Pleural & Mediastinal Pathology
Pathology · Respiratory · lean revision notes
Pleural & Mediastinal Pathology
The pleural space and the mediastinum are two compact "boxes" of the thorax that throw up a disproportionate number of NEET PG questions. This chapter covers pleural effusion (transudate vs exudate by Light's criteria), pneumothorax, mesothelioma, and the localisation-based differential of mediastinal masses — the recurring traps being the anterior-mediastinal 4 Ts and the biphasic histology of mesothelioma.
1. Pleural anatomy & physiology — the quick orientation
The pleura is a serosal membrane with two layers: the visceral pleura (covers the lung, insensitive to pain, supplied by bronchial circulation) and the parietal pleura (lines the chest wall/diaphragm/mediastinum, pain-sensitive via intercostal & phrenic nerves, supplied by systemic circulation). Between them lies a potential space holding ~10–20 mL of serous fluid, replenished and absorbed by Starling forces.
- Fluid enters mainly from the parietal capillaries (higher hydrostatic pressure).
- Fluid exits mainly through parietal pleural lymphatic stomata (NOT the visceral pleura — high-yield).
- Normal pleural fluid is a near-transudate: protein <1.5 g/dL, glucose ≈ plasma.
High-yield: Pleural lymphatics on the parietal (not visceral) surface are the chief route of fluid and protein clearance. Lymphatic obstruction (malignancy) therefore causes an exudate.
2. Pleural effusion — transudate vs exudate
A pleural effusion is abnormal accumulation of fluid (>15–20 mL). The single most important classification question is transudate vs exudate, because it splits the differential in half.
| Feature | Transudate | Exudate |
|---|---|---|
| Mechanism | Altered Starling forces (↑hydrostatic / ↓oncotic) | ↑Capillary permeability / lymphatic block |
| Pleural surface | Intact | Inflamed/diseased |
| Protein (fluid) | Low (<3 g/dL) | High (>3 g/dL) |
| Classic causes | CHF, cirrhosis, nephrotic syndrome, hypoalbuminaemia, hypothyroidism, peritoneal dialysis | Pneumonia (parapneumonic), TB, malignancy, PE, pancreatitis, collagen vascular disease |
| Appearance | Clear, straw-coloured | Turbid/cloudy/bloody |
Light's criteria (the criterion of choice)
An effusion is an exudate if any one of the following is met:
- Pleural fluid protein / serum protein > 0.5
- Pleural fluid LDH / serum LDH > 0.6
- Pleural fluid LDH > 2/3 (≈ 0.67) of the upper limit of normal serum LDH
High-yield: Light's criteria are very sensitive for exudates but tend to mis-label some transudates (e.g. diuretic-treated CHF) as exudates. If clinically a transudate is expected but Light's calls it exudate, check serum–pleural albumin gradient: > 1.2 g/dL favours transudate.
Mnemonic for transudates → "CHANT": CHF, Hypoalbuminaemia, Atelectasis, Nephrotic syndrome, Thyroid (myxoedema)/cirrhosis.
Special fluid analysis clues (frequently tested)
| Finding in pleural fluid | Points to |
|---|---|
| Glucose very low (<60 mg/dL, often <30) | Rheumatoid effusion (lowest), empyema, TB, malignancy |
| pH < 7.20 | Complicated parapneumonic effusion / empyema → needs chest-tube drainage |
| Milky, ↑triglycerides (>110 mg/dL), chylomicrons | Chylothorax (thoracic duct injury, lymphoma) |
| Bloody (Hct >50% of blood) | Haemothorax (trauma) |
| Amylase high | Pancreatitis, oesophageal rupture, malignancy |
| Lymphocyte predominant + ADA >40 U/L | Tuberculous effusion |
| Eosinophilia (>10%) | Air/blood in pleura, drugs, parasites, Churg-Strauss |
High-yield: Lowest pleural glucose = rheumatoid arthritis effusion. Raised ADA (adenosine deaminase) + lymphocytic exudate = tuberculosis — the investigation of choice in suspected TB pleurisy when AFB smear is negative.
