Triage options for positive high-risk HPV results from HPV-based cervical cancer screening: a review of the potential alternatives to Papanicolaou test cytology.

The American Cancer Society has recommended high-risk human papillomavirus (HPV) testing as the primary screening method for cervical cancer since 2020. Up to this point, the transition from Pap test cytology-based screening or co-testing with cytology and HPV testing has been slow and limited. However, more health systems in the United States are in the process of implementing this change. The transition to HPV-based screening requires a triage strategy for positive results. Genotyping to specifically detect HPV types 16 and 18 in conjunction with reflex cytology for the remaining high-risk HPV genotypes has been the recommended method. Testing options including Dual Stain for p16/Ki-67 and extended HPV genotyping are currently being incorporated into treatment algorithms as alternatives. Methylation testing is another promising method extensively investigated around the world. This review, performed by members of the Clinical Practice Committee of the American Society of Cytopathology, examines the rationale behind the switch away from reliance on Pap test cytology in the cervical cancer screening algorithm and the opportunities and problems associated with the most promising alternative approaches. Published studies that give insight into the performance characteristics of these newer tests are reviewed. At the present time, Pap test cytology remains a viable triage option for positive HPV screening results, but alternative tests have significant appeal and should be considered in tandem with the decision to offer primary HPV screening.

Genetically Determined Circulating Lactase/Phlorizin Hydrolase Concentrations and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.

Previous research has found that milk is associated with a decreased risk of colorectal cancer (CRC). However, it is unclear whether the milk digestion by the enzyme lactase-phlorizin hydrolase (LPH) plays a role in CRC susceptibility. Our study aims to investigate the direct causal relationship of CRC risk with LPH levels by applying a two-sample Mendelian Randomization (MR) strategy. Genetic instruments for LPH were derived from the Fenland Study, and CRC-associated summary statistics for these instruments were extracted from the FinnGen Study, PLCO Atlas Project, and Pan-UK Biobank. Primary MR analyses focused on a cis-variant (rs4988235) for LPH levels, with results integrated via meta-analysis. MR analyses using all variants were also undertaken. This analytical approach was further extended to assess CRC subtypes (colon and rectal). Meta-analysis across the three datasets illustrated an inverse association between genetically predicted LPH levels and CRC risk (OR: 0.92 [95% CI, 0.89-0.95]). Subtype analyses revealed associations of elevated LPH levels with reduced risks for both colon (OR: 0.92 [95% CI, 0.89-0.96]) and rectal cancer (OR: 0.92 [95% CI, 0.87, 0.98]). Consistency was observed across varied analytical methods and datasets. Further exploration is warranted to unveil the underlying mechanisms and validate LPH's potential role in CRC prevention.

American Society of Cytopathology Telecytology validation recommendations for rapid on-site evaluation (ROSE).

Telecytology has multiple applications, including rapid onsite evaluation (ROSE) of fine-needle aspiration (FNA) specimens. It can enhance cytopathology practice by increasing productivity, reducing costs, and providing subspecialty expertise in areas with limited access to a cytopathologist. However, there are currently no specific validation guidelines to ensure safe practice and compliance with regulations. This initiative, promoted by the American Society of Cytopathology (ASC), intends to propose recommendations for telecytology implementation. These recommendations propose that the validation process should include testing of all hardware and software, both separately and as a whole; training of all individuals who will participate in telecytology with regular competency evaluations; a structured approach using retrospective slides with defined diagnoses for validation and prospective cases for verification and quality assurance. Telecytology processes must be integrated into the laboratory's quality management system and benchmarks for discrepancy rates between preliminary and final diagnoses should be established and monitored. Special attention should be paid to minimize discrepancies that downgrade malignant cases to benign (false positive on telecytology). Currently, billing and reimbursement codes for telecytology are not yet available. Once, they are, recommendation of the appropriate usage of these codes would be a part of the recommendations. These proposed guidelines are intended to be a resource for laboratories that are considering implementing telecytology. These recommendations can help to ensure the safe and effective use of telecytology and maximize its benefits for patients.

Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 µg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.

Diagnostic performance of molecular testing in indeterminate (Bethesda III and IV) thyroid nodules with Hürthle cell cytology.

