Histological Variants Research Articles

Parotid Lipomas: Case Series and Literature Review – A Case Report

Background: Lipomas are the most frequent neoplasm of mesenchymal origin in the head-and-neck region. Around 15% of lipomas are found in the head-and-neck region. The usual site where lipomas can be found in the head-and-neck region is in the posterior triangle of the neck but they can also be found in the anterior neck, infratemporal fossa, submandibular space, larynx, pharynx, and parotid gland. The incidence of parotid lipoma ranges from 0.6% to 4.4% of all parotid neoplasms. There are two histological variants, focal lipoma and diffuse infiltrating variant. We describe two cases of rare focal lipoma of the parotid gland, therefore, must be reported. As rare as it may appear, existing relevant literature suggest management to includes definitive radiological investigations such as magnetic resonance imaging (MRI) and complete removal of lipoma with or without a cuff of parotid tissue. Case Report: Two cases were identified with a parotid lipoma on final histology. Case 1 is a 57-year-old male with a history of painless left parotid swelling for 2 years, reported to be 5 cm × 4 cm size on ultrasound, therefore, underwent superficial parotidectomy. Case 2 is a 67-year-old male who presented with right parotid swelling for 15 years, reported on ultrasound to be 5 cm × 5 cm, and underwent excision of intraparotid tumor. He later went on to develop breast carcinoma. The facial nerve was intact of both patients. Conclusion: Parotid lipomas are rare entities that should be a differential for clinically soft parotid swellings. Management includes definitive radiological investigations such as MRI and complete removal of lipoma with or without a cuff of parotid tissue instead of regular ultrasound followed by fine-needle aspiration cytology. Although our cases were managed on the same regular outlines, but reporting these cases would suffice the potential role of MRI and computed tomography scan for parotid swelling as per existing literature.

Clinical spectrum of frontotemporal dementia: schizophrenia-like symptoms and amyotrophic lateral sclerosis (family case study)

Frontotemporal dementia is a heterogeneous pathology with various clinical, histological, and genetic variants. The behavioral variant of frontotemporal dementia (bvFTD) in some cases presents differential diagnostic difficulties when distinguishing from primary mental disorders. The article provides an observation of patient K., who was observed at the initial stage of the disease with a diagnosis of schizophrenia. The comparison of psychopathological and behavioral symptoms with the presence of a family history of amyotrophic lateral sclerosis (ALS) served as a turning point to a different interpretation of the pathology and recognition and confirmation of the “definite diagnosis” — bvFTD.

Giant cell rich osteosarcoma of maxilla vs. giant cell granuloma: a diagnostic dilemma

Giant cell-rich osteosarcoma is a rare histological variant of osteosarcoma, accounting for 3% of all primary osteosarcomas and rarely occurring in the head and neck region. GCRO poses a significant diagnostic challenge radiologically and histopathologically, as it often presents with a benign appearance despite being a clinically aggressive osteosarcoma with a high tendency for recurrence. Meticulous surgical planning, a radical surgical approach, and postoperative radiotherapy are essential to prevent recurrence. We are discussing the case of a 21-year-old male patient diagnosed with Giant Cell-Rich Osteosarcoma of the maxilla. This case highlights the diagnostic dilemma associated with GCRO, the surgical approach employed, and the subsequent reconstruction process.

Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults: A retrospective study.

The Columbia classification identified five histological variants of focal segmental glomerulosclerosis (FSGS). The prognostic significance of these variants remains controversial. To evaluate the relative frequency, clinicopathologic characteristics, and medium-term outcomes of FSGS variants at a single center in Pakistan. This retrospective study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan on all consecutive adults (≥ 16 years) with biopsy-proven primary FSGS from January 1995 to December 2017. Studied subjects were treated with steroids as a first-line therapy. The response rates, doubling of serum creatinine, and kidney failure (KF) with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis, and Chi-square tests as appropriate. Data were analyzed by SPSS version 22.0. P-value ≤ 0.05 was considered significant. A total of 401 patients were diagnosed with primary FSGS during the study period. Among these, 352 (87.7%) had a designated histological variant. The not otherwise specified (NOS) variant was the commonest, being found in 185 (53.9%) patients, followed by the tip variant in 100 (29.1%) patients. Collapsing (COL), cellular (CEL), and perihilar (PHI) variants were seen in 58 (16.9%), 6 (1.5%), and 3 (0.7%) patients, respectively. CEL and PHI variants were excluded from further analysis due to small patient numbers. The mean follow-up period was 36.5 ± 29.2 months. Regarding response rates of variants, patients with TIP lesions achieved remission more frequently (59.5%) than patients with NOS (41.8%) and COL (24.52%) variants (P < 0.001). The hazard ratio of complete response among patients with the COL variant was 0.163 [95% confidence interval (CI): 0.039-0.67] as compared to patients with NOS. The TIP variant showed a hazard ratio of 2.5 (95%CI: 1.61-3.89) for complete remission compared to the NOS variant. Overall, progressive KF was observed more frequently in patients with the COL variant, 43.4% (P < 0.001). Among these, 24.53% of patients required kidney replacement therapy (P < 0.001). The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57 (95%CI: 1.87-113.49) as compared to patients with the TIP variant. In conclusion, histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