Stepwise approach to an effusion: Confirm clinically/imaging → diagnostic thoracocentesis → run protein, LDH, glucose, pH, cell count, cytology, ADA → apply Light's criteria → transudate? treat underlying systemic cause; exudate? pursue cytology/pleural biopsy/ADA → if empyema/pH<7.2 → tube thoracostomy.
3. Empyema & parapneumonic effusion
Parapneumonic effusions evolve in three stages:
- Exudative (simple): free-flowing, sterile, pH normal → antibiotics alone.
- Fibrinopurulent (complicated): bacterial invasion, loculation, pH <7.2, glucose <60, ↑LDH → drainage needed.
- Organising (empyema): frank pus, pleural peel of fibroblasts → may need decortication.
Empyema = pus in the pleural space. Classic organisms: Strep. pneumoniae, Staph. aureus, anaerobes. Empyema necessitans (tracking through chest wall) is classic for TB and actinomycosis.
4. Pneumothorax
Air in the pleural space → loss of negative intrapleural pressure → lung collapse.
- Primary spontaneous: tall, thin, young male smokers; rupture of apical subpleural blebs.
- Secondary spontaneous: COPD (commonest cause), TB, cystic fibrosis, Pneumocystis, Marfan, LAM, Langerhans cell histiocytosis.
- Traumatic / iatrogenic: subclavian line, biopsy, ventilation.
- Tension pneumothorax: one-way valve → progressive air trapping → mediastinal shift away from affected side, neck vein distension, tracheal deviation, hypotension. A clinical emergency — do NOT wait for X-ray.
High-yield: Tension pneumothorax → immediate needle decompression at the 2nd intercostal space, mid-clavicular line (or 4th–5th ICS anterior axillary line per newer ATLS), followed by chest tube. Trachea & mediastinum shift to the opposite side.
Pathologically, recurrent pneumothorax can produce reactive eosinophilic pleuritis. Catamenial pneumothorax (with menses) suggests thoracic endometriosis.
5. Pleural plaques, asbestos & benign pleural disease
- Pleural plaques: discrete, often calcified, hyaline fibrocollagenous thickening of the parietal pleura and diaphragm. They are the most common manifestation of asbestos exposure and are benign markers — they do NOT transform into mesothelioma.
- Diffuse pleural thickening / fibrothorax: can restrict the lung.
- Solitary fibrous tumour of pleura (old name "benign mesothelioma"): arises from submesothelial fibroblasts, NOT asbestos-related, CD34 +ve, keratin –ve, may cause hypoglycaemia (Doege–Potter syndrome) and hypertrophic osteoarthropathy.
High-yield: Pleural plaques = benign asbestos marker. Solitary fibrous tumour is CD34-positive and unrelated to asbestos — distinguishing it from malignant mesothelioma (keratin-positive, CD34-negative) is a classic IHC trap.
6. Malignant mesothelioma
A highly malignant tumour of mesothelial cells lining the pleura (also peritoneum, pericardium, tunica vaginalis).
- Strongest risk factor: asbestos — especially crocidolite (blue asbestos), the most carcinogenic amphibole. Long latency (20–40 years).
- Asbestos + smoking multiplies the risk of bronchogenic carcinoma but smoking does NOT add to mesothelioma risk (high-yield distinction).
- SV40 virus has been implicated as a cofactor.
Clinical: progressive dyspnoea, chest pain, recurrent haemorrhagic pleural effusion, pleural rind encasing the lung; chest wall invasion.
Histology (the recurring NEET PG trap)
Three patterns:
| Pattern | Features |
|---|---|
| Epithelioid | Commonest, best prognosis; tubulopapillary, mimics adenocarcinoma |
| Sarcomatoid | Spindle cells, worst prognosis |
| Biphasic (mixed) | Both components — classically described |
Asbestos (ferruginous) bodies: golden-brown, beaded, dumbbell-shaped fibres coated with iron & protein, stain with Prussian blue; found in lung tissue, indicate exposure.