BACKGROUND: Indeterminate thyroid nodules with Hürthle cell cytology remain a diagnostic challenge. The low benign call rate and positive predictive value of first-generation molecular tests precluded their use to rule out malignancy. We examined the diagnostic performance of current tests. METHOD: This subset analysis of our prospective randomized trial compared the benign call rate and positive predictive value of Afirma Gene Sequencing Classifier and Thyroseq v3 in Bethesda III and IV nodules with Hürthle cell cytology. Molecular test samples were obtained at initial fine-needle aspiration (8/2017-7/2022) and reflexively sent for processing. RESULTS: Molecular testing was performed on 140 Hürthle cell nodules. Of 79 nodules tested with the Afirma Gene Sequencing Classifier, the benign call rate was 84% (66/79). Nine of 66 nodules with benign results were resected, with no malignancies. Twelve of 13 nodules with suspicious results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and one Hürthle cell carcinoma (positive predictive value 25%). Of 61 nodules tested with Thyroseq v3, the benign call rate was 56% (34/61; (P < .01 versus Afirma Gene Sequencing Classifier). Five of 34 nodules with negative results were resected, with no malignancies. Nineteen of 27 nodules with positive results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and 1 Hürthle cell carcinoma (positive predictive value 16%). CONCLUSION: The high benign call rate of current molecular tests in Hürthle cell nodules strengthens their value in enabling patients to avoid surgery.

Pathologic response to neoadjuvant chemotherapy in ovarian cancer and its association with outcome: A surrogate marker of survival.

OBJECTIVE: We aimed to validate whether pathologic response (pR) to neoadjuvant chemotherapy (NACT) using a three-tier chemotherapy response score (CRS) is associated with clinical outcome in ovarian cancer (OC) and could be used as surrogate marker for survival. METHODS: We conducted a retrospective study of OC patients with FIGO stage III/IV disease who received NACT and graded response as no or minimal (CRS 1), partial (CRS 2), or complete/near-complete (CRS 3) pR using tissue specimens obtained from omentum. Uni- and multivariate survival analyses were performed accounting for age, FIGO stage, debulking and BRCA status as well as neoadjuvant use of bevacizumab. RESULTS: CRSs 1, 2 and 3 were found in 41(31%), 62 (47%) and 30 (22%) of the 133 examined cases. Response to NACT was associated with significantly improved progression-free (PFS, p < 0.001) and overall survival (OS, p = 0.011). Complete/ near-complete pathologic response (CRS3) was associated with improved PFS (median 24.8 vs. 12.5 months, unadjusted HR 0.28 [95%CI 0.15-0.54], p < 0.001; adjusted hazard ration (aHR) 0.31 [95% CI 0.14-0.72], p = 0.007) and OS (median 63.3 vs. 32.1 months, unadjusted HR 0.27 [95%CI 0.10-0.68], p = 0.006; aHR 0.32 [95% CI 0.09-1.11], p = 0.072) when compared to no or minimal response (CRS1). CONCLUSIONS: We validate a three-tier CRS for assessment of pathologic response to NACT in OC and demonstrate its prognostic independence of BRCA status or neoadjuvant bevacizumab use. Improving pR rates may be a useful goal of NACT in OC with the expectation of improved survival. The CRS may be a useful endpoint in clinical trials in OC.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Artificial Intelligence-Driven Morphology-Based Enrichment of Malignant Cells from Body Fluid.

Cell morphology is a fundamental feature used to evaluate patient specimens in pathologic analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with the high background of nonmalignant cells, restricting the ability of downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multidimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed a higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low levels or undetectable in presort patient samples. Our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multidimensional morphology analysis, and microfluidic sorting.

"SMART" cytology: The next generation cytology for precision diagnosis.

Cytology plays an important role in diagnosing and managing human diseases, especially cancer, as it is often a simple, low cost yet effective, and non-invasive or minimally invasive diagnostic tool. However, traditional morphology-based cytology practice has limitations, especially in the era of precision diagnosis. Recently there have been tremendous efforts devoted to apply computational tools and to perform molecular analysis on cytological samples for a variety of clinical purposes. Now is probably the appropriate juncture to integrate morphology, machine learning, and molecular analysis together and transform cytology from a morphology-driven practice to the next level - "SMART" Cytology. In this article we will provide a rather brief review of the relevant works for computational analysis on cytology samples, focusing on single-cell-based multiplex quantitative analysis of biomarkers, and introduce the conceptual framework of "SMART (Single cell, Multiplex, AI-driven, and Real Time)" Cytology.

Androgen Drives the Expression of SARS-CoV-2 Entry Proteins in Sinonasal Tissue.

