T. Tousseyn MD, PhD

Straight to the heart

SUMMARY

We report the case of a 56-year-old patient with medical history of acute myeloid leukaemia (AML), presenting with shortness of breath and lower extremity oedema. Transthoracic echocardiogram revealed an important amount of pericardial fluid and an infiltrating mass located at the left ventricular wall. A pericardial window with drainage was performed and a biopsy of the pericardium was taken. The pathological report was compatible with an extramedullary manifestation of AML. Further work-up with complete blood test and bone marrow biopsy confirmed a systemic AML relapse. The patient was treated with re-induction chemotherapy and cardiac radiotherapy followed by a second allogeneic stem cell transplantation, leading to a complete remission.

(BELG J HEMATOL 2023;14(7):304–7)

Primary vitreoretinal lymphoma: Single centre experience and review of literature

SUMMARY

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is a rare and difficult to diagnose lymphoma. The goal of this retrospective monocentric study was to obtain clinical characteristics, to evaluate median time to diagnosis, different treatment modalities and survival outcomes.

METHODS: PVRL cases were selected from the database of the University Hospitals Leuven (Belgium) from 1^st January 2012 until 1^st January 2021. A review of the available literature was performed.

RESULTS: We included eleven cases of PVRL with a median age of 76 years (Interquartile range (IQR): 68–81). Median time to diagnosis was seven months (Range: 3–16). Presenting symptoms were blurred vision (n=11, 100%) and floaters (n=3, 27%). Bilateral eye involvement was seen in 42% (n=5). Diagnosis was made by vitrectomy and immunocytochemistry in all cases. Histopathological diagnosis was diffuse large B-cell lymphoma in all cases. Flow cytometry was used in 55% (n=6) of patients to confirm diagnosis. Initial treatment included local therapy in all patients. A combination of local and systemic therapy was given to three patients (27%). Seven patients (64%) were diagnosed with CNS relapse. No systemic relapse was seen. Median progression-free survival (PFS) and overall survival (OS) were ten (IQR: 6–32) and 26 months (IQR: 12–37). Median PFS of patients treated with local versus combined therapy was 9.7 and 18 months, respectively. However, OS of patients with local versus combination therapy was 29 and 19 months, respectively.

CONCLUSION: We analysed the clinical characteristics of eleven patients with PVRL in our hospital. The majority of these cases will eventually progress to CNS lymphoma. We saw a prolonged PFS for patients treated with combination therapy in first-line, compared to local therapy alone. However, OS was longer in patients treated with local therapy only. Despite the small cohort, these results are comparable to previous literature. Based on larger retrospective studies we conclude that local therapy as first line treatment in PVRL results in similar OS rates with less systemic toxicity compared to combination therapy.

(BELG J HEMATOL 2022;13(6):228–235)

Advanced systemic mastocytosis: An uncommon cause of chronic diarrhoea and weight loss

SUMMARY

Introduction: Advanced systemic mastocytosis is a rare myeloproliferative disorder of mast cells, damaging the function of various organs and tissues. The diagnosis can be challenging due to its protean manifestations and rareness. Treatment options have improved over the last years. Currently, avapritinib, a novel tyrosine kinase inhibitor with activity against p.D816V mutated KIT, is under investigation.

Case: We report a case of a 64-year old man with chronic diarrhoea, fatigue, weight loss and ascites with hepatomegaly, developing an upper gastro-intestinal bleeding with multiple duodenal ulcers. Diagnostic work-up revealed hepatosplenomegaly and portal hypertension, a vertebral compression fracture and multiple ¹⁸F-FDG avid supra- and infradiaphragmatic lymph nodes and bone marrow. Based on the 2016 WHO criteria of systemic mastocytosis, and a concomitant chronic myelomonocytic leukaemia, the diagnosis of an aggressive systemic mastocytosis with an associated haematological neoplasm was made. The patient was consecutively treated with midostaurin, cladribine and avapritinib, the latter inducing a complete biochemical and molecular response.

