INTRODUCTION
Mastocytosis represents a clonal, neoplastic proliferation of
morphologically and immunophenotypically abnormal mast cells, organized
in multifocal clusters, in one or more organ systems.1 It is considered a rare hematological condition,
with a prevalence of 1 in 10.000 persons. 2 However,
mastocytosis remains underdiagnosed, due to the heterogeneous clinical
presentation.
3 Based on the site of the clonal proliferation,
mastocytosis can be divided into cutaneous mastocytosis and systemic
mastocytosis (SM). Cutaneous mastocytosis is generally benign, primarily
affects children within the first two years of life, and remits around
adolescence. It usually manifests with skin lesions, gastrointestinal
cramps, and anaphylaxis. 1,2 SM mainly affects adults.
The clonal proliferation involves the bone marrow, the skin, and other
organs and it has a chronic evolution, with a poor prognosis.4 Besides skin rashes and gastrointestinal symptoms,
patients with SM may experience cardiovascular problems, like
an irregular heartbeat; neuropsychiatric 5,6complications including anxiety or depression; osteoporosis due to mast
cell infiltration into bones; anaphylaxis and hypotension.
The pathophysiology of SM is represented primarily by mutations in the
KIT gene, particularly the KITD816V variant, which leads to uncontrolled
mast cell proliferation.1, 3, 7
The diagnosis of SM usually requires a bone marrow biopsy. A positive
diagnosis is based upon the 2016 WHO (World Health Organization)
criteria (Table 1): one major and one minor criterion is required, or in
the absence of the major criteria, three minor criteria need to be
met.1, 2, 3, 7
The treatment strategy of SM is highly reliant upon the subtype,3 mast cell leukemia having the worst prognosis out of
all the subtypes, with a median survival of 2 months.8 In this regard, easier forms, benefit supportive
treatment of mast cell mediator-related symptoms and osteoporosis. Mast
cell mediator-related symptoms can be treated with antihistamines,
H2-inhibitors, or aggressive treatment with epinephrine,
corticosteroids, leukotriene receptor antagonists, or omalizumab in case
of anaphylaxis. 9 Osteoporosis prevention and
treatment can be done with calcium+D3 supplements, bisphosphonates, or
alpha interferon. More advanced forms benefit from cytoreductive
therapy, often with Midostaurin because it is currently considered the
gold-standard treatment with a response rate of 60% and the best
results in the aggressive SM subtype.7 Usually it is
well tolerated, and it can also be used as a maintenance therapy after
an allogeneic stem cell transplant. There are very few studies that have
demonstrated the superiority of allogeneic stem cell transplants over
KIT inhibitors. Therefore, this treatment is reserved for cases of SM
with severe symptoms that are refractory to standard
therapy.3