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Granulomatous Conditions of the Nose - MS ENT University Exam Guide

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1. RHINOSCLEROMA

Aetiology

• Caused by Klebsiella rhinoscleromatis (= Klebsiella pneumoniae subsp. rhinoscleromatis), first isolated by von Frisch
• Gram-negative, short, non-motile, encapsulated rod (2-3 µm), always found in a gelatinous capsule
• Route: direct inhalation of droplets or contaminated material
• Endemic in Central/South America, Mexico, Southeast Asia, Central/Eastern Europe

Pathology - Histology (HIGH YIELD)

• Mikulicz cells: large foamy macrophages containing the bacilli - PATHOGNOMONIC
• Russell bodies: eosinophilic hyaline degenerated plasma cells - also characteristic
• Bacilli are best demonstrated with Warthin-Starry silver stain
• Other cells: plasma cells, spindle cells, fibrosis

Three Stages (HIGH YIELD)

Clinical Features

• Bilateral; slow, progressive; no systemic illness
• Most common site: anterior nasal septum and floor of nose
• Advanced stages: complete obstruction of nares, seropurulent exudation, gross facial disfigurement
• Can extend to nasopharynx, oropharynx, larynx

Diagnosis

• Biopsy with histology (Mikulicz cells + Russell bodies)
• Culture (Klebsiella on MacConkey)
• Complement fixation test (heat-killed antigen)
• Warthin-Starry stain for bacilli

Differential Diagnosis

Treatment

• Fluoroquinolones (drug of choice) - prolonged course of at least 3-4 months to prevent relapse (ciprofloxacin / rifampicin)
• Tetracyclines / streptomycin (older regimens)
• Corticosteroids in acute phase
• Surgical/CO2 laser for airway stenosis or deformity correction
• Usually progressive and resistant to short-term therapy

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2. GRANULOMATOSIS WITH POLYANGIITIS (GPA) / WEGENER'S GRANULOMATOSIS

Definition

Epidemiology

• Mean age at diagnosis: 40-50 years
• Male = female; predominantly Caucasian (>90%)
• Rare in children

Pathogenesis

• Autoimmune - strongly associated with c-ANCA (anti-PR3) - cytoplasmic ANCA specific for proteinase-3
• ANCA activates neutrophils → releases oxygen radicals, cytokines, lytic enzymes → kills vascular endothelial cells
• Association with chronic nasal Staphylococcus aureus carriage (more frequent relapses)

Classification

• Localized: respiratory tract only, no systemic vasculitis
• Early systemic / Generalized: multi-organ with features of vasculitis

Clinical Features - ENT (HIGH YIELD)

• Nose and sinuses involved in >80% - most common presenting site (73-93% of all cases)
• Symptoms: nasal obstruction, crusting, purulent/bloody discharge, epistaxis, facial pain
• Destruction of septum, turbinates → single large nasal cavity
• Septal perforation → Saddle nose deformity (collapse of nasal bridge)
• Key distinction: intranasal destruction BUT no gross destructive changes of midfacial skin (unlike NK/T-cell lymphoma)
• Subglottic stenosis in ~20%
• Otitis media with effusion (OME) due to eustachian tube involvement
• Sensorineural or conductive hearing loss

Systemic Features

• Kidneys: focal segmental glomerulonephritis (pauci-immune), may progress to renal failure
• Lungs: nodules, cavities, infiltrates; haemoptysis
• Eyes: proptosis, episcleritis, scleritis, orbital pseudotumour
• Constitutional: malaise, weight loss, fever

Investigations

• c-ANCA (PR3-ANCA): ~90% sensitivity in generalized disease, 60-70% in localized
• Urine: haematuria, proteinuria, red cell casts
• CXR/CT chest: nodules, cavities
• Biopsy: necrotizing granulomatous inflammation - best yield from upper respiratory tract
• CT sinuses: mucosal thickening, bony erosion

