Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

Use of nongynecologic cytologic-histologic correlation to identify patterns of error: An institutional experience.

BACKGROUND: Quality management practices empower cytology laboratories to deliver consistent, high-quality patient care. Monitoring of key performance indicators is one way by which laboratories can identify patterns of error and focus their improvement activities. Cytologic-histologic correlation (CHC) identifies error by retrospectively reviewing cytology cases when discordant surgical pathology diagnoses are reported. Analysis of CHC data can elucidate patterns of error and direct quality improvement initiatives. METHODS: CHC data of nongynecologic cytology specimens were reviewed over a 3-year period (2018-2021). Errors were separated by anatomic site and classified as either sampling or interpretive errors. RESULTS: A total of 364 discordant cases were identified out of 4422 cytologic-histologic pairs (a discordant rate of 8%). The majority (272; 75%) were sampling errors, with fewer interpretive errors (92; 25%). Sampling errors were found to occur most commonly in lower urinary tract and lung. Interpretive errors were most commonly found in lower urinary tract and thyroid. CONCLUSIONS: Nongynecologic CHC data can be a valuable resource for cytology laboratories. By studying the types of errors, quality improvement activities can be targeted toward problem areas.

Patterns of Major Frozen Section Interpretation Error: An In-Depth Analysis From a Complex Academic Surgical Pathology Practice.

OBJECTIVES: To establish baseline error rates due to misinterpretation and to identify scenarios in which major errors were most common and potentially preventable. METHODS: Our database was queried over a 3-year period for major discrepancies due to misinterpretation. These were stratified by histomorphologic setting, service, availability/type of prior material, and years of experience and subspecialization of the interpreting pathologist. RESULTS: The overall discordance rate between frozen section (FS) and final diagnoses was 2.9% (199/6,910). Seventy-two errors were due to interpretation, of which 34 (47.2%) were major. Major error rates were highest on the gastrointestinal and thoracic services. Of major discrepancies, 82.4% were rendered in subdisciplines outside those of the FS pathologist. Pathologists with fewer than 10 years' experience made more errors than those with more experience (55.9% vs 23.5%, P = .006). Major error rates were greater for cases without previous material compared to those with a prior glass slide (47.1% vs 17.6%, P = .009). Common histomorphologic scenarios in which disagreements were made involved discriminating mesothelial cells from carcinoma (20.6%) and accurately recognizing squamous carcinoma/severe dysplasia (17.6%). CONCLUSIONS: To improve performance and decrease future misdiagnoses, monitoring discordances should be a continuous component of surgical pathology quality assurance programs.

PTEN expression and morphological patterns in prostatic adenocarcinoma.

AIMS: Cribriform morphology, which includes intraductal carcinoma (IDCP) and invasive cribriform carcinoma, is an indicator of poor prognosis in prostate cancer. Phosphatase and tensin homologue (PTEN) loss is a predictor of adverse clinical outcomes. The association between PTEN expression and morphological patterns of prostate cancer is unclear. METHODS AND RESULTS: We explored the association between PTEN expression by immunohistochemistry, Gleason pattern 4 morphologies, IDCP and biochemical recurrence (BCR) in 163 radical prostatectomy specimens. IDCP was delineated from invasive cribriform carcinoma by p63 positive immunohistochemical staining in basal cells. Combined invasive cribriform carcinoma and IDCP were associated with a higher cumulative incidence of BCR [hazard ratio (HR) = 5.06; 2.21, 11.6, P < 0.001]. When including PTEN loss in the analysis, invasive cribriform carcinoma remained predictive of BCR (HR = 3.72; 1.75, 7.94, P = 0.001), while PTEN loss within invasive cribriform carcinoma did not. Glomeruloid morphology was associated with lower odds of cancer stage pT3 and lower cumulative incidence of BCR (HR = 0.27; 0.088, 0.796, P = 0.018), while PTEN loss within glomeruloid morphology was associated with a higher cumulative incidence of BCR (HR = 4.07; 1.04, 15.9, P = 0.043). CONCLUSIONS: PTEN loss within glomeruloid pattern was associated with BCR. The presence of any cribriform pattern was associated with BCR, despite PTEN loss not significantly associated with invasive cribriform carcinoma. We speculate that other drivers independent from PTEN loss may contribute to poor prognostic features in cribriform carcinoma.