Type Adenocarcinoma Research Articles

Unconventional Histopathological Features With KIAA1549::BRAF Fusion in Advanced Prostatic Adenocarcinoma.

This report delineates an intriguing example of advanced prostatic adenocarcinoma displaying distinctive histopathological characteristics associated with a KIAA1549::BRAF fusion, a genomic anomaly predominantly identified in central nervous system tumors. A 66-year-old man, presenting with acute renal failure, exhibited metastatic disease involving pelvic soft tissue, bladder, liver, and bone. Histological examination revealed a markedly unconventional morphology within the prostate, characterized by infiltrative tumor sheets exhibiting abundant vacuolated cytoplasm, hyperchromatic nuclei, and irregular nuclear membranes, distinct from typical prostatic adenocarcinoma. Immunophenotyping confirmed NKX3.1 positivity and GATA3 negativity. Molecular analysis revealed the rare KIAA1549::BRAF fusion alongside pertinent mutations in phosphatidylinositol 3-kinase, phosphatase and tensin homolog, and tumor protein 53 genes. Despite diverse therapeutic interventions targeting mitogen-activated protein kinase signaling and subsequent clinical trial enrollment, disease progression remained relentless, culminating in the patient's demise within 4 years of diagnosis. This report highlights the exceptional histopathological presentation associated with KIAA1549::BRAF fusion in prostatic adenocarcinoma, emphasizing the need for a deeper comprehension of its implications on disease behavior and therapeutic responsiveness in similar instances.

Accuracy of the preoperative estimation of esophageal invasion length of adenocarcinoma of the esophagogastric junction and its discrepancy with the pathological measurement.

The incidence of esophagogastric junction (EGJ) adenocarcinoma has increased worldwide. As the EGJ is located at the boundary between the thoracic and abdominal cavities, the optimal surgical approach is a subject of debate and estimation of the esophageal invasion length (EIL) is an important factor in its selection. Data from our in-house database were extracted for consecutive patients with Siewert type I, II and III EGJ adenocarcinoma (EIL ≤ 4cm), who underwent transhiatal or transthoracic surgical resection between 2010 and 2016. The clinical records of these patients were reviewed and the accuracy of EIL estimation and its discrepancy with the pathological measurement were analyzed. A total of 82 patients were included in the final analysis. We established that EIL was underestimated in 49 of these patients (59.8%). The mean-distance discrepancy between the preoperative and pathological diagnosis of EIL in the underestimation group was 7.0mm. Multivariate analysis revealed that submucosal cancer spread was an independent risk factor for underestimation (P < 0.01). The mean length of submucosal cancer spread was longer for undifferentiated histologic type EGJ adenocarcinomas. (P < 0.01). The EIL was underestimated in approximately 60% of EGJ adenocarcinomas requiring surgical treatment. Thus, careful management is necessary, especially for EGJ adenocarcinoma of the undifferentiated histologic type.

A rare incidence of signet ring cell carcinoma of the rectosigmoid junction: a case report

Introduction and importance: Signet ring cell carcinoma (SRCC) is a rare type of adenocarcinoma. SRCC comprises 1.0% of all colon cancer and 0.7% of all rectal cancer. The SRCC spreads both hematologically and through lymph nodes making it highly invasive. The pathophysiology of the colorectal SRCC involves an alteration in the function of the RNF43, CDH-1, and SMAD4 genes as well as TGF-B signaling pathways, which are responsible for epithelial-mesenchymal transitions and stem cell properties. This also shows a higher rate of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype positivity Case presentation: A 17-year-old female patient with no known comorbidities presented with copious, bright red colored per rectal bleeding along with painful defecation. Colonoscopy revealed an eccentric growth that led to luminal narrowing. Multiple biopsies confirmed a 4 cm × 6 cm neoplastic lesion with locoregional lymphadenopathy, but no metastasis. The patient underwent anterior resection of the rectum, colostomy, and rectal stump closure. The sigmoid colon was resected up to the middle up to the third mesorectum followed by multiple re-explorations. Discussion: SRCC presents at an advanced stage with a poor prognosis because signet ring cells infiltrate the mucosa without forming a significant mass, hindering early diagnosis of this carcinoma. Among the previously published large-scale studies, SRCC involves the proximal colon, i.e., the cecum, ascending, and transverse colon. However, our case presents a less common left-sided presentation in a less-commonly presented demographic, a 17-year-old girl. The patient’s non-specific symptoms contributed to a delayed diagnosis. Despite this, the absence of metastasis in our late-diagnosed case is atypical of SRCC. Conclusion: SRCC should be considered as a differential diagnosis for young adults presenting with per-rectal bleeding and other common symptoms often seen in frequently diagnosed conditions. Therefore, early diagnosis along with appropriate surgical intervention combined with supportive treatment are important for better patient outcomes.

Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion.

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.

Gastric Epithelial Neoplasm of Fundic-Gland Mucosa Lineage: Showed the Same Genetic Lineage and Ki67 May Help in Their Identification

Abstract Introduction/Objective Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare form of gastric tumors that encompasses oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the clinicopathologica and molecular characteristics of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms. Methods/Case Report The NGS and immunohistochemical staining were performed on 37 cases diagnosed with GEN-FGMLs with a thorough histological evaluation. Gene alternations were analysed and compared across histological subtypes. we used an artificial intelligence approach for the recognition of the Ki67 immunohistochemistry stained. Results (if a Case Study enter NA) The patient’s ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between GEN-FGMLs. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p&amp;lt;0.05) and had larger sizes (p&amp;lt;0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p&amp;lt;0.0001). The heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across histological subtypes. The top five mutational signatures in OGA were ROS1, CTNNA1, GNAS, BRCA2, and ZFHX3. The top five mutational signatures in GA-FG and GA-FGM were GNAS, MLL3, BRAF, MSH3, and EGFR. GNAS were both found in OGA, GA-FG and GA-FGM. Compared with well-differencent gastric adenocarcinoma, The top five mutational signatures in GEN-FGMLs were GNAS, BRAF, ROS1, MLL3, and MSH3. Recurrently mutated key signaling pathways across tumor types in GEN-FGML were Wnt signaling pathways. Conclusion GEN-FGMLs are a group of well-differentiated gastric tumors with favourable biological behaviours. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. GEN-FGMLs showed the same genetic lineage, the Wnt signalling pathway plays a role in the development and progression of GEN-FGMLs.

HPV-Independent Cervical Adenocarcinoma Discovered by Cytology-Based Screening: A case report of gastric type adenocarcinoma of the uterine cervix from cytopathology to histopathology

Abstract Introduction/Objective In recent years, the relative prevalence of adenocarcinoma has increased, comprising 20–25% of all cervical carcinomas in developed countries. Approximately 15% of cervical adenocarcinomas are unrelated to human papilloma virus (HPV) infection. With the shift toward HPV primary testing, an increased understanding of HPV-independent cervical adenocarcinomas becomes more important. Methods/Case Report This case report demonstrates a rare case of gastric-type adenocarcinoma (GAS) of the cervix discovered during a routine well-woman exam. Patient-reported episodes of vaginal spotting were noted prior to screening. HPV testing by PCR on the initial pap smear was negative. Cytology findings raised concerns about endocervical glandular cell abnormalities. Subsequent cervical biopsy revealed GAS, a finding supported by positive CK7, MUC5AC, CDX2, and aberrant (mutant) p53 expression by immunohistochemistry. HPV independence was further confirmed by negative results on mRNA ISH for high-risk HPV and HPV16/18. Results (if a Case Study enter NA) NA Conclusion Here we discuss the impact of cytology-based screening on HPV-independent cervical cancers, with focus on adenocarcinoma. While the move to primary HPV screening has been shown to be effective at identifying HPV-related neoplasms, it ineffectively addresses HPV-independent malignancies. In this particular population, cytology-based screening remains indispensable. The described case demonstrated subtle cytologic features consistent with endocervical glandular abnormality, ultimately correlating with subsequent histologic findings of HPV-independent GAS. Negative HPV results combined with subtle cytomorphologic changes displayed by some adenocarcinomas on PAP smear could present a significant diagnostic pitfall. Additionally, p16+ expression attributable to aberrant p53 pathways (rather than HPV) may further contribute to potential diagnostic errors. While further research into best practices for early detection of HPV-independent cervical neoplasias should be conducted, this team suggests both clinical survey and referral for cytologic screening following reports of abnormal vaginal bleeding and/or watery discharge and screener education focused on cervical GAS.

B-351 Genotoxic Producing Escherichia coli Protects and Promotes Breast Adenocarcinoma

Abstract Background Recent studies have linked certain colibactin producing subphylas of E. coli to colorectal cancer. The bacterium synthesizes colibactin via the pks genomic island containing a series of clbA to clbS genes. The genotoxin causes inter-strand DNA cross-links, which lead to double strand breaks and promotion of colorectal adenocarcinoma. The published studies have prioritized the colorectal regions of the body where E. coli is commonly found, but none have identified the same genotoxic relationship with other types of adenocarcinoma. In this study, we evaluate DNA damage and cellular changes of mammary breast tissue based on high and low levels of colibactin producing E. coli exposure. The goal is to evaluate if colibactin can affect cells in the mammary breast tissue promoting breast adenocarcinoma growth. Methods Two cell lines were acquired from ATCC: primary mammary epithelial cells (PCS-600-010) and MCF-7 breast adenocarcinoma cells (HTB-22). Both cell lines were split into six culture flasks and maintained until ∼80% confluence was reached using the ATCC cell culture protocols. Once all the flasks had reached the target confluence, they were divided into exposure groups of high and low concentrations of colibactin producing E. coli, a group of non-colibactin producing E. coli, a group exposed only to phosphate buffered saline, and a control group with no exposure. Cellular morphology was observed using light microscopy before, after exposure, and every 5 minutes up to 15 minutes. E. coli and colibactin DNA concentrations were quantified using quantitative polymerase chain reaction. Genomic DNA was extracted from each group of cells. The DNA from each group was whole genome sequenced and analyzed for genomic variation. Results The normal cells exposed to E. coli showed immediate lysing and continued to lyse after a 5 minute incubation; however, the adenocarcinoma positive cells showed no lysing up to 30 minutes incubation. Sequencing results show genomic variation between the groups and specific break points associated with the E. coli exposed groups. Conclusions Our results show that the presence of E. coli with mammary breast tissue can destroy normal tissue, promote lysis resistance, and allow adenocarcinoma cells to continue to grow. The colibactin producing E. coli does cause double stranded breaks and can lead to cell death. This new information points out a critical need to monitor the microbiome and infection levels of people at risk or in early stages of cancer to prevent adenocarcinoma growth and destruction of normal tissue. This study indicates that colibactin producing E. coli may play a larger role in tissue damage and promotion of other types of cancer. More research is needed to elucidate the molecular pathway and mechanisms of colibactin, which will lead to new diagnostics or therapeutics that monitor E. coli levels or inhibit colibactin’s toxic effects.

Mutational Landscape of Gastric Adenocarcinoma of the Fundic Gland Type Revealed by Whole Genome Sequencing.

Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features. We performed whole-genome sequencing (WGS) in formalin-fixed paraffin-embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA-FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA-FG disease. We characterized the genomic architecture of GA-FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored "Kataegis." Distinct genomic alterations between GA-FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non-silent alterations of formerly well-known drivers such as TP53, PIK3CA and KRAS were identified in GA-FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA-FG and conventional gastric cancer. Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA-FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease.

Specific cancer types and prognosis in patients with variations in the KEAP1-NRF2 system: A retrospective cohort study.

The KEAP1-NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C-CAT database, which contains the gene-panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in NRF2 and KEAP1 genes and their associations with clinical outcomes. Variants in the NRF2 gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The NRF2 variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the NRF2 variants in the ETGE motif were indicators of a worse prognosis. KEAP1 variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with KEAP1 and NRF2 variants. Our results indicate that genetic alteration of the KEAP1-NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in NRF2 and KEAP1 genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences.

Very Rare Case of Pulmonary Lepidic Adenocarcinoma at a Young Age Man

Introduction: Lung cancer remains one of the higher prevalence of cancer and leading cause of death in the world. Smoking and genetic factors are two important etiologies in lung cancer. Adenocarcinoma is the most common type of non-small cell lung carcinoma. Lepidic predominant adenocarcinoma is one type of adenocarcinoma that has a good prognosis. Case Illustration: A 24-year-old male came with chronic cough and chest pain. He had a history of smoking and no prior family history of cancer. Plain chest Xray and Thorax computed tomography (CT) showed pleural effusion and presence of lung mass with suggestion of bone and liver involvement, respectively. The cytology from pleural effusion and bronchial lavage initially found no malignancy cell. Later thoracostomy biopsy and pathology study suggested lepidic adenocarcinoma. Discussion: Lung cancer is still one of the leading causes of death in men. Even though rarely found in young male, patients with a history of smoking or genetic factor with clinical manifestation suggestive chronic respiratory condition with weight loss should be suspected of the diagnosis. Adenocarcinoma, as the most common non-small cell lung carcinoma, could be later divided into several subtypes. Lepidic adenocarcinoma is distinguished by the pathology finding of a large invasion focus of stromal, lymphatic, vascular, or pleural space. Considered one of the most favorable, lepidic predominant adenocarcinoma has a very high rate of 5 year survival when diagnosed early and responds well to lobe resection. Advanced state however has poor outcome due to limited choice of therapy. Promising trial of targeted chemotherapy have been reported and could improve outcome in the future. Conclusion: Lung cancer in young male is a rare disease but should be suspected in those with chronic cough, chest pain and weight loss. The history of smoking and family history are crucial for this suspicion. Lepidic predominant adenocarcinoma has a good prognosis when diagnosed early. Studies in the future could enhance overall survival in these patients.

