Magister Scientiae Dentium - MSc(Dent) / The aim of the study was to investigate and describe the incidence of Plasmablastic Lymphoma (PBL) diagnosed at the Divisions of Anatomical Pathology and Haematopathology at Tygerberg Hospital from 2005 to 2017, and to ascertain a possible correlation with HIV infection, by identifying the number of HIV positive and negative patients diagnosed with Plasmablastic Lymphoma. Method: This was a retrospective study using the case records of all newly diagnosed PBL patients from 2005 to 2017. Results: Fifty-seven cases of PBL were diagnosed from 2005-2017. The overall result shows an increasing incidence of PBL in the intended period with the maximum incidence occurring in 2017. Most of the cases, 40.4%, were diagnosed in the age range 40-49-years. Forty-five patients were HIV-positive (78.9%) with (P value 0.011) and the majority of the patients were males (66.7%).

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Anatomical Pathology Johannesburg, 2016 / Introduction: Plasmablastic lymphoma (PBL) is an uncommon variant of aggressive B-cell non-Hodgkin lymphoma that occurs in immune-compromised individuals, most commonly secondary to HIV infection. This tumour classically occurs in the oral cavity but has also been described in a variety of extra-oral locations. This is a clinicopathological study of 45 cases of extra-oral PBL (EPBL). Aim: To define the clinical parameters, histology and immunophenotypic features of extra-oral plasmablastic lymphoma (EPBL) and assess the extent to which Epstein–Barr virus (EBV) is associated with this tumour. Materials and Methods: This retrospective study on archival cases of EPBL included the patients‟ age, gender, race, HIV status where available and the site of tumour presentation. Of 49 archival cases retrieved, 4 were discounted owing to reclassification as diffuse large B-cell lymphoma (1 case), multiple myeloma or extramedullary plasma cell tumour (3 cases). The remaining 45 cases were reviewed histologically and classified according to whether they displayed a pure plasmablastic (PBm) morphology or a plasmablastic morphology with plasmacytic differentiation (PBm+PCd), and assessed immunohistochemically with CD45 (LCA), CD20, CD79a, PAX5, CD138, MUM1, BLIMP1, VS38c, Ki-67, BCL6, CD10, HHV8 and CyclinD1 using standard automated procedures. The presence of EBV was assessed by chromogenic in-situ hybridisation. Ethical clearance was obtained (M10750 and M120993). Results: 27of the 45 cases had a pure plasmablastic morphology. The remaining 18 cases showed plasmacytic differentiation. There was no site predilection according to histological pattern. 60% of the tumours were reported in males and 40% in females and all were black African patients. The anus was the favoured extra-oral site of presentation (13 of 45 cases, 28%), followed by soft tissue (11 of 45 cases, 24%). There was no significant difference in the age of presentation between males (38.5 years) and females (35.4 years). Of the 18 patients of known HIV status, 17 were HIV positive (94%). The immunohistochemical profile of EPBL recapitulated that found for both oral and extra-oral PBL in the literature, except for CD45 (leucocyte common antigen) which signalled positively in a higher percentage of cases. 36 of 42 cases (85.7%) were positive for CD45. The positive membrane signal for CD45 was of variable intensity, between 5 and 100% of tumour cells. EBV was positive by in situ hybridisation in 37 of 40 cases tested (92.5%). Conclusion: EPBL is identical to its oral counterpart in gender and age distribution, HIV status, morphological appearances, immunophenotypic profile and association with EBV. The high association with EBV as assessed by in-situ hybridisation studies mirrors that of oral-based PBL reported in the literature. EPBL should be regarded as the same tumour as that arising within the oral cavity. A peculiarity observed within this case cohort is the high level of expression of CD45 (leucocyte common antigen). This has been reported to be of low or near absent expression in most cases of PBL, as defined by the 2008 WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues. / MT2016

Plasmablastic lymphoma (PBL) was originally described in 1997 as an AIDS associated tumour although cases have been described in individuals not infected with HIV. Due to the high number of people living with HIV in South Africa, a substantial number of cases are diagnosed annually and 45 cases were included in this study. This represented the largest cohort of PBL affecting the oral mucosa published to date. Three main aspects of PBL were investigated: pathological features, viral status and certain genetic characteristics. The results from the genetic studies were the most important and interesting. These included rearrangements of the IGH gene in 63% and MYC- rearrangements in 62% of PBL’s. Seven of 43 cases (16%) showed rearrangement of both the IGH gene alleles, a finding never described before. New genetic findings also included increased CCND1 gene copy numbers in 17/41 (42%) and increased IGH gene copy numbers in 6/41 (15%) of cases. The exact role of MYC-rearrangements in the development of PBL is unclear. Many factors may be responsible for MYC deregulation but in the case of PBL of the oral cavity the possible role of Epstein Barr Virus (EBV) infection was considered. All but one of the patients with known HIV-status (32/45) was HIV positive and I supported the proposal that the diagnosis of PBL should serve as a sign of immunodeficiency, either as diagnostic thereof or as a predictor of a progressive state of immunodeficiency in patients with known HIV/AIDS status. The HIV-negative patient in this study was the only one that presented with an EBV-negative PBL on in situ hybridisation. The clinico-pathological features of the current study therefore strongly suggested an association between EBV, PBL and HIV/AIDS although the exact nature thereof remains uncertain. Routine genetic evaluation of tumours diagnosed as PBL should be introduced, as this may have prognostic and eventually treatment implications in the future. The exact panel of genes to be evaluated with a possible diagnosis of PBL should still be determined but examination of IGH and MYC for rearrangements should be included. This study proved the histomorphological features including the degree of plasmacytic differentiation not to have any diagnostic role although its prognostic value should be determined. The results of the immunohistochemical investigations performed in this study confirmed PBL always to be negative for CD20 but proved PBL not to be a morphological or immunohistochemical diagnosis by any means. In conclusion, it became clear that PBL should never be diagnosed without thorough clinical, systemic, pathological and genetic investigations, especially in the backdrop of HIV/AIDS. No pathologist should make the diagnosis of PBL and no clinician should accept such a diagnosis or decide on the treatment modality for the patient involved unless all other possibilities of systemic plasma cell disease have been excluded. / Thesis (PhD)--University of Pretoria, 2011. / Oral Pathology and Oral Biology / unrestricted