Histopathology of Caseous Granuloma

1. Granuloma
Dr Mohammad Manzoor Mashwani
Collection of modified macrophages
EPI-THE-LI-OIDCells
Immune Granuloma
1. Epithelioid Cells 2. Rim of lymphocytes 3. Giant
cells 4. Caseous Necrosis 5. Fibrous Cup

3. Tubercle/Granuloma- a type of ch. Inf.
Granuloma is defined as a circumscribed, tiny lesion, about
1 mm in diameter, composed predominantly of collection of
modified macrophages called epithelioid cells, and rimmed
at the periphery by lymphoid cells.
The word ‘granuloma’ is derived from granule meaning
circumscribed granule-like lesion, and -oma which is a suffix
commonly used for true tumours but here it indicates a localised
inflammatory mass or collection of macrophages.
Granuloma: Collection of epithelioid cells rimed by
lymphocytes.
EPITHELIOID

4. Granuloma
is NOT
a Granulation
Tissue

5. • Granulation tissue is a new connective tissue and
microscopic blood vessels that form on the surfaces
of a wound during the healing process (Repair).
• Granulation tissue typically grows from the base of
a wound and is able to fill wounds of almost any
size.
Granulation tissue is highly vascularized connective tissue composed of
1.Newly formed capillaries,
2.Proliferating fibroblasts and
3.Residual inflammatory cells.
A Young Scar = Granulation tissue
Healing: 1. Regeneration 2. Repair
Repair: 1. Granulation tissue formation 2. Contraction of wounds

6. Granulation tissue AppeArAnce
During the migratory phase of wound healing, granulation tissue is:
 light red or dark pink in color,
 being perfused with new capillary loops or "buds";
 soft to the touch;
 moist; and
 bumpy (granular) in appearance, due to punctate hemorrhages
 pulseful on palpation
 painless when healthy.

9. Types of granulomas:
1. Foreign body granuloma 2.Immune granuloma .
1. Foreign body granulomas – form when material
such as talc, sutures, or other fibers are large
enough to preclude (prevent) phagocytosis by a
single macrophage.
1. Foreign Body Granuloma
2. Immune Granuloma

10. Immune granulomas
2. Immune granulomas - caused by insoluble particles that are
capable of inducing a cell-mediated response. This type of immune
response produces granulomas when the inciting agent is poorly
soluble.
Tuberculosis
Tubercle= GRANULOMA

11. Immune Granuloma
• Macrophages engulf the foreign material and
process present some of it to appropriate
• T lymphocytes, causing them to become activated,
responding T cells produce cytokines, such as IL-2
which activates other T cells and IFN-γ which is
important in transforming macrophages into
epithelioid cells and multinucleate giant cells.
• MaMacrophages Epithelioid cells +
Giant cells

12. • The classic example for the immune granuloma is
that caused by the bacillus of tuberculosis. In this
disease, the granuloma is referred to as a
tubercle and is classically characterized
by the presence of central caseous necrosis.
• Caseating necrosis is rare in other granulomatous
diseases.
TUBERCLE = GRANULOMA

13. • Granuloma formation is a strategythat has evolved
to deal with those pathogens that have learned to evade
(escape) the host immune system by various means like
resisting phagocytosis and killing within the macrophages.
• Granulomas try to wall off these organisms and prevent
their further growth and spread.
Mechanism of Granuloma Formation
Wall off
Organisms

14. Granulomas try to wall
off these organisms and
prevent their further
growth and spread.

15.  Granuloma:
bacilli are inhaled by droplets
 Bacteria are phagocytosed by alveolar
macrophages
 After amassing (collect or gather) substances
that they cannot digest, macrophages lose their
motility, accumulate at the site of injury and
transform themselves into nodular collections;
the Granuloma
 A localized inflammatory response recruits
more mononuclear cells
 The granuloma consists of a kernel (inner) of
infected macrophages surrounded by foamy
macrophages and a ring of lymphocytes and a
fibrous cuff (containment phase)
 Containment usually fails when the immune
status of the patient changes; the granuloma
caseates, ruptures and spills into the airway
Containment
Phase

16. Main causes of granulomatous
inflammation:
• Mildly irritant ‘foreign’ material
• Mycobacteria: Tuberculosis, leprosy
• Syphilis
• Other rare infections e.g. some fungi
• Unknown causes: Sarcoid
Wegener’s granulomatosis
Crohn’s disease

