Faculty Bibliography

PURPOSE/OBJECTIVE:This study investigates the potential of DALL·E 3, an artificial intelligence (AI) model, to generate synthetic pathologic images of prostate cancer (PCa) at varying Gleason grades. The aim is to enhance medical education and research resources, particularly by providing diverse case studies and valuable teaching tools. METHODS:This study uses DALL·E 3 to generate 30 synthetic images of PCa across various Gleason grades, guided by standard Gleason pattern descriptions. Nine uropathologists evaluated these images for realism and accuracy compared with actual hematoxylin and eosin (H&E)-stained slides using a scoring system. RESULTS:< .05), with Gleason 5 images achieving the highest scores and accurately depicting critical pathologic characteristics. Limitations included a lack of fine nuclear detail, essential for identifying malignancy, which may affect the images' diagnostic utility. CONCLUSION/CONCLUSIONS:DALL·E 3 shows promise in generating customized pathologic images that can aid in education and resource expansion within pathology. However, ethical concerns, such as the potential misuse of AI-generated images for data falsification, highlight the need for responsible oversight. Collaboration between technology firms and pathologists is essential for the ethical integration of AI in pathology practices.

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.

Bladder cancer is a common type of urological cancer with high recurrence and mortality rates. Currently, it is diagnosed and monitored using minimal invasive cystoscopies and biopsies. Urinary cytology, the most widely accepted noninvasive and more economic urinary diagnosis method, aims to detect high grade urothelial carcinoma with a high specificity but low sensitivity, especially for detecting low-grade tumors. With advancements in molecular techniques, urine based liquid biopsy, artificial intelligence, and the growing interest in precision cytopathology, identification of urinary biomarkers for effective cancer screening, diagnosis, risk stratification, and therapeutic response monitoring has been a key focus of bladder cancer research and clinical practice guideline development. Urine allows noninvasive access to morphological, transcriptomic, epigenetic, and genomic materials from exfoliated cells in contact with tumor tissue. This review offers a comprehensive evaluation of the current utility of urinary biomarkers and technological innovations in cancer diagnosis and minimal residual disease detection. We also discuss the challenges and prospects for integrating molecular cytopathology into daily clinical practice.

OBJECTIVES/OBJECTIVE:TERT promoter mutations are not infrequently encountered in thyroid carcinomas; however, it is unclear if additional molecular alterations may play a role in determining tumor behavior. METHODS:Fine-needle aspiration (FNA) specimens from 32 patients with TERT promoter mutations detected by ThyroSeq v3 from 4 institutions were included in the study. FNA diagnoses, molecular results, and surgical follow-up were retrospectively reviewed and analyzed. RESULTS:There were 5 benign and 27 malignant neoplasms, including 7 high-grade thyroid carcinomas (HGCs) on histopathologic follow-up. Of 4 cases with an isolated TERT mutation, 3 (75%) cases were malignant. Of 17 cases harboring a co-occurring TERT mutation with 1 additional molecular alteration, 13 (76%) displayed malignancy on histopathologic follow-up. All 11 cases with TERT mutations plus 2 or more additional molecular alterations were malignant on follow-up. Furthermore, HGC was not seen in cases with an isolated TERT mutation, while 80% of cases harboring TERT mutations plus 3 additional molecular alterations showed HGC. CONCLUSIONS:TERT promoter mutations are commonly associated with malignancy, particularly HGCs, when multiple co-occurring molecular alterations are present. However, TERT promoter mutations may occasionally be detected in benign thyroid neoplasms when encountered in isolation or with fewer than 2 additional molecular alterations.

Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.

OBJECTIVES/OBJECTIVE:The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. METHODS:Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. RESULTS:There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. CONCLUSIONS:A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.