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Background: Fine‐needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine‐needle biopsy (FNB) in improving the diagnostic yield. Methods: The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed. Results: The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n = 6, 19%), negative for malignant cells/cyst contents (n = 7, 23%), atypical cells (n = 3, 10%), nonmucinous cyst (n = 11, 35%), and serous cystadenoma (n = 4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild‐type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%). Conclusions: This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA. Cytologic diagnosis of pancreatic serous cystadenoma remains challenging. Ancillary cyst fluid analysis, adjunct inhibin immunohistochemistry, and additional fine‐needle biopsy sampling help improve diagnostic yield. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare premalignant neoplasm that can progress to invasive adenocarcinoma. In this retrospective study, cases of IPNB were reviewed to examine cytomorphologic and molecular features. Methods: IPNB cytology cases with histopathologic confirmation were retrieved from the pathology archives. The cytomorphologic features such as cellularity, architecture, cell type, and cellular details were analyzed. Results: The cohort included 13 cases (six brushings, six fine‐needle aspirations [FNA], and one combined brushing and FNA). The lesions involved common bile duct in nine cases (69%) and hepatic duct in four cases (31%). Original cytological diagnoses included adenocarcinoma (five, 38%), suspicious for adenocarcinoma (one, 8%), neoplasm (three, 23%), atypical (three, 23%), and reactive (one, 8%). The cytomorphologic features included moderate/high cellularity (12, 92%), papillary and/or complex papillary architecture (10, 77%), columnar cells (11, 85%), vacuolated cytoplasm (12, 92%), enlarged nuclei (13, 100%), and fine granular chromatin (12, 92%). Background mucin, necrosis and acute inflammation were seen in four (31%), four (31%), and two (15%) cases, respectively. KRAS testing was performed in nine cases with mutant KRAS found in five (56%). Conclusions: Our study demonstrated that IPNB cytology specimens were relatively cellular with a wide spectrum of cytomorphology; however, most cases harbored adenocarcinoma or high‐grade dysplasia. The characteristic cytomorphologic features included papillary/complex papillary clusters of columnar cells with vacuolated cytoplasm, enlarged nuclei, and fine granular chromatin in relatively cellular specimens. KRAS mutations identified may have potential diagnostic and therapeutic implications. The current study demonstrates that intraductal papillary neoplasm of the bile duct has unique cytomorphologic features such as papillary and/or complex papillary clusters of columnar epithelial cells with variable cytologic atypia. KRAS mutation identified may be diagnostically helpful for the cases with indeterminate cytology. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biliary strictures can be caused by benign and malignant conditions. A biliary duct brushing diagnosis can be challenging because of low cellularity and overlapping morphology among different entities, leading to a variable reported sensitivity. This study aimed to assess the value of KRAS mutation testing in adding cytological diagnosis of biliary duct brushings. METHODS: With institutional review board approval, biliary duct brushing cytology specimens were collected from 269 patients with extrahepatic biliary stenosis between August 2011 and July 2021. The results of cytology and KRAS mutational analyses were evaluated in view of corresponding cytology examination and histopathological/clinical follow‐up. RESULTS: KRAS mutations were identified in 50 of 269 biliary stricture brushing cases (19%). Among the cases with available follow‐up, 72% (34 of 47) of biliary brushings had confirmed malignancy when there were KRAS mutations. The overall specificity and sensitivity of KRAS mutation testing was 92% and 36%, respectively. KRAS mutation was significantly more enriched in pancreatic duct adenocarcinoma than in cholangiocarcinoma (66% vs 5%, P <.001). The absolute risk of malignancy was 3%, 28%, and 71%, respectively, in negative, atypical, and suspicious cytological diagnostic categories and the risks increased to 14%, 68%, and 95% in corresponding categories with KRAS mutation. CONCLUSIONS: Our results suggested that KRAS mutational analysis can be considered supplementary to cytology diagnosis of biliary duct brushing for patients with extrahepatic biliary stenosis in clinical practice.; [ABSTRACT FROM AUTHOR]

