Preinvasive Lesions Research Articles

The Correlation Between the Natural Course, Pathologic Properties With Ki-67 Expression in Lung Adenocarcinoma Presenting as Ground-Glass Nodules.

With the increasing use of lung cancer screening, the detection of ground glass nodules (GGNs) has risen. However, the natural course of GGNs and their relationship to pathologic features remains unclear. Differentiating between invasive and pre-invasive lesions based on GGN growth may improve clinical intervention timing. Ki-67, a proliferation marker, holds value in assessing tumor malignancy. This study analyzes the association between GGN growth, pathology, and Ki-67 expression to provide new insights into early-stage lung cancer management. We retrospectively evaluated 183 GGNs with at least two preoperative CT scans. Nodule location, type, natural course, and volume doubling time (VDT) were compared between invasive adenocarcinoma (IAC) and pre-IAC groups. We also assessed differences in Ki-67 expression and correlated VDT with Ki-67 levels. A total of 183 nodules were finally included; gender, nodule location, smoking history, and duration of follow-up did not differ between the IAC group and the pre-IAC group, whereas age was statistically different between the two groups. Of the 183 nodules, 52 showed growth and the predominant pathologic type was IAC, these IACs showed more PSN in nodule type, while the IAC group showed more significant differences in nodule type, nodules growth, and VDT than the pre-IAC group. There were also differences in pathologic type and VDT between different Ki-67 expression groups, and Ki-67 expression gradually increased as VDT decreased. Lung adenocarcinoma (LUAD) presenting as GGNs exhibit distinct natural courses among pathologic subtypes. VDT effectively distinguishes these growth characteristics, with IACs showing shorter VDT. The significant correlation between VDT and Ki-67 expression suggests that combining these parameters may provide valuable insights into the biological behavior and invasiveness of LUAD.

Application of 18 F-fluorodeoxyglucose PET/computed tomography in the diagnosis of infiltrative subsolid nodules in lung adenocarcinoma.

To investigate the diagnostic value of 18 F-fluorodeoxyglucose(FDG) PET/computed tomography (CT) for infiltrative subsolid nodules at different stages of lung adenocarcinoma and to explore predictive factors for invasive adenocarcinoma, providing compelling evidence for timely intervention. A retrospective analysis was conducted on PET/CT imaging data of 170 subsolid nodules lesions confirmed postoperatively as lung adenocarcinoma or precursor glandular lesions. Lesions were categorized into preinvasive lesions including atypical adenomatous hyperplasia and adenocarcinoma in situ, microinvasive adenocarcinoma, and invasive adenocarcinoma. Compared the differences in imaging features and metabolic parameters among different groups and used a multifactor logistic regression model and receiver operating characteristic curve analysis to identify predictive factors for invasive adenocarcinoma. From preinvasive lesions through microinvasive adenocarcinoma to invasive adenocarcinoma, there was a gradual increase in nodule diameter, nodule area, and proportion of part-solid nodule. Statistical significance ( P < 0.05) was observed in the rates of spiculation and pleural indentation between preinvasive lesions versus microinvasive adenocarcinoma and invasive adenocarcinoma groups. The maximum standardized uptake value and maximum standardized uptake ratio show statistically significant differences ( P < 0.05) between the invasive adenocarcinoma group and the other groups. Logistic regression analysis indicated that nodule composition, nodule diameter, and maximum standardized uptake ratio were predictive factors for invasive adenocarcinoma ( P < 0.05). For part-solid nodules, the longest diameter of the solid component has a high diagnostic value. The imaging features of 18 F-FDG PET/CT contribute to the diagnosis of infiltrative subsolid nodules at different stages of lung adenocarcinoma, providing robust evidence for timely intervention.

Early-Stage and Locally Advanced Cervical Cancer during Pregnancy: Clinical Presentation, Diagnosis and Treatment.

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care.

Fractal Dimension Analysis of the Tumor Microenvironment in Cutaneous Squamous Cell Carcinoma: Insights into Angiogenesis and Immune Cell Infiltration

The global incidence of cutaneous squamous cell carcinoma (cSCC), a prevalent and aggressive skin cancer, has risen significantly, posing a substantial public health challenge. This study investigates the tumor microenvironment (TME) of cSCC by focusing on the spatial distribution patterns of immune and vascular markers (CD31, CD20, CD4, and CD8) using fractal dimension (FD) analysis. Our analysis encompassed 141 cases, including 100 invasive cSCCs and 41 specimens with pre-invasive lesions exclusively, and the rest were peripheral pre-invasive lesions from the invasive cSCC class. The FD values for each marker were computed and compared between pre-invasive and invasive lesion classes. The results revealed significant differences in FD values between the two classes for CD20 and CD31 markers, suggesting distinct alterations in B cell distribution and angiogenic activity during cSCC progression. However, CD4 and CD8 markers did not exhibit significant changes individually. Still, the CD4/CD8 ratio showed a significant difference, suggesting a potential shift in the balance between T helper and cytotoxic T cell responses, impacting the immune landscape as lesions progressed from pre-invasive to invasive stages. These findings underscore the complexity and heterogeneity of the TME in cSCC and highlight the potential of FD analysis as a quantitative tool for characterizing tumor progression. Further research is needed to elucidate the implications of these differences in the clinical management of cSCC.

7242 Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) In A Patient With Recurrent Carcinoid

Abstract Disclosure: F. Woron: None. T.L. Anderson: None. P. Madhavan: None. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare generalized proliferation of pulmonary neuroendocrine cells. It is considered to be a pre-invasive lesion for pulmonary carcinoid, a rare neuroendocrine tumor (NET). DIPNECH is thought to be underdiagnosed, as patients can be asymptomatic or present with nonspecific cough and dyspnea, though it is also associated with fibrotic lung changes. Long-term annual surveillance imaging is recommended for due to the potential for development and metastasis of carcinoid tumors. We present a patient with recurrent pulmonary carcinoid later diagnosed with probable DIPNECH based on CT findings. The patient is a 72-year-old female with a prior 15 pack-year smoking history, who initially had a left lower lobe typical carcinoid tumor diagnosed and resected in 2018, with no evidence of lymph node metastasis. The patient’s medical history also includes pulmonary sarcoidosis, adrenal adenoma, thyroid nodule, hiatal hernia, and prediabetes. She has no family history of neuroendocrine tumors. Physical exam showed stable vitals with blood pressure of 112/70 mmHg in the right upper arm, heart rate of 84 bpm, and a body mass index of 39. Physical exam was unremarkable except for thyroid nodularity and obesity. Extensive biochemical evaluation for markers including chromogranin A and 24-hour urine 5-HIAA levels were within normal limits. In 2022, surveillance CT imaging showed a new 9 mm nodule in the right lobe within the bronchus, which was shown to be carcinoid on FNA. She complained of dyspnea and wheezing at this time, which has been managed with an albuterol inhaler. In 2023, PET/CT copper 64 dotatate scan showed a focal area of activity related to the nodule in the superior segment, also identified on recent CT scan, with the nodule measuring approximately 2.05 cm x 1.8 cm with a maximal SUV of 4.2. Interestingly, somatostatin receptor scintigraphy did not show any pick-up in the lung in 2018 or 2022. In 2023, the patient underwent right lower lobe superior segmentectomy after the nodule was found to have increased in size. Pathology showed G1, well-differentiated 1.1 cm typical carcinoid tumor with margins negative for invasive carcinoma. All 18 regional lymph nodes were negative for tumor. Immunohistochemical tests show that the tumor cells were positive for INSM1 and chromogranin with a low Ki-67 proliferation index (&amp;lt;2%), supporting the diagnosis. The patient is currently being monitored by yearly CT imaging and followed by both endocrinology and pulmonology. Given this case, we propose that DIPNECH should be considered as a differential in cases of pulmonary carcinoid, especially recurrent ones. Given that DIPNECH is thought to be underdiagnosed and a precursor for carcinoid associated with fibrotic lung changes, it is essential for this disease to be identified in order for patients to receive appropriate long-term monitoring. Presentation: 6/1/2024

Using CT features of cystic airspace to predict lung adenocarcinoma invasiveness.

