1. Chronic granulomatous diseases of nose and paranasal sinuses
DR. Kamlesh Dubey

2. definition
term "granuloma" is derived from the Latin "granulum", referring to a small particle such as a grain
a focal area of chronic inflammation produced by circulating monocytes as part of an immunologic process

3. Pathophysiology
Neutrophils usually remove agents that incite acute inflammatory responses by phagocytosis and digestion
if an agent is indigestible, yet provokes an acute response- vicious cycle 
deplete the body’s white count
cause severe damage to local normal tissues
body deals with such indigestible substances and prolonged inflammatory reactions by forming granulomas
principal cells involved in granulomatous inflammation are macrophages and lymphocytes
Upon phagocytosis of an indigestible substance, macrophages:
 lose their motility and accumulate at the site of injury
undergo a structural change to become epithelioid cells
Nodular collections of these epithelioid cells form the heart of the granuloma
multinucleated giant cells, formed by the fusion of up to fifty macrophages
"Langhans Giant cell“-nuclei arranged in a horseshoe pattern
foreign body giant cell-fungal spore or silica particle, is found within the giant cell

5. Classification Immunologic : autoimmune diseases
Wegener’s granulomatosis
Relapsing polychondritis
SLE
Churg-Strauss syndrome(allergic granulomatosis & vasculitis)
Crohns disease

6. Classification Unknown etiology: Sarcoidosis
Idiopathic midline disease
Neoplastic granulomatous diseases:
Langerhans cell histiocytosis
Hand-Schuller-Christian disease
Eosinophilic granuloma
Fibrous histiocytoma
Pyogenic granuloma
Giant cell granuloma
Cholesterol granuloma

7. Classification Infectious : Bacterial: Tuberculosis Leprosy
Rhinoscleroma
Syphilis
Actinomycosis

8. Fungal :
Aspergillus
Histoplasmosis
Blastomycosis
Zygomycosis
Dermatocietes
Sporotrichiasis
Coccididomycosis

9. Protozoa :
Leishmaniasis
Miscellaneous:
Rhinosporidiosis

10. Tuberculosis
 least liable to invasion by acute tuberculosis of any part of the respiratory tract:
structure of mucosa
 respiratory movements of the cilia
bactericidal secretions
Route of spread:
Direct :
 air current by people sneezing or coughing 
 direct inoculation by finger borne infections and by instrumentation
Indirectly (secondarily):
 through the blood and lymph vessels
M. tuberculosis

11. Tuberculosis Types : Nodular : lupus vulgaris Begins in vestibule
Direct inoculation
Strong immunity
Pain unusual
Ulcer: pale granular base , undermined edges
Progressive scarring & deformity
Ulcerative

12. tuberculosis Paranasalsinus TB:
Tuberculosis of paranasal sinuses: S. Sanehi Chandrashekhar Dravid Neena Chaudhary V. P. Venkatachalam: Indian J. Otolaryngol. Head Neck Surg(January-March 2008) 60:85–87:
much rarer
Maxillary and ethmoid sinus most susceptible
disease is nearly always secondary to pulmonary or
extra pulmonary tuberculosis
Pathologically, three types can be recognized:
confined to the mucosa only
bony involvement and fistula formation
hyperplastic type

13. Tuberculosis Site : Nasal vestibule
 anterior portions of the inferior turbinate, nasal septum
Involvement of posterior nares is rare
nasal floor is almost always spared
Direct extension of infection from nose to sinuses
Clinical presentation:
nasal tuberculosis may not manifest themselves until the disease is well on its way
Earliest: Bloody nasal discharge, possibly the only, presenting symptom
Others: Pain, nasal obstruction and dryness in the nose or throat
eye symptoms : involvement of NLD
Headache: sinus involvement
 rapidly growing ulcer or tumour mass in the quadrangular cartilage of the nasal septum
Septal perforation

