Malignant Transformation Research Articles

Hepatocellular adenoma update: diagnosis, molecular classification, and clinical course.

Hepatocellular adenomas (HCA) are acquired focal liver lesions, that occur mainly in young-to-middle-aged women who are on long-term estrogen-containing contraceptives or young men after prolonged use of anabolic steroids. Furthermore, distinct underlying diseases, such as obesity, metabolic dysfunction-associated steatotic liver disease, glycogen storage disease, etc. are considered risk factors. The 2017 Bordeaux classification, in particular Nault et al, divided HCAs into eight subtypes according to their pheno- and genotypic characteristics. This includes HCAs with hepatocyte-nuclear-factor (HNF1-alpha mutation), HCAs with β-catenin mutation, and HCAs without either of these genetic mutations, which are further subdivided into HCAs with and without inflammatory cells. HCAs should no longer be classified as purely benign without histologic workup since three of the eight subtypes are considered high-risk lesions, requiring adequate management: malignant transformation of the pure (ßex3-HCA) and mixed inflammatory/β-catenin exon 3 (ßex3-IHCA) adenomas, as well as potential bleeding of the sonic hedgehog HCA and pure (ßex7/8-HCA) and mixed inflammatory/β-catenin exon 7/8 (ßex7/8-IHCA). Elective surgery is recommended for any HCA in a male, or for any HCA exceeding 5 cm. Although MRI can classify up to 80% of adenomas, if findings are equivocal, biopsy remains the reference standard for adenoma subtype.

Oral Lichen Planus: A Narrative Review Navigating Etiologies, Clinical Manifestations, Diagnostics, and Therapeutic Approaches.

Background/Objectives: Oral Lichen Planus (OLP) is a common immune-mediated inflammatory disorder affecting the oral mucosa, impacting 0.5% to 2% of the global population, primarily middle-aged women. Immunological dysregulation is a key factor in OLP's pathogenesis, involving CD4+ T helper and CD8+ T cytotoxic cells. The World Health Organization (WHO) classifies OLP as a potentially malignant disorder, with a risk of oral squamous cell carcinoma (OSCC) developing in up to 2% of lesions. This narrative review aims to provide a comprehensive overview of the etiopathogenesis, clinical manifestations, diagnostic criteria, and therapeutic strategies for OLP, informing clinical practice and guiding future research. Methods: A review of the literature from the PubMed and Google Scholar databases was conducted up to December 2023, focusing on studies addressing the etiopathogenesis, diagnosis, clinical manifestations, and treatment of OLP. Results: OLP's pathogenesis is driven by immune dysregulation, with CD4+ and CD8+ cells playing crucial roles. Clinically, OLP presents as reticular, erosive, bullous, and plaque-like lesions. Diagnosis relies on clinical examination, histopathology, and direct immunofluorescence. Recent advancements in diagnostic markers and imaging techniques have improved detection and monitoring. Treatment primarily involves corticosteroids, but novel therapies such as curcumin, retinoids, and laser therapy are increasingly used for their effectiveness and reduced side effects. These treatments show promise in symptom reduction and recurrence prevention, although long-term data are needed. Conclusions: Regular screenings and biopsies are essential due to OLP's likelihood of malignant transformation. This study urges further investigation into long-term results, improved diagnostic techniques, and evidence-based treatment regimens.

Beyond mere appendicitis: A case report on an unforeseen diagnosis of appendiceal schwannoma

IntroductionAppendiceal schwannomas are a rare diagnosis, with little evidence to guide management and follow-up. There are currently no case reports focusing on follow-up for appendiceal schwannomas after complete surgical resection. Presentation of caseA 64-year-old female presented to the emergency department, febrile, with migratory right iliac fossa pain and focal peritonism, consistent with acute appendicitis. The diagnosis was supported by a computed tomography scan and she underwent a laparoscopic appendicectomy. Histopathology was reported as acute appendicitis associated with a schwannoma at the appendiceal base. The patient underwent a colonoscopy six weeks after her initial surgery with no abnormal findings. Following multidisciplinary team discussion it was decided that no further follow up was required. DiscussionThere are only 15 case reports of appendiceal schwannomas in the literature. As a result, the management and follow up in this case was guided from evidence reported in studies of other schwannomas elsewhere in the gastrointestinal tract, standard management of benign appendiceal lesions and MDT discussion. One retrospective single-centre cohort study of histopathology records collected over a 20 year period showed that in 44 patients with GI schwannomas, there was no malignant transformation or recurrence during a mean follow up period of 5.0 ± 4.31 years (Singh et al., 2022). Based on this study there is a very low risk of malignant transformation associated with these lesions. ConclusionBased on limited published data resection remains the mainstay of management of appendiceal schwannomas. Colonoscopy is recommended to exclude any underlying lesion or synchronous pathology.

Long-standing pleomorphic adenoma in hard palate: A rare case report

Background: Pleomorphic adenoma (PA) is the most common benign tumor of the parotid gland, followed by the submandibular gland, and rarely in the minor salivary glands. However, it has the potential to turn malignant. The minor salivary gland in the hard palate is a rare site for PA. Purpose: This report aims to describe the clinical and histopathology findings and treatment with surgical excision of long-standing PA on the hard palate. Case: 40-year-old woman with an asymptomatic 6 x 4 x 4 cm hard palate tumor mass that had remained untreated for ten years and had no preceding trauma. Case Management: The tumor mass was removed surgically by creating an excision opening of 2–3 mm between the mass margin and the maxillary bone periosteum, extending to the posterior palate. Histopathology findings confirmed the diagnosis of PA in the minor salivary gland and revealed typical characteristics associated with malignant transformation. Observation after one month showed that the surgical wound had healed, and no symptoms of recurrence were visible. Conclusion: PA is a benign salivary gland tumor that has the potential to expand extensively. Appropriate surgical excision can improve the prognosis.

Transcriptomic analysis reveals transcription factors implicated in radon-induced lung carcinogenesis.

Radon, a potent carcinogen, is a significant catalyst for lung cancer development. However, the molecular mechanisms triggering radon-induced lung cancer remain elusive. Utilizing a radon exposure concentration of 20,000Bq/m3 for 20min/session, malignant transformation was induced in human bronchial epithelial cells (BEAS-2B). Radon-exposed cells derived from passage 25 (BEAS-2B-Rn) exhibited enhanced proliferation and increased colony formation. Analysis of differential gene expression (DEG) through transcription factors revealed 663 up-regulated and 894 down-regulated genes in radon-exposed cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant alterations in the malignant transformation pathway of cells, including those related to cancer and the PI3K/AKT signaling pathway. A PPI network analysis indicated a significant association of oncogenes, such as CCND1, KIT, and GATA3, with lung cancer among differentially expressed genes. In addition, the stability of the housekeeping gene was determined through RT-qPCR analysis, which also confirmed the results of transcriptome analysis. The results suggest that transcription factors may play a pivotal role in conferring a survival advantage to radon-exposed cells. This is achieved by malignant transformation of human bronchial epithelial cells into lung carcinogenesis cell phenotypes.

Dual Heterotropic Tissue Associated with a Type IV A Choledochal Cyst: A Rare Case Report

Abstract A choledochal cyst (CC) is one of the rare congenital diseases of the biliary tract and is more common in females. The association of ectopic pancreatic and splenic tissue with CC is an extremely rare condition. An 11-year-old girl child presented with a vague abdominal lump and intermittent dull abdominal pain for 5 months with early satiety and weight loss in the current case scenario. Her laboratory findings were normal. A type IV CC was discovered on ultrasonography, and the distal common bile duct displayed significant cystic dilatation on magnetic resonant cholangiopancreatography. After the CC was surgically removed, it was sent for histopathological examination. Sections revealed dual heterotropic elements, which included pancreatic and splenic tissues in a CC. It was very uncommon for both to exist independently in the CC and in this instance, both were observed together. This will be the first documented case, in which the CC contained dual ectopic tissue from the spleen and pancreas. Ectopic splenic tissue in the CC has never been documented in the literature. It is crucial to be aware of this entity when splenic or pancreatic tissue experiences changes due to inflammation, even though its clinical significance is uncertain. In the ectopic rests, bleeding, blockage, and malignant transformation are the possible outcomes.

DDHD2 is involved in the malignant progression of early luminal A breast cancer by changing cell membrane proteins and immune responses functionality

Abstract Background Luminal A breast cancer has the best prognosis of all malignant breast cancer types. In clinical practice, some patients with luminal A breast cancer present with small tumors (usually <20 mm) but with lymph node metastases or even distant organ metastasis. Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence, there is a significant gap in research on luminal A breast cancer with high invasiveness. This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms. Methods In this study, we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2 (DDHD2). We then evaluated the association between DDHD2 expression and patient prognosis, genetic material changes, and transcriptional, translational, and immune responses in luminal A breast cancer. We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms. Results The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases. Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration, regulating cell proliferation and apoptosis cycles, and suppressing immune responses. Moreover, a pathway through which DDHD2 inhibited immunity was preliminarily verified. Conclusions The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer. Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition, DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.

Malignant transformation of craniofacial fibrous dysplasia: A clinicopathological, immunohistochemical and molecular analysis of 15 cases in one single institution

ObjectiveMalignant transformation of craniofacial fibrous dysplasia (FD) is not common and its clinicopathological as well as molecular characteristics remain largely unknown with limited literature reports. Study designPatients diagnosed with FD including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD), accompanied by malignant transformation at our institution over the past 18 years (2005–2023) were retrospectively screened and analyzed to investigate the epidemiology and clinicopathological features of these tumors. ResultsThree hundred and five patients were diagnosed as FD in our hospital from 2005 to 2023, with 176 females (57.7 %) and 129 males (42.3 %). The average age at diagnosis was 28.35 years, ranging from 7 to 70 years. A total number of 15 (4. 9 %) cases of FD with malignant transformation were selected. Among these 15 patients, the age of the initial diagnosis of FD ranged from 6 to 54 years (mean age 28.87 ± 16.77), and the ages when malignant transformation occurred ranged from 18 to 57 years (mean age 38.53 ± 13.05). Among 15 patients, 12 patients were female (80 %) and 3 were male (20 %). Fifteen cases included MSA in 2 patients, PFD in 4 patients, and MFD in 9 patients. Of the anatomical sites in craniofacial bones, the most common site of the lesion was the maxilla, followed by the mandible. Malignant neoplasm arising in FD were osteosarcoma (12/15), chondrosarcoma (1/15) and high-grade sarcoma of uncertain differentiation (2/15). The 3- and 5-year overall survival rate was 33.3 % (5/15) and 20 % (3/15) respectively. In secondary osteosarcoma from FD, MDM2 and CDK4 positivity were 33.3 % and 41.7 % respectively, and only one case was MDM2-amplified and CDK4-amplified. ConclusionMalignant transformation in fibrous dysplasia was an exceedingly rare event and with a female predominance. The overall survival rate was poor. Osteosarcoma was the most common malignant neoplasm arising in FD. MDM2 and CDK4 expression may aid in the diagnosis of secondary osteosarcoma in FD.

Genetic variants of Nuclear Factor-Kappa B were associated with different outcomes of Hepatitis C virus infection among Egyptian patients.

Hepatitis C virus (HCV) is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC). Nuclear factor kappa B (NF-κB) is a transcription factor that functions in health and disease. Genetic variants of the NF-κB gene can affect its function and are associated with chronic inflammatory changes and malignant transformation. This case-control study is aimed to determine the possible association between NF-κB genetic variants and different outcomes of HCV infection among Egyptian patients. 295 subjects were recruited with allocation of participants in the representative group according to results of serological and molecular tests. Patients in the case group (group A) were further divided into three subgroups; subgroup I, mild chronic HCV, subgroup II, cirrhosis, and subgroup III, HCC subgroups (59 for each subgroup), group B included participants who experienced spontaneous viral clearance (n=59). All were compared to matched healthy control subjects, Group C (n=59). All participants were genotyped for NF-κB polymorphisms, rs11820062 by TaqMan assay and rs28362491 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Risk analysis indicated that subjects carrying the rs11820062 A genotype are more susceptible to HCV infection (OR: 3.1; 95%, CI= 1.4-6.9). Subjects carrying the rs28362491 insertion genotype are at more risk of progression to cirrhosis when compared to healthy-controls and patients with mild chronic HCV (OR:7.7; 95% CI=2.4-24.3 and OR:5.1, 95% CI= 1.7-15.7, respectively) and also are at more risk of developing HCC when compared to healthy controls (OR:2.6; 95% CI= 0.94-7.3). Polymorphisms affecting NF-κB different genes would modulate HCV infection susceptibility and clinical disease progression among Egyptian patients.

Clinical relevance of subtyping CTNNB1‐mutated hepatocellular adenomas: Different risk patterns according to the mutation type

AbstractBackground and AimsBeta‐catenin‐activated hepatocellular adenomas (b‐HCA) with exon 3 (ex3) non‐S45, ex3 S45 or ex7/8 mutations display different glutamine synthetase (GS)‐immunostaining patterns; the latter two show a GS‐positive/CD34‐negative rim contrasting with diffuse CD34 in the HCA core. Our objective was to determine whether discriminating the three b‐HCA mutation subtypes is clinically relevant.MethodsWe analysed the clinicopathological data of the three b‐HCA subtypes (37 resected cases) and compared it with the corresponding subtypes of beta‐catenin‐activated inflammatory HCA (b‐IHCA, 40 cases).ResultsThe mean age of b‐HCA ex7/8 and ex3 S45 were 25.9 and 27.3 years respectively. Clinical bleeding occurred in 67% and 63%, including five cases of pregnant women; malignant transformation was not observed in these two subtypes. The mean age of the b‐HCA ex3 non‐S45 subtype (41 years) was significantly higher; clinical bleeding occurred in 14% while all cases contained malignancy. Such differences in age and clinical complications were not found in the b‐IHCA subtypes. Additionally, we found abnormal vessels in b‐HCA ex3 S45 and ex7/8, near the GS+/CD34− rim, which was not seen in ex3 non‐S45. These vessels can function as an adjunct to discriminate between the b‐HCA subgroups.ConclusionIn our series, b‐HCA ex7/8 and ex3 S45 patients are significantly younger and have higher clinical bleeding risk than b‐HCA ex3 non‐S45 patients who have a higher malignant risk. Hence, in b‐HCA, due to the differences in clinical complications, it is clinically relevant to identify all three subtypes individually.

Early drivers of clonal hematopoiesis shape the evolutionary trajectories of de novo acute myeloid leukemia.

Mutations commonly found in AML such as DNMT3A, TET2 and ASXL1 can be found in the peripheral blood of otherwise healthy adults - a phenomenon referred to as clonal hematopoiesis (CH). These mutations are thought to represent the earliest genetic events in the evolution of AML. Genomic studies on samples acquired at diagnosis, remission, and at relapse have demonstrated significant stability of CH mutations following induction chemotherapy. Meanwhile, later mutations in genes such as NPM1 and FLT3, have been shown to contract at remission and in the case of FLT3 often are absent at relapse. We sought to understand how early CH mutations influence subsequent evolutionary trajectories throughout remission and relapse in response to induction chemotherapy. Here, we assembled a retrospective cohort of patients diagnosed with de novo AML at our institution that underwent genomic sequencing at diagnosis as well as at the time of remission and/or relapse (total n = 182 patients). Corroborating prior studies, FLT3 and NPM1 mutations were generally eliminated at the time of cytologic complete remission but subsequently reemerged upon relapse, whereas DNMT3A, TET2 and ASXL1 mutations often persisted through remission. Early CH-related mutations exhibited distinct constellations of co-occurring genetic alterations, with NPM1 and FLT3 mutations enriched in DNMT3A mut AML, while CBL and SRSF2 mutations were enriched in TET2 mut and ASXL1 mut AML, respectively. In the case of NPM1 and FLT3 mutations, these differences vanished at the time of complete remission yet readily reemerged upon relapse, indicating the reproducible nature of these genetic interactions. Thus, early CH-associated mutations that precede malignant transformation subsequently shape the evolutionary trajectories of AML through diagnosis, therapy, and relapse.

The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCCarising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant. Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.

Today's cancer research and treatment - highly sophisticated and molecularly targeted, yet firmly bolstered in the classical theories.

Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

Performance of explainable artificial intelligence in guiding the management of patients with a pancreatic cyst

Background/objectivesPancreatic cyst management can be distilled into three separate pathways – discharge, monitoring or surgery– based on the risk of malignant transformation. This study compares the performance of artificial intelligence (AI) models to clinical care for this task. MethodsTwo explainable boosting machine (EBM) models were developed and evaluated using clinical features only, or clinical features and cyst fluid molecular markers (CFMM) using a publicly available dataset, consisting of 850 cases (median age 64; 65 % female) with independent training (429 cases) and holdout test cohorts (421 cases). There were 137 cysts with no malignant potential, 114 malignant cysts, and 599 IPMNs and MCNs. ResultsThe EBM and EBM with CFMM models had higher accuracy for identifying patients requiring monitoring (0.88 and 0.82) and surgery (0.66 and 0.82) respectively compared with current clinical care (0.62 and 0.58). For discharge, the EBM with CFMM model had a higher accuracy (0.91) than either the EBM model (0.84) or current clinical care (0.86). In the cohort of patients who underwent surgical resection, use of the EBM-CFMM model would have decreased the number of unnecessary surgeries by 59 % (n = 92), increased correct surgeries by 7.5 % (n = 11), identified patients who require monitoring by 122 % (n = 76), and increased the number of patients correctly classified for discharge by 138 % (n = 18) compared to clinical care. ConclusionsEBM models had greater sensitivity and specificity for identifying the correct management compared with either clinical management or previous AI models. The model predictions are demonstrated to be interpretable by clinicians.

Risk factors for long-term urination and sexual function impairment following laparoscopic resection of presacral lesions

BACKGROUNDPresacral cysts are rare congenital lesions predominantly affecting females. Surgery is often recommended after diagnosis due to the risk of malignant transformation and complications associated with cyst enlargement. Laparoscopic excision is increasingly favored due to its enhanced visualization and precision.AIMTo assess long-term urinary, sexual function outcomes and quality of life in female patients undergoing laparoscopic resection of presacral cysts.METHODSWe conducted a retrospective review of female patients who underwent laparoscopic resection of presacral cysts between August 2012 and May 2020. Patient demographics, surgical outcomes, and postoperative complications were analyzed. The urinary function was assessed using the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Module (ICIQ-FLUTS), the sexual function was evaluated using the Female Sexual Function Index (FSFI), and quality of life was assessed using the 36-item Short-Form Health Survey (SF-36).RESULTSAmong the 32 female patients included, 10 experienced postoperative urinary incontinence, predominantly of the mixed type. The risk factors for urinary incontinence included abdominal distension and the proximity of the cyst to the rectum. Notably, urinary incontinence significantly impacted the overall lower urinary tract symptoms and quality of life. Additionally, seven patients reported postoperative sexual dysfunction, with previous abdominal or pelvic surgery and cyst location under S3 identified as risk factors, affecting the mental health aspects of their quality of life.CONCLUSIONLaparoscopic cyst resection in females poses risks of urinary and sexual dysfunction, potentially impacting quality of life. Thus, tailored management approaches are crucial.

Circ_0025373 inhibits carbon black nanoparticles-induced malignant transformation of human bronchial epithelial cells by affecting DNA damage through binding to MSH2

Carbon black nanoparticles (CBNPs) have been demonstrated to induce DNA damage in epithelial cells. However, the potential of the damage to initiate carcinogenesis and the underlying mechanism remain poorly understood. Therefore, we constructed an in vitro model of malignant transformation of human bronchial epithelial cells (16HBE-T) by treating 40 μg/mL CBNPs for 120 passages. We observed tumor-like transformation and sustained DNA damage. Using transcriptome sequencing and RIP-seq, we identified the overexpression of the critical DNA mismatch repair genes MutS homolog 2 (MSH2) and its related circular RNA, circ_0025373, in the 16HBE-T cells. Mechanistically, circ_0025373 was found to inhibit DNA damage by binding to MSH2, thereby modifying its expression and influencing its nuclear and cytoplasmic distribution, which lead to inhibition of CBNP-induced malignant transformation of human bronchial epithelial cells. Our findings provide novel evidence on the carcinogenicity of CBNPs, and offer biological insights into the potential epigenetic regulation and potential therapeutic targets for lung carcinogenesis.

Exploring TSGA10 Function: A Crosstalk or Controlling Mechanism in the Signaling Pathway of Carcinogenesis?

Cancer-specific antigens have been a significant area of focus in cancer treatment since their discovery in the mid-twentieth century. Cancer germline antigens are a class of antigens specifically overexpressed in germline tissues and cancer cells. Among these, TSGA10 (testis-specific gene antigen 10) is of great interest because of its crucial impact on cancer progression. Early studies explored TSGA10 expression in a variety of cancer types. More recent studies revealed that TSGA10 can suppress tumor progression by blocking cancer cell metabolism, angiogenesis, and metastasis. An open question regarding the TSGA10 is why cancer cells must express a protein that prevents their progression. To answer this question, we conducted a comprehensive review to engage the TSGA10 in the context of the current understanding of "malignant transformation". This review demonstrated that TSGA10 expression level in cancer cells depends on the cancer stage across malignant transformation. In addition, we evaluated how TSGA10 expression can prevent the "cancer hallmarks". Given this information, TSGA10 can be of great interest in developing effective targeted anti-cancer therapies.

The role of M1 (CD11c) and M2 (CD163) interplay in the pathogenesis of oral submucous fibrosis and its malignant transformation: An immunohistochemical analysis

ObjectivesThe M1/M2 macrophage framework is crucial in organ fibrosis and its progression to malignancy. This study investigated the possible role of M1/M2 macrophage interplay in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation by analysing immunohistochemical expression of CD11c (M1) and CD163 (M2) markers. MethodsImmunohistochemistry was performed using primary antibodies against CD11c and CD163 on ten formalin-fixed paraffin-embedded tissue blocks for each group: (i) Stage 1 OSF, (ii) Stage 2 OSF, (iii) Stage 3 OSF, (iv) Stage 4 OSF, (v) well-differentiated squamous cell carcinoma (WDSCC) with OSF, and (vi) WDSCC without OSF. Ten cases of healthy buccal mucosa (NOM) served as controls. ResultsEpithelial quick scores of M1 (CD11c) in NOM, Stages 1–4 OSF, and WDSCC with and without OSF were 0, 1.8, 2.9, 0.4, 0, 0, and 0, while connective tissue scores were 0, 3.2, 4.3, 2.7, 0.5, 1.2, and 2.4, respectively. Epithelial scores for M2 (CD163) were 0, 0.8, 0.8, 2.1, 0.6, 0.8, and 0.2, and connective tissue scores were 0, 1.8, 2.6, 3.9, 2.2, 5, and 4.4, respectively. Stages 3 and 4 OSF, WDSCC with and without OSF exhibited higher M2/M1 ratios compared to NOM and Stages 1–2 OSF. ConclusionThe interaction between M1 (CD11c) and M2 (CD163) macrophages, leading to M2 polarisation, plays a crucial role in the pathogenesis of OSF and its potential malignant transformation.

A Case of Hereditary Multiple Exostoses: Role of FNAC in diagnosis

Abstract Hereditary Multiple Exostoses (HME) is a rare autosomal dominant bone disease. It is characterized with numerous benign osteochondromas, which grow outward from the metaphyses of long bones. In many cases it is asymptomatic but can lead to considerable number of complications, like pressure symptoms, limb deformities, and can cause psychosocial problems. Malignant transformation is rarely seen. Surgery is the main modality of treatment.This paper aims to highlight the role of FNAC in diagnosis of HME.

Incidental brain tumor findings in children: prevalence, natural history, management, controversies, challenges, and dilemmas.

Incidental brain tumor findings in children involve the unexpected discovery of brain lesions during imaging for unrelated reasons. These findings differ significantly from those in adults, requiring a focus on pediatric-specific approaches in neurosurgery, neuroimaging, and neuro-oncology. Understanding the prevalence, progression, and management of these incidentalomas is crucial for informed decision-making, balancing patient welfare with the risks and benefits of intervention. Incidental brain tumors are observed in about 0.04-5.7% of cases, with most suspected low-grade lesions in children showing a benign course, though up to 3% may undergo malignant transformation. Treatment decisions are influenced by factors such as patient age, tumor characteristics, and family anxiety, with conservative management through surveillance often preferred. However, upfront surgery may be considered in cases with low surgical risk. Initial follow-up typically involves a comprehensive MRI after three months, with subsequent scans spaced out if the lesion remains stable. Changes in imaging or symptoms during follow-up could indicate malignant transformation, prompting consideration of surgery or biopsy. Several challenges and controversies persist, including the role of upfront biopsy for molecular profiling, the use of advanced imaging techniques like PET-CT and magnetic resonance spectroscopy, and the implications of the child's age at diagnosis. These issues highlight the need for further research to guide management and improve outcomes in pediatric patients with incidental brain tumor findings.