Treatment

• Induction: cyclophosphamide + high-dose prednisolone (generalized disease)
• Rituximab (anti-CD20): now preferred for induction in many centres, equivalent to cyclophosphamide
• Methotrexate + prednisolone: for localized/early systemic
• Maintenance: azathioprine or methotrexate
• TMP-SMX (Co-trimoxazole): reduces relapses by suppressing S. aureus carriage
• Surgical: septal reconstruction, subglottic dilatation, OME management

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3. EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) / CHURG-STRAUSS SYNDROME

Definition

Pathogenesis

• Associated with p-ANCA (MPO-ANCA) in ~40% of cases
• Eosinophilia and IgE deposition in vessels suggests allergic pathogenesis
• Reported after use of zafirlukast (leukotriene receptor antagonist) - actually unmasking of existing vasculitis as steroid dose reduced

Three Clinical Phases (HIGH YIELD)

Clinical Features

• Asthma in 99% - late-onset, precedes vasculitis by average 8 years
• Sinonasal: allergic rhinitis, CRS with nasal polyps in up to 75%; obstruction, rhinorrhoea, anosmia, crusting
• Mononeuritis multiplex in up to 76% - foot drop etc.
• Cutaneous: papules, nodules
• Cardiac involvement = major cause of mortality (granulomatous myocarditis)
• Renal involvement less common than in GPA

Diagnosis

• Peripheral eosinophilia >10% of white cell differential + biopsy
• p-ANCA positive in ~40%
• ACR criteria (≥4 of 6): asthma, eosinophilia >10%, neuropathy, non-fixed pulmonary infiltrates, paranasal sinus abnormality, extravascular eosinophils on biopsy

Treatment

• High-dose corticosteroids (mainstay for less severe disease)
• Cyclophosphamide for severe/refractory
• Mepolizumab (anti-IL-5) - newer biologic approved for relapsing EGPA

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4. EXTRANODAL NK/T-CELL LYMPHOMA / MIDLINE LETHAL GRANULOMA / STEWART'S GRANULOMA

Nomenclature History (HIGH YIELD)

• Stewart's granuloma (1933) - original description by JW Stewart
• Midline lethal granuloma or Lethal midline granuloma
• Midline malignant reticulosis
• Polymorphic reticulosis
• Current correct term: Extranodal NK/T-cell lymphoma, nasal type (WHO classification)
• Associated with Epstein-Barr virus (EBV)

Key Concept

Epidemiology

• More common in Asia, South America, Mexico (lower frequency in Western countries)
• Male predominance; middle-aged adults

Pathogenesis

• EBV-positive NK/T-cell lymphoma - cells express NK cell markers (CD56) and T-cell markers
• Progressive midface destruction driven by tumour infiltration + necrosis
• Ulcerates through nasal septum, palate, orbit, facial skin

Clinical Features (HIGH YIELD)

• Begins with non-healing nasal ulcer, nasal obstruction, epistaxis, offensive nasal discharge
• Relentlessly progressive midface destruction:
  • Destruction of nasal septum, turbinates, lateral nasal wall, palate
  • Involvement of orbital floor → proptosis
  • Perforation through facial skin → grotesque deformity
• No systemic vasculitis - key distinction from GPA
• Gross midfacial skin destruction - key distinction from GPA (which has only mucosal/bony destruction)
• Constitutional symptoms: fever, weight loss
• Usually fatal within months if untreated

Investigations

• Biopsy (may need multiple attempts): shows lymphomatous infiltrate + necrosis; granuloma-like pattern
• Immunohistochemistry: CD56+, CD3+, TIA-1+, EBV+ (EBER in situ hybridization)
• No ANCA
• CT/MRI: midface destruction, orbital involvement

Treatment

• Radiotherapy (locoregional) - primary modality for localized disease
• Chemotherapy: CHOP or SMILE regimen (Steroid, Methotrexate, Ifosfamide, L-asparaginase, Etoposide) - preferred for disseminated disease
• Combined chemoradiotherapy for advanced stages
• Prognosis: historically very poor; better with modern protocols

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5. SARCOIDOSIS (Nasal)

Definition

Aetiology

• Unknown; immunological response to unidentified antigen in genetically susceptible individuals
• Possible: mycobacteria, fungi, beryllium, zirconium, pine pollen
• Macrophage + T-cell activation → TNF release → granuloma formation
• Non-caseating granulomas (no central necrosis) - KEY histological feature

