Edmund S. Cibas

Background: Papillary renal neoplasm with reverse polarity is a recently recognized low‐grade neoplasm with a favorable prognosis. To date, its cytologic features have not been well documented.Methods: Two patients with papillary renal neoplasm with reverse polarity sampled by fine needle aspiration and core needle biopsy are described, one of whom is under active surveillance without clinical progression and the other is alive and well 16 years after partial nephrectomy.Results: The cytologic features included a mix of papillae and dispersed cells with abundant oncocytic cytoplasm and round, bland nuclei apically displaced away from the papillary core. Immunohistochemistry showed positive staining for GATA3 in both cases. Molecular studies on one of the cases showed a KRAS p.G12V mutation.Conclusions: The cytologic features of this distinctive, indolent neoplasm are important to recognize because patients with papillary renal neoplasm with reverse polarity may be excellent candidates for partial nephrectomy or even active surveillance.

Background: Leptomeningeal metastases occur across multiple solid and lymphoid cancers, and patients typically undergo cytopathologic assessment of cerebrospinal fluid (CSF) in this setting. For patients diagnosed with metastatic cancer, the detection of actionable somatic mutations in CSF can provide clinically valuable information for treatment without the need for additional tissue collection.Methods: The authors validated a targeted next‐generation sequencing assay for the detection of somatic variants in cancer (OncoPanel) on cell‐free DNA (cfDNA) isolated from archival CSF specimens in a cohort of 25 patients who had undergone molecular testing of a prior tumor specimen.Results: CSF storage time and volume had no impact on cfDNA concentration or mean target coverage of the assay. Previously identified somatic variants in CSF cfDNA were detected in 88%, 50%, and 27% of specimens diagnosed cytologically as positive, suspicious/atypical, and negative for malignancy, respectively. Somatic variants were identified in 81% of CSF specimens from patients who had leptomeningeal enhancement on magnetic resonance imaging compared with 31% from patients without such enhancement.Conclusions: These data highlight the stability of cfDNA in CSF, which allows for cytopathologic evaluation before triage for next‐generation sequencing assays. For a subset of cases in which clinical suspicion is high but cytologic or radiographic studies are inconclusive, the detection of pathogenic somatic variants in CSF cfDNA may aid in the diagnosis of leptomeningeal metastases.

Background: The burden of the COVID‐19 pandemic is often enumerated in lives lost, but the strain on health care resources and mobility limitations contributed to the burden of non–COVID related disease. In this study, we evaluated the impact of the pandemic through a time series review of cytology samples.Methods: Pathology reports for all cytology specimens received from January 2019 through April 2021 at our institution were reviewed. Time series analysis was performed using moving averages, time trend analysis, cross‐correlation, and tests of homogeneity.Results: During the first peak of the pandemic (March–June 2020), breakpoint analysis showed a downward shift in the number of gynecologic (−89.4%) and non‐gynecologic (−70.4%) cytology specimens within a week of declaration of an emergency. Cross‐correlation analysis showed a relationship between sample numbers and COVID‐19 cases during the initial phase of the pandemic (April–June 2020). During the second surge (October 2020–April 2021), despite the higher incidence of COVID‐19, there was a smaller impact on cytology samples (−20.1% and − 24.8% for gynecologic and non‐gynecologic samples, respectively). During the first 3 months of the pandemic, 154 fewer malignant cases were identified compared with the prior year. Although specimen numbers slowly returned to baseline following the first wave of the pandemic, the earlier decline in malignant diagnoses was not offset during the study period.Conclusions: The deleterious effects of COVID‐19 extend beyond direct mortality attributed to the disease. The significant decrease in diagnostic cytology specimens during this period has profound implications including delayed care and missed disease.

BACKGROUND: Thyroid nodules with atypia of undetermined significance (AUS) are challenging to manage because of their intermediate risk of malignancy. Subclassification of atypia can refine malignancy risk in adult AUS nodules but has not been evaluated in children.METHODS: This was a retrospective cohort study of pediatric patients (P < .001), whereas architectural atypia was not associated with malignancy (P = .8). Repeat FNA was performed in 42 of 68 nodules (62%). In nodules with initial nuclear and architectural atypia, benign repeat cytology had a high false‐negative rate (3 of 6; 50%).CONCLUSIONS: Pediatric AUS nodules with nuclear atypia have a high rate of malignancy, but architectural atypia is not associated with malignancy. In nodules with nuclear atypia, repeat FNA may inform clinical decisions regarding the need for resection. In the absence of suspicious clinical features, nodules without nuclear atypia might be considered for observation rather than resection or repeat FNA.