infectious
mononucleosis*burkitt's lymphoma*nasopharygeal
carcinoma
Pathology
Acute infection
is characterized by fever, pharyngitis, swollen eyes, swollen lymphatics
including cervical lymphadenopathy. Splenomegaly occurs in 50% of
cases, hepatomegaly in 10% (1).
Diagnosis
The presence
of anti-EBV IgM is an excellent diagnostic indicator for acute EBV infection.
Although the host will contain antibodies against EBV for life, after the
initial 3-6 months, IgM and IgD are replaced by IgG antibodies against
EBV. Five different immunoflourescence tests have been developed
to detect viral antibody in patient serum. Currently, EBV-VCA IgM is the
most effective test for diagnosis in cases lacking heterophil antibody
(1).
Burkitt's Lymphoma
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Burkitt's lymphoma (BL) is a cancerous lymphoma comprised of "a monomorphic outgrowth of undifferentiated lymphoid cells with little variation in size and shape, an amphophilic cytoplasm with clear vacuoles, and a noncleaved nucleus containing two to five basophilic nucleoli" (2). At low magnification, a 'starry sky' pattern is observed, as a result of macrophage invasion (2).
All BL cases are characterized by a B-cell chromosomal shift involving chromosome 8, usually transposing with chromosome 14, less commonly with chromosome 2 or 22 (2). The infected B-lymphocytes undergo proliferation, synthesizing heavy chain IgM and expressing light-chain in the majority of BL tumors (2). A viral oncogene, c-myc, is involved in the transformation of B-cells by EBV and may be translocated to a more easily activated position during the chromosomal shift (2).
Diagnosis
The epidemiological
involvement of EBV in Burkitt's Lymphoma is based on the recognition of
the EBV viral genome in tumor cells, based on DNA fingerprinting, using
techniques such as Southern blotting and PCR (2).
An elevated antibody titer against EBV (VCA) is also observed in BL patients
(2).
Pathology
The majority
of BL cases in Africa are characterized by facial and abdominal tumors.
In the instances of facial cancer, the tumor usually begins in the alveolar
process of the jaw and extends downward, loosening the teeth. It
can also invade the nasopharynx and the orbit of the eye. Airway
obstruction and the inability to close one's mouth are also characteristic
of this form of BL. In the United States, BL is much rarer and is
usually not associated with EBV or facial cancers. However, in both
areas, abdominal involvement, characterized by kidney, ovarian, liver,
and gastrointestinal cancers are found (2).
Role of
Malaria
Falciparum
malaria is found in high association with EBV transformed Burkitt's lymphomas.
There are several ways in which this parasitic disease is thought to exacerbate
BL:
1. Primary
infection of EBV is necessary for future immortalization of B cells.
2. Falciparum
malarial infection causes a huge proliferation of B cells, including a
mitogenic effect increasing the chances that a chromosomally altered B
cell will be increased in number and then no longer subject to growth control
mechanisms.
3. A constant
malarial burden may specifically impair EBV T-cell immunity.
4. Malaria
may increase the number of B cells in various stages of differentiation,
and cells at different stages may be more susceptible to a chromosomal
translocation (2).
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Nasopharyngeal Carcinoma
Pathology
The tumor
originates in the nasopharynx, as implied by the nomenclature. Most
often it causes cervical nodal enlargement, nasal complications such as
obstruction, discharge, and epistaxis, aural complications from eustachian
tube obstruction, and more rarely involvement of the cranial nerves, persistent
headache, and stiffness of the jaw. The tumor can be metastatic, invasive,
or a combination of the two. The initial metastases tend to occur
in the cervical lymph nodes while later, distant metastases are found in
the spine, liver, lung, and skin. In the invasive type, cancer spreads
from the nasopharyngeal area to adjacent muscles, bones, cranial nerves,
nasal sinuses, and veins. Most (59%) of all cases are a combination
of metastatic and invasive tumors (3).
Diagnosis
Nasopharyngeal
carcinomas are diagnosed via biopsy which will contain EBV latent membrane
protein if associated with EBV (5). When associated
with EBV, human serum also contains a distinct antibody pattern with a
particularly high EA expression in conjunction with elevated VCA and EBNA
responses. Epstein-Barr viral DNA is found in tumor tissue (3).
A useful diagnostic marker
for nasopharyngeal
carcinoma can be obtained using serum in western blot analysis, enzyme-linked
immunosorbent assay (ELISA), and immunofluorescence tests for antibodies
to the EBV-coded alkaline deoxyribonuclease (DNase), thymidine kinase,
and membrane antigen (gp340/220) produced in recombinant baculovirus or
bovine papillomavirus systems (4).
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References
1.
Niederman, J.C., Evans, A.S. "Epstein-Barr Virus." Viral
Infections of Humans: Epidemiology and Control. New York: Plenum,
1997, 253-283.
2.
Evans, A.S., Mueller, N.E. "Epstein-Barr Virus and Malignant Lymphomas."
Viral
Infections of Humans: Epidemiology and Control. New York: Plenum,
1997, 895-933.
3.
de-Thé, G. "Nasopharyngeal Carcinoma." Viral Infections of Humans:
Epidemiology and Control. New York: Plenum, 1997, 935-967.
4.
Littler, E., Baylis, S.A., Zeng, Y., Conway, M.J., Mackett, M., Arrand,
J.R. Diagnosis of nasopharyngeal carcinoma by means of recombinant Epstein-Barr
virus proteins. Lancet. 1991 Mar 23;337(8743): 685-689.
5.
Stewart, J.P., Arrand, J.R. Expression of the Epstein-Barr virus latent
membrane protein in
nasopharyngeal carcinoma biopsy specimens. Hum-Pathol. 1993
Mar; 24(3): 239-242.
6.
http://www.ultranet.com/~jkimball/BiologyPages/B/Burkitt'sLymphoma.html
7.http://research.studentadvantage.com/cgi-bin/clickthrough.pl?http%3A%2F%2Fradiology.uchc.edu%2FCode%2F1281.htm