1. Nasal Granulomas
Dr. Vishal Sharma

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

3. Classification of nasal granulomas

4. 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 ?

5. Rhinoscleroma or Respiratory Scleroma

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

7. 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)

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.

9. Rhinoscleroma nodules

10. Lesion in nose & palate

11. Hebra nose

12. Tapir Hebra

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 throat Larynx & tracheo-bronchial tree: Dry cough, hoarseness, respiratory distress

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.

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

16. Histopathology

17. Histopathology (magnified)

18. Warthin-Starry stain: Mikulicz cell

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

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

21. Tuberculosis

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

23. Acid Fast Bacillus

24. Histopathology

25. Histopathology magnified

26. 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

27. Lupus vulgaris

28. Apple jelly nodule

29. Syphilis

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

31. Primary syphilis chancre

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

33. Secondary syphilis rashes

34. Rash of secondary syphilis

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

36. Congenital syphilis: palatal rash & perforation

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

38. Tertiary syphilis gumma

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.

40. Sensitivity of serological tests
Primary (% +ve)
Secondary (% +ve)
Latent (% +ve)
Tertiary (% +ve)
VDRL
75 – 90
100
90 – 100
RPR 73
FTA-Abs
70 – 100 96
TPHA 94

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 Rhinoplasty for nasal deformity

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

43. Leprosy

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

45. Tuberculous Lepromatous

46. Saddle nose in leprosy

47. Erosion of anterior nasal spine

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

49. Rhinosporidiosis

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.

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

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

53. Classification Benign
a. Nasal %
b. Nasopharyngeal %
c. Mixed (naso-nasopharyngeal, nasolacrimal) -- 05%
d. Bizarre (Conjunctival / Tarsal / Cutaneous) --- rare
Malignant rare
Generalized, deep seated & difficult to eradicate

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

55. Nasal mass

56. Bleeding nasal mass

57. Nasal + Nasopharynx

58. Nasal + Nasopharynx

59. Oropharyngeal mass

60. Mass in uvula

61. Cutaneous granulomas

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

63. Life cycle

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.

66. Differential diagnosis
Infected antrochoanal polyp
Inverted papilloma
Other granulomas:
 Rhinoscleroma
 Tuberculosis
 Leprosy
 Fungal (aspergillosis, mucormycosis)
Malignancy of nose / paranasal sinus

67. Investigations Biopsy & Histo-pathological examination
Microscopic examination of nasal discharge for spores

68. Haematoxylin & Eosin stain

69. Periodic Acid Schiff stain

70. Gomori Methenamine Silver stain

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

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

73. Fungal granulomas

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 Fungal ball Saprophytic
Aspergillosis & Mucormycosis are common

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)

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

77. Black crusting

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

79. Surgical debridement

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)

81. Allergic fungal sinusitis

82. Allergic fungal sinusitis

83. C.T. scan coronal cuts

84. C.T. scan axial cuts

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

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

87. Aspergillosis Mucormycosis

88. Dichotomous branching
Aspergillosis hyphae
Mucormycosis hyphae
Narrow
Broad
Septate
Non-septate
Branching at 450
Branching at 900
Dichotomous branching
Singular branching

89. Immuno-fluorescent staining

90. Sarcoidosis

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 (?) Unidentified organism

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.

93. Lupus Pernio

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

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

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

97. Non-caseating granuloma

98. Non-caseating granuloma

99. Asteroid inclusion bodies

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

101. Hilar lymphadenopathy

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

103. Wegener’s granuloma

104. Definition
Autoimmune (?) condition characterized by necrotizing granulomas within nasal cavity & lower respiratory tract,
generalised vasculitis &
focal glomerulonephritis

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

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

107. Crusting in nasal cavity

108. External nasal deformity

109. Destruction of orbit & nose

110. 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

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

112. CT scan PNS: nasal destruction

113. CXR: nodular lesion with cavity

114. nodular lung infiltrate with cavitation
C.T. scan lungs
nodular lung infiltrate with cavitation

115. HPE: Granulomatous vasculitis
L = small pulmonary artery lumen surrounded by inflammatory infiltrate including a giant cell (black arrow)

116. Segmental glomerular necrosis
early crescent formation (black arrows)

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

118. C – ANCA by indirect immuno-fluorescence

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

120. Sinonasal lymphoma (not a granuloma)

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

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

123. Mid-face mutilation

124. 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

125. Atypical T lymphocytes
Investigation
Wegener’s Granuloma
Sinonasal Lymphoma
Vasculitis
present
absent
Granulomas
Giant cell
Atypical T lymphocytes
Angio-invasion
C-ANCA titre
raised
not raised

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

127. Thank You