Large cell carcinoma with neuroendocrine morphology of the lung.

Second Department of Surgery, Faculty of Medicine, Kagawa University, Japan.
The Japanese Journal of Thoracic and Cardiovascular Surgery 02/2006; 54(1):31-4. DOI: 10.1007/BF02743782
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a malignant neuroendocrine tumor clinicopathologically similar to and falling in-between atypical carcinoid tumor and small cell lung carcinoma (SCLC). The diagnosis of LCNEC is based mainly on a characteristic neuroendocrine morphology and biological neuroendocrine differentiation. In order to know the discrepancy between morphological and biological neuroendocrine differentiation, LCNEC was immunohistochemically and molecular biologically compared with large cell carcinoma with neuroendocrine morphology (LCCNM), which lacked only biological neuroendocrine differentiation among the criteria of LCNEC. Immunohistochemically, disruption of the RB pathway, namely a lack of RB expression and simultaneous overexpression of p16 protein, was characteristic of LCNEC, but not LCCNM. In G2/M cell cycle regulation, 14-3-3 sigma expression was markedly reduced in LCNEC. Moreover, the antibody 34 beta E12 recognizing a set of large-sized keratin gave a different staining pattern between LCNEC and LCCNM. The immunohistochemical data suggested that LCNEC has a similar biological marker profile to SCLC and different from LCCNM. However, a loss of heterozygosity (LOH) analysis using microsatellite markers showed a high frequency of LOH at 3p in both LCNEC and LCCNM as well as in SCLC. Morphological neuroendocrine differentiation might not be identical to biological neuroendocrine differentiation in large cell carcinoma of the lung.
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    ABSTRACT: 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. 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. 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. 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.
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    ABSTRACT: Large cell neuroendocrine carcinoma (LCNEC) of the lung is defined as a poorly differentiated and high-grade neuroendocrine tumor that is morphologically and biologically between atypical carcinoid and small cell lung carcinoma (SCLC). During a survey concerning bcl-2 protein expression in the subtypes of lung cancer, we noticed that two previously diagnosed non-SCLCs met the criteria for LCNEC. Because LCNEC is a newly recognized clinicopathologic entity and because all reported cases have been retrieved from the so-called "neuroendocrine tumor file," we suspected that LCNEC had been underdiagnosed. In the present study, we histologically reviewed 766 surgically resected lung cancers and were able to diagnose 22 (2.87%) LCNECs with the neuroendocrine features subsequently confirmed by immunostaining for multiple neuroendocrine markers. Each case stained positively for at least three general neuroendocrine markers, and 12 (54.5%) also were positive for neuroendocrine hormones. Histologically, most LCNECs showed a marked decrease in or a loss of organoid architecture and could be mistaken for poorly differentiated adenocarcinoma or squamous cell carcinoma. Because our LCNECs are the first to be identified by retrospective review of routinely diagnosed lung cancers, and 18 had been classified as non-SCLC, they may represent cases relatively difficult to diagnose. The present study shows that the most difficult diagnostic factor of LCNEC is the recognition of its light microscopic neuroendocrine features, and LCNEC must be distinguished not only from atypical carcinoid or SCLC, but also from common non-SCLC. Histologically, when an organoid architecture is subtle or absent, the rosettelike structure becomes the best marker for the recognition of neuroendocrine differentiation. Clinically, the prognosis for our LCNECs was significantly worse than that for stage-comparable non-SCLCs (p = 0.046).
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