Lung adenocarcinoma associated with cystic airspace (LACA) was once considered an uncommon manifestation of lung adenocarcinoma (LUAD), and understandings of it are limited; however, it is being observed more frequently in clinical practice. This study sought to assess the prevalence of LACA, and compare the high-resolution computed tomography (HRCT) features of LACA in patients with varying degrees of invasiveness. This study retrospectively reviewed the HRCT scans of 1,525 patients with LUAD ≤3 cm in diameter at the Shanghai Chest Hospital between January 2016 and May 2016. Each nodule was examined to detect the presence of cystic airspace. Additionally, we analyzed the qualitative HRCT findings of the cystic airspaces, including the pattern, number, wall component density, distribution, inner surface, mural nodules, septa, and vessels passing through the cystic airspace using the Pearson χ2 test or Fisher's exact test as appropriate. We also analyzed the quantitative measurements, such as the cystic airspace diameter, wall thickness, and thin-wall proportion, using a one-way analysis of variance or the Kruskal-Wallis rank-sum test as appropriate. LACAs were observed on HRCT in 11.5% (176/1,525) of the patients, of whom 7.1% (36/505) had pure ground-glass nodules, 13.5% (112/830) had mixed ground-glass nodules, and 14.7% (28/190) had solid nodules (P=0.001). The surgical procedures for LACAs varied (P=0.012). The incidence of LACAs increased as nodule diameter and invasiveness increased (both P<0.001). Statistically significant differences were observed in the wall component density, distribution, septa, vessels passing through the cystic airspace, cystic airspace diameter, wall thickness, and thin-wall proportion among the preinvasive lesion (PL), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) groups (P<0.001, P=0.024, P=0.001, P=0.025, P=0.001, P<0.001, and P<0.001, respectively). Wall component density increased as invasiveness increased (P<0.001). Unlike those in the MIAs and IACs, cystic airspaces in PLs typically lacked septa (P=0.001, and P<0.001, respectively). The IACs had larger cystic airspace diameters than the PLs (6.5 vs. 3.7 mm) (P<0.001). The IACs also had thicker wall thickness (11.8 vs. 6.8 mm, 11.8 vs. 8.3 mm) (P<0.001, and P<0.001, respectively) and smaller thin-wall proportions (181.5° vs. 264.8°, 181.5° vs. 223.8°) (P<0.001, and P=0.039, respectively) than the PLs and MIAs. The prevalence and characteristics of cystic airspaces on HRCT can be used to predict invasiveness in patients with LUADs ≤3 cm in diameter.

EP.07F.07 Role of Microbiome in the Outcome of the Preinvasive Lung Cancer Lesions

EP.07F.07 Role of Microbiome in the Outcome of the Preinvasive Lung Cancer Lesions

Abstract B019: Sensitivity and specificity of detecting premalignant pancreatic lesions by hyperpolarized magnetic resonance

