BTK and neoplasm: However, if splenectomy is undertaken, access to splenic tissue provides a unique opportunity to study tumour-microenvironmental interactions, let alone establish an unequivocal diagnosis; (5) patients who relapse after 2 years from initial rituximab treatment are candidates for re-treatment with the same regimen; (6) for those with early relapse or with refractory disease, Bruton’s tyrosine kinase (BTK) inhibitors, especially second-generation inhibitors zanubrutinib and acalabrutinib, have shown benefit in clinical trials.