High Proliferation Index Research Articles

The cellular-differential composition of the intestinal epithelium in various phases of inflammatory bowel diseases

BACKGROUND: The steady increase in the number of inflammatory bowel diseases and the absence of reliably significant diagnostic markers require the search for new morphological criteria for differential diagnosis. AIM: This study aimed to determine the cellular-differential composition of the intestinal epithelium in the phases of exacerbation and remission in Crohn’s disease and ulcerative colitis. MATERIALS AND METHODS: Tissue samples of 60 patients with inflammatory bowel diseases (Crohn’s disease, n=30; ulcerative colitis, n=30) and with irritable bowel syndrome (control group, n=15) were studied using histological, immunohistochemical, morphometric and statistical methods. RESULTS: Distinct features of the cellular-differential composition of the epithelium in the mucous membrane of the ileum, ascending colon, sigmoid colon, and rectum were identified across these conditions, with differences observed during exacerbation and remission in inflammatory bowel diseases. The proportion of goblet cells in the epithelial lining varied by intestinal region and disease type and phase. Goblet cell differentiation: 25.0% more goblet cells of the superficial epithelium between the crypts of the ileum in acute Crohn’s disease compared with remission (p=0.0002); 42.9% more goblet cells in the superficial epithelium of the ascending colon compared with irritable bowel syndrome (p=0.0001); 23.0% more goblet cells crypt in the sigmoid colon compared with ulcerative colitis in the acute stage (p=0.0024). There were no significant differences in the differentiation of Paneth cells. There was a threefold increase in endocrinocytes in the sigmoid colon in acute Crohn’s disease compared with irritable bowel syndrome (p=0.0238). Nonepithelial differon cells: fewer interepithelial lymphocytes in Crohn’s disease in remission compared with Crohn’s disease in the acute stage by 2.4 times in the sigmoid colon, 4.0 times in the rectum (p 0,0001); compared with irritable bowel syndrome by 4.8 times in the ileum, 2.7 times in the ascending intestine, 4.0 times in the sigmoid colon (p 0,05); 8.0 times in the rectum compared with ulcerative colitis in remission (p=0,0004). Additionally, the study found proliferative activity of crypt cells (mainly goblet-shaped) increased by 4.2 times in the sigmoid colon in acute Crohn’s disease compared with acute ulcerative colitis (p=0,0016). CONCLUSIONS: Morphometric parameters of the cellular-differential composition of the intestinal epithelium can serve as potential differential diagnostic criteria. Acute Crohn’s disease is characterized by a higher proliferation index in the sigmoid colon compared with acute ulcerative colitis, while Crohn’s disease in remission shows a lower number of interepithelial lymphocytes in the rectum compared with ulcerative colitis in remission.

Cardiac Angiosarcoma with Unusual Cytologic Features Causing Cardiac Tamponade in a Young Adult Patient

Abstract Introduction/Objective Cardiac angiosarcoma is a rare endothelial malignancy with poor prognosis, frequent metastasis, and short median survival of only a few months. The disease has a wide age spectrum and can occur in young adult patients. The cytological diagnosis of cardiac angiosarcomas is challenging as cases are rare and its cytology is not extensively described or reported in literature. Here, we describe a rare case of cardiac angiosarcoma with unusual cytologic features. Methods/Case Report Our patient is a 30 year old male presenting with three days of worsening dyspnea and palpitations and was discovered on ultrasound to have large pericardial effusion compressing the right ventricle and causing cardiac tamponade. CT/MRI imaging revealed a 4.5 x 4.3 x 2.6 cm mass inside the right ventricle with extra- cardiac invasion through the pericardium and into the anterior mediastinum. Pericardiocentesis yielded 1.5 liters of hemorrhagic, brown, pericardial fluid with elevated LDH and protein levels. Cytology of the pericardial fluid revealed numerous tumor cells occurring singly or in monolayered, acinar clusters or cohesive spheres containing amorphous, eosinophilic cores made of collagen as evidenced on trichrome stain. The tumor cells possessed hyperchromatic, irregular, variably sized nuclei, prominent nucleoli, and cytoplasmic vacuoles. The tumor cells were positive for vimentin, CD31, and CD34, and showed high Ki67 proliferation index > 50%. A catheter-mediated biopsy of the right ventricular mass revealed spindled and epithelioid tumor cells strongly positive for CD31, CD34, and vimentin, focally positive for Factor VIII and AE1/AE3, and showing high Ki67 proliferation index of roughly 50%. The cytological, histological, and immunohistochemical findings were most consistent with cardiac angiosarcoma as the diagnosis. The patient eventually developed worsening chronic left chest pain and expired from cardiac arrest six months after his diagnosis. Results (if a Case Study enter NA) NA Conclusion We report a rare case of cardiac angiosarcoma with unusual cytologic features, manifesting as acinar clusters and cohesive spheres with collagenous cores that are not typical of malignant endothelial neoplasms. Currently there are no effective, standardized therapies that can significantly prolong survival for this malignancy, and treatment is often palliative. The cytological diagnosis of cardiac angiosarcoma is challenging given the rarity of this disease and the paucity of literature describing its cytology.

A Rare Case of Diffuse Large B Cell Lymphoma Co-occurring with Small Lymphocytic Leukemia: De Novo Process or Richter’s Syndrome?

Abstract Introduction/Objective Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma and can arise either de novo or through transformation from indolent lymphomas, such as Chronic Lymphocytic Leukemia (CLL), known as Richter syndrome (RS). DLBCL derived from RS tends to exhibit more aggressive behavior compared to de novo DLBCL. Methods/Case Report We present a case of a 57-year-old female with no significant medical history, who initially presented with antibiotic and prednisone-resistant sinusitis, progressing to bilateral neck pain and eye congestion. Computed tomography (CT) imaging revealed a 3 cm mass in the right nasal cavity extending to the right maxillary sinus and medial right orbit. Histopathological examination showed diffuse sheets of intermediate to large cells with irregular nuclear contours, dispersed chromatin, variably conspicuous nucleoli, and moderate cytoplasm. Additionally, scattered foci of monotonous, atypical lymphoid cells with lower grade morphology, including small size and condensed chromatin, were also present. Immunohistochemical analysis revealed differential staining patterns between the two cell populations. The larger atypical cells expressed CD20, PAX5, CD10, BCL-6, MUM1, BCL-2, MYC, CD19 (dim), and exhibited a high Ki-67 proliferation index (>80%). In contrast, the smaller atypical cells were positive for CD5, CD19, CD20, PAX5, BCL-2, and CD23 (subset), with a lower Ki-67 proliferation index (<5%). Flow cytometry analysis of tissue samples revealed two distinct clones: Surface Kappa-restricted CD19 dim B cells (38.9%) with CD5- CD10 dim CD20+ and surface Lambda-restricted CD19+ B cells (58.7%) with CD5+ CD10- CD20+. FISH analysis revealed no gene rearrangements. The final diagnosis was Diffuse large B-cell lymphoma, germinal center B- cell phenotype, with aggressive features and focal involvement by small lymphocytic lymphoma/chronic lymphocytic leukemia. Results (if a Case Study enter NA) NA Conclusion The relationship between the large B-cell lymphoma and SLL/CLL remains uncertain; however, given the different immunophenotype and light chain expression observed by flow cytometry, they are likely to represent separate processes.

An unusual case of a de novo high-grade B cell neoplasm with MYC and BCL2 rearrangements, strong TdT expression, and BRAF V600E mutation

Abstract Introduction/Objective Aggressive de novo B cell neoplasms can rarely exhibit overlapping features of B- lymphoblastic leukemia/lymphoma (B-ALL) and high-grade B cell lymphoma (HGBL) making their definitive classification challenging. The distinction between mature and immature B cell neoplasms is critical as treatment approaches differ. We report a unique case of an aggressive B cell neoplasm that not only posed diagnostic difficulties but was also found to harbor a BRAF V600E mutation, an unusual finding in such cases. Methods/Case Report A 33-year-old man without any significant past medical history presented for evaluation of a large tonsil mass and diffuse lymphadenopathy. The tonsil was excised, and histologic examination showed a diffuse atypical infiltrate composed of medium to large monomorphic lymphoid cells with high-grade cytology. By immunohistochemistry, the atypical cells were positive for CD19, CD79a, CD22, PAX5, CD10 (strong), CD45 (strong), BCL2, MYC, and TdT (strong). Ki67 showed a high proliferation index (80%). The atypical cells were negative for CD20, CD34, CD1a, CD30, Cyclin D1, T cell markers, myeloid markers, HHV8, and EBER. Flow cytometry detected a CD10 positive B cell population that was negative for CD20, CD34, and surface light chain expression. Fluorescence in-situ hybridization (FISH) detected BCL2 and MYC rearrangements. Staging marrow showed diffuse involvement by a neoplastic infiltrate with similar features to those observed in the tonsil. Chromosome analysis showed a complex karyotype. The patient was treated with two cycles of da-EPOCH-R. A neck lymph node biopsy two months later showed persistent disease. Next-generation sequencing (NGS) on this sample demonstrated a BRAF V600E mutation at 31% allele frequency. A mutation-specific BRAF-VE1 immunostain was diffusely positive. Results (if a Case Study enter NA) NA Conclusion This was a diagnostically challenging case of a de novo B-cell lineage neoplasm with high-grade features, MYC and BCL2 rearrangements, and strong diffuse TdT expression. There is limited literature on mutational profiles and prognostic data for such cases, and whether they are best classified (and treated) as HGBL or B-ALL remains challenging and controversial. In our case, we also discovered an unexpected finding of a BRAF V600E mutation, which has not been reported in similar cases in the existing literature and could serve as a potential therapeutic target. Additional reporting and genetic profiling of such cases may help further elucidate their biology and guide treatment protocols.

Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene.

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Prognostic Impact of HER2 Low Status in Male Breast Cancer: Prospective Cohort Analysis.

Male breast cancer (MBC) is a rare disease, and the potential influence of low expression of human epidermal growth factor receptor 2 (HER2 low) remains unexplored. In this prospective cohort study, we evaluated 870 patients treated for MBC between May 2009 and June 2023 to assess HER2 low status and its prognostic implications. With a median follow-up of 43 months (range 1-175 months), 659 eligible patients were categorized into three groups based on HER2 status: 501 (76%) HER2 low, 81 (12.3%) HER2 zero, and 77 (11.7%) HER2 positive. HER2 positivity correlated with younger age, higher proliferation index, non-specific type histology, lymphovascular invasion (LVSI), and low differentiation grade. Notably, all these parameters were equally distributed between the HER2 zero and HER2 low groups. Additionally, HER2 positivity was significantly associated with increased occurrences of regional and distant lymph nodes and pulmonary metastases. However, no statistically significant difference was observed between HER2 zero and HER2 low. Disease-free and overall survival showed no significant disparities between the groups. Our findings suggest that HER2 low status is frequently detected in MBC. Despite this, HER2 low did not correlate with clinical and pathological parameters, nor did it impact patients' survival.

Surrogate Immunohistochemical Markers of Proliferation and Embryonic Stem Cells in Distinguishing Ameloblastoma from Ameloblastic Carcinoma

PurposeThe current study aimed to investigate the use of surrogate immunohistochemical (IHC) markers of proliferation and stem cells to distinguish ameloblastoma (AB) from ameloblastic carcinoma (AC).MethodsThe study assessed a total of 29 ACs, 6 ABs that transformed into ACs, and a control cohort of 20 ABs. The demographics and clinicopathologic details of the included cases of AC were recorded. The Ki-67 proliferation index was scored through automated methods with the QuPath open-source software platform. For SOX2, OCT4 and Glypican-3 IHC, each case was scored using a proportion of positivity score combined with an intensity score to produce a total score.ResultsAll cases of AC showed a relatively high median proliferation index of 41.7%, with statistically significant higher scores compared to ABs. ABs that transformed into ACs had similar median proliferation scores to the control cohort of ABs. Most cases of AC showed some degree of SOX2 expression, with 58.6% showing high expression. OCT4 expression was not seen in any case of AC. GPC-3 expression in ACs was limited, with high expression in 17.2% of ACs. Primary ACs showed higher median proliferation scores and degrees of SOX2 and GPC-3 expression than secondary cases. Regarding SOX2, OCT4 and GPC-3 IHC expression, no statistically significant differences existed between the cohort of ABs and ACs.ConclusionKi-67 IHC as a proliferation marker, particularly when assessed via automated methods, was helpful in distinguishing AC from AB cases. In contrast to other studies, surrogate IHC markers of embryonic stem cells, SOX2, OCT4 and GPC-3, were unreliable in distinguishing the two entities.

Updates in Systemic Treatment of Hormone Receptor-Positive Early-Stage Breast Cancer.

Hormone-receptor positive (HR +) and human epidermal growth factor receptor 2 (HER2) negative early breast cancer (eBC) is a heterogeneous disease with several contributing factors for increased risk of recurrence, including tumor features, individual biomarkers, and genomic risk. The current standard approach in the management of HR + /HER2neg eBC includes chemotherapy and endocrine therapy (ET), and additional therapies based on risk profile, menopausal status, and genetics are sometimes appropriate. The risk of recurrence is more pronounced in patients with high-risk eBC including large tumor size, nodal involvement, high proliferative index, and genetic predisposition. In premenopausal patients with high-risk eBC, ovarian function suppression in combination with adjuvant ET improves survival. In postmenopausal patients, extended aromatase inhibitor (AI) therapy can be considered. Recent trials have identified novel treatment approaches to reduce the risk of recurrence in high-risk HR + /HER2neg eBC including the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to adjuvant ET. For patients with germline BRCA1/BRCA2 mutations, adjuvant poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been shown to improve overall survival (OS). However, despite these recent advances, the risk of recurrence remains substantial, highlighting an area of unmet need. There are several ongoing clinical trials further investigating the role of CDK 4/6 inhibitors and immunotherapy in high-risk HR + /HER2neg eBC.

Epilepsy in Patients With Primary CNS Lymphoma: Prevalence, Risk Factors, and Prognostic Significance.

Epilepsy is a common comorbidity of brain tumors; however, little is known about the prevalence, onset time, semiology, and risk factors of seizures in primary CNS lymphoma (PCNSL). Our objectives were to determine the prevalence of epilepsy in PCNSL, to identify factors associated with epilepsy, and to investigate the prognostic significance of seizures in PCNSL. We performed an observational, retrospective single-center study at a tertiary neuro-oncology center (2011-2023) including immunocompetent patients with PCNSL and no history of seizures. We collected clinical, imaging, and treatment data; seizure status over the course of PCNSL; and oncological and seizure outcome. The primary outcome was to determine the prevalence of epilepsy. Furthermore, we aimed to identify clinical, radiologic, and treatment-related factors associated with epilepsy. Univariate analyses were conducted using the χ2 test for categorical variables and unpaired t test for continuous variables. Predictors identified in the unadjusted analysis were included in backward stepwise logistic regression models. We included 330 patients, 157 (47.6%) were male, median age at diagnosis was 68 years, and the median Karnofsky Performance Status score was 60. Eighty-three (25.2%) patients had at least 1 seizure from initial diagnosis to the last follow-up, 40 (12.1%) as the onset symptom, 16 (4.8%) during first line of treatment, 27 (8.2%) at tumor progression and 6 (1.8%) while in remission. Focal aware seizures were the most frequent seizure type, occurring in 43 (51.8%) patients. Seizure freedom under antiseizure medication was observed in 97.6% patients. Cortical contact (odds ratio [OR] 8.6, 95% CI 4.2-15.5, p < 0.001) and a higher proliferation index (OR 5.7, 95% CI 1.3-26.2, p = 0.02) were identified as independent risk factors of epilepsy. Patients with PCNSL and epilepsy had a significantly shorter progression-free survival (median progression-free survival 9.6 vs 14.1 months, adjusted hazard ratio 1.4, 95% CI 1.0-1.9, p = 0.03), but not a significantly shorter overall survival (17 vs 44.1 months, log-rank test, p = 0.09). Epilepsy affects a quarter of patients with PCNSL, with half experiencing it at the time of initial presentation and potentially serving as a marker of disease progression. Further research is necessary to assess the broader applicability of these findings because they are subject to the constraints of a retrospective design and tertiary center setting.

Comparison of different longan polysaccharides during gut Bacteroides fermentation

The bioactivity of polysaccharide was closely related to its fermentation utilization by gut Bacteroides, and its utilization degree was determined by various gut Bacteroides species and different polysaccharides characteristics. The effects of longan polysaccharide (LP) and LP treated by ultrasonic-assisted hydrogen peroxide for 8 h (DLP-8) on gut Bacteroides growth, and their fermentation utilization were compared. The results of LP and DLP-8 on the proliferation of six Bacteroides species showed that Bacteroides uniformis had the highest proliferation index. In fermentation by B. uniformis, DLP-8 (with a lower molecular weight), the viable count of which was higher than that of LP, was degraded more and especially utilized more glucose and glucuronic acid. The microstructure of the two polysaccharides changed differently during fermentation. Moreover, DLP-8 promoted greater short-chain fatty acids production than LP. These results indicated that the fermentation properties of DLP-8 by B. uniformis were superior to those of LP.

Is There a Link between Chronic Obstructive Pulmonary Disease and Lung Adenocarcinoma? A Clinico-Pathological and Molecular Study.

Chronic Obstructive Pulmonary Disease (COPD) and lung cancer are strictly related. To date, it is unknown if COPD-associated cancers are different from the tumors of non-COPD patients. The main goal of the study was to compare the morphological/molecular profiles of lung adenocarcinoma (LUAD) samples of COPD, non-COPD/smokers and non-COPD/non-smokers, and to investigate if a genetic instability also characterized non-pathological areas. This study included 110 patients undergoing surgery for a LUAD, divided into three groups: COPD/smoker LUAD (38), non-COPD/smoker LUAD (54) and non-COPD/non-smoker LUAD (18). The tissue samples were systemically evaluated by pathologists and analyzed using a 30-gene Next Generation Sequencing (NGS) panel. In a subset of patients, tissues taken far from the neoplasia were also included. The non-COPD/smoker LUAD were characterized by a higher proliferative index (p = 0.001), while the non-COPD/non-smoker LUAD showed higher percentages of lepidic pattern (p = 0.008), lower necrosis, higher fibrosis, and a significantly lower mutation rate in the KRAS and PIK3CA genes. Interestingly, the same gene mutations were found in pathological and normal areas exclusively in the COPD/smokers and non-COPD/smokers. COPD/smoker LUAD seem to be similar to non-COPD/smoker LUAD, particularly for the genetic background. A less aggressive cancer phenotype was confirmed in non-COPD/non-smokers. The genetic alterations detected in normal lungs from smokers with and without COPD reinforce the importance of screening to detect early neoplastic lesions.

Advancing Ki67 hotspot detection in breast cancer: acomparative analysis of automated digital image analysis algorithms.

Manual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment. Tissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol. Automated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95). Automated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.

Survival Outcomes of Breast Cancer Patients in South India Over 20 Years.

