Distinguishing Fibrous Pleuritis from Desmoplastic Mesothelioma: A Pathologist’s Guide

Why This Distinction Matters

If you think mesothelioma is already tough to diagnose, try distinguishing desmoplastic mesothelioma from fibrous pleuritis—one of the trickiest areas in mesothelioma pathology. These two conditions look remarkably similar under the microscope, and the wrong diagnosis can have serious medical and legal consequences.

• Fibrous pleuritis is a benign inflammatory reaction.
• Desmoplastic mesothelioma is a highly aggressive cancer.

Getting it wrong could mean:

• Unnecessary treatment for a benign condition or,
• A missed cancer diagnosis, leading to delayed or no treatment.

Let’s walk through the key histological features, pitfalls, and the best tools available to get this diagnosis right.

Cytology: Not the Best Tool Here

Why Effusion Cytology Doesn’t Help

If you’re relying on effusion cytology alone to differentiate desmoplastic mesothelioma from fibrous pleuritis, you’re in for a challenge. These fibrous tumors shed very few cells, making fluid cytology nearly useless in this setting.

• In rare cases, spindle-shaped mesothelial cells might show up in effusion fluids.
• More commonly, effusions lack mesothelial cells altogether.
• Lymphocytic effusions are typical in sarcomatoid/desmoplastic mesotheliomas.

Since effusion cytology rarely gives a definitive answer, biopsy is required.

Histology: The Key to Diagnosis

How to Tell the Difference

Both desmoplastic mesothelioma and fibrous pleuritis contain dense fibrous tissue with scattered spindle cells. But here’s how to tell them apart:

• Key Takeaway: Invasion is the most reliable diagnostic clue!

• If tumor cells infiltrate fat, muscle, or lung parenchyma → Mesothelioma.

• If no invasion is present, and the fibrous tissue is orderly → Fibrous pleuritis.

The Role of Immunohistochemistry (IHC)

Cytokeratin: A Useful, But Not Definitive, Marker

• Cytokeratin staining can highlight subtle invasion, but both fibrous pleuritis and mesothelioma express cytokeratin.

• Deep mesothelial cells in benign pleuritis can stain for cytokeratin, which can mimic invasion—so be careful.

• Pro Tip: If you see cytokeratin-positive spindle cells infiltrating fat or lung, that’s invasion, and that strongly favors desmoplastic mesothelioma.

EMA (Epithelial Membrane Antigen): Limited Use

• Unlike epithelioid mesothelioma, where EMA is a strong marker, desmoplastic mesothelioma is usually EMA-negative.
• Occasionally, small epithelioid foci in mesothelioma may be EMA-positive.

Bottom Line: EMA is not very useful for this particular distinction.

p53: Somewhat Helpful, But Not Perfect

• p53 staining is more common in mesothelioma but not specific.
• Some reactive pleuritis cases also show weak p53 staining.
• If p53 is strongly positive, mesothelioma is more likely—but use caution.

Proliferation Markers (Ki-67, MIB-1)

• Ki-67 (MIB-1) index tends to be higher in mesothelioma.
• Fibrous pleuritis has a very low proliferation index (<5%).
• Ki-67 alone isn’t enough, but it’s a good supporting clue.

Electron Microscopy: Still Useful?

• Most desmoplastic mesotheliomas lack classic mesothelial features like microvilli and desmosomes.
• Electron microscopy has limited diagnostic utility in this scenario.
• If desmosomes or microvilli are present, it supports mesothelioma—but their absence doesn’t rule it out.

The Role of Radiology in Diagnosis

Why Clinical Correlation is Critical

A good radiologist can be your best ally in tricky cases.

• If imaging shows a diffuse, infiltrative, and destructive pleural lesion → Favor mesothelioma.
• If the pleural thickening is well-demarcated and non-invasive → Favor fibrous pleuritis.

Guiding Biopsy

• Multiple core biopsies improve diagnostic accuracy.
• Targeted biopsy of the most suspicious areas (via CT or thoracoscopy) is key.

Practical Approach to Difficult Cases

So what should you do when you’re faced with a tricky biopsy?

Stepwise Diagnostic Strategy

1. Assess Clinical and Radiological Context

   • Is there an aggressive pleural lesion on imaging?
   • Does the patient have asbestos exposure history?

2. Look for Key Histological Features

   • Is there invasion into fat, lung, or muscle?
   • Is the collagen organized (pleuritis) or patternless (mesothelioma)?
   • Are there areas of bland necrosis?

3. Use Immunohistochemistry Wisely

   • Cytokeratin staining can highlight invasion.
   • p53 and Ki-67 can provide supportive evidence.
   • EMA is not very useful here.

4. Consider a Second Biopsy If Needed

   • If the first biopsy is inconclusive, a larger thoracoscopic biopsy may be required.

5. Follow-Up If Diagnosis is Uncertain

   • Some cases will require clinical and radiological follow-up to confirm progression.

Key Takeaways

• Invasion into fat, muscle, or lung parenchyma is the gold standard for diagnosing desmoplastic mesothelioma.
• Fibrous pleuritis is usually well-organized with perpendicular capillaries, while mesothelioma shows a storiform or whorled pattern.
• Cytokeratin staining can highlight invasion but is not specific to mesothelioma.
• p53 and Ki-67 can help but should be used as supporting evidence, not definitive markers.
• When in doubt, clinical and radiological correlation is essential for diagnosis.

This distinction is challenging but essential—using a multidisciplinary approach with histology, IHC, and imaging will maximize diagnostic accuracy.