CLL case presentation

Presented by: Reem Eshra

Supervised by: Prof. Dr. Nadia Zaki
Presentation
A 68 year old male presented to the ER in October 2019 with a 2
week history of acute onset progressive right hemipareisis
progressing to hemiplegia, expressive aphasia and urinary
incontinence.

Patient initially sought medical advice at time of onset where CT

and MRI Brain were done revealing:
Expanding left parietal intra-axial subcortical mid convexity 2.4cm
x 1.8cm well defined lesion associated with perifocal oedema..
Suggestive of primary cerebral neoplasm
 History, physical &
neurological examination, and
evaluation of neurosurgical
urgency are always the first !Work up of solitary brain lesion!
step!

MRI Brain with contrast

Usually the only test needed to suggest a brain tumor.

Screening for systemic malignancy

The likelihood that a lesion is metastatic should be assessed prior to proceeding to biopsy or resection.
Brain metastases are more common than primary brain tumors in adults. Although brain metastases
usually present in the context of overt systemic disease, they can occur as the initial manifestation of a
systemic malignancy (They are single in 20 to 30 percent of patients)
Role of glucocorticoids
High-dose glucocorticoids effectively reduce cerebral edema and can improve headaches and
neurologic deficits caused by peritumoral edema. In patients with severe symptoms or
threatened herniation, the usual initial dose of dexamethasone is 10 mg, followed by 4 mg every
four hours or 8 mg twice per day. Lower doses are often sufficient for less severe symptoms
 Lumbar puncture
The primary role of lumbar puncture is to explore infectious or inflammatory etiologies in patients
with atypical or unusual neuroimaging findings. If lymphoma is considered a possibility on the
basis of imaging characteristics, CSF should be sent for cytology & flow cytometry

Antiseizure drugs
Patients presenting with a seizure and those who provide a clinical history suggestive of seizure activity should
be treated with an antiseizure drug. Levetiracetam is commonly used in this setting. Antiseizure drugs are not
generally recommended in patients who have never had a seizure, aside from perioperative prophylaxis

Histopathological examination
Accurate diagnosis of a brain tumor requires an adequate tissue sample for histopathologic and molecular
study
At time of presentation he also suffered high grade fever, and his family gave
history of significant weight loss in the preceding month.
There was no history of bleeding episodes, recurrent blood transfusions, night
fevers nor night sweats.
CBC on admission: incidentally revealed lymphocytosis:
Hb – 9.1 g/dL
Plts – 103 x10^3
WBCs – 134.5 x 10^3
Neutrophil count: 0.942 x 10^3
Lymphocytic count: 115.93 x 10^3
On examination: patient was conscious, alert but unable to express words
Head & Neck: mild pallor, palpable bilateral cervical lymphadenopathy
picture of UMN facial palsy
Chest: BEAE, palpable right axillary lymphnodes
Abdomen: lax, palpable splenomegaly
Extremities: right upper and lower limb paralysis with brisky reflexes
Patient was admitted, sepsis work up was done and IV antibiotics
were started

CBC Film showed moderate normochromic normocytic anaemia,

marked leukocytosis with absolute lymphocytosis, lymphocytes are
small, discrete with condensed chromatin and ‘many smudge cells’,
and thrombocytopenia.

Flow cytometry on a sample of peripheral blood was done

Patient was then transferred to haematology ward and low dose steroids were started.
Neurosurgery department were consulted and considered the diagnosis of a cerebral
abscess vs. CNS infiltration and recommended stereotactic biopsy.
However due to technical purposes a biopsy wasn’t possible.
CRP: 5
Virology: -ve
Fundus examination: no signs of increased ICP
Meanwhile CSF was sampled and sent for flow cytometry:
Immunophenotyping of CSF mononuclear cells using CD5, CD19, CD20, kappa &
lambda revealed the presence of a population of B-lymphocytes (30% of the gated
lymphocytes) that is positive for CD5, CD19 and CD20 concluding the diagnosis of:
A case of CLL with CNS infiltration
 Intrathecal triple therapy was started 3 times weekly
(methotrexate, cytrabine, dexamethasone)

Patient improved drastically within the first week until he was

independently mobile after 6 doses of intrathecal chemotherapy, and able
to express full sentences.
Patient then received one cycle of CVP followed by 5 days of Leukeran
(2mg 1x3 D1-D5)
Follow up CT Brain showed a decrease in size of neoplasm to 1.5cm x
1cm
He was then discharged and planned for HD-MTX after 21 days, as well
as twice weekly intrathecal chemotherapy.

Unfortunately, the patient was neglected and presented 10 days later in

severe sepsis and was admitted in the ICU.
 CLL with CNS involvement
CNS involvement of CLL is a poorly studied phenomenon in literature. The clinical manifestations of
CLL involvement of the CNS are heterogeneous which include headache, cerebellar signs, cranial
nerve palsies, visual problems, and motor or sensory deficits. There appears to be no correlation
between CNS involvement and disease stage in CLL, duration of CLL, gender, age, peripheral
leukocyte count or immunologic phenotype and interestingly most cases of CNS involvement by CLL
occurred in early stage and previously untreated patients. The time from CLL diagnosis to CNS
documentation of disease varied from 0 days to 15 years (median - 4.5 years).
Imaging studies are neither specific nor sensitive in the detection of CLL
involvement of the CNS.
The cornerstone for the diagnosis of CLL leukemic infiltration of the CNS is
proving the monoclonality of the cytologically abnormal malignant lymphocytes
in the CSF; however, interpretation of CSF analysis can be particularly difficult.
Hence, flow cytometry is often needed to distinguish between reactive
lymphocytes and CLL B cells and the presence of CLL B cells in the CSF does
not necessarily indicate CLL as the etiology of the patient’s neurological
disease. CLL cells tend to traffic to sites of inflammation and can often be
present as an innocent bystander in patients with infections or other
inflammatory conditions. Contamination of the CSF by peripheral blood (due
to bloody tap) can also result in detection of CLL B cells in the CSF. Hence a
complete comprehensive work up is necessary to exclude other etiologies of
neurological symptoms rather than assuming the mere presence of CLL B cells
in the CSF as an indication that CLL is the etiology of the patient’s neurological
symptoms. The specificity of the presence of CLL B cells in the CSF study is
relatively poor.
At present, there are no established guidelines for treatment of CLL
patients with CNS involvement. Most patients have been treated with
intrathecal chemotherapy with or without radiation therapy or systemic
chemotherapy. Intrathecal rituximab has been found to be effective in
aggressive B-cell lymphomas, however its efficacy in CLL has not been
reported. For CLL patients with indolent leptomeningeal disease,
fludarabine-based therapy has been found to be effective and may be a
favorable therapeutic option.
References:
https://www.uptodate.com/contents/overview-of-the-clinical-features-
and-diagnosis-of-brain-tumors-in-adults

CLL with CNS Involvement - A Diagnostic Dilemma Rakul Nambiar K1,

Anoop TM2* and Prakash NP3
https://actascientific.com/ASCB/pdf/ASCB-01-0005.pdf