Background and objectives: Men have higher morbidity and mortality from COVID-19 than women, possibly due to androgen receptor-regulated viral entry protein expression. This led to a clinical trial of androgen deprivation therapy (ADT), which has not shown a significant benefit in the outcomes among hospitalized male COVID-19 patients. The aim of this study was to explore biological explanations for the failure of ADT to mitigate clinical outcomes in men with severe COVID-19 by assessing the role of androgen in regulating viral entry protein expression in the upper and lower respiratory tract. Methods: Immunohistochemistry was used to assess the expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) and how it correlated to androgen receptor expression in the sinonasal epithelium, minor salivary glands of the sinus, lacrimal glands, and lungs from mice pretreated with and without castration and ADT as well as the sinonasal epithelium obtained from healthy human donors and hospitalized COVID-19 patients. Results: In murine models, castration and ADT treatment downregulated the expression of TMPRSS2 and ACE2 in the sinonasal epithelium, minor salivary glands of the sinus, and lacrimal glands, but not in the lungs. Correlative analyses using human tissue also showed a potential role of ADT in men during the early sinonasal phase but not in the later lung phase of SARS-CoV-2 infection. Conclusions: Our study suggests a potential benefit of ADT in male patients with early COVID-19 when the virus enters the nasopharynx, but not in those with advanced disease. The downregulation of viral entry proteins in the upper respiratory system following androgen blockade may be a key mechanism for this effect.

Retrospective analysis of adjuvant treatment for localized, operable uterine leiomyosarcoma.

OBJECTIVE: Currently, there is no standard adjuvant treatment protocol for localized uterine leiomyosarcoma (uLMS) as clinical trials to address this question have been retrospective, underpowered, or undermined by slow accrual rates. The aim of this study is to determine the benefit of adjuvant chemotherapy for uLMS. METHODS: We reviewed the medical records of localized uLMS patients who had underwent adjuvant therapy after upfront surgery between 2000 and 2020. The cases were blinded for review. We evaluated the influence of various clinical characteristics and different types of adjuvant therapies on specific outcomes. RESULTS: Sixty-eight patients (median age: 50 years) were included for analysis. Forty of 68 (58.8%) patients received adjuvant chemotherapy +/- radiation therapy and 25 patients (38.6%) did not receive any adjuvant therapy. At a median follow-up time of 43.3 months, 45 patients (66.1%) had relapsed disease. The median disease-free survival (mDFS) for all patients was 23.1 months. Patients who received any adjuvant treatment (chemotherapy and/or radiation) trended toward a longer mDFS compared with those who did not receive any adjuvant therapy (29.7 vs. 14.1 months, p = 0.26). Patients who received adjuvant chemotherapy alone had a longer, but nonstatistically significant mDFS compared with those who did not receive any adjuvant treatment (22.2 vs. 14.1 months, p = 0.18). Additionally, univariate analysis found that tumor size large than 10 cm, and a mitotic rate >10/10hpf were independent prognostic factors for worse DFS. CONCLUSIONS: Though DFS was more favorable among those who received adjuvant therapy, it was not statistically significant, and thus based on this data adjuvant therapy for resected uLMS is still in question.

Familial Duodenal Somatostatinomatosis Not Associated With a Known Genetic Syndrome.

ABSTRACT: We report a father and his daughter who both had multiple somatostatinomas in the duodenal bulb without a known syndrome. The father, at age 68 years, was incidentally found to harbor 4 approximately 1.5-cm well-differentiated neuroendocrine tumors in the duodenal bulb. His preoperative somatostatin level was elevated. He underwent partial duodenectomy and regional lymph node dissection; one lymph node was positive for metastasis. One year postoperatively, a recurrence was found in the surgical bed; he was treated with octreotide for 2 years, which stabilized the recurrent tumor. Ten years postoperatively, the mucosa of his remaining duodenum was normal. His daughter, at age 53 years, was found to harbor multiple small neuroendocrine tumors in the duodenal bulb. Immunostaining of available specimens showed that the neuroendocrine tumors from the father and daughter both were strongly positive for somatostatin. Micronodules of somatostatin-expressing neuroendocrine cells were found in the parts of the specimens uninvolved with the tumors. Both patients exhibited no evidence of known syndromes associated with somatostatinoma. The daughter did not harbor mutations in 93 genes commonly found in genetic tumor syndromes. The 2 cases thus suggest a novel, autosomal dominant, genetic syndrome of familial duodenal somatostatinomatosis.

Cytokeratin 13 Is a New Biomarker for the Diagnosis of Limbal Stem Cell Deficiency.