Exploring Solitary Fibrous Tumors at a Tertiary Cancer Center: Clinicopathological and Immunomorphologic Profile.

Background Solitary fibrous tumor (SFT) is a distinct fibroblastic tumor that can occur at any anatomical site and can manifest a variety of histopathological features. NAB2-STAT6 gene fusion has recently emerged as a sensitive and specific molecular marker and its surrogate on immunohistochemistry, STAT6 has also displayed considerable efficacy. Nevertheless, its histologic diversity can result in diagnostic challenges, especially when classic features are not apparent. Methods A retrospective study was conducted at a tertiary cancer centre in North India over 3 years to document the clinicopathologic and immunomorphologic profile of SFTs. Immunohistochemical analysis of BCORand p53 were gauged additionally and patients were stratified according to Modified Demicco and Salas criteria for risk of metastasis. Results Sixteen patients of SFT were identified, affecting middle-aged men and women equally. Though lung/pleura are known to be involved commonly, SFT affects other sites such as the kidney, brain, buccal mucosa, liver, and penis as well. The majority endured localized disease while a lesser number suffered locoregional/distant spread. Two patients revealed features of a malignant profile. Risk stratification according to the Modified Demicco and Salas criteria evinced comparable results. No discernible relationship however was highlighted between the immunohistochemical expression of BCOR, p53, and any significant SFT parameter. Conclusion Although SFTs are very rare substantially benign mesenchymal neoplasms, pathologists must be conversant with their histological diversity and be vigilant of their malignant attributes. The worth of STAT6 immunohistochemistry for precise diagnosis and long-term studies for delineating clinical behavior cannot be overemphasized.

Accuracy of endometrial sampling in the diagnosis of endometrial cancer: a multicenter retrospective analysis of the JAGO-NOGGO

BackgroundAccurate preoperative molecular and histological risk stratification is essential for effective treatment planning in endometrial cancer. However, inconsistencies between pre- and postoperative tumor histology have been reported in previous studies. To address this issue and identify risk factors related to inaccurate histologic diagnosis after preoperative endometrial evaluation, we conducted this retrospective analysis.MethodsWe conducted a retrospective analysis involving 375 patients treated for primary endometrial cancer in five different gynaecological departments in Germany. Histological assessments of curettage and hysterectomy specimens were collected and evaluated.ResultsPreoperative histologic subtype was confirmed in 89.5% of cases and preoperative tumor grading in 75.2% of cases. Higher rates of histologic subtype variations (36.84%) were observed for non-endometrioid carcinomas. Non-endometrioid (OR 4.41) histology and high-grade (OR 8.37) carcinomas were identified as predictors of diverging histologic subtypes, while intermediate (OR 5.04) and high grading (OR 3.94) predicted diverging tumor grading.ConclusionWhen planning therapy for endometrial cancer, the limited accuracy of endometrial sampling, especially in case of non-endometrioid histology or high tumor grading, should be carefully considered.

Macro and Micro Anatomical Comparative Study for Liver, Kidney and Testis Between the Albino Rat and Pigeon

The present study was designed to demonstrate the anatomical and histological variations between the certain organs in both the rat as a model of experimental mammals and pigeon as an avian model. Five albino rats and five pigeons were utilized, the liver, kidney and the testicles were taken from those animals after scarifying and specimens were taken from those organs, fixed in 10 % formalin for 24 hours before transferred for histological technique, the slices were stained with hematoxylin and eosin. The anatomical observation indicated that the liver of rat was formed by right, left lobes and intermediate, located in the anterior part of abdomen, in the pigeon, had two lobes without gall bladder. The kidney of the rat was bean shaped, brown reddish color with idented medial border present in the abdominal cavity near and around the lumbar vertebrae, the kidney of pigeon was lobulated into three and the kidney was lodged on the ventral aspect of the synsacrum.&#x0D; The testis of rat was oval in shape present in the scrotum, and in the pigeon located in the abdominal and pelvic cavity. The histological result indicated the liver of rat was with columns of polygonal liver cells surrounded by blood sinusoids draining in the central vein, while in the pigeon, the cells were present in groups also had blood sinusoids with Kupffer cells and central vein for draining the blood outside the liver, the kidney of both types had an cortex and medulla with presence of glomeruli in the cortex, both had proximal and distal convoluted tubules , in the pigeon there is no thin segment of Henle loops .&#x0D; The testis was occupied by seminiferous tubules in both types and each tubule was containing the different types of spermatic cells and spermatozoa, also Leydig cells were present in groups, spermatogenesis was intensive in pigeon in cases of seasonal phase in conclusion, variation for the visceral organs in both rats and pigeon were determined also histological differences were present, otherwise similarities were also observed.

Angiofibrolipoma em cão

Angiofibrolipoma is a histological variation of lipoma, a benign tumor with low occurrence in domestic animals. Its diagnosis is based on histopathological examination. The treatment of choice was surgical resection of the tumor, with the surgical challenge being the identification of the prostate and urethra, which were obscured by the mass. Despite being a benign neoplasm, the veterinary surgeon must possess rigorous knowledge of anatomy and reconstructive skills when there is involvement of important anatomical structures. This study aims to report a case of rapidly progressing angiofibrolipoma in the abdominal cavity of a dog treated at the Veterinary Hospital of the Oeste Paulista University.

Abstract 4632: Lineage plasticity as a determinant of antibody-drug conjugate target expression in urothelial bladder cancer

Abstract Bladder cancers display a wide spectrum of morphologies that frequently co-exist within individual tumors. Several histologic variants, including plasmacytoid, neuroendocrine, and micropapillary subtypes, are associated with an increased bladder cancer recurrence risk and cancer-specific mortality. The molecular basis and therapeutic implications of this phenotypical plasticity remain poorly understood. Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has also emerged as a new standard-of-care for metastatic bladder cancer patients, but the association between lineage plasticity as manifested by morphologic heterogeneity in bladder cancer, Nectin-4 expression and ADC response remains poorly defined. Previous DNA-based molecular profiling studies of histologic variants revealed that CDH1 mutations were the pathognomonic molecular alteration in plasmacytoid urothelial carcinoma, but no recurrent driver mutations have been found to be unique to the aberrant histology regions of other mixed histology subtypes. Thus, to explore the molecular basis for the lineage plasticity of bladder cancers with aberrant histology and to define the association between lineage plasticity manifested as morphologic heterogeneity and the expression of Nectin-4, HER2 and other potential ADC targets, we performed RNA-seq of pure urothelial carcinomas (n=118, not otherwise specified, UC-NOS) and bladder tumors with divergent differentiation or histologic subtypes (n=199). Our cohort included a subset of tumors in which RNA-seq was performed on microdissected UC-NOS and variant histology regions of the same tumor. Tumors with neuroendocrine, sarcomatoid and squamous histology had the lowest Nectin-4 expression, whereas histologic subtypes that retained a luminal transcriptional profile such as micropapillary, plasmacytoid and nested histology had higher levels of Nectin-4 expression. In mixed histology tumors, Nectin-4 and/or HER2 expression was often restricted to only one of the two histologic components. Gene Set Enrichment Analysis noted enrichment of distinct oncogenic pathway gene sets in different histologic variants. Preliminary investigation into the mechanism(s) of Nectin-4 regulation using bladder cancer cell lines and patient-derived organoids (PDOs) has identified targetable pathways which when inhibited revert lineage plasticity and induce Nectin-4 expression. In sum, lineage plasticity manifested as heterogenous histomorphologies was associated with heterogeneous Nectin-4 expression in some but not all histologic variants of bladder cancer. Ongoing studies using PDOs from bladder cancer patients with mixed histology will seek to identify molecular pathways whose inhibition leads to increased expression of Nectin-4 or other ADC targets such as HER2 and thus increased sensitivity of ADCs targeting these cell surface proteins. Citation Format: Jiaqian Luo, Sizhi P. Gao, Fengshen Kuo, Gamze Gokturk Ozcan, Merve Basar, Florestan Koll, Jacob E. Tallman, Syed M. Alam, Carissa E. Chu, Ziyu Chen, Eugene J. Pietzak, Gopakumar Iyer, Jonathan E. Rosenberg, David B. Solit, Hikmat Al-Ahmadie. Lineage plasticity as a determinant of antibody-drug conjugate target expression in urothelial bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4632.

Abstract 6405: Identification of molecular targets in bladder cancer variants using single-cell analysis

Abstract Introduction and objectives: Variant subtypes in bladder cancer, also known as histologic variants, are clinically aggressive tumors associated with poor prognosis. The rarity of these tumors has made molecular characterization elusive using bulk transcriptional profiling. The aim of this study was to use single cell RNA sequencing to identify molecular features associated with variant subtypes that could be potential targets for therapy. Methods: Fresh tissue from bladder cancer patients undergoing surgery at our institution was sequenced using a bead-based single-cell RNA sequencing platform (Seq-Well) to generate an atlas of 9 tumors containing variants (micropapillary, nested, squamous differentiation, pleomorphic giant-cell like, plasmacytoid, small cell) and 3 tumors with pure urothelial carcinoma (UC) histology. Pathologic diagnoses were independently confirmed. Analysis was performed using the Seurat package in R Studio. Immunostaining validation was performed on a separately banked cohort. Bulk RNA sequencing data and clinical data were extracted and analyzed from The Cancer Genome Atlas (TCGA) database. Chimeric Antigen Receptor (CAR) T cells targeting TM4SF1 were generated by lentiviral transduction of primary human T cells and tested against publicly available bladder cancer cell lines. Results: Variant tumors were enriched in TM4SF1, a surface molecule that we demonstrate to be susceptible to CAR T therapy in vitro. Variants also share a cell state characterized by highly specific expression of MUC16 (CA125), which is enriched in metastatic sites, harbors transcriptional hallmarks of epithelial-mesenchymal transition and luminal-basal plasticity, and is associated with poor survival and resistance to chemotherapy. Finally, we find evidence of transcriptional mimicry between variants and similar appearing non-urothelial cells (e.g. plasmacytoid:plasma cell), suggesting common pathways between distinct cell types that could be exploited. Conclusion: We have identified several targetable molecular features within variant bladder cancer subtypes. These findings set a critical starting point for future therapeutic investigation. Funding: California Urology Foundation (HY)Conflicts of interest: noneKeywords: Single cell analysis, bladder cancer, variants, genomics, biomarkers Citation Format: Heiko Yang, Hanbing Song, Paul Allegakoen, Kevin Lu, Elizabeth Yip, Keliana Hui, Kevin Chang, Corynn Kasap, Janae Gayle, Bradley Stohr, Arun Wiita, Chien-Kuang C. Ding, Maxwell V. Meng, Jonathan Chou, Sima P. Porten, Franklin W. Huang. Identification of molecular targets in bladder cancer variants using single-cell analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6405.

Abstract 1610: Elucidating tumor evolution and heterogeneity in metastatic bladder cancer from rapid autopsies

Abstract Background: Bladder Cancer is a highly prevalent cancer with staggering mortality of about 20%. Metastatic BLCA (mBLCA) with variant histologies are aggressive and have a poor prognosis. The extent and impact of tumor heterogeneity in these variant subtypes are not fully understood. This work explores the intricate characterization of intra-patient and inter-patient tumor heterogeneity through genomic and transcriptomic analyses, drawing insights from a unique rapid autopsy cohort comprising 20 patients. The resulting revelations provide critical perspectives on heterogeneity and clonal evolution in mBLCA, underscoring the essential role of understanding these dynamics for the development of personalized treatment strategies. Approach: Our research focuses on the genetic and molecular characteristics of these tumors, including the vast landscape of tumor heterogeneity, clonal evolution, genomic alterations, mutational signatures, and structural variants. Within the tumor microenvironment, we identified diverse cell populations with distinct genetic profiles. A detailed examination of mutational signatures sheds light on the specific processes underlying genetic alterations, while the investigation of structural variants elucidates their consequential role in cancer development and progression. Advanced bioinformatics tools are deployed to process and interpret the vast genomic and transcriptomic datasets, facilitating the identification of clonal populations, their genetic features, and the trajectory of clonal evolution. Furthermore, statistical models are employed to discern correlations between mutational signatures, treatment responses, and clinical outcomes. Summary: The study unveils substantial inter-patient heterogeneity and discernible differences in mutational signatures, revealing intriguing correlations with treatment responses. These variations are intricately connected to underlying genomic alterations, copy number alterations, and gene expression patterns, offer a detailed perspective on the molecular landscape of mBLCA. Conclusion: This multi-omics exploration stands as the most extensive study of its kind, leveraging rapid autopsy samples of metastatic variant histology BLCA. The research provides unprecedented resolution of genomic alterations and intra- and inter-patient tumor heterogeneity. The exploration of clonal evolution enhances our appreciation of the temporal dynamics of tumor progression, establishing a robust foundation for future therapeutic interventions precisely targeting evolving tumor clones. As we advance into an era of personalized medicine, these findings pave the way for tailored therapeutic strategies in the challenging landscape of metastatic variant histology Bladder Cancer. Citation Format: Pushpa Itagi, Sonali Arora, Thomas Persse, Michael Yang, Patricia Galipeau, Yixin Lin, Funda Vakar-Lopez, John K. Lee, Petros Grivas, Robert B. Montgomery, Jonathan L. Wright, Hung-Ming Lam, Andrew Hsieh, Gavin Ha. Elucidating tumor evolution and heterogeneity in metastatic bladder cancer from rapid autopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1610.

Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification.

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as The Cancer Genome Atlas (TCGA) have revealed the importance of understanding the molecular genetics of thyroid tumors. Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on the cell of origin of tumors and their clinical risk. This paper outlines the following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDNs) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The framework for benign lesions has been revised. The WHO 5th introduces a new category: "developmental abnormalities". Benign FDNs comprise "thyroid follicular nodular disease", follicular thyroid adenoma (FTA), FTA with papillary architecture, and oncocytic adenoma (OA). "Hürthle cell adenoma/carcinoma" is renamed oncocytic adenoma/carcinoma of the thyroid (OA/OCA), which can be distinguished from FTA/FTC by its unique genetic background. 3. Low-risk tumors include NIFTP, TT-UMP, and HTT, and they have an extremely low malignant potential or an uncertain malignant potential. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to their shared genetic and prognostic features. 7. Other miscellaneous tumors are categorized as salivary-gland-type carcinomas of the thyroid, thyroid tumors of uncertain histogenesis, thymic tumors within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies.

Abstract 1737: METTL3-mediated m6A modification promotes tumor progression in upper tract urothelial carcinoma

Abstract Upper tract urothelial carcinoma (UTUC), comprising 5% of urothelial neoplasms, is a rare malignancy arising from the transitional epithelium of the renal pelvis and ureter. Its rarity and diverse histology pose diagnostic and therapeutic challenges, often lead to delayed diagnoses. The absence of targeted therapies, coupled with a limited understanding of molecular pathogenesis, underscores the ongoing research in urological oncology for effective UTUC management. N6-methyladenosine (m6A) is the predominant RNA methylation in mammalian cells, with its inscription primarily orchestrated by METTL3, a crucial methyltransferase. METTL3 has been implicated in various cancers, affecting critical processes like proliferation, migration, and tumor progression. However, the specific mechanisms and biological function of how METTL3/m6A regulates the progression of UTUC remain unclear. In our study, we found that m6A modification and METTL3 expression were elevated in aggressive UTUC, both are negatively correlated with unfavorable clinical outcomes and poor patient survival. By overexpressing METTL3 in less aggressive UTUC cell lines BFTC909 and KTCC28, the abilities of cell proliferation, migration, invasion, and colony formation increased. Notably, overexpression of METTL3 also increased tumor growth and metastasis in the in vivo orthotopic mouse model. In contrast, knockdown of METTL3 decreases tumor progression in a highly aggressive UTUC cell line KTCC28M. Furthermore, our comparative analysis of RNA-seq and m6A MeRIP-seq datasets unveiled the regulation of 1660 genes by METTL3. This diverse set includes genes associated with tumor growth and metastasis (such as MYC, JAK2, and STAT3), as well as RNA processing-related genes which their critical roles in modulating mRNA stability and splicing (such as GEMIN5 and PABPC1L). Together, we noticed METTL3/m6A is a crucial protagonist in the oncogenic landscape of UTUC, which suggested that it can be used as a target for novel therapeutic strategy for UTUC treatment. Citation Format: LI-JIE LIN, PEI-HUA PENG, KAI-WEN HSU. METTL3-mediated m6A modification promotes tumor progression in upper tract urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1737.

Primary Adenosquamous Carcinoma of the Prostate.

Prostate cancer accounts for 29% of malignant diagnoses among men in the United States and is the second leading cause of death from cancer. Effective screening methods and improved treatment have decreased the mortality rate significantly. This decreased mortality rate, however, does not apply to all histologic variants. Adenosquamous carcinoma of the prostate is an extremely aggressive neoplasm with no current known curative therapy. It is often diagnosed after chemotherapy, radiation, or androgen deprivation therapy for traditional prostatic adenocarcinomas. Primary carcinomas of the prostate with squamous features include, but are not limited to, pure squamous cell carcinoma and adenocarcinoma mixed with squamous cell carcinoma (SCC). Important distinguishable clinical features of adenosquamous carcinoma include normal prostate-specific antigen (PSA) levels, even with advanced disease and osteolytic versus osteoblastic metastatic lesions in adenocarcinoma. Additional entities to consider in the differential diagnosis are squamous metaplasia of the prostate, secondary involvement of pure SCC, and urothelial carcinoma with squamous differentiation. Here, we present a de novo case of adenosquamous carcinoma in a 48-year-old man who rapidly developed extensive metastatic disease.

Biomarkers in the Diagnosis of Endometrial Precancers. Molecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions.

Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.

Prognostic Value of P63 Expression in Muscle-Invasive Bladder Cancer and Association with Molecular Subtypes-Preliminary Report.

There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.

Predicting individual outcomes after radical cystectomy in urothelial variants with Cancer of the Bladder Risk Assessment (COBRA) score.

To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

Pulmonary Recurrence of Colorectal Mucinous Adenocarcinoma and Sarcoidosis on 18 F-FDG PET/CT.

A 67-year-old woman, previously diagnosed with pulmonary sarcoidosis and sigmoid colon mucinous adenocarcinoma with pulmonary metastasis, showed an enlarged pulmonary nodule in routine follow-up. Because of the absence of treatment for either condition over the past 3 years, the nodule raised concerns of cancer recurrence or sarcoidosis progression. Its distinctive 18 F-FDG PET/CT appearance, compared with other pulmonary lesions, suggested a mucinous histology. The diagnosis was confirmed by pathological examination. This emphasizes the importance of knowledge of the 18 F-FDG PET/CT phenotype of neoplastic histological variants to address challenging diagnostic scenarios.

Lung adenocarcinoma: selection of surgical approaches in solid adenocarcinoma from the viewpoint of clinicopathologic features and tumor microenvironmental heterogeneity.

Solid adenocarcinoma represents a notably aggressive subtype of lung adenocarcinoma. Amidst the prevailing inclination towards conservative surgical interventions for diminutive lung cancer lesions, the critical evaluation of this subtype's malignancy and heterogeneity stands as imperative for the formulation of surgical approaches and the prognostication of long-term patient survival. A retrospective dataset, encompassing 2406 instances of non-solid adenocarcinoma (comprising lepidic, acinar, and papillary adenocarcinoma) and 326 instances of solid adenocarcinoma, was analyzed to ascertain the risk factors concomitant with diverse histological variants of lung adenocarcinoma. Concurrently, RNA-sequencing data delineating explicit pathological subtypes were extracted from 261 cases in the TCGA database and 188 cases in the OncoSG database. This data served to illuminate the heterogeneity across lung adenocarcinoma (LUAD) specimens characterized by differential histological features. Solid adenocarcinoma is associated with an elevated incidence of pleural invasion, microscopic vessel invasion, and lymph node metastasis, relative to other subtypes of lung adenocarcinoma. Furthermore, the tumor microenvironment (TME) in solid pattern adenocarcinoma displayed suboptimal oxygenation and acidic conditions, concomitant with augmented tumor cell proliferation and invasion capacities. Energy and metabolic activities were significantly upregulated in tumor cells of the solid pattern subtype. This subtype manifested robust immune tolerance and capabilities for immune evasion. This present investigation identifies multiple potential metrics for evaluating the invasive propensity, metastatic likelihood, and immune resistance of solid pattern adenocarcinoma. These insights may prove instrumental in devising surgical interventions that are tailored to patients diagnosed with disparate histological subtypes of LUAD, thereby offering valuable directional guidance.