A case report published in Frontiers in Oncology describes a 13-year-old girl who was diagnosed with concurrent ovarian mixed germ cell tumor and mast cell leukemia (MCL), a subtype of systemic mastocytosis (SM).
“This case underscores the clinical and genetic overlap between germ cell tumors and hematological malignancies in pediatric patients, highlighting the role of KIT mutations as a potential unifying driver,” the authors wrote.
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
The patient originally presented with a fever, fatigue and nausea. A computed tomography scan revealed that she had a large mass within her abdominal and pelvic cavities. She was given cefazolin but experienced an anaphylactic reaction to the antibiotic.
Read more about SM prognosis
Blood testing demonstrated anemia, thrombocytopenia (low platelet count) and elevated markers of germ cell tumors, or tumors that develop from the reproductive cells. Exploratory surgery via laparotomy confirmed the diagnosis, and further analysis revealed tumor cells in the bone marrow, indicating potential metastasis.
The patient began chemotherapy with etoposide, cisplatin and bleomycin. Although levels of some tumor markers declined, her anemia and thrombocytopenia persisted.
The authors later performed whole genome sequencing on the tumor, identifying the KIT D816V mutation, along with mutations in the NRAS and TP53 genes. The patient then began additional treatment with avapritinib and ruxolitinib.
After several weeks on this treatment regimen, the patient still exhibited significant tumor cell infiltration in the bone marrow. Bone marrow sequencing demonstrated the same mutations that were observed in the germ cell tumor. The bone marrow also contained 80% abnormal mast cells. She was officially diagnosed with both stage IV mixed germ cell tumor and mast cell leukemia.
“Given the consistent co-occurrence of KIT mutations in previously reported similar cases, we propose the recognition of a distinct disease entity: ovarian germ cell tumor/mastocytosis with KIT mutations,” the authors stated.
The team began a new treatment regimen consisting of bortezomib, thalidomide, dexamethasone and arsenic trioxide. The patient soon developed sensory alterations in her limbs, leading the authors to suspect central nervous system leukemia. They chose not to perform a spinal tap to confirm the diagnosis, however, due to her thrombocytopenia.
Ultimately, the authors discontinued chemotherapy, and the patient died of multiple organ failure.
The case report highlights the need for early diagnosis with genetic testing and multidisciplinary collaboration in order to effectively diagnose and treat such malignancies. Future studies will be needed to identify potential combination therapies that can be used to treat these patients.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