14. Tuberculosis Workup : DDx:
midline granulomas (i.e. wegners granulomatosis, leprosy, sarcoidosis, subcutaneous phycomycosis, granulomatous syphilis etc.)
Carcinoma
rhinoscleroma, rhino- sporidium seeberi, rhinitis sicca, suppurative sinus disease and foreign bodies
History
Clinical examination: nasal endoscopy
Hemogram, ESR, CXR PA view, Monteux skin test
AFB staining , Culture
Serological : TB PCR
Radiological: CECT PNS
Biopsy: usually required to establish the diagnosis

15. Nasal secretions and swab specimens have a very low yield and should not be used to rule out nasal TB: Goguen LA, Karmody CS. Nasal tuberculosis. Otolaryngol Head Neck Surg 1995;113:131–5
Biopsy :

16. LABORATORY TESTS FOR EXTRA-PULMONARY TB
Sensitivity (%)
Specificity(%)
Timescale
Diffs atyp myco?
Comments
Skin test 79 76
72h
72 h
PPD
Microscopy
>98
41–65
1–2 h No
ZN stain most common
Culture
46–63 98
∼21 d
Yes
Faster results with liquid-based media
NAAT(nucleic acid amplification test) 78 96
<24 h
High unit cost
Interferon γ 85 95
16–24 h
Requires whole blood sample

17. Tuberculosis Treatment : adequate anti-tuberculosis therapy
excisional surgery:  if obstruction is significant
 reconstruction plastic surgery for perforation of nasal septum and cosmetic purpose

18. Leprosy Obligate intracellular Gram positive and acid fast bacilli
Short, thick, pink stained rods
Size: 5 X 0.5 
Arrangement: Single or in cigar-shaped bundles or in “globi”
Affinity for Schwan cells & cells of R-E system
Cannot grow in vitro but can grow in
mice and
nine banded armadillos

19. Reservoir of infection
Main reservoir: Human being
Lepromatous case> Non lepromatous cases
Animal reservoirs
9-banded armadillos
Chimpanzees
Mangabey monkeys

20. Ulcerated or broken skin of bacteriologically positive cases
Portal of entry:
Major portal of exit: Nose
LL cases harbour millions of M. leprae in their nasal mucosa
Ulcerated or broken skin of bacteriologically positive cases
Mode of transmission:
Transmission by inhalation
Droplet infection
Transmission by contact
Skin to skin contact with infectious cases
Skin contact with soil & fomites

22. WHO classification

23. Clinical features: depend on type of leprosy
Tuberculoid:
No mucosal involvement
Skin of nasal vestibule can be involved
Borderline : no mucosal involvement
Lepromatous :
Nasal mucosal involvement occurs early
Nasal obstruction
Crust formation
Blood stained discharge
hyposmia
Late disease: atrophic rhinitis, septal perforation, dorsal saddling

24. diagnosis
Early diagnosis essential : nasal discharge principle route of transmission
Diagnosis :
Clinical findings
Skin anesthesia
Thickened peripheral nerves, skin lesions
Bacteriological examination:
Microscopy : nasal discharge, scrappings of nasal mucosa
Histopathology of nasal mucosa
Skin biopsy in TT, IL

25. Treatment Anti leprosy therapy WHO treatment regimen:
Tuberculoid : x 6 months
Dapsone 100mg x od –unsupervised, 1-2mg/kg in children not more than 100mg/day
Rifampicin 600mg x monthly – supeprviced
Lepromatous : 1-2 years
Dapsone 100mg x od – unsuperviced
Clofazimin 50mg x od – unsuperviced
Clofazimin 300mg x od – superviced
Rifampicin 600mg x monthly – superviced
Direct intranasal rifampicin reduce bacterial load much faster than oral

26. Rhinoscleroma
chronic granulomatous condition of the nose and other structures of the upper respiratory tract
caused by Klebsiella rhinoscleromatis—subspecies of Klebsiella pneumoniae— a gram- negative, encapsulated, nonmotile, rod-shaped bacillus (diplobacillus)
Historical facts:
Hans von Hebra (1847–1902) wrote classical description of disease in a paper published January 1870 
Polish surgeon Johann von Mikulicz in Wroclaw described histologic features in 1877
von Frisch identified the organism in 1882
In 1932, Belinov proposed the use of the term scleroma respiratorium
1961, Steffen and Smith demonstrated that K rhinoscleromatis conformed to Koch's postulates

27. Syphilis Congenital : Early Late Acquired : Primary (chancre)
Secondary
Tertiary (gumma)

28. Clinical features Early congenital : Purulent nasal discharge
Fissuring & excoriation of nasal vestibule
Late congenital:
Gummatous lesion destroy nose structure
Corneal opacity
Deafness
Hutchinson’s teeth

29. Complications Vestibular stenosis Perforation nasal septum
Secondary atrophic rhinitis
Saddle nose deformity

30. Investigations Specific treponemal tests:
Treponemal enzyme immunoassay (EIA) 
Fluorescent treponemal antibody absorbed test (FTA-abs)
Cardiolipin or non-treponemal tests:
VDRL
Demonstration of T. pallidum:
Dark field microscopy.
Direct fluorescent antibody (DFA) test.
Polymerase chain reaction (PCR).

31. Management Primary, secondary, early latent syphilis:
benzathine penicillin 2.4 mega units (intramuscular (IM), single dose)
oral azithromycin single dose
 procaine penicillin 600,000 units (IM, once daily for 10 days) 
doxycycline 100 mg twice daily for 14 days
Late latent syphilis:
benzathine penicillin weekly for three weeks is first-line

32. Clinical stages 1. catarrhal :
Foul smelling, purulent nasal discharge(carpenter glue), no response to conventional antibiotics
2. atrophic :
Foul smelling, honey comb colored crusting in stenosed nasal cavity(in contrast to roomy nasal cavity in atrophic rhinitis
3. nodular :
Non ulcerative painless nodules (soft bluish red →pale, hard) → widen lower nose(hebra nose)
4. cicatrizing:
Coarse & distorted external nose (Tapir nose)
Lower external nose & upper lip → wooden feel

33. Epidemiology :
Slightly more females than males are affected 
Age : usually 10 to 30 years of age
 Africa (Egypt, tropical areas), Southeast Asia, Mexico, Central and South America, and Central and Eastern Europe
Five percent of all cases occur in Africa
Risk factors: crowded conditions, poor hygiene, and poor nutrition 
Mortality/Morbidity:  rarely lethal, unless it causes airway obstruction

34. Diagnosis Culture : in MacConkey agar is diagnostic
culture results are positive in only 50-60% of patients
Staining :  periodic acid-Schiff, Giemsa, Gram, and silver stains
Immunoperoxidase technique: of a biopsy specimen
HPE:
Mikulicz (foam cells):
Histiocytes with foam vacuolated cytoplasm + central nucleus & containing frisch bacilli
Warthin-Starry stain
Russel (hyaline) body:
Degenerated plasma with large round eosinophil material

35. Treatment Medical treatment: Total duration: 6 weeks-6 months
Negative culture from two consecutive biopsy materials
Streptomycin 1gm x OD I.M + Tetracycline 500mg x QID
Rifampicin 450mg x OD
2% Acroflavin solution apply locally x OD
RT: 35 Gy over 3 weeks + antibiotics → to halt progress of resistant cases
Sx :
removal of granulation & nodular lesion
Dilatation of airway combined with insertion of airway tube for 6-8 weeks
Plastic reconstruction surgery after three negative cultures from biopsy

36. Rhinosporodiosis
 chronic granulomatous infection of the mucous membranes 
 described by Seeber in 1900 in an individual from Argentina
 reported from about 70 countries with diverse geographical features
highest incidence has been from India and Sri Lanka
India : Kerala, Karnataka, Tamil Nadu

37. activated macrophage :
increase in the functional activity of the macrophage
a new functional activity has appeared
increase their nuclear euchromatin content
develop prominent nucleoli
extensive cytoplasm
free ribosomes
abundant Golgi apparatus
large lysosomes

38. Etiology
Rhinosporidiosis is an infective disease in the sense that the tissue lesions are always associated with the presence of the pathogen
Rhinosporidium seeberi, has never been successfully propagated in vitro
Initially thought to be a parasite, for more than 50 years
Bizarre fungus: obsolete theory
Alhuwalia KB, Maheshwari N, Deka RC. Rhinosporidiosis: a study that resolves etiologic controversies. Am J Rhinol. 1997;11:479-83:
R. seeberi is a prokaryote cyanobacterium within the genus Microcystis
Herr RA, Tarcha EJ, Taborda PR, Taylor JW, Ajello L, Mendoza L. Phylogenetic analysis of Rhinosporidium seeberi's 18S small-sub unit ribosomal DNA groups this pathogen among members of the protistan Mesomycetozoa clade. J Clin Microbiol. 1999;37: :
R. seeberi is a eukaryote microbe within the Mesomycetozoa

39. The taxonomy and phylogenetics of the human and animal pathogenRhinosporidium seeberi: A critical review(Vilela, Raquel; Mendoza, Leonel  Rev Iberoam Micol. 2012;29:185-99:
is a mesomycetozoa microbe based on DNA and phylogenetic analysis

40. Epidemiology Age : 15-40 years Sex : M/F 4:1 Curious feature:
while several hundreds of persons bathe in the stagnant waters, as in Sri Lanka, only a few develop progressive disease
existence of predisposing factors:
only patient factor on which there is some data is blood groups
In India the highest incidence of rhinosporidiosis was in Group O (70%) 
Jain S. Aetiology and Incidence of Rhinosporidiosis. Indian Journal of Otorhinology, :
 reported that the blood group distribution was too variable to draw any conclusion
In a small series of 18 Sri Lankan patients, the distribution was different; Groups A Rh+ and O Rh+ having 33% each, Group B Rh+ with 22%, and Group AB Rh+ with the lowest of 11%

41. Mode infection:
through the traumatised epithelium ('transepithelial infection')most commonly in nasal sites:Karunaratne WAE. The pathology of rhinosporidiosis. J Path Bact
occurrence of rhinosporidiosis in river-sand workers, in India and in Sri Lanka, is particularly relevant to such a mode of infection
Mode of spread:
'Auto-inoculation‘(Karunaratne WAE. Rhinosporidiosis in Man: (The Athlone Press, London) 1964):
explanation for the occurrence of satellite lesions adjacent to granulomas especially in the upper respiratory sites and for local spread

42. Haematogenous spread:
evidence for haematogenous spread of rhinosporidiosis to anatomically distant sites i.e development of subcutaneous granulomata in the limbs, without breach of the overlying skin
Lymphatic spread :
 is controversial
 first report on the occurrence of inguinal lymphadenitis in a case of disseminated rhinosporidiosis which involved the lower limbs was made in 2002
 rarity might be related to the diverse mechanisms of immune evasion by R.seeberi

43. Clinical features
 polyps are pink to deep red, are sessile or pedunculated, and are often described as strawberrylike in appearance.
anterior nares, the nasal cavity - the inferior turbinates, septum and floor
Posteriorly, rhinosporidial polyps occur in the nasopharynx, larynx, and soft palate
 buccal cavity is only rarely affected
Suggestion : that the primary site of rhinosporidiosis is the lacrimal sac with downward spread to the nasal passages through the naso-lacrimal duct(disputed)
H/o: epistaxis, viscid nasal discharge, nasal block

44. Features of nasal rhinosporidiosis
Chronicity
Recurrence
Dissemination
Chronicity :
 immune suppression
 Immune Deviation 