Epidemiology

• Young adults, peak 3rd-4th decade
• Slightly more common in women
• 10-20x more common in African-Americans
• Incidence: 6-16/100,000; up to 64/100,000 in Scandinavia

ENT Features

• Lupus pernio: violaceous indurated plaques on nose, cheeks, lips - almost pathognomonic of sarcoidosis; associated with chronic pulmonary sarcoidosis
• Nasal: crusting, obstruction, epistaxis, anosmia
• Intranasal: pale nodular mucosal swellings (especially on septum and inferior turbinate)
• Subglottic stenosis
• Facial palsy (from parotid or temporal bone involvement)
• Bilateral parotid enlargement + uveitis + facial palsy = Heerfordt's syndrome (uveoparotid fever)
• Bilateral parotid enlargement + anterior uveitis + fever = Mikulicz syndrome (used loosely)

Systemic Features

• Lungs: bilateral hilar lymphadenopathy (BHL) - most common finding on CXR
• Eyes: uveitis, keratoconjunctivitis sicca
• Skin: erythema nodosum (acute), lupus pernio (chronic)
• Liver, spleen, lymph nodes
• Cardiac: arrhythmias, sudden death

Investigations

• CXR: bilateral hilar lymphadenopathy (staging: Stage I-IV)
• Serum ACE (angiotensin-converting enzyme): elevated in ~75% - useful for monitoring
• Kveim-Siltzbach test: intradermal injection of sarcoid tissue extract → positive granuloma formation (rarely used now)
• Serum calcium: hypercalcaemia (from 1-alpha-hydroxylase produced by macrophages)
• Biopsy: non-caseating epithelioid granulomas with Langhans giant cells, no acid-fast bacilli
• BAL: lymphocytosis with elevated CD4:CD8 ratio
• Gallium scan / PET: uptake in affected nodes

Treatment

• Many cases resolve spontaneously
• Oral corticosteroids: mainstay for symptomatic/progressive disease
• Methotrexate, azathioprine, hydroxychloroquine for chronic/steroid-sparing
• Anti-TNF (infliximab) for refractory cases
• Nasal: topical steroids, saline douching; endoscopic surgery for significant obstruction

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6. NASAL TUBERCULOSIS

Pathology

• Caused by Mycobacterium tuberculosis
• Caseating (central necrosis) granulomas - KEY distinguishing feature from sarcoidosis
• Langhans-type giant cells, epithelioid macrophages, lymphocytes, caseation
• AFB on ZN stain

Clinical Features

• Most common site: cartilaginous part of nasal septum
• Crusting, septal perforation, nodular thickening of mucosa, ulceration
• Lupus vulgaris: painful nodular tuberculoid lesion; characteristic "apple jelly" appearance on diascopy
• Purulent rhinorrhoea, nasal fissures
• Saddle nose deformity with progression

Investigations

• Mantoux/TST or IGRA
• Biopsy: caseating granuloma + AFB
• Culture (gold standard)
• HIV testing

Treatment

• Standard anti-TB therapy (RHEZ for 2 months, RH for 4 months)

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7. LEPROSY (Nasal)

• Caused by Mycobacterium leprae
• Nose is the most frequently affected site in leprosy - often the first site involved
• Route of infection: respiratory droplet from nasal secretions
• Features: epistaxis, crusting, nasal obstruction, anosmia
• Early: friable granulomatous intranasal lesions
• Advanced: septal perforation, nasal deformity, atrophy of nasal spine and premaxillary alveolar process, oroantral fistula
• Histology: Virchow cells (foamy macrophages laden with AFB = "globi") in lepromatous; epithelioid granulomas in tuberculoid
• Treatment: WHO multidrug therapy (dapsone + rifampicin ± clofazimine)

