Primary central nervous system lymphoma.ppt

Overview of presentation and management of 1ry CNS lymphoma

1. OCMU
Mansoura University
Oncology Center
by
Mohamed abdelfatah
1ry CNS lymphoma

2. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
Introduction
Primary central nervous system lymphoma (PCL) is an
uncommon variant of extranodal non-Hodgkin lymphoma
(NHL) that involves the brain, leptomeninges, eyes, or
spinal cord without evidence of systemic disease.
PCL represents approximately 4 percent of newly
diagnosed primary central nervous system (CNS) tumors
More common in age between 45 and 70 years of age
with median age 50 years
Rare in children

3. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
PREDISPOSING FACTORS
The most notable risk factor for the development of PCL is
immunodeficiency .
This includes HIV infection, iatrogenic immune
suppression, and congenital immune deficiency
In addition, patients with autoimmune diseases such as
rheumatoid arthritis, systemic lupus erythematosus,
myasthenia gravis, sarcoidosis, and vasculitis may be
predisposed to develop PCL

4. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
PATHOGENESIS
The CNS normally lacks lymphoid aggregates
The cells of origin in PCL may be derived from neoplastic
lymphocytes that are eradicated from the periphery by an
intact immune system, but which are able to survive in
CNS
The high incidence of PCL in immunodeficient states
strongly support role of the immune system in the
pathogenesis of PCL.
(EBV) may have a causal link to the development of PCL
through EBV-mediated clonal expansion and malignant
transformation of B-lymphocytes

5. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
CLINICAL PRESENTATION
PCL can manifest in the brain, its coverings, the eye,
spinal cord or cranial ,, spinal nerve roots
1-brain : symptoms may include headaches, blurred
vision, motor difficulties, and personality changes ,
psychosis, confusion, memory impairment , or visual
hallucinations
2-leptomeningeal : 25 percent of patients with PCL will
develop meningeal involvement. On the other hand, it is
extremely rare for patients without brain involvement to
present with primary meningeal involvement and
manifested with worsening headaches, cranial nerve
palsies, and hydrocephalus.

6. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
3-intra ocular : initially presents in the eye with or without
concurrent central nervous system (CNS) involvement,,
Diagnosis can be made by biopsy of the involved vitreous,
choroid, or retina ,, should be differentiated from retro-
orbital lymphoma, which is frequently associated with
systemic extranodal disease ,, it can be the initial
presentation In almost half of patients ,, tends to involve
the posterior segment of the eye, including the vitreous,
choroid, or retina
4-spinal : < 1 % of ptns ,, progressive myelopathy ,,Back
pain or Evidence of lower motor neuron involvement on
examination (areflexia or flaccid paralysis )

7. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
5-cranial or spinal nerve roots : sensory ,, motor
dysfunction

8. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
Work up
1-Radiology :
-Contrast-enhanced magnetic resonance imaging (MRI) of
the brain is the preferred imaging modality
-Contrast-enhanced computed tomography (CT) may be
used for patients with contraindications to MRI
-MRI may detect lesions missed by CT, although both CT
and MRI commonly fail to detect leptomeningeal or vitreal
diseas
-detected lesions may be solitary ( imunocompetent ptns )
or multifocal ( imunosupressed ptns )

9. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
-The lesion tends to be a solitary non-hemorrhagic mass,
situated in the deep white matter adjacent to the
ventricular surface ,, The borders are sharply
circumscribed in the majority of lesions but may be ill-
defined ,, surrounding edema is present in the majority of
cases
-Calcification, necrosis, cystic appearance, and ring
enhancement are uncommon ,, However, cystic
appearance may present in immunosupressed ptns
-CT chest , neck , abd , pelvis : to exclude presence of any
nodal or extranodal affection

10. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
2-CSF analysis :
-+ve in about 30 % of cases
-should be performed either before or at least one week
after surgical biopsy to avoid false-positive results
-The CSF analysis should include cell counts, protein and
glucose ,cytology, flow cytometry, and immunoglobulin
heavy-chain gene (IgH) rearrangement studies by
polymerase chain reaction (PCR)
-IPT using antibodies against lymphocytic antigens is
helpful in detecting the lymphoid origin and clonality of the
malignant cells, differentiate between B-and T subtype

11. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
3-Slit Lamp examination :
-used to exclude occular involvment
-also ocular involvement can be evaluated with biopsy of
the vitreous, choroid, or retina
4-biopsy :
-Stereotactic needle biopsy of involved tissue is the
diagnostic procedure of choice for PCL
-Tumors evaluated based on morphology and
immunophenotype ,, most of tumors are of aggressive
diffuse large cell subtypes, and almost all are of B-cell
origin

12. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
-The most common histopathologic subtype of PCL is
diffuse large B-cell lymphoma
-Tumors tend to infiltrate along the perivascular spaces
and surrounding parenchyma, occasionally invading the
blood vessel wall
-use of corticosteroids prior to biopsy better to be avoided
as these agents are lymphocytotoxic and single injection
is known to affect proper histopathologic evaluation

13. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
PRETREATMENT EVALUATION
Full lab including CBC, chemistries with liver and renal
function and electrolytes, (LDH), and serologic testing for
HIV
slit lamp examination even in the absence of visual
symptoms
CSF analysis
Pan CT
BMA ,, BMB
Performance status
Spine MRI if symptomatic or +ve CSF

14. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
INITIAL TREATMENT
1-role of surgery :
-usually limited to stereotactic biopsy for tissue diagnosis.
-Extensive resection is usually impractical, because of
deep location and multifocal nature of most of these
tumors.
-There is also no evidence that extensive surgical
resection provides removal of infiltrating margins of PCL.
The median survival time of patients with PCL treated with
surgery alone is less than four months ,, However surgical
resection may be considered in patients with an increased
risk of herniation, uncontrolled mass effect, or single ,
well-defined, and easily accessible lesion

15. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
2-cortico steroids :
dexamethasone is the most commonly used preparation,
and is often given at a starting dose of 4 mg PO four times
per day,,should be continued at full doses until the
radiation course has been completed. The dose can then
be tapered
3-Anticonvulsants :
Used for patients with documented seizure activity

16. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
4-Radiation therapy :
-PCL is extremely sensitive to radiation therapy
-Radiation alone had been the initial therapy of choice
prior to studies of high-dose systemicmethotrexate, which
provided superior survival rates with less long-term toxicity
-Radiation therapy remains an option for the palliative
treatment of patients who are not candidates for high dose
systemic chemotherapy.
-corticosteroids should be administered to avoid cerebral
edema and symptomatic elevation of intracranial pressure.
caused by XRT-induced brain edema

17. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
-in younger patients RTH cane be used after
chemotherapy
-but in older patients its option to postpone whole brain
radiation therapy until disease progression to avoid side
effects specially neurotoxicity
-radiation plus corticosteroids may be used for the
palliation of patients who are not candidates for
chemotherapy
-standard dose is 20 to 40 cGy
-with RTH alone survival 10-18 m ,, the disease tends to
recur in >90 % of patients within one year of treatment

18. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
5-chemotherapy :
-use of chemotherapy increase survival to 44 m
-Chemotherapy regimens that use high dose
systemicmethotrexate( 3.5 : 8 gm / m2 every 2 w for 6-8
doses) appear more effective than without MTX
-for younger patients with a good performance status , the
goal of induction therapy is to achieve a complete
response ,, its suggested to use combination of MTX plus
cytarabineor the combination of MTX,rituximab,
andtemozolomide(MTR) or rituximab,
methotrexate,procarbazine,vincristine(R-MPV)

19. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
-The administration of high-doseMTX must be performed
at specialized centers with laboratory support for the
measurement of its levels. Adjustment for renal
dysfunction is necessary.
-HDMTX can cause an acute elevation in the serum
transaminases from two to twenty-fold normal levels, even
in patients who receiveleucovorinrescue ,, rarely cause
elevation of bilirubin ,, specially in patients with liver
cirrhosis when total dose exceed 3 gm
-other include renal ,, hematological ,, GIT ,, neurotoxicity

20. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
6-palliation :
-For older patients who are unable to tolerate high-dose
systemicMTX >> either WBRTH or temozolamide +
rituximab
7-role of transplant :
-High dose chemotherapy supported by autologous
hematopoietic cell transplantation (HCT) is being
investigated in younger patients with a good performance
status who have achieved a complete response as at least
half of patients with PCL who achieve CR will relapse
within five years

21. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
8-IT chemotherapy : limited to patients with +ve
lymphomatous infiltration in CSF analysis ,, given twice
weekly untill CSF become –ve then at least two more
doses are given
9-for 1ry occular lymphoma : in addition to systemic
therapy ,, we can use occular radiation ,, intravitreal MTx
or intravitreal rituximab

22. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
Response to treatment :
1-CR : if there is complete disappearance of all enhancing
abnormalities on gadolinium-enhanced MRI and the
patient has not received any corticosteroids for at least
two weeks. Patients who had prior ocular involvement
should have no evidence of active ocular lymphoma.
Patients with previous cerebrospinal fluid (CSF)
involvement should have negative CSF studies
2-PR : no new sites of disease, at least a 50 percent
decrease in the contrast-enhancing lesion seen on MRI
compared with baseline, and a decrease in the vitreous
cell count ,, CSF
3-stable or progressive disease

23. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
TREATMENT OF REFRACTORY OR
RELAPSED DISEASE
-Retreatment withMTX(ie, 3 to 8 g/m
2
) or MTX-based
combination chemotherapy if there has been a prior
complete remission with this agent.
-Alternative chemotherapy regimens
(eg,topotecan,cytarabine,temozolomide(100 to 200
mg/m
2
on days 1 to 7 and 15 to 21) + Rituximab (750
mg/m
2
on days 1, 8, 15, and 22),including high dose
chemotherapy followed by autologous hematopoietic cell
transplantation (HCT).
-Whole brain radiation therapy in previously non-irradiated
patients. Stereotactic radiotherapy may be an option for
patients who have received whole brain radiation

24. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
TREATMENT OF REFRACTORY OR
RELAPSED DISEASE
-Retreatment withMTX (ie, 3 to 8g/m
2
)or MTX-based
combination chemotherapy if there has been a prior CR
with this agent.
-Alternative chemotherapy regimens
(eg,topotecan,cytarabine,temozolomide(100 to
200mg/m
2
on days 1 to 7 and 15 to 21)+ rituximab
(750mg/m
2
on days 1, 8, 15, and 22),including high dose
chemotherapy followed by autologous hematopoietic cell
transplantation (HCT).
-Whole brain radiation therapy in previously non-irradiated
patients. Stereotactic radiotherapy may be an option for
patients who have received whole brain radiation

25. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center

26. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center

27. 1ry CNS lymphoma
OCMU
Mansoura University
Oncology Center
Prognosis
-PCL associated with high recurrence rates
-different factors associated with poor prognosis as :
Age >60 years
ECOG performance status >1
Elevated serum level of lactate dehydrogenase
Elevated CSF protein concentration
Involvement of deep regions of the brain (periventricular
regions, basal ganglia, brainstem, and/or cerebellum)