Investigation of Various Factors for Discriminating Between Cytologic Diagnosis of “Atypical” vs “Suspicious” in Fine Needle Aspiration Biopsy of Head and Neck Lymph Nodes

Summary: Introduction: ""Atypical"" (ATY) and ""suspicious for malignancy"" (SUS) categories are associated with the highest rate of interobserver variability in all classification systems due to lack of consensus for objective and reproducible criteria for each category. We investigated possible factors that may prompt ATY vs SUS diagnoses in head and neck (H&N) lymph node (LN) cytology. Materials and Methods: Patients with ATY or SUS diagnosis on H&N LN fine needle aspiration (FNA) biopsy 2020-2023 were evaluated. Health records and archival slides were reviewed to document 22 variables for each case. Risk of malignancy (ROM) for both categories was calculated. Cases were analyzed based on whether cytologic evaluation suggested a hematologic neoplasm. Results: 118 cases were included (83 ATY, 35 SUS). All but 5 cases had definitive final diagnosis. ROM differences for ATY vs SUS were striking and statistically significant (p=0.0005). In hematologic cases, presence of concurrent biopsy and proportion of abnormal population by flow cytometry were significantly different between ATY vs SUS cases (p=0.014 and p=0.037, respectively). In non-hematologic cases, clinical concern and presence of abnormal ancillary tests showed significant differences between ATY vs SUS cases (p=0.001 and p=0.019, respectively). Conclusions: Cytopathologists are very skilled at visually discerning levels of concern for malignancy. All cases with SUS cytology and concurrent biopsy had final diagnosis of hematologic malignancy, suggesting an association with obtaining additional core biopsy where clinical suspicion for lymphoma is high. Proportion of abnormal cells detected by flow cytometry was higher in SUS vs ATY in hematologic cases, and presence of abnormal ancillary tests was higher in SUS vs ATY in non-hematologic cases. Further studies are needed to understand and refine employment of these WHO diagnostic categories, including subjective pathologist visual assessments, and to maximize the clinical utility of LN FNA.