Vasculitides in Surgical Neuropathology Practiceamz.xcdsystem.com/9427052B-EB87-B001-574B51E4E8F34C4B... · 2018-02-06 · AANP Companion Meeting PRESENTATION TITLE - CNS Vasculitis

Vasculitides in Surgical Neuropathology Practice

PRESENTATION TITLEAANP Companion Meeting - CNS Vasculitis

USCAP requires that all faculty in a position to

influence or control the content of CME disclose any relevant financial

relationship WITH COMMERCIAL INTERESTS which they or their

spouse/partner have, or have had, within the past 12 months, which relates to

the content of this educational activity and creates a conflict of interest.

Dr. Anthony T. Yachnis declares he has no conflict(s) of interest

to disclose.


Brain lesions with angiocentric pattern

• Primary CNS Lymphoma Whole brain RT & vs. treated lymphoma High dose methotrexate

• Vasculitis Immunosuppressive

• Infections Antibiotics

Disease Entity Therapy


Angiocentric CNS lesions• Establish whether true vasculitis is present (i.e. vs.

perivascular inflammation)• Rule out vascular/perivascular neoplasm – lymphoma• Establish whether vasculitis is intracranial vs. extracranial• Determine whether vasculitis is primary in the CNS or

secondary – systemic• Is the process granulomatous, lymphocytic, or necrotizing?


Vasculitis affecting the Nervous System• Primary CNS vasculitis (“Primary angiitis of the CNS”)

• Systemic vasculitis involving CNS• Large arteries Medium sized arteries

• Giant cell arteritis Polyarteritis nodosa

• Takayasu arteritis Kawasaki syndrome

• Small vessels• Granulomatosis with polyangiitis (Wegener’s disease)

• Churg-Strauss syndrome

• Secondary vasculitis affecting the CNS• INFECTIONS: Bacterial, viral, fungal, other• SLE; Sjogren’s disease• Drug or Malignancy-related


• Synonyms: “Primary angiitis of the central nervous system” “Granulomatous angiitis”

• Incidence: 2.4 cases per million

• Location: Multifocal involvement of small and medium-sized vessels limited to the brain and spinal cord

• Age range: Peak incidence between 40 – 60 years (rare in children)

Slight female predominance

A clinicopathologic diagnosis

Primary CNS vasculitis:


Primary CNS vasculitis: Diagnostic Criteria• Clinical: Acquired neurologic deficit that remains unexplained

after thorough evaluation• Must exclude “Reversible vasoconstriction syndrome” (RCVS)

• Imaging:• Alternating stenosis and dilatation of vessels (angiography)• Variable ischemic-like lesions on MRI (non-specific)

• Criteria for Exclusion:• No systemic vasculitis • No infection• No neoplastic condition


Primary CNS vasculitis: Imaging

Parenchymal & leptomeningeal enhancementIncreased signal intensity on T2 and FLAIRInfarctions in about 50% of cases

Alternating stenosis and dilatation of vessels


Challenges of biopsy for PCNSV:• Sampling error due to lesion focality

• 37% non-diagnostic despite positive angiogram• 26% positive biopsy despite negative angiogram

• Small risk of hemorrhage or other complication• Biopsy should include: leptomeninges, cortex, white matter• Some involved arteries too small for angiographic detection• Increased probability of success if lesion targeted for biopsy

• Must see vascular wall destruction with relatively little infiltration of surrounding CNS tissue


Primary CNS VasculitisHistological Patterns:

• Granulomatous• Most common• Type seen in Ab-related cerebral amyloid

angiopathy

• Lymphocytic• Most common type seen in children

• Necrotizing• Least common• Frequently associated with hemorrhage



• Primary CNS vasculitis (“Primary angiitis of the CNS”)

• Systemic vasculitis involving CNS

• Large arteries Medium sized arteries

• Giant cell arteritis Polyarteritis nodosa• Takayasu arteritis Kawasaki syndrome

• Small vessels

• Granulomatosis with polyangiitis (Wegener’s disease)

• Churg-Strauss syndrome

• Secondary vasculitis affecting the CNS

• INFECTIONS: Bacterial, viral, fungal, other

• SLE; Sjogren’s disease

• Drug or Malignancy-related

Vasculitis affecting the Nervous System


§ Most common primary vasculitis affecting the nervous system§ Incidence: 15-25 / 100,000§ Female/male: 2:1§ Peak incidence: 75-85 y/o

§ Disorder of cell-mediated immunity with CD4+T lymphocytes playing a key pathogenic role in the activation of monocytes/macrophages and the formation of multinucleated giant cells.

