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Over the past decade, immunotherapy has emerged as one of the most promising cancer treatments. Several monoclonal antibodies targeting the programmed death 1 (PD‐1)/ programmed death ligand‐1 (PD‐L1) pathway have been integrated into standard‐of‐care treatments for a wide range of cancer types. Although all the available PD‐L1 immunohistochemistry (IHC) assays have been developed on formalin‐fixed histological specimens, a growing body of research has recently suggested the feasibility of PD‐L1 testing on cytological samples. Although promising results have been reported, several important issues still need to be addressed. Among these are pre‐analytical issues, cyto‐hystological correlation, and inter‐observer agreement. This review will briefly summarise the knowledge gaps and future directions of cytopathology in the immuno‐oncology scenario. Programmed death ligand‐1 (PD‐L1) assays have been developed on formalin‐fixed histological specimens, and a growing body of research is being dedicated to confirming the feasibility of applying these assays to cytological samples. Promising results have been reported but several important issues still need to be addressed. This review summarizes the current status, knowledge gaps and future directions of cytopathology in the context of immuno‐oncology. [ABSTRACT FROM AUTHOR]

Background: Thyroid fine‐needle aspiration (FNA) is a reliable and cost‐effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7‐gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis. Methods: In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting Thyroid Cytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow‐up. Results: In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7‐gene test confirmed the high positive predictive value of BRAFV600E and BRAF‐like mutations (80%) and the moderate positive predictive value of RAS‐like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation‐positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. Conclusions: The 7‐gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation‐positive FNAs is related to the risk of malignancy of each diagnostic class. The 7‐gene panel test improves the preoperative risk stratification of indeterminate thyroid fine‐needle aspirations, especially when considering the biologic significance of the different types of mutations (ie, BRAF‐like and RAS‐like alterations). Moreover, the rate of mutation‐positive thyroid fine‐needle aspirations is related to the risk of malignancy of each diagnostic class, supporting the establishment, from a molecular standpoint, of prognostically relevant cytologic diagnostic categories. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) includes fine‐needle aspiration (FNA) specimens that cannot straightforwardly be classified as benign or malignant. To determine whether morphological subcategorization based on atypia qualifiers and molecular testing could improve malignancy risk stratification of AUS/FLUS patients, this study assessed the correlation between these qualifiers and the molecular alterations commonly harbored by thyroid neoplasms. METHODS: A total of 162 AUS/FLUS cases were subcategorized by atypia qualifiers (Hürthle cell changes, architectural atypia, and cytologic atypia [CyA]) and were tested for BRAF, N‐H‐KRAS, RET/PTC, and paired box 8 (PAX8)/peroxisome proliferator activated receptor γ (PPARg) mutations. RESULTS: CyA was observed more frequently in mutation‐positive AUS/FLUS (14 of 37 [37.84%]) than mutation‐negative AUS/FLUS (20 of 125 [16.00%]; P < .0084), and it specifically harbored the BRAFV600E point mutation. Malignancy was confirmed in the available follow‐up. Conversely, although RAS was the most frequent mutation identified in AUS/FLUS FNA specimens (26 of 37 cases [70.27%]; P < .0001), it was distributed across various AUS/FLUS subcategories and was not significantly associated with a specific atypia qualifier or malignant outcome according to the available follow‐up. Rearrangements of both RET/PTC (n = 1) and PAX8/PPARg (n = 3) were rarely retrieved in the FNA samples. CONCLUSIONS: BRAF and RAS mutations are associated with different AUS/FLUS qualifiers and hence have different risks of malignancy. Consequently, a hybrid molecular and morphological subcategorization system could improve the malignancy risk stratification of thyroid FNA samples diagnosed as AUS/FLUS. Cancer Cytopathol 2018;126:317‐25. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

In advanced stage non-small cell lung cancer (NSCLC) patients, Kirsten Rat Sarcoma Viral Oncogene Homolog ( KRAS ) testing may soon acquire a predictive significance to select patients for AMG510 treatment. Since tissue samples are not always available, liquid biopsy may represent a viable option for KRAS testing. Here, we review the last three years clinical practice performed on 194 plasma based liquid biopsies by next generation sequencing (NGS) SiRe ® panel. In particular, 36 (18.6%) KRAS mutated cases were identified, with an overall median allelic frequency of 5.0% (ranging between 0.2% and 46.8%). No concomitant mutations were observed in the other NSCLC clinical relevant genes included in the SiRe ® panel, such as epidermal growth factor receptor ( EGFR ) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Exon 2 p.G12C was the most common detected mutation (13/36, 36.1%). In conclusion, our data update and confirm that SiRe ® NGS panel represents a robust analytical tool to assess KRAS mutational status on circulating tumor DNA. Further investigation is required to design more cost-effective diagnostic algorithms to harmonize clinical relevant biomarker testing on tissue and blood in advanced stage NSCLC clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.01.19). The series “Improving Outcomes in Lung Cancer Through Early Diagnosis and Smoking Cessation” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)