CD44 and CD133 protein expression might serve as a prognostic factor for early occurrence castration-resistant prostate cancer.

BACKGROUND: The occurrence of castration-resistant prostate cancer (CRPC) varies in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). The rate of occurrence of CRPC may be related to the presence of prostate cancer stem cells (CSC). Thus, this study aims to evaluate the presence of CSC markers (CD44 and CD133) in histopathology tissue at the time of diagnosis and their correlation with the occurrence of CRPC in patients with advanced PCa within 2 years of ADT. METHOD: A retrospective case-control study was conducted to evaluate the incidence of CRPC within 2 years. The inclusion criteria were patients with PCa who had received treatment with ADT and a first-generation anti-androgen (AA) for 2 years. We classified patients based on whether they developed CRPC within 2 years (CRPC) of the therapy or did not experience CRPC within 2 years (non-CRPC) of the therapy. We performed immunohistochemical (IHC) staining for CD44 and CD133 on the prostate biopsy tissue samples. RESULTS: Data were collected from records spanning 2011-2019. We analyzed a total of 65 samples, including 22 patients with CRPC and 43 patients with non-CRPC who had received treatment with LHRH agonists and AA for up to 2 years. Our findings showed a significant H-score difference in CD44 protein expression between CRPC prostate adenocarcinoma samples 869 (200-1329) and non-CRPC 524 (154-1166) (p = 0.033). There was no significant difference in CD133 protein expression between the two groups (p = 0.554). However, there was a significant difference in the nonoccurrence of CRPC between the high expressions of both CD44 and CD133 groups with other expressions of CD44/CD133 groups (25% vs. 75%; p = 0.011; odds ratio = 4.29; 95% confidence interval [1.34, 13.76]). CONCLUSION: This study found a low expression of at least one CD44/CD133 protein in the patients without early occurrence of CRPC. This result might suggest that CD44/CD133 may function as a potential prognostic marker for PCa, especially in a low expression, to identify patients who have a better prognosis regarding the occurrence of early CRPC.

A multidisciplinary approach of a patient with pheochromocytoma presenting as recurrent acute fulminant myocarditis: A rare case report and comprehensive review of literature.

Fulminant myocarditis (FM) is a rare illness characterized by abrupt and severe widespread cardiac inflammation, which frequently results in mortality due to cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Pheochromocytoma is an uncommon and difficult-to-diagnose cause of FM, and it is associated with a significant risk of recurrent acute myocarditis. There is, however, little information on reoccurring acute FM. Herein, we report a rare case of recurrent acute FM due to pheochromocytoma. We present the case of a 22-year-old woman who was admitted to our hospital three days previously with acute dyspnea. Five months prior, the patient was diagnosed with post-acute myocarditis, and a massive tumor on the right adrenal gland was discovered, which lead to pheochromocytoma diagnosis. In this present admission, following the exclusion of infection, autoimmune, and metabolic derangements, pheochromocytoma was presumed to be the reason for the recurrence and more severe acute FM during the current hospitalization. The patient responded favorably to high-dose steroids combined with heart failure therapy regimens. To detect recurrent acute myocarditis related to pheochromocytoma, a multidisciplinary approach was used, including several laboratory biomarkers and imaging findings. Following pheochromocytoma removal and biopsy, the patient recovered satisfactorily. Our findings may provide beneficial contributions to the literature as pheochromocytoma is an uncommon but important cause of recurrent acute myocarditis. A multidisciplinary approach is essential in identifying acute FM and determining the underlying causes of this malady.

Giant cementoblastoma involving multiple teeth: A rare case report and review of differential diagnoses.

Cementoblastoma, a rare odontogenic benign tumor characterized by calcified cementum-like deposits produced by cementoblasts fused with the tooth root, represents a minute proportion of all odontogenic tumors, with a prevalence ranging from less than 1% to 6.2%. We present a case of a 19-year-old female experiencing pain, progressive swelling, and facial asymmetry in the left lower region over the 1 year ago. Physical examination revealed diffuse swelling in the left mandibular area, demonstrating tenderness and bony hardness on palpation. Radiographic findings displayed a giant, well-defined, relatively round, radiopaque mass, partially delineated by a thin radiolucent halo, and adhered to the roots of the teeth. Computed Tomography imaging revealed an osteoblastic hyperdense mass with extensive buccal and lingual extension. Sagittal images illustrated the mass's continuity with the root apex of the first molar, accompanied by a well-defined hypodense border. A biopsy confirmed the diagnosis of cementoblastoma, leading to the patient undergoing a left hemimandibulectomy. Given the various periapical radiopaque lesions that serve as potential differential diagnoses for cementoblastoma, the ability of the radiologist to distinguish their imaging characteristics plays a crucial role in determining an accurate diagnosis.

Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression.

The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This retrospective study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive models for BRAFV600E and RAS-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the BRAF and RAS genes. Multivariate logistic regression was employed to develop prediction models. Independent predictors of the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology subtype, and pERK1/2 levels exceeding 10% (X2 = 0.128, p > 0.05, AUC = 0.734, p < 0.001). The RAS mutation predictive model includes follicular histology subtype and pERK1/2 expression > 10% (X2 = 0.174, p > 0.05, AUC = 0.8, p < 0.001). We propose using the prediction model concurrently with four potential combination group outcomes. PTC cases included in a combination of the low-BRAFV600E-scoring group and high-RAS-scoring group are categorized as RAS-like (adjOR = 4.857, p = 0.01, 95% CI = 1.470-16.049). PTCs included in a combination of the high-BRAFV600E-scoring group and low-RAS-scoring group are categorized as BRAF-like PTCs (adjOR = 3.091, p = 0.001, 95% CI = 1.594-5.995). The different prediction models indicate variations in biological behavior between BRAF-like and RAS-like PTCs.

Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital.

Introduction: BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics. Methods: Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics. Results: Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048-10.259), tall-cell variants (p ≤0.001, OR: 41.143; 95% CI: 11.979-141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008-8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018-3.592), extrathyroidal extension (p = <0.001, OR: 3.983; 95% CI: 1.970-8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224-4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690-18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161-5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052-7.940) were associated with RAS mutations. Conclusion: A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.

A Rare Case of Ruptured Malignant Ovarian Brenner Tumor.

BACKGROUND Ovarian cancer is the leading cause of death in women with gynecological cancers. Ovarian Brenner tumor (BT) is an extremely rare type of epithelial ovarian cancer that accounts for about 1-3% of all ovarian cancers. Herein, we report a rare case of ruptured malignant ovarian Brenner tumor. CASE REPORT A 39-year-old P0A0 woman came to the Emergency Department (ED) with abdominal pain and tenderness. Perforated appendicitis was initially suspected and an emergency laparotomy was performed by the General Surgery Department. Then, a 25×20×15 cm grayish cystic mass originating from the right adnexa was found. We consulted intraoperatively with the Gynecology Oncology Department and decided to perform complete surgical staging. Histopathological examination confirmed the diagnosis of malignant Brenner tumor (MBT). The patient was then given adjuvant chemotherapy with a paclitaxel carboplatin regimen. In this case report, we present our case along with a review of the current literature regarding the diagnosis and therapy of malignant Brenner tumor. CONCLUSIONS Ovarian MBT is an extremely rare ovarian cancer. Diagnosing MBT can be challenging as there are no clinical, laboratory, or imaging features typical for it. Surgery is the mainstay treatment in MBT cases. The role of adjuvant chemotherapy in MBT is still being debated.

Multiple intracranial metastasis from lung adenocarcinoma in a pregnant young woman: A case report.

Lung cancer remains one of the leading causes of cancer-related deaths in both men and women worldwide. Although its occurrence during pregnancy is rare, it is fast becoming an emerging issue globally. Lung cancer is exceedingly rare in young individuals but is distinct, with adenocarcinoma and stage IV presentation being the most common features. This study presents the case of a 30-year-old woman who came to the emergency department with headache, loss of sensation in the left side of the body, progressing diplopia, and diabetes insipidus that first appeared when the patient was 6-month pregnant. Clinical examination showed right cranial nerve III paresis, bitemporal hemianopsia, and left hemiparesis, while MRI indicated multiple intracranial metastases proven by pathology anatomy. This study highlights the role of imaging in assessing lung adenocarcinoma with intracranial metastasis in a young pregnant woman.

Prospect of Exosome in Ligament Healing: A Systematical Review.

Aim: The relationship between ligaments and bone is a complex and heterogeneous junction involving bone, mineralized fibro cartilage, non-mineralized fibro cartilage and ligaments. Mesenchymal stem cells (MSC) can be used in vivo to control inflammation and aid in tissue repair, according to studies. This review focused on using exosomes as an alternative to MSC, as a cell-free therapy for modulating the remodelling process. Methods: To conduct a systematic review of the literature, the phrases "exosome" and "ligament" or "tendon" and "extracellular vesicle" and "stem cells" were used as the search keywords in PubMed (MEDLINE), OVID, the Cochrane Library, and Science Direct. From the literature, 73 studies in all were found. Six studies were included in this systematic review after full-text evaluation. Results: Six included studies covered a range of MSC types, isolation techniques, animal models, and interventions. Biomechanical results consistently indicated the beneficial impact of conditioned media, vesicles, and exosomes on treating tendons and ligaments. Noteworthy findings were the reduction of inflammation by iMSC-IEVs, chondrocyte protection by iPSC-EVs (extracellular vesicles generated by inflammation-primed adipose-derived stem cells), osteolysis treatment using DPSC-sEVs (small extracellular vesicles derived from dental pulp stem cells), and the contribution of exosome-educated macrophages to ligament injury wound healing. Conclusion: Exosomes may serve as a cell-free therapeutic substitute for modulating the remodelling process, particularly in ligament healing.

High-Risk Histopathologic Features of Retinoblastoma Treated at a Tertiary Hospital in West Java, Indonesia.

PURPOSE: To evaluate the histopathological characteristics of clinically advanced retinoblastoma (RB) and its relationship with tumor differentiation. METHODS: This was a cross-sectional study of primary enucleated group D/E intraocular RB using medical records from 2017 to 2020 in a tertiary referral hospital. Cases with incomplete histopathological results were excluded. Tumors were classified into well, moderately, and poorly differentiated and undifferentiated. High-risk histopathological features were classified as per Thaung and Karaa [Community Eye Health. 2018;31(101):17-3]. RESULTS: This study included 121 patients (129 eyes), of which 32.2% were diagnosed at 25-36 months. High-risk features (HRFs) were found in 100/129 eyes, and of 73 complete histopathological results, the 2 most common HRFs were postlaminar optic nerve invasion and massive choroidal invasion. RB was poorly differentiated in 69.9% and well differentiated in 12.3% of eyes. There was no statistically significant association between any HRFs and tumor differentiation, with age >2 years associated with tumor differentiation (p < 0.05). CONCLUSION: The frequency of HRFs is 77.5% of primary enucleated eyes, mainly poorly and undifferentiated cells, particularly in children aged >2 years old.

Programmed death ligand-1 protein expression difference in basal like and non-basal like triple negative breast cancer and its association with disease free survival and overall survival: A systematic review.

The study aims to summarize the literature and explore the strength of evidence for PD-L1 expression difference in basal like TNBC and non-basal like TNBC, and association of PD-L1 expression with disease free survival and overall survival in each group. A systematic search of the original research literature through November 29th, 2020, reported according to PRISMA guideline. Eligible studies investigated must have a primary outcome and at least one secondary outcome. Two reviewers independently searched, selected, and assessed quality of studies and risk of bias. Any discrepancies will be resolved by consensus or by consulting a third and fourth author. A total of 6813 articles were screened from which five articles were selected and assessed for quality of studies and risk of bias. Of 5 articles, no similar findings are found regarding the level of PD-L1 expression and its correlation with recurrence and overall survival. There is not enough substantial evidence to support the difference PD-L1 protein expression level in basal and non-basal like TNBC and its association with recurrence and overall survival. Hence, further studies are needed specifically to focus on this problem.

High Immunoexpression of COX-2 as a Metastatic Risk Factor in ccRCC without PD-L1 Involvement.

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most lethal type of malignancy of the urinary tract system as it is resistant to chemotherapy and radiation and has a survival rate of less than 5% in cases of metastasis. Inflammation plays an essential role in the metastasis of ccRCC. Cyclooxygenase-2 (COX-2) is an inflammatory protein that affects the processes of carcinogenesis, invasion, migration, metastasis, and angiogenesis. COX-2 can modulate programmed death ligand-1 (PD-L1) expression and play a role in immune evasion, meaning that tumor cells are able to escape the body's immune response and more easily metastasize. PURPOSE: This study aims to determine the role of COX-2 and PD-L1 in the occurrence of ccRCC metastases. MATERIALS AND METHODS: This study is an observational analytical study, which employed a cross-sectional approach to examine the paraffin block samples of 40 ccRCC cases from Dr. Hasan Sadikin Hospital Bandung, Indonesia, between 2014 and 2021. Immunoexpression was measured using immunohistochemical staining for COX-2 in tumor cells and for PD-L1 in immune cells. PD-L1 calculation was measured using Qupath 0.2.3. digital software. Metastatic data were obtained using radiological imaging and pathological examinations. Meanwhile, the data were analyzed using the chi-square test for COX-2 and Fischer's exact test for PD-L1. RESULTS: The research results revealed a significant association between COX-2 and the occurrence of metastases in ccRCC (p=0.001) with a prevalence odds ratio of 10.28. Positive PD-L1 immunoexpression of the immune cells (≥1%) was found in 14% (3/21) of the metastatic group and 5% (1/19) of the non-metastatic group (p=0.607). There was no association between COX-2 and PD-L1 immunoexpression (p=0.278). CONCLUSION: This study shows that metastases in ccRCC patients are ten times as likely to be associated with high COX-2 immunoexpression than low COX-2 immunoexpression. COX-2 plays a role in the process of ccRCC metastasis without PD-L1 involvement.

A Rare Case of Early Transformation of Gestational Trophoblastic Neoplasia Following Molar Pregnancy.

BACKGROUND Gestational trophoblastic disease (GTD) encompasses a group of disorders that arise from abnormal growth of trophoblastic tissue. The spectrum of GTD includes 2 major groups: benign and malignant. The benign form is a hydatidiform mole, either complete or partial; the malignant forms, referred to as gestational trophoblastic neoplasia (GTN), consist of invasive moles, choriocarcinomas, placental site trophoblastic tumors, and epithelioid trophoblastic tumors. Most patients who undergo evacuation of a hydatidiform mole by curettage have a disease-free period before a new tumor develops that can be considered malignant. In rare cases, metastasis occurs rapidly and manifests coincidentally before the hydatidiform mole can be evacuated. CASE REPORT A 19-year-old woman in Bandung City, West Java, Indonesia, was diagnosed with a molar pregnancy with early evidence of a mass in her vagina that was suspicious for stage II GTN. The early emergence of a vaginal mass was a rare case of early transformation of a molar pregnancy into GTN. CONCLUSIONS Careful evaluation is warranted of patients with characteristics typical of an intrauterine molar pregnancy who have an early presentation of a vaginal mass because of the possibility that the diagnosis could be GTN.

Comparison of Fixation Methods for Preservation Cytology Specimens of Cell Block Preparation Using 10% Neutral Buffer Formalin and 96% Alcohol Fixation in E-cadherin and Ki-67 Immunohistochemical Examination.

BACKGROUND: Cytological and molecular examinations are among the most important examinations in cancer diagnosis. 96% alcohol is a fixative solution commonly used by clinicians for cytological samples because of its accessibility and affordability. Cellblock preparation from cytology specimen may increase morphology detail and may be used for further biomarker analysis. E-cadherin is an adhesion protein expressed in the cell membrane of most carcinoma. Ki67 is a protein expressed in nuclei of malignant cells that used as a proliferation marker. AIM: This study was designed to investigate the effect of fixation duration in 96% alcohol on protein preservation for immunohistochemistry (IHC) evaluation compared to 10% neutral buffered formalin (NBF) as the gold standard. METHODS: Twenty-five fine-needle aspiration biopsy (FNAB) specimen diagnosed as carcinoma were fixed in 10% NBF and 96% alcohol for 1 hour, 6 hours, 24 hours, 48 hours and 72 hours. Cell blocks preparation were made from those 6 groups of specimens. E-cadherin and Ki67 IHC were done to cell blocks section and evaluated. The data were statistically analysed using the Friedman test with p-value < 0.05 of a significant level. RESULTS: There were significant differences between E-cadherin and Ki67 expression in cell block preparation from 96% alcohol-fixed cytology specimen for 1 hour, 6 hours, 24 hours, 48 hours and 72 hours to 10% NBF (p = 0.0001). CONCLUSION: The result indicated that 96% alcohol is not suitable as a fixative solution for cell block preparation in E-cadherin and Ki-67 IHC examination.

The Role of Osteocalcin and Alkaline Phosphatase Immunohistochemistry in Osteosarcoma Diagnosis.

BACKGROUND: The diagnosis of Osteosarcoma (OSA) is not always straightforward. OSA may resemble Other Primary Bone Tumours (OPBT). The diagnosis of osteosarcoma is sometimes difficult especially in a very small specimen. Immunohistochemistry is one of ancillary testing types that can help the diagnosis of many tumours. The aim of this study was to evaluate the validity of Osteocalcin (OCN) and Alkaline Phosphatase (ALP) immunohistochemistry in discriminating OSA from OPBT. METHOD: This study included 50 selected human primary bone tumours, 25 cases of OSA and 25 cases of OPBT. Immunohistochemical evaluation of OCN and ALP was done for all cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. RESULT: The mean age of OSA and OPBT patients was 19.6 ± 13.6 and 40.0 ± 16.3 years, respectively. Osteocalcin was positive in 17/25 (68%) cases of OSA and 16/25 (64%) cases of OPBT (p = 0.061). Alkaline Phosphatase was positive in 24/25 (96%) cases of OSA and 5/25 (20%) cases of OPBT (p < 0.001). The sensitivity of OCN in OSA diagnosis was 68%, with specificity, PPV, NPV, and overall accuracy being 36%, 52%, 53%, and 52%, respectively. The sensitivity of ALP in OSA diagnosis was 96%, with specificity, PPV, NPV, and overall accuracy being 80%, 82.7%, 95.2%, and 88%, respectively. CONCLUSION: ALP immunohistochemistry is useful in discriminating OSA from OPBT. ALP is superior to OCN in OSA diagnosis. OCN cannot be used to differentiate between OSA and OPBT.

Cystic pilomyxoid astrocytoma on suprasellar region in 7-year-old girl: Treatment and strategy.

Pilomyxoid astrocytoma (PMA) is a recently described entity with similar features to pilocytic astrocytoma but with a rare occurrence. As a new diagnosis, no treatment guideline of PMA has been established; but generally, as for any low-grade gliomas, radical resection is performed if the location is favorable. In this report, we wished to share our experience treating the PMA. The authors presented a case of a 7-year-old girl with bitemporal hemianopia. From the history, the patient had a 4-month history of headache, following with nausea and projectile vomiting 1 week before hospital admission. Past history of seizure, weakness of left extremities, and decreased consciousness were reported. Computed tomography (CT) scanning showed acute obstructive hydrocephalus and an isohypodense mass at suprasellar region with the cystic component. We performed ventriculo-peritoneal-shunt to reduce the acute hydrocephalus, followed by craniotomy tumor removal 2 weeks later. The patient underwent radiotherapy and medical rehabilitation. Diagnosis of PMA was made on the basis of pathologic anatomy result, which showed a myxoid background with pseudorosette. Postoperative CT showed a residual tumor at right parasellar area without hydrocephalus. After the surgery, the treatment was followed with radiotherapy for 20 times within 2 months. Postradiation CT performed 1-year later showed a significant reduction of the tumor mass. There were no new postoperative deficits. The patient had improvement of the visual field and motor strength. The authors reported a case of a 7-year-old girl with PMA. Surgical resection combined with radiotherapy was performed to control the growth of PMA. More observation and further studies are required to refine the treatment methods.