Abstract Introduction: The high mortality rate of pancreatic cancer (PC) results from a lack of methods for early detection. The progression of PC occurs primarily via two precursor pathways, either through microscopic pancreatic intraepithelial neoplasias (PanINs) or macroscopic cystic lesions, of which intraductal papillary mucinous neoplasms (IPMNs) are the most common. The progression from either PanIns or IPMN to PC, provides an opportunity for early detection of this lethal disease. PC cells have extensively reprogrammed metabolism and we have successfully employed hyperpolarized 1-13C pyruvate metabolic imaging (HP MR) to measure non-invasively the metabolic plasticity as the disease initiates and evolves. Concurrently, the specificity of HP MR of detecting premalignant lesions will be determined by imaging pancreatitis induced mice at different timepoints and compare them to the premalignant models. Methods: HP 1-13C Pyruvate MRS was employed to study the metabolic processes in tamoxifen inducible GEM models (P48CreERT2;LSL-KrasG12D (iKC)) with pre-invasive PanIN precursor lesions, invasive PC model (P48CreERT2;LSL-KrasG12D;LSL-p53R172H (iKPC)) and control animals (P48CreERT2 (iC)). These mice were imaged at different time points, before tamoxifen induction, 10-, 20-, and 30-weeks post induction. HP MR was also employed on IPMN mouse model (p48Cre;LSL- KrasG12D;Rosa26R-LSL-rtTA-TetO-GnasR201C) that develop premalignant cystic lesions, that progresses to PC on doxycycline diet (Dox+) for 15 weeks and control mice on normal diet (Dox-). These mice were imaged after 15 weeks of (Dox±) treatment. Simultaneously, wildtype, iC and iKC mice were treated with caerulein for three weeks for the development of pancreatitis and imaged 24 hours after treatment. Results: In the PanIN model, the lactate-to-pyruvate (lac/pyr) ratio increased in the PC models compared to the control model. For the aggressive iKPC mouse model, at the 20-week post induction imaging there was a significant increase of the lac/pyr ratio (0.28±0.04) compared to the 10-week time point (0.22±0.03). At the 20-week time point, the iKPC ratio was higher than the iKC and control ratios, (0.28±0.04 compared to 0.23±0.03 and 0.22±0.02 respectively) indicating the invasive nature of the cancer. Even in the iKC model there is a slight increase of the lac/pyr ratio at 20-weeks (0.23±0.03) compared to control (0.22±0.02). Mice treated with caerulein developed pancreatitis as demonstrated by tissue histology. Surprisingly, the lac/pyr ratio remained constant in both iC and iKC mice that developed pancreatitis, around 0.15±0.03 for both groups. In the IPMN model, IPMN mice feed with doxycycline showed increase pancreatic lesions and an increased lac/pyr ratio (0.43±0.05) compared to mice on normal diet (0.24±0.05). Conclusion: HP MR can detect metabolic shift to lactate in two different models of PC premalignancy representing two different pathways of PC progression. This finding can be potentially translated to the clinic for detection of premalignant pancreatic lesions in high-risk populations. Citation Format: José S Enriquez, Rian M Howell, Olivereen Le Roux, Shivanand Pudakalakatti, Prasanta Dutta, Florencia McAllister, Pratip K Bhattacharya. Sensitivity and specificity of detecting premalignant pancreatic lesions by hyperpolarized magnetic resonance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B019.

Review of triage strategies for atypical squamous cells of undetermined significance among young women.

In the present study we reviewed the existing literature regarding management approaches for ASC-US and highlight their pros and cons. The ASC-US entity emerged from Bethesda classification 2001. We conducted this review using search words ASC-US triage, ASC-US management in young women, triage tests for ASC-US, and ASC-US outcome from the English literature. We included different cervical cancer policies (American, European and for WHO) and research articles published on ASC-US in young women from the year 2001. We searched in Google Scholar, PubMed, MEDLINE (NCBI) library, Embase (Elsevier), Wiley online library as well as Cochrane library. We defined young women as aged 30 years and below. We identified 52 articles which focused on management approaches of ASC-US, seven articles focused on young women aged <30 years. Five of these articles combined ASC-US with low-grade squamous intraepithelial lesions (ASC-US/LSIL) while only two addressed ASC-US as a standalone entity. The limited number of articles restricts the evidence base supporting the adoption of triage strategies. There is yet, no consensus in the literature regarding the management of ASC-US, more so in young women below the age of 30 years. Researchers, however, agree on a few aspects, which include the necessity for applying a conservative strategy for managing ASC-US in young women, avoiding direct referral for colposcopy at the initial detection of ASC-US, and avoiding the use of human papillomavirus (HPV) testing on young women (unless living with HIV). Newer techniques such as HPV E6/E7 messenger RNA (mRNA), and dual staining p16/ki-67, may serve as better triage to identify cases of HPV persistence and integration which may subsequently lead to preinvasive or invasive lesions.

The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma

BackgroundA better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.MethodsWe utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.ResultsWe revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.ConclusionsTogether with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.

Cancer-specific alterations in nuclear matrix proteins determined by multi-omics analyses of ductal carcinoma in situ.

Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC. Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS. Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques. These genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment.

Transcriptome and microbiome-immune changes across preinvasive and invasive anal cancer lesions.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk Human papillomavirus (HPV) infection, which develops from precursor lesions like Low-Grade Squamous Intraepithelial Lesions (LGSIL) and High-Grade Squamous Intraepithelial Lesions (HGSIL). ASCC incidence varies across populations, posing increased risk for People Living with HIV (PLWH). Our investigation focused on transcriptomic and metatranscriptomic changes from Squamous Intraepithelial Lesions (SILs) to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptome analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low- or high-risk progression to malignancy.

From Self-Collected HPV Sampling to Self-Administered Treatment Cervical Pre-Invasive Lesions: A Dream to Reality

From Self-Collected HPV Sampling to Self-Administered Treatment Cervical Pre-Invasive Lesions: A Dream to Reality

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Pre-invasive Lesion of Cervix Among Healthy and Immune Compromised Individuals Using Histopathological Examination: A Hospital Based Cross-Sectional Study

Pre-invasive Lesion of Cervix Among Healthy and Immune Compromised Individuals Using Histopathological Examination: A Hospital Based Cross-Sectional Study

LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment.

Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.

Adaptively learning visual model of surgical resection images via coarse-to-fine–grained strategy for pathological invasiveness prediction in indeterminate stage IA lung adenocarcinoma.

1563 Background: Indeterminate nodules with high risk of malignancy are suggested to receive video-assisted thoracoscopy biopsy. Frozen section assists surgeons to decide surgical strategies for stage IA lung adenocarcinoma (LUAD) intraoperatively, which is time-consuming and may misdiagnosis due to limited sampling and poor tissue quality. Methods: We prospectively enrolled stage IA LUAD patients underwent complete resection between June 2020 and September 2023 in Guangdong Provincial People's Hospital (GDPH), Affiliated Hospital of Guangdong Medical University, Meizhou People's Hospital. All the resected lung nodules were finally diagnosed as pre-invasive lesion (PIL), minimally invasive adenocarcinoma (MIA) or invasive lung adenocarcinoma (IAC) by FFPE pathological diagnosis. Images of the whole section of the lung nodules were taken by smartphones under natural lighting condition in operating theaters without shadowless surgical lights. Patients received preoperative anti-cancer therapy and with low-quality tumor section images were excluded. Images of nodules section, FS reports, FFPE diagnosis and clinical information were prospectively collected. Predictive artificial intelligence (AI) model was developed by a three-step process, which first predict the IAC and non-IAC region at coarse level, and identify fine level features through the high-risk region. The coarse and fine labels were then coordinated through risk ranking loss to reach a final predictive result. Results: We prospectively enrolled 1516 patients with 1638 indetermined lung nodules from preoperative chest CT following the inclusion and exclusion criteria, with 2438 images acquired from intraoperative nodule sections. The included patients have median age of 57 years old and 38.6% male patients. The pathological diagnosis for included lung nodules are 122 PIL nodules, 502 MIA nodules and 1014 stage IA LUAD. A multi-task artificial intelligence based on Coarse-to-Fine-Grained Strategy has been established to classify the indetermined lung nodules during the surgery. For binary classification, AI model reach an AUC of 0.86 in differentiation between IAC or non-IAC. For 3-classification level, AI model reach an AUC of 0.87 in differentiation between PIL, MIA or IAC. We further defined the IAC nodules into G1, G2 and G3 according to IASLC lung adenocarcinoma grading system. For 5-classification level, AI model reach an AUC of 0.86 in differentiation between PIL, MIA, IAC-G1, IAC-G2 and IAC-G3. Conclusions: Our AI models based on images of intraoperative surgical resection could effectively classify indetermined lung nodules, which can assist thoracic surgeons diagnose the nodules rapidly during the surging and decide the following surgical strategies. Clinical trial information: ChiCTR2300075999 .

Role of Conventional Pap Smear in Current Times

Abstract Cervical cancer is the fourth most common malignancy among females after breast, colon, and lung cancers and a leading cause of mortality among gynecologic malignancies. Over 85% of new cases are diagnosed in resource-limited countries. Several screening techniques have been developed to detect precancerous changes timely. The most common of which is conventional Pap smear (CPS). It is based on the cytological and morphology assessment of exfoliated cervical cells to detect preinvasive lesions of the cervix. Despite high specificity, a single Pap test has a low-to-moderate sensitivity. CPS can have false-negative and false-positive results because of inadequate sampling and slide preparation and errors in laboratory detection and interpretation. To overcome these shortcomings, liquid-based cytology (LBC) was introduced. LBC can be a better alternative to CPS because of a lower rate of unsatisfactory smears. The liquid reserve can be used for ancillary testing, such as human papillomavirus DNA tests (as reflex test and co-test). The cost of this technique is a limiting factor. In most of the developed countries, CPS is replaced by the LBC. There are several studies with conflicting results, and no method has been shown to be superior in terms of all parameters. Relevant studies were searched using PubMed/MEDLINE and Google Scholar. This article puts forward the results of various studies comparing the efficacy of CPS and LBC and highlights the advantages and disadvantages of both methods.

Comparison of Sexual Function after Thermal Ablation Versus Loop Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia (CIN 2 and 3): A Randomized Controlled Trial.

The prevention of cervical cancer can be achieved by treating high-grade cervical precancerous lesions. Treatment options for cervical precancer include excisional procedures, and ablation treatments. Despite the long pre-invasive course of the disease, literature addressing sexual function post-treatment for cervical pre-invasive lesions is scarce. This study aims to bridge this gap and assess the sexual function and the acceptability, efficacy, safety, and complications of loop electrosurgical excision procedure (LEEP) versus thermal ablation. The prospective open-label randomized controlled trial recruited women aged 22-55 with histologically confirmed Cervical Intraepithelial Neoplasia (CIN) 2 and 3 lesions. Participants were randomly allocated to either thermal ablation or LEEP. All cases were followed up with a Pap smear at three- and six-months post treatment. Sexual health assessments were conducted using a questionnaire at baseline and 3 months post-procedure. Secondary outcome measures included comparison of acceptability, pain, and side effects between the two treatment measures. Out of 1356 screened cases, 60 were included in the study and randomized in two groups. The groups had similar baseline characteristics. Duration of LEEP was longer than thermal ablation (25.33 vs. 20.67 minutes), with higher pain reported 10 minutes post-procedure in the LEEP group. Three months post-procedure, both groups showed comparable acceptability and symptom relief. Sexual function parameters significantly improved in the thermal ablation group compared to LEEP, including satisfaction, desire, lubrication, flexibility, and ability to reach climax. LEEP and thermal ablation are effective treatments for CIN with similar efficacy at 6 months. Thermal ablation demonstrated advantages in procedure time and post-procedural pain but exhibited varying effects on sexual function, improving satisfaction and desire. In contrast, LEEP showed a decrease in satisfaction and potential alterations in lubrication and flexibility. Larger-sample, longer-term studies are recommended for further insights.

Vulva lesions seen at a tertiary health centre in southwest Nigeria

Background: Some researchers have emphasised the need for more studies on vulvar cancers. The aim of our study is to describe the vulvar lesions identified in biopsies seen in our department over a five-year period to serve as baseline data for future studies. Methods: We conducted a five-year cross-sectional study on all vulva specimens received by the department of Morbid Anatomy and Forensic medicine at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria. From the departmental records, we retrieved data on the patients' biodata, medical history, and vulva lesion diagnosis. Results: We recorded 15 vulva biopsies during the study period, with an age range of 13 to 80 years. Two cases were benign tumours, and two cases were inflammatory in nature. A case of a pre-malignant lesion was seen. Nine cases were malignant tumours, all of which are epithelial in origin. We saw two non-neoplastic lesions. These are acute on chronic inflammation and lichen sclerosus et atrophicus. Of the malignant tumours seen, five were well-differentiated squamous cell carcinoma (SCC), two were moderately differentiated SCC, and two were cases of verrucous carcinoma. One case of verrucous carcinoma and a well-differentiated SCC had a background HIV. Conclusion: Vulva lesions are rarely seen at our centre. The absence of preinvasive lesions in our study may be due to the late presentation of cases in clinics or the reluctance of gynaecologists to take biopsies of non-tumoral lesions of the vulva. HIV may be associated with an increased risk of HPV-related cancers.