Low Ki-67 Research Articles

Mesothelioma of Uncertain Malignant Potential (MUMP) of the Tunica Vaginalis: Proposal for Reclassification as "Complex Mesothelial Tumor of the Tunica Vaginalis".

A well-differentiated papillary mesothelial tumor (WDPMT) and malignant mesothelioma are 2 well-recognized entities arising from the testis tunica vaginalis. Another mesothelial lesion exclusively seen at this site is mesothelioma of uncertain malignant potential (MUMP)-a lesion reminiscent of WDPMT yet demonstrating variable proportions of more complex architectural patterns that could be confused with invasion. MUMP was first described in 2010 with a total of 11 cases reported to date. Herein, we describe 19 additional patients who underwent hydrocelectomy, excision, and/or orchiectomy. Novel morphologic patterns found in addition to the 2010 series include spindle cells, keloidal-type collagen, and multicystic architecture lined by bland mesothelial cells. Clinical follow-up in 9 patients for more than 1 year (1.5 to 22.5y, median 4.5y) revealed no evidence of disease recurrence or metastases. Despite greater architectural complexity, MUMP has (1) bland cytology; (2) merging in with WDPMT areas; (3) low mitotic rate and Ki-67 nuclear labeling index; (4) retention of MTAP and BAP1 expression; and (5) benign clinical follow-up. If these cases were malignant mesotheliomas, one would have expected at least some of the patients to demonstrate disease recurrence/progression without adjuvant therapy within the available follow-up time, particularly with limited resection in most patients. Thus, we propose that "mesothelioma of uncertain malignant potential" be renamed as "complex mesothelial tumor of the tunica vaginalis." Using the term "complex" draws a contrast with the simple cuboidal lining and simple papillary architecture seen in WDPMT. Also, labeling the lesion as "tumor" removes the stigmata of "uncertain malignant potential" and "mesothelioma" that are alarming to patients and clinicians, and potentially could unduly lead to more extensive surgery in an attempt at "complete" resection. At the same time, not definitively labeling the lesion as benign allows recommendations for follow-up.

Apparent diffusion coefficient in intrahepatic cholangiocarcinoma diffusion-weighted magnetic resonance imaging noninvasively predicts Ki-67 expression.

Tumor Ki-67 expression reflects prognosis and cancer grade, and biopsy-based preoperative assessment of Ki-67 expression is key to treatment. Apparent diffusion coefficient (ADC) values obtained with this imaging may noninvasively predict Ki-67 by reflecting tumor cell density and limited water molecule movement from irregular alignment. This study aimed to investigate the ability of ADC values to predict Ki-67 expression in intrahepatic cholangiocarcinoma (ICC). We retrospectively analyzed 39 cases of ICC confirmed by surgical pathology. All patients had undergone magnetic resonance imaging, and ADC values (mean, minimum, and maximum) were calculated. Ki-67 expression was assessed by immunohistochemistry, and patients were divided into groups of high (n=18) and low (n=21) Ki-67 expression. To assess the diagnostic performance of the ADC values for Ki-67 expression, we used the receiver operating characteristic curve and compared the areas under the curve (AUC). The mean and minimum ADC values were significantly lower in the group with high Ki-67 expression. For predicting high Ki-67 expression, the AUC values were 0.701 for mean ADC, 0.818 for minimum ADC, and 0.571 for maximum ADC. The diagnostic sensitivity and specificity of the minimum ADC values were 88.9% and 76.2%, respectively. In addition, with ADC values combined, the AUC increased to 0.831. Apparent diffusion coefficient is a useful predictor of Ki-67 expression level in ICC. Apparent diffusion coefficient values, especially minimum ADC values, can noninvasively predict ICC associated with high Ki-67 expression.

Solid basal adenoid cystic carcinoma of the breast: A case report and literature review.

Adenoid cystic carcinoma (AdCC) is a rare malignancy of the breast with a low Ki-67 index and good prognosis. Owing to the rarity of breast AdCC, the misdiagnosis rate is as high as 50%, and there is no consensus or recognized guidelines for the treatment of this disease. Therefore, it is necessary to conduct a detailed clinical and pathological analysis in combination with a literature review to improve our understanding, diagnosis, and treatment of the disease. A 68-year-old woman sought medical attention due to a recently increasing mass in the breast. The left breast mass was 1.3 cm × 1 cm in size. We analyzed the morphology, immunohistochemistry, and molecular characteristics of the tumor removed by surgery, and reviewed relevant literature. Solid basal AdCC of the breast. We performed biopsy, immunohistochemistry and molecular testing on surgical resection specimens. Combining morphological and immunohistochemical features, it is consistent with solid basal AdCC of the breast, and Fish detected MYB gene break. Due to the high misdiagnosis rate of AdCC, accurate histopathological diagnosis is particularly important. At present, breast conserving surgery and local tumor resection are mainly used for the treatment of breast AdCC, and postoperative adjuvant radiotherapy is feasible.

Therapeutic Potential of Bipolar Androgen Therapy for Castration-Resistant Prostate Cancer: In Vitro and In Vivo Studies.

Androgen deprivation therapy (ADT) is a primary treatment for advanced prostate cancer (PCa), but resistance often leads to castration-resistant PCa (CRPC). CRPC remains androgen receptor (AR)-dependent, and AR overexpression causes vulnerability to high doses of androgen in CRPC. Bipolar androgen therapy (BAT) refers to the periodic administration of testosterone, resulting in oscillation between supraphysiologic and near-castrate serum testosterone levels. In this study, we evaluated the efficacy of BAT against CRPC in a preclinical setting. To emulate CRPC characteristics, PCa cell lines (LNCaP, VCaP, and 22Rv1) were cultured in phenol red-free RPMI-1640 medium supplemented with 10% dextran-coated charcoal treated FBS (A- cell line). Cell viability, AR, and AR-V7 expression were evaluated using the Cell Counting Kit-8 and Western blotting. In vivo studies involved 12 castrated NOG mice injected with LNCaP/A- cells, treated with testosterone pellets or controls in 2-week cycles. Tumor sizes were measured post a 6-week treatment cycle. Bicalutamide inhibited PCa cell viability but not in the adapted cell lines. Supraphysiologic androgen levels suppressed AR-expressing PCa cell growth in vitro. In vivo, high AR-expressing LNCaP cells proliferated under castrate conditions, while BAT-treated xenografts exhibited significant growth inhibition with low Ki-67 and mitotic indexes and a high cell death index. This study provides preliminary evidence that BAT is effective for the treatment of CRPC through rapid cycling between supraphysiologic and near-castrate serum testosterone levels, inducing an anti-tumor effect.

A Model Combining Conventional Ultrasound Characteristics, Strain Elastography and Clinicopathological Features to Predict Ki-67 Expression in Small Breast Cancer.

To establish a predictive model incorporating conventional ultrasound, strain elastography and clinicopathological features for Ki-67 expression in small breast cancer (SBC) which defined as maximum diameter less than2 cm. In this retrospective study, 165 SBC patients from our hospital were allocated to a high Ki-67 group (n = 104) and a low Ki-67 group (n = 61). Multivariate regression analysis was performed to identify independent indicators for developing predictive models. The area under the receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff value were compared. Conventional ultrasound parameters (spiculated margin, absence of posterior shadowing and Adler grade 2-3), strain elastic scores and clinicopathological information (HER2 positive) were significantly correlated with high expression of Ki-67 in SBC (all p < .05). Model 2, which incorporated conventional ultrasound features and strain elastic scores, yielded good diagnostic performance (AUC = 0.774) with better sensitivity than model 1, which only incorporated ultrasound characteristics (78.85%vs. 55.77%, p = .000), with specificities of 77.05% and 62.30% (p = .035), respectively. Model 3, which incorporated conventional ultrasound, strain elastography and clinicopathological features, yielded better performance (AUC = 0.853) than model 1 (AUC = 0.694) and model 2 (AUC = 0.774), and the specificity was higher than model 1 (86.89% vs. 77.05%, p = .001). The predictive model combining conventional ultrasound, strain elastic scores and clinicopathological features could improve the predictive performance of Ki-67 expression in SBC.

Prognostic factors in non-metastatic HER2 'low' and HER2 'negative' breast cancer: single institute experience.

Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer. In aretrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. Atotal of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group. The HER2 low group had significantly longer 5‑year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5‑year DFS. Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients.

Clinicopathological features associated with CD44 and CD63 expression in breast cancer.

CD44 is a cell-surface transmembrane glycoprotein that participates in the regulation of many cellular processes, including cell division, adhesion, migration and stem-like characteristics. CD63 is involved in the exocytosis process. To evaluate the relationship between CD44 and CD63 expression and clinicopathological features, including tumor-infiltrating lymphocytes (TILs), phosphoinositide 3-kinase (PIK3CA) mutation and survival. CD44 and CD63 were stained in samples from 101 breast cancer cases from Peruvian women. Median age was 52 years, most were most were grade-3 (68%), estrogen receptor (ER)+ (64%) and stage II-III (92%). Median ki67 was 30%, median stromal TIL was 30% and PIK3CA mutation was found in 49%. Longer survival was associated with earlier stages (p = 0.016), lower ki67 (p = 0.023), ER+ (p = 0.034), luminal phenotype (p = 0.029) and recurrence (p < 0.001). CD44 was classified as high cell density staining in 57% and high intensity in 55%. High CD44 density was associated with younger age (p = 0.043), triple-negative phenotype (p = 0.035) and shorter survival (p = 0.005). High CD44 expression was associated with short survival (p = 0.005). High CD63 cell density was found in 56% of cases and was associated with ER-positive (p = 0.045), low TIL levels (p = 0.007), Luminal-A (p = 0.015) and low CD44 intensity (p = 0.032). CD44 expression was associated with aggressive features and low CD63 density staining.

Immunohistochemical expression of cytochrome P4A11 (CYP4A11), carbonic anhydrase 9 (CAIX) and Ki67 in renal cell carcinoma; diagnostic relevance and relations to clinicopathological parameters

BackgroundCytochrome P4A11 (CYP4A11) is a member of cytochrome p450 family, which is involved in arachidonic acid metabolism that participates in promoting malignant cell proliferation, progression, and angiogenetic capacity. Carbonic Anhydrase 9 (CAIX) is a transmembrane protein that plays an integral part in regulating hypoxia which affects cancer cell metabolism, proliferation and promotes metastasis. The aim of this study was to evaluate the immunohistochemical expression of CYP4A11, CAIX and ki67 in RCC subtypes in relation to clinicopathological parameters and to evaluate the diagnostic significance of CYP4A11 and CAIX in differentiating renal cell carcinoma (RCC) subtypes. Materials and methodsone hundred primary RCC cases, collected from Pathology Department, Faculty of Medicine, Tanta University and from private laboratories, were evaluated for immunohistochemical expression of CYP4A11, CAIX and ki67. ResultsCYP4A11 was expressed in 59% of RCC; with 91.7% sensitivity and 90% specificity in differentiating clear cell and non-clear cell subtypes. CAIX was expressed in 50% of RCC; with 95% sensitivity, 80% specificity. High expression of CYP4A11 was statistically positively associated with higher tumor grade, high expression of CAIX was statistically positively associated with lower tumor grade and absence of necrosis and high ki67 labeling index was significantly associated with clear cell subtype, larger tumor sizes, higher tumor grade, advanced tumor stage, fat invasion and vascular invasion. ConclusionsCYP4A11 and CAIX can be used as diagnostic markers to differentiate clear cell RCC from other subtypes. CYP4A11 is more diagnostically accurate and specific than CAIX. High expression of CYP4A11, low CAIX expression and high ki67 labeling index were related to features of aggressive tumor behavior.

Immunohistochemical markers Ki67 and P16 help predict prognosis in locally advanced cervical cancer

ObjectiveTo investigate the relationship between Ki-67 and P16 expression levels after neoadjuvant chemotherapy, and the clinicopathological characteristics and prognosis of patients with locally advanced cervical cancer. MethodsPatients with FIGO 2009 stage IB2 or IIA2 cervical cancer, who underwent neoadjuvant chemotherapy combined with radical hysterectomy at the First Affiliated Hospital of Chongqing Medical University between January 2015 and December 2019, were identified retrospectively to correlate postoperative Ki-67 and P16 expression levels with clinicopathological factors. The optimal threshold for predicting recurrence was analysed using receiver operating characteristic (ROC) curves for the Ki-67 index, and univariate and multi-factorial Cox regression analysis were used to investigate the association between clinicpathological features including Ki-67 and P16 and recurrence-free survival. ResultsIn total, 334 patients were included after screening. The cut-off value of Ki-67 for determining recurrence was 67.5 % according to the ROC curve. On multi-factorial Cox analysis, lymphatic vascular space (p = 0.003) and Ki-67 index (p = 0.005) were shown to increase the risk of recurrence, and were independent prognostic factors for recurrence, while the expression of P16 was not significantly associated with the risk of recurrence (p = 0.097, odds ratio = 0.319). Patients with cervical cancer in the high Ki-67 expression group (Ki-67 ≥ 67.5 %) had lower recurrence-free survival and overall survival than patients in the low Ki-67 expression group (Ki-67 < 67.5 %) (p = 0.001 and 0.036, respectively). ConclusionThe expression levels of Ki-67 and P16 after neoadjuvant chemotherapy for locally advanced cervical cancer correlated with tumour differentiation. High expression of Ki-67 (Ki-67 ≥ 67.5 %) may indicate poorer recurrence-free survival and overall survival.

Primary Rectal Perineurioma: A Rare Incidental Finding

Abstract Perineurioma is a rare benign peripheral nerve sheath tumor which can occur intraneurally or uncommonly in the extraneural soft tissues. The majority of the perineuriomas of the gastrointestinal tract occur distal to the splenic flexure as polypoid pedunculated or sessile lesions. Lesions are often discovered incidentally during routine colonoscopy for cancer screening. Diagnosis is mainly histological with the majority of the cases showing mucosal/submucosal bland spindle cell proliferation with expression of perineurial markers. We report a rare case of rectal perineurioma in a 42-year-old female who presented with the complaint of intermittent episodes of painless rectal bleed associated with defecation. A pedunculated polypoid lesion in the rectum measuring 12 mm in greatest dimension was seen on colonoscopy. The patient underwent endoscopic mucosal resection of the mass. Microscopically, the lesion showed proliferation of spindle cells with oval-to-spindle nuclei, bland chromatin, and moderate amount of pale to eosinophilic cytoplasm with indistinct cell borders. Overlying mucosa showed hyperplastic crypt epithelium. Spindle cells were positive for epithelial membrane antigen and CD 34 and negative for S100, with low Ki-67 marked cycling cell population (&lt;1.0%) and negative Progesterone receptor (PR) and CD 117, these features confirming the diagnosis of perineurioma.

Pathological characteristics predicting sentinel lymph node metastasis in early breast cancer patients.

In this study, we aimed to identify the predicting pathological factors affecting sentinel lymph node biopsy (SLNB) in patients with clinically node-negative breast cancer. Our single institution retrospective study was conducted at the Cancer Research Center of Shahid Beheshti University of Medical Sciences from 2018 to 2021. Data were imported into and analyzed using SPSS Version 28 for Windows (IBM Corp., Armonk, NY, USA). Of the 76 patients who underwent SLNB, 43 (56.6%) had negative SLNB and 33 (43.4%) had positive SLNB which led to axillary lymph node dissection (ALND). The relationship between hormone receptor status (ER/PR/Her2), pathology type (IDC, ILC, DCIS, LCIS), tumor size, and Ki67 expression was assessed. According to the results, axillary lymph node involvement can be predicted based on the scores and results of the three variables: IDC tumor type, lympho vascular invasion (LVI), and Ki67 expression. The positive relationship between IDC tumor type and LVI with SLNB indicates that with positive IDC tumor type and LVI, there is a higher probability of positive axillary lymph nodes (3.88 times higher probability for IDC tumor type and 6.75 times higher probability for the LVI factor). However, when the Ki67 expression is lower, the probability of positive axillary lymph nodes is higher (3.58 times higher probability). IDC tumor type, LVI, and lower Ki67 expression are independent predictive factors of positive SLNB.

Uterine tumor resembling ovarian sex-cord tumor - a rare gynecological neoplasm.

Uterine tumor resembling ovarian sex-cord tumor is a rare group of uterine neoplasms with unknown histogenesis and differentiation towards ovarian sex-cord elements. They are benign in nature with low malignancy potential. Diagnosis is based on immunohistochemistry and morphological features, and the distinction from other more malignant differentials is paramount to correctly individualizing treatment.

Assessment of Ki-67 expression levels in IDH-wildtype glioblastoma using logistic regression modelling of VASARI features.

To investigate the value of using VASARI signs preoperatively to assess Ki-67 proliferation index levels in patients with IDH-wildtype glioblastoma (GB).Pathological and imaging data of 154 patients with GB confirmed by surgical pathology were retrospectively analysed, and the level of Ki-67 proliferative index was assessed in tumour tissue samples from patients using immunohistochemistry (IHC) staining. Patients were divided into a high and low Ki-67 proliferation index expression group. Two radiologists analysed MRI images of patients with IDH-wildtype GB using the VASARI features system. VASARI parameters between the two groups were statistically analysed to identify characteristic parameters with significant differences and their predictive performance was determined using ROC curves.Among the obtained clinical and VASARI features of IDH-wildtype GB patients, the distribution of Maximum diameter, Proportion of necrosis and Hemorrhage was significantly different between the two groups (all p < 0.05). Multivariate logistic regression analysis showed that Maximum diameter and Hemorrhage were independent risk factors distinguishing the group with high and low expression of Ki-67 proliferative index. ROC curve analysis showed that the logistic regression model achieved an AUC value of 0.730 (95% CI: 0.639, 0.822), sensitivity of 0.628 and specificity of 0.756.Logistic regression modelling of preoperative VASARI features can be used as a reliable tool for predicting the level of Ki-67 proliferative index in IDH-wildtype GB patients, which can help in preoperative development of treatment and follow-up strategies for patients.

Correlation analysis of dynamic enhanced energy spectrum CT parameters with Ki-67 high expression in hepatocellular carcinoma

Objective: To investigate the correlation between dynamic enhanced energy spectral CT parameters and Ki-67 high expression in hepatocellular carcinoma (HCC). Methods: A cross-sectional study. This retrospective case-control study analyzed the clinical data of 101 patients with pathologically confirmed HCC in Xiamen Hospital of Traditional Chinese Medicine and Zhongshan Hospital of Xiamen University from December 2017 to March 2023. These 101 patients included 84 males and 17 females, and the age[M(Q1, Q3)] was 59.0(49.0,66.0)years. These patients were divided into two groups according to the immunohistochemical Ki-67 expression levels in tumor tissues: the high expression group (Ki-67%>20%, n=59) and the low expression group (Ki-67%≤20%, n=42).CT values on 70 keV and 140 keV monochromatic energy images (HU70 keV-a, HU140 keV-a, HU70 keV-p, HU140 keV-p) and water density (Dwater-a, Dwater-p) were measured in arterial phase and portal vein phase, and the difference of HU70 keV, HU140 keV, Dwater values between portal vein and arterial phase (ΔHU70 keV, ΔHU140 keV, ΔDwater), as well as ratio of HU70 keV, HU140 keV, Dwatervalues between portal vein and arterial phase (HU70 keVratio, HU140 keVratio, Dwaterratio) were calculated. Spearman correlation analysis was used to analyze the correlation between the CT spectral parameters and Ki-67%. Multivariate logistic regression model was used to determine the factors associated with high expression of Ki-67. The receiver operating characteristics (ROC) curves were used to indicate the efficacy of dynamic enhanced spectral CT in evaluating Ki-67 high expression in HCC. Results: The high Ki-67 expression group revealed higher alpha fetal protein levels, larger tumor diameter and more irregular tumor shape compared with the low Ki-67 expression group,and the differences were statistically significant (all P<0.05). Spearman correlation analysis showed that the HU140 keV-p, Dwater-p, HU70 keV ratio, HU140 keV ratio, Dwater ratio, ΔHU70 keV, ΔHU140 keV, ΔDwater were positively correlated with Ki-67 positivity rate (r:0.31-0.50, all P<0.05). The spectral CT parameters (HU70 keV-p, HU140 keV-p, Dwater-p, HU70 keV ratio, HU140 keV ratio, Dwater ratio, ΔHU70 keV, ΔHU140 keV, ΔDwater) in high Ki-67 expression group were significantly higher than those in low Ki-67 expression group (all P<0.05). Multivariate logistic regression model shows that Dwater-p(OR=1.16, 95%CI: 1.05-1.29, P=0.005), ΔHU140 keV(OR=1.39, 95%CI: 1.20-1.62, P<0.001) and irregular tumor morphology (OR=5.25, 95%CI: 1.61-17.12, P=0.006) were correlative factors for high Ki-67 expression. The HU140 keV ratio and ΔHU140 keV alone evaluated the highest AUC of high Ki-67 high expression in HCC, which were 0.82 (95%CI: 0.74-0.90), the sensitivity were 61.0%, and the specificity were 88.1% and 85.7%. The combined analysis of Dwater-p, ΔHU140 keV and irregular tumor morphology had an increased AUC of 0.88 (95%CI: 0.81-0.95) in assessment high Ki-67 expression, with the sensitivity of 84.7% and the specificity of 78.6%. Conclusions: Dynamic enhanced spectral CT parameters were positively correlated with the Ki-67 expression in HCC. Spectral CT provides a non-invasive method to evaluate the proliferation status of HCC cells, and the efficiency could be improved by multi-parameter analysis combining spectral CT parameters and morphologic features.

Receptor Positive Breast Lesions and Status of Axillary Lymph Node.

Objective This study aimed to examine the axillary pathological condition through the development of an assessment framework for hormone receptor-positive breast cancer subsequent to neoadjuvant chemotherapy (NAC). Furthermore, the primary objective of this study was to examine the association between axillary status and breast tumors that are positive for hormone receptors following neoadjuvant chemotherapy. Methodology The present retrospective investigation encompassed a cohort including 300 individuals who were administered neoadjuvant chemotherapy before receiving surgical intervention. The data collection period for this study was from September 2021 to December 2022. All patients received neoadjuvant chemotherapy, per the guidelines established by the National Comprehensive Cancer Network (NCCN). We divided patients into two distinct groups: a test set of 250 patients and a validity set of 50 patients. Patients with no evidence of lymphoid involvement underwent a biopsy of sentinel lymph nodes (SLNB) and would have undergone axillary dissection if the biopsy results had indicated positive findings. A logistic regression analysis was employed to investigate the variables linked to the presence of residual positive axillary lymph nodes in the test set. Subsequently, a multivariate analysis was conducted on the variables that exhibited a p-value below 0.2 in the univariate study. In addition, a value of 1 was assigned to all risk factors to construct a comprehensive correlation prediction model. Results The participants included in this study had a mean age and body mass index (BMI) of 46.24 ± 9.1 years and 25.8 ± 2.5 kg, respectively. The present investigation examined the presence of pathological axillary metastases in a cohort of 188 patients, which accounted for 62.55% of the total sample, by utilizing core-needle biopsy. Furthermore, the incidence rates of individuals presenting with clinical T1 were reported as 14.6%, while 55.2% cases of T2, 17.8% cases of T3, and 13% cases of T4 tumors were reported, respectively. Of the overall occurrences, the prevailing histological subtype was invasive ductal carcinoma, accounting for 91.4% (222 out of 243) of the cases. Multiple criteria were identified as independent predictors of the presence of residual positive axillary lymph nodes. The factors under consideration encompass lymphovascular invasion (odds ratio= 7.108; 95% breast cancer stage (odd ratio = 5.025; 95%, HER2 negativity (odd ratio= 2.997), low Ki-67 expression (odd ratio = 4.231), and suspected positive axillary lymph nodes before surgical intervention. Conclusion The present study presents a novel prediction model that integrates imaging and pathology data, aiming to assist patients and healthcare practitioners in evaluating the efficacy of NACfor hormone-receptor-positive breast tumors. The model holds particular significance for individuals who exhibit clinical positivity in their lymph nodes (LNs). Consequently, the model has the potential to provide guidance for the management of axillary lymph nodes and prevent unnecessary dissection.

Histopathological prognostic factors in post NACT ovarian cancers: A retrospective study

Epithelial ovarian carcinoma is the most common type of all the ovarian cancers. The patients with advanced stage are initially treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The high mortality rate is mainly due to advanced stage disease at initial presentation. This a retrospective study carried out in department of pathology at Bhagwan Mahaveer cancer hospital, Jaipur. The retrospective cases data was collected and analyzed from patient records on basis of inclusion and exclusion criteria.: Patients of advanced ovarian cancer with fibrosis grade 3, necrosis grade 2, presence of psammoma bodies, presence of collagen deposition, low Ki67 index, positive ER status were associated with longer DFS (p value= 0.014,0.029,0.033,0.028,0.001 and 0.001 respectively) and OS (P value 0.025,0.005,0.002,0.015,0.001 and 0.001 respectively).We propose that the prognostic histopathological parameters analysed in our study in post NACT patients of ovarian carcinoma should be reported in final histopathological report, as these factors can provide an extra tool for clinicians to optimize patient management and care.

Abstract A003: A novel treatment strategy for high-risk and relapse/refractory hepatoblastoma

Abstract Background: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To better understand these aggressive phenotypes, our lab has developed a preclinical testing pipeline consisting of patient-derived spheroids (PDSp) and orthotopic xenograft models for chemotherapy and targeted therapy testing. We hypothesized that with this preclinical pipeline we could find an effective combination treatment strategy utilizing pan-histone deacetylase (HDAC) inhibition. Methods: RNA sequencing, microarray, NanoString, and immunohistochemistry (IHC) data of patient HB samples were analyzed for expression of all HDAC classes. HB cell lines were used to screen HDAC inhibitors. PDSp were used to screen which combination of standard chemotherapy regimens with a HDAC inhibitor. HB patient derived xenograft (PDX) mice models were developed and treated based off the lowest viability of PDSp drug screen. Mice were started on study when tumor volume reached 0.1-0.4 cm3 and were sacked when tumors reached diameter of 1.5 cm or at the end of the 6-week study period. Tumors were sectioned and evaluated for Ki67% and necrosis. Results: HDAC RNA and protein expression was elevated in HB tumors compared to normal livers. Four unique HB PDX models, including high risk, relapse and treatment refractory cases, were developed and validated from treatment-refractory patient tumors. Panobinostat (IC50 of 0.013-0.059 mM) showed strong in vitro effects with the lowest cell viability compared to other HDAC inhibitors. PDSp demonstrated the highest level of cell death with combination treatment of vincristine/irinotecan/panobinostat (VIP). After 6 week of treatment[SV1] , all four models had a limited response to VI therapy; however, showed a much improved response with VIP. All four models responded to therapy with a decrease in tumor size compared to placebo and survival to 6 weeks. Two of our four models that had showed some initial response to VI therapy demonstrated necrotic cell death, lower Ki67%, decreased serum alpha fetoprotein (AFP) and reduced tumor burden compared to paired vincristine/irinotecan (VI) and placebo. Conclusions: Utilizing a preclinical pipeline for HB, we have shown that panobinostat in combination with VI chemotherapy can induce an effective tumor response in models developed from high risk, relapse, and treatment refractory HB patients. This clinically relevant methodology can be used to screen novel targeted combination therapies with the VI backbone in order to create novel treatment strategies for future clinical trials. Citation Format: Andres F Espinoza, Roma Patel, Sai Govindu, Pavan Kureti, Bryan Armbruster, Sarah Woodfield, Sanjeev A Vasudevan. A novel treatment strategy for high-risk and relapse/refractory hepatoblastoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A003.

Concurrent metastatic melanoma and follicular lymphoma diagnosis on liver fine needle aspiration and biopsy

Abstract Introduction/Objective The liver is commonly involved in metastatic neoplasms, such as colorectal, breast, esophageal, stomach, pancreatic, lung, and kidney. Fine needle aspiration (FNA) and core needle biopsy (CNB) are frequently used to establish an accurate diagnosis of liver masses. Here we report the coexistence of metastatic malignant melanoma (MM) and follicular lymphoma (FL) involving the liver. To our knowledge, This is the first reported case, and we hope to add to the literature. Methods/Case Report The patient is a 75 -year-old woman diagnosed with stage I skin melanoma in 2004, and systemic low-grade FL in 2009. She presented with fatigue, weight loss, and difficulty swallowing. CT scan showed new pulmonary, hepatic, and splenic nodules with stable abdominal lymphadenopathy. Smears from the liver nodule FNA showed numerous single tumor cells with moderate cytoplasm and eccentrically located hyperchromatic nuclei. CNB showed fragments of liver parenchyma infiltrated by metastatic melanoma and a focal portal area with expansile lymphoid aggregates of small lymphocytes. The lymphoid cells were positive for CD10, CD20, PAX5, and BCL2 and negative for CD3, CD5, BCL6 and BCL1, with a low Ki-67 proliferative index (&amp;lt;5%). Although not characteristic of an FL, this immunophenotype was most consistent with FL given her clinical history. The metastatic MM was positive for SOX10 and Melan-A, while negative for CD45 and CK AE1/AE3. Despite neoadjuvant therapy, the patient died just two months after diagnosis. Results (if a Case Study enter NA) NA Conclusion A tremendous variety of neoplasms can occur in the liver. Different morphologies under a microscope should broaden the list of differential diagnoses. Familiarizing with morphological features and using ancillary studies are essential for accurate diagnosis and proper patient management. FNA and CNB combined with ancillary studies can successfully establish the diagnosis of malignancies involving the liver.

EBV positive plasmacytoma in immunocompetent patients: A diagnostically challenging rare entity

Abstract Introduction/Objective Epstein-Barr Virus (EBV)-positive plasmacytoma is a rare entity that shows morphological and immunophenotypic overlap with plasmablastic lymphoma and can cause a diagnostic dilemma. Here we discuss a unique case of EBER-positive plasmacytoma arising from nasal polyps. Methods/Case Report A 61-year-old immunocompetent male presented with nasal polyps, right maxillary sinus lesions, and an enlarging sternal lesion. Multiple biopsies were obtained which revealed a diffuse infiltration by atypical plasma cells, that were positive for CD138, MUM1, CD79a, CD56, lambda-in situ hybridization, and Ki67- proliferation index of 20-30%. In situ, hybridization for EBV-encoded viral RNA (EBER) was positive in the neoplastic cells. B- and T- cell markers were negative. The flow cytometry studies detected monotypic lambda-restricted CD38/CD138 positive plasma cells with an aberrant expression of CD56 and CD117. Molecular studies for B-and T- cell gene rearrangement were also negative. A final diagnosis of EBER-positive plasmacytoma was made. The patient was treated with cyclophosphamide, vincristine, doxorubicin, and carboplatin followed by four cycles of RVD, and is doing well. Results (if a Case Study enter NA) NA Conclusion EBER-positive plasmacytoma poses a diagnostic challenge with plasmablastic lymphoma, specifically in immunocompetent individuals. The useful differentiating clues pointing towards EBER positive plasmacytoma could be a spectrum of morphology ranging from mature to anaplastic, low Ki67 proliferation index, aberrant CD56 and CD117 positivity, and high M- spike on protein studies. Comprehensive clinical, morphologic phenotypic, and genetic investigations are necessary to make a specific diagnosis as the two entities differ in their management.

A Rare Case of Incidental Primary Follicular Lymphoma Co-Existing With Grade Group 5 Prostatic Adenocarcinoma

Abstract Introduction/Objective Primary lymphoma of the prostate is an exceedingly rare entity comprising less than 0.1% of all prostatic cancers with follicular lymphoma making up only 12% of primary prostatic lymphomas. There is very limited literature owing to their rarity and underdiagnosis. To the best of our knowledge, prostatic adenocarcinoma with an incidental follicular lymphoma presenting as a prostate imaging reporting and data system 4 (PI-RADS 4) lesion on multiparametric magnetic resonance imaging (mpMRI) with mildly elevated serum prostate specific antigen (PSA) has not been previously described. Methods/Case Report A 73 year old male presented to Danbury Hospital for follow up on benign prostatic hyperplasia (BPH) diagnosed in 2020. The patient was experiencing nocturia and had a serum PSA of 4.8. Multiparametric MRI revealed an enlarged, 5.5 x 4.1 x 3.3 cm, prostate gland (estimate weight of 45.5 grams) with a 1.2 cm PI-RADS 4 lesion in the right anterior mid gland. There was no evidence of metastatic disease on his most recent body imaging. He was subsequently scheduled for prostate needle biopsy. Histopathology showed a high grade prostatic adenocarcinoma, with a Gleason score 4 + 5=9, along with a focally prominent dense lymphoid infiltrate in four of four cores from the same area of abnormality that was detected on mpMRI. The latter comprised of ill defined follicles and sheets of small cleaved atypical lymphoid cells consistent with centrocytes and very few centroblasts. By immunohistochemical staining, the atypical cells in lymphoid follicles and interfollicular areas were positive for CD20, CD10 and BCL2 and negative for cyclin D1. CD21 stain highlighted the follicular dendritic cell meshwork in the germinal centers with a low Ki67 proliferation index. A final diagnosis of low grade follicular lymphoma (grade1-2) coexisting with the prostatic adenocarcinoma was rendered. The patient is currently undergoing lymphoma staging as the treatment for adenocarcinoma is planned. Results (if a Case Study enter NA) NA Conclusion Primary lymphoma of the prostate usually presents with non specific obstructive voiding symptoms and normal or near normal PSA levels which makes it challenging for physicians to suspect lymphomas. The lymphocytic infiltrate, originally thought to be prostatitis, underwent further evaluation with immunohistochemistry due to its monotonous appearance, which clinched the final diagnosis. Careful evaluation of prostate core needle biopsies is necessary even after spotting carcinoma in order to rule out low grade lymphomas.