Introduction
Epidemiology
Primary central nervous system lymphoma (PCNSL) has an incidence of ∼0.4 per 100,000,
increasing with age and seen more in males, immunocompromised individuals, and Western
populations.[1]
Molecular Pathogenesis and Classification
PCNSL, also known as reticulum cell sarcoma, diffuse histiocytic lymphoma, and microglioma,
accounts for ∼90% of cases of diffuse large B cell lymphoma (DLBCL), with the remaining
cases consisting of T cell lymphomas, poorly characterized low-grade lymphomas, or
Burkitt lymphoma.[1]
[2]
The DLBCL subtype of PCNSL is marked by immunoblasts or centroblasts arranged around
blood vessels, showing an angiocentric growth pattern.[2] Though of lymphoid origin, PCNSL is classified as a brain tumor due to its central
nervous system (CNS) localization.[2] Treatment is complicated by the blood–brain barrier and risks of cerebral toxicity.[2] Immunoglobulins contribute by binding to CNS-expressed self-proteins. Genetic alterations
often involve B cell receptor signaling, toll-like receptors, and nuclear factor κ-light-chain-enhancer
of activated B cells pathways. Clinical presentation depends on the specific CNS regions
affected.[2]
Early genetic alterations in DLBCL PCNSL include mutations in the B cell receptor
pathway and alterations in myeloid differentiation primary response 88 (MYD88), CD79B,
and the loss of CDKN2A. These genetic changes suggest that these pathways may significantly
contribute to the initial tumorigenesis of PCNSL.[2]
In the context of the human immunodeficiency virus (HIV) associated with PCNSL, Epstein–Barr
virus (EBV) plays a crucial role in the malignant transformation of cells. EBV induces
the expression of oncogenic genes, including latent membrane proteins (LMP-1 and LMP-2),
EBV nuclear antigen, and EBV-encoded RNAs). Although EBV is not replicated within
the CNS, infected cells are believed to originate outside the CNS and infiltrate as
the patient's immune system deteriorates.[3]
Presentation
PCNSL) often presents with rapidly progressing neurological symptoms that may mimic
conditions such as multiple sclerosis or manifest as vitritis. Common features include
personality changes, cognitive decline, and limb weakness due to white matter involvement,
especially in the corpus callosum and internal capsule. Hemorrhagic lesions can cause
language deficits and paresis. Signs of cerebral edema—headache, vomiting, and hiccups—are
frequent. In patients with acquired immunodeficiency syndrome (AIDS), seizures are
a more common presentation. Though primarily a CNS disease, systemic involvement may
occasionally coexist.
Diagnosis
Diagnosis is typically established through computed tomography (CT) or magnetic resonance
imaging (MRI). Whole body CT or positron emission tomography (PET) is done to rule
out the occurrence of any systemic malignancy, ophthalmic examination, cerebrospinal
fluid (CSF) analysis, and stereotactic needle biopsy.[1]
Treatment
Following diagnostic confirmation, the mainstay of therapy involves high-dose methotrexate
(HD-MTX) with or without cytarabine, whole-brain radiotherapy (WBRT), and rituximab.
First-line treatment typically involves induction and consolidation stages. Induction
therapy is based on MTX with or without rituximab or cytarabine. Consolidation therapy
may include low-dose WBRT, Ara-C (cytarabine), etoposide, and autologous stem cell
transplantation (ASCT) with thiotepa-based conditioning.[2]
The few available treatment regimens for PCNSL are rituximab, methotrexate, procarbazine,
and vincristine (R-MPV); methotrexate, temozolomide, and rituximab (MTR); HD-MTX,
Ara-C (cytarabine), Thiotepa, Rituximab (MATRix); HD-MTX, De Angelis; WBRT alone; and ASCT. The pros and cons are
summed up in [Table 1].
