Nasal

Granulomas

Dr. Vishal Sharma

 Definition of granuloma
Granulomas result from chronic inflammation &

consist of: a. macrophages

b. epithelioid cells (active macrophages

resembling epithelial cells)

c. multi-nucleated giant cells

+ d. vasculitis

+ e. necrosis
 Classification of
nasal granulomas
A. Bacterial C. Fungal

1. Rhinoscleroma 1. Mucormycosis

2. Tuberculosis 2. Aspergillosis

3. Syphilis D. Non-specific:

4. Leprosy 1. Sarcoidosis

B. Aquatic parasite 2. Wegeners granuloma

1. Rhinosporidiosis 3. Allergic granuloma

4. Sinonasal lymphoma ?
 Rhinoscleroma or
Respiratory Scleroma
 Definition
Rhinoscleroma or scleroma is progressive

granulomatous disease caused by gram negative

Klebsiella rhinoscleromatis [von Frisch bacillus]

Commences in nose nasopharynx, para nasal

sinus, oropharynx, larynx, trachea & bronchi

 Nasal involvement staging
1. Catarrhal Stage: foul smelling purulent nasal

discharge (carpenters glue), not responding to

conventional antibiotics

2. Atrophic stage: foul smelling, honey-comb

coloured crusting in stenosed nasal cavity (in

contrast to roomy nasal cavity of atrophic rhinitis)

 Nasal involvement staging
3. Nodular/ granulation stage: Non-ulcerative,

painless nodules (soft & bluishred pale &

hard)which widen lower nose (Hebra nose)

4. Cicatrizing stage: Adhesions & stenosis

coarse & distorted external nose (Tapir nose).

Lower external nose & upper lip have woody feel.

Rhinoscleroma nodules
Lesion in nose & palate
Hebra nose
Tapir Hebra
 Involvement of other sites
Nasopharynx: Ear block & ed hearing (fibrosis of

eustachian tube orifice). Nasal intonation & nasal

regurgitation (fibrosis of soft palate).

Oropharynx: Sore throat

Larynx & tracheo-bronchial tree: Dry cough,

hoarseness, respiratory distress

 Investigations
X-ray PNS: sinusitis + bone destruction

Nasopharyngoscopy: obliteration of nasopharynx

due to adhesions b/w deformed V-shaped soft
palate & posterior pharyngeal wall (Gothic sign)

Flexible laryngoscopy: subglottic stenosis

Biopsy & H.P.E.: Mikulicz cell & Russel body

Complement fixation test: b/w pts serum & Frisch

bacillus suspension. Done if biopsy is inadequate.
 Histopathology
Granulomatous tissue characterized by:

1. Mikulicz (foam) cells: histiocytes with foamy

vacuolated cytoplasm + central nucleus &

containing Frisch bacilli

2. Russel (Hyaline) body: degenerated plasma cells

with large round eosinophilic material

Histopathology
Histopathology (magnified)
Warthin-Starry stain: Mikulicz cell
 Medical treatment
Total duration = 6 wk to 6 months (or negative

cultures from 2 consecutive biopsy materials)

Streptomycin: 1g OD intramuscularly

+ Tetracycline: 500 mg QID

orally

Rifampicin: 450 mg OD orally

2% Acriflavine solution: applied locally OD

 Radiotherapy & Surgery
R.T.: 3500 cGy over 3 wk along with antibiotics
halts progress of resistant cases

Removal of granulations & nodular lesions with

cautery or laser
Dilatation of airway combined with insertion of
Polythene tubes for 6 8 wk

Plastic reconstructive surgery: after 3 negative

cultures from biopsies
Tuberculosis
 Sino-nasal Tuberculosis
Rare. Usually due to spread from pulmonary TB

Ulcers, nodules, polypoid masses in cartilaginous

part of septum, lateral wall & inferior turbinate

H.P.E.: epithelioid granulomas with Langhans

multi-nucleate giant cells, caseating necrosis

AFB may be found on nasal smears

Treatment: INH + Rmp + Etb + Pzn X 6 9 mth

Acid Fast Bacillus
Histopathology
Histopathology magnified
 Lupus Vulgaris
Tuberculosis of skin (of nose & face)

Can mimic a squamous cell carcinoma

Rapid course / indolent chronic form

Nodules have apple jelly appearance on diascopy

Nodules ulcerate & crust scarring + distortion

of nasal alae, nasal tip & vestibule

Tx: A.T.T. surgical reconstruction if required

Lupus vulgaris
Apple jelly nodule
Syphilis
 Primary syphilis
Lesions develop 3-4 wks after contact

