Histologic Features Of Tumor Research Articles

Https://doi.org/10.18019/1028-4427-2022-28-4-579-583 Гистологическая характеристика гигантоклеточной опухоли оболочек сухожилий, сочетанной с ладонным фасциальным фиброматозом (случай из практики)

Giant cell tumor of the tendon sheaths and palmar fascial fibromatosis are both fibrohistiocytic diseases. There is no information about their combination in the available literature. Aim To analyze the histological characteristics of a giant cell tumor of the tendon sheath associated with palmar fascial fibromatosis. Materials and methods Case history and pathomorphological examination of the surgical material of patient M with recurrent palmar fascial fibromatosis and Dupuytren's contracture of the 5th ray of the right hand in grade 3 and a neoplasm of the 2nd finger of the right hand Results A neoplasm with a thin fibrous capsule, permeated with blood vessels, many of them had abnormally thickened fibrous walls and completely obliterated lumens. The cellular composition of the tumor is mixed: fibroblast-like cells, small histiocytes, siderophages, osteoclast-like giant multinucleated cells, xanthoma and plasma cells. The frequency of mitoses is less than one per 10 fields of view, apoptotic bodies from zero to several per field of view. In the composition of fibromatous cords in the projection of the V beam, giant multinucleated cells (possibly cells of foreign bodies) were found. Conclusion For the first time, a clinical case of a giant cell tumor of the tendon sheaths, which developed against the background of a long-term recurrent palmar fascial fibromatosis, is presented. Taking into account the pathomorphological characteristics of the surgical material, the risk of its recurrence and malignancy in patient M. is low. However, the unpredictability of the histogenesis of this tumor known from the literature is an indication for active clinical observation.

CXCL8 expression is associated with advanced stage, right sidedness, and distinct histological features of colorectal cancer.

CXCL8 is an inflammatory chemokine elevated in the colorectal cancer (CRC) tumour microenvironment. CXCR2, the major receptor for CXCL8, is predominantly expressed by neutrophils. In the cancer setting, CXCL8 plays important roles in neutrophil chemotaxis, facilitating angiogenesis, invasion, and metastasis. This study aimed to assess the spatial distribution of CXCL8 mRNA expression in CRC specimens, explore associations with clinical characteristics, and investigate the underlying biology of aberrant CXCL8 levels. CXCR2 expression was also assessed in a second cohort of unique CRC primary tumours and synchronously resected matched liver metastases. A previously constructed tissue microarray consisting of a cohort of stage I–IV CRC patients undergoing surgical resection with curative intent (n = 438) was probed for CXCL8 via RNAscope®. Analysis was performed using HALO® digital pathology software to quantify expression in the tumour and stromal compartments. Scores were assessed for association with clinical characteristics. Mutational analyses were performed on a subset of these patients to determine genomic differences in patients with high CXCL8 expression. A second cohort of stage IV CRC patients with primary and matched metastatic liver tumours was stained via immunohistochemistry for CXCR2, and scores were assessed for clinical significance. CXCL8 expression within the stromal compartment was associated with reduced cancer‐specific survival in the first cohort (p = 0.035), and this relationship was potentiated in right‐sided colon cancer cases (p = 0.009). High CXCL8 within the stroma was associated with driving a more stromal‐rich phenotype and the presence of metastases. When stromal CXCL8 scores were combined with tumour‐infiltrating macrophage counts or systemic neutrophil counts, patients classified as high for both markers had significantly poorer prognosis. CXCR2+ immune cell infiltration was associated with increased stromal invasion in liver metastases (p = 0.037). These data indicate a role for CXCL8 in driving unfavourable tumour histological features and promoting metastases. This study suggests that inhibiting CXCL8/CXCR2 should be investigated in patients with right‐sided colonic disease and stroma‐rich tumours.

Inflammatory Myofibroblastic Tumor of the Bladder in an 8-Year-Old Girl: About a Case with Review of the Literature

Introduction: The inflammatory myofibroblastic tumor is a rare tumor. It most often occurs in the bladder in the genitourinary sphere. This benign and aggressive spindle cell tumor affects children and frequently girls. The objective of this work is to describe from a clinical case, the clinical, radiological, and histological characteristics of an inflammatory myofibroblastic tumor in an 8 years old girl. Case Presentation: An 8-year-old girl was followed for an inflammatory myofibroblastic tumor of the bladder revealed by micturition burns complicated by hematuria. She underwent an ultrasound and radiological workup demonstrating an anterior bladder parietal mass reaching the rectus abdomen is muscle. Subsequently, an excisional biopsy was performed and histological and immunohistochemical examination revealed an inflammatory myofibroblastic tumor. Discussion: Inflammatory myofibroblastic tumors of the bladder are benign tumors with aggressive features usually revealed by voiding symptoms, pelvic pain, and pelvic mass. Treatment is based on Trans urethral resection of the bladder. Anatomical pathology examination shows spindle-shaped myofibroblast and fibroblast cells, a collagenous or myxoid matrix, and inflammatory cells composed of plasma cells, lymphocytes, and eosinophils. The diagnosis is confirmed by immunohistochemistry with an expression of CAM5.2, desmin, aSMA, and vimentin and especially of Anaplasic Lymphoma Kinase (ALK). Conclusion: Rare tumor process, whose malignant potential remains unknown. Management is by conservative surgery of the bladder.

Catalytic activity of serum and immunoglobulins of classes G and A in patients with breast cancer

The objective of this study was to investigate DNase, various types of proteolytic and oxidoreductase serum and abzyme activities, as well as the serum contents of free DNA in patients with breast tumors in accordance with the clinical, pathological and immunohistochemical characteristics of the tumors. It was found that catalytic antibodies isolated from blood serum of patients with breast oncopathology exhibit proteolytic, DNase and oxidoreductase activity, which varies depending on the course of the disease. It is worth noting that catalytic activity of IgAs (per unit of Ig concentration) can be 1-2 orders of magnitude higher than the analogous activity of IgGs. It was found that DNase, proteolytic (cathepsin G, cathepsin B) serum enzymatic activities and cathepsin G-like activity of IgG and IgA differ in patients with malignant and benign breast tumors and in healthy individuals. These parameters depend on the advance of the tumor process, histological and immunohistochemical characteristics of the tumor, as well as on the probability of tumor progression. In particular, the progression of the tumor process is accompanied by an increase of the activity of serum DNase and cathepsin B, decline of the concentration of patients` serum DNA, being also followed by marked changes of the nuclease, proteolytic and oxidoreductase activity of IgG and IgA.

Abstract 4088: A novel real world clinico-genomics data platform identifies breast cancer histologic and molecular characteristics as candidate predictors for time to distant metastasis

Abstract Introduction: Currently, the NCCN guidelines for invasive breast cancer (BC) surveillance are the same regardless of tumor pathology. The length of time between initial diagnosis and documented distant metastasis based on tumor subtypes has not been well-studied in real-world settings, which means that for any given patient, generalized screening recommendations may be either too stringent or too relaxed. Here, we report how tumor histologic and molecular characteristics analyzed from a real-world data platform correlate with the average time to distant recurrence. This information can guide more personalized surveillance for BC patients. Methods: Ciitizen (a wholly owned subsidiary of Invitae) leverages HIPAA right of access on behalf of patients to collect their medical records, extracts relevant clinical information into a standardized and validated longitudinal dataset, and - with their consent - enables research use of this data. From our current invasive BC cohort (n=1011), we identified a subcohort who were diagnosed at Stage I-III with associated histology and/or molecular characterization, then ultimately went on to develop distant metastases (n=195 cases involving 321 sites: bone, brain, liver, and/or lung). We calculated time from initial diagnosis to confirmation of distant metastasis at each site, and statistically analyzed differences using pooled hypothesis testing. Results: In addition to finding expected associations between molecular type and site(s) of metastasis, i.e. bone and brain more common in Hormone Receptor Positive (HR+) subtypes vs HR-, we also characterized the average time to distant metastasis (TDM) to identify other statistically significant associations: Molecular Type: HR-/HER2- (n=30) has an average TDM of 1124 days, which is significantly faster than HR+/HER2- (2224 days; n=197) and HR+/HER2+ (2159 days; n=32) (p=0.0043). BRCA: Individuals with BRCA1/2 pathogenic germline variants have an average TDM of 1043 days (n=15), significantly earlier than individuals with normal BRCA1/2 (2238 days; n=179) (p <0.0001). Histology: Ductal carcinomas have an average TDM of 2262 days (n=242) and lobular carcinomas have an average TDM of 2812 days (n=24), both of which are significantly longer than the rarer metaplastic (739 days; n=11) and inflammatory (978 days; n=5) (p=0.0001). Conclusions: These real-world findings characterize average time to metastasis and reveal statistically significant associations based on histologic and molecular type, which taken together can inform more personalized screening recommendations for BC patients. Since the Ciitizen data platform also includes additional treatment and outcome variables, future studies can explore the relationships between these various features towards more granular prognostic and predictive classifications. Citation Format: Amanda Nottke, Anthony B. Cardillo, Hana E. Littleford, Lisandra West-Odell, Alexandra Berk. A novel real world clinico-genomics data platform identifies breast cancer histologic and molecular characteristics as candidate predictors for time to distant metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4088.

HGG-20. PRMT5 promotes the formation and growth of pediatric high-grade glioma by maintaining tumor stem cell populations

BACKGROUND: Pediatric high-grade gliomas (PHGG) are aggressive, undifferentiated CNS tumors comprising two broad subtypes: diffuse midline glioma with H3K27M mutations (DMG) and cortical high-grade glioma (H3K27-wild-type (wt) PHGG). During normal development, PRMT5 promotes stem cell self-renewal through methylation of arginine residues in histone tails. We hypothesized that PRMT5 controls self-renewal essential to the proliferation of PHGG tumor initiating cells (TICs). METHODS: We identified PRMT5 as potentially oncogenic in PHGG through a screen of 4,139 shRNAs targeting 406 genes with epigenetic activity. To elucidate PRMT5’s activity, we used lentiviral shRNA delivery to knock down (KD) PRMT5 expression in four DMG and one H3K27-wt PHGG cell lines. We performed in vitro growth, cell cycle, apoptosis, limiting dilution and bulk RNA-Seq assays to determine the phenotypic effects of PRMT5 KD. To identify PRMT5’s gene targets, we performed cleavage under targets & release using nuclease (CUT&RUN) followed by qPCR and are currently performing CUT&RUN-Seq. We orthotopically implanted PRMT5 KD PHGG cells into mice and tracked survival, tumor growth and tumor histological characteristics. RESULTS: In vitro, PRMT5 KD reduced cell growth (p<0.001), slowed cell cycle progression and increased apoptosis. PRMT KD also slowed neurosphere formation, demonstrating reduced self-renewal (p<7E-9). Geneset expression analysis showed PRMT5 KD reduced expression of self-renewal genes and increased expression of differentiation genes (FDR<0.0001). In vivo, PRMT5 KD reduced tumor growth, as monitored by bioluminescence and MRI, and aggressiveness, based on Ki-67 staining (p<0.05), leading to increased survival (p<0.001). CUT&RUN-qPCR results showed PRMT5 KD led to decreased expression and H3K4me3 promoter occupancy at PAX3, and decreased expression and increased H3K27me3 occupancy at S100A6. PAX3 and S100A6 are oncogenes that preserve TIC self-renewal. CONCLUSION. In vitro experiments show that PRMT5 KD epigenetically reduces TIC self-renewal. In vitro and in vivo, PRMT5 KD reduced PHGG tumor cell growth and aggressiveness.

Evaluation of the 18F-FDG-PET/CT uptake association with pathological and immunohistochemistry features in esophagogastric adenocarcinoma.

The present study aimed to analyze the association between 18F-fluorodeoxyglucose (FDG) uptake and histologic panel in esophagogastric adenocarcinoma. We retrospectively enrolled 26 patients with histologically confirmed esophageal, gastroesophageal junction and gastric adenocarcinoma that have been submitted to pretreatment FDG-PET/CT. We collected the cancer tissue sample of each patient and performed immunohistochemical analyses of the glucose transport protein 1 (GLUT-1), Ki-67, cysteine aspartate-specific proteinases (Caspase)-3 and hexokinase-1, and evaluated the association of these parameters with FDG uptake. The FDG uptake was measured by tumor standardized uptake value (SUV), metabolic tumor volume (MTV), and Total Lesion Glycolysis (TLG). Besides, we analyzed the association of FDG uptake and tumor location, Lauren's histologic subtype, grade of cellular differentiation and intratumoral inflammatory infiltrate. We found a positive association between GLUT-1 with SUV and TLG, Caspase-3 and SUV and inflammation grade with SUV. Tumor inflammation infiltrate, GLUT-1 and Caspase-3 correlated with 18F-FDG uptake in PET/CT in esophagogastric adenocarcinoma. These findings may help understand the pathologic PET/CT significance in cancer. Understanding the meaning of the 18F-FDG uptake in the field of tumor histologic and immunohistochemistry features is essential to allow the evolution of PET/CT application in esophageal and gastric carcinomas.

Role of Autophagy Markers (Light Chain 3B and Beclin-1) in Pathogenicity of Breast Cancer in a Sample of Iraqi Women: A Pilot Study

Background: Breast cancer (BC) is the most common malignancy in women and the second greatest cause of cancer death. There are relatively little data available on the role of autophagy markers in pathogenicity of breast cancer in the Iraqi population. We have therefore investigated the role of Baclin-1 and LC3-B in pathogenicity of breast cancer in Iraqi women. Methods: A case-control study was conducted to assess the role of Bacline-1 and LC3-B in pathogenicity of breast cancer in Iraqi women. The study included 50 patients with BC age matched with 50 healthy individuals served as a control group. The Baclin-1 and LC3-B concentrations were determined by enzyme-linked immunosorbent assay (ELISA) technique. Results: Body mass index (BMI) were significantly increase in patients with BC compared to the controls. Serum Baclin-1 and LC3-B levels in cases were significantly higher (P= 0.001) than those in controls. According to histological tumor characteristics. Grade 2 and stage IIA were significantly higher in BC patients and the tumor grade and stage did not show any significant associations with serum levels of Bacline-1 and LC3-B. No significant correlation between serum levels of Baclin-1 and LC3-B (r = 0.034; P = 0.812). Conclusion: The study indicated that the Beclin-1 and LC3-B my consider a good biomarkers for progression of BC and it could be a therapeutic target to reduce the aggressiveness of disease. Keywords: Breast cancer; Baclin-1; Light Chain3B.

Association of histological features with laryngeal squamous cell carcinoma recurrences: a population-based study of 1502 patients in the Netherlands

BackgroundRecurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival.Material and methodsDemographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010–2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis.ResultsIn total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68–1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63–3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48–4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found.ConclusionIn this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions.

Circulating Exosomal-DNA in Glioma Patients: A Quantitative Study and Histopathological Correlations-A Preliminary Study.

Glial neoplasms are a group of diseases with poor prognoses. Not all risk factors are known, and no screening tests are available. Only histology provides certain diagnosis. As already reported, DNA transported by exosomes can be an excellent source of information shared by cells locally or systemically. These vesicles seem to be one of the main mechanisms of tumor remote intercellular signaling used to induce immune deregulation, apoptosis, and both phenotypic and genotypic modifications. In this study, we evaluated the exosomal DNA (exoDNA) concentration in blood samples of patients affected by cerebral glioma and correlated it with histological and radiological characteristics of tumors. From 14 patients with diagnosed primary or recurrent glioma, we obtained MRI imaging data, histological data, and preoperative blood samples that were used to extract circulating exosomal DNA, which we then quantified. Our results demonstrate a relationship between the amount of circulating exosomal DNA and tumor volume, and mitotic activity. In particular, a high concentration of exoDNA was noted in low-grade gliomas. Our results suggest a possible role of exoDNAs in the diagnosis of brain glioma. They could be particularly useful in detecting early recurrent high-grade gliomas and asymptomatic low-grade gliomas.

Acoustic Bioprinting of Patient-Derived Organoids for Predicting Cancer Therapy Responses.

Cancer models, which are biologically representative of patient tumors, can predict the treatment responses and help determine the most appropriate cancer treatment for individual patients. Here, a point-of-care testing system called acoustically bioprinted patient-derived microtissues (PDMs) that can model cancer invasion and predict treatment response in individual patients with colorectal cancer (CRC), is reported. The PDMs are composed of patient-derived colorectal tumors and healthy organoids which can be precisely arranged by acoustic bioprinting approach for recapulating primary tissue's architecture. Particularly, these tumor organoids can be efficiently generated and can apprehend histological, genomic, and phenotypical characteristics of primary tumors. Consequently, these PDMs allow physiologically relevant in vitro drug (5-fluorouracil) screens, thus predicting the paired patient's responses to chemotherapy. A correlation between organoid invasion speed and normalized spreading speed of the paired patients is further established. It provides a quantitative indicator to help doctors make better decisions on ultimate anus-preserving operation for extremely low CRC patients. Thus, by combing acoustic bioprinting and organoid cultures, this method may open an avenue to establish complex 3D tissue models for precision and personalized medicine.

Tumor-Infiltrating T Cells Can Be ExpandedSuccessfully from Primary Uveal Melanoma after Separation from Their TumorEnvironment.

PurposeTo evaluate whether expanded tumor-infiltrating lymphocytes (TILs) can be obtained from primary uveal melanoma (UM) for potential use as adjuvant treatment in patients at risk of developing metastatic disease.DesignExperimental research study.ParticipantsFreshly obtained primary UM from 30 patients.MethodsThree different methods were used to expand TILs: (1) direct culture from small fragments of fresh tumor tissue, (2) single-cell tissue preparation by enzymatic digestion and subsequent enrichment of mononuclear cells, and (3) selection of CD3+ T cells using magnetic beads. Surface expression of costimulatory and inhibitory T-cell markers and T-cell reactivity against autologous tumor cells was assessed. Clinical, histopathologic, genetic, and immunologic characteristics of the tumors were compared with the capacity to expand TILs and with their reactivity against autologous tumor cells.Main Outcome MeasuresThe feasibility of expanding TILs from primary UM, testing their reactivity to autologous UM cells, and evaluating the impact of an immunomodulatory environment.ResultsDirect culture of tumor parts led to successful TIL culture in 4 of 22 tumors (18%), enrichment of mononuclear cells gave rise to TILs in 5 of 12 tumors (42%), while preselection of CD3+ T cells with magnetic beads resulted in TIL expansion in 17 of 25 tumors (68%). In 8 of 17 tumors (47%), the TIL cultures comprised UM-reactive T cells. The presence of UM-reactive T cells among TILs was not related to clinical, histologic, genetic, or immunological tumor characteristics. Interestingly, RNA-Seq analysis showed that approximately half of the UM tumors displayed an increased expression of immunomodulatory molecules related to T-cell suppression, such as galectin 3, programmed death-ligand 1, cytotoxic T-lymphocyte-associated protein 4, indoleamine 2,3-dioxygenase 1, and lymphocyte activating 3, potentially explaining why T cells require optimal removal of tumor components for expansion.ConclusionsThe need to separate TILs from their tumor microenvironment for their successful expansion and the presence of UM-reactive T cells among TILs suggests that these UM-reactive T cells are strongly suppressed in vivo and that UM is immunogenic. These findings indicate that adoptive TIL therapy could be an option as an adjuvant treatment in primary UM patients at high risk of developing metastatic disease.

Independent Assessment of the Children’s Hepatic Tumors International Collaboration Risk Stratification for Hepatoblastoma and the Association of Tumor Histological Characteristics With Prognosis

Hepatoblastoma is the most common pediatric liver malignant neoplasm, and accurate risk stratification is essential for guiding treatment. To validate the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) in an independent cohort of patients with hepatoblastoma and evaluate the association of pretreatment hepatoblastoma histological subtype with prognosis. This is a single-institution retrospective cohort study of 96 pediatric patients with hepatoblastoma diagnosed and treated between June 1, 2000, and December 31, 2016, with recent therapy and independent of the CHIC-HS discovery cohort. Each patient was assigned a risk group according to CHIC-HS. The histological characteristics of each tumor were assessed based on the International Pediatric Liver Tumor Consensus Classification. Data were analyzed from May 2018 to May 2019. The main outcomes were event-free survival (EFS) and overall survival (OS). Cox regression analysis was used to examine the associations of patient characteristics and tumor histological characteristics with survival. A total of 96 patients (median [range] age, 1.9 [0.4-18] years; 36 [38%] girls and 60 [63%] boys) were assessed, including 15 with very low risk, 28 with low risk, 23 with intermediate risk, and 30 with high risk, according to CHIC-HS criteria. There were a total of 13 cancer-related deaths; median (range) follow-up was 3.5 (0.1-17.8) years for those alive at the last follow-up. The estimated 5-year OS rates were 100% in the very low-risk group, 94.7% (95% CI, 68.1%-99.2%) in the low-risk group, 89.2% (95% CI, 63.1%-97.2%) in the intermediate-risk group, and 57.9% (95% CI, 34.6%-75.5%) in the high-risk group. In a multivariable analysis, we confirmed that CHIC-HS significantly estimated EFS (high-risk group vs very low- and low-risk groups: hazard ratio [HR], 45.59; 95% CI, 9.39-209.5; P < .001) and OS (high-risk group vs very low- and low-risk groups: HR, 21.95; 95% CI, 2.76-174.29; P < .001). In the subcohort of 84 patients for whom pretreatment tumor histological data were available, tumor epithelial histological subtypes were found to be significantly associated with both EFS and OS. Patients in the CHIC-HS high-risk group and with embryonal-only histological subtype had the highest risk of relapse or disease progression (high-risk: HR, 42.62; 95% CI, 9.91-203.9; embryonal: HR, 3.28; 95% CI, 1.21-8.9) and death (high-risk: HR, 18.78; 95% CI, 2.31-152.84; embryonal: HR, 7.12; 95% CI, 1.51-33.52). This cohort study found that CHIC-HS performed as expected in an independent cohort that was more recently treated. Incorporation of pretreatment tumor histological data into CHIC-HS may provide additional prognostic value.

Establishment of childhood hepatoblastoma xenografts and evaluation of the anti-tumour effects of anlotinib, oxaliplatin and sorafenib.

Hepatoblastoma (HB) is a common primary malignant liver tumour in children, mainly treated by means of traditional chemotherapy using platinum and doxorubicin (ADM). There has been limited progress in the research and development of new drugs for treating HB. A tumour biopsy from a child with HB was implanted into immunodeficient mice. The primary tumour and patient-derived xenograft (PDX) tumour were extensively characterised by histology, immunohistochemistry (IHC), and humanisation identification. We used the PDX model to evaluate the anti-tumour effects of anlotinib oxaliplatin (L-OHP) and sorafenib on childhood HB. The established PDX model maintained the histological characteristics of the primary tumour. Anlotinib, L-OHP, and sorafenib can significantly inhibit the tumour growth in the PDX model. There was no obvious damage of the drugs to the heart, liver and kidney of the mice, and the side effects observed were light. We have successfully established a PDX model of childhood HB. The model retains important molecular characteristics of human primary tumours. Using the model, it was found that anlotinib, L-OHP, and sorafenib have a good inhibitory effect on the growth of childhood HB. This provides a preliminary research basis for the clinical application of the drugs.

The diagnostic value of core needle biopsy in cervical cancer: A retrospective analysis.

