Guidelines and diagnostic algorithm for patients with suspected systemic mastocytosis: a proposal of the Austrian competence network (AUCNM)

Abstract

Systemic mastocytosis (SM) is a hematopoietic neoplasm characterized by pathologic expansion of tissue mast cells in one or more extracutaneous organs. In most children and most adult patients, skin involvement is found. Childhood patients frequently suffer from cutaneous mastocytosis without systemic involvement, whereas most adult patients are diagnosed as suffering from SM. In a smaller subset of patients, SM without skin lesions develops which is a diagnostic challenge. In the current article, a diagnostic algorithm for patients with suspected SM is proposed. In adult patients with skin lesions and histologically confirmed mastocytosis in the skin (MIS), a bone marrow biopsy is recommended regardless of the serum tryptase level. In adult patients without skin lesions who are suffering from typical mediator-related symptoms, the basal serum tryptase level is an important diagnostic parameter. In those with slightly elevated tryptase (15-30 ng/ml), additional non-invasive investigations, including a KIT mutation analysis of peripheral blood cells and sonographic analysis, is performed. In adult patients in whom i) KIT D816V is detected or/and ii) the basal serum tryptase level is clearly elevated (> 30 ng/ml) or/and iii) other clinical or laboratory features are suggesting the presence of occult mastocytosis, a bone marrow biopsy should be performed. In the absence of KIT D816V and other indications of mastocytosis, no bone marrow investigation is required, but the patient's course and the serum tryptase levels are examined in the follow-up.

Keywords: KIT D816V; Mastocytosis; diagnostic algorithm; staging; tryptase.

Figure 1

In adult patients without evidence of mastocytosis in the skin (MIS) but suspected systemic mastocytosis (SM), the basal serum tryptase level is an important initial screen parameter. In patients who have a clearly elevated basal tryptase, a bone marrow biopsy has to be considered. In patients with normal or slightly elevated tryptase, peripheral blood cells should be examined for the presence of KIT D816V using a highly sensitive test. In patients in whom typical signs and symptoms (osteoporosis, histamine-symptoms, anaphylaxis with negative allergy-test) or KIT D816V are detected, a bone marrow biopsy should be performed. If the KIT mutant is not detectable and symptoms are non-specific or can be explained by another disorder involving mast cells (e.g. allergy), the patient will be examined in the follow up, including repeated examinations of blood counts and serum tryptase levels.