Challenging diagnosis of indolent systemic mastocytosis isolated to the GI tract

Discussion

Mastocytosis is a rare group of heterogeneous disorders defined by abnormal growth and accumulation of mast cells in one or more organ system.2 The estimated prevalence of mastocytosis of any type is 1 in 10,000.3 The life expectancy for patients with indolent SM is similar to that of patients without the condition. The mortality risk to patients in this subgroup is from the potential for anaphylaxis secondary to mast cell degranulation.1 Otherwise, clinical manifestations often depend on the organ system involved. Symptoms of indolent SM are largely due to mast cell degranulation, while symptoms in aggressive SM are more commonly due to tissue infiltration and subsequent dysfunction.4 Overall, approximately 80% of patients with mastocytosis present with cutaneous involvement; the indolent form of SM often presents with skin lesions, whereas the aggressive form normally does not.4

Typical skin findings include lesions caused by aggregates of mast cells that urticate when stroked (Darier’s sign), red-brown to yellowish macules, papules or nodules of varying diameter from millimetres to several centimetres (urticaria pigmentosa), with telangiectasias (telangiectasia macularis eruptive perstans), brown plaques or nodules typically 4–5 cm in diameter (mastocytoma), or diffuse skin infiltration with spontaneous blistering (diffuse cutaneous mastocytosis).3

Mastocytosis is separated into two broad categories: pure cutaneous (CM) and SM.4 5 CM is more common and generally occurs in the paediatric population and typically resolves by adolescence, whereas adults more commonly present with SM, which is more likely to persist.6

Despite the majority of patients with indolent SM presenting with some level of skin involvement, our patient lacked any cutaneous manifestations of the disease, making diagnosis difficult. However, polypectomy findings revealed that our patient met the WHO criteria for the diagnosis of SM (figure 3). The patient displayed one major and two minor criteria (atypical mast cells on histology (figure 1) that stained positive for CD25 (figure 2)). Though the patient’s serum tryptase did not meet the cut-off of 20 ng/mL, the KIT 816 mutation was not found, and the cells were not positive for CD2—the satisfaction of one major and one minor WHO criteria merit a diagnosis of SM.5 Despite this, it is difficult to definitively say that the patient’s symptoms were solely due to her SM as she opted not to start mast cell stabilisation therapy. On follow-up, the patient felt that her symptoms were manageable with dietary changes and avoidance of triggers alone. As such, it is possible that these pathology findings were incidental.

Figure 3

WHO criteria for diagnosis of SM require one major and one minor criteria or three minor criteria to be met.5 SM, systemic mastocytosis.

Importantly, up to 80% of patients with SM experience GI symptoms such as abdominal pain, diarrhoea, nausea and vomiting.7 In the absence of skin involvement, these non-specific symptoms combined with subtle characteristic histopathological features (easily missed small aggregates of mast cell infiltrate) make the diagnosis of SM with GI involvement challenging. Clinically, it may mimic more common conditions such as irritable bowel syndrome and inflammatory bowel disease.4 7–9 Despite this, clinicians should consider indolent SM when presented with a case of chronic GI symptoms, refractory to medical management, without characteristic skin findings or obvious histopathology, as SM can have a subtle presentation, as described in this case.