45. Pathology Appearance :
polypoidal, granular, red in colour due to pronounced vascularity
with a surface containing yellowish pin head-sized spots(represent underlying mature sporangia)
 Naso-pharyngeal polyps are often multi-lobed

46. Diagnosis
definitive diagnosis: by histopathology on biopsied or resected tissues
with the identification of the pathogen in its diverse stages
Pitfalls in the histopathological diagnosis of rhinosporidiosis:
Microscopic examination of nasal discharge for spore
Serologic testing:
Immunoblot (dot – enzyme-linked immunosorbent assay [ELISA]) identification of antirhinosporidial antibody

47. Life cycle :
 release of the endoconidia
 increase in size (10–70(μm) 
 juvenile sporangia (JS)
JS increases in size 70–150(μm) IS
 early mature sporangia 
Mature sporangia

48. Treatment cases of spontaneous regression have been recorded
Total excision of the polyp, preferably by electro-cautery
 Pedunculated polyps permit of radical removal
excision of sessile polyps with broad bases : recurrence due to spillage of endospores
 dapsone (4,4-diaminodiphenyl sulphone):
arrest the maturation of the sporangia and to promote fibrosis in the stroma
100 mg/day x 1year
 No innovations in treatment since surgery and dapsone were introduced

49. Nasal leishmaniasis Presentation of cutaneous leishmaniasis (CL)
Infecting organism :
protozoan parasites belonging to the genus Leishmania
Vector :
 bite of a tiny – only 2–3 mm long – insect vector, thephlebotomine sandfly
500 known phlebotomine species: 30 only transmit infection
 Only the female sandfly transmits the parasites.
Over a period of between 4 and 25 days, parasites develop in the sandfly

50. Nasal leishmaniasis
 frequently been mentioned in the literature as a presentation of CL
 nasal affliction in CL: most exposed and unprotected part of the face
can have a variety of appearances:
psoriasiform plaques
furunculoid nodules
lupoid plaques
erysipeloid or mucocutaneous 
Rhinophymous(rhinophyma-like plaque)
Visceral and cutaneous leishmaniasis in patients with AIDS 

51. A proposed new clinical staging system for patients with mucosal leishmaniasis (Hélio A. Lessa et.al Trans R Soc Trop Med Hyg. 2012 June; 106(6): 376–381
Stage I: nodular lesion
Stage II: Fine granular lesions:
superficial ulcerations observed at the inferior conchae and the floor of the nasal fossa
Stage III:Deep ulceration 
more intense tissue reaction and clearly visible tissue granulation and mucosa infiltration
Stage IV: Septal perforation
visible tissue granulation and mucosa infiltration of the posterior nasal septum and inferior conchae
Stage V:
Destruction of nasal architecture and altered facial structure

52. Nasal clinical features
Symptoms
Signs
Rhynorrhea
Mucosal infiltration
Pruritus
Ulcer
Obstruction
Septum perforation
Epistaxis
Cartilagenous septum destruction

53. Diagnosis Montenegro skin test :
similar to the purified protein derivative (PPD)
 to determine delayed-type hypersensitivity reactions
made locally from killed promastigotes
Biopsy  :
from the raised edge of an active lesion
aline aspiration, tissue scrapings, or slit incisions
Direct visualization: hematoxylin and eosin staining, Giemsa staining
Culture tissue samples and aspirates: Nicolle-Novy-MacNeal (NNN) medium
inoculating tissue into the footpad and nose of hamsters
Serology : PCR, isoenzyme electrophoresis, or monoclonal antibody speciation

54. Treatment Medical : Injectable : Pentavalent antimony compounds:
Sodium stibogluconate
Meglumine antimmonate
Amphotericine B
Pentamidine
Oral :
Dapsone x 6 weeks, ketoconazole, fluconazole
Miltefosine : 2.5mg/kg x 4-6 weeks
Topical :
Parmomycin : ointment 15% parmomycin+12% methylbenzethonium chloride

