InBrief
Large-cell carcinomas are a diagnosis of exclusion when a lung malignancy does not meet the criteria of small-cell lung cancer (SCLC), adenocarcinoma, or squamous-cell carcinoma based on light microscopy and immunohistochemical-marker expression.
Large-cell carcinomas are aggressive and represent about 5%-10% of lung cancers. Histologically, they are malignant epithelial neoplasms (poorly differentiated) without glandular or squamous differentiation or small-cell features.
Causes and Risk Factors
Smoking is the primary risk factor for all lung cancers, including large-cell carcinoma. The median age of presentation is 61 years; men are three times more likely than women to develop these cancers.
Signs and Symptoms
Large-cell carcinoma can present with signs and symptoms similar to those of other types oflung cancer, including cough, chest pain, dyspnea, and hemoptysis.
Diagnostic Evaluation and Differential Diagnosis
On imaging, large-cell carcinoma typically presents as a peripheral mass with or withoutnecrosis. Diagnosis requires biopsy with histologic confirmation that rules out glandular,squamous, and neuroendocrine differentiation. Electron microscopy plus immunohistochemistrycan sometimes better classify tumors and may be required before a diagnosis of large-cellcarcinoma can be made.
Differential diagnoses include other types of lung carcinoma, including small-cell,adenocarcinoma, and neuroendocrine carcinomas; metastatic lesions of the lung; and benignlesions (eg, hamartomas, fibromas).
Treatment Options
Treatment of large-cell carcinoma varies based on the patient’s comorbidities and tumor stage.It may be treated with combinations of surgery, chemotherapy, immunotherapy, and radiationtherapy.
Summary of Lung Cancer Classification
Small-cell lung cancers (SCLCs) include small-cell carcinoma (oat-cell cancer), combinedsmall-cell carcinoma, and neuroendocrine lung cancer (NET).
Nonsmall-cell lung cancers (NSCLCs) include adenocarcinoma, squamous-cell carcinoma,and large-cell carcinoma.
Other large-cell carcinomas include neuroendocrinelarge-cell lung cancers, which tend to bemore aggressive than other neuroendocrine tumors.
Summary of Lung Cancer Classification
Pulmonary Neuroendocrine Tumors (NET)
Pulmonary Carcinoid Tumors
Typical Carcinoid Tumors
Atypical Carcinoid Tumors
Large Cell Neuroendocrine Carcinomas
Small Cell Lung Carcinomas
Carcinoid tumors is also a type of neuroendocrine lung cancer NET's) but represents only asmall percentage of primary lung cancer (less than 1%). Carcinoid lung tumors typically presentas a low grade, well-differentiated, slow-growing tumor. Less commonly they may present asatypical high-grade, poorly differentiated carcinomas. All NETs may produce circulatingneuropeptides.
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References:
Travis WD, Brambilla EW, Burke AP, Marx A, Nicholson AG, eds. WHO Classification of Tumours of the Lung, Pleura, Thymus, and Heart. Lyon, France: IARC Press; 2015.
Clinical Lung Cancer Genome Project; Network Genomic Medicine. A genomics-based classification of human lung tumors. Sci Transl Med. 2013;5(209):209ra153.
Rajdev K, Hasan Siddiqui A, Ibrahim U, Patibandla P, Khan T, El-Sayegh D. An unusually aggressive large cell carcinoma of the lung: undiagnosed until autopsy. Cureus. 2018;10:e2202.
Derks J, Hendriks L, Buikhuisen W, Groen H, Thunnissen E, Van Suylen RJ, Houben R, Damhuis R, Speel E, Dingemans AM. Clinical features of large cell neuroendocrine carcinoma: a population-based overview. European Respiratory Journal 2016 47: 615-624; DOI: 10.1183/13993003.00618-2015.
Limaiem F, Tariq M, Wallen J. Lung Carcinoid Tumors. StatPearls. Last Update: October 16, 2020.
Pulmonary Neuroendocrine Tumors. Memorial Sloan Kettering Cancer Center. https://www.mskcc.org/cancer-care/types/lung/types/pulmonary-neuroendocrine-tumors.