Tut1- patho

GRANULOMATOUS INFLAMMATION
● What is granuloma?
☆A granuloma is a focus of chronic specific inflammation
consisting of:
-A microscopic aggregation of macrophages that are
transformed into epithelium-like cells (epitheloid cells)
surrounded by a collar of mononuclear leukocytes, principally
lymphocytes and occasionally plasma cells.
Offending agent could be mostly detected.
● Why do granuloma develop?
○ Substances that can not be adequately degraded by PNL and
macrophages.
○ Immune response.
❖ There are three types of granulomas, which differ in their
pathogenesis.
1-Infective granulomas are caused by microbes that are
capable of inducing a cell – mediated immune response.
2-Foreign body granulomas:
Are caused by insoluble particles.
3- Granuloma of unknown cause: e.g. sarcoidosis and Crohn’s
disease
● Examples of granulomatous inflammation:
Bacterial
○ Tuberculosis (Mycobacterium tuberculosis)
○ Leprosy (Mycobacterium leprae)
○ Syphilitic gumma (Treponema pallidum)
○ Cat-scratch disease (Bartonella henselae)
Parasitic
○ Schistosomiasis (Schistosoma mansoni, S. haemotobium, S.
japonicum)
Fungal
○ Histoplasma capsulatum
Blastomycosis
○ Cryptococcus neoformans
○ Coccidioides immitis

1|Page
 Tut1- patho

Inorganic Metals or Dusts

○ Silicosis
○ Berylliosis
Foreign Body
○ Suture, breast prosthesis, vascular graft
Unknown
○ Sarcoidosis
○ Crohn’s disease
A:Foreign body granuloma,
as caused by a thorn. The
granuloma contains
macrophages, giant cells, and
fibroblasts, but no lymphocytes.
B, C :Immune granulomas, as
caused by Mycobaterium
tuberculosis. The core is made of
epithelioid cells (some with
bacilli) surrounded by
lymphocytes, macrophages, plasma cells, giant cells and perhaps dendritic cells.
☆ Necrosis may develop in the center .
● Foreign body granulomas:
○ Foreign material:
Suture material, glass, vegetable matter
○ Extravasation:
Sperm granuloma, keratin (ruptured epidermal cyst), bile (PBC) ●foreign body granuloma:
☆ In these responses, macrophages engulf the foreign material
and process and present some of it to appropriate T
lymphocytes, causing them to become activated. The
responding T cells produce chemical mediators
☆ The granuloma tend to be smaller and contain fewer cells
than their immune counterparts; the foreign body is usually
visible in the center of the granuloma. Epithelioid cells and
giant cells form and are apposed to the surface surround the foreign body.
● silica granuloma:

2|Page
 Tut1- patho

● Postsurgical due to suture material: ● Due to tattoo pigment:

❖ SARCOIDOSIS :
○ This is a systemic disorder of uncertain cause that is
commonly manifested in lungs .
○ However immunologic mechanisms have been implicated
and abnormalities of the immune system are usually present.
○ Women are more commonly affected between 20-30 years
and usually presented with bilateral lymphadenopathy .
● Pathology:
Grossly:
The lung showed granulomas in the alveolar
septa and along pulmonary lymphatics together
with interstitial fibrosis.
The granuloma may also be found in lymph
nodes, liver, spleen, skin, bones and many other organs.
❖ SARCOIDOSIS:
Microscopically:
○ Showed small NON-CASEATING EPITHELIOID CELL GRANULOMAS
contain langerhan’s type giant cells and associated with fibrosis.
○ Several types of inclusions may be present as:
■ Schaumann (calcium and protein inclusions inside of
Langerhans giant cells as part of a granuloma; basophilic laminated
rounded conchoidal structures) and
■ Asteroid bodies (small, intracytoplasmic, eosinophilic star
shaped structure also present in tuberculoid leprosy, berylliosis and atypical facial necrobiotic
xanthogranuloma)
○ These bodies although characteristic of sarcoidosis but are not pathognomonic.
○ The cells in the granuloma secrete angiotensin converting enzyme.
○ Detection of elevated levels of this enzyme in serum is diagnostic of sarcoidosis

3|Page
 Tut1- patho

❖ Granulomas of sarcoidosis in
a lymph node:
○ They consist mainly of packed
macrophages (epithelioid cells) with a
few lymphocytes.
○ Note the presence of a giant cell in
the central granuloma and the
absence of central necrosis.
○ Capillaries are also absent, as in all granulomas.
❖ Giant cell containing a typical asteroid body:

