Cristiane M. Ida, M.D.Cristiane M. Ida, M.D.Caterina Giannini, M.D. Ph.D.Caterina Giannini, M.D. Ph.D.

Julie E. Hammack, M.D. Julie E. Hammack, M.D. Jonathan M. Morris, M.D.Jonathan M. Morris, M.D.

52nd Annual Diagnostic Slide 52nd Annual Diagnostic Slide Session 2011Session 2011

Case 3Case 3

June 24, 2011June 24, 2011

CaseCase• 37 y/o man37 y/o man

• H/o H/o • Mild short-term memory loss x 1 yrMild short-term memory loss x 1 yr• Right neck mass (~ golf ball) and Right neck mass (~ golf ball) and

general malaise x 1 mogeneral malaise x 1 mo• Progressive gait ataxia x 2 wks Progressive gait ataxia x 2 wks

• PMH: polysubstance abuse (mainly PMH: polysubstance abuse (mainly cannabis), depression, anxiety, cannabis), depression, anxiety, hypertension hypertension

MRIMRI

CTCT//PET ScanPET Scan

Lab TestsLab Tests

CSF Results Ref RangePROTEIN (mg/dL) 78 14-45GLUCOSE (mg/dL) 52 50-80 NUCLEATED CELL COUNT (cells/µL) 42 0-3

(87% lymphocytes, 13% monocytes)CYTOLOGY Negative ──MICROBIOLOGY CULTURES (Bacteria & Fungi) Negative ──MICROBIOLOGY PCR (VZV & JC virus) Negative ──

CSF AnalysisCSF Analysis

• Following 2 wks: Following 2 wks: • Non-ambulatoryNon-ambulatory• Significant cognitive impairmentSignificant cognitive impairment• Mild left upper extremity weakness & Mild left upper extremity weakness &

apraxiaapraxia• Urinary retentionUrinary retention

Case - Cont’dCase - Cont’d

MRIMRI

VesselVessel

Differential DiagnosisDifferential Diagnosis

CaseCase• 37 y/o man37 y/o man

• H/o H/o • Mild short-term memory loss x 1 yrMild short-term memory loss x 1 yr• Right neck mass (~ golf ball) and Right neck mass (~ golf ball) and

general malaise x 1 mogeneral malaise x 1 mo• Progressive gait ataxia x 2 wks Progressive gait ataxia x 2 wks

• PMH: polysubstance abuse (mainly PMH: polysubstance abuse (mainly cannabis), depression, anxiety, cannabis), depression, anxiety, hypertension hypertension

CT/PET ScanCT/PET Scan

CD30CD30 CD15CD15

CD45CD45PAX5PAX5

Classical Hodgkin’s Lymphoma, Classical Hodgkin’s Lymphoma, Nodular Sclerosing SubtypeNodular Sclerosing Subtype

DiagnosisDiagnosis

Granulomatous Angiitis Granulomatous Angiitis (GA) of CNS associated (GA) of CNS associated

with Hodgkin's Lymphomawith Hodgkin's Lymphoma

GA of CNS associated with GA of CNS associated with Hodgkin's Lymphoma (HL)Hodgkin's Lymphoma (HL)

37yrs37yrs

(20-58 yrs)(20-58 yrs)

11M11M:8F:8F

32% Death32% Death

68% 68% Recovery Recovery (Partial/ (Partial/

Complete)Complete)

Case Age Sex Time of Diagnosis VZV Infection Outcome1 37 M HL prior GA N GA-related death2 31 F HL prior GA N GA-related death3 32 F HL prior GA Y GA-related death4 40 F HL prior GA Y Partial recovery5 20 M HL prior GA Y GA-related death6 29 F HL prior GA Y Partial recovery7 43 M HL prior GA N GA-related death8 55 M HL simultaneous GA N GA-related death9 38 M HL simultaneous GA Y Complete recovery10 38 M HL simultaneous GA N Complete recovery11 58 F HL simultaneous GA N Partial recovery12 28 M HL simultaneous GA N Partial recovery13 27 F HL simultaneous GA N Complete recovery14 52 M HL simultaneous GA N Complete recovery15 20 F HL simultaneous GA N Partial recovery16 55 M HL simultaneous GA N Complete recovery17 26 F HL simultaneous GA N Complete recovery18 28 M HL simultaneous GA N Partial recovery19 37 M HL simultaneous GA N Complete recovery

• Pathogenesis: Pathogenesis: • VZV reactivation?VZV reactivation?• Paraneoplastic mechanismParaneoplastic mechanism

• Treatment:Treatment:• CorticosteroidsCorticosteroids• Chemotherapy/Radiotherapy (HL)Chemotherapy/Radiotherapy (HL)

GA of CNS associated with GA of CNS associated with Hodgkin's Lymphoma (HL)Hodgkin's Lymphoma (HL)

Case - Follow-upCase - Follow-up• Chemotherapy (ABVD) & Chemotherapy (ABVD) &

Radiotherapy (neck & mediastinum): Radiotherapy (neck & mediastinum): complete remissioncomplete remission

