a mimicker of wegener’s granulomatosis combined meeting ... · ddx - sarcoidosis - ocular tb....
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a mimicker of Wegener’s Granulomatosis
Combined Meeting October 2009
a story of 2 ladies
Madam Madam JAJA
Madam Madam RHRH
56 year-old56 year-old
36 year-old36 year-old
Madam JA56 year-old
May Jun Jul Aug Sept Oct Nov 2008
Apr2008
Madam JA56 year-old
Skin vasculitis under dermatology follow-up since 2003
Referred to ophthalmology in April 2008 - diagnosis: Right eye granulomatous panuveitis
DDx - Sarcoidosis - Ocular TB
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
Nov 2008
Apr2008
Madam JA56 year-old
Treated with a course of steroids, trial of TB treatment, no improvement
Further history - congested nose past 1/12 with reduced hearing
Madam JA56 year-old
Investigations:FBC, RP, LFT normalESR 2ANA –ve, ANCA –veUFEME protein –ve blood -veCXR lung fields clear
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
CTPNS
Nov 2008
Apr2008
CT paranasal sinuses 7th July 2008
CT paranasal sinuses 7th July 2008
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
CTPNS
Diagnosis:WG
Nov 2008
Apr2008
Madam JA56 year-old
Nasal biopsy done July 08Report:Inconclusive
Madam JA56 year-old
Symptoms worsening, left eye involved as well
Diagnosis: Wegener’s Granulomatosis - sight-threatening involvement Started IV Cyclophosphamide (monthly cycle), initiated by ophthalmology
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
CTPNS
Diagnosis:WG
Conditionimproves
Nov 2008
Apr2008
Madam JA56 year-old
Repeated biopsy taken Aug 08 - negative for granuloma/ malignancy/ vasculitis
In Aug 08, patient appeared to improve repeat CT paranasal sinus: pansinusitis
steroids tapered down
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
CTPNS
Diagnosis:WG
Conditionimproves
Nov 2008
Apr2008
Madam JA56 year-old
In Sept, condition worsened started on mycophenolate mofetil 1g bd
in (by opthalmology)
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
CTPNS
Diagnosis:WG
Conditionimproves
Apr2008
Nov 2008
Madam JA56 year-old
pt reviewed again in October, ocular condition worsening, general condition worse with sensorineural deafness
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Treatedempirically
CTPNS
Diagnosis:WG
Conditionimproves
CT PNS
Apr Nov 2008
CT orbit/brain/PNS 30th Oct 08
Madam JA56 year-old
May Jun Jul Aug Sept Oct
Nov 2008
Treatedempirically
CTPNS
Diagnosis:WG
Conditionimproves
CT PNS
Apr
Madam JA56 year-old
Diagnosis of WG in question IV Cyclophosphamide and mycophenolate
mofetil subsequently with-held (completed 4 cycles of IV
Cyclophosphamide) Repeated biopsy taken Nov 08 Diagnosis: ???
a story of 2 ladies
Madam Madam JAJA
Madam Madam RHRH
56 year-old56 year-old
36 year-old36 year-old
Madam RH36 year-old
Feb Mar Apr MayJan2009
Jun 2009
Referred for WG
Muscleweakness
Rash
Sinusitis
10 years ago
Molarpregnancy
Bell’s palsy(Prednisolone)
Madam RH36 year-old
CNS - normal upper limbs - power 2-4/5 over both lower limbs with hypotonia and patchy sensory impairment - normal cranial nerves
- no cerebellar signsno lymphadenopathy
Madam RH36 year-old
InvestigationsANA, ANCA negativeTFT normal ESR 36FBC, RP, LFT, CK, LDH normalCXR - unremarkableskin biopsy - lymphocytic vasculitisMRI brain – normal muscle biopsy - lipid storage myopathy
Madam RH36 year-old
CT paranasal sinuses: right maxillary sinusitis with mucosal
thickening within the right nasal cavityNCS asymmetrical sensory motor axonal
polyneuropathy of the lower limbsnasal endoscopy friable mass
Madam RH36 year-old
Diagnosis: possible systemic vasculitis ie Wegener’s
granulomatosis - sinusitis - skin rash - resolved Bell’s palsy (?mononeuritis
multiplex) - sensory and motor polyneuropathy
Madam RH36 year-old
Differential diagnosis: lymphoma paraneoplastic syndrome amyloidosis TB
Madam RH36 year-old
Based on preliminary diagnosis, patient was started on IV Hydrocortisone, then changed to oral prednisolone
not much improvement Developed CN VII LMN palsy
Madam RH36 year-old
Further investigations skin biopsy Subcutaneous panniculitis like T- cell
lymphoma TB work-up negative nasal biopsy no malignancy seen
Madam RH36 year-old
Feb Mar Apr MayJan2009
10 years ago
Rash
Sinusitis
Muscleweakness
Molarpregnancy Jun 2009
Final Diagnosis
Madam Madam JAJA
Madam Madam RHRH
56 year-old56 year-old
36 year-old36 year-old
Final biopsy: Diffuse NK/T-cell lymphoma, nasal type
Repeat nasal biopsy:Atypical lymphoid infiltrate highly suggestive of NK/T-cell lymphoma
Final Diagnosis
Vasculitis mimics
Other vasculitis mimics Cocaine induced vasculitis (midline destructive lesion; CIMDL)
Other vasculitis mimicsNK/T-cell lymphoma