Table 1
Summing up the pros and cons of different regimes available
|
Regimen
|
Pros
|
Cons
|
|
R-MPV
|
Effective and shows a high response
|
Adverse effects are neurotoxicity; however, its intensive nature can be a pro and
a con
|
|
MTR
|
Good for the elderly and people showing immunocompromised status or organ dysfunction
|
Slightly lower complete response rate
|
|
MATRix
|
Highly effective
|
Very toxic
|
|
This is usually repeated for two to four cycles, often followed by consolidation with
autologous stem cell transplant or whole-brain radiotherapy in eligible patients
|
|
|
HD-MTX
|
Simple
|
Low response
|
|
De Angelis
|
One of the first to show high complete remission rates
|
However, concerns about neurotoxicity, particularly in older patients, have led to
the development of alternative regimens with better tolerability
|
|
WBRT alone
|
Quick relief
|
Not durable
|
|
ASCT
|
Excellent long-term outcomes in fit patients
|
|
Abbreviations: ASCT, autologous stem cell transplantation; HD-MTX, high-dose methotrexate;
MTR, methotrexate, temozolomide, and rituximab; MATRix, HD-MTX, Ara-C (cytarabine),
Thiotepa, Rituximab; R-MPV, rituximab, methotrexate, procarbazine, and vincristine; WBRT, whole-brain
radiotherapy.
- De Angelis typically includes the following agents:
Drugs used in immunotherapy are: monoclonal antibodies, such as rituximab, checkpoint
inhibitors, such as nivolumab and pembrolizumab, bispecific T cell engagers, including
blinatumomab (CD19 × CD3), chimeric antigen receptor T cell anti-CD-19 (currently
under trials); others, lenalidomide, pomalidomide, and mechanistic target of rapamycin
inhibitors.
An optimal diagnostic workup for PCNSL includes neurological and ophthalmological
evaluation, contrast-enhanced MRI or CT of the brain, and spinal MRI if indicated.
Diagnosis requires a stereotactic brain biopsy, ideally before corticosteroid use.
CSF analysis should include cytology, flow cytometry, and EBV polymerase chain reaction.
For ocular involvement, slit-lamp examination and vitreous biopsy are advised. Systemic
disease must be ruled out with PET-CT, bone marrow biopsy, and testicular ultrasound
(in males). Baseline laboratory tests should include complete blood count, liver and
renal function tests, lactate dehydrogenase, HIV, hepatitis B and C serologies, and
cardiac evaluation.
This report presents five cases of primary CNS lymphoma to discuss the clinical presentation,
diagnostic approach, and treatment strategies.
Case Series
Case 1
A 59-year-old man with a known history of Type II diabetes mellitus presented with
complaints of headache and vomiting persisting for 15 days. Additionally, the patient
exhibited acute-onset neuropsychiatric symptoms of the same duration, which were rapidly
progressive. These included decreased sleep, aimless searching behavior, paranoid
ideation, fearfulness, irrelevant speech, self-talking, confusion, irritability, and
diminished oral intake. The clinical picture progressed to persistent nocturnal wakefulness
and a disoriented state suggestive of delirium, possibly due to PCNSL. Routine serum
electrolyte analysis was within normal limits.
A contrast-enhanced computed tomography (CECT) scan of the brain demonstrated a well-defined
hypodense lesion with peripheral ring enhancement located in the body of the corpus
callosum. Further neck, chest, abdomen, and pelvis imaging showed no abnormalities.
Subsequently, an open brain biopsy was advised, and the patient was referred to a
tertiary care center specializing in psychiatric, neurological, and neurosurgical
conditions.
Histopathological analysis revealed sheets of small- to medium-sized lymphoid cells
with crushed artifacts, a finding characteristic of lymphoma. The diagnosis of Grade
II PCNSL was confirmed through histopathology and supported by immunohistochemistry
(IHC) ([Fig. 1]).
Fig. 1 (A) ×10, (B) ×40, and (C) ×100. Histopathology showing small- to medium-sized lymphoid
cells in sheets with a crush artifact.
The patient was initiated on the R-MPV chemotherapy protocol, which includes rituximab,
methotrexate, procarbazine, and vincristine. The treatment regimen comprised the following
dosing schedule: methotrexate 3.5 g/m2 intravenous (IV) on days 2 and 16; procarbazine 100 mg/m2 orally on days 7 through 13; vincristine 1.4 mg/m2 (maximum dose 2.0 mg) IV on days 2 and 16; and rituximab 500 mg/m2 IV on days 1 and 15. A total of six chemotherapy cycles was planned.
Follow-up MRI showed tumor regression with marked clinical improvement, and the patient
has remained well on regular follow-up for 5 years.
