies (Martini) of N1 lung cancer was found to have a 49 per cent survival rate following resection. The N2 group of lung cancers where the mediastinal tumor was surgically removable and followed by external radiation therapy had a 27 per cent survival rate at five years. Those tumors with solitary brain metastases where the solitary brain metastasis could be resected and the primary tumor controlled, gave a 27 per cent survival rate at six years. The group of advanced N2 disease where the mediastinum could not be completely cleared were a serious group of cancers. A study of 100 patients treated from 1977 to 1980 with surgery plus internal radiotherapy followed by external radiotherapy had an overall 22 per cent survival rate for four to eight years with most of the deaths occurring because of metastases outside the chest. More recently chemotherapy has been used pre-operatively for those individuals with advanced lung cancer in the chest then followed by a combination of surgery, internal radiotherapy, external radiotherapy and more chemotherapy, if chemotherapy sensitive. This is the so-called multidisciplinary approach. In our present early studies it seems that those so treated who are chemotherapy sensitive have a 44 per cent, two year survival rate in a group of patients considered to have extremely poor prognosis. Director Kriser Lung Cancer Center, Chief Thoracic Surgery, Director Clinical Cancer Programs, Beth Israel Medical Center Chief Medical Officer Emeritus, Attending Surgeon, Member of Board of Overseers, Memorial-Sloan-Kettering Cancer Center This report is the gist of a paper read by E.J.B. at the 87th Annual Congress of the Japanese Surgical Society, Tokyo, Japan, 1987.     

Large cell neuroendocrine carcinoma of the lung with a cystic appearance on computed tomography

Almost all reported cases of large cell neuroendocrine carcinoma (LCNEC) of the lung are solid-type tumors. We encountered a rare case of LCNEC displaying a cystic shape. An abnormal cystic shadow was revealed on chest computed tomography in a 71-year-old man who underwent total gastrectomy due to gastric cancer 5 years earlier. The cystic lesion enlarged from 7 mm to 16 mm over 7 months, so surgery was performed for definitive diagnosis and therapy. Microscopy revealed rosette patterns, a high mitotic rate and a large area of necrosis. Neuroendocrine differentiation was confirmed on immunohistochemical examinations using chromogranin, synaptophysin and NCAM (CD56). Given these findings, LCNEC was diagnosed. This is the first report of LCNEC with a cystic shape. This case challenges preconceptions regarding the radiographic appearance of LCNEC. (Jpn J Thorac Cardiovasc Surg 2006; 54:174-177)     

Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) and large cell carcinoma with neuroendocrine morphology of the lung are both currently classified as subtypes of large cell carcinomas according to the World Health Organization IASLC classification system for lung and pleural tumors. Prognosis is reported as similar to that of small cell carcinomas. There is no consensus on management of this subset and adjuvant chemotherapy is recommended by some for early stage LCNEC to impact long-term prognosis. We retrospectively reviewed a cohort of patients at our institution who had this type of tumor to determine factors that might influence survival. METHODS: Twenty-one cases of LCNEC and large cell carcinoma with neuroendocrine morphology were identified in the files of the Royal Brompton Hospital between 1986 and 1999. All patient data were reviewed, and complete follow-up was achieved with 20 of these patients. RESULTS: Of the 21 patients identified, 20 underwent resection with systematic nodal dissection in 18. There was no in-hospital mortality. Of those patients fully staged by systematic nodal dissection, 9 were stage I, 5 were stage II and 4 were stage III. Median follow-up was 25 months (range, 2 to 120 months). At the time of review, 11 patients were alive and free of disease. One patient was alive and free of disease when lost to follow-up. Nine patients had died, 7 related and 2 unrelated to disease. The 5-year actuarial survival for the entire group was 47%. The actuarial survival of accurately staged, stage I patients at 5 years was 88%. The actuarial survival of patients in stage II and III was 28% at 5 years. CONCLUSIONS: LCNEC and large cell carcinoma with neuroendocrine morphology are aggressive tumors, but patients with completely resected disease after systematic nodal dissection have a better prognosis than previously described. Patients with more advanced disease have a poor prognosis.     

Pneumonectomy for non-small cell lung cancer

Purpose

To assess the mortality, complications and major morbidity of pneumonectomy for non-small cell lung cancer (NSCLC) and to establish the importance of various prognostic factors.

Methods

We reviewed retrospectively the hospital records of 71 consecutive patients who underwent pneumonectomy for NSCLC between 1992 and 2007 to evaluate the significance of risk factors for an adverse outcome. Patients were divided into two period groups according to the period when they were treated: early (1992–1999; n?=?47) and late (2000–2007; n?=?24).

Results

Both the 30-day and the in-hospital mortality rates were 4.2?% (3/71). Complications developed in 31.3?% (22/71) and overall 5-year survival was 23.1?%. Pathological stage III or more, T3 or more, and N2 or more were risk factors of an adverse outcome. Survival was not significantly influenced by histological type, the side of surgery, or curability. The 5-year survival rates for the early and late periods were 19.6 and 32.9?%, respectively. There were more patients with clinical N2 or 3 disease in the early period than in the late period (66.0 vs. 33.3?%).

Conclusions

Pneumonectomy is associated with acceptable overall morbidity and mortality; however, patients with pathological stage III or more, T3 or more, and N2 or more disease require special consideration. Pneumonectomy should be performed only in selected patients.     

Angiogenesis in non-small cell lung cancer

Two processes are necessary for a tumor colony to grow and become invasive: angiogenesis and basement membrane degradation. Angiogenesis is the formation of new blood vessels from the endothelium of existing vasculature, in response to the metabolic demand of the tumor. Assessment of the degree of tumor angiogenesis may improve risk stratification in patients with lung cancer, especially those with early-stage disease. In addition, the strategy of blocking the mechanism of angiogenesis may prove to be an effective therapeutic alternative for patients with nonsmall cell lung cancer. Clinical trials evaluating novel antiangiogenic agents, including antibodies to vascular endothelial growth factor (VEGF) and compounds directed at the tyrosine kinase receptor, are ongoing.