Lung Carcinoma

In the context of lung cancer, the most common types found are actually metastases, particularly from breast, colon, and renal cancers. Notable risk factors for developing lung cancer include smoking, which elevates the risk by a staggering 20-fold, radiation to the chest, pulmonary fibrosis, and occupational exposures to substances like asbestos, radon, metals, and aromatic hydrocarbons. Patients often present with symptoms such as dyspnea, weight loss, decreased appetite, and, particularly in younger patients, chest pain. Other specific symptoms can include coughing, wheezing, recurrent pneumonia, and hemoptysis, especially when the tumors are centrally located.

The disease manifests primarily as four subtypes: small cell lung carcinoma, squamous cell carcinoma (non-small cell lung carcinoma), adenocarcinoma (non-small cell lung carcinoma), and large cell carcinoma (non-small cell lung carcinoma). Among these, adenocarcinoma is the most prevalent, affecting both smokers and non-smokers and is particularly common in women and patients under 40. It reveals glandular characteristics on histology, such as acinar, papillary, and mucinous formations. A precursor, known as adenocarcinoma in situ (AIS), features tall columnar cells that appear to thicken the alveolar walls, showing a lepidic growth pattern, and may mimic pneumonia on chest X-rays

Squamous cell carcinoma often originates from squamous metaplasia and can progress to dysplasia before becoming invasive. In its well-differentiated form, this carcinoma displays keratin pearls and intercellular bridges, and may also exhibit central necrosis and cavitation. Small cell carcinoma (SCC) is a neuroendocrine tumor that is notorious for early metastasis, often appearing diffusely in both lungs. It is composed of sheets of round, basophilic cells with scant cytoplasm and granular ‘salt and pepper’ chromatin. Additionally, it tests positive for the neuroendocrine marker chromogranin and is sensitive to both radiation and chemotherapy. Paraneoplastic syndromes like SIADH and Lambert-Eaton Myasthenic Syndrome (LEMS) are often associated with SCC. Large cell carcinoma is characterized by large, undifferentiated anaplastic cells with prominent nucleoli and large nuclei.

Lung cancer can lead to localized complications, such as Pancoast syndrome, which occurs with tumor spread to the superior pulmonary sulcus and can cause arm and shoulder pain due to invasion of the brachial plexus. Additionally, Pancoast tumors may result in Horner's syndrome due to spread to the sympathetic chain ganglia, causing ptosis, miosis, and anhidrosis. Lung cancer may also extend medially to involve mediastinal structures, causing symptoms like hoarseness and SVC syndrome.

Systemic effects often manifest as paraneoplastic syndromes. These include SIADH and Lambert-Eaton Myasthenic Syndrome (LEMS) associated with SCC; the latter causing symmetrical proximal muscle weakness due to blocked presynaptic calcium channels. Humoral hypercalcemia of malignancy is another paraneoplastic syndrome, particularly associated with squamous cell carcinoma, and is induced by parathyroid hormone-related protein (PTHrP) release from the tumor. Additional syndromes include Cushing's syndrome in SCC, hypertrophic osteoarthropathy in adenocarcinoma, and a variety of neurological syndromes in SCC due to autoimmune responses.