17. Granuloma comprises:
1. Epithelioid Cells
2. Caseous Necrosis
3. Giant cells
4. Rim of lymphocytes
5. Fibrous Cup
1.Caseous Necrosis
2.Epithelioid cells
3.Giant cells
4.Fibrous cup
5.Rim of Lymphocytes
Infected
Macrophages

18. Epithelioid cells
• Epithelioid histiocytes (Epithelioid cells) are
activated macrophages resembling epithelial cells:
• elongated, with finely granular, pale eosinophilic (pink)
cytoplasm and
• central, ovoid nucleus (oval or elongate), which is
less dense than that of a lymphocyte.
• They have indistinct shape contour, often appear
to merge into one another and can form aggregates
known as giant cells.

20. Giant cell
• A giant cell is a mass formed by the union of several
distinct cells (usually macrophages), often forming a
granuloma.
• It can arise in response to an infection, such as
from tuberculosis, herpes, or HIV, or foreign body.

21. Types of Giant Cells
1. Langhans giant cell
2. Foreign-body giant cell
3. Touton giant cells
4. Giant-cell arteritis
5. Reed–sternberg cell
Also as in subependymal giant cell astrocytoma

22. 1. Langhans giant cell
• This particular form of giant cell was named after a German
pathologist, Theodor Langhans.
• Epithelioid cells fuse to form giant cells containing 20 or more nuclei.
• The nuclei are arranged peripherally and form a circle or
semicircle related to the shape of a horseshoe.
• Langhans giant cell is said to be related to
tuberculosis and it occurs in many types of
granulomatous diseases.
Horseshoe

24. Slide 3.41

26. Langhans type giant cell -
Tuberculosis

27. 2. Foreign-body giant cell
• Foreign-body giant cells form when a subject is
exposed to a foreign substance. Exogenous
substances include talc or sutures.
• In this form of giant cell, the nuclei are arranged in
an overlapping manner.
• This giant cell is often found in tissue because of
medical devices, prostheses, and biomaterials.

28. Foreign body type giant cells

30. 3.Touton giant cells
Touton giant cells are a type of multinucleated
giant cell seen in lesions with
high lipid content such as
fat necrosis, xanthoma, and xanthogranulomas.
They are also found in dermatofibroma.

31. • Touton giant cells are named for Karl Touton,
a German botanist and dermatologist.Karl
Touton first observed these cells in 1885 and
named them "xanthelasmatic giant cells", a
name which has since fallen out of favor.

32. • They contain a ring of nuclei surrounding a central
homogeneous cytoplasm, while foamy cytoplasm
surrounds the nuclei.
Two cytoplasms:
1. Central homogeneous
cytoplasm
2. Peripheral foamy
cytoplasm
Touton: T for Two
cytoplasms

33. Touton Giant cell

34. Necrosis: A series of morphological changes in a lethally injured cell (irreversible cell injury).
Coagulative Necrosis + Liquefactive Necrosis
Soft, friable, whitish-grey/Yellowish debris
Resembling dry cheese

35. • Fibrous connective tissue often surrounds granulomas (remodeling of tissue)
• Areas within the granuloma can undergo necrosis (prototype: caseous necrosis in
tuberculosis).
• Necrosis can lead to calcification or liquefaction and formation of a cavern
(cave)if drained.
Fibrous Cup
Dystrophic Calcification
(Laminated)
1. Caseous Necrosis 2. Epithelioid Cells 3.
Giant Cells 4. Lymphocytes 5. Fibrous cup

36. Morphology of Granuloma
Grossly, foci of caseous necrosis, as the name implies,
resemble dry cheese and are soft, granular and Whitish grey or
yellowish.
This appearance is partly attributed to the histotoxic
effects of lipopolysaccharides present in the capsule of the
tubercle bacilli, Mycobacterium tuberculosis.
Lipopolysaccharides

37. 1. Caseous Necrosis 2. Epithelioid Cells 3. Giant Cells 4.
Lymphocytes 5. Fibrous cup
Microscopically,
1. the necrosed foci are structureless, eosinophilic, and contain
granular debris.
2. The surrounding tissue shows characteristic
granulomatous inflammatory reaction consisting of
epithelioid cells with
3. interspersed giant cells of Langhans’ or foreign body type
and
4. peripheral mantle (layer, covering, Ring, collar) of lymphocytes.
5. Fibrous cup.

41. Langhans Giant Cell
Caseous Necrosis
Epithelioid Macrophage
Lymphocytic Rim

46. Caseating granulomas

47. THANKS