Mycosis Fungoides and EBV

[H.M.S.]

Hello,

Can anyone tell me anything about the connection between Epstein Barr
Virus and Mycosis Fungoides (or Cutaneous Lymphoma)?

Years ago (8?) I had a mystery virus with enlarged liver, spleen, and
various lymph nodes and EBV was detected.

Currently, I am awaiting my 5th biopsy result for suspected Mycosis
Fungoides. Apparently, they are looking for "some type of cell" on
this test, so the results will take weeks.

Thanks.

[Dr. Tullio Simoncini]

Dear friend,
have you ever thought that the Mycrobiology and Oncology at the moment are
wandering in the dark?
My opinion is that fungi and virus are the same thing, that is fungi
generate virus, so that their mutual passage is comprehensible.
This is not reported in the Virology treatises, on the contrary her first
axiom (virus is an obligatory intracellular microrganism) is completely
contradictory.
How he reaches cells? It is impossible to answer.
That's why Virology wanders in the dark.
In short: EBV can become Mycosis Fungoides; cancer comes down from Fungi.
Regards,
Dr.Tullio Simoncini Rome Italy
email: t.sim...@flashnet.it

H.M.S. ha scritto nel messaggio <36D55CA3...@ionline.net>...

[Tom Crabtree]

There is an excellent, low traffic, listserv group for mycosis fungoides
(cutaneous t-cell lymphoma) and Sezary syndrome patients. You can join
from the Oncolink CTCL page or if you send me a private email, I can
give you more information. It can be very empowering to correspond with
or listen to the experiences of others who are dealing with this weird
disease.
The EBV- mycosis fungoides link has been examined for a number
of years, and while a link has been proposed, no cause-effect
relationship has been found that I am aware of. EBV is a very common
virus. Links have also been proposed between MF and HTLV-I, but this
theory has also produced conflicting results.
One key to treating mycosis fungoides is management by a
Dr who specializes in mycosis fungoides, whether dermatologist or
oncologist. Let me know if you need more info on the CTCL-MF listserv or
if you would like me to forward you some CTCL-MF websites. regards,
Tom Crabtree crab...@webtv.net

Living well is the best revenge

[Scientific Office]

In article <7b41ls$p9h$1...@news.flashnet.it>, "Dr. Tullio Simoncini"
<t.sim...@flashnet.it> writes

>Dear friend,
>have you ever thought that the Mycrobiology and Oncology at the moment are
>wandering in the dark?

A little superficial reading would be enough to tell you that there are
a number of viruses which have had their full genome sequenced and that
there is an increasingly clear understanding of the cell cycle of
mammalian cells and how this goes wrong in cancer. There is a huge
number of unanswered questions in microbiology and oncology but to
suggest that they are wandering in the dark reveals your ignorance not
that of the scientists.

>My opinion is that fungi and virus are the same thing, that is fungi
>generate virus, so that their mutual passage is comprehensible.

Your opinion is utter twaddle. By adding viruses to a virus free cell
culture it is possible to infect the cells, no amount of fungus added to
a culture will generate viral infection. The simple fact is that viruses
produce viral protein and DNA or RNA which assembles to form a virus,
fungi generate fungal proteins and fungal DNA which generates a fungus
and one will NEVER, repeat NEVER turn into the other.

>This is not reported in the Virology treatises, on the contrary her first
>axiom (virus is an obligatory intracellular microrganism) is completely
>contradictory.
>How he reaches cells? It is impossible to answer.

The mechanism by which viruses enter cells is very clearly understood,
the virus DNA (or RNA in retroviruses) codes for the production by the
cell of proteins. It is because the virus completely lacks protein
producing machinery of its own that it is an obligate intracellular
parasite. One or more of the proteins produced by the parasite is
capable of binding to the target cell and causing it to "swallow" the
virus particle.

>That's why Virology wanders in the dark.

The only person wandering in the dark is yourself. I suggest that you,
and any other reader seeking some enlightenment should visit
http://www.tulane.edu/~dmsander/WWW/224/BS224.html
where you will find excellent tutorials on both virology and mycology
(the study of viruses and the study of fungi respectively).

>In short: EBV can become Mycosis Fungoides; cancer comes down from Fungi.

I was initially unclear as to why you began waffling about fungi in this
context. Your final sentence makes this clear, you obviously think that
mycosis fungoides has something directly to do with fungoides. Mycosis
fungoides (MF) is a form of T-cell lymphoma affecting that population of
T-cell which normally prefers to remain in skin tissues. The skin
eruptions in MF show a superficial similarity to fungal infections of
the skin. For this reason when they were first described, long before
there was any clear awareness of their nature they were named for their
appearance, fungoides means "fungus-like". There is absolutely no
evidence to support the premise that fungal infection is in any way
related to the cause or progress of MF. It is possible that, like other
patients with diseases which affect the immune system, MF patients may
be more prone to fungal infection - if so this is secondary to the
disease.

I do not feel competent to comment on whether there is any evidence
implicating EBV in the causation of MF, for that reason I will keep my
electronic mouth shut and allow others, better qualified than I, to
address that question.

I will repeat a plea I have made before on this newsgroup, please do not
post purported statements of facts in fields where you are ignorant -
opinions are free, facts are sacred. Many of the readers of this
newsgroup are not from a scientific or medical background and it is
important that they can rely on factual statements as being reliable.

>Regards,
>Dr.Tullio Simoncini Rome Italy
>email: t.sim...@flashnet.it
>
>H.M.S. ha scritto nel messaggio <36D55CA3...@ionline.net>...

Ken Campbell
Information Officer, Leukaemia Research Fund
E-mail: l...@leukaemia.demon.co.uk
Web site: www.leukaemia-research.org.uk
Information and views expressed are my own and do not necessarily reflect those
of my employer

[stanbro]

Some people suspect a link between EBV infection and mycosis fungoides or other cutaneous lymphomas. EBV is know to preferentially infect lymphocytes, and to lurk around in these cells sometimes for many years. Whether it causes cancerous transformation of these cells directly by affecting their genes or indirectly by causing chronic immunostimulation that eventually leads to cancer is still argued. In any case, EBV has been associated with many kinds of malignancies, mostly involving lymphocytic cells--lymphomas of various kinds, Hodgkin's disease, post-transplant lymphoproliferative syndromes etc. Here are a few references about the association of this virus with cutaneous lymphomas:

Acta Derm Venereol 1994 Sep;74(5):355-7
Presence of Epstein-Barr virus in cutaneous lesions of mycosis fungoides
and Sezary syndrome.
Dreno B, Celerier P, Fleischmann M, Bureau B, Litoux P
Department of Dermatology, Hotel-Dieu, Nantes, France.

It has been suggested that prolonged antigenic stimulation contributes to the development of epidermotropic cutaneous T cell lymphoma (CTCL), mycosis fungoides and Sezary syndrome, characterized by a cutaneous infiltration of proliferating helper T cells. Since Epstein-Barr virus (EBV) antibodies were increased in CTCL sera, we investigated a possible etiologic role for EBV in epidermotropic CTCL by looking for the EBV genome in 25 cutaneous biopsies of mycosis fungoides or Sezary
syndrome and 12 reactional inflammatory skin lesions. The use of a non-isotopic in situ hybridization procedure based on the
detection of Epstein-Barr encoded RNAs with biotinylated oligonucleotide probes (EBER) revealed 32% of the lesions with CTCL to be positive for EBV (3 in dermis, 3 in epidermis, 2 both in dermis and epidermis), as compared to no detection of the EBV genome in the reactional inflammatory skin lesions. Moreover, a combined hybridization (EBER probe) and
immunochemistry technique (anti-CD3 or anti-Kil monoclonal antibody) permitted the identification of EBV in T cells of dermis
and in keratinocytes, respectively. The identification of EBV in epidermotropic CTCL suggests that this virus could play a role
in the development of these CTCLs, either as an etiological agent or more probably as a chronic activating agent. Indeed, the infection of keratinocytes by EBV could activate them and so induce the production of in situ cytokines (IL1a, IL6, TNFa) playing a role in the development of tumoral infiltrate.
___________________________________________________