PURPOSE: The purpose of this study was to evaluate the expression of cytokeratin (K) 13 on the corneal surface and to validate its application in the diagnosis of limbal stem cell deficiency (LSCD). METHODS: This prospective comparative study included 26 corneal impression cytology (IC) specimens from patients diagnosed with LSCD. Twenty-three IC specimens from normal donors served as controls. K12 and K13 expression were detected on the IC specimens by immunohistochemistry study. The number of K12 + or K13 + cells in all areas of the IC was quantified using ImageJ software. RESULTS: The epithelial cells harvested from IC specimens from control corneas were all K12 + . In eyes with LSCD, K13 + and K12 + /K13 + cells accounted for 93.8% and 2.6%, respectively, in the cornea. In eyes with sectoral LSCD, the median number of K13 + cells in the clinically affected area was higher than that in the unaffected area (810.0 vs. 115.0 cells/mm 2 ; P < 0.001). No significant correlation was found between the LSCD severity and the number of K12 + cells (r = -0.284, P = 0.16) or K13 + cells (r = -0.011, P = 0.95). The presence of at least 16 K13 + cells/mm 2 was suggestive of LSCD. CONCLUSIONS: Identification of K13 + cells on IC specimens provides a simple and reliable method to detect conjunctival epithelial cells on the cornea. K13 is a marker for diagnosing LSCD and localizing the involved area in sectoral LSCD.

Cancer cell mechanobiology: a new frontier for cancer research.

The study of physical and mechanical features of cancer cells, or cancer cell mechanobiology, is a new frontier in cancer research. Such studies may enhance our understanding of the disease process, especially mechanisms associated with cancer cell invasion and metastasis, and may help the effort of developing diagnostic biomarkers and therapeutic drug targets. Cancer cell mechanobiological changes are associated with the complex interplay of activation/inactivation of multiple signaling pathways, which can occur at both the genetic and epigenetic levels, and the interactions with the cancer microenvironment. It has been shown that metastatic tumor cells are more compliant than morphologically similar benign cells in actual human samples. Subsequent studies from us and others further demonstrated that cell mechanical properties are strongly associated with cancer cell invasive and metastatic potential, and thus may serve as a diagnostic marker of detecting cancer cells in human body fluid samples. In this review, we provide a brief narrative of the molecular mechanisms underlying cancer cell mechanobiology, the technological platforms utilized to study cancer cell mechanobiology, the status of cancer cell mechanobiological studies in various cancer types, and the potential clinical applications of cancer cell mechanobiological study in cancer early detection, diagnosis, and treatment.

The Relieving Effects of a Polyherb-Based Dietary Supplement ColonVita on Gastrointestinal Quality of Life Index (GIQLI) in Older Adults with Chronic Gastrointestinal Symptoms Are Influenced by Age and Cardiovascular Disease: A 12-Week Randomized Placebo-Controlled Trial.

Chronic gastrointestinal symptoms (CGS) negatively affect the quality of life in about 15-30% of the population without effective drugs. Recent studies suggest that dietary supplement may improve CGS, but inconsistent results exist. The goal of this study is to evaluate the effect of a polyherbal-based supplement ColonVita on the gastrointestinal quality of life index (GIQLI) in 100 old adults with CGS (63.1 ± 9.6 years) who were randomly assigned to daily ColonVita or placebo tablets (n = 50/group) for 12 weeks in a double-blind, randomized controlled trial design. No significant fibrdifferences were found between ColonVita and placebo in the baseline total GIQLI score (101.12 ± 16.87 vs. 101.80 ± 16.48) (P > 0.05) or postintervention total GIQLI score (114.78 ± 9.62 vs. 111.74 ± 13.01) (P > 0.05). However, ColonVita significantly improved 16 scores of the 19 core GI symptoms compared with 10 items improved by placebo. The ColonVita group significantly improved the remission rate of 5 core GI symptoms compared to placebo and significantly improved the total GIQLI scores (118.09 ± 7.88 vs. 109.50 ± 16.71) (P < 0.05) and core GI symptom scores (64.61 ± 3.99 vs. 60.00 ± 8.65) (P < 0.05) in people ≥60 years of age (n = 49) but not in those under 60 y (n = 51). ColonVita significantly improved the total GIQLI scores and core GI symptom scores in people without cardiovascular diseases (CVD) (n = 56) (116.74 ± 9.38 vs. 110.10 ± 14.28) (P < 0.05) and (63.11 ± 4.53 vs. 59.93 ± 8.03) (P=0.07), respectively, but not in those with CVD (n = 44). Thus, ColonVita was beneficial for old adults with CGS, especially those ≥60 years of age and without CVD. Because a heterogenous pathogenesis of CGS-like irritable bowel syndrome (IBS) and inflammatory bowel disease (ISD) is differentially associated with CVD, different comorbidities may have influenced the outcomes of different trials that should be controlled in further studies.