Learning Points
Primary CNS lymphoma can present with rapidly progressive neuropsychiatric symptoms,
especially when midline structures are involved. Diagnosis requires biopsy and IHC
due to nonspecific imaging findings. The R-MPV regimen is the standard first-line
treatment, with high-dose methotrexate as its cornerstone. Early diagnosis and prompt
therapy are essential for optimal outcomes. This case demonstrates durable remission
with a 5-year disease-free follow-up.
Case 2
A 64-year-old man presented with complaints of abdominal pain persisting for 1 month,
accompanied by two to three episodes of vomiting daily. To evaluate the underlying
cause, a whole-body PET/CT scan was performed. Imaging revealed metabolically active,
ill-defined enhancing lesions in the subependymal region of both the lateral third
and fourth ventricles. No other metabolically active lesions were identified in the
rest of the body. Laboratory reports were sought, and serum creatinine was 1.4 mg/dL.
Based on these findings, the patient was initiated on the MTR chemotherapy regimen
comprising methotrexate, temozolomide, and rituximab. He was admitted and received
methotrexate 8 g/m2 intravenously on days 1 and 15; temozolomide 150 mg/m2 orally on days 7 through 11; and rituximab 375 mg/m2 intravenously on days 3 and 17. A total of six chemotherapy cycles was planned.
The patient tolerated the immunochemotherapeutic regimen well and demonstrated symptomatic
improvement. Upon completion of the planned treatment, a follow-up whole-body and
brain PET/CT scan was advised 1 month later. The posttreatment scan, dated January
16, 2025, compared with the baseline scan from August 20, 2024, demonstrated resolution
of the previously identified metabolically active lesions in the subependymal regions
of both lateral ventricles and the third and fourth ventricles. No new metabolically
active lesions were identified in the whole-body survey. These findings indicated
a favorable response to therapy ([Fig. 2]).
Fig. 2 Pre- and postchemotherapy scans suggest good tolerance to treatment, with favorable
comparative findings.
Learning Points
Primary CNS lymphoma can present as isolated subependymal and intraventricular lesions
without systemic involvement. The MTR regimen is effective for such presentations.
PET/CT is essential for both diagnosis and treatment monitoring. Early therapy can
achieve complete metabolic remission, as seen in this case.
Case 3
A 61-year-old man presented with complaints of imbalance and headache for 2 days,
accompanied by progressive weakness in both lower limbs. The onset of symptoms was
gradual, with steady deterioration. The patient had a known history of chronic liver
disease.
A noncontrast CT scan of the brain revealed ill-defined heterogeneous density lesions
in the bilateral cerebellar hemispheres, extending into the bilateral middle cerebellar
peduncles and the pons. Additionally, a lesion was noted involving the pons and bilateral
dentate nuclei, with diffuse hypodensity across the pons ([Fig. 3]). A whole-body PET/CT scan was performed, which showed no other metabolically active
lesions elsewhere in the body.
Fig. 3 Space-occupying lesion in the cerebellum extending to the pons (lesion marked with
red arrow).
The patient was admitted with a presumptive diagnosis of PCNSL and planned for MTR
chemotherapy. However, treatment was initially delayed due to the development of pneumonia
caused by Klebsiella pneumoniae. Following stabilization with appropriate antibiotic therapy, the patient was initiated
on the MTR chemotherapy regimen, similar to the second case. This included MTR, with
six planned cycles. The patient completed four cycles before being lost to follow-up.
Despite this, clinical improvement was observed, with signs of neurological recovery
and symptomatic relief noted during treatment.
Learning Points
Primary CNS lymphoma can involve the cerebellum and brain stem, presenting with imbalance
and limb weakness. PET/CT is vital to confirm isolated CNS disease. The MTR regimen
is effective but may be delayed by infections in immunocompromised patients. Even
partial treatment can lead to neurological improvement, as seen in this case.
Case 4
A 74-year-old woman with a known history of Type II diabetes mellitus presented with
acute-onset memory loss lasting 1 day. There was no associated history of headache,
trauma, fever, visual disturbances, loss of consciousness, giddiness, seizures, or
vomiting.
MRI of the brain revealed a lesion in the left frontal region with both intra- and
extracranial extension, resulting in displacement of the frontal lobe. Based on clinical
and radiological evaluation, an initial diagnosis of invasive meningioma was considered.
The patient underwent a bicoronal incision with frontal craniotomy and complete excision
of the lesion, followed by mesh placement under general anesthesia. The intra- and
extracranial components and the involved bone were submitted for histopathological
examination.
