Oncology · Thoracic Oncology

Lung Cancer

USMLE2PANCE
7

Bets

The facts most likely to be tested

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1

Smoking is the dominant risk factor; classic presentation is persistent cough, hemoptysis, dyspnea, and constitutional weight loss.

Confidence:
2

The most accurate diagnostic test is tissue biopsy (bronchoscopic, transthoracic needle, or surgical) after chest x-ray and CT characterize the lesion.

Confidence:
3

Small cell carcinoma is associated with paraneoplastic SIADH and ectopic ACTH (Cushing), whereas squamous cell produces PTHrP-mediated hypercalcemia.

Confidence:
4

For localized non-small cell lung cancer, surgical resection is the mainstay when adequate post-resection lung function remains.

Confidence:
5

Small cell carcinoma is unresectable in 95% of cases due to early dissemination and is treated with chemotherapy and radiation.

Confidence:
6

Surgery is precluded by bilateral disease, contralateral nodes, malignant pleural effusion, or involvement of the heart, carina, aorta, or vena cava.

Confidence:
7

Pancoast tumors cause shoulder pain and Horner syndrome; mediastinal spread causes SVC syndrome or hoarseness from recurrent laryngeal nerve palsy.

Confidence:

Vignette unlocked

A 64-year-old man with a 45-pack-year smoking history presents with cough, fatigue, and a 6 kg weight loss over 3 months. Laboratory studies reveal a serum sodium of 119 mEq/L with low serum osmolality, high urine osmolality, and euvolemia. A chest CT demonstrates a central hilar mass. Bronchoscopic biopsy shows small, dark cells with scant cytoplasm and nuclear molding.

Which of the following is the most likely diagnosis?

+Reveal answer

Small cell lung carcinoma.

A central mass in a heavy smoker with paraneoplastic SIADH (euvolemic hyponatremia, concentrated urine) and small cells with nuclear molding is classic for small cell carcinoma. It is treated with chemotherapy and radiation because it is unresectable in roughly 95% of cases.

Mo

Depth

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High yield triage

Etiology / Epidemiology

Smoking is the dominant risk factor; non-small cell (adeno, squamous, large cell) vs small cell carcinoma.

Clinical Manifestations

Cough, hemoptysis, weight loss, dyspnea; paraneoplastic syndromes (SIADH, ectopic ACTH with small cell).

Diagnosis

Chest x-ray then CT; biopsy is the most accurate diagnostic test; staging CT chest/abdomen.

Treatment

Surgical resection for localized NSCLC; small cell is unresectable in 95% and treated with chemo/radiation.

Prognosis

Poor overall; depends on stage and resectability; small cell carries the worst prognosis.

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Epidemiology & Etiology

Lung cancer is a leading cause of cancer death and is overwhelmingly driven by cigarette smoking. It is broadly divided into non-small cell lung cancer (adenocarcinoma, squamous cell, large cell) and small cell lung cancer. The USPSTF recommends annual low-dose chest CT screening in patients age 50-80 with a 20 pack-year smoking history; screening is not needed if the patient quit more than 15 years ago. Ectopic hormone production (e.g., ACTH, ADH) is associated with lung cancer.

Pertinent Anatomy

Tumors arise from the bronchial/bronchoalveolar epithelium. Squamous cell carcinoma is classically central (arising in proximal bronchi) while adenocarcinoma is typically peripheral. Central tumors can invade adjacent mediastinal structures; involvement of the heart, carina, aorta, or vena cava, or a malignant pleural effusion renders a tumor unresectable. Apical (Pancoast) tumors may invade the brachial plexus and sympathetic chain.

Pathophysiology

Carcinogens in tobacco smoke induce malignant transformation of airway epithelium. Local growth produces airway obstruction, postobstructive pneumonia, and hemoptysis; mediastinal extension can cause SVC syndrome or hoarseness. Paraneoplastic syndromes reflect ectopic secretion: small cell is associated with SIADH and ectopic ACTH (Cushing), while squamous cell classically produces PTHrP-mediated hypercalcemia. Small cell carcinoma typically disseminates early, explaining its near-universal unresectability.

Clinical Manifestations

Common features are persistent cough, hemoptysis, dyspnea, chest pain, and constitutional weight loss. Paraneoplastic presentations include SIADH-induced hyponatremia and ectopic-ACTH Cushing syndrome (both small cell), and hypercalcemia (squamous cell). Pancoast tumors may cause shoulder pain and Horner syndrome; mediastinal spread may produce SVC syndrome or recurrent laryngeal nerve palsy with hoarseness. A malignant pericardial or pleural effusion may cause dyspnea or tamponade.

Diagnosis

Initial imaging is a chest radiograph, followed by CT to characterize the lesion. The most accurate diagnostic test is tissue biopsy (bronchoscopic, transthoracic needle, or surgical). Staging uses CT of the chest and abdomen and assessment of nodal/distant spread to determine resectability. Surgery is precluded by bilateral disease or contralateral nodes, malignant pleural effusion, or involvement of the heart, carina, aorta, or vena cava.

Treatment

For localized non-small cell lung cancer, surgical resection is the mainstay when adequate post-resection lung function remains; lesion size alone does not determine resectability. Small cell carcinoma is considered unresectable in 95% of cases because it is metastatic or has spread beyond one lung, and is treated with chemotherapy and radiation. Advanced NSCLC is managed with chemotherapy, targeted agents, immunotherapy, and/or radiation depending on molecular markers and stage.

Prognosis

Prognosis is poor overall and dominated by stage at diagnosis. Resectable localized NSCLC offers the best survival, whereas advanced disease and small cell carcinoma carry the worst outcomes. Low-dose CT screening of high-risk smokers lowers lung cancer mortality by detecting earlier, resectable disease.

Differential Diagnosis

Tuberculosis: cavitary upper-lobe disease with risk factors, positive acid-fast smear; can mimic malignancy radiographically.

Pneumonia / lung abscess: acute febrile illness with infiltrate that resolves on treatment rather than a persistent mass.

Pulmonary metastasis from another primary: multiple nodules; search for an extrathoracic primary tumor.

Hamartoma / benign solitary pulmonary nodule: stable over time with benign calcification pattern (popcorn calcification).

Histoplasmosis: can produce cavities and mimic TB or cancer ('anything TB can do, histo can do').