The in situ hybridization technique in the above article would probably be a lot quicker than whatever they are doing that takes "weeks" in your case. Maybe your doctor could look into the possibility of doing this test.
________________________________________________________________

r J Dermatol 1997 Feb;136(2):212-6

Increased anti-Epstein-Barr virus antibodies in epidermotropic cutaneous
T-cell lymphoma: a study of 64 patients.

Jumbou O, Mollat C, N'Guyen JM, Billaudel S, Litoux P, Dreno B

Department of Dermatology, Hotel Dieu, Nantes, France.

Epstein-Barr virus (EBV) is often associated with non-Hodgkin's T-cell lymphomas and has recently been found in the lesions
of mycosis fungoides and Sezary syndrome. We sought to determine whether the anti-EBV antibody profile was disturbed in
mycosis fungoides and Sezary syndrome and whether there are particular profiles characteristic of disease stage. Anti-EBV
antibodies (anti-VCA, -EA and -EBNA) were studied in the sera of 64 patients. An immunoenzymatic technique was used,
and the results were compared with the same number of age- and sex-matched healthy controls. Patients with mycosis
fungoides and Sezary syndrome developed higher anti-VCA antibody titres (median 1200) than controls (median 320).
Thirty-seven patients had anti-VCA > or = 1200 vs. 19 controls (P < 0.01). These elevated anti-VCA antibody titres were
associated with positive EA in 19 patients versus three controls. No differences were found between the illness stages.
Anti-EBV antibodies were most often found in mycosis fungoides and Sezary syndrome when the serological profile was similar
to that of cellular immune deficiencies and EBV-related non-Hodgkin's lymphoma. EBV could be involved, either directly on
lymphocytes or, more likely, indirectly by chronic antigenic stimulation.
__________________________________________________________

Br J Dermatol 1996 Feb;134(2):276-81

Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell
lymphoproliferations.

Anagnostopoulos I, Hummel M, Kaudewitz P, Korbjuhn P, Leoncini L, Stein H

Klinikum Benjamin Franklin, Free University Berlin, Germany.

Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)-negative patients with primary cutaneous
T-cell lymphoproliferations, including mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large cell
lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the presence of Epstein-Barr virus (EBV) through
a combined approach. Polymerase chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization (ISH)
for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and immediate early Bam H-fragment; lower
frame (BHLF) RNA, and immunohistology (IH) for the identification of EBV-encoded latent membrane protein 1 (LMP1) and
of nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76 cases (19.7%). EBER-ISH
combined with IH identified a variable, usually very low, number of infected neoplastic cells in only seven of the 15
EBV-DNA-harbouring cases. This discrepancy between the results obtained with PCR and ISH is apparently caused by the
low number of the infected cells per tissue section. The PMTCL entity produced the greatest number of positive cases, whilst
ALCL and LyP cases were almost constantly devoid of the virus. BHLF transcripts were not detectable in any case, nor did
any of the EBER-positive cells show an LMP1 or EBNA2 expression. These data show that primary cutaneous T-cell
lymphoproliferations display an infrequent association with a latent EBV infection and that the pathogenic role of the virus in the
positive cases remains obscure as the virus frequently infects only a minority of the atypical cells.

_________________________________________________________

It probably is more important to find out for sure if you have mycosis fungoides than it is to know whether or not it is EBV-associated. If it does turn out to be EBV-related, there is beginning to be some interest in the possibility of using anti-EBV adoptive cellular immunotherapy (where they immunize some of your own lymphocytes against EBV and then inject them back into you to fight the lymphoma) for EBV-related post-transplant lymphoproliferative diseases. If that works, it might also help with your condition, although as the last article stated, perhaps not all the cells have viral genomes in them. Let us know what they decide!  Best of luck--Helen S.