Table 4.
Proposed Refined B-findings and C-findings.
| B-findings | C-findings (SM-induced Organ Damage) |
|---|---|
| High MC burden: | - |
| Infiltration grade (MC) in BM ≥30% in histology (IHC) and/or serum tryptase ≥200 ng/mLa and/or KIT D816V VAF ≥10% in BM or PB leukocytes | |
| Signs of myeloproliferation and/or myelodysplasiab: | Cytopenia/s: |
| Hypercellular BM with loss of fat cells and prominent myelopoiesis ± left shift and eosinophilia ± leukocytosis and eosinophilia and/or discrete signs of myelodysplasia (<10% neutrophils, erythrocytes, and megakaryocytes) | ANC < 1 × 109/L |
| Hb < 10 g/dL | |
| PLT < 100 × 109/L | |
| (one or more found) | |
| Organomegaly: | |
| Palpable hepatomegaly without ascites or other signs of organ damage or/and palpable splenomegaly without hypersplenism and without weight loss or/and lymphadenopathy palpable or visceral LN-enlargement found in ULS or CT (>2 cm) | Hepatopathy: |
| Ascites and elevated liver enzymesc ± hepatomegaly or cirrhotic liver ± portal hypertension | |
| Spleen: | |
| Palpable splenomegaly with hypersplenism ± weight loss ± hypalbuminemia | |
| GI tract: | |
| Malabsorption with hypoalbuminemia ± weight loss | |
| Bone: | |
| Large-sized osteolysis (≥2 cm) with pathologic fracture ± bone pain |
aIn the case of a known HαT, the basal serum tryptase level should be adjusted. Although the optimal way of adjustment still needs to be defined, one way is to divide the basal tryptase level by 1 plus the extra copy numbers of the alpha tryptase gene. Example, when the tryptase level is 300 and 2 extra copies of the alpha tryptase gene are found in a patient with HαT, the HαT-corrected tryptase level is 100 (300/3 = 100) and would thus not qualify as a B-finding.
bSigns of myeloproliferation and/or myelodysplasia must be discrete and stable (neither disappear nor progress) and must not reach diagnostic criteria of an MPN, MDS, or MPN/MDS in which case the diagnosis changes to SM-AHN. The presence of a myeloid AHN excludes B-findings and SSM by definition.
cAlkaline phosphatase levels are typically elevated in patients with advanced SM and SM-induced liver damage. In some of these patients, only elevated liver enzymes but no (clinically relevant) ascites is found.
AHN = associated hematologic neoplasm; ANC = absolute neutrophil count; BM = bone marrow; CT = computed tomography; GI = gastrointestinal; HαT = hereditary alpha-tryptasemia; Hb = hemoglobin; IHC = immunohistochemistry; LN = lymph node; MC = mast cells; MDS = myelodysplastic syndrome; MPN = myeloproliferative neoplasm; PB = peripheral blood; PLT = platelet count; SM = systemic mastocytosis; SSM = smoldering systemic mastocytosis; ULS = ultrasound; VAF = variant allele frequency.