Microscopic evaluation revealed sheets of a cellular neoplasm composed of large atypical
cells with regular nuclear membranes, hyperchromatic nuclei, prominent nucleoli, and
moderate cytoplasm. The tumor cells were interspersed with thin-walled blood vessels
([Fig. 4]). IHC showed that the neoplastic cells were positive for CD45 and CD3, indicating
a T cell lineage ([Fig. 5]). The final diagnosis was PCNSL, T cell type, involving the frontal lobe.
Fig. 4 (A) Histopathology showing sheets of lymphoid cells (hematoxylin and eosin [H & E],
×40). (B) Histopathology showing sheets of small- to medium-sized lymphoid cells having
hyperchromatic nuclei (H & E, ×100).
Fig. 5 (A) Immunohistochemistry showing CD45 positivity (×200). (B) Immunohistochemistry
showing CD3 positivity (×200).
The patient was initiated on the R-MPV chemotherapy regimen following the protocol
described in Case 1. Six cycles of chemotherapy were planned. Three weeks after completing
chemotherapy, the patient was started on radiotherapy, receiving a total dose of 54
Gy in 30 fractions over 6 weeks.
Upon completion of both chemotherapy and radiotherapy, the patient was advised to
follow-up with a CECT) scan of the brain after 1 month. The imaging showed regression
of the previously noted lesion.
However, 2 months later, the patient presented with new-onset behavioral disturbances
and disorientation. A repeat MRI of the brain demonstrated postoperative changes in
the left frontal lobe with gliosis and a subacute hematoma. Real-time ultrasonography
of the abdomen revealed additional findings, leading to a final diagnosis of recurrent
PCNSL postchemotherapy and radiotherapy, with newly diagnosed metastatic carcinoma
of the pancreas, metabolic encephalopathy, and obstructive jaundice.
Given her declining condition and poor prognosis, the patient's relatives declined
further radiotherapy. Repeat cycles of R-MPV chemotherapy were initiated; however,
her clinical condition continued to deteriorate. The patient was transitioned to symptomatic
and supportive care and ultimately succumbed to complications of PCNSL.
Learning Points
Primary CNS lymphoma can mimic invasive meningioma, especially with intra- and extracranial
extension. This case highlights the rare, aggressive T cell variant of PCNSL, confirmed
by CD45 and CD3 positivity. Despite initial response to R-MPV chemotherapy and radiotherapy,
recurrence and systemic complications led to poor prognosis, emphasizing the need
for vigilant follow-up.
Case 5
A 39-year-old woman, known to be HIV positive and on antiretroviral therapy consisting
of tenofovir 300 mg, lamivudine 300 mg, and dolutegravir 50 mg, presented with a history
of persistent headaches over the past 6 months. Clinical evaluation revealed altered
sensorium and disorientation, symptoms that had gradually worsened over the previous
3 months. The neurological decline followed intermittent episodes of fever accompanied
by chills and headache.
Initial investigations conducted at an external facility included CSF analysis, CT
of the head, and both plain and contrast MRI of the brain. Additionally, PET/CT of
the whole body was performed to rule out systemic malignancy. Based on the clinical
and radiological findings, a diagnosis of PCNSL was established.
The patient was noted to be emotionally distressed, particularly apprehensive about
the future care of her children. Progressive memory impairment was observed, and a
secondary diagnosis of depressive disorder due to an organic condition was made. Laboratory
findings revealed elevated total leukocyte and platelet counts. MRI of the brain demonstrated
significant contrast enhancement of altered signal intensity foci in the splenium
of the corpus callosum and the right gangliocapsular region.
The patient was scheduled to receive the MTR chemotherapy regimen, consisting of methotrexate,
temozolomide, and rituximab, following the same protocol described in Case 2. A total
of six chemotherapy cycles was planned. Three weeks after initiation of chemotherapy,
the patient underwent focal radiotherapy to the lesion, receiving a dose of 14.4 Gy
in eight fractions.
During the administration of the sixth cycle of immunochemotherapy, the patient developed
pneumonia and experienced difficulty maintaining adequate oxygen saturation on room
air. She was managed with a non-rebreather mask and intravenous antibiotics after
being transferred to the intensive care unit. Despite supportive treatment, her condition
deteriorated due to underlying immunosuppression, and she ultimately succumbed to
opportunistic infections, likely exacerbated by low CD4+ T cell counts.
Learning Points
Primary CNS lymphoma is common in immunocompromised patients, especially those with
HIV/AIDS. This case highlights PCNSL involving the corpus callosum and basal ganglia
in an HIV-positive patient, treated with MTR chemotherapy and focal radiotherapy.
Opportunistic infections, such as pneumonia, are a major cause of mortality during
treatment due to immunosuppression and low CD4+ counts. The case underscores the need
for infection vigilance and supportive care in HIV-associated PCNSL.
A summary of the case series is noted in [Tables 2] and [3].
Table 2
Summary of case series
|
Case number
|
Presentation
|
Diagnosis
|
Treatment
|
Survival and follow-up
|
|
1
|
59-year-old man with Type II diabetes, headache, vomiting, abnormal behavior, delirium
|
PCNSL Grade II confirmed by biopsy and IHC
|
R-MPV
|
Regression of tumor size with symptomatic improvement. Regular follow-up planned
|
|
2
|
64-year-old man with abdominal pain and vomiting, metabolically active
|
PCNSL diagnosed through imaging (PET/CT).
Lesions on PET/CT in subependymal regions
|
MTR
|
Good response to therapy. No new lesions observed in follow-up PET/CT
|
|
3
|
61-year-old man with imbalance, headache, and weakness
|
PCNSL suspected based on CT findings. Confirmed by biopsy and imaging.
CT showed lesions in cerebellar hemispheres and pons
|
MTR
|
Improvement during initial treatment but failed to complete all planned cycles due
to non-compliance.
|
|
4
|
74-year-old woman with memory loss
|
PCNSL diagnosed as T cell type by biopsy and IHC. Lesion in left frontal region on
MRI. Suspected invasive meningioma
|
R-MPV chemotherapy and radiotherapy (54 Gy/30 fractions)
|
Recurrent symptoms posttreatment developed pancreatic metastasis. Eventually succumbed
to the disease
|
|
5
|
39-year-old woman with HIV, progressive memory disturbances
|
PCNSL diagnosed based on imaging (MRI), confirmed by biopsy. Contrast enhancement
in corpus callosum and gangliocapsular region
|
MTR chemotherapy and radiotherapy (54 Gy/30 fractions)
|
Developed pneumonia during treatment, succumbed to opportunistic infections due to
low CD4+ counts
|
Abbreviations: IHC, immunohistochemistry; HIV, human immunodeficiency virus; MRI,
magnetic resonance imaging; MTR, methotrexate, temozolomide, and rituximab; PCNSL,
primary central nervous system lymphoma; PET/CT, positron emission tomography/computed
tomography; R-MPV, rituximab, methotrexate, procarbazine, and vincristine.
Table 3
Summary of demographic and clinical variables in five PCNSL cases
|
Variable
|
Value/distribution
|
|
Number of cases
|
5
|
|
Mean age (y)
|
59.4 (39–74)
|
|
Sex distribution
|
3 males, 2 females
|
|
Comorbidities
|
Diabetes: 2
HIV: 1
Chronic liver disease: 1
|
|
Initial presentation
|
Headache: 4
Cognitive changes: 3
Vomiting: 3
|
|
Lesion locations
|
Corpus callosum: 2
Frontal: 1
Cerebellum/pons: 1
Subependymal: 1
|
|
Chemotherapy regimens used
|
R-MPV: 2
MTR: 3
|
|
Survival status
|
Alive and under follow-up: 2
Lost to follow-up: 1
Deceased: 2
|
|
Follow-up duration
|
4 mo to 5 y
|
Abbreviations: HIV, human immunodeficiency virus; MTR, methotrexate, temozolomide,
and rituximab; PCNSL, primary central nervous system lymphoma; R-MPV, rituximab, methotrexate,
procarbazine, and vincristine.
Discussion
PCNSL remains a rare and aggressive malignancy, frequently presenting with nonspecific
neurological symptoms such as headache, memory loss, and behavioral changes. Our cohort
reflected this, with headache being the most common symptom and the corpus callosum
emerging as a frequently involved site[4] ([Table 3]).
PCNSL is known to occur in both immunocompetent and immunocompromised patients. Among
the latter, especially HIV-positive individuals, the disease tends to have an aggressive
course with a median CD4+ count of 16 cells/μL at diagnosis.[3] Diagnostic imaging plays a crucial role; MRI and PET/CT help localize lesions and
differentiate PCNSL from mimics such as gliomas or infections. The classic imaging
features—iso- or hypointense on T1, slightly hyperintense on T2, and hyperintense
on fluid-attenuated inversion recovery, with strong gadolinium enhancement—are consistent
with PCNSL.[4]
[5]
[6]
[7] Involvement of the corpus callosum can produce a characteristic “butterfly lesion,”
and lesions may mimic gliomas or tumefactive demyelination, necessitating accurate
differentiation[8] ([Table 4]).
Table 4
Radiological differences between PCNSL and gliomas
|
Feature
|
PCNSL
|
Glioma
|
|
Typical location
|
Deep periventricular regions (e.g., corpus callosum, basal ganglia)
|
Anywhere in the brain; often lobar (frontal, temporal)
|
|
Enhancement pattern
|
Homogeneous, strong enhancement
|
Heterogeneous; often ring enhancing in high-grade gliomas
|
|
Edema
|
Mild to moderate vasogenic edema
|
Often marked vasogenic edema
|
|
Necrosis
|
Usually absent
|
Common in high-grade gliomas
|
|
Margins
|
Well defined
|
Often irregular and infiltrative
|
|
DWI
|
Restricted diffusion due to high cellularity
|
Variable; typically less restricted than PCNSL
|
|
MR spectroscopy
|
Elevated lipid/lactate peaks, decreased NAA
|
Elevated choline, decreased NAA, and creatine
|
|
Response to steroids
|
Marked reduction in size/enhancement
|
Minimal or no response
|
|
Contrast uptake
|
Intense, solid enhancement
|
Patchy or ring-like, especially in glioblastomas
|
Abbreviations: DWI, diffusion-weighted imaging; MR, magnetic resonance; NAA, N-acetylaspartate;
PCNSL, primary central nervous system lymphoma.
Histopathology and IHC remain the gold standards for confirming diagnosis. Our cases
demonstrated classic PCNSL features—sheets of atypical lymphoid cells with high nuclear-to-cytoplasmic
ratios and crush artifacts, confirmed by CD markers. While most PCNSL are B cell derived,
Case 4 was a rare CD3+ T cell lymphoma.
Treatment centered on high-dose methotrexate-based chemotherapy.[5]
[6]
[7]
[8] In immunocompetent patients with stable disease profiles (Cases 1 and 4), the R-MPV
regimen was used, followed by radiotherapy in Case 4.[9]
[10]
[11] In elderly or immunocompromised patients (Cases 2, 3, and 5), the MTR regimen was
preferred due to its safer toxicity profile. Radiotherapy was used postchemotherapy
in Cases 4 and 5.
Surgical intervention, though limited in PCNSL due to its infiltrative nature, was
done in Case 4, where the lesion was initially suspected to be a meningioma, later
confirmed as a rare T cell variant. This underlines the importance of tissue biopsy
before steroid initiation to avoid diagnostic confusion.
Outcomes varied: Cases 1 and 2 improved and are under follow-up; Case 3 showed an
initial response but was lost to follow-up; Case 4 relapsed and later succumbed; and
Case 5, an HIV-positive individual, died of opportunistic infections despite therapy.
These patterns align with the literature, which reports a 33% 5-year survival rate.[12]
[13] Quality of life improved notably in Cases 1 to 3 during therapy ([Tables 2] and [3]).
Emerging biomarkers such as MYD88 L265P and CD79B mutations, along with elevated CSF
cytokines such as CXCL13 and interleukin 10, are under investigation for diagnostic
and prognostic roles.[14]
[15] Liquid biopsy using CSF-derived circulating tumor DNA (ctDNA) may soon complement
tissue-based diagnostics, though validation is needed. The International Extranodal
Lymphoma Study Group prognostic score remains a helpful tool, especially in immunocompetent
individuals with deep brain involvement.[16]
Overall, PCNSL management requires early diagnosis, multimodal therapy, and personalized
care tailored to immune status, lesion site, and comorbidities. Our series highlights
real-world diagnostic and therapeutic variability, including uncommon variants such
as T cell PCNSL. While emerging biomarkers show promise, their integration into routine
clinical practice remains limited. This article reinforces the need for validated
prognostic tools, standardized treatment protocols, and long-term studies to optimize
PCNSL outcomes.
