primary cns lymphoma

Primary CNS Lymphoma (PCNSL)

Mohamed Wael Samir MDProfessor of neurosurgery

Ain Shams University

ILOS

Discuss pathogenesis of PCNSLDiscuss the epidemiological data of PCNSLDescribe the microscopic, macroscopic and immunohistochemical

characters of PCNSLDiscuss presentation, D.D., and investigations of PCNSLTabulate management protocol for a patent with PCNS

Introduction

Introduction Classification of CNS lymphoma:

Primary CNS lymphoma (PCNSL) Secondary CNS lymphoma

Definition of PCNSL:Brain Spinal cord Ocular structure

Synonyms of PCNSL:Reticulum cell sarcoma, Perivascular sarcoma, Immunoblastic sarcoma, Microgliomatosis Malignant reticulosis.

Pathology

Pathology

1) Cell of origin & pathogenesis 2) Epidemiology 3) Macroscopic features 4) Microscopic features 5) Immunohistochemistry 6) Genetic features 7) Radiological features 8) Growth pattern & spread 9) Grading & behavior 10) Prognosis

Pathology: Cell of origin & Pathogenesis

Theories of PCNSLCNS infection → inflammatory process → Neoplastic

processSystemic lymphoma cells eradicated by the immune system

but CNS is an immunologically protected Systemic lymphoma ceils but have special receptors to CNS

vessels

Pathology


Pathology: Epidemiology Incidence:

1-2% of intracranial tumors 10 % of systemic lymphomas will have CNS mets.A similar percentage develop systemic disease after brain

involvement. 10 % of AIDS patients will have PCNSL

Sex: Immunocompetent: ♂:♀ = 1.5:1 Immunocompromised: even more

Race: Age:

Immunocompetent: 6th decade Immunocompromised: 4th decade

Risk factors: Immune compromise

Pathology


Pathology: Macroscopic features

Site: PCNS: Supratentorial, periventricular Mets: Leptomeningeal

Size: Number: mostly solitary Characters:

Well circumscribed, irregularly margined or diffuse infiltrate Yellow-brown Areas of focal hemorrhage or necrosis Cut surface firm, soft, friable or granular

Pathology


Pathology: Microscopic Features

Mostly diffuse large B-cell lymphomas (DLBCLs) Other cells found are

- Histocytes - Plasma cells - reactive astroytes- Microglia

Diffuse infiltrate rather than nodular At the periphery, the neoplastic infiltrate tends to be

perivascular Deposition of reticulin fibers arranged in concentric layers

Pathology


Pathology: Immunohistochemistry

Stain positive to the leukocyte marker CD45

CD45 immunological markers

Pathology


Pathology: Genetic & Ultra structures Features

EBV genomic material is identified in over 90% of PCNSL tissue from immunocompromised patients

Pathology


Pathology: Radiological Features CT: MRI: MRS: PET:

Pathology


Pathology: Growth Pattern & Spread Spread along fibers of C.C Spread along ependymal surface. The eye, however, is an important site for tumor

spread, with intraorbital involvement occurring in approximately 5% of patients at presentation.

Pathology


Pathology: Grading & Behavior

Most CNS NHMLs are high-grade lesions corresponding to

large B cells.

MIB-l, proliferation index, usually high, 50%

Pathology


Pathology: Prognosis Median survival in Immunocompetent patients is 17-45

months Median survival in Immunocompromise less than 3 months Despite a high initial response rate, radiotherapy alone

rarely leads to long-term survival; only 7% of patients are alive 5 years after treatment

Radio + Chemo = ↑ the 5-year survival rate from 7 to 20-30%.

Patient’s Factors:

• Older• Immunocompromise• Lower Karnofsky performance

Tumor’s Factors:•Deeper regions of the brain•Multiplicity of lesions

TTT’ Factors: • No chemotherapy

Presentation

Cranial or spinal masseIncrease intracranial pressure:Seizure:Neurological deficits Hormonal disturbance mainly DI or SIDH

lymphomatous meningitis: 5–65% Radicular or plexus invasion by lymphoma

(neurolymphomatosis) in the absence of brain or spinal fluid involvement

Infarcts Primary intraocular lymphoma (Lymphoma invading the

vitreous, retina, and optic nerves ): 10–15%

Investigations

To diagnose CNS lymphoma:Radiological features: Increase suspicious CSF examination !!!No steroid test Tissue diagnosis

To differentiate systemic lymphoma from PCNSL (esp. in Immunocompromised patient):General examination esp. to L.Ns. & testicleCT chest, abdomen & pelvis Bone marrow biopsy

To diagnose extent of PCNSL Cranial: Spinal: Orbital: Slit lamp examination

To define the competence of the immune system: HIV testing

Differential Diagnosis

Hypometabolism PET in Toxoplasmosis Hypermetabolism PET in PCNSL

Management

Surgery

Stereotactic biopsy: Relief of hydrocephalus Excision:

Radiotherapy

Highly radiosensitive Recurrence Lesion radiation # whole brain radiation 40-50 Gy to the primary tumor

Chemotherapy

Radio + Chemo = ↑ mean survival from 16 to 44.5 months Radio + Chemo = ↑ the 5-year survival rate from 7 to 20-

30%.

Management Protocol in Immunocompromised Patients

Immunocompromised patient presented with intracranial mass

MRI ? PCNSL # Toxoplasmosis PET if available or Test therapy with

Pyrimethamine and sulfadiazine: orTrimethoprim-sulfamethoxazole (Septrin D.S tab 160/800mg

): Dose 5 mg/kg TMP and 25 mg/kg SMX PO

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