Midline granuloma syndrome (MGS) Clinical description of a broad spectrum of
disease Aggressive and progressive destruction of
mucosa and adjacent structures of the midface and upper aerodigestive tract
DDx - WG - malignant lymphoma
- idiopathic midline destructive disease
NK/T-cell lymphoma Extranodal natural killer/T-cell lymphoma,
nasal-type OR nasal NK/T-cell lymphoma Most common cause of the ‘lethal midline
granuloma’ Older names: angiocentric lymphoma,
malignant granuloma, malignant midline reticulosis, polymorphic reticulosis
NK/T-cell lymphoma Natural killer cell – cytolytic cell, part of
bodies’ immune surveillance >95% EBV positive More common in Asia and South America,
very rare in whites Median age – 43 years Male:female 2:1
NK/T-cell lymphoma Patients have localised disease with nasal
obstruction Destructive mass involving nose,sinuses
and palate HPE: vascular invasion with necrosis,
demonstration of NK/T-cell markers and EBV
NK/T-cell lymphoma Treatment
Radiotherapy + CHOP regime
Aggressive cancer Overall worse prognosis in Asian studies Poor response to treatment, high relapse
rate 2 year survival rate 45%
Wegener’s Granulomatosis of the head and neck
Presents with ulceration of nasal septum, sinus mucosa, oral mucosa, external ear canal, destruction of vocal cord
Non-neoplastic necrotising lesion Less likely to be ANCA +ve
Nasal NK/Tcell lymphoma mimicking Wegener’s Granulomatosis
4 case reports:1. Sinonasal NK/T-cell lymphoma mimicking
Wegener’s granulomatosis: a case report [article in Turkish] Tuberk Toraks 2006; 54(3): 277-80
Typical WG with isolated sinonasal tract involvement with clinical and radiological findings with the final diagnosis of NK/T-cell lymphoma by repeated biopsies.
Nasal NK/Tcell lymphoma mimicking Wegener’s Granulomatosis2. Natural killer cell nasal lymphoma
mimicking localized Wegener’s disease [article in French]Rev Med Interne 2001 June; 22 (6): 571-5
38 year old man presented with a chronic maxillary sinusitis. Treated for WG. However responded poorly to treatment. Biopsy finally showed NK cell nasal lymphoma. Patient died of septic shock with multivisceral failure
Nasal NK/Tcell lymphoma mimicking Wegener’s Granulomatosis
3. Angiocentric T/NK cell lymphoma: a special clinico-pathological entity of lethal midline granuloma. A case report
[article in German] Laryngorhinootologie 2001 Jul;80(7):410-535 year old male presented with chronic recurrent sinusitis. Patient was treated for WG for 2 years. After the 3rd surgery, diagnosis of angiocentric lymphoma made. Patient died from multi-organ failure.
Nasal NK/Tcell lymphoma mimicking Wegener’s Granulomatosis4. A case of nasal T cell lymphoma with lethal
midline granuloma which is clinically indistinguishable from Wegener’s granulomatosis
Modern Rheumatology Sept 1997; 7 (3) 183-188 Patient presented with fever, bilateral otitis media, destructive
necrosis of the nasal cavity and multiple lung nodules. The patient fulfilled the ACR classification criteria for Wegener’s granulomatosis and was also diagnosed as having WG. However, the diagnosis of T cell lymphoma was finally made by cervical lymph node biopsy, 2 years after disease onset. Rheumatologists should therefore be aware of the pitfall of using diagnostic criteria and repetitive biopsy is strongly recommended for accurate diagnosis of WG.
How to unmaskthe mimic?
How to unmask the mimic?1. Diagnostic criteria2. Serology – ANCA3. Definitive – biopsy
1. Diagnostic criteriaACR criteria Nasal or oral inflammation Abnormal CXR Abnormal urinary sediment Granulomatous inflammation on biopsy
≥2 criteria ⇒ sensitivity 88% specificity 92%
How to unmask the mimic?
Approximate sensitivity and specificity of antineutrophil cytoplasmic antibody in detecting primary vasculitides
Sensitivity (%) Specificity (%)
WG
cANCA 64 95
PR-3 66 87
PR-3 + ANCA 55 99
MPA
pANCA 58 81
MPO 58 91
MPO + ANCA 49 99
WG or MPA
PR-3 + cANCA or MPO + pANCA 67–73 99
How to unmask the mimic?
Hagen et al Kidney Int 1998 53; 743-753
2. Serology Small subset of patients with generalized
WG who do not have ANCA Limited forms – 40% ANCA –ve Negative ANCA ≠ no disease
How to unmask the mimic?
How to unmask the mimic?3. Biopsy Nasopharnyngeal biopsy noninvasive but
findings may not be conclusive Repeated biopsies may be needed; from
multiple sites Communicate suspicion of lymphoma
How to unmask the mimic?
have a high index of suspicion
a story of 2 ladies..ending..
Madam JAMadam JA
Madam RHMadam RH
56 year-old56 year-old
36 year-old36 year-old
Developed sepsis; marrow infiltrationTransferred to Ampang Hospital for treatment but died soon after transfer
Died at home