Immunohistochemistry — mesothelioma vs adenocarcinoma
| Marker | Mesothelioma | Adenocarcinoma (e.g. lung) |
|---|---|---|
| Calretinin | Positive | Negative |
| WT-1 | Positive | Negative |
| CK5/6 | Positive | Negative |
| D2-40 (podoplanin) | Positive | Negative |
| CEA | Negative | Positive |
| TTF-1 | Negative | Positive (lung adeno) |
| MOC-31 / Ber-EP4 / claudin-4 | Negative | Positive |
| Mucin (PAS-D) | Negative | Positive |
High-yield: Mesothelioma = calretinin / WT-1 / CK5/6 / D2-40 POSITIVE and CEA / TTF-1 / MOC-31 NEGATIVE. Electron microscopy shows long, slender, bushy microvilli (vs short stubby microvilli of adenocarcinoma).
Investigation of choice: contrast CT thorax for staging; diagnosis confirmed by pleural biopsy (thoracoscopy/VATS) with IHC — cytology alone is often insufficient. Prognosis is poor (median survival ~12 months).
7. Mediastinal anatomy & compartments
The mediastinum is divided (clinical/4-compartment scheme) into:
- Superior mediastinum (above the plane from sternal angle to T4/5).
- Anterior (between sternum and pericardium).
- Middle (heart, pericardium, great vessels, trachea, hila).
- Posterior (behind pericardium — paravertebral).
The compartment a mass occupies localises the differential diagnosis — examiners love this.
| Compartment | Common masses |
|---|---|
| Anterior (4 Ts) | Thymoma, Teratoma (germ cell), Thyroid (retrosternal), Terrible lymphoma (also thymic carcinoma, parathyroid) |
| Middle | Lymphadenopathy (lymphoma, sarcoid, mets), bronchogenic cyst, pericardial cyst, vascular (aneurysm), tracheal lesions |
| Posterior | Neurogenic tumours (schwannoma, neurofibroma, ganglioneuroma, neuroblastoma), meningocele, oesophageal lesions, descending aortic aneurysm, extramedullary haematopoiesis |
High-yield: Anterior mediastinal mass = 4 Ts (Thymoma, Teratoma, Thyroid, Terrible lymphoma). Posterior mediastinal mass = neurogenic tumours (commonest overall mediastinal tumours in children are neurogenic; in adults, anterior compartment & thymoma/lymphoma dominate).
Add a 5th "T" — Thymic carcinoma, and remember the anterior mediastinal mass mnemonic also includes parathyroid adenoma.
8. Thymoma & the thymus
- Commonest anterior mediastinal tumour in adults; peak in 40–60 years.
- Arises from thymic epithelial cells (the lymphocytes within are reactive, non-neoplastic).
- Associations (very high-yield):
- Myasthenia gravis (~30–45% of thymoma patients have MG; ~15% of MG patients have thymoma).
- Pure red cell aplasia, hypogammaglobulinaemia (Good syndrome), SLE.
- Histology: mixture of epithelial cells + immature T lymphocytes; encapsulated (benign behaviour) vs invasive (malignant behaviour). Malignancy is defined by capsular/local invasion, NOT cytological atypia — a frequent trap.
- Thymic carcinoma shows overt cytological malignancy and is more aggressive.
High-yield: A thymoma is judged benign vs malignant by invasion of the capsule and surrounding structures, not by how the cells look under the microscope. Myasthenia gravis is the classic association.
9. Germ cell tumours & other anterior masses
- Teratoma: commonest mediastinal germ cell tumour; usually mature/benign, may contain hair, teeth, cartilage; midline anterior.
- Seminoma: anterior mediastinum in young men; radiosensitive.
- Non-seminomatous GCT: associated with ↑β-hCG / ↑AFP, and notably with Klinefelter syndrome and haematological malignancy (e.g. AML).
- Retrosternal goitre moves with swallowing, continuous with cervical thyroid.
- Lymphoma: Hodgkin (esp. nodular sclerosis subtype — classic young woman with anterior mediastinal mass) and primary mediastinal large B-cell lymphoma.
High-yield: Nodular sclerosing Hodgkin lymphoma is the classic mediastinal lymphoma; mediastinal non-seminomatous GCT is linked to Klinefelter syndrome.
10. Posterior & middle mediastinal lesions
- Neurogenic tumours (posterior): in adults usually nerve-sheath (schwannoma/neurofibroma); in children, neuroblastoma / ganglioneuroblastoma / ganglioneuroma (sympathetic chain). May cause rib notching/widened neural foramina; dumbbell extension into the spinal canal.
- Bronchogenic cyst (middle): congenital foregut duplication cyst near the carina, fluid-filled, lined by respiratory epithelium.
- Oesophageal duplication cyst (posterior).
11. Complications & key differentials
Complications across these pathologies:
- Effusion → respiratory compromise, empyema, fibrothorax, trapped lung.
- Tension pneumothorax → obstructive shock, cardiac arrest.
- Mesothelioma → encasement, local invasion, poor prognosis.
- Mediastinal mass → SVC obstruction (facial plethora, distended neck veins — most often lymphoma or lung cancer), tracheal/oesophageal compression, myasthenia (thymoma), hormonal (parathyroid, thyroid).
Differentials to keep straight:
- Mesothelioma vs metastatic adenocarcinoma to pleura → IHC panel (above).
- Thymoma vs lymphoma vs teratoma vs goitre → anterior 4 Ts, age, markers, MG.
- Transudate vs exudate → Light's criteria / albumin gradient.
Recently asked / exam angle
- Light's criteria — which value defines an exudate (protein ratio >0.5, LDH ratio >0.6, LDH >2/3 ULN). Single-best-answer favourite.
- Lowest pleural fluid glucose → rheumatoid arthritis.
- Calretinin / WT-1 positive, CEA negative tumour → mesothelioma; "bushy long microvilli" on EM.
- Crocidolite = most carcinogenic asbestos; latency 20–40 yrs; smoking does NOT increase mesothelioma risk.
- Anterior mediastinal mass 4 Ts — image- or one-liner-based.
- Thymoma + myasthenia gravis / pure red cell aplasia / Good syndrome.
- Posterior mediastinum = neurogenic tumour; commonest mediastinal tumour in children = neurogenic.
- Doege–Potter syndrome (hypoglycaemia) with solitary fibrous tumour, CD34+.
- Tension pneumothorax management & direction of tracheal shift.
- ADA + lymphocytic exudate = tuberculous pleurisy.
Rapid revision
- Pleural fluid is cleared by parietal lymphatic stomata, not the visceral pleura.
- Light's criteria (any one → exudate): protein ratio >0.5, LDH ratio >0.6, LDH >2/3 serum ULN.
- Diuretic-treated CHF can be mis-called exudate; use serum–pleural albumin gradient >1.2 g/dL = transudate.
- Lowest pleural glucose = rheumatoid effusion; pH <7.2 = drain (empyema).
- ADA >40 + lymphocytes = TB; milky + ↑TG = chylothorax.
- Primary spontaneous pneumothorax = tall thin young male, apical blebs; tension → trachea shifts to opposite side, needle decompress.
- Pleural plaques = benign asbestos marker; do not become mesothelioma.
- Mesothelioma: crocidolite, 20–40 yr latency; calretinin/WT-1/CK5-6/D2-40 +ve, CEA/TTF-1 −ve; biphasic histology; long bushy microvilli.
- Anterior mediastinum = 4 Ts (Thymoma, Teratoma, Thyroid, Terrible lymphoma).
- Thymoma = commonest anterior mass in adults; malignancy defined by invasion, associated with myasthenia gravis.
- Posterior mediastinum = neurogenic tumours; most common mediastinal tumour in children.
- Solitary fibrous tumour = CD34+, keratin−, non-asbestos, Doege–Potter (hypoglycaemia).