• Corticosteroids x 7 mo Corticosteroids x 7 mo

• Significant improvementSignificant improvement

• Residual cognitive deficitResidual cognitive deficit

Granulomatous Angiitis Granulomatous Angiitis of CNSof CNS

• Primary CNS Primary CNS vasculitisvasculitis

• a.k.a. “Primary a.k.a. “Primary angiitis of CNS”angiitis of CNS”

• Secondary CNS Secondary CNS vasculitisvasculitis

• Systemic Systemic vasculitis/CTDvasculitis/CTD• VZV/HIVVZV/HIV• SarcoidosisSarcoidosis• HLHL/NHL/NHL

• Morphological patternMorphological pattern

ReferencesReferences• Rosen CL, DePalma L, Morita A. Primary Angiitis of the Central Nervous System as a First Rosen CL, DePalma L, Morita A. Primary Angiitis of the Central Nervous System as a First

Presentation in Hodgkin’s Disease: A Case Report and Review of the Literature. Presentation in Hodgkin’s Disease: A Case Report and Review of the Literature. NeurosurgeryNeurosurgery, 2000; 46, 1504., 2000; 46, 1504.

• Greco FA Greco FA et alet al. Hodgkin's disease and granulomatous angiitis of the central nervous . Hodgkin's disease and granulomatous angiitis of the central nervous system. system. CancerCancer. 1976;38:2027.. 1976;38:2027.

• Sheehy N, Sheehan K, Brett F, Kay E, Grogan L, Delanty N. Hodgkins disease presenting with Sheehy N, Sheehan K, Brett F, Kay E, Grogan L, Delanty N. Hodgkins disease presenting with granulomatous angiitis of the central nervous system. granulomatous angiitis of the central nervous system. J NeurolJ Neurol. 2003 Jan; 250(1):112-3.. 2003 Jan; 250(1):112-3.

• Miyazaki Y, Tajima Y, Sudo K, Matsumoto A, Tashiro J, Kikuchi S, Sasaki H, Tashiro K Miyazaki Y, Tajima Y, Sudo K, Matsumoto A, Tashiro J, Kikuchi S, Sasaki H, Tashiro K Hodgkin's disease-related central nervous system angiopathy presenting as reversible Hodgkin's disease-related central nervous system angiopathy presenting as reversible posterior leukoencephalopathy. posterior leukoencephalopathy. Intern MedIntern Med. 2004 Oct; 43(10):1005-7.. 2004 Oct; 43(10):1005-7.

• Roggerone S, Traverse-Glehen A, Derex L, Honnorat J, Berger F, Salles G, Rousset H, Roggerone S, Traverse-Glehen A, Derex L, Honnorat J, Berger F, Salles G, Rousset H, Trouillas P, Nighoghossian N. Recurrent cerebral venous thrombosis revealing Trouillas P, Nighoghossian N. Recurrent cerebral venous thrombosis revealing paraneoplastic angiitis in Hodgkin's lymphoma. paraneoplastic angiitis in Hodgkin's lymphoma. J NeurooncolJ Neurooncol. 2008 Sep;89(2):195-8. . 2008 Sep;89(2):195-8.

• Salvarani C, Brown RD Jr, Calamia KT, Christianson TJ, Huston J 3rd, Meschia JF, Giannini Salvarani C, Brown RD Jr, Calamia KT, Christianson TJ, Huston J 3rd, Meschia JF, Giannini C, Miller DV, Hunder GG. Primary central nervous system vasculitis: analysis of 101 C, Miller DV, Hunder GG. Primary central nervous system vasculitis: analysis of 101 patients. patients. RheumatologyRheumatology (Oxford). 2008 Nov;47(11):1671-7. (Oxford). 2008 Nov;47(11):1671-7.

• Miller DV, Salvarani C, Hunder GG, Brown RD, Parisi JE, Christianson TJ, Giannini C. Biopsy Miller DV, Salvarani C, Hunder GG, Brown RD, Parisi JE, Christianson TJ, Giannini C. Biopsy findings in primary angiitis of the central nervous system. findings in primary angiitis of the central nervous system. Am J Surg PatholAm J Surg Pathol. 2009 . 2009 Jan;33(1):35-43.Jan;33(1):35-43.

• Gerstner ER, Abrey LE, Schiff D, Ferreri AJ, Lister A, Montoto S, Tsang R, Thiel E, Graus F, Gerstner ER, Abrey LE, Schiff D, Ferreri AJ, Lister A, Montoto S, Tsang R, Thiel E, Graus F, Behringer D, Illerhaus G, Weaver S, Wen P, Voloschin A, Harris NL, Batchelor TT. CNS Behringer D, Illerhaus G, Weaver S, Wen P, Voloschin A, Harris NL, Batchelor TT. CNS Hodgkin lymphoma. Hodgkin lymphoma. BloodBlood. 2008 Sep 1;112(5):1658-61.. 2008 Sep 1;112(5):1658-61.

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