When Mast Cells Run Amok: A Comprehensive Review and Case Study on Severe Neonatal Diffuse Cutaneous Mastocytosis

Abstract

Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is in the KIT gene. We report a rare case of a boy, born at term, already presenting at birth with generalized subcutaneous nodules on the face, scalp, trunk, back, hands, and feet. The spleen, liver, and inflammatory markers were normal at birth. Tryptase was significantly elevated. A bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin-fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical and inguinal adenopathy, while the skin nodules persisted, especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation; however, compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive, and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.

Keywords: KIT gene; case report; neonatal diffuse cutaneous mastocytosis; review; systemic mastocytosis.

Figure 1

Clinical presentation at age 1 month with generalized subcutaneous nodules, including on the face, scalp, hands, and feet (Panels (A–C)). Darier’s sign was positive, suggesting mast cell degranulation (ovals Panel (A)). Punch biopsy of two skin nodules (Panel (C) arrows indicating the site of the punch biopsy) showed a thin epidermis and the diffuse infiltration of mast cells in the superficial dermis with extension in the deep dermis, some forming aggregates around adnexal structures and blood vessels. Panel (E) shows aggregates of mast cells in the superficial dermis, panel (F) arrows show bundles of collagen, and in panel (G) the oval and arrow indicate a perivascular aggregation of mast cells (Panels (D–K)). Toluidine Blue shows mast cells with intracytoplasmic purple granules (Panel (H)). The mast cells were diffusely positive for CD117 (Panels (I–K)). Panels (L–N): clinical presentation at the age of 2 years. Panel (L) shows aggregates of nodules on the scalp, panel (M) shows the thorax and abdomen, with less visible signs of nodules, and panel (N) shows legs and feet with visible plaque-like lesions showing hyperkeratosis.

Figure 2

Plotted growth parameters of the patient, using the World Health Organization reference [8]. WHO. Anthro App Software for Assessing Growth of the World’s Children and Adolescents; Available online: https://www.who.int/tools/growth-reference-data-for-5to19-years (accessed on 5 May 2020).