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TVCS scientific
meeting and AGM, 15 February 2001, at University College, London
Dr Gabrijela
Kocjan from University College Hospital provided an overview
of the changing patterns of HIV-associated disease in the era of
Highly Active Anti-Retroviral Therapy (HAART) together with a description
of the cytological appearances of the various disease processes
that were pertinent.
Recent advances
in HIV medicine include the introduction of HAART, together with
greater understanding of the underlying pathology and improved assays.
HAART suppresses viral replication and improves CD4 count, although
it may produce novel clinical syndromes as the immune system is
rapidly restored, producing inflammatory responses to pre-existing
infectious organisms.
Problems associated
with immunosuppression, both HIV-associated and otherwise, essentially
fall into two groups - opportunistic infections and malignancies.
Dealing with the first of these categories, Dr Kocjan informed us
that the incidence of Pneumocystis Carinii pneumonia (PCP), at one
time among the commonest of opportunistic infections, has fallen
dramatically with the advent of HAART.
In Europe, cases
now tend to occur in those who are unaware of their HIV status or
who refuse prophylaxis. When the infection does occur, it tends
to have an insidious onset. This is in contrast to the situation
in non-HIV immunosuppression, when it often produces an acute fulminant
pneumonia. The mainstay of cytological detection remains a combination
of Pap, MGG and Grocott stains (although we were alerted to potential
false positives such as red cells and air bubbles). PCR produces
high sensitivity but low specificity and the usefulness of immunofluorescence
has not fulfilled its early promise. The detection rate of PCP in
bronchioloalveolar lavage (BAL) specimens is up to 90%, higher than
biopsy or induced sputum.
Mycobacteria
now tend to produce a classic granulomatous appearance, with restoration
of the immune system following HAART. Detection relies on traditional
morphological and tinctorial methods (sensitivity 50%) augmented
by PCR (overall sensitivity 84%, specificity 100%).
CMV has become less relevant clinically but is still most often
detected using BAL and immunocytochemistry increases sensitivity.
Aspergillus
may be found in BAL but requires confirmatory culture before a clinically
relevant infection can be diagnosed. The overall diagnostic yield
of BAL is high - 76% in a 10-year study of 947 lavages at St. Mary's.
44% of all lavages contained PCP, but the commonest group of pathogens
was bacteria - emphasizing the point that fulminant bacterial infection
as a clinical presentation of opportunistic infection in HIV is
becoming more common.
The risk
of developing malignancy in HIV disease is greater than in the non-HIV
population (16x in men and 3x in women).
These tumours
include Kaposi's sarcoma (KS), non-Hodgkin lymphomas, squamous cell
carcinoma (of the cervix and other sites), leiomyosarcoma (in childhood),
seminoma and others. Most of these tumours are associated with known
viral aetiologies such as Human Herpes Virus (HHV) - 8, HPV and
so on. Kaposi's sarcoma is associated with HHV8.
Dr Kocjan reiterated
the cytological appearances and stressed that accurate diagnosis
and distinction from other spindle-cell lesions remains a morphological
task.
Non-Hodgkin's lymphomas occur at a late stage of HIV disease and
at an incidence roughly 60 times that in non-HIV infected people.
They are usually high grade, B-cell lymphomas that often present
extra-nodally and are aggressive. Newer entities that we were introduced
to included primary effusion lymphoma (also associated with HHV8
and occurring in body cavities without lymphadenopathy or a mass)
and plasmablastic lymphoma.
Cervical
carcinoma was the commonest AIDS-related malignancy in women (55%)
according to one 1997 study from a single, high-risk institution
in Brooklyn, USA, followed by lymphoma (29%) and KS (16%).
However, while
this does reflect a greater incidence compared with non-HIV women,
the reasons for this are complex and probably have as much to do
with increased exposure to HPV as immunosuppression. For (probably)
similar reasons, HIV-infected women have a higher incidence of CIN
(up to 34%) with a higher proportion of high-grade lesions. They
also tend to have more extensive disease with a concomitantly higher
recurrence rate following conventional treatment. This was a useful
practical point as it suggested a role for more frequent surveillance.
Dr Kocjan briefly
reviewed the cytological appearances of progressive generalised
lymphadenopathy, which is the most common finding following aspiration
of an enlarged lymph node in the context of HIV disease, depending
on one's referral practice. The florid phase contains many blast
cells with a few follicular dendritic cells and small lymphocytes
while the "resting" phase many dendritic cells (which
can be shown to contain cytoplasmic p24 HIV antigen) with fewer
blasts.
Finally, there
was a mention of occupational risk. The rate of seroconversion following
needlestick injury is 0.2%. In order to prevent injury happening
in the first place, the single most useful piece of advice is -
do not resheath needles. If injury has occurred, then counselling
and the administration of zidovudine within one hour are indicated
as the latter reduces seroconversion by 78%.
Overall, this
was a comprehensive and informative overview of recent developments
in this rapidly changing field, which described both clinical background
and morphological features. Furthermore, Dr Kocjan should be congratulated
for her spirited improvisation during the misbehaviour of the slide
projector.
This tour-de-force
yielded the department's website which you can find at http://www.uclcyto.org.uk.
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