Page 241 - Textbook of Pathology, 6th Edition

discussed earlier and directly affect cell growth by following of EBV in the first two human tumours is given below while 225
mechanisms: others have been discussed elsewhere in relevant chapters.
i) HPV integrates in to the host cell DNA which results in Burkitt’s lymphoma. Burkitt’s lymphoma was initially
overexpression of viral proteins E6 and E7 from high risk noticed in African children by Burkitt in 1958 but is now
HPV types. E6 and E7 from high-risk HPVs has high affinity known to occur in 2 forms—African endemic form, and sporadic
for target host cells than these viral oncoproteins from low- form seen elsewhere in the world. The morphological aspects CHAPTER 8
risk HPVs. of the tumour are explained in Chapter 14, while oncogenesis
ii) E6 and E7 viral proteins cause loss of p53 and pRB, the is described here.
two cell proteins with tumour-suppressor properties. Thus There is strong evidence linking Burkitt’s lymphoma, a
the breaks in cell proliferation are removed, permitting the B-lymphocyte neoplasm, with EBV as observed from the
uncontrolled proliferation. following features:
iii) These viral proteins activate cyclin A and E, and inactivate a) Over 90% of Burkitt’s lymphomas are EBV-positive in
CDKIs, thus permitting further cell proliferation. which the tumour cells carry the viral DNA. Neoplasia
iv) These viral proteins mediate and degrade BAX, a b) 100% cases of Burkitt’s lymphoma show elevated levels
proapoptotic gene, thus inhibiting apoptosis. of antibody titers to various EBV antigens.
v) These viral proteins activate telomerase, immortalising c) EBV has strong tropism for B lymphocytes. EBV-infected
the transformed host target cells. B cells grown in cultures are immortalised i.e. they continue
to develop further along B cell-line to propagate their progeny
ii) Polyoma virus. Polyoma virus occurs as a natural in the altered form.
infection in mice. d) Though EBV infection is almost worldwide in all adults
In animals—Polyoma virus infection is responsible for and is also known to cause self-limiting infectious
various kinds of carcinomas and sarcomas in mononucleosis, but the fraction of EBV-infected circulating
immunodeficient (nude) mice and other rodents. In view of B cells in such individuals is extremely small.
its involvement in causation of several unrelated tumours in e) Linkage between Burkitt’s lymphoma and EBV infection
animals, it was named polyoma. is very high in African endemic form of the disease and
In humans—Polyoma virus infection is not known to probably in cases of AIDS than in sporadic form of the
produce any human tumour. But it is involved in causation disease.
of polyomavirus nephropathy in renal allograft recipients However, a few observations, especially regarding spora-
and is also implicated in the etiology of progressive dic cases of Burkitt’s lymphoma, suggest that certain other
demyelinating leucoencephalopathy, a fatal demyelinating
disease. supportive factors may be contributing. Immunosuppression
appears to be one such most significant factor. The evidence
iii) SV-40 virus. As the name suggests, simian vacuolating in favour is as follows:
virus exists in monkeys without causing any harm but can Normal individuals harbouring EBV-infection as well as
induce sarcoma in hamsters. There is some evidence of cases developing infectious mononucleosis are able to mount
involvement of SV-40 infection in mesothelioma of the pleura. good immune response so that they do not develop Burkitt’s
2. HERPESVIRUSES. Primary infection of all the lymphoma.
herpesviruses in man persists probably for life in a latent In immunosuppressed patients such as in HIV infection
stage which can get reactivated later. Important members of and organ transplant recipients, there is marked reduction
herpesvirus family are Epstein-Barr virus, herpes simplex in body’s T-cell immune response and higher incidence of
virus type 2 (HSV-2) and human herpesvirus 8 (HHV8), this neoplasm.
cytomegalovirus (CMV), Lucke’s frog virus and Marek’s It is observed that malaria, which confers immuno-
disease virus. Out of these, Lucke’s frog virus and Marek’s suppressive effect on the host, is prevalent in endemic
disease virus are implicated in animal tumours only (renal proportions in regions where endemic form of Burkitt’s
cell carcinoma and T-cell leukaemia-lymphoma respectively). lymphoma is frequent. This supports the linkage of EBV
There is no oncogenic role of HSV-2 and CMV in human infection and immunosuppression in the etiology of Burkitt’s
tumours. The other two—EBV and HHV are implicated in lymphoma.
human tumours as under.
Anaplastic nasopharyngeal carcinoma. This is the other
EPSTEIN-BARR VIRUS (EBV). EBV infects human B- tumour having close association with EBV infection. The
lymphocytes and epithelial cells and long-term infection tumour is prevalent in South-East Asia, especially in the
stimulates them to proliferate and development of Chinese, and in Eskimos. The morphology of nasopharyngeal
malignancies. EBV is implicated in the following human carcinoma is described in Chapter 18. The evidence linking
tumours—Burkitt’s lymphoma, anaplastic nasopharyngeal EBV infection with this tumour is as follows:
carcinoma, post-transplant lymphoproliferative disease, a) 100% cases of nasopharyngeal carcinoma carry DNA of
primary CNS lymphoma in AIDS patients, and Hodgkin’s EBV in nuclei of tumour cells.
lymphoma. It is also shown to be causative for infectious b) Individuals with this tumour have high titers of
mononucleosis, a self-limiting disease in humans. The role antibodies to various EBV antigens.