Interactions Between Adiponectin-Pathway Polymorphisms and Obesity on Postmenopausal Breast Cancer Risk Among African American Women: The WHI SHARe Study.

BACKGROUND: A decreased level of serum adiponectin is associated with obesity and an increased risk of breast cancer among postmenopausal women. Yet, the interplay between genetic variants associated with adiponectin phenotype, obesity, and breast cancer risk is unclear in African American (AA) women. METHODS: We examined 32 single-nucleotide polymorphisms (SNPs) previously identified in genome-wide association and replication studies of serum adiponectin levels using data from 7,991 AA postmenopausal women in the Women's Health Initiative SNP Health Association Resource. RESULTS: Stratifying by obesity status, we identified 18 adiponectin-related SNPs that were associated with breast cancer risk. Among women with BMI ≥ 30 kg/m2, the minor TT genotype of FER rs10447248 had an elevated breast cancer risk. Interaction was observed between obesity and the CT genotype of ADIPOQ rs6773957 on the additive scale for breast cancer risk (relative excess risk due to interaction, 0.62; 95% CI, 0.32-0.92). The joint effect of BMI ≥ 30 kg/m2 and the TC genotype of OR8S1 rs11168618 was larger than the sum of the independent effects on breast cancer risk. CONCLUSIONS: We demonstrated that obesity plays a significant role as an effect modifier in an increased effect of the SNPs on breast cancer risk using one of the most extensive data on postmenopausal AA women. IMPACT: The results suggest the potential use of adiponectin genetic variants as obesity-associated biomarkers for informing AA women who are at greater risk for breast cancer and also for promoting behavioral interventions, such as weight control, to those with risk genotypes.

Long-Term Exposure to PM2.5, Facemask Mandates, Stay Home Orders and COVID-19 Incidence in the United States.

Long-term PM2.5 exposure might predispose populations to SARS-CoV-2 infection and intervention policies might interrupt SARS-CoV-2 transmission and reduce the risk of COVID-19. We conducted an ecologic study across the United States, using county-level COVID-19 incidence up to 12 September 2020, to represent the first two surges in the U.S., annual average of PM2.5 between 2000 and 2016 and state-level facemask mandates and stay home orders. We fit negative binomial models to assess COVID-19 incidence in association with PM2.5 and policies. Stratified analyses by facemask policy and stay home policy were also performed. Each 1-µg/m3 increase in annual average concentration of PM2.5 exposure was associated with 7.56% (95% CI: 3.76%, 11.49%) increase in COVID-19 risk. Facemask mandates and stay home policies were inversely associated with COVID-19 with adjusted RRs of 0.8466 (95% CI: 0.7598, 0.9432) and 0.9193 (95% CI: 0.8021, 1.0537), respectively. The associations between PM2.5 and COVID-19 were consistent among counties with or without preventive policies. Our study added evidence that long-term PM2.5 exposure increased the risk of COVID-19 during each surge and cumulatively as of 12 September 2020, in the United States. Although both state-level implementation of facemask mandates and stay home orders were effective in preventing the spread of COVID-19, no clear effect modification was observed regarding long-term exposure to PM2.5 on the risk of COVID-19.

Advances in Imaging Modalities, Artificial Intelligence, and Single Cell Biomarker Analysis, and Their Applications in Cytopathology.

Several advances in recent decades in digital imaging, artificial intelligence, and multiplex modalities have improved our ability to automatically analyze and interpret imaging data. Imaging technologies such as optical coherence tomography, optical projection tomography, and quantitative phase microscopy allow analysis of tissues and cells in 3-dimensions and with subcellular granularity. Improvements in computer vision and machine learning have made algorithms more successful in automatically identifying important features to diagnose disease. Many new automated multiplex modalities such as antibody barcoding with cleavable DNA (ABCD), single cell analysis for tumor phenotyping (SCANT), fast analytical screening technique fine needle aspiration (FAST-FNA), and portable fluorescence-based image cytometry analyzer (CytoPAN) are under investigation. These have shown great promise in their ability to automatically analyze several biomarkers concurrently with high sensitivity, even in paucicellular samples, lending themselves well as tools in FNA. Not yet widely adopted for clinical use, many have successfully been applied to human samples. Once clinically validated, some of these technologies are poised to change the routine practice of cytopathology.