Infections

of the SNC

1

Difine probable site of infection

•Meninges

– Acute meningitis

– Chronic meningitis

– Recurrent meningitis

• Brain

– Acute encephalitis

– Chronic encephalitis

– Space-occuring lesions

– Toxin-mediated syndromes

– Encephalopathy with systemic syndrome

– Postinfectious syndrome

•Spinal cord

– Acute encephalomielitis

– Chronic encephalomielitis

– Space-occuring lesions

– Toxin-mediated syndromes

– Postinfectious syndrome

2

Infections of the central nervous system

• Fungal: Cryptococcus, Coccidiodes, Aspergilus, Histoplasma, Candida

• Protozoal: Toxoplasmosis, Plasmodium, Amoeba, Cysticercosis

• Bacterial: Bac. men, Tbc, Neuroborreliosis, Neurosyphilis

• Virlal:

– HSV, HZV, CMV

– Encephalitis: Japanese, West Nile, St. Louis, Estern equine, California

– Mumps, Measles, Rabies, Poliomyelitis

– Slow virus: HIV, progressive multifocal leucoencephalopathy, subacute

sclerosing panencephalitis

• Prionic: Creutxfeldt-Jacob, etc

• Post-infectious diseases of the CNS:

– PANDAS (Pediatric autoimmune neuropsychiatric disorders associated

with streptococcal infections)

– Acute disseminated encephalomyelitis

– Guillain-Baree syndrome

3

4

PATHOGENESIS CNS INFECTION

5

6

7

Meningitis in infants

– All cardinal signs of meningitis (fever, vomiting, stiff neck) are rarely present.

– paradox irritability (ie, quiet when stationary, cries when held), crying, lethargy, alertness changes

– High-pitched cry

– poor feeding and/or vomiting, diarrhea

– seizures (30-40% - rarely the sole manifestation)

– altered sleeping or eating patterns.

– respiratory distress

– bulging fontanelle may be present late in disease

– hypotonia

– fever may be not present in neonates • A febrile child who is playful, smiling, or interactive is unlikely to

have meningitis in the absence of other signs/symptoms

– 6% DIC and endotoxinic schock

8

9

Meningitis in elderly patients

Older pts, immunocompromised:

fever may not be present

early behavioral problems

Cushing reflex (bradycardia, hypertension, irregular

respirations)

reduced level of consciousness (inability to answer 2

consecutive questions correctly or to follow 2 consecutive

commands, abnormal language, obtundation/coma)

papilledema

dilated pupils, anizocoria, poorly reactive

rigid posture or posturing

VI nerve palsies (abducens supplies the lateral rectus

muscle) gaze palsy

~ facial palsy

seizures

hypertermia

focal paralysis in any of the limbs or trunk

arrithmya

10

cerebral herniationSigns of raised ICP and cerebral edema:

11

12

four tubes of CSF,

each containing about 1mL of fluid

Normal CSF

• Gross appearance: clear and colorless.

• CSF opening pressure: 50–180 mmH2O

• Glucose: 40–85 mg/dL (2.8–4.4 mmol/L)

• N glucose ratio CSF : serum = 0.6 (0.3 for diabetics)

• (In term neonates, a ratio of 0.6 is considered to be abnormal)

• Protein (total): 15–45 mg/dL (albumin 2/3 of total)

• Lactate dehyrogenase: 1/10 of serum level (<35 mg/dL)

•Leukocytes (WBC):

• 0–5/µL (adults / children)

• up to 30/µL (newborns)

• Differential:

• 60–70% lymphocytes;

• up to 30% monocytes and macrophages;

• Stain: negative

•Culture: sterile

• Specific gravity: 1.006–1.009

13

Incidence of various pathogens in different age groups and with specific risk

factors for bacterial meningitis

14

Acute Community-Acquired Bacterial Meningitis

15

Healthcare-Acquired Meningitis

and Ventriculitis

= infections that complicate:

• craniotomies,

• CSF shunt,

• drain surgeries.

most common:

1. Gram-positive

• Staph. epidermidis / aureus

2.Gram-negative bac

• Escherichia coli,

• Klebsiella ,

• Pseudomonas ,

• Acinetobacter

3.anaerobes

• Propionibacterium acnes

Neiseria

meningitidis

-Acute oncet

- winter&early spring

-I peak children <5yo; II - 15-24yo

-nasopharyngitis

-meningococcemia

~ attention: Waterhouse-Friderichsen

Str. pneumonia -asplenism,

-Ig deficiency

- pneumonia

-endocarditis

-otitis media

-paranasal sinusitis

-skull fracture

Haemophilus

influenzae

age < 5 years, unvaccinated

In adults: presence of an underlying

medical disorder (sinusitis, otitis,

alcoholism, CSF leak following head

trauma)

-epiglottitis

-otitis media

-sinusitis

-traheobronh.

