Mastocytosis is a term broadly referring to tissue mast cell hyperplasia. This proliferation is generally classified as either cutaneous, with or without systemic involvement, or systemic without cutaneous disease. Mastocytosis most commonly manifests as cutaneous disease (urticaria pigmentosa, mastocytoma), seen more often in children with involvement typically limited to the skin. In contrast, adult cutaneous variants frequently have systemic disease. See telangiectasia macularis eruptiva perstans (TMEP).
Systemic mastocytosis is a less common myeloproliferative variant composed of a heterogeneous disease compilation. In general there is no age or sex predilection.The adult systemic condition has been further stratified numerous ways based on clinical criteria as well as on associated mutations, namely activating c-kit mutations. This discussion is based on the most recent 2008 World Health Organization (WHO) classification. WHO classified four major subtypes of extracutaneous systemic mastocytosis: (1) indolent systemic mastocytosis, (2) systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease (SM-AHNMD), (3) aggressive systemic mastocytosis, and (4) mast cell leukemia.
Indolent systemic mastocytosis is most frequently seen. Mast cells primarily, yet modestly, infiltrate the bone marrow and may involve other organs, including the spleen, liver, and gastrointestinal tract. Because the disease is typically limited in children and often chronic and stable in adults, prognosis is favorable.
Systemic mastocytosis with a chronic myeloproliferative neoplasia (SM-AHNMD) has a course and prognosis determined by efficacy of management of the underlying disease.
Aggressive systemic mastocytosis, in which there is organ destruction from a mast cell infiltrate, is rare and should promote investigation for mast cell leukemia or other hematologic disorders such as myelodysplastic syndromes, myeloproliferative or myelodysplastic disorders, acute myeloid leukemia, and chronic myeloproliferative neoplasia.
Mast cell leukemia is seen in two-thirds of patients with aggressive systemic mastocytosis and portends rapid progression that could potentially result in multi-organ failure. It is defined as greater than or equal to 20% mast cells in bone marrow smears and by circulating mast cells, often greater than or equal to 10% in peripheral smears. Pancytopenia can occur and may explain instances in which peripheral mast cells comprise less than 10% of the differential.
ICD10CM: Q82.2 – Mastocytosis
SNOMEDCT: 397016004 – Systemic Mast Cell Disease
Differential Diagnosis & Pitfalls
Mast cell activation syndrome – The more recently termed mast cell activation syndrome (MCAS) describes patients who have multiple mast cell mediator-induced symptoms that do not meet the WHO criteria (see Best Tests) for diagnosis of systemic mastocytosis when other underlying diseases have been excluded.
Pheochromocytoma – Patients with an underlying pheochromocytoma present with paroxysms of hypertension, tachycardia, and diaphoresis. Pallor is often seen during these paroxysms, with flushing following resolution of the attack.
Carcinoid syndrome – Patients with foregut carcinoid tumors may suffer from carcinoid syndrome, which classically manifests with gastrointestinal complaints. Chronic watery diarrhea with associated weight loss is the most frequent complaint; however, patients may also complain of abdominal pain, constipation, and nausea. A persistent and intense salmon-pink to red flushing occurs in these patients. As opposed to foregut carcinoid tumors, patients with midgut tumors typically demonstrate a more cyanotic flushing. Due to an acquired niacin deficiency, pellagra-like cutaneous symptoms are also seen.