Nasal Granulomas Dr. Vishal Sharma Definition of granuloma

Nasal Granulomas Dr. Vishal Sharma Definition of granuloma

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 2. Tuberculosis 1. Mucormycosis 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 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 Secondary

(% +ve) Latent (% +ve) Tertiary (% +ve)

VDRL Primary (% +ve) 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 Life cycle

Life cycle begins as oval / spherical Trophocyte [8 m] with single nucleus. m] with single nucleus. Nuclear + cytoplasmic division of Trophocyte results in intermediate Sporangium. This enlarges into a mature Sporangium [120 300 m] with single nucleus. m] with chitinous wall & contains 16,000 Endospores. Mature sporangium

ruptures during sporulation & releases infective endospores via its Germinal pore. Endospores 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, nonseptate, 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 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 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 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 S.L.E. Allergic granulomatosis

Loefflers syndrome Rheumatoid arthritis PULMONARY + RENAL

Sjogrens syndrome Goodpastures syndrome OTHER GRANULOMAS NEOPLASM Specific T.B.

Sinonasal lymphoma 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 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 Wegeners 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

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