Giant cell arteritis (temporal arteritis)


• Normal sed. rates in up to 17% of cases

• Sensitivity of C-reactive protein: 97%• Sensitivity of ESR and CRP: 99%

• About 30-40% of patients with GCA will also have polymyalgia rheumatica

• Responsive to therapy: Glucocorticoids, Tocilizumab

Giant cell arteritis


• Gold standard for diagnosis: Temporal artery biopsy

• Medium and large extracranialbranches of the aorta

• Internal and external carotids• Subclavian and axillary arteries• Superficial temporal • Ophthalmic, posterior ciliary• Vertebral

Giant cell arteritisPanarteritis – grossly nodular thickenings


Temporal artery Giant cell arteritis


Giant cell arteritis:Granulomatous inflammation with multinucleated giant cells centered on internal elastic lamina


Giant cell arteritis:Granulomatous inflammation with multinucleated giant cells centered on internal elastic lamina


Giant cell arteritis:

Length of TA Biopsy-positive – GCA

5 mm (or less) 20%6-20 mm 71-77%> 20 mm 89%

Length of temporal artery biopsy: Size matters!

Breuer GS, Nesher R, Nesher G: Effect of biopsy length on the rate of positive temporal artery

biopsies. Clin Exp Rheumatol 2009, 27(Suppl 52):S10–S13.


Polyarteritis nodosa§ Typically affects medium to small-sized

arteries § CNS involved in 20-40% of cases§ PNS involved in > 50% of cases

§ Mononeuropathy multiplex§ Due to focal, segmental inflammation with an

infiltrate of polymorphonuclear neutrophils and fibrinoid necrosis

§ 30% of patients in the U.S. are positive for serum hepatitis B antigen


Polyarteritis nodosa


• If granulomatous: Rule out Ab-related cerebral amyloid angiopathy (ABRA)

• If lymphocytic: Rule out encephalitisRule out lymphoma

• If necrotizing: Rule out systemic vasculitis - polyarteritis nodosaRule out INFECTION

Primary CNS vasculitis Differential Diagnosis


Vasculitis (lymphocytic) EncephalitissEncephalitis• Intramural lymphocytes

• Less parenchymal lymphocytes – usually perivascular

• Microglial activation• Perivascular• No microglial nodules• Neuronophagia none/rare

• Edema – perivascular• Leptomeningeal involvement:

• Yes

• Perivascular lymphocytes• Diffuse parenchymal

lymphocytes• Microglial activation

• Diffuse• Microglial nodules• Neuronophagia

• Edema – diffuse• Leptomeningeal involvement:

• Yes


• Granulomatous• Fungal, tuberculous, other infections

• Lymphocytic• Viral, others

• Necrotizing• Bacterial• Toxoplasmosis• Amoebic (Acanthamoeba)

Secondary CNS vasculitis associated with infection


Angioinvasive CNS fungal infection• Young patient with severe

combined immunodeficiency disorder

• Multifocal hemorrhagic infarcts


CNS fungal infection


CNS tuberculous infection

• Granulomatous inflammation localized to basal subarachnoid space and vessels

• Persistent infection results in endarteritis obliterans


CNS Syphyllis

• Meningovascularneurosyphilis –

• “Hubner’s arteritis”

• Also may result in endarteritis obliterans


Viral encephalitis• Perivascular lymphoid “cuffing”

and microglial nodules are non-specific histological features

• Varicella-zoster virus and HIV may produce vasculitis

• Syphilis, Lyme disease, Rickettsial diseases may also cause vasculitis


Necrotizing vasculitis: infectiousGranulomatous Amoebic Encephalitis:Acanthamoeba species


Cerebral Toxoplasmosis: Cyst with bradyzoites


CNS Vasculitis: Take Home Points

• Establish whether true vasculitis is present (i.e. vs. perivascular

inflammation)

• Rule out vascular/perivascular neoplasm – lymphoma

• Establish whether vasculitis is intracranial vs. extracranial

• Determine whether vasculitis is primary (PCNSV) or secondary

(PAN)

• Is the process granulomatous, lymphocytic, or necrotizing?


CNS Vasculitis: Take Home Points• If granulomatous, rule out infections and ABRA

• If lymphocytic:• Consider altered lymphoid cell content under prior glucocorticoid therapy• Often etiology cannot be established without epidemiological, clinical, serological

correlation• Even after extensive work-up, most cases of vasculitis (especially lymphocytic)

remain without clear etiology

• If necrotizing:• Assess whether patient is immunocompromised (HIV)• Inquire about recreational or therapeutic drugs that might be causative.


THANK YOU

• B.K. Kleinschmidt DeMasters, MD• Caterina Giannini, MD• Murat Gokden, MD• Christopher Dunham, MD

With special thanks to:

Documents

Vasculitides in Surgical Neuropathology Practiceamz.xcdsystem.com/9427052B-EB87-B001-574B51E4E8F34C4B... · 2018-02-06 · AANP Companion Meeting PRESENTATION TITLE - CNS Vasculitis