-pneumonia

-CSF leak following head trauma

Listeria

monocytogenes

-neonates >3 d & <3mo

-adults >50-60 yo, cancer, diabetis

-food-borne: milk products; vegetables,

undercooked meat, soft cheese

-grow at refrigerator temperatures

+/- gastrointestinal symptoms

-20% no neck stiffness

-multiple CN deficits: VI, VII

-CSF:1/3 - limph, 2/3 neutro

16

Clinical criteria for the etiological diagnosis of meningitis

CSF findings suggestive of bacterial meningitis:

• High WBC 1000–5000 cells/mm3 (100-100,000 cells/mm3)

• low: head trauma, brain abscess, neurosurgery, AIDS

• low WBC count (<20 cells/µL+ high bacterial load = poor prognosis)

• PMN predominance >80-90%

• early in mening. <24-36 ho lymph. predom. (60-70%)

• Low glucose <40 mg/mL, ratio <0.4

• Impaired transport from blood, decreased gluc. receptor expression,

• ↑ anaerobic glycolysis by leucocytes & brain cells

• High protein >100 to 500 mg/dL (N = 45-60 mg/dL)

• Gram staining pos: 70-85% without previous atb; 40-60% with

• ↑ CSF lactate concentrations:

recommend. in postoperative neurosurgical pts initiate empirical atb if lactate >4.0 mmol/L

↑ serum polypeptide procalcitonin polypeptide = in pts with severe bac. Inf.17

18

Test Turnaround

time

Result

interpretation

Advantages Disadvantages

Microscopic

examination

0.5–1 hours Direct if

correlated with

symptoms

Rapid. Poor sensitivity and

specificity; special skills

are needed for

interpretation

Rapid

antigen

15–30 min Direct if

correlated with

symptoms

Rapid False positive results

Culture 2–14 days Definite For phenotypic

drug

susceptibility

testing

Time-consuming; poor

sensitivity; limited

microorganisms are

culturable

Serology 2–8 hours Indirect Automation Results are generally

retrospective; cross-

reactions;

immunosupressed host

may be unable to mount

a response

Molecular

diagnostic

2–8 hours Direct without

knowing

microbial viability

High sensitivity

and specificity

Not the test of cure;

clinical relevance need

to be determined

Laboratory methods used for diagnosis of CNS infections

19

CSF Gram stain: sensitivity 60-90%

CSF concentration of bac. Pos stain

103 colony-forming units/mL 25%

103 – 105 CFU/mL 60%

>105 97%

pos Gr stain

Str. pneumoniae 90%

H.influenzae 86%

N. meningitidis 75%

gram-neg bacilli, 50%

Listeria m. 30%

Bacterial Meningitis Empiric Therapy

Younger than 1

month:

group B Strept (GBS),

E.coli, Listeria monocytogen.,

Klebsiella species.

Ampicillin + cefotaxime /

+aminoglycoside

(gentamicin / tobramycin)

One to 23 months Neisseria meningitidis

Strepto. pneumoniae,

group B Strept (GBS), E coli.

Haemophilus influenzae type b,

Vancomycin +

Ceftriaxone /Cefotaxime

Neisseria men.:benzylpen. /

ceftriaxone / cefotaxime)

Two to 50 years: N meningitides

S pneumoniae

Vancomycin +

Ceftriaxone /Cefotaxime

Older than 50

years:

S pneumoniae, N meningitidis,

L monocyt., aerobic gr-neg rods

Ampicillin + Vancomycin +

Ceftriaxone / Cefotaxime

Immunocompr. S pneumoniae, N meningitidis,

Listeria species, anaerob Gr-neg

Ampicillin + Vancomycin +

Ceftriaxone / Cefotaxime

Basilar skull

fracture

S pneumoniae, H influenzae

Strept. pyogenes

Vancomycin +

Ceftriaxone /Cefotaxime

Penetrating

trauma

neurosurgery

Staph aureus / epidermidis,

aerobic gram-neg bacilli.

Vancomycin +

Cefepime / ceftazidime /

meropenem

Cerebrospinal

fluid (CSF) shunt:

Staph epidermidis / aureus,

aerobic gr-neg bacilli,

Propionibacterium acnes.

Vancomycin +

Cefepime / ceftazidime /

meropenem

21

22

Adjunctive dexamethasone therapy

• Dexametazon (not Metilprednisolon)– I dose 10-20 min prior atb / at least concomitent

(dexamethasone treatment can still be started up to 4 h after the firstdose of antibiotics)

– 0,15 mg/kg q6h (adults 8-12mg primary, then 4-8mg q6h)– length 2 - 4 days– not recommended in treatment of edema secondary to

stroke or haemorrhage)– not recommended in neonates concern regarding effects

on neurodevelopment– The guideline advises to consider discontinuation of

dexamethasone if pathogens otherthan S. pneumoniae or H. influenzae are identified.

23

“For infants and children 6 weeks of age and older, adjunctive therapy with

dexamethasone may be considered after weighing the potential benefits and

possible risks. Experts vary in recommending the use of corticosteroids in pneumococcal

meningitis; data are not sufficient to demonstrate clear benefit in children”

24

25

COMPLICATIONS OF SEPTIC MENINGITIS

1.Cerebral edema (may lead to herniation)

2.Subdural effusion or empyema

3.Vasculitis

• Arteritis (stroke)

• Cortical venous thrombosis (stroke, seizures)

• Venous sinus thrombosis (increased intracranial

pressure)

4.Hydrocephalus

5.Cranial nerve palsies

6.Disseminated intravascular clotting

7.Lactic acidosis

8.Inappropriate ADH secretion

9.Diabetes insipidus

10.Residual findings

• Cranial nerve palsies

• Mental retardation

• Seizures

26

Chemoprophylaxis for high- risk contacts

27

Aseptic meningitis

28

CAUSES OF ASEPTIC MENINGITIS / MENINGOENCEPHALITIS

Viral (Enteroviruses, HSV, VZV, EBV, CMV, HIV, Mumps, LCMV

(lymphocytic choriomeningitis virus), Arbovirus

Bacterial:

• Mycobacterium tuberculosis, MAC,

• Treponema pallidum,

• Brucella,

• Borrelia,

• Rickettsial infections

Fungal meningitis

Protozoal or helminthic infections

Sarcoidosis

Noninfectious causes

• Chemical meningitis (after pneumoencephalography, myelogram,

cisternogram, spinal anesthesia, intrathecal therapy, etc.)

• Toxins (lead, arsenic)

• Tumors

• Demyelinating disease

• Vascular diseases (Vasculitis / Stroke / Subarachnoid hemorrhage)

Enteroviruses

coxsackievirus gr.A 2,4,7,9, gr.B 2-5, echovirus 4,6,9,11,30, enterovirus 71

transmission: hand-to-mouth contact & rarely: respiratory and fecal routes.

temperate climates spring – autumn, outbreaks / sporadic

acute onset of nonspecific febrile illnesses, ~ diphasic pattern

associated findings: sore throat; maculo-papular / hemorrhagic rash;

diarrhoea & abdominal pain; muscle pains & joint aches; very rarely - acute

flaccid paralysis.

•self-limited and resolves in 1-2 weeks.

•~Rombencephalitis (echo 71) myoclonus, sleep disturbance, ataxia

•~Diffuse encephalitis; ~Paralytic syndromes

CSF:

WBC 500- 2,000/mm3

limph. predom. 80-90%

~ first 1-2 days >PMN

glucose – N (↓ in severe)

protein – N / mildly elevated

ARN of enterovirus by PCR from CSF

Stool isolation = misleading can be excreted 12-17 we after inf.29

HSV 1 encephalitis

Patients do not usually have concurrent cold

sores or genital herpes.

• There is often a prodrome for several days

– headache, fever, lethargy, somnolence,

– personality changes (involvement of the

limbic system)

– difficulty with recent memory (involv. temporal

lobe (hippocampi),

– decreased or lost sense of smell (anosmia)

(involv. olfactory bulbs).

• Rapid progression to severe CNS dysfunction:

seizures , focal weakness, cranial nerve defects,

aphasia, hemiparesis

• 20% atypical form: without focal features

• Meningeal signs may not be present

• Papilledema 20%

• Mortality 60–80% untreated.

30

HSV-1 encephalitis

CSF:

• WBC 50-500 (mean of 200 cells/mm3)

• Lymphocytes 80-90%

• RBCs (negative early; present later 10-500/mL)

• midly elevated protein (60-700 mg/dL, average 100)

• normal // mildly decresed glucose (30-40 mg/dL)

• large granular plasma cells (Mollaret cells) seen by Papanicolaou stain

• CSF Ab > serum Ab to HSV-1, not detected until 2 wks

• PCR can be neg in early stages, repeat 3-7 days– 80% - edema and mass effect

– 90% - evidence of temporal lobe involvement

attack a set of interconnected brain structures responsible for the integration of emotion, memory, complex behavior ("limbic system“) 31

HSV-1 encephalitis CT - hypodense lesions in:

•temporal lobes,

•inferior frontal lobes,

•insula,

•predilection for the medial temporal lobes with a sharp transition

MRI -` high signal on T2-weighted scans

` beginning unilaterally, progressing to bilateral` exaggerated signal does not extend beyond the insular cortex (thin arrow),

` but does involve the cingulate gyrus (thick arrow).

foci of hemorrhage occasionally can be observed

32

HSV-1 encephalitis

HSV encephalitis should be considered in any patient with: – a progressively deteriorating level of consciousness,

– fever,

– abnormal CSF,

– focal neurological abnormalities in the absence of any other causes

Treatment:

– Acyclovir, IV, 10 mg/kg q8h for 14–21 days.

– Valacicolvir (expensiv)

– Foscarnet (in severe aciclovir-resistant)

– Administer each dose slowly over 1 hour.

– Crystal-induced nephropathy may occur >> adequately hydrating the patient (eg, 1 mL fluid per day for each 1 mg/d of acyclovir)

• Combating the host inflammatory response with steroids33

Recurrent benign lymphocytic (Mollaret‘s) meningitis

• Age range 5 - 57 years

• Sudden oncet of 3 - 10 episodes of fever + men. signs

• Episodes lasts 2 - 5 days, with spontaneous recovery.

• ½ of pts have transient neurologic manifestations (including seizures,

hallucinations, diplopia, and cranial nerve palsies).

• CSF: hundreds to thousands cells, mixed lymph. and PMN, and large cells

(Mollaret's) cells, protein mildly elevated, glucose N.

• Causative agent: HSV-2 in the majority of cases (PCR)

• Treatment with acyclovir may be beneficial in:

– decreasing the severity

– decreasing the duration of attacks

– preventing further episodes.

34large monocytes with variable shapes

of nuclei (Mollaret's cells)

35

Virus Family Reservoir Primary Vector Distribution

Flaviviridae

Japanese encephalitis Birds, Pigs Culex mosquito SE Asia, Pacific Rim

Murray Valley enceph. Birds Culex mosquito Australia

St. Louis enceph. Birds Culex mosquito Americas

West Nile Virus Birds Culex, Aedes North America, Africa,

Europe, Asia, Australia

Bunyaviridae

California enceph. Rodents, rabbits Aedes mosquito North America

La Crosse virus Chipmunks,

squirrels

Aedes North America

Rift Valley fever Sheep, cattle Aedes, Culex Africa

Toscana virus Bats, humans Phlebotomine flies Europe

Alphaviridae (Togaviridae)

Chikungunya virus Primates, humans Aedes Africa, India, SE Asia

Eastern equine enceph. Birds Aedes Americas

Venezuelan equine

encephalitis virus

Rodents, horses Aedes Americas

Western equine

encephalitis virus

Birds, mammals Culex North America36

Major etiological agents of arboviral meningo-encephalitis

37

West Nile virus (WNV)

• first identified in the West Nile subregion of Uganda,

• now endemic in temperate and tropical regions throughout the world, c

• yearly outbreaks of encephalitis, more likely to occur in adults

• mortality rate 5 - 10 %

• can be transplacentally transmitted during pregnancy

• cause symptomatic inf. in adults, especially chronically ill, immunosup., or elderly

•  > 90 % rate of survival with ~50 % incidence of cognitive disturbance

• WNV can spread:i. along neurons via retrograde axonal microtube-mediated transport, than

ii. hematogenous spread

• Neuronal damage and loss can occur by either direct arboviral infection or indirectly

by uncontrolled immune responses to the replicating virus

• Neuronal degeneration, necrosis, and apoptosis

• There are currently no approved antiviral medications for the treatment of neurologic

infections with arboviruses.

