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Title: Angioimmunoblastic T-cell lymphoma : histologic, immunophenotypic and molecular genetic characterisation of the disease
Author: Attygalle, Ayoma Deepthi
ISNI:       0000 0001 3432 6197
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2007
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Angioimmunoblastic T-cell lymphoma (AITL), although initially thought to be an atypical reactive process - angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), has since been proved to be a T-cell lymphoma and is categorised as a subtype of peripheral T-cell lymphoma. It is an aggressive disease, in which the biology is poorly understood. Defining histological criteria apply only to typical examples, while many features overlap with reactive conditions and other lymphomas. In this thesis, CD10 was investigated as a possible phenotypic marker of AITL. As the neoplastic cells comprise the minority, individual CD 10 positive lymphoid cells were microdissected for molecular genetic analysis. The results showed that the neoplastic T-cells in AITL expressed CD 10, thus providing a marker to identify the neoplastic T-cell. It was also shown that in the assessment of nodal peripheral T-cell lymphomas, CD 10 expression appears to be a sensitive and specific marker for AITL. CD 10 expression was maintained in most extranodal sites of involvement, and correlated well with the presence of a follicular dendritic cell meshwork. AITL showed 3 overlapping histological patterns, depending on the presence of hyperplastic follicles (pattern I), regressed follicles (pattern II) or absence of identifiable follicles (partem III). Histologic progression was studied in consecutive biopsies and it was shown that pattern I represented early lymph node involvement, which progressed to pattern III with disease progression. Furthermore, when AITL was complicated by a "large cell lymphoma" it was usually an EBV-associated diffuse large B-cell lymphoma. EBV-associated B-cell proliferations complicated 25% of cases. Using CD 10 as a phenotypic marker of the neoplastic cell it was shown that the latter expressed CXCL13 and BCL-6 consistent with a germinal centre T-cell origin. Finally, the correlation between EBV-load and histological patterns was studied and the presence of HHV-8 investigated. A high EBV load was mainly observed in pattern III histology, a feature that probably parallels the increasing degree of immune suppression. HHV-8 infection was not found to be a feature of AITL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available