Baylor University Medical Center Proceedings October 2017 - 443

Epstein-Barr virus-positive diffuse large B-cell lymphoma
Stacey L. Murthy, MD, Michael A. Hitchcock, MD, Tiana R. Endicott-Yazdani, MD, John T. Watson, MD, and John R. Krause, MD

While the World Health Organization included Epstein-Barr virus (EBV)-
positive diffuse large B-cell lymphoma (DLBCL) as a provisional entity of
a lymphoma occurring in older individuals without any known immunodeficiency in 2008, it has since been recognized that this entity may occur
in younger individuals. As a result, the 2016 revision has substituted the
modifier "elderly" with "not otherwise specified" (NOS). The NOS highlights that there are more specific entities with neoplastic EBV-positive
large B cells such as lymphomatoid granulomatosis. Diagnosis requires
that there be no other cause of immunodeficiency and that other more
specific entities with neoplastic EBV plus large B cells be excluded.
We present the case of an 81-year-old woman hospitalized for generalized weakness, increasing confusion, unexplained weight loss, and
intermittent fevers. Examination showed lymphadenopathy, lesions in the
liver and small intestine, and a very high EBV viral load. She experienced
a rapid demise and at autopsy was found to have EBV+ DLBCL, NOS.

CASE PRESENTATION
An 81-year-old white woman presented to the emergency
department after increased confusion and generalized weakness
followed by an unwitnessed fall at home. She had a 20-pound
weight loss over 2 months and intermittent fevers during the same
time. Her past medical history was notable for a cerebrovascular
accident 4 years prior, vascular dementia, diabetes mellitus type 2,
paroxysmal atrial ﬁbrillation, hyperlipidemia, gastroesophageal
reﬂux disease, and hypothyroidism. On admission, she had a temperature of 97.7°, blood pressure of 118/58 mm Hg, and heart
rate of 100 beats/min. Her blood work showed a white blood cell
count of 3.2 K/μL and a platelet count of 94 K/μL. Cultures and
testing for HIV, hepatitis B, hepatitis C, cytomegalovirus, and
parvovirus B19 were all negative. Her Epstein-Barr virus (EBV)
viral load was >1,100,000 IU/mL by polymerase chain reaction.
A computed tomography (CT) scan of the chest, abdomen, and
pelvis found multiple prominent lymph nodes. The abdominal
ultrasound showed thickening of the gallbladder, but no overt
cholecystitis. A CT of the head was negative. The patient was
started on broad-spectrum antibiotics for continued fever and
leukopenia, but treatment was discontinued because no source of
infection was identiﬁed. The patient continued to decline and did
not desire invasive life-sustaining measures; thus, comfort measures
were started on hospital day 13, and she died shortly thereafter.
Proc (Bayl Univ Med Cent) 2017;30(4):443-444

An autopsy was performed and revealed diﬀuse lymphadenopathy, especially in the paratracheal, periaortic, and peripancreatic areas. Microscopically, the lymph nodes showed massive
eﬀacement with inﬁltrates of large lymphoid cells (Figure 1a).
These cells had scant to moderate amounts of basophilic cytoplasm, large irregular nuclei, and prominent nucleoli, and they
focally extended through the capsules into the surrounding
adipose tissue and into lymphatic vessels. Similar collections
of atypical lymphoid cells were found in the lung interstitium,
liver portal tracts and sinusoids, splenic white and red pulp,
gastric submucosal vessels, epicardium, left atrium, and bone
marrow. Immunohistochemistry testing showed that the tumor was positive for CD20 (Figure 1b), MUM1, and BCL2,
had a proliferative index (Ki-67) of 60%, and was negative
for BCL6, CD3, cMYC, and CD10. In situ hybridization for
EBV (EBER-ISH) was positive (Figure 1c). The morphologic
and immunophenotypic results represent a diﬀuse large B-cell
lymphoma (DLBCL), post-germinal center type, consistent
with EBV-positive DLBCL, not otherwise speciﬁed (NOS).
DISCUSSION
EBV is a double-stranded, enveloped virus that belongs
to the Herpesviridae family. EBV shows tropism for epithelial
cells as well as B-cell lymphocytes (1, 2). Almost all humans
are exposed to EBV at some point in their life, and after exposure EBV confers a lifelong latency. This can cause problems
in the aging population. With age, the immune system enters
a state of immunosenescence characterized by a decrease in the
diversity of B cells, causing an in vivo clonal expansion. At the
same time, T-cell lymphocytes are decreasing in number with a
decline in naive T cells and T-cell receptor diversity (3). These
changes result in more circulating cells with EBV-speciﬁc receptors. Cells with latent EBV infection express EBER protein and
may express other proteins such as EBNA and LMP proteins (3).
EBV also induces the NFκB pathway, which may be required
for survival of the cells in DLBCL (2).
From the Departments of Pathology (Murthy, Hitchcock, Krause) and Internal
Medicine (Endicott-Yazdani, Watson), Baylor University Medical Center at Dallas,
Texas.
Corresponding author: John R. Krause, MD, Section of Hematopathology,
Department of Pathology, Baylor University Medical Center at Dallas, 3500 Gaston
Avenue, Dallas, TX 75246 (e-mail: jkrause@BSWHealth.org).
443

Table of Contents for the Digital Edition of Baylor University Medical Center Proceedings October 2017