Pediatric Mast Cell Sarcoma of Temporal Bone With Novel L799F (2395 C>T) KIT Mutation, Mimicking Histiocytic Neoplasm

Abstract

Mast cell sarcoma (MCS) is an extremely rare neoplasm with a clinically aggressive course. Because of its rarity, its morphologic and molecular characteristics are still not well defined. We report a case of a 15-year-old girl with MCS of the temporal bone extending into the posterior fossa creating a mass effect. The lesion mimicked a histiocytic neoplasm morphologically, but showed a novel KIT missense mutation, L799F (2395 C>T). The KIT D816V mutation is frequently found in systemic mastocytosis, but it has not been documented in the few reported human MCS cases. However, 1 reported case of MCS has shown a different alteration in the KIT gene. Our case is the first MCS case with L799F mutation, located between the catalytic loop (790 to 797) and the activation loop (810 to 837) of the KIT gene, and only the second case of MCS with KIT mutation documented in the literature. Proximity of the L799F mutation to the enzymatic region of the KIT tyrosine kinase domain may induce resistance to tyrosine kinase inhibitors.

Paediatric mastocytosis: a systematic review of 1747 cases

“…Mutations in exon 17 including D816V were detected in 34% of patients . Mutations outside exon 17 were found in 18% of cases (Del419, F522C, ITD502–503, K509I, M541L, L852L) . In 48% of cases, KIT mutational status was mentioned as wild‐type .…”

“…About 3% of cases of paediatric mastocytosis are aggressive and progress to MCS or MCL and systemic disease with a fatal outcome. The development of such aggressive forms several years after the onset of ‘benign’ paediatric mastocytosis (mastocytoma, n = 2 or UP, n = 5) stresses the importance of long‐term follow‐up for these patients, and reports of a mortality rate > 50% in patients with MCL and MCS clearly show that paediatric mastocytosis does not always have a benign course . Finally, two cases of mastocytosis were associated with ovarian malignant germ cell tumours and a fatal outcome .…”

“…In these cases, the disease may remain active throughout adolescence, with a risk of systemic disease in adulthood. Finally, some rare but very severe forms of mastocytosis, such as mast cell sarcoma (MCS) and mast cell leukaemia (MCL), are reported in children . Factors predicting the course and severity of childhood‐onset mastocytosis have not yet been completely identified.…”

KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis

“…Other non codon 816 KIT mutations can be found{Ryan, 2013 #45;Kim, 2013 #42;Georgin-Lavialle, 2013 #301}…”

Mast cell sarcoma: new cases and literature review

“…Local radiotherapy has been proposed for localized disease. The radiotherapy dosage was variable (40 to 50 Grays), but the efficacy was temporary [ 4 , 8 - 13 ]. Interestingly, no acute MCAS have been described following the use of irradiation, but symptomatic therapy could be applied before radiation as a preventive anti-MCAS therapy.…”