Clinical challenge for gastroenterologists–Gastrointestinal manifestations of systemic mastocytosis: A comprehensive review

Table 1 Systemic mastocytosis criteria according to World Health Organization 2016

Major SM criterion	Multifocal dense infiltrates of MCs (≥ 15 MCs in aggregates) in BM biopsies and/or in sections of other extracutaneous organ(s)
Minor SM criteria	(a) > 25% of all MCs are atypical cells (type I or type II) on BM smears or are spindle-shaped in MC infiltrates detected on sections of visceral organs
	(b) KIT point mutation at codon 816 in the BM or another extracutaneous organ
	(c) MCs in BM or blood or another extracutaneous organ exhibit CD2 and/or CD25
	(d) Baseline serum tryptase level >20 ng/mL (in case of an unrelated myeloid neoplasm, item d is not valid as an SM criterion)

If at least 1 major and 1 minor or 3 minor systemic mastocytosis (SM) criteria are fulfilled, the diagnosis of SM can be established. BM: Bone marrow; MCs: Mast cells; SM: Systemic mastocytosis.

Table 2 B and C Findings in systemic mastocytosis

B and C Findings in systemic mastocytosis
B Findings
BM biopsy showing > 30% infiltration by MCs (focal, dense aggregates) and serum total tryptase level > 200 ng/mL
Myeloproliferation or signs of dysplasia in non-MC lineage(s), no prominent cytopenias; criteria for AHN not met
Hepatomegaly and/or splenomegaly on palpation without impairment of organ function and/or lymphadenopathy on palpation/imaging (> 2 cm)
C Findings1
Cytopenia(s): ANC < 1 × 109/L, Hb < 10 g/dL, or platelets < 100 × 109/L
Hepatomegaly on palpation with impairment of liver function, ascites, and/or portal hypertension
Skeletal lesions: Osteolyses and/or pathologic fractures
Palpable splenomegaly with hypersplenism
Malabsorption with weight loss from gastrointestinal tract MC infiltrates

¹Must be attributable to the mast cell infiltrate. AHN: Associated hematological neoplasm; ANC: Absolute neutrophilic count; BM: Bone marrow; MCs: Mast cells.

Table 3 Differential diagnosis between systemic mastocytosis and gastrointestinal diseases

Symptoms	Differential diagnosis
Chronic diarrhea	Irritable bowel syndrome; Inflammatory bowel disease; Celiac disease; Thyreopathies (i.e. hyperthyroidism, medullary thyroid cancer); Pancreatopathyes
Epigastric pain, dyspepsia, heartburn	Functional dyspepsia; Peptic ulcer; Gastroesophageal reflux disease; H. pylori related gastritis; Zollinger-Ellison Syndrome
Flushing	Neuroendocrine neoplasms
Hepato-splenomegaly, portal hypertension	Cirrhosis; Non cirrhotic portal hypertension