Distinguishing non-small-cell carcinoma from its histological mimics: diagnostic challenges in pulmonary pathology

Pulmonary pathologists often must make a diagnosis based on small specimens derived from aspirated or solid tissue fragments, extracted under radiological guidance, containing limited diagnostic material. This poses a diagnostic challenge. Advances in treatment also demand tissue is analysed for multiple molecular anomalies therefore pathologists must be judicious in their use of ancillary tests such as immunohistochemistry. Whilst the majority of tumours encountered are non-small cell lung carcinomas, the lungs and thorax are a common metastatic site and can display a wide variety of different tumour types. Some tumours can closely mimic the appearances of non-small cell carcinomas and failure to recognise these can result in misdiagnosis and incorrect treatment and management for the patient. In this article we specifically focus on a variety of different tumours that can masquerade as non-small cell carcinomas. This includes both benign and malignant primary lung tumours, sarcomas, melanomas and germ cell tumours. We describe how to approach and recognise these entities, with specific focus on the histological and immunohistochemical appearances, and identify potential pitfalls to avoid in routine practice.