❖ Schaumann bodies:

● Fate:
○ About 65% of patients undergo spontaneous remission, however steroids are effective in
controlling the disease.
❖ What’s leprosy?
○ Leprosy (Hansen’s Disease) is a chronic
infectious disease that primarily affects the
peripheral nerves, skin, upper respiratory
tract, eyes, and nasal mucosa (lining of the
nose).
○ Causing discoloration and lumps on the
skin and, in severe cases, disfigurement and
deformities.
○ Leprosy is now mainly confined to tropical Africa and Asia.

4|Page
 Tut1- patho

❖ LEPROSY:
○ Etiology: the causative bacteria are MYCOBACTERIUM LEPRAE.
○ Mode of transmission: through nasal mucosa (inhalation) or
through skin abrasions, after prolonged contact with a patient.
Long incubation period (up to several years).
○ Transmission: inhaled M. leprae is taken up by alveolar
macrophages spreading through blood to all body organs but it only grows in relatively cool
tissue like skin and extremities.
○ Pathogenesis: Mycobacterium leprae do not secrete toxins, but its cell wall containing
“lepromin

5|Page
 Tut1- patho

❖difference between lepromatous and tuberculoid

Lepromatous leprosy Tuberculoid leprosy
(nodular leprosy) (Maculo-anesthetic leprosy)
○ The tissue reaction is called leproma. ○ The tissue reaction consists of epithelioid
○ It consists of large numbers of macrophages cells, giant cells and lymphocytes, but with no
with pale foamy cytoplasm (bacterial lipids). caseation.
○ These foam cells contain large numbers of ○ They differ from sarcoidosis in:
rapidly multiplying bacilli. 1- Few lepra bacilli may be detected (by the
○ Partial lysis of the wals of these bacilli results Ziehl-Neelsen stain).
in the foam appearance of the cells (lysis is not 2- The tuberculoid granulomas occur along
complete due to defective digestion). side nerves associated with nerve destruction.
○These foam cells are called lepra cells.

❖ Tuberculoid leprosy of the skin. The dermis is packed

with granulomas; almost every one contains one or more giant
cells. This pattern corresponds to a vigorous response of the
immune system
❖Lepromatous leprosy. There is a diffuse, although not very
obvious, inflammatory infiltrate of the dermis, with no tendency
to form granulomas. This is the pattern of an
immunocompromised patient

6|Page
 Tut1- patho

❖ Diagnosis of leprosy:
○ Demonstration of bacilli in nasal
discharge or nasal scrapping.
○ Biopsy from skin nodules or thickened
nerve
○ Lepromin (intradermal) test.

❖ SYPHILIS:
○ Definition: infective granulomas caused by
a spirochaete called TREPONEMA PALLIDUM .
○ Syphilis is a venereal disease.
○ Mode of infection: there are 2 main modes of transmission
➢ Acquired syphilis:
■ Venereal type (most common). Bacteria are
transmitted by sexual contact.
■ Non-venereal type:
1- Touching syphilitic lesions.
2- Blood transfusion from syphilitic donor.
➢ Congenital syphilis:
Due to transplacental transmission of spirochaetes from
syphilitic mother to her fetus.
● ACQUIRED SYPHILIS (VENEREAL TYPE)
Venereal syphilis can be divided into 3 stages:
○ Primary stage: about 2 weeks (incubation period) after the onset of infection.
○ Secondary stage: about 2 months after healing of the primary stage.
○ Tertiary stage: (in one third of untreated cases); after 2-10 years from the secondary stage.
♡ Tissue reaction:
Characterized by:
☆ Early marked endarteritis obliterans.
☆ Proliferative reaction composed of perivascular
infiltrates of plasma cells and other chronic
inflammatory cells.
☆ Granulation tissue and fibrosis occur.
☆ Considerable necrosis may be noted in the tertiary stage.

7|Page
 Tut1- patho

❖ Primary syphilis (chancre):

○ Chancre is hard painless small papule which ulcerates
(hard sore), followed by minimal fibrosis.
○ The regional lymph nodes are enlarged and discrete.
Site:
a) Genitalia: penis, vulva, vagina and cervix.
b) Extragenital: lips, tongue, nipple and anus (in
homosexuals)

➢ immunohistochemical staining for Treponema pallidum identified spirochetes in

the granulation tissue overlying the ulcer, as well as in the walls and lumen of the capillaries at
its margin (Panel B, arrows
➢ The epidermis is ulcerated, and the underlying tissue is infiltrated
by predominantly plasma cells, macrophages, and lymphocytes.