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8. RHINOSPORIDIOSIS

• Caused by Rhinosporidium seeberi (currently classified as a protist/mesomycetozoea, not true fungus)
• Endemic in India, Sri Lanka, parts of Africa
• Route: contact with stagnant water/sand
• Most common site: nasal cavity (also conjunctiva, nasopharynx)
• Classic presentation: strawberry-like, pedunculated, vascular polyp in nose; bleeds easily on touch; multiple white dots on surface (sporangia)
• Histology: large sporangia (up to 300 µm) containing endospores within a fibrovascular stroma; inflammatory granuloma around ruptured sporangia
• Treatment: surgical excision with base cauterization (dapsone may reduce recurrence rate)
• Recurrence common

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9. COCAINE-INDUCED MIDLINE DESTRUCTIVE LESION (CIMDL)

Clinical Importance

• Mimics GPA (Wegener's) and NK/T-cell lymphoma clinically and radiologically
• Caused by chronic intranasal cocaine use (vasoconstriction → ischaemia → necrosis)

Features

• Nasal septal perforation, saddle nose, palatal perforation
• No systemic vasculitis
• May have positive ANCA (due to non-specific inflammation) - can cause confusion with GPA

Key Distinguishing Features from GPA

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10. SYPHILITIC GUMMA (Tertiary Syphilis)

• Caused by Treponema pallidum
• Nasal gumma: destructive granulomatous lesion of septum/bridge
• Saddle nose deformity (cartilage/bone destruction) - classic
• Histology: gummatous necrosis, obliterative endarteritis, plasma cells, lymphocytes, absence of AFB
• VDRL/TPHA positive
• Treatment: penicillin G

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11. EOSINOPHILIC GRANULOMA (Langerhans Cell Histiocytosis)

• Proliferation of Langerhans cells (CD1a+, S100+, Birbeck granules on EM)
• Unifocal bone lesion - can affect nasal bones, sinuses
• Usually young males
• Lytic bone lesion on X-ray
• Histology: Langerhans cells, eosinophils, giant cells
• Treatment: curettage, low-dose radiotherapy, or conservative

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12. GIANT CELL GRANULOMA

• Benign giant cell lesion of jaw/sinuses
• Two types: central (within bone) and peripheral (on gingiva)
• Contains multinucleated giant cells in fibrovascular stroma
• May cause nasal obstruction if involving maxilla/sinuses
• Treatment: surgical excision; systemic steroids for aggressive lesions

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13. CHOLESTEROL GRANULOMA

• Foreign body reaction to cholesterol crystals precipitating in sinus (from old haemorrhage + poor ventilation)
• Also called "chocolate cyst" or orbital cholesteatoma
• Most common in frontal sinus, also maxillary sinus
• CT: expansile cyst with bony erosion, no enhancement
• MRI: hyperintense on both T1 and T2 (diagnostic)
• Histology: granulation tissue with foreign body-type giant cells surrounding cholesterol clefts
• Treatment: surgical drainage and marsupialization (endoscopic or external)

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COMPARATIVE SUMMARY TABLE (HIGH YIELD for Exams)

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HIGH-YIELD EXAM POINTS SUMMARY

1. Mikulicz cells (foamy macrophages) + Russell bodies (plasma cell derivatives) = Rhinoscleroma
2. Warthin-Starry stain demonstrates Klebsiella in rhinoscleroma
3. c-ANCA (anti-PR3) = GPA (Wegener's); p-ANCA (anti-MPO) = EGPA / MPA
4. Saddle nose = TB, syphilis, leprosy, GPA, CIMDL (cartilage/bone destruction)
5. Stewart's granuloma = Midline Lethal Granuloma = Extranodal NK/T-cell lymphoma (EBV-driven)
6. Non-caseating granuloma = Sarcoidosis; Caseating = TB
7. Asthma + eosinophilia + vasculitis = Churg-Strauss (EGPA)
8. Lupus pernio = cutaneous sarcoidosis of the nose/face (nearly pathognomonic)
9. Kveim test and elevated serum ACE = Sarcoidosis
10. Rhinosporidiosis = strawberry polyp; sporangia on histology; treated by surgical excision
11. NK/T-cell lymphoma = destructive midfacial skin lesion + EBV + CD56+ on IHC
12. GPA destroys mucosa/bone internally but spares facial skin; NK/T lymphoma destroys facial skin externally

