Diagnosis of advanced SM. (A) Diagnostic algorithm in advanced SM. After having established the diagnosis SM by SM criteria, the patient is examined for the presence of B-findings and C-findings. C-findings are indicative of severe organ damage caused by the SM-infiltrate and are typically found in ASM and MCL, but not in ISM or SSM. The smoldering variant is defined by the presence of at least 2 B-findings. To differentiate between ASM and MCL, the BM and peripheral blood smear have to be examined. When the percentage of MCs in the BM smear is more than or equal to 20%, the diagnosis is MCL. (B) Definition of C-finding. End-organ damage in SM is diagnosed in a stepwise manner. First, organopathy is judged as being typical for advanced SM (eg, huge osteolyses plus bone fractures, enlarged liver with ascites, SM-based severe cytopenia). In a second step, a histology of the affected organ is obtained to confirm that organ damage is indeed caused by a devastating mast MC infiltrate. Then, organ damage can be regarded as a C-finding and the final diagnosis is established: ASM or MCL with or without an AHNMD.