Chancre on external nose / vestibule

Hard, painful, ulcerated papule

Enlarged, rubbery, non-tender node

Spontaneous regression in 6-10 wks

Primary syphilis chancre
 Secondary syphilis
Most infectious stage

Symptoms appear 6-10 wks after inoculation

Persistent, catarrhal rhinitis

Crusting / fissuring of nasal vestibules

Mucous patches in nose/pharynx

Roseolar, papular rashes on skin

Pyrexia, shotty enlargement of lymph nodes

Secondary syphilis rashes
Rash of secondary syphilis
 Congenital syphilis
Infants: snuffles, 3 wks to 3 mth after birth

Fissuring / excoriation of upper lip / vestibule

Mucosal rashes, atrophic rhinitis, saddle nose

deformity, palatal perforation

Prenatal h/o syphilis, stillbirths, miscarriages

Hutchinsons incisors, Moons mulberry molars,

interstitial keratitis, corneal opacities, SNHL

Congenital syphilis:
palatal rash & perforation
 Tertiary syphilis
Commonest manifestation of nasal syphilis

Gumma: red, nodular, submucous swelling with

infiltration. Ulcerates with putrid discharge /

crusting. Ulcer margins irregular, overhanging,

indurated, bare bone underneath.

Sites: mucosa, periosteum, bony septum, lateral

wall, floor of nose, nasal dorsum, nasal bones

Tertiary syphilis gumma
 Investigations
Dark-ground illumination examn of nasal smear

Venereal Disease Research Laboratory test

Rapid Plasma Reagin

Fluorescent Treponemal Antibody Absorption

Treponema Pallidum Haem-agglutination Assay

H.P.E.: peri-vascular cuffing by lymphocytes &

plasma cells. Endarteritis: narrowing of

vascular lumen, necrosis, ulceration.

Sensitivity of serological tests
Test Primary Secondary Latent Tertiary
(% (% +ve) (% +ve) (% +ve)
+ve)
VDRL 75 90 100 90 100 40 - 90

RPR 77 - 99 100 95 - 100 73

FTA-Abs 70 100 100 100 96

TPHA 70 - 90 100 97 - 100 94

 Treatment
1. Benzathine penicillin G, IM, 2.4 MU single dose

2. If penicillin allergic: Doxycycline or Tetracycline

Doxycycline: 100 mg orally BD for 2 weeks

Tetracycline: 500 mg orally QID for 2 weeks

3. Sequestrectomy

4. Augmentation Rhinoplasty for nasal deformity

 Complications of untreated
syphilis
Secondary infection with pyogenic organisms

Sequestration of bone

Perforation & collapse of bony nasal septum

Perforation of hard palate

Scarring / stenosis of choanae

Atrophic rhinitis

Meningitis
Leprosy
 Leprosy
Etiology: Mycobacterium leprae
Types: a. tuberculous
b. lepromatous
c. borderline
C/F: nodules, inflammation of nasal mucosa, nasal
obstruction, septal cartilage perforation
X-ray: erosion of anterior nasal spine
Sequelae: saddle nose, atrophic rhinitis, stenosis
Tuberculous Lepromatous
Saddle nose in leprosy
Erosion of anterior nasal spine
 W.H.O. treatment regimen
A. Tuberculoid (pauci-bacillary) leprosy: for 6 mth
Dapsone: 100 mg daily, unsupervised
+ Rifampicin: 600 mg monthly, supervised
B. Lepromatous (multi-bacillary) leprosy: for 12 yr
Dapsone: 100 mg daily unsupervised
+ Clofazimine: 50 mg daily unsupervised
+ Rifampicin: 600 mg monthly supervised
+ Clofazimine: 300 mg monthly supervised
Rhinosporidiosis
 Definition
Chronic granulomatous infection by Rhinosporidium

seeberi, mainly affecting mucous membranes of

nose & nasopharynx; characterized by formation of

friable, bleeding or polypoidal lesions

Other sites: lips, palate, antrum, conjunctiva,

lacrimal sac, larynx, trachea, bronchus, ear, scalp,

skin, penis, vulva, vagina, hand & feet.

What is Rhinosporidium seeberi?
Bizarre fungus: obsolete theory

Microcystis aeruginosa: a unicellular prokaryotic

cyanobacterium (Karwitha Aluwalia)

Aquatic parasite (Protoctistan Mesomycetozoa)

according to recent 18S ribosomal ribonucleic

acid (rRNA) gene analysis

 Epidemiology
88 95% cases are found in India & Sri Lanka

Common in Kerala, Karnataka & Tamil Nadu

Age : 20 40 yrs.

Male: Female ratio = 4 : 1

People with blood group O more susceptible

 Classification
Benign

a. Nasal ---------------------------------------------------- 78%

b. Nasopharyngeal -------------------------------------- 16%

c. Mixed (naso-nasopharyngeal, nasolacrimal) -- 05%

d. Bizarre (Conjunctival / Tarsal / Cutaneous) --- rare

Malignant ------------------------------------------------- rare

Generalized, deep seated & difficult to eradicate

 Clinical Presentation
Epistaxis + viscid nasal discharge + nose block

Nasal mass: papillomatous or polypoid, granular,

friable, bleeds on touch, pedunculated or sessile,
pink surface studded with white dots [Strawberry
apperance], involves septum & turbinates

Nasal mucosa: edematous, hyperemic, covered with

copious viscid secretions containing spores

Lymph nodes: not affected

Nasal mass
Bleeding nasal mass
Nasal + Nasopharynx
Nasal + Nasopharynx
Oropharyngeal mass
Mass in uvula
Cutaneous granulomas
 Mode of transmission
1. Bathing (head dipping) in infected water: infective

spores enter via breached nasal mucosa

2. Droplet infection by cattle dung dust

3. Contact transmission: contaminated fingernails

are responsible for cutaneous lesions

4. Haematogenous: to other sites in infected pt

Life cycle
Life cycle begins as oval / spherical Trophocyte

[8 m] with single nucleus. Nuclear + cytoplasmic

division of Trophocyte results in intermediate

Sporangium. This enlarges into a mature

Sporangium [120 300 m] with chitinous wall &

contains 16,000 Endospores. Mature sporangium

ruptures during sporulation & releases infective

endospores via its Germinal pore. Endospores

enter another host & grow into trophocyte.

 Differential diagnosis
1. Infected antrochoanal polyp
2. Inverted papilloma
3. Other granulomas:
Rhinoscleroma
Tuberculosis
Leprosy
Fungal (aspergillosis, mucormycosis)
4. Malignancy of nose / paranasal sinus
 Investigations

1. Biopsy & Histo-pathological examination

2. Microscopic examination of nasal discharge

for spores
Haematoxylin & Eosin stain
Periodic Acid Schiff stain
Gomori Methenamine Silver stain
 Medical Treatment
Dapsone: arrests maturation of spores (inhibits

folic acid synthesis) & increases granulomatous

response with fibrosis

Dose: 100 mg OD orally (with meals) for one year

Give Iron & Vitamin supplements

Side effects: Methemoglobinemia & anemia

 Surgical management
At least 2 pints blood to be kept ready
General anesthesia with Oro-tracheal intubation
2% Xylocaine (with 1:2 lakh adrenaline) infiltrated
till surrounding mucosa appears blanched
Mass avulsed using Lucs forceps & suction
After removal of mass, its base cauterized
Avoid traumatic implantation during surgery
Laser excision: minimal bleeding, no implantation
Fungal granulomas
 Fungal Sinusitis
A. Invasive (hyphae present in submucosa)

1. Acute invasive or fulminant (< 4 weeks)

2. Chronic invasive or indolent (> 4 weeks)

Granulomatous Non - granulomatous

B. Non-invasive

1. Allergic 2. Fungal ball 3. Saprophytic

Aspergillosis & Mucormycosis are common

Predisposing factors for invasive
fungal infection
Uncontrolled diabetes mellitus
Profound dehydration
Severe malnutrition
Severe burns
Leukemia, lymphoma
Chronic renal disease, septicemia
Long term tx with (steroids, anti-metabolites,
broad spectrum antibiotics)
 Clinical Features
Acute invasive fungal sinusitis by Mucormycosis

Unilateral nasal discharge + black crusts due to

ischaemic necrosis, proptosis, ophthalmoplegia

Cerebral & vascular invasion may be present

Significant inflammation with fibrosis & granuloma

formation seen in chronic invasive fungal sinusitis

Locally destructive with minimal bone erosion

Black crusting
 Treatment
Remove precipitating factors

Surgical debridement of necrotic debris

Amphotericin B infusion: 1 mg / kg / day IV daily /

on alternate days (total dose of 3 g). Liposomal

Amphotericin B less toxic & more effective

Itraconazole: 100 mg BD for 6-12 months

Hyperbaric oxygen: fungistatic + tissue survival

Surgical debridement
 Allergic fungal sinusitis
Associated with ethmoid polyps & asthma

Unilateral thick yellow nasal discharge with

mucin, eosinophils & Charcot Leyden crystals

C.T. scan: radio-opaque mass with central area

of hyper density (due to hyphae)

Tx: Surgical debridement + anti-histamines +

steroids (oral & topical)

Allergic fungal sinusitis
Allergic fungal sinusitis
C.T. scan coronal cuts
C.T. scan axial cuts
Fungal ball (Mycetoma)
Refractory sinusitis with foul smelling cheesy
material in maxillary sinus

Tx: Surgical removal. No anti-fungal drugs.

Saprophytic fungal sinusitis

Seen after sino-nasal surgery due to proliferation
of fungal spores on mucous crusts

Tx: Surgical removal. No anti-fungal drugs.

 Investigations
Biopsy & HPE: Tissue invasion by broad, non-
septate, 900 branching hyphae. Fungal penetration
of arterial walls with thrombosis & infarction.
Staining by Periodic Acid Schiff or Grocott
Gomori Methenamine Silver nitrate stain.

X-ray PNS: Sinusitis + focal bone destruction

CT scan: rule out orbital & intracranial extension

MRI: for vascular invasion & intracranial extension

Aspergillosis Mucormycosis
Aspergillosis Mucormycosis
hyphae hyphae
Narrow Broad

Septate Non-septate

Branching at 450 Branching at 900

Dichotomous branching Singular branching

Immuno-fluorescent staining
Sarcoidosis
 Definition & etiology
Synonym: Boecks sarcoid or Besnier Boeck

Schaumann syndrome

Definition: chronic systemic disease of unknown

etiology which may involve any organ with non-

caseating (hard) granulomatous inflammation

Etiology: 1. Special form of Tuberculosis (?)

2. Unidentified organism
 Clinical features
Nasal discharge, nasal obstruction, epistaxis

Mucosal: reveals yellow nodules surrounded by

hyperaemic mucosa on anterior septum & turbinates

Skin (Lupus Pernio or Mortimers malady): nasal tip

shows symmetrical, bulbous, glistening violaceous
lesion (resembling perniosis or cold induced injury)
Similar lesions on cheeks, lips & ears [Turkey ears].
Diascopy reveals yellowish brown appearance.
Lupus Pernio
 Heerfordts syndrome
Synonym: Waldenstrms uveo-parotid fever

Special form of sarcoidosis with:

1. Transient B/L Facial palsy

2. Parotid enlargement

3. Uveitis

4. Fever
 Probe test
Probing of nodular lesion to look for penetration

Negative in sarcoidosis: probe does not penetrate

nodular swelling because of hard granulomas

Positive in Lupus vulgaris: probe penetrates up to

soft granulation tissue in centre of nodule

 Investigations
Biopsy of nodule & HPE: Non-caseating hard
granuloma with ill-defined rim of surrounding
lymphoid cells (naked tubercle). Giant cells
contain asteroid inclusion or Schaumann bodies

Kveim Siltzbach Test: Intradermal injection of

spleen extract from case of sarcoidosis followed 6
wks later by skin biopsy shows development of
non-caseating nodules
Non-caseating granuloma
Non-caseating granuloma
Asteroid inclusion bodies
 Chest X-ray findings
Stage I = B/L Hilar lymph node enlargement

Stage II = B/L Hilar lymph node enlargement +

diffuse parenchymal infiltrates

Stage III = Diffuse parenchymal infiltrates without

Hilar lymph node enlargement

Stage IV = Diffuse parenchymal infiltrates +

fibrosis with cor pulmonale

Hilar lymphadenopathy
 Treatment
1. Prednisolone: 1 mg/kg/d x 6 wk, taper over 3 mth.

Good response in mucosal disease only.

2. Chloroquine / Methotrexate + Prednisolone:

in pt not responding to steroids

Chloroquine = 250 mg PO on alternate days x 9 mth

Methotrexate = 5mg PO weekly x 3mth

3. Cutaneous lesions: excised & skin grafted

Wegeners
granuloma
 Definition
Autoimmune (?)
condition characterized
by necrotizing
granulomas within
nasal cavity & lower
respiratory tract,

generalised vasculitis &

focal glomerulonephritis
 Clinical Features
Nose & paranasal sinus: epistaxis, nasal block,

extensive crusts, septal destruction & nasal

collapse. Rule out nasal substance abuse.

