Granulomatous lesions of nose

Granulomatous lesions of noseBALASUBRAMANIAN THIAGARAJAN

OTOLARYNGOLOGY ONLINE

IntroductionFeatures of granula of nose:

1. Presence of granuloma which contains – macrophages, epithelioid cells, and multinucleated giant cells

2. Presence of vasculitis which may be primary or secondary

3. Majority of these conditions have systemic manifestations


Classification of granulomatous lesions of nose1. Infective

2. Inflammatory

3. Neoplastic


Infective causes Bacterial

Tuberculosis – Mycobacterium tuberculosis

Leprosy – Mycobacterium Leprae

Rhinoscleorma – Klebsiella Rhinoscleromatis

Syphilis – Treponema Pallidum

Actinomycosis – Actinomyces israeli


Infective causes Fungal & protozoalAspergillus – Fumigatous, Flavus and Niger

Zygomycosis – Conidiobolus coronatus, Rhizopus oryae

Dermatacietes – Curvularia, Alternaria and Bipolaris

Rhinosporidiosis – Rhinosporidium seeberi

Blastomycosis – Blastomyces dermatitidis and Cryptococcus neoformans

Histoplasmosis – Histoplasma Capsulatum

Sporotrichosis – Sporotrichum schenkii

Coccidioidimycosis – Coccidioidi immitis

Leishmaniasis (protozoal) – Leishmania donovani


InflammatoryWegner’s granulomatosis

Sarcoidosis

Churg-strauss syndrome

Cholestrol granuloma

Eosinophilic granuloma


Neoplastic

T-cell lymphoma (Lethal midline granuloma)


SarcoidosisSystemic condition of unknown etiology

Can involve any part of the human body. Commonly involves nodes, lungs, upper airway, eyes, liver and small bones of hand and feet

Commonly affects young adults between third and fifth decades

Nasal manifestations are part of multisystem involvement

Female preponderance 2:1


EtiologyUnknown

Infective agents suspected

Exposure to Beryllium, zirconium, pine pollen and peanut dust have been implicated

Type 4 delayed hypersensitivity reactions depressed in these patients

Cell mediated immunity is normal

Gamma globulin levels are increased

The entire process seems to be initiated by antigen presenting cells of alveoli

Failure of suppressor regulatory mechanism is responsible for persistence of granuloma


Clinical Features - SarcoidosisNasal stuffiness / obstruction

Crusting

Blood stained nasal discharge

Purulent discharge

Facial pain

Mucoid discharge

Anosmia (rare)


Nasal findings - sarcoidosisGranular in appearance – “Strawberry skin”

Erythematous mucosa with tiny pale granulomas

Nasal mucosa is friable causing nasal congestion, bleeding

Mucosal crusting are also evident

Perforation of nasal septum (anterior portion). If septoplasty is ventured in these patients there could be associated collapse of the bridge of nose

Nasal bones may be involved causing expansion of the dorsum of the nose and thickening of skin in that area. (Responds well to medical management).


Histology - SarcoidosisNon caseating granuloma

Presence of epithelioid cell tubercles

Fibrinoid necrosis could be seen at the center which gets converted into hyaline fibrous tissue on healing

Schaumann bodies (crystalline/calcified inclusion bodies) are seen


Persistent granuloma - causes

Increased production of calcitriol by monocytes

Continued antigenic stimulation

Failure of suppressor mechanism

Abnormalities in the regulation of cytokine network


Other systems - sarcoidosisLung infiltrates

Peripheral node involvement

Skin involvement

Liver

Eye

Spleen

Heart

Kidneys

Larynx

Joints

Uterus

Lacrimal glands


Sarcoidosis – Diagnostic testsKveim test – Skin test Risk of virus / Prion transfer

Elevated angiotensin converting enzyme

X-ray chest – pulmonary infiltrates

Biopsy of nasal mucosa will help only if found abnormal

X-ray nasal bones – rarefaction / osteolysis if they are involved


Sarcoidosis - ManagementSpontaneous remission – probable

Oral steroids / methotrexate / hydroxycholoquine

Nasal steroid spray

Nasal saline douching to remove crusts

Surgery is contraindicated


Wegner’s granulomaGranulomatous inflammation of respiratory tract and kidneys

Necrotizing vasculitis involving small – medium sized vessels

Triad of airway, lung and renal disease common

Can occur in any age


Wegner’s granuloma - EtiologyUnknown

Inflammatory – hypersensitivity reaction with immune response to unknown stimuli (bacteria)

Deposition of immune complexes could cause vasculitis

cANCA elevated in Wagner's


Wegner’s granuloma-clinical featuresSymptoms disproportionate to clinical findings

Malaise, pyrexia and sense of ill well

This disease is lethal. Pts usually die within 6 months due to renal failure

Nasal block

Epistaxis

Nasal septal destruction, collapse of bridge of nose

Facial pain

Nasal surgeries cause destruction of nasal septum and nasal bridge collapse

Cough, hemoptysis and pleural pain

Glomerulonephritis – renal casts and RBC in urine (mid urine sampling)


Wegner’s granuloma – Ocular symptomsConjunctivitis

Dacryocystitis

Episcleritis

Corneal ulceration

Proptosis due to orbital granuloma

Blindness


Wegner’s granuloma – oral symptomsHyperplastic granular lesion involving gingiva of interdental area

Loosening of tooth

Cavities fail to heal

Extensive ulcerative stomatitis


Wegner’s granuloma – otologial symptomsAOM

Otitis media with effusion

Facial nerve paralysis

Middle ear filled with necrotizing granulation tissue

Conductive / sensorineural hearing loss


Wegner’s granuloma-Miscellaneous symptomsSkin ulceration over distal arms and legs

Polymyalgia / polyarthritis

Nervous system involvement


Wegner’s granuloma - DiagnosiscANCA test positive

ESR elevated

Elevated CRP level

Serum urea, creatinine and serum angiotensin converting enzyme levels to be assessed

Biopsy

CT imaging – nasal mucosal thickening. Pt with h/o previous nasal surgery showing bone destruction and new bone formation is virtually diagnostic


Wegner’s granuloma - histologyVasculitis is mandatory

Fibrinoid vascular necrosis is common

Presence of giant cell granuloma


Wegner’s granuloma - TreatmentSteroids

Cytotoxic drugs – cyclophosphamide, azathioprime, mycophenolate mofetil

Treatment to be initiated before renal damage sets in


Churg Strauss syndromeSystemic vasculitis, bronchial asthma

Eosinophilic rich granuloma

Small and medium sized vasculitis

Nasal polyposis, nasal crusting, septal perforation

Can be managed with oral steroids


Eosinophilic granuloma

Involves clonal proliferation of Langerhans cells associated with heterogenous inflammatory infiltrate of eosinophils, histiocytes, lymphocytes, plasma cells and neutrophils. This condition may also be considered as a manifestation of histiocytosis x.


Eosionophilic granuloma - featuresAll organs may be affected

Predominantly involves bones (temporal, frontal and parietal bones)

Males are commonly affected, twice as common as females

Commonly affects individuals in the first three decades of life

Painful swelling over involved bone followed by cervical adenopathy

Mandibular lesions tooth ache, gum ulceration and loosening of teeth

Involvement of temporal bone will simulate acute mastoiditis


Eosinophilic granuloma - imaging

Punched out bony lesions in the jaw with radiolucent areas around teeth

Skull lesions show beveled margins due to angular destruction of bone


Eosinophilic granuloma - ManagementLocalized disease can be managed by curettage and irradiation if need be.

Solitary disease is more common

Regimen of etoposide & steroids for 12 months has proved promising

Recent regimen also include alpha interferon and bone marrow transplantation


Cholesterol granulomaThis condition results from hemorrhage / trauma

Granulomatous reaction is directed against cholesterol crystals

Shows male preponderance, without any age preponderance

This lesion is known to affect frontal / maxillary sinus causing swelling and cosmetic deformity

Proptosis could also be evident

Lesion produces a cyst like expansion of the affected bone. The sinus cavity appears opaque and does not show contrast enhancement

Histology shows giant cell granuloma

Surgery and curettage of the lesion helps


Lethal midline granuloma

Also known as “T cell lymphoma” stewartgranuloma

Extensive destruction of mid face

Can involve patients of any age group

Male preponderance has been observed

EB virus infections have been implicated


Midline granuloma – clinical featuresProdromal stage – May last for many years. Nasal obstruction and rhinorrhea are the classic features

Period of activity – Necrosis develops around nasal cavity. Purulent discharge + crusting+ tissue loss+ There is progressive destruction of nasal framework, palate, upper lip, orbit and skull base. Pyrexia may be present due to super added infection

Terminal stage – Bleeding, gross disfigurement and ultimately death


Midline granuloma - DiagnosisIt is a challenge because atypical cells are dispersed in necrotic areas

Biopsy material should be taken from under the slough / crust

Immunohistochemistry is a clincher

Absence of granulomas / giant cells is a feature

There is always associated thrombosis and necrosis


Midline granuloma - ManagementInitially low dose radiotherapy was preferred

Now a days full course of radiotherapy is administered covering the entire area

Development of disseminated lymphoma is a problem

Chemotherapy is indicated only for high grade lesions


Nasal tuberculosisRare

Always associated with primary PT

Features include – ulcers, polypoidal lesions and nodules

Ulcers if present are typically seen in the anterior portion of nasal septum and inferior turbinate

Lupus vulgaris – is an indolent infection involving the skin and mucosal lining of nasal cavity

Nose picking commonly causes this condition


TB Nose – Clinical featuresNasal discharge / obstruction

Presence of non foul smelling crusts

Epistaxis

Presence of ulceration can cause mild fetor

Ulceration of nasal mucosa is followed by fibrosis, and contraction of nares

Extensive involvement of turbinates can lead to secondary atrophic rhinitis

Apple jelly nodules – Early lesion. Reddish brown nodule at the mucocutaneous junction

Cartilagenous portion of nasal septum undergoes destruction


Lupus - FeaturesCan cause extensive scarring of vestibule and may extend up to the skin of face. These lesions are nodular in nature.

Features of lupus nodules:

Blanching on pressure

Bacterial examination

Biopsy

When pressure is applied to adjoining nasal mucosa using glass slide, pinkish nodules will stand out because the adjacent areas undergo blanching

Biopsy of the lesion is always diagnostic


Nasal tuberculosis - Histopathology

Presence of tuberculous granuloma

In the center of the lesion collection of RE cells +

Giant cells are seen throughout the tubercle

Coagulation necrosis is a feature


Nasal tuberculosis - complicationsDacryocystitis

Lupus of the face

Atrophic rhinitis

Development of epithelioma - very rare


Nasal leprosyTuberculoid leprosy – skin lesions may extend up to nasal vestibule. Nasal mucosa is not involved. Cutaneous anesthesia is a feature.

Lepromatous leprosy – Highly infectious discharge from nasal cavity. Nasal crust formation, serosanguinous nasal discharge. Presence of nodular thickening of nasal mucosa is the earliest feature. These nodules are commonly seen in the anterior end of inferior turbinate. Nasal obstruction is classically out of proportion to mucosal oedema visualized. Collapse of the anterior bridge of the nose with destruction of anterior nasal spine is a feature. Both bony and cartilagenous portions of nasal septum are destroyed. Radiological evidence of destruction of anterior nasal spine is virtually diagnostic of lepromatous leprosy.

Borderline leprosy – poor immunological tolerance. Skin around nose and eyes are involved. Nasal mucosa is free of disease


Nasal syphilisPrimary syphilis - commonly seen in the vestibule of the nose. Usually appears as hard, non painful ulcerated papule. Always associated with enlarged rubbery non tender lymphadenopathy. Spontaneous resolution is seen in 6 weeks. Smears from the lesion are positive. VDRL +

Secondary syphilis – infective stage. Catarrhal rhinitis, crusting, fissuring of nasal vestibule, and enlarged non tender lymph nodes.

Tertiary syphilis – Bony portion of nasal septum involved. Septal perforation involving bony portion of nasal septum is seen


Nasal syphilis - symptomsPain & headache – worse during night

Swelling / obstruction of nose

Diminished olfaction

Perforation of bony nasal septum with collapse of bridge of nose

Secondary atrophic rhinitis

Lesion is usually unilateral

Tenderness over the bridge of the nose is a characteristic sign

Swollen nasal mucosa that does not shrink with decongestants


Congenital syphilisAlso known as snuffles

Usually begins classically during 3rd week of life

Begins as serous rhinitis, which later becomes purulent

Excoriation of upper lip and vestibule of nose


RhinoscleromaProgressive granulomatous lesion begins at the nose and extends up to nasopharynx

Larynx, trachea and lower airway can rarely be involved

Can occur at any age, and can affect all age groups

Causative organism – Klebsiella rhinoscleromatis

Granulomatous infiltrates in the submucosa is a feature. Accumulated inflammatory cells include: Plasma cells, lymphocytes, eosinophils and scattered large foam cells (Mikulicz cells). These foam cells have a central nucleus and a vacuolated cytoplasm containing bacillli


Rhinoscleroma – Clinical featuresAtrophic stage – Changes appear in the nasal mucous membrane. This stage clinically resembles atrophic rhinitis

Granulation / nodular stage – Nodules are non ulcerative in nature. These nodes are initially bluish red and rubbery. Later these nodes become a little paler and harder

Cicatrizising stage – Adhesions and scarring is a feature of this stage. Stenosis distort normal nasal anatomy. Shape of the nose changes and is classically name the Tapir’s nose. Lymphatic spread is uncommon because of extensive scarring. This disease may involve nasopharynx, maxillary sinus and lower airways too.


Rhinoscleroma - Investigations

Levin test – complement fixation test based on reaction of patient’s serum with suspensions of K. rhinoscleromatis

High titres of antibodies to K. rhinoscleromatis has been demonstrated in these individuals

Tissue biopsy is diagnostic


Rhinosporidiosis

It is a chronic granulomatous disease characterised by production of nasal polypiand other manifestations of hyperplastic nasal mucosa. Etiologic agent has been hypothesized to be Rhinosporidium seeberi. It has also been described as a strawberry like mulberry mass.


Rhinosporidiosis - History1892 – Malbran observed the organism in nasal polyp

1900 – Seeber described the organism

1903 – O’kineley described the histology of the lesion

1905 – Minchin & Fantham restudied O’Kineley’s slide and named the organism as Rhinosporidium Kineley

1913 – Zschokke reported a similar lesion in horses and named the organism Rhinosporidium equi

1923 – Ashworth described for the first time life cycle of rhinosporidium seeberi

1924 – Forsyth described a skin lesion for the first time

1953 – Demellow described mode of transmission of the disease


Rhinosporidiosis – Special characteristics

More than 90% of these patients have been reported from India and Srilanka

Madurai, Thirunelveli, Ramnad and Kanyakumari districts of Tamilnadu are considered to be endemic zones

Disease transmission is probably due to taking bath in common ponds where cattle also bathe


Rhinosporidiosis – Theories of spread

Demellow’s theory of direct transmission

Autoinoculation theory of Karunarathne (responsible for satellite lesions)

Hematogenous spread (spread to distant sites)

Lymphatic spread (rare)


Karunarathne’s theory

Rhinosporidium seeberi existed in dimorphic state.

It existed in saprophyte form in soil and water.

Inside tissues it took yeast form

According to karunarathne, this dimorphic existance helped organism to survive hostile environmental conditions


Rhinosporidiosis – Reasons for endemicity

Physical characteristics of water in the ponds

Presence of synergistic aquatic organism

Genetic predisposition of affected patients

Host immunity status


Life cycle (Ashworth)Spore is the basic infecting unit

It is about 7 microns in size

It is also known as spherule

It has clear cytoplasm filled with 15-20 vacuoles containing food matter

It is enclosed in a chitinous membrane

These spores are commonly found in connective tissue spaces and is very rarely intracellular


Life cycle Ashworth (contd)Spores begin to increase in size

At 50-60 microns size granules begin to appear

Nucleus prepare for cell division

Mitosis begins – 4,8,16, 32 and 64 nuclei are formed

At 7th division size becomes 100 microns

Fully mature sporangium – 150 microns

Mature spores are found in the centre and immature ones at the periphery


Life cycle - Recent

Juvenile sporangium also known as trophozoite – size ranging from 6-100 microns

It has a single nucleus at 7 micron stage and multiple nuclei at 100 microns stage

Lipid granules begin to appear within the cytoplasm

Intermediate sporangium – 100-150 microns. Has bilamellar cell wall, outer chitinous and inner cellulose. Only immature spores are seen within the cytoplasm. No mature spores are seen


Mature sporangiumSize – 100 – 400 microns

Cell wall is thin and bilamellar with one weak spot known as operculum

Inside cytoplasm mature and immature spores are seen

Spores are embedded in mucoid matrix

Mature spores are covered with mucoid material resembling a comet (comet of Beattee)

Mature spores give rise to electron dense granules which are the ultimate infecting unit


Clinical classification

Nasal

Nasopharyngeal

Mixed

Bizarre (ocular / genital)

Malignant rhinosporidiosis (cutaneous)


Common sites affected

Nose – 78%

Nasopharynx – 68%

Tonsil – 3%

Eye – 1%

Skin – very rare


Nasal rhinosporidiosis - FeaturesLesions are polypoidal reddish and granular

Lesions may be multiple, pedunculated and friable

Surface studded with whitish dots (sporangia)

Nasal lesions highly vascular and bleeds on touch

Entire mass could be clothed with mucous secretion

Lesion is restricted to nasal mucous membrane and does not cross the mucocutaneous junction


Rhinosporidiosis - HistologyPapillomatous hyperplasia of mucous membrane with rugae formation

Epithelium over sporangia thinned out and giant cells could be seen in this area

Accumulation of mucous + in crypts

Increased vascularity due to angiogenesis factor

Spores stain with sudan black and Bromphenolblue


Nasal rhinosporidiosis - Features

Chronicity

Recurrence

Dissemination


Chronicity - ReasonsAntigen sequestration

Antigenic variation

Immune suppression

Immune distraction

Immune deviation

Binding of host immunoglobulins


Treatment

Surgery

Dapsone 100 mg/day – 6 months


Granulomatous lesions of nose

Healthcare

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