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Internal Maxillary Artery (IMAX) Ligation - MS ENT University Exam Guide

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ANATOMY OF THE INTERNAL MAXILLARY ARTERY (HIGH YIELD)

Three Segments (Mnemonic: "DAB" / based on relations)

Key Surgical Anatomy Points

• The 3rd (pterygopalatine) segment is the surgical target for IMAX ligation
• Accessed via the posterior wall of the maxillary sinus (antrum)
• The IMAX terminates as the sphenopalatine artery (SPA), which is the main blood supply to the nasal cavity
• Branches identified in pterygopalatine fossa fat: proximal IMAX + descending palatine + sphenopalatine branches
• Infra-orbital nerve runs in the roof of the maxillary sinus and must be preserved

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INDICATIONS FOR INTERNAL MAXILLARY ARTERY LIGATION

Primary Indication: Intractable Posterior Epistaxis

1. Failure of conservative measures for posterior epistaxis:
   • First-aid measures (pinching, cold compress) failed
   • Anterior nasal packing failed
   • Posterior nasal packing (Foley catheter balloon / Brighton balloon / post-nasal pack) failed for 24-48 hours
   • Patient unfit to continue with packing
2. Repeated episodes of severe posterior epistaxis despite adequate packing
3. Epistaxis from a specific vascular territory supplied by IMAX / sphenopalatine artery:
   • Most posterior and inferior nasal bleeding (Little's area excluded)
   • Bleeding from posterior septum or lateral nasal wall
4. Bleeding from nasal tumours supplied by IMAX branches (pre-operative or palliative)
   • Juvenile nasopharyngeal angiofibroma (JNA) - as adjunct to surgery
   • Other vascular nasal tumours
5. Traumatic epistaxis - post-facial fractures (LeFort, NOE) not controlled by packing
6. Hereditary Haemorrhagic Telangiectasia (HHT / Osler-Weber-Rendu) - recurrent epistaxis refractory to local treatment
7. Failed embolization - when angiographic embolization is unavailable, contraindicated, or has failed

Note on Hierarchy of Surgical Options

• Controls bleeding closer to the nasal source
• Higher success rate (approaching 100% in some series)
• Less morbid than open trans-antral approach
• IMAX ligation is now used when ESPAL has failed or when more proximal vascular control is needed

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METHODS / SURGICAL APPROACHES TO IMAX LIGATION

Approach 1: TRADITIONAL TRANS-ANTRAL (SUBLABIAL / CALDWELL-LUC) APPROACH

Pre-operative Preparation

• General or local anaesthesia with hypotensive technique
• Nasal pack removed just before procedure
• Patient supine, head-up 15° tilt
• Orotracheal intubation preferred
• Topical vasoconstrictor in nose

Step-by-Step Technique

• Horizontal incision in the upper gingivobuccal sulcus (sublabial), from canine fossa region extending laterally
• Incision carried down to bone
• Preserve the infra-orbital nerve (exits infra-orbital foramen ~1 cm below infra-orbital rim)

• Periosteum elevated off anterior wall of maxilla
• Anterior wall of maxillary sinus removed with osteotomes or burr - creating an antrostomy (canine fossa antrostomy)
• Entry into maxillary sinus (antrum) confirmed

• Mucosa of the posterior wall of the maxillary antrum is carefully elevated
• A window is made through the posterior wall of the antrum into the pterygopalatine fossa
• Use fine osteotomes or Kerrison punch to remove this bony wall

• The branches of the internal maxillary artery are identified pulsating within the fat of the pterygopalatine fossa
• The fossa contains: IMAX and branches, maxillary nerve (V2), pterygopalatine ganglion
• Careful blunt dissection in the fat to expose the vessels
• The proximal IMAX, descending palatine artery, and sphenopalatine artery branches are all identified

• Each vessel is carefully dissected out
• Haemostatic clips (silver/titanium) are applied to the proximal IMAX, descending palatine branch, and sphenopalatine branch
• Vessels are ideally clipped and divided
• Multiple clips applied to ensure complete control
• Bipolar diathermy may supplement clipping

• Sinus mucosa repositioned
• Gingivobuccal incision closed with absorbable sutures
• Nasal pack may be replaced