Advances on Molecular Mechanism and Clinical Treatment in Invasive Mucinous Adenocarcinoma

Invasive mucinous adenocarcinoma (IMA) is a special type of lung adenocarcinoma that accounts for 2% to 10% of all lung adenocarcinoma. Surgical treatment is preferred for IMA, and traditional chemotherapy drugs and targeted therapy drugs have poor efficacy in this disease. IMA has unique prognostic, imaging and molecular features. The incidence of IMA is very low, so thoracic surgeons may lack of knowledge to the disease and misdiagnose it as benign diseases such as pneumonia and tuberculosis. This article reviews and discusses the imaging, clinicopathological features, treatment methods and prognosis of IMA. .

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan.

Objective In this study, we sought to elucidate the relationship between demographic and clinical factors and epidermal growth factor receptor tyrosine kinase (EGFR-TK) positivity in patients with advanced-stage lung cancer at a tertiary care center in Pakistan. Methods This analytical cross-sectional study was conducted from February 2020 to July 2023 at Shaikh Zayed Hospital, Lahore, Pakistan, in collaboration with the Centre of Excellence in Molecular Biology (CEMB), University of the Punjab. The study included 70 consecutive patients with advanced-stage lung cancer, and aimed to identify common EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation), determine their frequency, and correlate EGFR-TK mutation positivity with clinical and non-clinical factors. Tissue acquisition and processing involved bronchoscopy, pleuroscopy, or percutaneous ultrasound-guided lung mass biopsy, followed by molecular analysis using polymerase chain reaction (PCR) extraction, amplification, and sequencing. The study employed convenient sampling and included adults aged over 18 years with histologically confirmed lung cancer. Results We enrolled 70 lung cancer patients, with a mean age of 60.87 years, and a male-to-female ratio of 1.4:1. The majority (61.4%) had adenocarcinoma, and 34.3% harbored a mutant EGFR-TK. EGFR mutations were more common in adenocarcinoma (91.7%) and associated with female non-smokers. Binary logistic regression analysis revealed that age <50 years and adenocarcinoma type were significant predictors of EGFR mutations. We found no significant associations with gender, smoking status, or other variables. These findings have implications for personalized treatment approaches in lung cancerpatients. Conclusions Our study reveals a high frequency of occult EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation) in non-small cell lung cancer (NSCLC) patients, particularly among male smokers and female non-smokers. These findings emphasize the importance of routine EGFR mutation testing to identify patients who may benefit from targeted therapies, ultimately improving treatment outcomes.

The impact of postoperative adjuvant therapy on EGFR-mutated stage IA lung adenocarcinoma with micropapillary pathological subtypes

BackgroundMicropapillary (MPP) adenocarcinoma is considered one of the most aggressive pathological types of lung adenocarcinoma (LADC). This retrospective study aimed to evaluate the prognostic significance and benefit of postoperative adjuvant therapy (PAT) in stage IA LADC patients with different proportions of MPP components.Materials and methodsWe retrospectively examined clinical stage IA LADC patients who underwent surgical resection between August 2012 and December 2019. In terms of the proportion of MPP components (TPM), the tumors were reclassified into three categories: MPP patterns absent (TPMN); low proportions of MPP components (TPML); and high proportions of MPP components (TPMH). The dates of recurrence and metastasis were identified based on physical examinations and were confirmed by histopathological examination.ResultsOverall, 505 (TPMN, n = 375; TPML, n = 92; TPMH, n = 38) patients harboring EGFR mutations were enrolled in the study. Male sex (P = 0.044), high pathological stage (P < 0.001), and MPP pathological subtype (P < 0.001) were more frequent in the TPM-positive (TPMP) group than in the TPM-negative (TPMN) group. Five-year disease-free survival (DFS) rates were significantly lower in the TPMP group than in the TPMN group (84.5% vs. 93.4%, P = 0.006). In addition, patients with high proportions (greater than 10%) of MPP components had worse overall survival (OS) (91.0% vs. 98.9%, P = 0.025) than those with low proportions (5%≤ TPM ≤ 10%). However, postoperative EGFR tyrosine kinase inhibitors (TKIs) or adjuvant chemotherapy (ACT) cannot improve DFS and OS between EGFR-mutated patients with different proportions of MPP components.ConclusionMPP was related to earlier recurrence and shortened survival time, even in stage IA. Further research needs a larger sample size to clarify that EGFR-mutated stage IA patients with MPP components obtain survival benefits from adjuvant therapy.

