Peripheral T-Lymphomas
Summary
Peripheral T-lymphomas, so named because of their post-thymic origin, account for about 10% of non-Hodgkin lymphomas in Europe and North America. They group together all the clonal proliferations derived from the different populations lymphocyte T mature (TCRαβ and γδ) and NK. The WHO classification distinguishes three groups of peripheral T lymphomas: Leukemia presentation lymphomas (adult leukemia/t lymphoma, prolymphocytaire t leukemia, NK cell leukemia, granular T leukemia), localization lymphomas Extraganglionnaire (NK/t nasal type lymphoma, enteric-associated T-lymphoma, hepatosplenic T-lymphoma, subcutaneous panniculitis-type T-lymphoma, primitive cutaneous T-lymphomas), and ganglionic localization lymphomas (T-lymphoma Angioimmunoblastique, large-cell systemic anaplastic lymphoma, peripheral T-lymphoma with no other specificity.
Introduction
Peripheral T-lymphomas, so named
Because of their post-thymic origin, represent
About 10% of non-Hodgkin lymphomas
In Europe and North America. They bring together
All clonal proliferations derived from
Different populations lymphocyte T mature
(CRT and) and NK. The WHO classification distinguishes
Three groups of peripheral T-lymphomas:
Leukemia presentation lymphomas (Leukemia/lymphoma
T Adult, Prolymphocytaire leukemia
T, NK cell leukemia, T leukemia
Granular), Extraganglionnaire localization lymphomas
(NK/T lymphoma of nasal type, lymphoma
T associated with enteric, T-lymphoma
Hepatosplenic, T-type lymphoma Panniculitis
Subcutaneous, primitive cutaneous T-lymphomas), and
Lymph node localization lymphomas (lymphoma
T Angioimmunoblastique, anaplastic lymphoma
Systemic with large cells, T-lymphoma
Device without any other specificity). These lymphomas
are defined on clinical arguments, histological
and Immunophénotypiques, and with the exception
Anaplastic lymphoma with large cells, their
Chromosomal and molecular anomalies are poorly
Known. Peripheral T-Lymphomas pose
Difficult diagnostic and therapeutic problems,
And, generally speaking, their prognosis is less
Good as lymphoma B. This chapter
Objective to describe the main sub-types of lymphomas
Peripherals with the exception of lymphomas
Skin (Mycosis fungoïdes, syndrome of
Sezary, primitive cutaneous anaplastic lymphoma).
Adult T-cell leukemia/lymphoma
Leukemia/lymphoma, ATLL) (1, 2)
Adult T leukemia/lymphoma is a hemopathy
Associated aggressive post-thymic lymphoid
To HTLV-1. It corresponds to the malignant proliferation
of a CD4 + T clone
Carrier of HTLV-1 Provirus
Integrated. ATLL is the first human disease
Linked to a retroviral infection. It usually occurs
In regions of the world where HTLV-1
is endemic (Japan, Caribbean, South America,
Sub-Saharan Africa, Iran and Melanesia). Although the
This virus can be transmitted by blood or
Sex, vertical transmission via breastfeeding
is required for its development. The ATLL
Occurs in 2 to 3% of infected subjects after
A long latency period of 30 to 60 years characterized
By the persistent oligo/polyclonal expansion
Infected lymphocytes associated with a large
Genetic instability. The Oncoprotein viral Tax plays
A central role in the initiation of transformation
Malignant. Four clinical subtypes have been identified
: The acute form, leukemia (60%), the form
(15%), the progressive form (5%) and the
Lymphomateuse form (20%). Tumor syndrome
is particularly important in the forms of
The most aggressive (acute and lymphomateuse) and
Characterized by a hepatosplenomegaly, voluminous
Adenopathies Peripherals, lesions
And the invasion of numerous
Organs, especially the skin and lungs. A
Associated Hypercalcemia is common. The sick
are immunocompromised and subject to many
Opportunistic infections. The diagnosis is mentioned
On a set of morphological, phenotypic data
And Serological and is confirmed by the
Demonstration of a monoclonal integration of the
Provirus in malignant cells. Thus, the ATLL is
Characterized in cytology by the presence of "flower
cells, corresponding to malignant T lymphocytes
To the lobulé nucleus and the basophile cytoplasm. The Immunophénotype
ATLL cells are evocative:
CD2 +
CD3 +
CD4 +
CD5 +
CD25 +
But CD7 –
and CD8 –
. This
Profile usually allows to distinguish the ATLL
Other malignant T peripheral proliferations.
