Prevalence and Characteristics of Cutaneous Mastocytosis in Adult-Onset Mastocytosis in the Skin

INTRODUCTION

Mastocytosis in the skin (MIS) is a provisional diagnosis until systemic mastocytosis (SM) is ruled out. Cutaneous mastocytosis (CM) is the most common form of mastocytosis in children, but it is rarely described in adults, with an unknown prevalence. Additionally, there are patients with MIS who meet minor criteria for SM but insufficient criteria for diagnosing SM. These patients are still diagnosed of CM, and there is a growing interest in this population as it may represent an undiagnosed form of SM. The objective of this study is to determine the prevalence and characteristics of CM patients with adult-onset MIS.

MATHERIALS AND METODS

A retrospective observational study involving patients with adult-onset MIS who were referred to the Multidisciplinary Mastocytosis Unit between 1995 and 2023 was conducted. We described the epidemiological, biological, and histological characteristics of the patients. Afterwards, we meticulously reviewed the diagnostic criteria of patients with MIS and CM to determine if they had a true CM or SM. Finally, a receiver operating characteristic (ROC) curve analysis was used to determine the most accurate cutoff for tryptase level in our cohort. All procedures were in accordance with the Declaration of Helsinki and local Ethics Committees.

RESULTS

Ninety-nine patients with adult-onset MIS were included in the study. The median age was 47 years (range 20-85). 75 (75%) had indolent SM (ISM), 13 (13%) had CM, 2 had smoldering SM, 1 had advanced SM, 1 had SM associated with a hematological neoplasm, and 1 had well-differentiated SM. In 6 (6%) patients, the diagnosis was still MIS because a bone marrow biopsy was not performed due to patient preference.

Regarding the diagnosis of patients with ISM (n=75), 92% of patients met the major criterion. The aberrant expression of CD2/CD25/CD30 in mast cells was the commonest fulfilled minor criterion (91% of patients), followed by abnormal cytomorphology (90%), KIT D816V mutation (87%) and tryptase ≥20 μg/L (61%). The median tryptase value was 21.8 μg/L (mean 39.8), and only 9% of patients had a tryptase <10 μg/L. Mast cell purification was performed in 19% of patients, and KIT D816V was detected in all of them.

Concerning patients with CM (n=13), none of them met the major criterion and 7 (54%) did not meet any minor criteria. 3 (23%) met one minor criterion and 3 (23%) met two minor criteria. The median tryptase level was 5.5 μg/L (range 3-13.3), with three patients having >10 μg/L. Regarding patients that met at least one minor criterion, abnormal cytomorphology was present in 80% patients, aberrant antigen expression was found in 80% of patients, KIT D816V mutation was found in one patient (mast cell purification was performed in 33% of patients), and none had a tryptase ≥20 μg/L.

Finally, we tried to identify the most accurate tryptase cutoff with a ROC curve, optimizing sensitivity and specificity. In our cohort, a cutoff of 20 μg/L has a sensitivity of 61.3% and a specificity of 100% for ISM. Lowering the cutoff to 10 μg/L, the sensitivity would be 92% with a specificity of 76.9%. Using this value, 2 (15%) of the patients with CM with minor criteria would be re-diagnosed as having ISM, and all patients with ISM would still have an ISM diagnosis.

DISCUSSION

CM is infrequent in patients with adult-onset MIS, with a prevalence of 13% in our cohort. However, more than half of these patients meet some minor criteria or have an incomplete work-up, raising the question if we might be facing an incorrect diagnosis of SM. A tryptase cutoff of 10 μg/L might help to correctly diagnose some CM patients who fulfill other minor criteria as SM.

Bolea:Novartis: Other: travel grants, Research Funding; Incyte: Other: travel grants, Research Funding. García Gutiérrez:BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; CTA: Honoraria; GSK: Consultancy; Novartis, Incyte: Speakers Bureau; Novartis, Incyte, GSK, Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis BMS Pfizer Incyte GSK: Consultancy. Piris-Villaespesa:Novartis: Consultancy, Speakers Bureau; GSK: Consultancy, Speakers Bureau; BluePrint: Consultancy, Research Funding, Speakers Bureau.