ABSTRACT
NUT carcinoma (NC) is a highly aggressive, poorly differentiated carcinoma that harbors a t(15:19) translocation, leading to the fusion of the NUTM1 gene. While the upper aerodigestive tract along the midline (head, neck, thorax, and mediastinum) is commonly reported as the primary site of NC, subsequent cases have emerged in diverse locations. Achieving a definitive diagnosis based solely on morphology is challenging; however, it can be achieved using immunohistochemistry (IHC) specific to the NUT antibody or by demonstrating the characteristic BRD4::NUTM1 fusion. Accurate and timely diagnosis can potentially inform patient management and guide treatment. While histologic documentation of NC is commonly found, there is a limited description of its cytologic features. A 39-year-old male with a history of sinonasal squamous cell carcinoma (SCC) presented with a right parotid mass aspirated via fine needle aspiration cytology (FNA). Histologic examination of the previous sinonasal pathology reviewed at our institution revealed sheets of primitive-appearing, monotonous, undifferentiated cells with distinct, prominent nucleoli. Additionally, there were foci of abrupt keratinization, accompanied by a notable neutrophilic infiltrate. The initial diagnosis of SCC was reclassified to NC and confirmed through NUT IHC and molecular testing. Although the parotid FNA initially suggested the possibility of a variety of small round blue cell tumors, it exhibited morphological similarities to the sinonasal tumor, leading to the diagnosis of metastatic NC. Cytomorphologic features of NC are limited and can overlap with various small round blue cell tumors. Correct classification is especially pivotal in the era of targeted therapy, considering the ongoing development and evaluation of BET inhibitors targeting BRD4.
ABSTRACT
Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and target proteins involved in ototoxicity are still unknown. The objective of the present study was to identify target proteins involved in gentamicin-induced cytotoxicity to better characterize the molecular pathways involved in sensory cell damage following ototoxic drug administration using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We identified several unique proteins involved in gentamicin-induced cytotoxicity, expression of which were further confirmed using confocal microscopy. Further investigation of these pathways can inform the design and discovery of novel treatment modalities to prevent sensory cell damage and preserve their function.