HTLV-1 serology is almost always positive
(Rare false negatives of immunocompromised patients)
Chapter
92 Rare Malignant tumors
and monoclonal integration can be highlighted
By Southern blot, reverse PCR or ligation PCR
of Oligonucleotide. Patients with
Acute form or lymphomateuse have a bad prognosis,
With survival medians of 6 and 10 months
Respectively. Only 5% of patients are still
Alive at the age of four. The difference between these two clinical types
Mainly depends on the flooding of
Blood, massive in the acute form and less than
1% in the form lymphomateuse. The Variations
Chronic (median 24-month survival; 27% of
Survival at 4 years) and progressive (62% projected survival
to 4 years) have a more indolent evolution.
Due to insufficient chemotherapy results
Conventional, new approaches to
Therapies have been developed. The Bitherapy
Antiretroviral drug AZT-IFN has resulted in
Complete remission rate significantly better
That conventional treatments with no side effects
Major. Arsenic trioxide (As2
O3
) was
have shown encouraging results in the models
ATLL, particularly in association with IFN.
Several studies have studied the effect of touttransrétinoïque acid
: The latter acts in synergy with
The AS2
O3 When the cells express the receiver
Retinoic acid (RAR). Different antibodies
have been tested in the ATLL, in vitro
Or in vivo: we can cite anti-CD25 antibodies,
Cold or hot, anti-CD2 and anti-CD52. Recently
A monoclonal antibody directed against the
Transferrin membrane receptor gave
Satisfactory results by inducing apoptosis
of ATLL cells. Some studies have tested the
Effects of proteasome inhibitors or inhibitors
Deacetylases histones, with results
Encouraging. Recently, Japanese studies
On the allograft of patients with ATLL
have shown promising results.
NK/T-type nasal lymphoma (NK/T-cell
Lymphoma, NKTCL) (3, 4)
NK/T Nasal type lymphoma is a lymphoma
T peripheral Extranodal Aggressive, more
In Asia and Latin America, associated with the
EBV. Epidemiological studies conducted at the
Japan, Korea and China have shown a risk of
Increased among farmers (OR = 4.1), farmers
(or = 2.8) and pesticide users (or = 4).
Lymphoma classically affects the nasal cavity
and adjacent structures like the sinuses
Or the palace and causes local destruction with
Necrosis and ulceration, related to its angiocentrique character
and Angiodestructeur (formerly "Granuloma
Malin Lethal "). This lymphoma can sometimes
Have an extra-nasal location, touching
Other sites of the upper gastrointestinal tract or
Other organs (skin, digestive tract, testicles,
Bone marrow). The disease can be localized or
disseminated to the diagnosis. This lymphoma affects
Adults about 60 years old with a predominance
Male. The general state is good in the majority
of cases. B symptoms are present in 60%
of cases. LDH is high in 60% of patients.
Anemia is present in most cases.
Albumin is low in two thirds of the cases. The
Bone marrow is invaded in 15% of cases. On
The histological plan, the tumor cells are
Variable morphology, and are often accompanied by
By a population of reaction cells
(Plasma, Histiocytes, eosinophils). The immunophenotyping
Shows characteristics of
Normal NK cells (CD2 +
CD56 +
, negativity of
CD3 membrane, CD5, CD4 and CD8),
But with a negativity of CD16 and CD7. The cells
Neoplastic express the chain of CD3
In their cytoplasm. Cytotoxicity Markers
are positive (Perforin, Granzyme B, TIA1).
As in normal NK cells, there is no
Rearrangement of the TCR genes or immunoglobulins.
EBV, detected by FISH (EBER: EBV
Encoded small RNAs), is constantly present
In tumor cells in the form of a clone
Épisomal, type II latency. In Cytogenetics,
Many anomalies are found, the most
Frequent being the 6q deletion. On the molecular level,
Mutations in p53, C-Kit and FAs have
been described, with a very variable frequency
Depending on the geographical area.
On the therapeutic level, there is no consensus.
Localized forms often respond to the association
Chemo-radiation therapy. Chemotherapy
Type CHOP (cyclophosphamide, doxorubicin, vincristine,
Prednisone) has been disappointing, with
Overall survival of 40% to five years in locations
Nasal, and only 10% in the locations
Extra nasal. Recently, retrospective studies
showed that L-Asparaginase had
Excellent activity in relapsing diseases
Or refractory, especially in disseminated forms.
On this basis, L-Asparaginase is currently
Evaluated in the context of prospective studies.
T-lymphoma associated with enteric
(Enteropathy-type T-cell lymphoma, ETCL) 5
This is a rare form of lymphoma, the majority
Intestinal lymphomas being B phenotype.
The median age for diagnosis is 61 years, with no difference
Significant by sex. There is a link
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