38

Tick-borne encephalitis (Flavivirus)

•Scandinavia; W & C Europe; Asia

•bite of ixodes ticks, incub 7-14 (4-28) days

•unpasteurized dairy products cows, goats, sheeps

•I phase: 2-10 days, t0, pseudoinflu., GI simptoms

•Asimptomatic: 1-33 days

•II phase: meningoencephalitis, encephalomyelitis,

encephaloradiculitis

•far eastern subtype - monophasic, no asymptom

•no specific antiviral therapy for TBE.

39

Lymphocytic Choriomeningitis Virus (LCMV = arenavirus)

•main reservoir: house mouse, but also hamsters and domestic mice

•infection by:

– inhaling aerosolized particles of rodent urine, feces, or saliva,

– ingesting contaminated food

– contamination of mucus membranes with infected body fluids,

– directly exposing cuts or other open wounds to virus-infected blood.

– mouse and hamster bites

•Incubation 1 - 2 weeks.

•Infection in people:

– often subclinical;

– “influenza-like symptoms” ;

– meningitis (stiff neck, fever, headache, malaise, muscular pain)

– Orhitis, myocarditis, arthritis, maculopapular rash

•Pregnant women to the fetus:

– fetal or neonatal death

– hydrocephalus, or psychomotor retardation

– chorioretinitis 40

Specific therapy viral meningitis

• HSV: Aciclovir, valaciclovir, foscarnet in severe aciclovir-

resistant

• HZV: acyclovir, ganciclovir an alternative

• CMV: I line: ganciclovir, valganciclovir, II line: foscarnet,

cidofovir

• EBV: acyclovirnot recommended; corticosteroids beneficial

• HHV 6: ganciclovir or foscarnet

• Influenza virus: oseltamivir

• Measles virus: ribavirin

• West Nile virus: ribavirin is not recommended

• St. Louis encephalitis virus: IFN-2a

41

• HIV/AIDS

42

43

44

45

HIV encephalopathy

• is a diagnosis of exclusion

• Damage occurs mainly in the subcortical gray matter, especially - basal

ganglia

• Neurologic deficits usually progress insidiously we - mo

Early signs:

• Cognitive

– forgetfulness associated with slowed mental

– Decreased attention / concentration

– Inability to perform complex task

• Motor

– Poor balance

– loss of fine motor skills (e.g. tremors, clumsiness)

– loss of balance and leg weakness

– progressive loss of mobility

• Behavioral

– apathy and social withdrawal (mistakenly diagnosed as

depression)46

HIV encephalopathy in children (younger than 15 years)

47

• diffuse enlargement of the lateral

ventricle

• cortical sulci are prominent given the

age of the subject

• hyperintense signal throughout the

periventricular white matter

• small children basal ganglia

calcification

• excluding other causes

HIV encephalopathy

48

49

Tuberculous meningitis (TBM) risk factors:

HIV, excessive alcohol use, diabetes, weakened immune system prior tbc history: 50% of children, 10% of adults primary focus on Rx = 30% Formation of small subpial or subependymal foci of metastatic

caseous lesions (Rich focus) ruptures into the subarachnoid spaceTubercles rupturing into the subarachnoid space = meningitis.Tubercles deeper in the parenchyma = tuberculomas /abscesses.

Thick gelatinous exudate infiltrates the cortical / meningeal vessels inflammation, obstruction, infarction.

Tuberculomas

Tuberculous meningitis (TBM)

– duration of symptoms prior to diagnosis 2- 3 weeks• low-grade fever• intermittent headache• light sensitivity• behavioral changes, lethargy, agitation, coma

– mening. Signs + / +++– cranial nerve palsies (CN VI; III, VII)Basal meningitis CN III, VI, VII, eventually leading to obstructive

hydrocephalus from obstruction of basilar cisterns.