Pulmonary: Cough, haemoptysis

Renal: Hematuria & oliguria

Otological: Otalgia, deafness, facial nerve palsy

Oral & pharyngeal: Hyperplastic, granular lesions

 Clinical Features
Laryngo-tracheal: laryngitis, subglottic stenosis

Ophthalmological: scleritis, conjunctivitis, corneal

ulceration, dacryocystitis, proptosis,

optic neuritis, blindness

Others: Skin ulceration, polymyalgia, polyarthritis

If untreated: death within 6 mth due to renal failure

Crusting in nasal cavity
External nasal deformity
Destruction of orbit & nose
 Differential diagnosis
VASCULITIS GRANULOMAS + VASCULITIS
Polyarteritis nodosa Allergic granulomatosis
S.L.E. Loefflers syndrome
Rheumatoid arthritis PULMONARY + RENAL
Sjogrens syndrome Goodpastures
syndrome
OTHER GRANULOMAS NEOPLASM
Specific Sinonasal lymphoma
T.B. Metastatic bronchial cancer
Syphilis OTHERS
Non-specific Nasal substance abuse
Sarcoidosis Systemic myiasis
 Investigations
E.S.R.: raised

Urine microscopic examn: RBC casts & RBCs

CT PNS: bone destruction in nasal cavity

Chest X-ray & CT scan: pulmonary nodules

Serum urea & creatine: ed renal function

Biopsy of lesion & HPE: Granulomas + Vasculitis

+ Fibrinoid vascular necrosis

CT scan PNS: nasal destruction
CXR: nodular lesion with cavity
 C.T. scan lungs

nodular lung infiltrate with cavitation

HPE: Granulomatous vasculitis

L = small pulmonary artery lumen surrounded by

inflammatory infiltrate including a giant cell (black arrow)
Segmental glomerular necrosis

early crescent formation (black arrows)

 c-A.N.C.A.
Anti-Neutrophil Cytoplasmic Antibody (ANCA) titre

by immuno-fluorescence.

c-ANCA = cytoplasmic fluorescence

Raised c-ANCA titres = 65-96% sensitive in WG

Becomes -ve when disease is controlled

p-ANCA = peri-nuclear fluorescence

p-ANCA titres raised in Polyangitis

C ANCA by indirect
immuno-fluorescence
 Medical Treatment
1. Triple therapy:

Prednisolone: 1 mg/kg/d x 1 mth Taper over 3 mth

+ Cyclophosphamide: 2mg/kg / day x 6-12 mth

+ Cotrimoxazole: 960 mg OD X indefinitely

2. Plasma exchange & intravenous immunoglobulin

3. Alkaline nasal douche for crusts

Sinonasal lymphoma
(not a granuloma)
 Synonyms
Stewarts granuloma

Lethal midline granuloma

Non-healing midline granuloma

Idiopathic midline destructive disease (IMDD)

Sinonasal T-cell lymphoma

Necrosis with atypical cellular exudate (NACE)

Midline malignant reticulosis

 Clinical Features
Prodromal stage: Blood-stained nasal discharge

Active stage: Nasal crusting, ulceration, septal

perforation

Terminal stage: Tumour sloughing, mid-face

mutilation

D/D: Wegeners granuloma, Basal cell carcinoma

Rx: Radiotherapy (5000 cGy) + chemotherapy

Mid-face mutilation
 Wegeners Sinonasal
Granuloma Lymphoma
Bilateral involvement Unilateral involvement

Slowly progressive Rapidly progressive

Diffuse ulceration Focal ulceration

Extensive crusting Moderate crusting

Absence of gross Gross destruction of

destruction of mid-face mid-face present
Pulmonary & renal No pulmonary or renal
involvement present involvement
Investigation Wegeners Sinonasal
Granuloma Lymphoma
Vasculitis present absent

Granulomas present absent

Giant cell present absent

Atypical T absent present
lymphocytes
Angio-invasion absent present

C-ANCA titre raised not raised

 Churg & Strauss Syndrome
Synonym: allergic granulomatosis

C/F: nasal polyps + bronchial asthma

Chest X-ray: pulmonary lesions

HPE of nasal polyp: necrotizing granulomas with

abundant eosinophils without vasculitis

Tx: 1. Corticosteroids (topical & systemic)

2. Nasal polypectomy
Thank You