Conclusion: This case illustrates the challenging clinical presentation of systemic mastocytosis. A deep response to avapritinib was observed despite prior use of midostaurin and cladribine, underlining its promise in advanced systemic mastocytosis.

(BELG J HEMATOL 2022;13(2):84–91)

Diagnosis and treatment of peripheral T-cell lymphomas: Update recommendations of the Belgian Hematology Society (BHS)

SUMMARY

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive diseases associated with poor outcomes. Recent progress in understanding of the biology and pathogenesis based on molecular profiling and next-generation sequencing has led to the introduction of new provisional entities in the World Health Organization (WHO) classification system of 2017 and to the emergence of new drugs.¹ Previous Belgian guidelines were published in 2013.² This review will discuss the diagnosis, work-up and treatment of PTCL including these advances as well as the limitation of the availability of drugs according to the Belgian reimbursement rules.

(BELG J HEMATOL 2022;13(2):65–80)

Immunity, the Epstein-Barr virus and the microenvironment in lymphoma

SUMMARY

Immune regulation therapy or ‘immunotherapy’ has been a major evolution in the field of cancer therapy in the last decade. The goal of this thesis was to better characterise multiple rare lymphoproliferative disorders in order to guide therapy development, predictive biomarker discovery and ultimately help ensuring that these novel therapies can get to the patients who stand to benefit from them. Many lymphoma types arise in a context of altered immune system function with potential implications for immunotherapy. One example of lymphoma arising in the context of chronic immune stimulation is Helico bacter Pylori infection, which is known as mucosa associated lymphoid tissue (MALT) lymphoma of the stomach. For this lymphoma we reviewed the literature and described how it is an excellent model to understand lymphomas arising in an immune stimulated context.¹ Other lymphomas arise in a context of immunosuppression, of which post-transplant lymphoproliferative disorders (PTLD) are the best characterised. Besides the immune state, the presence of a virus such as the Epstein-Barr virus has major effects on lymphomas and their (immune) microenvironment with potential impact on immunotherapy. A review of EBV-related effects on PTLDs was done.² Lymphoproliferative disorder’s (LPDs) arising in the context of treatment with immunomodulatory (IM)/immunosuppressive (IS) drugs for various auto-immune diseases are lesser-known. These are called immunomodulation related lymphoproliferative disorders (IARLPD). For this thesis, we characterised one of the largest single centre case series of IARLPD.³ Finally, some lymphomas arise in specific ‘immune-privileged’ sites such as the central nervous system (CNS) called Primary central nervous system lymphoma (PCSNL). Digital slide analysis method and the novel MILAN multiplex staining technique were used to study the tumour microenvironment (TME) in PCNSL confirming the relevance of the microenvironment in the clinical behaviour of this lymphomas, highlighting potential relevance of immunotherapy and confirming the usefulness of the mentioned techniques in the study of the TME.⁴ For the purpose of this dissertation presentation we will focus primarily on this latter work.

(BELG J HEMATOL 2021;12(6):280-2)

EBV-induced double hit transformation of splenic (marginal zone) lymphoma, in a patient with a chronic Hepatitis B virus hepatitis

SUMMARY

We report a case of an EBV-induced large-cell transformation of a splenic marginal zone lymphoma in an 81-year-old female with a simultaneous finding of hepatitis B viral infection.

(BELG J HEMATOL 2021;12(6):275-9)

The role of the pathologist in the diagnosis of lymphoma

The diagnosis of lymphomas requires multiple immunohistochemical (IHC) analyses in combination with additional tests, such as fluorescent in situ hybridization (FISH) and/or polymerase chain reaction (PCR) tests. During his lecture at the 2021 BHS general annual meeting, Dr. Thomas Touseyn discussed the contemporary role of the pathologist in the diagnostic work-up of aggressive lymphomas.