Pathogenesis of Testicular Acute Lymphoblastic Leukaemia (pp. 61-81)
Authors: El Morsi, Hisham and Jewell, Andrew (Kingston University, Surrey) Yong, Kwee Lan and Patterson, Keith (University College London, London)
Abstract: Treatment for childhood Acute Lymphoblastic Leukaemia (ALL) improved dramatically during the second half of the twentieth century, with four-year survival rates of up to 60% being recorded. Extramedullary relapse in the central nervous system (CNS) required the introduction of cranial irradiation and intrathecal methotrexate. The second most common extramedullary site to show ALL relapse is the testis. The development of more intensive treatment protocols has reduced the incidence of testicular relapse, but relapse in the testis may still occur 13 years after initial treatment. However the pathogenesis of testicular leukaemia remains unclear. It is not known whether malignant lymphoblasts survive longterm in the testicular interstitium, or spread into the testis from subclinical leukaemic involvement on the bone marrow. Animal models, and some clinical data, may provide evidence for a role as a sanctuary site from chemotherapeutic agents. In addition, the local micro-environment in the testis may provide cytokines and growth factors which support the survival and proliferation of the malignant lymphoblasts. This review summarises the current state of our understanding of which of these factors may be important in the testis, and of the known effects on ALL cells.