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50years) and intervals (2/5/10years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20mm in size, and the deep submucosal invasion rate was less than 30%. A mathematical simulation model revealed that screening every 5years starting at 45years of age could efficiently assist in identifying HpNGNs at an early stage.

EGFR mutation based on lung laterality in adenocarcinoma type of non-small cell lung cancer

Targeted therapies have shown promise in improving survival rates for lung adenocarcinoma, a common and deadly malignancy. EGFR-targeting tyrosine kinase inhibitors (TKIs) are particularly effective among these therapies in cases with EGFR mutations. Detecting these mutations before TKI treatment is essential. Various radiological features have been linked to EGFR mutations. However, the relationship between tumor location and mutation types in Indonesian lung adenocarcinoma patients remains unexplored. This study aimed to identify the frequency of EGFR mutation in local lung adenocarcinoma cases based on the tumor location. Clinical data of lung adenocarcinoma patients (n = 272) diagnosed between 2018 and 2022 were retrospectively taken from the Department of Anatomical Pathology, Dr. Sardjito General Hospital, Yogyakarta. The qRT-PCR data of EGFR mutation status was obtained from the Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta. Descriptive analysis was performed using STATA version 14.0. EGFR mutations were found in 60.7% of patients, with 58.2% having exon 19 mutations and 21.2% exhibiting exon 21 L858R mutations. Mutation status was found to be significantly different based on the patient's gender (p = 0.022) and age (p = 0.029) but not with lung laterality (p = 0.093). The proportion of exon 19, exon 21 L858R, and uncommon mutations in the right and left lung adenocarcinoma was similar across all samples. This study found no difference between specific EGFR mutation types and tumor location in lung adenocarcinoma.

The Diagnostic Value of Ultrasound Combined with Serum VEGF and TSGF Levels Detection for Differentiated Thyroid Cancer

Objective: To explore the diagnostic value of ultrasound combined with serum VEGF (vascular endothelial growth factor) and TSGF (tumor specific growth factor test) levels in differentiated thyroid cancer, and analyze clinical and pathological characteristics. Methods: Multiple patients with differentiated thyroid cancer who received diagnosis and treatment in a certain hospital in China from February 2021 to February 2023 were selected for the experiment. 50 patients were randomly selected as the experimental group. Based on the type of adenocarcinoma, these 50 patients were further divided into the thyroid follicular carcinoma group and the thyroid papillary carcinoma group. Fifty patients with thyroid sarcoidosis were selected as the control group during the same period. Compare the ultrasound examination results and serum levels of VEGF and TSGF between two experimental groups to explore their relationship with the clinical and pathological characteristics of differentiated thyroid cancer. Results: Through experimental observation, it can be concluded that the sensitivity of ultrasound combined with serum VEGF and TSGF levels in the diagnosis of differentiated thyroid cancer is relatively high, and it will significantly exceed the diagnostic sensitivity of ultrasound alone, with P&lt;0.05. And the combination of ultrasound and serum VEGF, TSGF level detection will exceed the specificity and positive predictive value of ultrasound detection in both positive predictive value and specificity. Conclusion: Ultrasound combined with serum VEGF and TSGF levels detection has a relatively high diagnostic value for differentiated thyroid cancer, and can determine the correlation between tumor invasion and metastasis in patients with differentiated thyroid cancer and their serum VEGF and TSGF levels.

Prostate Type Malignancies Arising in Ovarian Teratomas - A Report of Two Patients.

The identification of benign prostatic tissue within ovarian and testicular mature teratomas is an unusual occurrence. While a few documented reports exist in the literature regarding the emergence of benign prostatic tissue within teratomas, the occurrence of prostatic-type adenocarcinoma in a mature ovarian teratoma is an exceptionally rare phenomenon. To date, only two prior reports have documented such instances, and no tumors have been previously reported with prostate-type tissue with morphologically two different malignancies. We outline our experience with two tumors involving prostatic-type carcinoma, both arising in ovarian mature teratomas. Microscopic examination of the first tumor revealed small areas of infiltrative atypical glandular proliferation within the mature teratoma. In the second tumor, prostate-type tissue exhibited a low-grade basal cell carcinoma. Additionally, adjacent minute foci of adenocarcinoma of the prostate (Gleason score 3 + 4 = 7, <5% pattern 4) were identified. Goblet cell adenocarcinoma of appendiceal type was also evident in the latter tumor. In both tumors, immunostains (NKX3.1, PSA) were performed to establish the prostatic origin of these atypical glands and PIN4 was performed to document the absence of basal cell in the atypical glands. On clinical follow-up, both patients have no signs of recurrence at 14 and 11 months after the surgery. Further reports on such neoplasms would contribute to a better understanding of the prognosis and management of such occurrences.

Antacids and reflux esophagitis as a risk factor for gastric neoplasm of fundic-gland type: A retrospective, matched case-control study.

Since the first report of gastric adenocarcinoma of the fundic-gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic-gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. We conducted a single-center, retrospective, matched case-control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values <0.1 and antacid use. A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P=0.036). Factors antacids and duodenitis had P values <0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio=3.68 [95% confidence interval: 1.04-11.91] and 3.25 [95% confidence interval: 1.11-9.35]). Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG.

Small-bowel Metastasis from Gastric Sarcomatoid Carcinoma: A Case Report

Sarcomatoid carcinoma, distinguished by its histological presentation of undifferentiated, spindle-shaped cells, is a rare variant of gastric cancer when contrasted with the more typical adenocarcinoma. Gastric cancer rarely metastasizes to the small bowel; these cancers typically arise from breast, lung, or melanoma origins. Herein, we present the case of a 70-year-old male who experienced melena and significant weight loss over 3 months. An esophagogastroduodenoscopy revealed an extensive ulcerative lesion in the lower curvature of the high body of the stomach, which is consistent with the results of the computed tomography scans. Surgery involving total gastrectomy and resection of multiple segments of small-bowel tumors was conducted. Pathological examination confirmed the presence of sarcomatoid carcinoma with poorly differentiated adenocarcinoma, along with metastases to the small intestine. This report highlights the aggressiveness of gastric sarcomatoid carcinoma, as well as the potential for the small bowel to be a potential metastasis site.

The Clinicopathological and Molecular Characteristics of Endocervical Gastric-Type Adenocarcinoma and the Use of Claudin18.2 as a Potential Therapeutic Target

Endocervical gastric-type adenocarcinoma (GAS) is an aggressive type of endocervical mucinous adenocarcinoma characterized as being unrelated to human papillomavirus (HPV) and resistant to chemo/radiotherapy. In this study, we investigated the histology, immunohistochemistry patterns, and molecular characteristics in a large cohort of GAS (n = 62). Histologically, the majority of GAS cases exhibited a distinct morphology resembling gastric glands, although 2 exceptional cases exhibited HPV-associated adenocarcinoma morphology while retaining the characteristic histology of GAS at the invasive front. By immunohistochemistry, Claudin18.2 emerged as a highly sensitive and specific marker for GAS. Additionally, the strong expression of Claudin18.2 in patients with GAS indicated the potential of anti-Claudin18.2 therapy in the treatment of GAS. Other immunohistochemistry markers, including Muc6, p16, p53, Pax8, ER, and PR, may provide additional diagnostic clues for GAS. Quantitative methylation analysis revealed that the overexpression of Claudin18.2 in GAS was governed by the hypomethylation of the CLDN18.2 promoter CpG islands. To further elucidate the pathogenic mechanisms of GAS and its relationship with gastric adenocarcinoma, we performed whole exome sequencing on 11 GAS and 9 gastric adenocarcinomas. TP53, CDKN2A, STK11, and TTN emerged as the most frequently mutated genes in GAS. Mutations in these genes primarily affected cell growth, cell cycle regulation, senescence, and apoptosis. Intriguingly, these top mutated genes in GAS were also commonly mutated in gastric and pancreaticobiliary adenocarcinomas. Regarding germline variants, we identified a probably pathogenic variant in SPINK1, a gene linked to hereditary pancreatic cancer syndrome, in one GAS sample. This finding suggests a potential pathogenic link between pancreatic cancers and GAS. Overall, GAS exhibits molecular characteristics that resemble those observed in gastric and pancreaticobiliary adenocarcinomas, thereby lending support to the aggressive nature of GAS compared with HPV-associated adenocarcinoma.