❖ Secondary syphilis:
○ This is the most infective stage .
○ It is characterized by:
➢ Skin lesions:
♡ Generalized skin rash
♡Alopecia (loss of scalp hair).
♡Condyloma latum: a large raised cutaneous
swelling occurring in moist areas as vulva and
axilla.
♡ Leukoderma.
➢Mucous patches:
➢Generalized lymph node enlargement.

8|Page
 Tut1- patho

❖ Tertiary syphilis:
○ Any organ may be affected.
○ There are two types of lesions:
1- Gumma: (localize affection)
● Gross picture, sites and effects:
➢It may be single or multiple.
➢It is a circumscribed pale yellowish gray rubbery mass.
➢Variable in size.
♡ Histopathologic examination of the ulcer border –
endothelitis with obliteration of a large vessel in the
lower dermis
2- Diffuse syphilitic inflammation:
○ It is more common than gumma.
○ Microscopic picture:
Minimal scattered foci of necrosis, associated with diffuse inflammation, endateritis,
granulation tissue and fibrosis.

❖ Aortic lesion in syphilis:

Syphilitic aortitis: any part of thoracic aorta is affected. The
affected aortic wall is fibrotic and the intima appears wrinkled

❖CONGENITAL SYPHILIS:
■ It is due to transplacental infection.
■ The possibilities include:
♡ Abortion or stillbirth.
♡ The baby survives and develops two groups of lesions:
■ Early manifestations: these develop during the first two years of life (often between the
second and tenth weeks).
■ These lesions largely resemble those of the secondary stage of acquired syphilis:
➢Skin and condyloma.
➢Mucous patches.
➢ Generalized lymph node enlargement.

9|Page
 Tut1- patho

■ Late manifestations (2-30 years):

Hutchinson’s teeth: the permanent central incisors are short,
notched and widely separated.
Deafness due to affection of the 8th cranial nerves.
Gumma of palate (perforation) and nose (saddle nose).

❖ACTINOMYCOSIS:
☆ It is a chronic suppurative granulomas caused by a GRAM
POSITIVE ANAEROBIC BACILLUS (or fungus) called actinomyces bovis
and actinomyces Israeli.
● Cause:-
- Actinomyces Israelii “anaerobic bacteria” is a normal inhabitant of the
flora of oropharynx, and intestinal tract.
Pathology:
● Gross features:
Multiple abscesses with indurated fibrotic walls.
These abscesses open onto the skin by multiple sinuses that discharge pus and bacterial
colonies which grossly appear like sulphur granules.
● Microscopic features:
➢Bacterial colonies: consist of peripherally arranged red-stained clubs and centrally interlacing
gram-positive branching filaments which are stained deep blue.
➢Inflammatory cells surround the colonies. These consist of neutrophils, pus cells, foam
macrophages, lymphocytes and plasma cells.
➢Granulation tissue and fibrosis are seen at the periphery.
● Sites and microscopic picture.

10 | P a g e
 Tut1- patho

❖RHINOSCLEROMA:
➢It is a chronic infective granulomas caused by Klebsiella
rhinoscleromatous.
➢It is endemic in Egypt and affect the mucous membrane of:
♡ Nose (rhinoscleroma).
♡ Tonsils (tonsilloscleroma).
♡ Pharynx (Pharyngoscleroma).
♡ Larynx (Laryngoscleroma).
➢ Macroscopic:
The lesion starts as diffuse thickening or small firm nodule at one side of the nose, gradually
increase and infiltrate the surrounding, e.g. upper lip and sinuses.
➢ Microscopic:
Squamous metaplasia.
Vascular connective tissue core, chronic inflammatory cells and fibrosis.
♡ Mickulicz cells: large rounded cells with clear or foamy cytoplasm and dark central or
eccentric pyknotic nuclei. It is due to hydropic degeneration in histiocytes.
♡ Russel bodies: Ovar or round red bodies with or without peripheral nuclei. It is due to
hyalinosis in plasma cells.
➢Effects:
○ Ulceration, secondary infection and epistaxis.
○ Obstruction; nasal or laryngeal.
○ Precancerous.

11 | P a g e