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Nasal Granulomas






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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)
Nasal Granulomas

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Slide 1

Nasal Granulomas

Dr. Vishal Sharma

Slide 2

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

Slide 3

Classification of nasal granulomas

Slide 4

A. BacterialC. Fungal

1. Rhinoscleroma1. Mucormycosis

2. Tuberculosis2. Aspergillosis

3. Syphilis D. Non-specific:

4. Leprosy1.Sarcoidosis

B. Aquatic parasite2.Wegener’s granuloma

1.Rhinosporidiosis3.Allergic granuloma

4. Sinonasal lymphoma ?

Slide 5

Rhinoscleroma or Respiratory Scleroma

Slide 6

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

Slide 7

Nasal involvement staging

1. Catarrhal Stage: foul smelling purulent nasal discharge (carpenter’s glue), not responding to conventional antibiotics2. Atrophic stage:foul smelling, honey-comb coloured crusting in stenosed nasal cavity (in contrast to roomy nasal cavity of atrophic rhinitis)

Slide 8

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.

Slide 9

Rhinoscleroma nodules

Slide 10

Lesion in nose & palate

Slide 11

Hebra nose

Slide 12

Tapir Hebra

Slide 13

Involvement of other sites

Nasopharynx:Ear block & ed hearing (fibrosis of eustachian tube orifice). Nasal intonation & nasal regurgitation (fibrosis of soft palate).Oropharynx: Sore throatLarynx & tracheo-bronchial tree:Dry cough, hoarseness, respiratory distress

Slide 14

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.

Slide 15

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

Slide 16

Histopathology

Slide 17

Histopathology (magnified)

Slide 18

Warthin-Starry stain: Mikulicz cell

Slide 19

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

Slide 20

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

Slide 21

Tuberculosis

Slide 22

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

Slide 23

Acid Fast Bacillus

Slide 24

Histopathology

Slide 25

Histopathology magnified

Slide 26

Lupus Vulgaris

  • Tuberculosis of skin (of nose & face)

  • Can mimic a squamous cell carcinoma

  • Rapid course / indolent chronic form

  • Nodules have apple jelly appearanceon diascopy

  • Nodules ulcerate & crust  scarring + distortion of nasal alae, nasal tip & vestibule

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

Slide 27

Lupus vulgaris

Slide 28

Apple jelly nodule

Slide 29

Syphilis

Slide 30

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

Slide 31

Primary syphilis chancre

Slide 32

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

Slide 33

Secondary syphilis rashes

Slide 34

Rash of secondary syphilis

Slide 35

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

Slide 36

Congenital syphilis: palatal rash & perforation

Slide 37

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

Slide 38

Tertiary syphilis gumma

Slide 39

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.

Slide 40

Sensitivity of serological tests

Slide 41

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 Rhinoplastyfor nasal deformity

Slide 42

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

Slide 43

Leprosy

Slide 44

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

Slide 45

Tuberculous Lepromatous

Slide 46

Saddle nose in leprosy

Slide 47

Erosion of anterior nasal spine

Slide 48

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

Slide 49

Rhinosporidiosis

Slide 50

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.

Slide 51

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

Slide 52

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

Slide 53

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

Slide 54

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

Slide 55

Nasal mass

Slide 56

Bleeding nasal mass

Slide 57

Nasal + Nasopharynx

Slide 58

Nasal + Nasopharynx

Slide 59

Oropharyngeal mass

Slide 60

Mass in uvula

Slide 61

Cutaneous granulomas

Slide 62

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

Slide 63

Life cycle

Slide 64

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.

Slide 66

Differential diagnosis

  • Infected antrochoanal polyp

  • Inverted papilloma

  • Other granulomas:

     Rhinoscleroma

     Tuberculosis

     Leprosy

     Fungal (aspergillosis, mucormycosis)

  • Malignancy of nose / paranasal sinus

Slide 67

Investigations

  • Biopsy & Histo-pathological examination

  • Microscopic examination of nasal discharge for spores

Slide 68

Haematoxylin & Eosin stain

Slide 69

Periodic Acid Schiff stain

Slide 70

Gomori Methenamine Silver stain

Slide 71

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

Slide 72

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

Slide 73

Fungal granulomas

Slide 74

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

Slide 75

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)

Slide 76

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

Slide 77

Black crusting

Slide 78

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

Slide 79

Surgical debridement

Slide 80

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)

Slide 81

Allergic fungal sinusitis

Slide 82

Allergic fungal sinusitis

Slide 83

C.T. scan coronal cuts

Slide 84

C.T. scan axial cuts

Slide 85

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.

Slide 86

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

Slide 87

Aspergillosis Mucormycosis

Slide 89

Immuno-fluorescent staining

Slide 90

Sarcoidosis

Slide 91

Definition & etiology

  • Synonym:Boeck’s 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

Slide 92

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.

Slide 93

Lupus Pernio

Slide 94

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

Slide 95

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

Slide 96

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

Slide 97

Non-caseating granuloma

Slide 98

Non-caseating granuloma

Slide 99

Asteroid inclusion bodies

Slide 100

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

Slide 101

Hilar lymphadenopathy

Slide 102

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

Slide 103

Wegener’s granuloma

Slide 104

Definition

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

generalised vasculitis &

focal glomerulonephritis

Slide 105

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

Slide 106

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

Slide 107

Crusting in nasal cavity

Slide 108

External nasal deformity

Slide 109

Destruction of orbit & nose

Slide 110

Differential diagnosis

VASCULITISGRANULOMAS + VASCULITIS Polyarteritis nodosa  Allergic granulomatosis S.L.E.  Loeffler’s syndrome Rheumatoid arthritis PULMONARY + RENAL Sjogren’s syndrome  Goodpasture’s syndromeOTHER GRANULOMASNEOPLASMSpecific Sinonasal lymphoma T.B. Metastatic bronchial cancer SyphilisOTHERSNon-specific Nasal substance abuse Sarcoidosis  Systemic myiasis

Slide 111

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

Slide 112

CT scan PNS: nasal destruction

Slide 113

CXR: nodular lesion with cavity

Slide 114

C.T. scan lungs

nodular lung infiltrate with cavitation

Slide 115

HPE: Granulomatous vasculitis

L = small pulmonary artery lumen surrounded by inflammatory infiltrate including a giant cell (black arrow)

Slide 116

Segmental glomerular necrosis

early crescent formation (black arrows)

Slide 117

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

Slide 118

C – ANCA by indirect immuno-fluorescence

Slide 119

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

Slide 120

Sinonasal lymphoma (not a granuloma)

Slide 121

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

Slide 122

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

Slide 123

Mid-face mutilation

Slide 126

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

Slide 127

Thank You


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