Success Rate

• Trans-antral ligation controls haemorrhage in ~89% of cases
• Comparable to embolization in both cost and efficacy

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Approach 2: ENDOSCOPIC TRANS-ANTRAL APPROACH (Modern Variation)

• A middle meatus antrostomy is performed as an instrument port
• A 4 mm endoscope is inserted through a small canine fossa antrostomy
• Posterior antral wall is removed endoscopically
• IMAX branches identified and clipped under endoscopic vision
• Useful when control of a damaged sphenopalatine artery is lost during ESPAL
• Less facial dissection than open sublabial approach

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Approach 3: ENDOSCOPIC SPHENOPALATINE ARTERY LIGATION (ESPAL) - Now the Procedure of Choice

• Under GA or LA
• Incision made approximately 8 mm anterior to and under cover of the posterior end of the middle turbinate
• Incision carried down to bone; mucosal flap elevated posteriorly
• Crista ethmoidalis (small crest of perpendicular plate of palatine bone, anterior to sphenopalatine foramen) - key landmark
• Sphenopalatine foramen lies just inferior to the horizontal attachment of the middle turbinate
• Fibro-neurovascular sleeve arising from the sphenopalatine foramen identified
• Haemostatic clips applied and vessel divided, or bipolar diathermy used
• Important: identify and control all branches (97% specimens have ≥2 branches medial to crista ethmoidalis)

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COMPLICATIONS OF IMAX LIGATION (TRANS-ANTRAL)

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WHY IMAX LIGATION MAY FAIL

1. Collateral circulation from contralateral side via anastomoses
2. Ethmoidal artery contribution - anterior and posterior ethmoidal arteries (from internal carotid via ophthalmic artery) supply the superior nasal cavity and are not addressed by IMAX ligation
3. Wrong identification of vessels (venous plexus mistaken for artery)
4. Incomplete clipping - only one branch clipped; others continue to bleed
5. In such cases, anterior/posterior ethmoidal artery ligation or external carotid artery ligation may be needed as adjuncts

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COMPARISON OF SURGICAL OPTIONS FOR INTRACTABLE EPISTAXIS

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HIERARCHICAL MANAGEMENT OF EPISTAXIS (SUMMARY)

STEP 1: First aid - compress Little's area, head-forward, cold compress
STEP 2: Anterior rhinoscopy + cauterization of bleeding point (silver nitrate / electrocautery)
STEP 3: Anterior nasal packing (ribbon gauze / BIPP / Merocel)
STEP 4: Posterior nasal packing (Foley balloon / Brighton balloon / post-nasal pack) 24-48 hrs
STEP 5: SURGICAL OPTIONS (if above fail):
   a. ESPAL (1st choice - endoscopic sphenopalatine artery ligation)
   b. Endoscopic / trans-antral IMAX ligation (if ESPAL fails)
   c. Ethmoidal artery ligation (adjuvant / ethmoidal bleed)
   d. Embolization (if available and packing has failed)
   e. External carotid artery ligation (extreme/non-specialist)

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HIGH-YIELD EXAM POINTS

1. IMAX = 2nd terminal branch of external carotid artery (larger of the two, the other being superficial temporal)
2. Surgical target is the 3rd (pterygopalatine) segment of IMAX
3. Classical approach: sublabial (Caldwell-Luc) → canine fossa antrostomy → posterior antral wall removed → pterygopalatine fossa entered → clips on IMAX branches
4. Three vessels clipped: proximal IMAX + descending palatine + sphenopalatine branch
5. Key landmark in ESPAL: crista ethmoidalis (identifies sphenopalatine foramen)
6. IMAX ligation does not control ethmoidal artery bleeding (these come from internal carotid / ophthalmic artery)
7. Prior IMAX ligation hampers later embolization (superselective catheterization of SPA becomes impossible)
8. Success rate of trans-antral IMAX ligation: ~89%
9. Most feared complication: blindness (rare, from ophthalmic artery territory involvement)
10. ESPAL has now largely replaced IMAX ligation as the procedure of choice for intractable posterior epistaxis

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