Background: Anaplastic thyroid carcinoma (ATC) is nearly always fatal. Large studies on ATC are exceedingly rare. We aimed to study the clinical, genotypic, and histologic characteristics of ATC in the largest retrospective cohort of ATC to date. Methods: Three hundred sixty patients with ATC from two tertiary centers were studied. Molecular testing was performed in 126 cases including 107 using next-generation sequencing. Results: The median patients' age was 68 years. Differentiated thyroid carcinoma (DTC) was present in 208 cases (58%), the most common being papillary carcinoma (n = 150). The 1-, 2-, 3-, and 5-year overall survival (OS) was 36%, 17%, 13%, and 11%, respectively. On univariate analysis, age, resectability, chemotherapy, radiotherapy, margin status, encapsulation, gross residual disease, gross extrathyroidal extension, percentage, and size of ATC in the primary tumor predicted OS ( p < 0.05). Age, resectability, chemotherapy, and gross residual disease were independent prognostic factors in the entire cohort, while gross residual disease was the only independent predictor of OS in patients who had resection of their tumor. BRAF, RAS, TERT promoter, TP53, PIK3CA, E1F1AX, and PTEN mutations were detected in 45%, 24%, 75%, 63%, 18%, 14%, and 14% of ATC, respectively. Concomitant BRAF/RAS and TERT mutations were associated with worse outcome than mutation in only one of the genes. BRAF-mutated and RAS-mutated ATCs had similar frequency of nodal and distant metastasis. Twelve cases were pure squamous cell carcinoma, 60% of which carried BRAF V600E mutation and showed a similar OS to other ATCs. Conclusions: (i) Gross residual disease remains the most crucial indicator of outcome in ATC. (ii) Encapsulation, margin status, percentage, and size of ATC in the primary were prognostically relevant. (iii) Pure thyroid squamous cell carcinoma may be considered as ATC given a BRAF V600E genotype and similar outcome. (iv) In contrast to DTC, BRAF-mutated and RAS-mutated ATCs have similar metastatic spread. (v) Concomitant mutations of BRAF or RAS with TERT confer a worse prognosis.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

No abstract