a mimicker of wegener’s granulomatosis combined meeting ... · ddx - sarcoidosis - ocular tb....

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