55. Surgical therapy:
Leishmania : are temperature sensitive
Local treatment with cold/heat :
Cryotherapy : seconds freeze-thaw-refreeze cycle x 1-2 weeks
Thermosurgery : heats skin by radiofrequency waves (directed to specified area and depth)

56. Autoimmune disorder

57. Wegener’s granulomatosis
Definition :
A condition, characterized by granulomatous inflammation involving
Respiratory tract
Necrotizing vasculitis affecting small-medium sized vessels
Necrotizing vasculitis
Dr Friedrich Wegener, a German pathologist who first described the disease as rhinogenic granulomatosis in 1936:
Wegener, F.1939: A peculiar rhinogenic granulomatosis with particular involvement of the arterial system and the kidneys. Beitraege zur Pathologie 102:

58. Profile of Organ Involvement in Wegener Granulomatosis
Organ Site
Frequency at Presentation, %
Frequency During Disease Course, %
Upper airway 73 92
Lower airway 48 85
Kidney 20 80
Joint 32 67
Eye 15 52
Skin 13 46
Nerve 1

59. Variants Head and neck alone Head and neck and pulmonary
Head and neck, pulmonary, and renal
Cadoni G, Prelajade D, Campobasso E. Wegener's granulomatosis: a challenging disease for otorhinolaryngologists. Acta Otolaryngol. Oct 2005;125(10):
Cummings CW, Haughey BH, Thomas JR, et al. Otolaryngology - Head and Neck Surgery. 4th ed. St. Louis, MO: Mosby, Inc; 2005: ;

60. Etiology belongs to the heterogeneous group of systemic vasculitides.
multifactorial pathophysiology of WG supposedly caused by yet unknown environmental influence(s) on the basis of genetic predisposition
 Presence of ANCA in the plasma of ~90%→autoimmune
 ANCAs are mostly directed against proteinase 3 (PRTN3)
primary azurophil granules of polymorph nuclear neutrophils (PMN)
lysosomes of monocytes

61. Clinical features
nose and paranasal sinuses are involved in up to 80% of Wegener granulomatosis (WG) cases
Gubbels SP, Barkhuizen A, Hwang PH. Head and neck manifestations of Wegener's granulomatosis.Otolaryngol Clin North Am. Aug 2003;36(4): :
Chronic sinusitis affects 40-50% of patients 
mucosal edema with obstruction, rhinorrhea, ulcerations, crusting, and epistaxis
osteocartilaginous destruction  :
Saddle nose deformity
Septal perforation
Pain at the nasal dorsum, which suggests chondritis
Osteocartilaginous destruction does not correlate closely with active disease

62. Diagnosis c-ANCA +ve in 95%-generalized: 60%- localized disease
The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis(Leavitt RY. Et.al. Arthritis Rheum. 1990 Aug;33(8): )
presence of 2 or more of these 4 criteria was associated with a sensitivity of 88.2% and a specificity of 92.0%

63. Treatment
Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic review. Clin Exp Rheumatol. September-October 2008;26:S94-S104:
Untreated generalized or severe Wegener granulomatosis (WG) typically carries poor prognosis
with up to 90% of patients dying within 2 years, usually of respiratory or renal failure
Even non-renal WG carries a mortality rate of up to 40%.

64. Mukhtyar C, Guillevin L, Cid MC, et al
Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. March 2009;68: :
 European Vasculitis Study Group recommends grading disease :
Localized - Upper and/or lower respiratory tract disease without any other systemic involvement or constitutional symptoms
Early systemic - Any, without organ-threatening or life-threatening disease
Generalized - Renal or other organ-threatening disease, serum creatinine level less than 5.6 mg/dL
Severe - Renal or other vital-organ failure, serum creatinine level exceeding 5.6 mg/dL
Refractory - Progressive disease unresponsive to glucocorticoids and cyclophosphamide

65. Treatment Remission Induction: Cyclophosphamide
 daily oral route or intermittent intravenous route in combination with high-dose glucocorticoids.
daily oral dose of cyclophosphamide is 2mg/kg/day (not to exceed 200mg/day)
Pulsed (intravenous) cyclophosphamide (15mg/kg every 2 weeks for the first 3 pulses, then every 3 weeks for the next 3-6 pulses) 
continued until there is significant disease improvement or remission, typically 3-6 months
Prophylaxis against Pneumocystis (carinii) jiroveci pneumonia: TMP-SMZ at 160/800 mg 3 times weekly
Rituximab
375 mg/m2 weekly times 4
with high-dose glucocorticoids represents an alternative to cyclophosphamide for induction of remission

66. Plasma exchange
in patients with rapidly progressive renal disease (serum creatinine level >5.65mg/dL)
mechanism of action of plasma exchange in AAV includes removal of pathologic circulating factors (eg, ANCA, activated lymphocytes)
removal of excess physiologic factors (eg, complement, coagulation factors, cytokines/chemokines)
Adverse effects:
 electrolyte disturbances, anaphylaxis, hemorrhage, and transfusion-related lung injury
Methotrexate
Localized, milder disease
20-25 mg/wk, oral or subcutaneous + Daily folic acid 1 mg/day 

67. Remission Maintenance
continued for at least 18 months, often longer
Azathioprine:
2 mg/kg/day)
 higher relapse rates than cyclophosphamide
Methotrexate
Leflunomide
20-30 mg/day
may be used in patients with renal insufficiency
 associated with increased peripheral neuropathy symptoms

68. Alternative or Promising Therapies
Intravenous immunoglobulin
Etanercept
Infliximab
Mycophenolate mofetil
Alemtuzumab
Abatacept
Stem cell transplantation

69. sarcoidosis
Synonyms : boeck’s sarcoidosis, besner-boeck-schoumann syndrome
Definition :
A disease characterized by formation in all of several affected organs or tissues of epithelioid cell tubercules, without caseation though fibronoid necrosis may be present at centres of a few proceeding either to resolution or to conversion into hyaline fibrous tissue( Scalding & Mitchell 1985)
Similar histologic features seen in :
Berylliosis
Fungal diseases

70. Epidemiology Age : young adults , 3-5th decades Sex : F/M -2:1
Aetiology :
Unknown
Suspicion :
Various infective agents :
(?special form of TB)
Propionibacterium acnes: 70% active disease after bronchoalveolar lavage
disease has also been reported by transmission via organ transplants
Chemicals : beryllium, zirconium
Pine pollen, peanut dust
Possible : Vitamin D dysregulation, Hyperprolactinemia, Thyroid disease
Autoimmune

71. Clinical features
Wilson R. et.al. Upper respiratory tract involvement in sarcoidosis and its management. European Respiratory Journal. 1998;1:269-7
90% will have evidence of thoracic involvement : lung/ affecting lymphnodes

72. Clinical features Mucosal :
Yellow nodules surrounded by hyperaemic mucosa on anterior septum& turbinate
Skin : lupus pernio
Nasal tip: symmetrical bulbous, glistening violaceous lesion
Similar lesion on cheeks, lip, ear (turkey ear)
Diascopy : yellowish brown appearance
Probe test:
Probing of nodular lesion to look for penetration
Negative in sarcoidosis/positive in lupus vulgaris

73. Diagnosis No test pathognomic Most reliable: Kveim-Siltzbach test
Spleen extract from cases of sarcoid → intradermal injection
Followed 6 weeks later by skin biopsy→ non-caseating granulomas
Hemogram , ESR, ACE(↑83% active sarcoid)
Imaging :
CXR, CT , MRI
Perfusion studies
Bronchoalvelar lavage
Gallium-67 scanning
Biopsy : nasal mucosa (92% negativity on random biopsy)

74. Treatment Spontaneous remission Systemic therapy: Prednisolone :
1mg/kg x 6 weeks , taper over 3 months
Good response in mucosal disease only
Methotrexate :
5mg /weekly x 3 months
Chloroquine :
250mg /alternate day

75. Churg-Strauss syndrome
Churg & Strauss described in 1951
Syndrome of: systemic vasculitis , asthma
Eosinophil rich & granulomatous inflammation involving respiratory tract and necrotizing vasculitis + asthma +eosinophilia
Nasal clinical features:
Nasal polyps
Nasal crusting
Septal perforation
DD’s: Wegener's granulomatosis
Treatment : oral steroids

76. Giant cell granuloma first described by Jaffe in 1953
Benign granuloma like aggregates of giant cell in fibrovascular stroma
Giant cell reparative granuloma/giant cell reaction of bone
Age : children, young adults
Sex : F/M- 2:1
Imaging: soap bubble center and well demarcated edges
Not true giant cells tumor: do not contain multiple nuclei
B/L symmetrical involvement jaw-cherubism
DD’s: aneurysmal bone cyst, hyperparathyroidism
Treatment:
Curettage ( 15% recurrence)
Total excision (where possible)

77. Cholesterol granuloma
Definition :
Granulomatous reaction to cholesterol crystals precipitated in tissues (presumed to result from haemorrhage and/or trauma)
Age /Sex: years(mean-38) / male predominant
Clinical features:
Affect maxilla, frontal sinuses
Expansion of bone cosmetic deformity, displacement of adjacent structures
Imaging :CT/MRI
Cyst like expansion
Opaque , does not enhance on contrast
High signal on all MRI sequences

78. Choleterol granuloma Histology :
Typical appearance of granulation tissue with foreign body type giant cells
Treatment :
Surgical excision

79. Neoplastic granulomatous disease

80. Granulomatous neoplasia
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

81. Introduction T/NK cell lymphoma
Responsible for classical destruction of midface
Great controversy and pathological debate
MacBride P. A case of rapid destruction of nose ad face. Journal of Laryngology and Otology.1897;12:64-6: first description of disease
Death resulted from:
Intercurrent infection of disseminated lymphoma:
Failure of diagnosis
Insufficiently aggressive oncologic treatment
DD’s: substance abuse (Cocaine)

82. Epidemiology Age : 10-90years ( meadian 5th/6th decade)
Sex : male predominance
Location: south-east asia, south & central america
Etiology :
Suzuki R, Yamaguchi M, Izutsu K, et al. Prospective measurement of Epstein-Barr virus-DNA in plasma and peripheral blood mononuclear cells of extranodal NK/T- cell lymphoma, nasal type. Blood 2011; 118:6018.:
positivity for Epstein-Barr virus (EBV)
exact mechanism of malignant transformation via EBV has not been elucidated.
designated NK/T because of uncertainty regarding its cellular lineage
 Gene rearrangement studies support a natural killer cell origin in most cases
small minority has clonal T cell receptor gene rearrangements and appears to be derived from cytotoxic T cells

83. Clinical features
Polymorphic neoplastic infiltrate with angioinvasion and angiodestruction
Classical division in three stages:
Prodromal :
Last for many years
Persistent nasal obstruction, rhinnorhoea
Active stage:
Nasal crusting, ulceration, septal perforation
3. terminal stage:
Haemorrhage
Gross mutilation of face
DD’s: Wegener’s granulomatosis , BCC

84. Diagnosis Histopathology :
Good quality representative biopsy material( from beneath slough and crust
Immunohistochemistry : (against T-cell differentiation)
Granulomas and giant cells are not present
Thrombosis & necrosis
EBV serology
Imaging

85. Treatment RT: Radical radiotherapy: 55Gy or more CT
Disseminated/Recurrence
5 year survival : %
Relapse : within few months-20 years