Background: Activating point mutations of the RAS gene (NRAS, HRAS, and KRAS) can be seen in benign and malignant thyroid tumors; among these, NRAS mutations are more commonly seen. This study was conducted to evaluate the thyroid risk of malignancy (ROM) associated with RAS mutations in thyroid fine‐needle aspiration (FNA) at the authors' institution. Methods: The authors searched their electronic database system between January 2015 and May 2021 for thyroid FNA cases with any type of RAS mutation. Molecular alterations were identified with the ThyroSeq Genomic Classifier, ThyGeNEXT (thyroid oncogene panel)/ThyraMIR (miRNA classifier), or ThyroSure gene panel. Results: A total of 127 cases (age, 51 ± 14 years; 100 females and 27 males) were identified, and 72 had histologic follow‐up. The overall ROM associated with RAS mutations (with or without any other molecular alterations) was 29%, whereas the ROM was lower (18%) with RAS mutations only. Isolated NRAS, HRAS, and KRAS mutation–associated ROMs were 15%, 27%, and 14%, respectively. Among these RAS‐mutated cases, the cases with a Bethesda category IV cytologic diagnosis had a higher ROM than the cases with a category III diagnosis (38% vs 17%). Twenty‐one histologically confirmed malignant cases were mostly classified on cytology as category IV lesions (14 of 34; 41%), and the remainder were either category III (6 of 35; 17%) or V lesions (1 of 1; 100%). Conclusions: This study demonstrated that the overall RAS mutation–associated ROM in thyroid FNA was intermediate (29%), and isolated HRAS mutations appeared to have a higher ROM (27%) than NRAS and KRAS mutations (15% and 14%, respectively). A RAS mutation can be seen in benign or malignant thyroid diseases. The risk of malignancy is higher when an RAS mutation is associated with other molecular alterations, especially in Bethesda category IV cases. [ABSTRACT FROM AUTHOR]

Background: Hürthle cell features are frequently observed on the fine‐needle aspiration (FNA) cytology of thyroid nodules and often pose a diagnostic challenge because of a significant overlap between cytomorphologic features seen in benign and malignant lesions. Molecular alterations (MAs) associated with these lesions are not well described. The objective of the current study was to evaluate the molecular profile of Hürthle cell lesions classified as Hürthle cell neoplasm (HCN) on cytologic evaluation. Methods: The authors retrospectively reviewed their electronic database for cytologic diagnoses of HCN from January 1, 2017 to March 31, 2020. Results: In total, 279 cases from 275 patients who had a diagnosis of HCN were included in the study. Molecular testing results were available in 85 cases (51 with MAs and 34 without MAs) and, of those, 42 had histologic follow‐up available. Eight of 10 malignant cases had MAs, whereas the remaining 2 cases were negative for MAs. The most frequently encountered predominant genetic alterations or classifier findings were chromosome copy number alterations (n = 15), followed by NRAS (n = 8), KRAS (n = 7), suspicious (n = 6), EIF1AX (n = 4), TSHR (n = 3), gene overexpression (n = 3), positive microRNA classifier (n = 2), and 1 each of BRAF K601E, TERT, and HRAS mutations. One hundred thirty‐seven cases had histologic follow‐up available; of those, 28 were classified as malignant, and 109 were classified as benign (neoplastic and nonneoplastic). The overall risk of malignancy associated with HCN was 20%, and the risk of HCN with MAs was 25%. Conclusions: The cytologic diagnosis of HCN includes various MAs without any obvious trend, and most malignant cases (80%) have some type of MA. Cases with a cytologic diagnosis of Hürthle cell neoplasm exhibit various molecular alterations, but no consistent association is observed in histologically benign or malignant cases. Because molecular data pertinent to Hürthle cell neoplasms are evolving, identifying additional molecular findings along with the fine‐needle aspiration results may direct future larger cohort studies to discover any association. [ABSTRACT FROM AUTHOR]

