Neoadjuvant PD-1 blockade may be efficacious in some individuals with high-risk, resectable oral cavity head and neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 individuals displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, or JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T cell clones. A high ratio of regulatory T to T helper 17 cells in pretreatment blood predicts low T cell receptor repertoire diversity in pretreatment blood, a low cytolytic T cell signature in pretreatment tumors, and innate resistance. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for individuals with resectable head and neck cancer.

Patients with spinal cord injury (SCI) commonly experience central neuropathic pain (CNeP), which is challenging to treat. Mirogabalin is effective for peripheral neuropathic pain, but evidence for CNeP is lacking.

Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease. Onset is usually in the 3rd to 5th decade with hearing loss and an indolent course. ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC). Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). Comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostaines for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC.