Case Study 5
Gabrielle Yeaney, M.D.
Question 1
63-year-old female with progressive weakness of upper
and lower extremities, in additiona to confusion, who is
s/p CABG 2 years prior; history of smoking 2-1/2 packs a
day for several years.
Describe the MRI findings (location, enhancement, mass
effect).
MRI T2 FLAIR images
MRI T1 pre and post contrast
MRI side-by-side FLAIR and postcontrast images
Answer
Several abnormal FLAIR lesions are noted in bilateral
cerebral peduncles, basal ganglia and deep white
matter. Areas of enhancement include (1) left posterior
limb of the internal capsule; (2) right basal ganglia; (3)
deep and peripheral white matter of the right centrum
semiovale posteriorly; (4) right cerebral peduncle (not
pictured). There is no midline shift and no effacement of
the sulci or ventricles.
Question 2
Give a differential diagnosis based on MRI.
Answer
 Lymphoma
 Metastasis
 Gliomatosis cerebri
 Infectious disease (Toxoplasmosis, Amebic
encephalitis, Viral, PML)
 Demyelinating lesion (Multiple sclerosis)
 Multiple infarcts (Embolic / Vasculopathy)
Question 3
A stereotactic biopsy of the left internal capsule is
performed. Before you leave the OR, you ask the
surgeon for additional clinical history. What might be
helpful given what you know about the patient's history?
Answer
Given her age and history of smoking, it would be helpful
to know if full body CT was performed and were there any
masses. Also, is there any previous history of
malignancy? An signs/symptoms of infection? What did
CSF show? Did she receive any previous treatment
(steroids)?
Question 4
The surgeon tells you that a full body CT showed no
masses, an HIV test was negative and the CSF showed
lymphocytes. You receive 2 cores of tissue in
consultation for intraoperative guidance. Describe the
cytologic features of the touch prep and smear.
Click here to view slides.
Answer
The smear is more cellular than normal white
matter. Both the touch prep and smear show abundant
large cells with high N:C, nuclear pleomorphism, clumped
chromatin, multiple nucleoli. The tumor cells are
dyshesive. There are several mitotic figures, apoptotic
figures and lymphoglandular bodies.
Question 5
What is your intraoperative diagnosis? (A.
Neoplastic/Defer/Non-neoplastic, B. ________)
Answer
A. Neoplastic
B. Lymphoma
Question 6
What immunohistochemical studies would you get on the
permanent sections to validate your diagnosis?
Answer
LCA, CD20/L26 & CD3. Other hematopoietic markers (ie
CD79a, kappa, lambda, CD10, MUM-1, etc) and
vimentin/GFAP (to highlight gliosis) might also be helpful
in certain cases.
Question 7
Review the permanent section and describe the
microscopic features.
Click here to view slide.
Answer
Neoplastic cells are arranged in sheets with foci of
perivascular cuffing. The neoplastic cells are large-tomedium sized with atypical nuclear contours, moderate
amphophilic cytoplasm, vesicular chromatin and multiple
prominent nucleoli. There are frequent apoptotic figures
and mitotic figures.
Question 8
Review the following immunohistochemical studies and
reticulin stain and give your interpretation.
Click here to view slides.
Answer
Immunohistochemical studies show that the large atypical
cells express CD20, LCA and BCL2. There are scattered
small CD3-positive T cells in the background. GFAP
highlights reactive astrocytes. Ki-67 shows a very high
proliferation index (>95%). A reticulin stain highlights an
increase in perivascular reticulin fibers in areas with tumor
cells.
Question 9
What is your final diagnosis?
Answer
(Primary) Diffuse large B-cell lymphoma or Large cell
lymphoma, CD20-positive (previously known as reticulum
cell sarcoma due to the bands of reticulin that form
around vessel walls--see reticulin slide Q8).
Question 10
Secondary involvement by lymphoma is most common in
what part of the CNS?
Answer
Dura / leptomeninges
Question 11
What is the most common type of primary CNS
lymphoma?
1.Hodgkins lymphoma
2.Lymphoblastic lymphoma
3.T-cell lymphoma
4.Diffuse large B-cell lymphoma
Answer
Diffuse large B-cell lymphoma
Question 12
What are some diseases associated with PCNSL?
Answer
 HIV infection
 Immunosuppressive therapy (post transplantation)
 Hodgkin's disease
 Epstein-Barr virus
 Primary immunodeficiency syndromes: Wiskott-Aldrich,
X-linked lymphoproliferative, Severe combined
immunodeficiency, Ataxia-telangiectasia
Question 13
True or False.
Intravascular lymphomatosis affects multiple organ
systems but rarely involves the CNS.
Answer
False
Question 14
In a separate case, a 70-year-old woman who presented with two
weeks of imbalance, right lower extremity weakness, decrease in
taste, decrease in short-term memory, blurred vision on the left, and
decreased hearing on the left. MRI showed an enhancing left
posterior corona radiata lesion extending to the corpus callosum. She
was placed on corticosteroids with improvement in her
symptoms. Biopsy was done, and a diagnosis of primary central
nervous system lymphoma (PCNSL) was rendered. Review this
patient's biopsy. Note the differences from the previous case. What
do you think caused the histologic differences in this patient
compared to the previous case?
Click here to view slides.
Answer
Cellularity is relatively lower, gliosis is more prominent
and apoptotic figures abound in this biopsy. This case
could easily be mistaken for infection or glioma without
immunohistochemical studies to reveal the CD20-positive
tumor cells. Why? This patient received steroids prior to
surgery.