a mimicker of Wegener s Granulomatosis
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1 a mimicker of Wegener s Granulomatosis Combined Meeting October 2009
2 a story of 2 ladies Madam JA 56 year-old Madam RH 36 year-old
3 Madam JA 56 year-old Apr 2008 May Jun Jul Aug Sept Oct Nov 2008
4 Madam JA 56 year-old Skin vasculitis under dermatology followup since 2003 Referred to ophthalmology in April 2008 diagnosis: Right eye granulomatous panuveitis DDx - Sarcoidosis - Ocular TB
5 Madam JA 56 year-old Apr 2008 May Jun Treated empirically Jul Aug Sept Oct Nov 2008
6 Madam JA 56 year-old Treated with a course of steroids, trial of TB treatment, no improvement Further history - congested nose past 1/12 with reduced hearing
7 Madam JA 56 year-old Investigations: FBC, RP, LFT normal ESR 2 ANA ve, ANCA ve UFEME protein ve blood -ve CXR lung fields clear
8 Madam JA 56 year-old CT PNS Apr 2008 May Jun Treated empirically Jul Aug Sept Oct Nov 2008
9 CT paranasal sinuses 7th July 2008
10 CT paranasal sinuses 7th July 2008
11 Madam JA 56 year-old CT PNS Apr 2008 May Jun Treated empirically Diagnosis: WG Jul Aug Sept Oct Nov 2008
12 Madam JA 56 year-old Nasal biopsy done July 08 Report: Inconclusive
13 Madam JA 56 year-old Symptoms worsening, left eye involved as well Diagnosis: Wegener s Granulomatosis - sight-threatening involvement Started IV Cyclophosphamide (monthly cycle), initiated by ophthalmology
14 Madam JA 56 year-old CT PNS Apr 2008 May Jun Treated empirically Diagnosis: WG Jul Aug Condition improves Sept Oct Nov 2008
15 Madam JA 56 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
16 Madam JA 56 year-old CT PNS Apr 2008 May Jun Treated empirically Diagnosis: WG Jul Aug Condition improves Sept Oct Nov 2008
17 Madam JA 56 year-old In Sept, condition worsened started on mycophenolate mofetil 1g bd in (by opthalmology)
18 Madam JA 56 year-old CT PNS Apr 2008 May Jun Treated empirically Diagnosis: WG Jul Aug Condition improves Sept Oct Nov 2008
19 Madam JA 56 year-old pt reviewed again in October, ocular condition worsening, general condition worse with sensorineural deafness
20 Madam JA 56 year-old CT PNS Apr May Jun Treated empirically Diagnosis: WG Jul Aug Condition improves Sept Nov 2008 Oct CT PNS
21 CT orbit/brain/pns 30th Oct 08
22 Madam JA 56 year-old CT PNS Apr May Jun Treated empirically Diagnosis: WG Jul Aug Condition improves Nov 2008 Sept Oct CT PNS
23 Madam JA 56 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:???
24 a story of 2 ladies Madam JA 56 year-old Madam RH 36 year-old
25 Madam RH 36 year-old Referred for WG Sinusitis Molar pregnancy 10 years ago Jan 2009 Rash Feb Bell s palsy (Prednisolone) Mar Apr Muscle weakness May Jun 2009
26
27 Madam RH 36 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 signs no lymphadenopathy
28 Madam RH 36 year-old Investigations ANA, ANCA negative TFT normal ESR 36 FBC, RP, LFT, CK, LDH normal CXR - unremarkable skin biopsy - lymphocytic vasculitis MRI brain normal muscle biopsy - lipid storage myopathy
29 Madam RH 36 year-old CT paranasal sinuses: right maxillary sinusitis with mucosal thickening within the right nasal cavity NCS asymmetrical sensory motor axonal polyneuropathy of the lower limbs nasal endoscopy friable mass
30 Madam RH 36 year-old Diagnosis: possible systemic vasculitis ie Wegener s granulomatosis - sinusitis - skin rash - resolved Bell s palsy (?mononeuritis multiplex) - sensory and motor polyneuropathy
31 Madam RH 36 year-old Differential diagnosis: lymphoma paraneoplastic syndrome amyloidosis TB
32 Madam RH 36 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
33 Madam RH 36 year-old Further investigations skin biopsy Subcutaneous panniculitis like T- cell lymphoma TB work-up negative nasal biopsy no malignancy seen
34 Madam RH 36 year-old Sinusitis Molar pregnancy 10 years ago Jan 2009 Rash Feb Jun 2009 Mar Apr Muscle weakness May
35 Final Diagnosis Final Diagnosis Madam JA 56 year-old Madam RH 36 year-old Final biopsy: Diffuse NK/T-cell lymphoma, nasal type Repeat nasal biopsy: Atypical lymphoid infiltrate highly suggestive of NK/T-cell lymphoma
36 Vasculitis mimics
37 Other vasculitis mimics Cocaine induced vasculitis (midline destructive lesion; CIMDL)
38 Other vasculitis mimics NK/T-cell lymphoma
39 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
40 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
41 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
42 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
43
44 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%
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
46 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): Typical WG with isolated sinonasal tract involvement with clinical and radiological findings with the final diagnosis of NK/T-cell lymphoma by repeated biopsies.
47 Nasal NK/Tcell lymphoma mimicking Wegener s Granulomatosis 2. Natural killer cell nasal lymphoma mimicking localized Wegener s disease [article in French] Rev Med Interne 2001 June; 22 (6): 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
48 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): 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.
49 Nasal NK/Tcell lymphoma mimicking Wegener s Granulomatosis 4. 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) 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.
50 How to unmask the mimic?
51 How to unmask the mimic? Diagnostic criteria Serology ANCA Definitive biopsy
52 How to unmask the mimic? 1. Diagnostic criteria ACR criteria Nasal or oral inflammation Abnormal CXR Abnormal urinary sediment Granulomatous inflammation on biopsy 2 criteria sensitivity 88% specificity 92%
53 How to unmask the mimic? Approximate sensitivity and specificity of antineutrophil cytoplasmic antibody in detecting primary vasculitides Sensitivity (%) Specificity (%) canca PR PR-3 + ANCA panca MPO MPO + ANCA WG MPA WG or MPA PR-3 + canca or MPO + panca Hagen et al Kidney Int ;
54 How to unmask the mimic? 2. Serology Small subset of patients with generalized WG who do not have ANCA Limited forms 40% ANCA ve Negative ANCA no disease
55 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
56 How to unmask the mimic? have a high index of suspicion
57 a story of 2 ladies..ending.. Madam JA 56 year-old Madam RH 36 year-old Developed sepsis; marrow infiltration Transferred to Ampang Hospital for treatment but died soon after transfer Died at home
58
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