Background: This study investigated p16 by immunohistochemistry (IHC) on cellblocks (CBs) and human papillomavirus (HPV) by polymerase chain reaction (PCR) in fine‐needle aspiration (FNA) of head and neck squamous cell carcinoma (HNSCC). Methods: Receiver operating characteristic (ROC) curve analysis was used to assess test performance in CBs compared with p16 IHC in 42 surgical specimens from patients with HNSCC and in correlation with HPV by PCR in cytology specimens. The study assessed HPV by PCR in FNA specimens as a substitute for p16 IHC in surgical specimens. Results: Of 42 cases, 38 CBs showed malignant cells as cohesive clusters of viable cells with or without single tumor cells, whereas 4 specimens were composed exclusively of single tumor cells and degenerated cells. All p16‐negative surgical specimens showed an absence of p16 staining in the corresponding CBs (n = 16). In the p16‐positive surgical cases (n = 26), corresponding CBs with tumor clusters (n = 23) showed heterogeneous p16 expression ranging from 40% to 100%; however, scoring single cells was challenging and unreliable because of cellular degradation. ROC curve inspection showed the optimal threshold to be at least 40% p16 staining in tumor clusters with 100% sensitivity and specificity. In cases with inadequate CBs, HPV by PCR on needle rinse showed 88% sensitivity and 100% specificity for p16 expression in surgical specimens. Conclusions: A cutoff of at least 40% p16 expression in tumor clusters may be appropriate for p16 positivity in cytology CB specimens. A positive HPV finding by PCR on needle rinse can be used as a substitute for p16 expression in surgical specimens. Cytology fine‐needle aspiration specimens with tumor clusters in cellblock sections are reliable in determining p16 status by immunohistochemistry in head and neck squamous cell carcinoma. A cutoff of at least 40% in tumor clusters correlates with positive human papillomavirus in cytology specimens and p16 immunohistochemistry in surgical specimens. [ABSTRACT FROM AUTHOR]

Background: Neurotrophic tyrosine kinase receptor (NTRK) rearrangement has been reported in a subset of papillary thyroid carcinoma (PTC) cases. Little is known about the cytomorphologic features of NTRK‐rearranged PTC. Methods: We report an institutional series of 13 fine‐needle aspiration (FNA) specimens of NTRK‐rearranged PTC with a predominantly indeterminate cytology diagnosis. NTRK3 or NTRK1 rearrangements were detected on FNA or surgical specimens by next‐generation sequencing. Results: The 13 patients had a median age of 18 years; 10 patients were female and 3 patients were male. In 10 (77%) cases, cytology was indeterminate, and histopathologic follow‐up was predominantly the follicular variant of PTC (n = 8 [62%]), mostly infiltrative subtype. Of 12 FNA specimens available for review, a predominant loosely cohesive group pattern was the most commonly encountered architectural pattern (n = 5 [41%]), followed by single cell (n = 3 [25%]), thick cord (n = 2 [17%]), and microfollicular pattern (n = 2 [17%]). Background lymphocytic thyroiditis was observed in 9 cases. At the cellular level, the cytoplasm was moderate and granular, occasionally vacuolated. Classic PTC nuclear features (eg, nuclear enlargement, elongation, grooves, and nuclear membrane irregularity) were present but were often focal and subtle. Chromatin was often granular. Intranuclear pseudoinclusions were absent or rare. Conclusion: Our study demonstrates that most cases of NTRK rearrangement lack classic PTC cytomorphologic characteristics. Loosely cohesive groups and single cells with granular, sometimes vacuolated cytoplasm and subtle nuclear features are often seen on FNA specimens. Recognizing these characteristics may be helpful to preoperatively prompt molecular testing, including NTRK rearrangement analysis. Fine‐needle aspirates of NTRK‐rearranged papillary thyroid carcinoma (PTC) show loosely cohesive groups and single cells in addition to microfollicles and thick cords. At the cellular level, classic nuclear features of PTC are subtle, whereas moderate to abundant granular and vacuolated cytoplasm and often granular chromatin are distinctive characteristics. [ABSTRACT FROM AUTHOR]