Primary Thyroid NUT Carcinoma With High PD-L1 Expression and Novel Massive Gene Fusions: A Case Report With Treatment Implications and Literature Review.

BACKGROUND

Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma.

METHOD

Ultrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC.

RESULTS

We describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the gene on chromosome 15q14. The NGS results revealed a gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of occurred in the exon region, and the mutation site was 15q14. Moreover, single-nucleotide variation (SNV) occurs in the 3' UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery.

CONCLUSION

Thyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of gene fusions in addition to the fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy.