High Mitotic Index Research Articles

Prognostic impact of fibrosclerotic changes in non-papillary, non-anaplastic, follicular cell-derived thyroid carcinomas.

In non-papillary follicular cell-derived thyroid carcinomas, prognostic factors are scarce. Intratumoral fibrosis was identified as an adverse factor in papillary and medullary carcinomas, but it has not been investigated in other subtypes. We aimed at exploring the presence of intratumoral fibrosclerosis in a cohort of 132 non-papillary follicular cell-derived thyroid carcinomas (53 follicular and 31 oncocytic carcinomas, including 10 high grade differentiated thyroid carcinomas and 48 poorly differentiated carcinomas) and correlating its presence and extent with clinical and pathological features and survival. For each case, all available hematoxylin and eosin slides were reviewed, and the presence of fibrosclerosis was assessed as the percentage of tumor area and semi-quantitatively scored as absent, mild (≤ 10%) or extensive (> 10%). In addition, digital image analysis was applied in 65 cases. Scoring of intratumoral fibrosis showed a strong agreement between two observers and between observers and digital image quantification. The presence and extent of intratumoral fibrosis were significantly associated with poorly differentiated carcinoma histology, large tumor size, extent of vascular invasion, presence of necrosis, high mitotic index, positive nodal status, and aggressive clinical outcome, and with a shorter disease-free and disease-specific survival, the former also in follicular and oncocytic carcinomas analyzed separately. These data support the potential use of fibrosis in the clinical practice since it is both easily assessable and significantly associated with the presence of parameters of aggressiveness. In addition, fibrosis is correlated with decreased survival rate independently from the tumor histotypes, suggesting its potential role as novel prognostic factor in non-papillary follicular cell-derived thyroid carcinomas.

Exploration of plasma tryptophan levels along with Ki-67 expression binomial investigation for forecasting tumor aggressiveness within invasive ductal breast cancer.

Ki-67 is a histological marker indicating cancer aggressiveness, while tryptophan (TRP) depletion modulates immune responses, including tumor aggressiveness. The study evaluates Ki-67's predictive value in relation to plasma TRP levels in invasive ductal carcinoma of breast cancer, aiming to improve understanding of tumor characteristics and clinical behavior. A study involving 165 women, measured plasma TRP levels and Ki-67 and analyzed their relationship with tumor aggressiveness markers using statistical analyses and predictive models. Our study highlighted a significant correlation between decreased plasma levels of TRP and a high mitotic index, measured by the Ki-67 marker (Pearson correlation coefficient r = -0.402; p = 0.011). Tryptophan levels below 40 µmol/L were associated with a Ki-67 level above 15%, suggesting more active tumor growth in patients. Additionally, several risk factors for BC were identified within the studied population. The demographic and clinical characteristics of the participants include an average age of 63 years, plasma glucose levels above 1.2 g/L, and plasma TRP levels below 40 µmol/L, which are associated with an increased risk of BC. Furthermore, various polynomial logistic regression models indicate that TRP levels may be predicted based on Ki-67 expression, providing a promising approach to refine prognostic assessments. The study showed a correlation between low levels of tryptophan (TRP) and a high Ki-67 mitotic index in breast cancer patients, particularly in invasive ductal carcinoma, which is strongly linked to the aggressiveness of the disease. The integration of these markers into routine practice remains a technical and economic challenge.

Distinct Transcriptomic and Tumor Microenvironment Profiles in Sinonasal Mucosal Melanoma and Aggressive Cutaneous Melanomas.

Background/Objectives: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis compared to cutaneous melanoma (CM). Despite advances in molecular characterization, SNMM remains underexplored, posing a clinical challenge and highlighting the need for detailed molecular profiling. This study aimed to identify the molecular features of SNMM, elucidate its clinical behavior and prognostic implications, and provide insights for improved therapeutic strategies. Methods: This retrospective study analyzed 37 primary melanoma tumors diagnosed at the Hospital Clinic of Barcelona. Gene expression was examined using 1402 immuno-oncology-related probes through next-generation sequencing. Hierarchical clustering analysis (HCA), differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and the xCell algorithm were performed. The statistical methods comprised descriptive statistics, clinical variable associations, and survival analyses. Results: HCA revealed two primary clusters. Cluster A exclusively contained CM tumors (20/24), while cluster B included all SNMMs (13/13) and some CMs (4/24). Cluster B showed a higher average age at diagnosis (p = 0.018), higher mitotic index (p = 0.0478), fewer BRAF mutations (p = 0.0017), and poorer melanoma-specific survival (p = 0.0029). Cluster B showed 602 DEGs with cell cycle pathways enriched, immune pathways diminished, lower immune scores (p < 0.0001), and higher stromal scores (p = 0.0074). Conclusions: This study revealed distinct molecular characteristics and an altered tumor microenvironment in SNMMs and certain aggressive CMs. Identifying specific genes and pathways involved in cell cycle progression and immune evasion suggests potential prognostic markers, offering new avenues for enhancing treatment strategies and improving patient survival rates.

A Case of a Clinically Proliferating Trichilemmal Cyst Following the Take of Febuxostat and Calcium Carbonate

Trichilemmal cysts or pilar cysts are keratin-filled cysts that originate in the outer root sheath. They are typically found on the scalp of middle-aged women. They are inherited as an autosomal dominant trait. Trichilemmal cysts range from simple trichilemmal cysts to benign and malignant proliferative trichilemmal cysts. Proliferation can be clinical or histological. Clinically, it may present as an increase in size with the onset of an ulceration. Histologically, it translates as the acquisition of certain features which are the dermal proliferation of a squamous epithelium that arranges in a lobular fashion with clear cells containing glycogen in some areas surrounded by a somewhat cellular and glassy stroma; and especially the trichilemmal keratinization in the centre of lobules. There are also certain histopathological criteria to distinguish benign from malignant proliferating trichilemmal cysts. A malignant trichilemmal cyst is characterized by a high mitotic index, atypical mitoses, significant nuclear polymorphism, and tumor invasion of adjacent tissues. Immunohistochemistry can also confirm the benign character by expression of cytokeratin 10 and involucrin. We report here a case of a clinically proliferating trichilemmal cyst following the introduction of calcium carbonate and febuxostat in a patient undergoing treatment for hypertension and renal failure, but retaining a typically simple and benign character on histology.

Automatic discrimination between neuroendocrine carcinomas and grade 3 neuroendocrine tumors by deep learning of H&E images

Neuroendocrine neoplasms (NENs) arise from diffuse neuroendocrine cells and are categorized as either well-differentiated and less proliferative Neuroendocrine Tumors (NETs), divided into low (G1), middle (G2), and high grades (G3), or poorly differentiated, and more proliferative Neuroendocrine Carcinomas (NECs). Low-grade NENs typically necessitate surgical intervention, whereas high-grade ones often require chemotherapy. However, low-grade NENs may exhibit aggressive behavior. Therefore, it is crucial to precisely refine the diagnosis of NENs. This refinement is achievable when differentiation/non-differentiation is evident or when the Ki-67 or mitosis index is low. The challenge arises in cases of morphologically undifferentiated instances with a high Ki-67 percentage and/or high mitotic index. To address this challenge, we developed a Deep Learning (DL) system named NEToC, designed to differentiate between NETs and NECs using exclusively morphological information from immunohistochemistry images, without relying on Ki-67 or mitosis assessments. NEToC was developed using 95 NEN cases from the period 2015 to 2018 at Parc Tauli Hospital in Spain, comprising 588 images. Implemented as a Graphical User Interface (GUI) system, NEToC is intended for deployment in pathological departments of hospitals to perform federated supervision. We tested the performance of NEToC with 119 images that were not used during the Artificial Neural Network (ANN) training phase, and evaluated its robustness across various resolutions: 64 × 64, 128 × 128, 256 × 256, and 512 × 512 pixels. The achieved accuracies for these resolutions were 74 %, 98 %, 98 %, and 100 %, respectively, for an underrepresented NET G3 experiment, and 66 %, 89 %, 95 % and 94 % for a represented NET G3 experiment. Based on several measured performance metrics, the optimal resolution appears to be between 128 × 128 and 256 × 256 pixels, considering computational resources and accuracy requirements. However, we found that the 256 × 256-pixel resolution is more robust to classify underrepresented classes in the learning phase. These results imply that the information to discriminate between NECs and Grade 3 NETs needs to be resolved in regions with a pixel resolution of no more than 4 μm/pixel. Most of the misclassifications were false negatives, where NET G1-type images were erroneously classified as NEC-type. Our results demonstrate that a DL-based diagnostic algorithm provides a more accurate diagnosis in NEN cases where physicians face challenges. NEToC has been initially trained with and used to classify gastrointestinal NENs. Since the NEN morphology does not change among the different organs, the use of NEToC can be extrapolated to NENs from different organs. NEToC facilitates federated supervision, allowing pathologists to collect interchangeable files based on NEToC classification predictions. NEToC is an easy-to-use, adaptable software that integrates multiple ANNs to improve standardization and accuracy NEN diagnosis, opening up possibilities for combining DL and histological diagnosis in federated supervision systems. A future goal is to classify not only NETs, but also the three-tier system (NET G1, NET G2, and NET G3) based solely on tissue differentiation information.

TMOD-11. ADVANCED MRI ANALYSIS TO ASSESS CHEMO-RADIATION RESPONSE IN PEDIATRIC EPENDYMOMA MODELS

Abstract Pediatric Ependymoma (EPN) is an aggressive brain tumor for which the benefits of chemo-radiation (CR) therapy have yet to be established. Our team has previously reported behavior patterns of EPN, including high tumor cellularity, cytological anaplasia, high mitotic index, tumor necrosis, and the presence of inflammatory cells such as M2-type macrophages. Recently, we have established advanced MRI protocols and computational algorithms for cell- and vessel-size imaging. The goal of this study is to develop advanced MRI analysis for CR response biomarkers (including tumor size, cell- and vessel-size correlates, and texture analysis) in mice with patient-derived xenografts (PDX) of pediatric EPN. Female severely immune deficient (SCID) mice were used for intracranial orthotopical inoculation of disaggregated tumors from pediatric EPN patients. All multi-parametric MRI sequences (fast spin echo, FLAIR, diffusion weighted, quantitative T2- and r2*-maps) were acquired on a Bruker 9.4 Tesla MRI scanner prior to CR, followed by 2 days and 2 weeks after CR treatment. All radiation treatment was performed using an animal image-guided precision XRAD irradiator (2Gyx5days), using MRI and CT guided EPN localization with added 30 mg/kg 5-fluoracil. All MRI analysis was performed using Bruker ParaVision software and MATLAB based modeling. The sensitivity of T2w-MRI scans was 0.2 mm for the smallest tumor detected; the median tumor volume at baseline was 2.5 mm3. Untreated mice showed rapid progression of tumor growth from small to intermediate to large EPN. The increased tumor sizes in untreated EPN were characterized by low ADC, highly elevated blood vessel density and large tumor cell size. A significant decrease in vessel size density and an increase in inflammatory cells were seen as soon as 2 days after CR therapy. The late response (2 weeks post CR) is characterized by increased ADC values and decreased cell size, resulting in significantly decreased tumor volumes.

Análisis de ganglios coincidentes con SentiMag® y técnica estándar en la BSGC del cáncer de mama

IntroductionIn breast cancer surgery, there are techniques for sentinel lymph node biopsy (SLNB) that do not require nuclear medicine, such as SentiMag®, which uses ferromagnetic particles. The main purpose of this analysis is to study the degree of concordance in SLNB between SentiMag® and the standard method (Tc99 radiotracer). The secondary objective is to identify factors that impact in sentinel node detection rate and matching detection rate between both probes. MethodsObservational and retrospective study performed from January to December 2021 focused on patients undergoing breast surgery and SLNB who were injected with both tracers, the ferromagnetic SentiMag® and Tc99 radiotracer. Once the diagnostic accuracy tests were performed, a further evaluation of the detection rate for each probe and the concordance between probes were accomplished. After those results, a deeper analysis of differences in detection rates for each probe and concordance between probes were assessed for various factors: neoadjuvant therapy, BMI, mitotic index, and triple-negative immunohistochemical profile. ResultsThe clinical study had a sample size of 70 patients. The overall false-negative rate (FNR) was 4.3%. The detection rate was the same for each technique (85.7%). A total of 106 nodes were biopsied, with a concordance rate of 70.75%. Significant differences were found in concordant nodes according to neoadjuvant therapy (p-value 0.012). For the Ki-67 factor (<20 or ≥20), significant differences were found in detected nodes (p-value 0.031 gamma probe; p-value 0.124 SentiMag®). ConclusionsThe detection rates of SentiMag® and the gamma probe are equivalent. The application of the dual technique minimizes the FNR. A high mitotic index affects the detection rate of the gamma probe, and neoadjuvant therapy negatively impacts the concordance rate.

PATHOMORPHOLOGICAL AND PATHOHISTOLOGICAL CHARACTERISTICS OF PRIMARY VULVAR CARCINOMA

The purpose of the study was to determine pathomorphological and pathohistological characteristics of primary vulvar carcinoma. Materials, methods, and study design: A retro- and prospective comprehensive morphological study of 117 patients was conducted at Bondar Regional Cancer Research Center (Donetsk) over the period from 2002 to 2019. Out of 117 we identified 44 patients with primary vulvar cancer without previous inflammatory diseases (cancer de novo). The materials were fixed in formalin and examined using standard methods of histological staining and morphometry. Statistical analysis methods were used to process the data. Results and Discussion: The differentiated VIN type occurred in 61.2% of cases, the undifferentiated type – in 37.8%. VIN1 was characterized by basal cell hyperplasia, VIN2 – by abnormal vertical anisomorphy, VIN3 – by significant abnormal cell stratification and differentiation. Cell proliferative activity increased with VIN severity, with the highest mitotic index and nuclear-cytoplasmic ratio in VIN3. In VIN1, a positive reaction to nuclear proliferation antigen was observed in the lower third of the epithelial layer. In VIN2 and VIN3, the positive reaction covered most of the epithelium. Well-differentiated SCC (G1) was characterized by polymorphic cell complexes with a small number of pathological mitoses and apoptosis. Moderately differentiated SCC (G2) had a pronounced inflammatory reaction and necrosis, with disruption of the basement membrane. Poorly differentiated SCC (G3) demonstrated loss of vertical anisomorphy, high mitotic index and presence of tumor emboli in vessels. Conclusions: The study showed significant differences in the morphological and morphometric characteristics of different types of VIN and invasive vulvar carcinoma. The results will help to improve the diagnosis and treatment of primary vulvar cancer, especially in understanding its pathogenesis and prognostic factors.

Performance of radiomics in preoperative determination of malignant potential and Ki-67 expression levels in gastrointestinal stromal tumors: a systematic review and meta-analysis.

Empirical evidence for radiomics predicting the malignant potential and Ki-67 expression in gastrointestinal stromal tumors (GISTs) is lacking. The aim of this review article was to explore the preoperative discriminative performance of radiomics in assessing the malignant potential, mitotic index, and Ki-67 expression levels of GISTs. We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library. The search was conducted up to 30 September 2023. Quality assessment was performed using the Radiomics Quality Score (RQS). A total of 35 original studies were included in the analysis. Among them, 26 studies focused on determining malignant potential, three studies on mitotic index discrimination, and six studies on Ki-67 discrimination. In the validation set, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of radiomics in the determination of high malignant potential were 0.74 (95% CI=0.69-0.78), 0.90 (95% CI=0.83-0.94), and 0.81 (95% CI=0.14-0.99), respectively. For moderately to highly malignant potential, the sensitivity, specificity, and AUC were 0.86 (95% CI=0.83-0.88), 0.73 (95% CI=0.67-0.78), and 0.88 (95% CI=0.27-0.99), respectively. Regarding the determination of high mitotic index, the sensitivity, specificity, and AUC of radiomics were 0.86 (95% CI=0.83-0.88), 0.73 (95% CI=0.67-0.78), and 0.88 (95% CI=0.27-0.99), respectively. When determining high Ki-67 expression, the combined sensitivity, specificity, and AUC were 0.74 (95% CI=0.65-0.81), 0.81 (95% CI=0.74-0.86), and 0.84 (95% CI=0.61-0.95), respectively. Radiomics demonstrates promising discriminative performance in the preoperative assessment of malignant potential, mitotic index, and Ki-67 expression levels in GISTs.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung.

Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors. The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Match detection analysis on SentiMag® system and standard technique in SLNB of breast cancer

IntroductionIn breast cancer surgery, there are techniques for sentinel lymph node biopsy (SLNB) that do not require Nuclear Medicine, such SentiMag®, which uses ferromagnetic particles. The main purpose of this analysis is to study the degree of concordance in SLNB between SentiMag® and the standard method (Tc99 radiotracer). The secondary objective is to identify factors that impact in sentinel node detection rate and matching detection rate between both probes. MethodsObservational and retrospective study performed from January to December 2021 focused on patients undergoing breast surgery and SLNB who were injected with both tracers, the ferromagnetic SentiMag® and Tc99 radiotracer. Once the diagnostic accuracy tests were performed, a further evaluation of the detection rate for each probe and the concordance between probes were accomplished. After those results, a deeper analysis of differences in detection rates for each probe and concordance between probes were assessed for various factors: neoadjuvant therapy, BMI, mitotic index, and triple-negative immunohistochemical profile. ResultsThe clinical study had a sample size of 70 patients. The overall false-negative rate (FNR) was 4.3%. The detection rate was the same for each technique (85.7%). A total of 106 nodes were biopsied, with a concordance rate of 70.75%. Significant differences were found in concordant nodes according to neoadjuvant therapy (p-value 0.012). For the Ki-67 factor (<20 or ≥20), significant differences were found in detected nodes (p-value 0.031 gamma probe; p-value 0.124 SentiMag®). ConclusionsThe detection rates of SentiMag® and the gamma probe are equivalent. The application of the dual technique minimizes the FNR. A high mitotic index affects the detection rate of the gamma probe, and neoadjuvant therapy negatively impacts the concordance rate.

Evaluation of Cyto-Genotoxic Effects of Mucuna Bracteata DC. Ex Kurz Leaf Extracts by Allium Cepa

This study was conducted to evaluate the cyto-genotoxicity of leaf decoctions of Mucuna bracteata by Allium cepa bioassay. This kind of study can be used as a baseline monitoring system for plant products before their use. It is an inexpensive, simple, and reliable test to determine the cytotoxic and genotoxic effects of various plant extracts on living organisms. In this experiment, Allium cepa bulbs were placed in five concentrations (0.5 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 7.5 mg/mL, and 10.0 mg/mL) of leaf decoction, with tap water as the negative control and 20.0 µL/L EMS (Ethylmethene sulphonate) as the positive control. Each concentration had five replicates. The cyto-genotoxicity assay exhibited a dose-dependent influence on the mitotic index. The mitotic index of the negative control and the positive control were 16.8 ± 0.37% and 6.86 ± 1.71%, respectively. The lowest dose of the extract, 0.5 mg/mL, had the highest mitotic index (14.2 ± 0.73%), while the highest dose, 10.0 mg/mL, had the lowest (9.6 ± 0.40%), and all indices were significantly higher than the positive control. Except for the 10 mg/mL concentration, the mitotic indices of other concentrations were significantly lower than the negative control. Different types of chromosome disorders, namely, disorderly prophase, sticky chromosomes, chromosome bridges, laggard chromosomes, pole deviation, vagrant chromosomes, nuclear filaments with terminal expansion, c-mitosis, micronuclei, and elongated nuclei, were observed. Various changes in root size, growth, and color were revealed by macroscopic examinations. Tumors were formed in roots at the highest doses but not at lower concentrations. Therefore, M. bracteata leaf extract showed cytotoxic and genotoxic effects on the Allium root meristem. J. Bio-Sci. 32(2): 71-82, 2024

Safety, effectiveness and the optimal duration of preoperative imatinib in locally advanced gastric gastrointestinal stromal tumors: A retrospective cohort study.

The optimal duration of preoperative imatinib (IM) remains controversial. This study aimed to evaluate the safety, therapeutic effectiveness, and optimal duration of preoperative IM in patients with locally advanced gastric gastrointestinal stromal tumors (GIST). The clinicopathologic data of 41 patients with locally advanced gastric GIST who received preoperative IM and underwent surgical resection from January 2014 and December 2021 were retrospectively analyzed. After a median of 7.0 (IQR: 4.5-10) months of preoperative IM treatment, 30 patients experienced adverse events (AEs), 80% of which were grade 1/2 AEs. The mean tumor size decreased from 12.71 ± 5.34 cm to 8.26 ± 4.00 cm, with a reduction rate of 35%. Setting 8 months as the cut-off value according to the results of ROC analysis. The proportion of laparoscopic surgery was higher in patients with short-term (≤8 months) versus long-term (>8 months) preoperative IM. Compared with the subtotal/total gastrectomy group, patients in the local gastrectomy group exhibited less intraoperative blood loss, shorter length of postoperative hospital stay, and fewer postoperative complications. The 3-year recurrence-free survival (RFS) and overall survival (OS) rates were 82.9% and 97.6%, and the expected 5-year RFS and OS rates were 75.6% and 90.2% respectively. RFS was better in the short-term than in the long-term preoperative IM treatment group, and it was also better in pre- plus postoperative IM treatment group than that in the preoperative IM alone group. Both univariate and multivariate COX analysis showed that a higher mitotic index and long-term preoperative IM treatment were associated with worse RFS, while postoperative IM treatment could significantly improve RFS. The study suggests that in patients with locally advanced gastric GIST, preoperative short-term (≤8 months) use of IM is associated with higher RFS than long-term use.

Aggressive Prolactinoma with Progression to Pituitary Carcinoma: A Case Report.

Adenomas of the pituitary gland, predominantly prolactinomas, can exhibit aggressive behavior. Aggressive prolactinomas are characterized by radiographic invasion, rapid growth, clinically significant progression despite standard therapies, and recurrence after surgery or radiotherapy. Pituitary carcinoma is rare (0.1-0.2% of pituitary tumors) [1, 2]. Case Presentation: In 2005, a 50-year-old man presented with bitemporal hemianopsia and severe asthenia due to a large pituitary tumor. Hormonal tests revealed hyperprolactinemia and panhypopituitarism; he received hormonal replacement and dopamine agonists (DA) therapy with a reduction in prolactin levels. Ten years later, he experienced tumor regrowth consistent with pituitary apoplexy and VI cranial nerve palsy. MRI showed a macroadenoma with suprasellar extension and compression of the optic structures. The patient underwent transsphenoidal surgery in view of the partially resistant disease. Histopathology showed a pituitary macroadenoma, and immunohistochemistry showed a high mitotic index (Ki-67 80%). In 2016, the patient developed a partial deficit of the left sixth cranial nerve. He underwent a new surgery but with incomplete resection. In view of the aggressive and resistant nature of the disease, he received radiotherapy. In 2020, prolactin levels began to increase again. MRI showed an occipital- temporal lesion. Subsequently, he underwent radiotherapy and started chemotherapy with temozolomide, resulting in the normalization of prolactin levels in the absence of DA therapy. The patient is currently in remission, with no evidence of tumor recurrence. Conclusion: It was found that 15% of prolactinomas are resistant to DAs, and resistance to DA may signal malignant transformation. Therefore, multimodality therapy and molecular analysis are critical for aggressive prolactinomas and pituitary carcinoma.

Exploring the role of 28-homobrassinolide in regulation of temperature induced clastogenic aberrations and sugar metabolism of Brassica juncea L.

The present research primarily focuses on Brassica juncea's physiological and cytological responses to low and high temperature stress at 4 °C and 44 °C respectively, along with elucidating the protective role of 28-Homobrassinolide (28-homoBL). Cytological investigations performed in floral buds of Brassica juncea L. under temperature (24, 4, 44 °C) stress conditions depict the presence of some abnormalities associated with cytomixis such as chromosome stickiness or agglutination, pycnotic nature of chromatin, irregularities in spindle formation, disoriented chromatins, and non-synchronous chromatin material condensation in Brassicaceae family that subsisted at diploid level (2n = 36). Spindle abnormalities produce various size pollen grains such as sporads micronuclei at some stages of microsporogenesis, polyads, triads, dyads that irrupted the productiveness of pollen grains. Furthermore, sugars play an imperative role in protecting plants under stress besides being energy sources. Therefore, the present study revealed accumulation of total soluble sugars (TSS), with 28-homoBL treatment which pinpoints protective role of 28-homoBL under temperature stress. Sugar profiling was done by using high-performance liquid chromatography (HPLC) which helped in analyzing different sugars both quantitatively and qualitatively under 28-homoBL and temperature stress conditions. The results indicate that the 28-homoBL treatment substantially enhances plant tolerance to heat stress, as evident by higher mitotic indices, fewer chromosomal abnormalities, and significantly more sugar accumulation. The findings of the study acknowledge the potential of 28-homoBL in inducing temperature stress tolerance in B. juncea along with improving the metabolic stability thereby implying application of 28-homoBL in crop strengthening under variable temperature conditions.

Sentinel lymph node positivity in melanoma: Which risk prediction tool is most accurate?

BackgroundSentinel lymph node biopsy for melanoma determines treatment and prognostic factors and improves disease-specific survival. To risk-stratify patients for sentinel lymph node biopsy consideration, Memorial Sloan Kettering Cancer Center and Melanoma Institute Australia developed nomograms to predict sentinel lymph node positivity. We aimed to compare the accuracy of these 2 nomograms. MethodsA multi-institutional study of patients with melanoma receiving sentinel lymph node biopsy between September 2018 and December 2022 was performed. The accuracy of the 2 risk prediction tools in determining a positive sentinel lymph node biopsy was analyzed using receiver operating characteristic curves and area under the curve. ResultsIn total, 532 patients underwent sentinel lymph node biopsy for melanoma; 98 (18.4%) had positive sentinel lymph node. Increasing age was inversely related to sentinel lymph node positivity (P < .01); 35.7% of patients ≤30 years had positive sentinel lymph node compared with 9.7% of patients ≥75 years. When we analyzed the entire study population, accuracy of the 2 risk prediction tools was equal (area under the curveMemorial Sloan Kettering Cancer Center: 0.693; area under the curveMIA: 0.699). However, Memorial Sloan Kettering Cancer Center tool was a better predictor in patients aged ≥75 years (area under the curveMemorial Sloan Kettering Cancer Center: 0.801; area under the curveMelanoma Institute Australia: 0.712, P < .01) but Melanoma Institute Australia tool performed better in patients with a higher mitotic index (mitoses/mm2 ≥2; area under the curveMemorial Sloan Kettering Cancer Center: 0.659; area under the curveMelanoma Institute Australia: 0.717, P = .027). Both models were poor predictors of sentinel lymph node positivity in young patients (age ≤30 years; area under the curveMemorial Sloan Kettering Cancer Center: 0.456; area under the curveMelanoma Institute Australia: 0.589, P = .283). ConclusionThe current study suggests that the 2 risk stratification tools differ in their abilities to predict sentinel lymph node positivity in specific populations: Memorial Sloan Kettering Cancer Center tool is a better predictor for older patients, whereas Melanoma Institute Australia tool is more accurate in patients with a higher mitotic index. Both nomograms performed poorly in predicting sentinel lymph node positivity in young patients.

Extending culture time to improve Mitotic Index for cytogenetic dosimetry

Purpose To analyze the effects of extending lymphocyte cultivation time on the Mitotic Index, frequency of first-division cells, and dose estimation after irradiating blood samples with different doses of radiation. Materials and methods Blood samples from two healthy male volunteers were separately irradiated with three doses (3, 5, and 6 Gy) using a 60Co gamma source (average dose rate: 1.48 kGy.h−1) and cultivated in vitro for conventional (48 h) and extended (56, 68, and 72 h) amounts of time. Colcemid (0.01 µg.mL−1) was added at the beginning of the culture period. Cells were fixed, stained with fluorescence plus Giemsa (FPG), and analyzed under a light microscope. The effects of prolonged culture duration on the Mitotic Index (MI), frequency of first-division cells (M1 cells), and the First-Division Mitotic Index (FDMI) were investigated. The estimation of delivered doses was conducted using a conventional 48h-culture calibration curve. Results Overall, cells presented higher MI (up to 12-fold) with the extension of culture, while higher radiation doses led to lower MI values (up to 80% reduction at 48 h). Cells irradiated with higher doses (5 and 6 Gy) had the most significant increase (5- to 12-fold) of MI as the cultivation was prolonged. The frequency of M1 cells decreased with the prolongation of culture for all doses (up to 75% reduction), while irradiated cells presented higher frequencies of M1 cells than non-irradiated ones. FDMI increased for all irradiated cultures but most markedly in those irradiated with higher doses (up to 10-fold). The conventional 48h-culture calibration curve proved adequate for assessing the delivered dose based on dicentric frequency following a 72-hour culture. Conclusion Compared to the conventional 48-hour protocol, extending the culture length to 72 hours significantly increased the Mitotic Index and the number of first-division metaphases of irradiated lymphocytes, providing slides with a better scorable metaphase density. Extending the culture time to 72 hours, combined with FPG staining to score exclusively first-division metaphases, improved the counting of dicentric chromosomes. The methodology presented and discussed in this study can be a powerful tool for dicentric-based biodosimetry, especially when exposure to high radiation doses is involved.

Endoscopic semiotics and pathological characteristics of primary malignant esophageal melanoma: a case report

Primary malignant melanoma of the esophagus is defined as a tumor, the frequency of which is 0.1-0.2% of all malignant lesions of the esophagus. This type of neoplasia is difficult to diagnose and is characterized by rapid progression, high recurrence rate and metastasis. Despite the diagnostic capabilities of X-ray examination methods, which make it possible to identify a tumor and determine its localization, the correct diagnosis can only be established by endoscopic examination of the upper digestive tract with biopsy and subsequent pathological and immunohistochemical studies. A 78 year-old male patient was admitted to the Herzen Moscow State Medical Institute with suspected esophageal cancer. It is known from the anamnesis, that the patient for 6 months notes a dysphagia, pain in the chest area. Based on the data of our expert endoscopic examination, we suspected primary esophageal melanoma with a mixed growth - exophytic and flat-type. According to the results of pathological examination of the biopsies, pigment epithelial-cell melanoma of the esophagus with high mitotic index (up to 3 mitosis figures per 1 sq.mm) with infiltrative growth type. This clinical case demonstrates the importance of a detailed endoscopic examination and performing a targeted biopsy, followed by expert pathological examination in the differential diagnosis of esophageal diseases characterized by pigmentation of mucosa.

Canine Oral Melanoma: Questioning the Existing Information through a Series of Clinical Cases.

Twelve dogs with oral malignant melanomas (MM) were evaluated in this study, with demographic details indicating a balanced distribution of gender, age, and weight among various breeds. Tumor locations varied, with diverse surgical procedures being performed, including mandibulectomies and maxillectomies. Lymphadenectomies were conducted, revealing a 16.66% metastatic rate in regional lymph nodes. At the time of surgery, clinical staging identified stages I, II, and III, with most cases having non-infiltrated margins and a high mitotic index. Follow-up revealed local recurrences and metastases, prompting additional surgeries and affecting survival rates. This study reports varying outcomes, with some dogs completing one year without recurrence, while others experienced progressive disease, leading to six oral melanoma-related deaths. The characteristics of melanotic melanoma and amelanotic melanoma are observed in order to study differences between them, the degree of aggressiveness, the mortality rate and the possibility of future therapeutic targets. Although high pigmentation has been correlated with a better outcome, we could not find any significant correlation between survival and achromia. Oral benign melanomas might exist, and this could justify variabilities between stage and survival; however, carefulness is required due to their unpredictable behavior. The findings underscore the complexity of oral melanoma cases and highlight the need for further research on effective management strategies.

Abstract PO2-25-11: Incidence of Breast Cancer in Louisiana Compared to the United States

Abstract Aside from skin cancer, breast cancer is the most common cancer in American women. More specifically, one in eight women will develop breast cancer during their lifetime. Breast cancer is classified into subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). ER+/PR+/HER2- tumors are the most common form of breast cancer and are typically associated with risk factors including older age, nulliparity, obesity following menopause, alcohol and tobacco use, sedentary lifestyle, and hormone therapy. ER-/PR-/HER2+ tumors comprise approximately 15-20% of breast cancers and are caused by overexpression of the HER2 gene. These tumors have similar risk factors to ER+/PR+/HER2- tumors, except for age. Women with HER2+ breast cancer are likely to be younger compared to ER+PR+/HER2-. Tumors lacking hormone receptors are classified as ER-/PR-/HER2-, otherwise known as triple-negative breast cancer (TNBC). TNBC represents 10%-20% of breast cancers and carries a poorer prognosis, shorter survival, and unresponsiveness to hormone therapy compared to other forms of breast cancer. TNBC has been associated with African American race, socioeconomically deprived population, younger age at diagnosis (most frequently in women ages 40-50), more advanced disease stage, higher grade, high mitotic indices, family history of breast cancer and BRCA1 mutations. The primary aim of this study is to compare incidence of ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2- (TNBC) in Louisiana to the national population. The Louisiana Tumor Registry (LTR) was utilized to obtain state and national level data. The LTR is a participant of the National Cancer Institute’s Surveillance, Epidemiology and End Results Program, and the Centers for Disease Control and Prevention’s National Program of Cancer Registries. Our study evaluated women in Louisiana diagnosed with ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2- from 2010-2019. The populations were subdivided by age at time of diagnosis. Data was subdivided into ages 0-49, and &amp;gt;50. Rates were calculated per 100,00 and age-adjusted to the 2000 United States Standard Population (19 age groups - Census P25-1130). A p-value of &amp;lt; 0.05 indicates a significantly different rate in Louisiana comparative to the United States (SEER). Our results are as follows. Unexpectedly, Louisiana has a significantly lower rate of ER+/PR+/HER2- cancer in women ages 0-49 and ages &amp;gt;50 compared to the United States. Based on epidemiological risk factors, Louisiana should have a much higher rate of ER+/PR+/HER2- comparative to the United States population. Louisiana has a significantly higher rate of ER-/PR-/HER2+ cancer in women ages &amp;gt;50 and ER-/PR-/HER2- (TNBC) in women ages 0-49 and ages &amp;gt;50 compared to the United States. These findings are discordant with traditional epidemiologic studies regarding breast cancer and require further investigation. Breast Cancer Incidence Rates1 by Age from 2010-2019 in Louisiana and the United States Table 1: Breast Cancer Incidence Rates in women ages 0-49 and ages &amp;gt;50 from 2010-2019 in Louisiana Compared to the United States. Citation Format: Avery Daily, Julie Cupp, Krystle Trosclair. Incidence of Breast Cancer in Louisiana Compared to the United States [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-11.