BACKGROUND: Theranostics is a combined diagnostic and treatment approach to individualized patient care. Kostmann syndrome, or severe congenital neutropenia, is an autosomal recessive disease that affects the production of neutrophils. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy associated with gene alterations, including in the mitogen-activated protein kinase (MAPK) signaling pathway gene. Translocation of the ETS variant 6/neurotrophic receptor tyrosine kinase 3 (ETV6/NTRK3) gene has been implicated in radiation-induced and pediatric forms of thyroid carcinoma but has rarely been described in sporadic PTC. This report is of a case of PTC in a patient with Kostmann syndrome associated with ETV6/NTRK3 gene translocation.

CASE REPORT: A 32-year-old woman with a history of Kostmann syndrome, acute myeloid leukemia (AML), and chronic graft versus host disease (GVHD) was diagnosed with PTC with cervical lymph node metastases and soft tissue invasion following total thyroidectomy and bilateral modified radical neck dissection. Her postoperative radioactive iodine (RAI) scan confirmed lymph node metastasis. Gene expression studies identified increased expression of iodine-handling genes and ETV6/NTRK3 gene fusion. Because of the bone marrow compromise due to Kostmann syndrome and AML, a careful genomic and molecular analysis was performed to guide therapy.

CONCLUSIONS: This is the first reported case of the association between PTC, Kostmann syndrome, and ETV6/NTRK3 gene translocation in which multimodality treatment planning was optimized by genomic profiling.

Keywords: Gene Fusion, Genomics, Iodine Radioisotopes, Nanomedicine, Neutropenia, Congenital Bone Marrow Failure Syndromes, Proto-Oncogene Proteins c-ets, Receptor, trkC, Repressor Proteins, Theranostic Nanomedicine, Thyroid Cancer, Papillary