This document discusses oral granulomatous diseases. It defines granulomas as chronic inflammatory lesions composed of macrophages, epithelioid cells, and multinucleated giant cells. Granulomas form in response to infection, foreign bodies, or immune responses. The document classifies granulomatous diseases including those of infectious etiology like tuberculosis, leprosy, and actinomycosis. It describes the histopathological features of granulomas and provides photomicrographs. Specific conditions like sarcoidosis, Crohn's disease, and Melkersson-Rosenthal syndrome are also summarized.

1. ORAL GRANULOMATOUS DISEASES

2.  DEFINITION
 INTRODUCTION
 PATHOPHYSIOLOGY OF GRANULOMA FORMATION
 CLASSIFICATION OF GRANULOMATOUS DISEASES
 GRANULOMATOUS LESIONS OF ORAL CAVITY
 CONCLUSION
 REFERENCES

3. DEFINITION:
Defined as a specific variety of chronic
inflammation in which cells of the mononuclear phagocyte
system are predominant & take the form of macrophages,
epithelioid cells & multinucleated cells. These cells are
aggregated into well demarcated focal lesions called
granulomas.

4.  Granulomatous diseases have plagued humans for million
years, with evidence of tuberculosis infection in Egyptians
mummies & description of the syphilis described by
Hippocrates & was recognized as a venereal disease in the
fifteenth century.
 In seventeenth century, the minute granules (milliary) in host
tissues were noted. Robert koch developed a method of
staining & identified bacteria & was able to differentiate
infectious, noninfectious granulomatous diseases.
 Actinomycosis was isolated in vivo & associated
with sulfur granule production in the late nineteenth century

5.  Granulomas are inflammatory lesions that evolve in response to irritation,
infectious agents, and foreign bodies.
 Localized masses of fibrovascular granulation tissue accompanied
by a nonspecific chronic or sometimes subacute inflammatory infiltrate as seen
microscopically are simple granulomas.
 In the oral cavity, lesions of this nature are most frequently encountered
intraosseously as endodontically related periapical granulomas.
 Simple granulomas in the oral cavity are generally localized to the gingiva, yet
may actually arise anywhere in the mouth or on the facial skin, where they
appear as cherry-red tumefactions, termed pyogenic granulomas.
 The peripheral giant cell granuloma of the gingiva and alveolar ridge is a reactive
lesion without an infectious etiology.
 specific granulomas are usually associated with mycobacteria or deep invasive
fungi, appearing microscopically as caseating and noncaseating granulomas.

6. Two types:
 Foreign body granuloma
 Immune granuloma

7. Foreign body reaction:
The foreign material is composed of particles that are usually too
large to be phagocytosed by macrophages. Because the
material is typically inert, it usually does not evoke an immune
response.Instead, in an attempt to eliminate the foreign substance
steady streams of macrophages are recruited to the site. There they
become activated, transform into epithelioid macrophages &
organize into granuloma.

8.  Distinct form of delayed-type (cell mediated) hypersensitivity.
Immune granulomas typically develop in response to infection by
various mycobacterial & fungal organisms.
 initial exposure to a non-degradable antigen derived from an
organism (usually a protein), there is an accumulation of
predominantly, (CD4- positive) T- lymphocyte around blood vessels
in the area where the antigens lie. Over time, the T cells
differentiate, become activated T- helper (Th) cells, & begin
secreting various cytokines that recruit macrophages to the site of
the foreign antigen.
 If the antigens persist & remain nondegradable, the recruited
macrophages eventually transform into epitheliod cells, organize &
form granuloma.