Cervical carcinoma is a major cause of morbidity and mortality among women worldwide. Histological subtype, lymphovascular space invasion and tumor grade could have a prognostic and predictive value for patients' outcome and the knowledge of these histologic characteristics may influence clinical decision making. However, studies evaluating the diagnostic value of various biopsy techniques regarding these parameters of cervical cancer are scarce. We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative core needle biopsy (CNB) assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying LVSI and tumor grade. CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma, 92.9% and 96.6% for adenocarcinoma, 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of LVSI was 61.9% and was positively influenced by tumor size in preoperative magnetic resonance imaging and negatively influenced by strong peritumoral inflammation. High tumor grade (G3) was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. In conclusion, CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques.

Metástase pulmonar de ameloblastoma malígno: revisão e relato de caso

ABSTRACT Despite being a benign tumor of the maxillofacial region, some cases of ameloblastoma can be categorized as malignant ameloblastoma (or metastasizing) when metastases occur. The aim of this study is to report a rare case of lung metastasis from mandibular ameloblastoma, in order to review its risk and analyze the main anatomic sites that can occur with this disease. The case of a 48-year-old woman is described. She presented a metastatic pulmonary ameloblastoma 7 years after the removal of a mandibular ameloblastoma. During routine exams, a tumor in the left lung was observed. It was asymptomatic, near to the mediastinum, measured 7x5.5 cm. Transthoracic needle biopsy revealed ameloblastoma with the same histological characteristics of the primary tumor. After radiotherapy, the patient presented regression of the tumor. The patient has been under follow-up for 5 years and there is no presence of tumor. Ameloblastoma is an aggressive tumor not only in the region of origin, but also in distant regions, mainly in cases of recurrence. Metastases can cause high rates of morbidity, a fact that requires early treatment.

Comparison between Histological Features and Strain Elastographic Characteristics in Canine Mammary Carcinomas.

Elastography is a sonographic technique that provides a noninvasive evaluation of the stiffness of a lesion. The objective of this work was to evaluate the accuracy of strain elastography, the most accessible modality in clinical practice, to discriminate between different histological types of malignant mammary neoplasms in the canine species, which can provide complementary information in real time to the diagnosis and thus help in the choice of surgical technique. A total of 34 females with 56 mammary carcinomas were selected and classified into three histological groups according to their aggressiveness. The histological and elastographic characteristics of these malignant tumors were analyzed and compared to evaluate the diagnostic accuracy of strain elastography. Visual score presented a sensitivity of 88.0%, specificity of 58.1%, and accuracy of 71.43% in distinguishing the most aggressive group of carcinomas. The strain ratio had a sensitivity of 84.0%, specificity of 61.1%, and accuracy of 69.64%. On the other hand, intratumoral strain ratio obtained a sensitivity of 71.40% and specificity of 61.90% when intratumoral fibrosis was taken as reference, with an accuracy of 66.07%. Similarly, peritumoral strain ratio was also positively related to fibrosis in the periphery of lesions (p ≤ 0.001), with a sensitivity of 93.80%, specificity of 77.50% and an accuracy of 92.87%. In conclusion, accuracy of this elastographic modality can be a useful method to differentiate more aggressive histological types. Therefore, it represents an additional diagnostic technique useful in the daily clinic thanks to the short time required for the examination, which allows real-time visualization and immediate interpretation of the results.

Patient-Derived Xenografts of High-Grade Serous Ovarian Cancer Subtype as a Powerful Tool in Pre-Clinical Research.

(1) Background. PDX models have become the preferred tool in research laboratories seeking to improve development and pre-clinical testing of new drugs. PDXs have been shown to capture the cellular and molecular characteristics of human tumors better than simpler cell line-based models. More recently, however, hints that PDXs may change their characteristics over time have begun to emerge, emphasizing the need for comprehensive analysis of PDX evolution. (2) Methods. We established a panel of high-grade serous ovarian carcinoma (HGSOC) PDXs and developed and validated a 300-SNP signature that can be successfully utilized to assess genetic drift across PDX passages and detect PDX contamination with lymphoproliferative tissues. In addition, we performed a detailed histological characterization and functional assessment of multiple PDX passages. (3) Results. Our data show that the PDXs remain largely stable throughout propagation, with marginal genetic drift at the time of PDX initiation and adaptation to mouse host. Importantly, our PDX lines retained the major histological characteristics of the original patients' tumors even after multiple passages in mice, demonstrating a strong concordance with the clinical responses of their corresponding patients. (4) Conclusions. Our data underline the value of defined HGSOC PDXs as a pre-clinical tumor model.

Machine Learning Frameworks to Predict Neoadjuvant Chemotherapy Response in Breast Cancer Using Clinical and Pathological Features.

Neoadjuvant chemotherapy (NAC) is used to treat locally advanced breast cancer (LABC) and high-risk early breast cancer (BC). Pathological complete response (pCR) has prognostic value depending on BC subtype. Rates of pCR, however, can be variable. Predictive modeling is desirable to help identify patients early who may have suboptimal NAC response. Here, we test and compare the predictive performances of machine learning (ML) prediction models to a standard statistical model, using clinical and pathological data. Clinical and pathological variables were collected in 431 patients, including tumor size, patient demographics, histological characteristics, molecular status, and staging information. A standard multivariable logistic regression (MLR) was developed and compared with five ML models: k-nearest neighbor classifier, random forest (RF) classifier, naive Bayes algorithm, support vector machine, and multilayer perceptron model. Model performances were measured using a receiver operating characteristic (ROC) analysis and statistically compared. MLR predictors of NAC response included: estrogen receptor (ER) status, human epidermal growth factor-2 (HER2) status, tumor size, and Nottingham grade. The strongest MLR predictors of pCR included HER2+ versus HER2- BC (odds ratio [OR], 0.13; 95% CI, 0.07 to 0.23; P < .001) and Nottingham grade G3 versus G1-2 (G1-2: OR, 0.36; 95% CI, 0.20 to 0.65; P < .001). The area under the curve (AUC) for the MLR was AUC = 0.64. Among the various ML models, an RF classifier performed best, with an AUC = 0.88, sensitivity of 70.7%, and specificity of 84.6%, and included the following variables: menopausal status, ER status, HER2 status, Nottingham grade, tumor size, nodal status, and presence of inflammatory BC. Modeling performances varied between standard versus ML classification methods. RF ML classifiers demonstrated the best predictive performance among all models.

The Unique Genetic and Histological Characteristics of DMBA-Induced Mammary Tumors in an Organoid-Based Carcinogenesis Model.

Here, we report a model system using in vitro 7,12-dimethylbenz[a]anthracene (DMBA; 0.6 μM)-treated mammary tissue-derived organoids generated from heterozygous BALB/c-Trp53 knockout mice to induce tumors after injection into the nude mouse subcutis. In parallel, a single oral dose of DMBA (50 mg/kg bodyweight) to the same murine strain induced mammary adenocarcinomas, characterized by biphasic structures differentiated into luminal and myoepithelial lineages and frequent Hras mutations at codon 61. In the present study, the genetic and histological characteristics of DMBA-induced tumors in the organoid-based model were evaluated to validate its similarities to the in vivo study. The organoid-derived tumors were low-grade adenocarcinomas composed of luminal and basal/myoepithelial cells. When the organoid-derived carcinomas were passaged to other nude mice, they partly progressed to squamous cell carcinomas (SCCs). Whole exome sequencing revealed no mutations at Hras codon 61 in the organoid-derived tumors. However, various mutations were detected in other genes such as Tusc3 and Tgfbr2, which have been reported as cancer-associated or homeostatic squamous cell genes. The most common mutational pattern observed in these genes were the G:C to T:A transversions and G:C to A:T transitions, which are not typical of the mutations caused by DMBA treatment. In conclusion, DMBA exhibited carcinogenicity in the both the ex vivo and in vivo mammary carcinogenesis models, albeit with distinct histological and genetical alterations. Further studies are needed to clarify whether organoid-based carcinogenesis models generated following chemical treatment in vitro could be applied to the clarification of the novel mode of action of chemical carcinogenesis.