Transcript Document

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. Wegener’s 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 (carpenter’s 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 & bluish–red  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 pt’s 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 Langhan’s
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
• Hutchinson’s incisors, Moon’s 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
(% +ve)
Secondary
(% +ve)
Latent
(% +ve)
Tertiary
(% +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 1–2 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 μm] with single nucleus. Nuclear + cytoplasmic
division of Trophocyte results in intermediate
Sporangium. This enlarges into a mature
Sporangium [120 – 300 μm] 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 Luc’s 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: Boeck’s sarcoid or Besnier – Boeck –
Schaumann syndrome
• Definition: chronic systemic disease of unknown
etiology which may involve any organ with noncaseating (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 Mortimer’s 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
Heerfordt’s syndrome
Synonym: Waldenström’s 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
Wegener’s
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.
 Loeffler’s syndrome
 Rheumatoid arthritis
PULMONARY + RENAL
 Sjogren’s syndrome
 Goodpasture’s 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
• Stewart’s 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: Wegener’s granuloma, Basal cell carcinoma
• Rx: Radiotherapy (5000 cGy) + chemotherapy
Mid-face mutilation
Wegener’s
Granuloma
Sinonasal
Lymphoma
Bilateral involvement
Unilateral involvement
Slowly progressive
Rapidly progressive
Diffuse ulceration
Focal ulceration
Extensive crusting
Moderate crusting
Absence of gross
destruction of mid-face
Gross destruction of
mid-face present
Pulmonary & renal
involvement present
No pulmonary or renal
involvement
Investigation Wegener’s
Granuloma
Sinonasal
Lymphoma
Vasculitis
present
absent
Granulomas
present
absent
Giant cell
present
absent
Atypical T
lymphocytes
absent
present
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