– seizures especially in children and elderly people– ophthalmoscopic – papilloedema

Tuberculous meningitis (TBM)CSF:

– Pleocytosis in hundreds 50 – 500 WBC/ml (< 750)

– 60- 80% lymphocytes (PMN ~ predominate first 10 days) – protein: N raised (>1.0 g/L), spider-web clot– low glucose <40 mg/dL, ratio CSF/blood <0.5– low chloride

– Ziehl-Neelsen 10% (acid-fast bacillus )

– acellular CSF in elderly, HIV / AIDS pts

– PCR CSF low sensitivity

– Culture for M.tbc 3-6 weeks

• Once specific therapy has begun, a so-called therapeutic paradox may occur

and is characterized by clinical worsening and by a shift of the CSF

lymphocytic pleocytosis into a polymorphonuclear response. It must not be

interpreted as a failure in treatment

52

Tuberculous meningitis

• exudate in the basal cisterns

• basilar meningeal thickening

• infarcts in the middle cerebral

artery territory

• edema

• hydrocephalus

• tuberculoma formation

Post-contrast MRI:

basal cistern enhancement:

more prominent on

contrast enhanced T1-W image53

Criptococcal neoformans / gattii var neoformans infection

immunosuppressed hosts

54

asymptomatic or

symptomatic

pneumonia

environmental exposure

worldwide distribution

no human to human transmission

55

Criptococcal meningitis

• subacute illness (>2we), low grade fever

• confusion, change in behavior

• cranial nerve palsies and papilledema

• less often altered mental status

• mortality rate of meningitis 6-25%

• 2/3 - without signs of meningeal irritation

Associated signs:

• Skin lesion

• Oral ulcers

• Myocarditis

• Pulmonary involv. 1/3

• GI

56

Cryptococcal meningitis CSF:

• pleocytosis (20-500 cells),

• lymphocytes 80-90%

• reduced glucose in severe cases,

• elevated protein level

• CSF opening pressure elevated

• cryptococcal antigen test 90% sensitive

• India ink and specific fungal culture.

Yeast are identified through the halo effect because of the glucuronoxylomann

capsule

DD. Aspergillus and related fungi result in neutrophilic meningitis.57

58http://www.hivwebstudy.org/cases/ois-treatment/39-year-old-headache-fever-and-

confusion-text-added-andrew-draft

Cerebral toxoplasmosis

• 3% to 40% of pts CD4 counts < 200 cells/mm3

• most cases - reactivation of a previously acquired toxo

• clinical manifestations – headache (55%),

– confusion (52%),

– fever (47%),

– lethargy (43%),

– seizures (29%).

– focal neuro signs 69%: hemiparesis, ataxia, cranial nerve palsies

• CSF examination in toxoplasmosis is nondiagnostic

• CSF: Ab to Toxo are not sensitive for Toxo encephalitis

• MRI is more sensitive than CT

59

MRI is more sensitive than CT m

multiple ring-enhancing lesion surrounded by variable degrees of vasogenic edema

predilection for cortex and deep gray-matter structures such as the basal ganglia

cerebellum and brain stem are less commonly involved

Cerebral toxoplasmosis

MRI T1 weight + gadolinium

60

61

62

63

Progressive multifocal leukoencephalopathy (PML)

• JC virus (papovavirus)

• enter the body via the respiratory or oral route

• becomes latent in kidneys, lymphoreticular tissues, brain

• primary infection is asymptomatic

• HIV reactivation of the endemic JC

• Viral particles carried to CNS via B-lymph. In systemic dissem.

• infection of oligodendrocytes

• leads to demyelination dL 4-6 mo. If +HAART 2 years

• insidious onset and steady progression of focal symptoms:

• behavioral, speech, cognitive, motor, visual impairment.

•multifocal nature of the disease,

•evolves over several weeks

• PML more rapid progression than AIDS dementia complex

•Pts with more preserved immune slower progression

• As lesions expand manifest. worsen, involve larger territory

•Seizures a rare manifestation of PML (if + = demyelinating

lesions immediately adjacent to the cortex)

64

Primary Central Nervous System Lymphoma

MRI after the administration of intravenous contrast

T1 T2

single or multiple

focal ring and/or nodular enhancing mass lesion(s)

with surrounding edema

primary CNS lymphoma resembles toxoplasmosis in 50-80% of the cases

Rapid progression of the mass(es) on serial imaging studies also favor lymphoma 65