9. 1.Infection
Bacterial Fungal Spirochetal Parasitic
Tuberculosis Histoplasmosis Syphilis. Leishmaniasis
leprosy Blastomycosis Myiasis
Non tuberculous
Phycomycosis
Mycobacterial
(Mucormycosis)
infections
Toxoplasmosis
Actinomycosis Aspergillosis.
Klebsialla
Candidiasis.
rhinoscleromatis
Anthrax Cryptocoecosis
Brucellosis Rhinosporidiosis

10. 2) Traumatic Etiology:
i) Pyogenic granuloma
ii) Reparative granuloma
3) Foreign Body etiology:
i) Oral foreign body reactions.
(Suture, hair, amalgam, endodontic sealer,
hyaluronic acid etc.)
ii) Cholesterol granuloma
iii) Cocaine induced midline granuloma
iv) Gout

11. 4) Neoplastic
i)Histocytosis X
a)Eosinophilic granuloma
b) Hand schuller Christian Disease.
c) Letterersiwe disease.
ii) Benign Fibrous histiocytoma
iii) Neorotizing sialometaplasia.
iv) Polymorphic recticulosis (lethal midline
granuloma)

12. 5) Unknown Etiology:
i) Sarcoidosis,
ii) Crohn’s disease
6) Autoimmune & Vascular disease:
i) Wegener’s Granulomatosis
ii) Systemic Lupus erythematoses
iii) Sjogren’s syndrome.
7) Developmental:Melkerson Rosenthal syndrome
8) Congenital chronic Granulomatous disease of
Childhood.

14. Histopathological features:
 Highly vascular tissue – granulation tissue.
 Endothelium lined channels – engorged with RBC.
 Lobular channels.
 Surface – ulcerated – thick fibrinopurulent membrane.
 Neutrophils, plasma cells, lymphocytes.
 Neutrophils – ulcerated surface.
 Older lesions – fibrous appearance.

16. Clinical:
 Peripheral giant cell granuloma.
 Peripheral ossifying fibroma.
 Primary or metastatic malignancy.
Histopathological:
 Gingival fibromas.
 Polypoid capillary hemangioma.
 Inflammed lobular hemangioma.
•Conventional granulation tissue.
•Hyperplastic gingival inflammation.
•Kaposi’s sarcoma.
 Granulation tissue type hemangioma.
•Plasma cell granuloma.
•Kaposi’s sarcoma.
•Angiosarcoma.

17. Tuberculosis (TB)
Tuberculosis is a systemic infectious
disease of worldwide prevalence & of
varying clinical manifestations caused by
bacillus mycobacterium tuberculosis.
Mycobacterium tuberculi, is an important
cause of life–threatening disease, especially
in individuals infected with HIV.

18. As the lesion progresses tubercles coalesce to
form a confluent area of consolidation.
This may convert to fibro calcified scar or walled
by hyaline collageneous connective tissue, under
favorable conditions in their late lesion, the
multinucleated giant cells tends to disappear.
A Biopsy exhibiting granulomatous inflammation
& microscopic evidence of mycobacterial
organisms is often suggestive of Tuberculosis.

19. Histopathologically tuberculous
granulomas are composed of epithelioid
cells surrounded by a zone of fibroblasts &
lymphocyte that usually contains langhans
giant cells & some necrosis (caseation) is
usually present in the center of the
tubercles

20. Hansen’s Disease Or Leprosy
Leprosy is a slowly progressive infectious
disease caused by Mycobacterium
leprae. Affecting skin & peripheral nerves,
resulting in disabling deformities.
Histopathologically the typical
Granulomatous nodule shows collections
of epithelioid cells & lymphocytes in a
fibrous stroma.
Langhans type giant cells are variably
present with vacuolated macrophages
called lepra cells these are scattered
throughout the lesions & often contain the
bacilli.

21. Sarcoidosis:
Sarcoidosis is a relatively common multisystem
disease of unknown etiology.
Histopathologically-classic noncaseating
Granulomas, each composed of an aggregate
of highly clustered epitheloid cells, often with
langerhans or foreign body type gaint cells
and in chronic cases a fibrous rim may be
seen. Although various inclusion bodies, such
as Schaumann bodies (laminated concretions
composed of calcium and proteins) and
Asteroid bodies (stellate inclusions ) are seen
in over 90% of cases, though they are not
pathognomonic for sarcoidosis.

