Mastocytosis may present with varied clinical manifestations depending on the mast cell burden and the extent of tissue involvement. Children are primarily represented on the benign end of the disease spectrum, with disease limited to skin and diagnosed with one of three cutaneous variants; maculopapular cutaneous mastocytosis (MPCM), diffuse cutaneous mastocytosis (DCM) or mastocytoma (MTOMA). Systemic mastocytosis is typically seen in adults with somatic mutations in KIT. However, children may also have systemic disease, with similar mutations in KIT and as early as infancy.The use of allelespecific quantitative polymerase chain reaction to identify KIT D816V in the peripheral blood of adults with mastocytosis has been reported to have value in the diagnosis, assessment of disease burden and management of this disease. To examine the value of this assay in children with cutaneous manifestations of mastocytosis, we assessed data on 65 patients with all variants of paediatriconset mastocytosis, including those known to have systemic disease, to correlate KIT mutation status with clinical findings, serum tryptase levels and bone marrow histopathology. The PB ASqPCR for the KIT D816V mutation was consistently negative in patients with cutaneous disease only (MCPM, DCM and MTOMA, n = 37) and without a history of organomegaly documented to be associated with systemic disease in paediatric patients. Of the 23 patients diagnosed with systemic disease (ISM), the PB ASqPCR was positive in 16/23 samples (0047384%). PB ASqPCR was negative in two ISM patients with organomegaly that had KIT D816Yassociated systemic disease (serum tryptase values 184 and 244 ng/ml), one patient with a bone marrow diagnosis of ISM and no KIT mutations detected in the marrow samples, as well as four patients diagnosed with ISM by bone marrow biopsy. These latter four patients had a low mast cell disease burden in bone marrow biopsies (mast cells 5% of total marrow cells); but positive KIT D816V mutation by RTPCR/RFLP in their marrow samples. As PB ASqPCR for the KIT D816V mutation was not performed at the time of the original bone marrow biopsy procedure in these four patients, we obtained their frozen PB samples collected at the time of the bone marrow biopsy procedure and analyzed them using ASqPCR for the KIT D816V mutation. The results were negative in all four samples. In addition, there has been a significant improvement in their clinical status, as evidenced by a major or complete resolution of skin lesions, a significant decrease in serum tryptase (average 339 to 110 ng/ml) and a decrease in medication usage to as needed medications from daily dosing over a period of 713 years. The specificity of PB ASqPCR KIT D816V assay was 100% for all variants of cutaneous disease. The sensitivity for the detection of the systemic disease when documented with a marrow biopsy, was 696%. We performed followup PB ASqPCR testing in most patients (615%). Data was found to yield consistent results when followed up to 36 months. Patients with a positive value remained positive and these results continued to correlate with serum tryptase values. In addition, the patients with negative values remained negative. These findings were the basis of the development of an algorithm to assist in the decision for when to perform a bone marrow biopsy in children presenting with cutaneous manifestations of mastocytosis.
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