The study aimed to investigate the distribution and clinicopathologic features of breast cancer patients in South India, while also examining the overall survival (OS) and identifying predictive factors affecting it. Additionally, we aimed to assess the influence of risk factors on Disease Free Survival (DFS) and Distant Disease-Free Survival (DDFS). This retrospective cohort study on breast cancer trends used comprehensive follow-up including regular patient contact, medical record review and collaboration with healthcare providers. Patients without follow-up information for more than 12 months were contacted by telephone, while those with no follow-up after 2 years were labelled as lost to follow-up. A total of 3256 patients were identified from a single cancer institute in India. The median follow-up time was 8.1 years. The 5-year survival rates were 89%, 84%, 85%, 88% and 10-year were 82%, 78%, 79%, 83% for luminal cancers, Triple Negative Breast Cancers, HER2 enriched and luminal with HER2 enriched respectively. Poorer survival rates were seen among those with pT3/4 tumors, nodal involvement at diagnosis, Estrogen receptor negative status, high Ki67 proliferative index and higher TNM stage at diagnosis of the disease. Although our patients were younger and had more aggressive types of cancer, their DFS, DDFS and overall survival were comparable to other developed nations.

The role of tumor-associated neutrophils in early luminal HER2-negative breast cancer progression

BACKGROUND: Luminal HER2-negative breast cancer is the most common type of tumor in women diagnosed with early-stage breast cancer. Stromal cells and immune cells in tumor microenvironment have been reported to play a significant role in cancer prognosis. The prognostic role of tumor-associated neutrophils in early breast cancer remains mostly unclear. AIM: To study predictive role tumor-associated neutrophils in early luminal HER2-negative breast cancer. MATERIALS AND METHODS: The dataset consisted of 60 patients with early luminal HER2-negative breast cancer treated in S.P. Botkin City Clinical Hospital (Moscow, Russia). We first estimated basic morphological signs: tumor size, tumor grade (by Nottingham Histologic Score), tumor-infiltrating lymphocytes, lymphovascular invasion, hormonal receptors status, proliferative index, regional lymph nodes status. The expression of intratumoral neutrophils was studied using immunohistochemistry with CD15. RESULTS: High tumor-associated neutrophils concentration was correlated with tumor size, high grade tumors, proliferative index, tumor-infiltrating lymphocytes, lymphovascular invasion and positive regional lymph nodes. CONCLUSION: Tumor-associated neutrophils predicted a worse prognosis in early luminal HER2-negative breast cancer.

PATH-14. A CLINICAL CONUNDRUM - INFANTILE POSTERIOR FOSSA EPENDYMOMA WITH YAP1:MAML FUSION?

Abstract BACKGROUND Ependymomas of infancy (0-18months) have been reported to comprise distinct clinical, pathological and genetic entities. Young age is typically associated with posterior fossa group A (PF-A) tumours and therefore a poor prognosis. Treatment of these infants is challenging with limited therapeutic options that have significant long-term sequelae. METHOD We report a single case of a 4-month old baby girl who presented with obstructive hydrocephalus and a presumed posterior fossa mass. RESULTS Imaging demonstrated a large fairly well-defined solid lesion with multiple T1 high and corresponding T2 intermediate signal intensity foci scattered throughout the lesion and marked mass effect on the cerebellum and fourth ventricle. The lesion was inseparable from the pineal gland, habenula and tectum and only mild diffusion restriction. Whilst initially considered to be a posterior fossa tumour, the presence of a claw sign with the tectal plate, favoured a tectal origin. Histological appearances, together with immunohistochemistry findings (GFAP positive and EMA patchy perinuclear dot expression) were consistent with classic ependymoma. Grading was difficult as mitotic activity was relatively low, although focal areas of high ki67 proliferation index were noted suggesting at least focal grade 3 areas. Retained expression of tumour cells for H3K27me3 on immunohistochemistry suggested the likely posterior fossa group B (PF-B) ependymoma. Local SNP chromosome microarray found no acquired clonal abnormality; with no detection of gain chromosome 1q; loss/LOH 6q; Loss/LOH 9p21.3 [CDKN2A, CDKN2B], chromothripsis 11q [ZFTA::RELA], Loss/LOH 17p13 [TP53] or Loss/LOH 22q [NF2]. Additional NGS sequencing identified a YAP1::MAML2 fusion (confirmed with targeted RT-PCR followed by subsequent Sanger sequencing). CONCLUSION This case highlights the challenges with overlapping clinical, pathological and radiological features in an infant with ependymoma, necessitating a molecular diagnosis. After 21months, the patient remains in complete remission following surgery alone.

Immunohistochemical Analysis of Dentigerous Cysts and Odontogenic Keratocysts Associated with Impacted Third Molars-A Systematic Review.

This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars. A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods. Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, p < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, p < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, p < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, p < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy. The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery.

Breast cancer recurrence rate after mastectomy in young females.

e12591 Background: Breast cancer is the most commonly diagnosed female cancer worldwide and the most common cause of cancer mortality in women. Surgical treatment of early breast cancer includes lumpectomy or mastectomy with or without reconstruction. Despite the surgeon’s best effort to perform a radical resection of the breast tissue during mastectomy to achieve locoregional control, residual fibroglandular tissue was found in 20% of breasts on postoperative breast MRI, which carries a risk of recurrence. Younger women with breast cancer have inferior survival rates despite receiving more aggressive therapy. Tumors in young women are more likely to be poorly differentiated, hormone receptor-negative, have a high proliferation index, and more lymphovascular invasion, which is partially explained by patients’ genetic profile. Another factor that could contribute to poor outcomes is the advanced stage at the time of diagnosis, including larger tumor size and higher rates of axillary lymph node positivity. This knowledge has motivated us to conduct this study that is dedicated to looking at the recurrence rate in young females following mastectomy. Methods: This is a retrospective study that collected data from young female patients who were diagnosed with breast cancer between January 2010 and August 2018, had an age at diagnosis of 18-45 years old, and underwent unilateral or bilateral mastectomy with or without reconstruction. The study also looked at the patient’s risk factors and genetic profile. Results: A total of 115 patients were diagnosed with early-stage breast cancer between January 2010 and August 2018 and underwent mastectomy. 81.74% were Caucasian females, and 8.7% were African American females. The mean age of diagnosis was 36.9 years. The mean BMI was 30.5 kg/m2. 59.13% of patients had a family history of breast cancer. The most common genetic mutations were BRCA1 at 7.83% and BRCA2 at 8.7%. 71% of patients underwent a bilateral mastectomy. 76% of patients had reconstruction. 77% of tumors were ER-positive, 68% PR-positive, and 26% HER2-positive. 49.4% of tumors were Nottingham grade 3. 52% of patients had no nodal involvement, while 35% had N1 disease. 34.6% had lymphovascular invasion. We found that 18/115 patients had recurrence of breast cancer following mastectomy. 5/17 patients had locoregional recurrence, while 12/17 patients had a distant recurrence; 1 patient’s recurrence data was unavailable. The median time to recurrence was 1147.5 days (335 to 3107). The 5-year recurrence free survival rate is 86% ± 3%. Conclusions: Our study found that 15.65% of young females had recurrence after mastectomy. To our knowledge, this is the first dedicated study to look at the recurrence rate after mastectomy in this young, high-risk patient population. Our study aims to encourage larger studies in young females with breast cancer to help tailor the treatment plan in this population.

Proliferation and apoptosis dynamics of the normal canine mammary gland during the oestrous cycle evaluated by Ki-67 and Caspase-3 indexes.

Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.

IL-38 promotes the development of prostate cancer.

Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment. The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics. There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients. These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.

Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2's protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort (n = 1980) and TCGA cohort (n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p-values < 0.0001), and shorter survival (p = 0.006), especially in luminal BC (p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival (p = 0.01). In DCIS, high nuclear/low cytoplasmic co-expression showed significant association with a high tumour grade (p = 0.043), triple-negative and HER2-enriched molecular subtypes (p = 0.01), Comedo necrosis (p = 0.024), negative ER status (p = 0.004), negative PR status (p < 0.0001), and a high proliferation index (p < 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact.