Adenoid Cystic Carcinoma

While initially intended to identify adenocarcinoma, IMI with pafolacianine targets a broad histological cross-section of malignant and nonmalignant primary and metastatic lesions in the lung. As real-world use expands, additional insight will continue to inform utility of pafolacianine in clinical practice and may broaden clinical applicability.

These cases highlight the critical role of integrating cytological, clinical and histopathological data to navigate the diagnostic complexities of thyroid and salivary gland lesions. A multidisciplinary approach and standardized algorithms are essential for improving diagnostic accuracy and patient outcomes.

P=N/A, N=167, Completed, Taproot Health | Recruiting --> Completed | N=100000 --> 167 | Trial completion date: Oct 2031 --> Oct 2024 | Trial primary completion date: Oct 2029 --> Oct 2024

TRPS1 is not an entirely specific marker for breast carcinoma. TRPS1 positivity was noted in a substantial number of salivary gland malignant neoplasms. Cases demonstrating discordance in TRPS1 staining pattern on cytology-surgical correlation warrant further exploration.

RhoC is highly expressed in SACC, and RhoC silencing may target the downstream ROCK1/p38MAPK/TWIST1 signaling pathway, thereby inhibiting the proliferation, invasion, migration, and EMT of SACC while promoting its apoptosis. On the contrary, miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC, and there may be binding sites between the two genes.

P1, N=19, Completed, Groupe Oncologie Radiotherapie Tete et Cou | Suspended --> Completed | N=32 --> 19 | Trial completion date: Sep 2027 --> Oct 2024 | Trial primary completion date: Sep 2026 --> Oct 2024

Decreased membranous and increased cytoplasmic expression could predict malignant behavior and invasive potential.

No abstract available

Additionally, it may not help differentiate SDC or SGTs from each other. Further studies with larger cohorts are needed.

The study improved the understanding of AdCC providing the first documentation of tumor clinical behavior associated with MYB::MPDZ and FUS::MYB fusions and reporting potentially actionable SEC16A::NOTCH1 fusion and MET exon 14 skipping mutation. Further research is needed to explore the therapeutic utility of MET inhibition and the efficacy of γ-secretase inhibitors against rare NOTCH1 fusions in AdCC.

P=N/A, N=600, Recruiting, Ohio State University Comprehensive Cancer Center | N=360 --> 600 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=572, Recruiting, Seagen Inc. | N=430 --> 572 | Trial completion date: Jan 2027 --> Nov 2027 | Trial primary completion date: Jun 2025 --> Nov 2027

P2, N=38, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024 | Trial primary completion date: Mar 2025 --> Nov 2024

Single-cell RNA sequencing (scRNA-seq) of blood from metastatic ACC identified a cluster of circulating tumor cells (CTCs) expressing MYB. Here, we report a sensitive, cost-effective, and minimally invasive diagnostic test that leverages tumor-specific signatures to screen for metastatic ACC disease, potentially enhancing detection earlier than the current clinical standard.

We show that the majority of salivary gland tumor fusions can be effectively detected with a single rapid NanoString based assay, which can serve as a useful adjunctive tool for routine diagnostic head and neck pathology. The assay is low cost with a rapid turnaround time (30 h total assay time per sample batch, with minimal technician input required) compared to alternate detection methods.

P1, N=14, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

The detection of MYB expression using immunohistochemistry varies significantly depending on the antibody used. Comparison with MYB fusion and transcription levels, as determined by NGS, reveals that MYB has a complex relationship between genetic alterations, transcript levels, and protein abundance.

Accordingly, we achieved a complete response in a radiotherapy (RT) and chemotherapy (CT)-refractory patient with locally recurrent lacrimal gland (LG) ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters, especially in "immune-cold" cancer types.

Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Here, we present a case of high grade ACC lacking NR4A3 gene translocation but harbouring a hitherto undescribed SYN2::PPARG gene fusion of uncertain clinical significance. Clinical, radiological, histological and genomic features of the case are discussed alongside a brief review of the literature.

The identification of characteristic genetic alterations and/or immunohistochemical surrogates in many of these tumors has practical applications to establishing an accurate diagnosis and directing clinical management. This review highlights the histopathologic and genetic characteristics of salivary gland-like breast tumors and the implications of the diagnosis for current clinical management.

P=N/A, N=32, Recruiting, Dana-Farber Cancer Institute | N=66 --> 32

Systemic treatments contribute to the survival of patients with salivary gland cancer at relapsed or newly advanced stages. The response to treatment is heavily influenced by histological subtype and treatment specificity.

Salivary glands' ACC shows imbalance of the MMR complex and loss of expression of its components is associated with the overall survival of these patients.

P2, N=10, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Sep 2024 --> Dec 2024

The trial failed to meet the pre-specified 6-month PFS and BOR targets. We hypothesize that TKI efficacy may be reliant upon an interplay between kinase inhibition and the ACC immune microenvironment, while programs promoting cell cycle progression may contribute to TKI resistance. These observations suggest that trials evaluating CDK4/6 inhibition plus a VEGFR-TKI should be considered.

P2, N=64, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.

Overall, we conclude that the presence of Gipie has a confounding role during the ACC-immune cell interaction.

This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in EP300 and the overexpression of MYB may serve as molecular targets for personalized therapy.

Adenoid cystic carcinoma arising in the external auditory canal is rare, and even rarer are cases with sebaceous differentiation mimicking sebaceous carcinoma. This case with clinical, radiologic, gross, and histologic images exemplifies an unusual occurrence of adenoid cystic carcinoma in the external auditory canal with sebaceous differentiation, confirmed by MYB::NFIB fusion.

P2, N=5, Enrolling by invitation, Mayo Clinic | Not yet recruiting --> Enrolling by invitation

The tumor cells showed p63 immunoreactivity in basaloid tumor cells and were negative for CD117 and S-100P. This tumor should be differentiated from adenoid basal cell hyperplasia, which has a favorable outcome, and adenoid cystic carcinoma, with a dismal course.

In conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

Also, 1 case with an ESRRG::DNM3 fusion of unknown significance is described in this study. These discoveries illustrate how broad molecular profiling will expand understanding of changes in known entities.

The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.

Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26). IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.

Our findings revealed a novel reciprocal loop between neural and tumor cells driven by the CCL2/CCR2 axis and exosomal ITGβ5 during PNI of SACC. The present study may provide a prospective diagnostic and anti-PNI treatment strategy for SACC patients via targeting the nerve-tumor interactions.

Although MYB protein expression alone lacks diagnostic precision, protein expression >60% predicted the MYB::NFIB fusion in all tumors.

The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets.

P2, N=64, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.