22. Photomicrograph showing granulomas with
lymphocytes and epitheloid cells with
Langhans giant cells

23. Actinomycosis:
 Actinomycosis is a chronic infectious
disease caused by the organisms of
the order Actinomycetase.
 Actinomyces are strict facultative
anerobes. They require an organic
nitrogen source and an atmosphere
containing atleast 5% CO2 for their
growth.
 A.isrelli is an organism most
commonly incriminated in the human
bodies.

24.  Histopatologically the actinomycotic granuloma
isolated mass of granulomatous inflammatory
response with a central area of suppurative
necrosis or a multitude of microscopic
suppurative field in the centre of necrosis.
Sulfur granules are found, in the form of masses
of filaments extending in a radiating, sporelike
fashion as a “sunburst radiation” or fiery
appearance.
 Colonies are surrounded by polymorphonuclear
infiltration peripheral to which are plasma cells,
lymphocytes,
multinucleated giant cells, macrophages and a
fibrous capsule are usually seen surrounding
these inflammatory focus

25. The filamentous mass is mineralized and cemented by host calcium
phosphate resulting from phosphatase activity from tissue
inflammation.
At the end of these filaments are club shaped extensions or rossets
formed by the adherence of neutrophils.
They are also encased in a polysaccharide protein complex. The
central core of the rosette stains basophilic& the peripheral clubs
stains eosinophilic with H & E stain.
Methanamine silver is useful because they color older filaments very
well.

26.  Crohn’s Disease
Crohn’s disease is a chronic Granulomatous disorder that may
involve any portion of the GIT including the oral cavity.
 The exact etiology remains unknown.
 Crohn’s disease is a Th1 disorder, Environmental and genetic
factors seem to play an important role in the pathogenesis.
 Recently mutations in the CARD15 /NoD2 gene on the Chromosome
16 also have been identified in 25% of patients with crohn’s disease.
 Histopathology: – noncaseating Granulomatous inflammation in
50% of cases and in the remaining cases of nonspecific perivascular
lymphocytic infiltrate.
 Gut biopsies characteristically show transmural inflammation.

28. A classic triad - nodular lip swellings, fissured
tongue, and unilateral facial palsy
Clinically, the lower lip is involved more
diffusely than the upper lip, being enlarged
with palpable nodularity throughout the
submucosa.
Microscopically, multiple granulomas are
seen to replace or infiltrate the lip minor
salivary glands. Nodular tumefactions that are
firm to palpation may be encountered in the
buccal mucosa, vestibule, and tongue.

29. Melkersson-Rosenthal syndrome. A, Fissured tongue; B,
granulomatous cheilitis; C, facial nerve palsy.

30.  Granulomas located as multiple nodules throughout the
lips constitute cheilitis granulomatosa, provided these
lesions are the only manifestation of the condition.
lip granulomas with identical appearance to cheilitis
granulomatosa are encountered in the Melkersson-Rosenthal
syndrome.
 The lower, upper, or both lips may be involved Although the
swelling may appear to be diffuse, palpation discloses multiple
and often confluent nodules within the submucosa.
 Biopsy shows multiple noncaseating granulomas replacing
minor salivary lobules

31. Cheilitis granulomatosa. A, lip lesions are diffuse; B, noncaseating
granuloma (arrow) replacing the minor salivary glands located
in the submusoa.

32.  Wegener granulomatosis
Often included as a form of midline lethal granuloma, Wegener
granulomatosis represents an inflammatory destructive disease that
may have widespread systemic involvement.
 The granulomas of Wegener granulomatosis are usually localized in
the lung and kidneys. The middle ear, gingiva, and nasal mucosa are
also commonly affected.
 Microscopically, vasculitis is a dominant finding, along with fibrinoid
necrosis. The adjacent granulation tissue is often infiltrated with
eosinophils and occasional multinucleated giant cells are seen.

33.  Antibodies directed to neutrophil cytoplasmic antigens (ANCA) are
detected using indirect immunofluorescence with neutrophils as
substrate, being positive in over 90% of cases.

34. HISTOPLASMOSIS:
 Common systemic fungal
infection in the united states.
 Caused by histoplasma
capsulatum, is dimorphic,
growing as a yeast at body
temperature in the human
host and as a mold in its
natural environment.
 Air-borne spores of the
organism are inhaled,pass
into the terminal passages of
the lungs &germinate.
 TYPES :
Acute,chronic,disseminated
histoplasmosis.

