Well-differentiated systemic mastocytosis showed excellent clinical response to imatinib in the absence of known molecular genetic abnormalities

Abstract

Introduction:Well-differentiated systemic mastocytosis (WDSM) is a rare, recently recognized provisional subvariant of systemic mastocytosis (SM). We report a case of WDSM that showed excellent clinical and cutaneous response to imatinib in the absence of known molecular genetic abnormalities.Clinical Findings/Diagnoses:We present a 24-year-old woman with childhood onset of skin manifestations that progressed to mediator-related systemic events, and a gastrointestinal tract mastocytoma. A subsequent bone marrow examination showed WDSM. Treatment with imatinib resulted in complete resolution of cutaneous lesions and systemic symptoms, which relapsed with the discontinuation of the drug. Targeted next-generation sequencing-based mutation analysis did not demonstrate any mutations in the coding regions of KIT or other genes commonly associated with myeloid neoplasms.Conclusions:The diagnosis of WDSM is challenging in the absence of spindle-shaped mast cells, CD2 or CD25 expression, and KIT D816 mutation. This case illustrated the need for recognizing this unique variant of SM for diagnostic and therapeutic implications.

Systemic Mastocytosis and Other Entities Involving Mast Cells: A Practical Review and Update

“…In addition, one study revealed that approximately 20% of ISM patients lack mast cell clusters in the bone marrow, and ~30% of ISM patients show a serum tryptase level below 20 ng/mL [ 30 ]. Of note, serum tryptase levels are correlated with mast cell activation of all the mast cells in various organs and do not solely reflect neoplastic mast cell activity [ 31 ]. Furthermore, normal mast cells demonstrate a range of activation, and the biology of the secretory phenotype and mediator release patterns have not been fully elucidated [ 32 ].…”

“…A limited number of WDSM cases have been reported to date [ 28 , 31 , 36 , 38 , 39 , 40 , 41 , 42 , 43 ]. Clinically, WDSM has an early onset presentation with familial aggregation, female predominance, and cutaneous involvement.…”

“…On the other hand, aberrant CD30 expression appears to be a recurrent/reliable feature in reported WDSM cases [ 31 ]; this raises the question whether CD30 expression should be implemented as evidence of clonality to mitigate CD2 and CD25 negativity in this setting. Alvarez-Twose et al suggested the following minor diagnostic criteria for WDSM: (1) adult women who started in childhood or with familial aggregation, (2) clustering of bone marrow mast cells in pairs or triplets, (3) expression of CD30 and over-expression of tryptase by flow cytometry analysis, and (4) mutations involving any codon in the KIT gene [ 36 ].…”

Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee

“…17 However, mast cells in WDSM are less likely to have KIT mutations, are often morphologically normal (round), and do not show aberrant expression of CD2 and CD25; thus, they often do not fulfill the WHO criteria for SM. However, establishing the diagnosis of WDSM is important because this form of SM is often responsive to imatinib, 113 and thus alternative diagnostic criteria were proposed. 17 Clinical criteria for suspecting WDSM are not fully established, but they include persistence of skin disease, female sex, and familial mastocytosis.…”

Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis

“…Wild-type KIT can be currently targeted by a progressively higher number of small tyrosine-kinase inhibitor (TKI) molecules including some that—e.g., midostaurin (PKC412) or imatinib—have proven beneficial for SM [10,11,12,13]. However, overall CR rates, even with these new drugs still remain low, except among the few WDSM patients presenting with mutations at exons 9 and 10 of KIT [14,15,16,17,18]. Altogether, this highlights the need for further improvement in the treatment of SM, particularly for advanced SM [19].…”