Respiratory Infections & Lung Cancer
Read the pneumonia pattern, then map each lung cancer to its cell type and paraneoplastic tell
Pneumonia patterns and organisms
Three anatomic patterns. Pneumonia is classified by how it distributes in the lung, and the pattern hints at the organism. Lobar pneumonia consolidates an entire lobe; bronchopneumonia forms patchy, peribronchiolar foci that are often bilateral and multilobar; interstitial (atypical) pneumonia diffusely inflames the alveolar walls while the airspaces stay relatively clear.
| Pattern | Distribution | Classic organisms |
|---|---|---|
| Lobar | Entire lobe consolidated with intra-alveolar exudate | S. pneumoniae (>95%); Klebsiella (alcoholics, aspiration) |
| Bronchopneumonia | Patchy, centered on bronchioles; often bilateral, multilobar | S. aureus, H. influenzae, Klebsiella, Pseudomonas, S. pyogenes |
| Interstitial (atypical) | Diffuse inflammation of alveolar septa | Mycoplasma, Chlamydophila, viruses (RSV, influenza, CMV), Coxiella, Legionella |
Lobar pneumonia. Streptococcus pneumoniae causes >95% of lobar pneumonia. Klebsiella causes it in alcoholics and after aspiration, with thick, blood-tinged "currant-jelly" sputum from its heavy mucoid capsule. Untreated, lobar pneumonia evolves through four stages over about a week:
- CongestionDays 1–2: red, engorged vessels, bacteria-rich fluid
- Red hepatizationDays 3–4: RBCs, fibrin, and neutrophils fill alveoli; firm, liver-like lobe
- Gray hepatizationDays 5–7: RBCs lyse; fibrinosuppurative exudate persists
- ResolutionDay 8 onward: macrophages clear debris by enzymatic digestion
Bronchopneumonia. Patchy consolidation centered on bronchioles, often bilateral, caused by Staphylococcus aureus, Haemophilus influenzae, Klebsiella, Pseudomonas, and Streptococcus pyogenes. Secondary S. aureus bronchopneumonia after influenza is a classic scenario.
Interstitial (atypical) pneumonia. Mycoplasma pneumoniae is the classic cause in young adults (students, military recruits), producing a mild "walking pneumonia." It lacks a cell wall, so it is invisible on Gram stain and unaffected by β-lactams (macrolides or doxycycline work), and it induces IgM cold agglutinins that can cause hemolysis. Other causes include Chlamydophila, viruses (RSV, influenza, CMV), Coxiella, and Legionella.
Typical vs atypical pneumonia
Clinical contrast. Typical organisms produce an abrupt illness with purulent sputum and lobar consolidation. Atypical organisms cause an insidious illness with dry cough, low-grade fever, extrapulmonary symptoms, and a diffuse interstitial pattern that often looks worse on x-ray than the patient does.
| Feature | Typical | Atypical |
|---|---|---|
| Organisms | S. pneumoniae, H. influenzae, Klebsiella | Mycoplasma, Chlamydophila, Legionella, viruses |
| Onset and fever | Abrupt, high fever | Insidious, low-grade fever |
| Cough | Productive, purulent sputum | Dry |
| Imaging | Lobar consolidation | Diffuse interstitial infiltrates |
| Extrapulmonary symptoms | Uncommon | Common (headache, myalgia, hemolysis) |
Legionella is the "atypical" organism that often behaves like a typical one: severe pneumonia with consolidation, high fever, GI symptoms, and hyponatremia; the urine antigen test aids diagnosis.
Lung cancer: location and cell type
Overview. Lung cancer is the leading cause of cancer death, and smoking is the main risk factor (radon and asbestos add risk). Non-small cell carcinomas make up ~85% (adenocarcinoma, squamous, large cell) and small cell lung cancer (SCLC) ~15%. Location is a key clue: the two "S" tumors, squamous and small cell, are central (hilar) and have the strongest smoking link, whereas adenocarcinoma and large cell carcinoma are peripheral.
| Type | Location | Histology, markers | Associations |
|---|---|---|---|
| Small cell (oat cell) | Central | Neuroendocrine Kulchitsky cells; chromogranin, synaptophysin, NSE; myc amplification | SIADH, ectopic ACTH, Lambert-Eaton, anti-Hu; chemo/radiation, not surgery |
| Squamous cell | Central | Keratin pearls, intercellular bridges | PTHrP → hypercalcemia; cavitation |
| Adenocarcinoma | Peripheral | Glandular, often mucinous | Most common overall and in nonsmokers, women; EGFR, ALK, KRAS; clubbing |
| Large cell | Peripheral | Undifferentiated, anaplastic | β-hCG → gynecomastia; poor prognosis |
| Bronchial carcinoid | Often endobronchial | Well-differentiated neuroendocrine; chromogranin | Low grade; carcinoid syndrome uncommon |
Cell types and their paraneoplastic tells
Small cell carcinoma. Sheets of small, dark neuroendocrine cells with scant cytoplasm derived from Kulchitsky cells, often with myc amplification. It is very aggressive and usually metastatic at diagnosis, so it is treated with chemotherapy and radiation rather than resection. Its neuroendocrine nature explains its paraneoplastic syndromes:
- SIADH: ectopic ADH → euvolemic hyponatremia with inappropriately concentrated urine.
- Ectopic ACTH: Cushing syndrome, often with marked hypokalemia.
- Lambert-Eaton myasthenic syndrome: antibodies against presynaptic P/Q-type voltage-gated Ca²⁺ channels reduce ACh release; proximal weakness IMPROVES with repeated use, the opposite of myasthenia gravis.
- Anti-Hu antibodies: paraneoplastic encephalomyelitis and sensory neuropathy.
Squamous cell carcinoma. A central, often cavitating tumor closely tied to smoking. Histology shows keratin pearls and intercellular bridges. It secretes PTHrP, causing hypercalcemia with a suppressed PTH.
Adenocarcinoma. The most common lung cancer overall and the most common in nonsmokers and women; peripheral, gland-forming, often mucinous. Driver alterations in EGFR, ALK, and KRAS can be targeted with specific inhibitors. It is associated with hypertrophic osteoarthropathy and clubbing.
Large cell carcinoma and bronchial carcinoid. Large cell carcinoma is peripheral and undifferentiated, carries a poor prognosis, and may secrete β-hCG, causing gynecomastia. Bronchial carcinoid is a well-differentiated, low-grade neuroendocrine tumor (chromogranin positive). Carcinoid syndrome (flushing, diarrhea, wheezing) is uncommon and usually signals liver metastases, although bronchial tumors drain directly into the systemic circulation and occasionally cause it without them.
Local complications: Pancoast and SVC syndromes
Pancoast (superior sulcus) tumor. An apical tumor invades neighboring structures:
- Cervical sympathetic chain → Horner syndrome: ipsilateral ptosis, miosis, anhidrosis.
- Brachial plexus (C8–T1) → shoulder and arm pain, atrophy of the intrinsic hand muscles.
- Recurrent laryngeal nerve → hoarseness.
Superior vena cava syndrome. A central tumor (most often small cell or squamous) compresses the SVC and obstructs venous return from the head, neck, and arms: facial plethora and edema, distended neck and arm veins, dyspnea, and head fullness, and intracranial pressure can rise. Thrombosis around indwelling catheters is another cause. It is an oncologic urgency.
Other local effects of a hilar tumor: phrenic nerve compression (elevated hemidiaphragm), airway obstruction with postobstructive pneumonia, and malignant pleural effusion.