35. HISTOPATHOLOGICAL
FEATURES:
 Diffuse infiltrate of
macrophages or more
commonly collections of
macrophages organized
into granulomas.
 Multinucleated giant cells
are seen in association
with the granulomatous
inflammation.
 Special stains such as the
PAS & Grocott-Gomari
methenamine silver
methods.

36.  Synonyms- Mucormycosis,Phycomycosis
 Zygomycota are extremely abundant saprobic
fungi found in soil, water, organic debris, and food.
 Genera most often involved are Rhizopus, Absidia,
and Mucor.
 Usually harmless air contaminants invade the
membranes of the nose, eyes, heart, and brain of
people with diabetes and malnutrition, with severe
consequences.

37. ORAL MANIFESTATIONS:
 Rhinocerebral form is most relevant to the
oral health care provider.
 Zygomycosis is noted especially in insulin-dependent
diabetics who have uncontrolled
diabetes and are ketoacidotic.
 Ketoacidotic inhibits the binding of iron to
transferin, allowing serum iron levels to rise.

38. H/P:
 Extensive necrosis
with numerous
large (6-30 micro
m)
 branching
nonseptate hyphae
at the periphery.
 The hyphae tend to
branch at
90°angles.

39.  Coccidioides immitis - causes
coccidioidomycosis
 Distinctive morphology – blocklike
arthroconidia in the free-living stage and
spherules containing endospores in the lungs
 Lives in alkaline soils in semiarid, hot climates
and is endemic to southwestern U.S.
 Arthrospores inhaled from dust, creates
spherules and nodules in the lungs
 Amphotericin B treatment

40. Blastomyces dermatitidis- causes
blastomycosis
Dimorphic
Free-living species distributed in soil of a
large section of the midwestern and
southeastern U.S.
Inhaled 10-100 conidia convert to yeasts
and multiply in lungs
Symptoms include cough and fever.
Chronic cutaneous, bone, and nervous
system complications
Amphotericin B

42. HISTOPATHOLOGICAL FEATURES:
 Mixture of acute inflammation and
granulomatous inflammation surrounded
by yeasts.
 These organisms are 8-20 micro meter in
diameter.
 B.dermatitidis can be detected-special
stains such as gromatt-Gomori
methenamine silver&PAS.

43. Very common airborne soil fungus
 600 species, 8 involved in human disease; A.
fumigatus most commonly
 Serious opportunistic threat to AIDS,
leukemia, and transplant patients
 Infection usually occurs in lungs – spores
germinate in lungs and form fungal balls; can
colonize sinuses, ear canals, eyelids, and
conjunctiva
 Invasive aspergillosis can produce necrotic
pneumonia, and infection of brain, heart, and
other organs.
 Amphotericin B and nystatin

45. TOXOPLASMOSIS:
 Common disease caused by the obligate intracellular
protozoal organism T. gondii.
 T. godii multiplies in the intestinal tract of the cat by
means of a sexual life cycle, discharging numerous
oocysts in the cat feces. Another animal or human can
ingest these oocysts , resulting in the production of
disease.
CLINICAL FEATURES:
 Often Asymptomatic
 If symptomatic they are usually mild and resemble
infectious mononucleosis.
 Pt’s may have a low grade fever , cervical
lymphadenopathy.

46.  In immunosuppressed patients ,
toxoplasmosis represent a new,primary
infection or reactivation of previously
encysted organism.
 The principal groups at risk –
AIDS
Transplant recipients
Cancer patients

47. DIAGNOSIS AND TREATMENT:
 Identification of rising serum antibody titers
to T.gondii within 10-14 days after
infection.
 Biopsy of an involved lymphnode may
suggest the diagnosis and serologic
studies if possible.
 Folinic acid and sulfadiazine,if allergic to
sulfa drugs clindamycin can be used.

