32. Granuloma. Granulomatous inflammation

A granuloma is a circumscribed chronic inflammation with many activated macrophages and lymphocytes clustered around pathogens that can’t be broken down. This is the way of our immune system to trap these kinds of pathogens, so they don’t spread further.

Causes

Like mentioned above, some pathogens can resist being phagocytosed or degraded inside the phagocytes, and therefore will the activated macrophages cluster around it. Some macrophages in a granuloma will have a pink, granular cytoplasm with indistinct cell boundaries, the so-called epithelioid cells. These cells get their name from their resemblance to epithelial cells due to their oblong shape. Macrophages can also fuse together, creating different types of giant cells.

Giant cells

Three types of giant cells exist. Langhans giant cells have their nuclei along the periphery of the cell. Foreign body giant cells have their nuclei disorganized in the whole cell. Touton giant cells have a foamy morphology.

Langhans cells are seen mainly in tuberculosis, while foreign body giant cells can mostly be found in granulomas formed in response to foreign bodies. However, both types can be found in any type of granuloma.

Touton giant cells however occur only in lesions with high fat contents, like in xanthogranulomatous inflammation.

Let’s study some different granuloma types and examples of diseases.

Examples of non-immune granulomas

Non-immune granulomas are not related to type IV hypersensitivity.

• Lipogranuloma

It is a chronic inflammation in soft tissue after fat necrosis. It’s associated with injections and trauma.

• Foreign-body granuloma

This happens if some non-degradable materials somehow get into the body, like a leaking silicone implant or sutures.

Keratin, cholesterol and sperm in wrong places can also cause this. Recall from embryology that the Sertoli cells protects the sperm from the host immune system.

• Xanthogranulomatous inflammation

This is the chronic inflammation of lipid rich areas like the kidney, gall bladder or sebaceous glands. It involves clustering of foam cells (fat-containing macrophages) in the granulomas.

Subcutaneous macrophages can form xanthomas, and small xanthomas on the eyelids are called xanthelasma.

Immune granulomas

These granulomas are due to the type IV hypersensitivity. Since tuberculosis was discussed in the previous topic, we won’t mention it here. However, it’s important to mention it on the exam if you pick this topic.

• Leprosy

This is caused by mycobacterium leprae. It gives inflammation in the skin, peripheral nerves and upper airways.

• Syphilis

Caused by treponema pallidum, this sexually transmitted disease consists of three phases.

Primary syphilis shows after 2-5 weeks as a painless ulcer.

Secondary syphilis shows after 6-8 weeks with skin lesions, lymph node enlargement and warts on the genitalia.

Tertiary syphilis forms gummas, a form of necrotic granuloma in the skin, bones and mucosa. Also, there will be aortitis and neurosyphilis.

So, use condoms y’all, you don’t want this to happen to you!

• Cat scratch disease

Don’t worry, you can still cuddle with cats. This only happens if a cat with bartonella henselae scratches or bites you. This gives suppurating granulomas, a type of granuloma in the periphery with central abscess formation, often consisting of histiocytes. Nearby lymph nodes also get inflamed.

Sarcoidosis

The aetiology of sarcoidosis is unknown, although it usually affects young women. Sarcoidosis consists of non-caseating granulomas with asteroid and Schaumann bodies. These granulomas are hard because there is no soft, necrotic mass. Sarcoidosis is most common in individuals between 20 and 40 years and takes 1-2 years to resolve.

The signs of sarcoidosis:

• Lungs

In 90 % of the cases will there be an interstitial lesion in the lung. Lung fibrosis is also possible, but it’s rare.

• Lymph nodes

It makes the lymph nodes of the pulmonary hila enlarge, also called bilateral hilar lymphadenopathy (BHL).

• Skin

Can cause Erythema nodosum, inflammation of the fat tissue under the skin, giving red patches.

• Glands

Heerfordt syndrome – swelling of parotid gland

Mikulicz syndrome – swelling of all salivary glands

• Haematology

Sarcoidosis can lead to anaemia and leukopenia.