Extranodal Natural Killer/T-cell Lymphoma, Nasal Type Occurring After Actinomyces Infection: A Case Report.

The pathogenesis of extranodal natural killer/T-cell lymphoma (ENKTL) remains largely unknown. Herein, we present a case of ENKTL that may have occurred during the treatment of Actinomyces infection. A 69-year-old woman was admitted to our hospital with nasal bleeding, and a nasopharyngeal mass was observed. The patient was diagnosed with Actinomyces infection on biopsy, and oral antibiotics were administered. The tumor decreased in size; however, swelling of the nasal mucosa and perforation of the nasal septum were observed. A biopsy revealed a recurrence of Actinomyces infection, and oral antibiotics were again administered. The mucosal swelling improved temporarily, but the condition gradually deteriorated. The patient was diagnosed with ENKTL based on a third biopsy. Retrospective evaluation of the biopsies showed that there were no CD56-positive cells in the first specimen; however, the number of CD56-positive cells gradually increased in the second and third specimens. We retrospectively observed the occurrence of ENKTL under chronic inflammatory conditions due to Actinomyces infection in this case. In addition, this case suggests that the possibility of malignancy must be considered when managing such patients with Actinomyces infection.

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. METHODS: This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. RESULTS: After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. CONCLUSION: Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:228-235, 2024.

TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas.

BACKGROUNDS: The importance of TERT promoter (pTERT) mutation of oral cavity squamous cell carcinoma (OCSCC) with clinical features and genetic alterations are not well recognized. METHODS: We retrospectively analyzed genetic data from multiple databases, including 260 cases from the C-CAT database, 407 cases from the MSK-MetTropism database, and 40 OCSCC datasets from in-house clinical samples. RESULTS: From C-CAT database, TP53 (66%), CDKN2A (51%), and pTERT (29%) were the most frequent mutations observed. pTERT mutations were more prevalent in OCSCC (63%), younger individuals, and women (46%), with lower rates of alcohol abuse and smoking and co-mutated with TP53, HRAS, and CASP8. MSK-MetTroposim data validated with the enrichment of pTERT mutations in OCSCC, among women and Asian individuals. In-house datasets OCSCC with pTERT mutation (50%) characterized by fewer recurrent neck metastases. CONCLUSION: The study suggests that OCSCC with pTERT mutation represents a distinct subgroup with unique clinical and genetic characteristics.

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database.

BACKGROUND: Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed. METHODS: We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher's exact test, Kaplan-Meier analysis, log-rank test and Cox regression models were used for statistical analysis. RESULTS: In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival. CONCLUSION: CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.

p16 status and high-risk human papilloma virus infection in squamous cell carcinoma of the nasal vestibule.

OBJECTIVE: The status of human papilloma virus (HPV) and p16 overexpression for nasal vestibule squamous cell carcinoma (NVSCC) is unclear. The purpose of this retrospective study was to analyze the presence of HPV and the role of p16 overexpression as a surrogate marker in cases of NVSCC. METHODS: Retrospective analysis was performed on patients who were diagnosed and treated for NVSCC at the University of Tokyo Hospital, Japan. p16 immunohistochemistry was considered positive with at least moderate staining intensity and diffuse staining (≥75% of tumor cells), according to the 8th edition of the American Joint Commission on Cancer. HPV-DNA testing was performed using multiplex polymerase chain reaction. RESULTS: Five patients were included in the study. Ages ranged from 55 to 78 years; there were two men and three women; two had T2N0, and three had T4aN0. Surgery was performed in one case, surgery plus radiation therapy (RT) in one case, and chemoradiation therapy (CRT) in three cases. Four of the five tumors showed p16 overexpression. One of five cases had an HPV-16 genotype. The mean follow-up period was 73 months, and all the patients survived. One patient with p16-negative carcinoma had local recurrence and underwent salvage surgery. Of the four patients with p16-positive carcinoma, one with CRT and one with surgery plus RT, each had delayed cervical lymph node metastasis, which was salvaged with neck dissection subsequent RT. CONCLUSIONS: In NVSCC, four of the five cases were p16-positive, and one was high-risk HPV infection.