48. HISTIOCYTIC:
Eosinophilic granuloma(unifocal eosinophilic granuloma):
 Lichtenstein and jaffe in 1940
 A lesion of bone which is primarily a histiocytic proliferation with an
abundance of eosinophilic leukocytes but no intracellular lipid
accumulation.
 Primarily in older children and young adults.
 M:F- 2:1
C/F:
 No physical signs & symptoms
 Incidental radiographic findings.

49. Common sites: skull and mandible
Other sites: Femur,humerus,ribs & other bones.
Radiographic: Irregular radiolucent areas usually
involving superficial alveolar bone.
H/P:
Prmary cell is histocyte which grows in sheets or
sheetlike collections. The histiocyte may coalesce
& form multinucleated giant cells- uncommon.
Early lesion- large no of collections of
eosinophils,lesion matures , fibrosis occurs & less
no of eosinophils. Then similar H/P picture of hand
schuller christian disease.

50. Synonym: multifocal eosinophilic granuloma:
Widespread skeletal & extraskeletal & a chronic clinical course.
 It occurs primarily in early life, before the age of 5.
 More common in boys than girls.
C/F:
Classic triad- single/multiple punched out bone destruction in the
skull
Unilateral or bilateral exophthalmos
Diabetic insipidus
the complete triad occurs only 25% of affected patients.

51. Eosinophilic
granuloma
Hand-schuller-christian
disease
Letter-siwe disease
Proliferative cell is
histiocyte
histiocytes histiocytes
Only bone is affected,
less soft tissue
Skeletal& soft tissue
involvement
Acute, fulminating
disease with skeletal &
extraskeletal& skin.

52. Oral manifestations:
 oral involvement 5-75%
 Often non specific & include sore mouth,with or without ulceratve
lesion
 Halitosis
 Gingivitis
 Suppuration
 Unpleasant taste
 Loose & sore teeth.
Radiographic features:
Skull- sharply outlined
Jaws- more diffuse.

53. Histologic features:
Four stages:
 A proliferative histiocytic phase-eosinophilic leukocytes scattered
throughout the sheets of histiocytes.
 A vascular granulomatous phase-histiocytes & eosinophils(some
foam cells)
 Diffuse xanthomatous phase-Abundance of foam cells
 Fibrous or healing phase.
LAB FEATURES:
Anemia, leukopenia& thrombocytopenia-rare.

54. CHOLESTEROL
GRANULOMA
Photomicrographs showing
histopathological features of the
cholesterol granuloma; large number of
white spindle-shaped clefts
representing cholesterol clefts, with
lymphocytes(arrows) infiltration.
No epithelial cells are seen.
FOREIGN BODY SUTURE MATERIAL

56.  Triad- Keratoconjuctivitis sicca
Xerostomia
Rheumatoid arthritis
Primary sjogren syndrome-
Dry eyes & dry mouth
Secondary sjogrens:
SLE
Polyarteritis nodosa
Scleroderma
Rheumatoid arthritis
Etiology:
Genetic
Hormonal
Infections & immunologic

57. c/f:
Females are more common over 40 yrs
Ratio- 10:1
Radiographic : cherry blossom or branchless
fruit laden tree effect.
H/P:
 intense lymphocytic infiltration
 Lobular architecture is preserved
 Epimyoepithelial islands are present.

58. The lobular architecture of the
seromucinous glands is preserved. The
seromucinous acini show squamous
metaplasia with slight reactive atypia.
 Non neoplastic inflammatory condition
Etiology:
Trauma
Radiation therapy/ surgery
Vascular ischemia
Tobacco – risk factor
C/F:
Minor salivary gland-palate
Others retromolar pad, BM,tongue,incisive
Canal & labial mucosa
Clinical presentation:
Crateriform ulcer of the palate that similates
A malignant process.
1-3cm & unilateral

59. H/p:
Coagulative necrosis of glandular acini
Squamous metaplasia
Mucin poolng is present
Inflammatory infiltrate of
macrophages,neutrophils,&
lymphocyes(less),plasma cells &
eosinophils.
Pseudo epitheliomatous hyperplasia
D/D: Scc & mec