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Human Pathology Jun 2024Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have...
Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis.
Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.
PubMed: 38876201
DOI: 10.1016/j.humpath.2024.06.006 -
Thyroid : Official Journal of the... Jun 2024Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images...
Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images (WSIs) of thyroid fine-needle aspiration cytology (FNA), incorporating z-stacking, from institutions across the nation to develop an AI model. We conducted a multicenter retrospective diagnostic accuracy study using thyroid FNA dataset from the Open AI Dataset Project that consists of digitalized images samples collected from 3 university hospitals and 215 Korean institutions through extensive quality check during the case selection, scanning, labeling, and reviewing process. Multiple z-layer images were captured using three different scanners and image patches were extracted from WSIs and resized after focus fusion and color normalization. We pretested six AI models, determining Inception ResNet v2 as the best model using a subset of dataset, and subsequently tested the final model with total datasets. Additionally, we compared the performance of AI and cytopathologists using randomly selected 1031 image patches and reevaluated the cytopathologists' performance after reference to AI results. A total of 10,332 image patches from 306 thyroid FNAs, comprising 78 malignant (papillary thyroid carcinoma) and 228 benign from 86 institutions were used for the AI training. Inception ResNet v2 achieved highest accuracy of 99.7%, 97.7%, and 94.9% for training, validation, and test dataset, respectively (sensitivity 99.9%, 99.6%, and 100% and specificity 99.6%, 96.4%, and 90.4% for training, validation, and test dataset, respectively). In the comparison between AI and human, AI model showed higher accuracy and specificity than the average expert cytopathologists beyond the two-standard deviation (accuracy 99.71% [95% confidence interval (CI), 99.38-100.00%] vs. 88.91% [95% CI, 86.99-90.83%], sensitivity 99.81% [95% CI, 99.54-100.00%] vs. 87.26% [95% CI, 85.22-89.30%], and specificity 99.61% [95% CI, 99.23-99.99%] vs. 90.58% [95% CI, 88.80-92.36%]). Moreover, after referring to the AI results, the performance of all the experts (accuracy 96%, 95%, and 96%, respectively) and the diagnostic agreement (from 0.64 to 0.84) increased. These results suggest that the application of AI technology to thyroid FNA cytology may improve the diagnostic accuracy as well as intra- and inter-observer variability among pathologists. Further confirmatory research is needed.
Topics: Humans; Biopsy, Fine-Needle; Thyroid Neoplasms; Retrospective Studies; Artificial Intelligence; Thyroid Gland; Thyroid Cancer, Papillary; Reproducibility of Results; Sensitivity and Specificity; Thyroid Nodule; Cytology
PubMed: 38874262
DOI: 10.1089/thy.2023.0384 -
Nature Communications Jun 2024Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are...
Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
Topics: Humans; Thyroid Cancer, Papillary; Chernobyl Nuclear Accident; Lymphatic Metastasis; Male; Adult; Female; Thyroid Neoplasms; Mutation; Iodine Radioisotopes; Adolescent; Proto-Oncogene Proteins B-raf; Young Adult; Lymph Nodes; Proto-Oncogene Proteins c-ret; Child; Genomics; Middle Aged; Homeodomain Proteins; Gene Expression Profiling; MicroRNAs; Neoplasms, Radiation-Induced; Neck; Gene Expression Regulation, Neoplastic
PubMed: 38871684
DOI: 10.1038/s41467-024-49292-z -
International Journal of Gynecological... Jul 2024Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of...
Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.
Topics: Humans; Female; Ovarian Neoplasms; Carcinoma, Endometrioid; Middle Aged; Adult; Aged; Immunohistochemistry; Biomarkers, Tumor; Adenocarcinoma; GATA3 Transcription Factor; PAX8 Transcription Factor; Cell Differentiation; Endometriosis
PubMed: 38870078
DOI: 10.1097/PGP.0000000000001002 -
Frontiers in Oncology 2024With a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the...
BACKGROUND
With a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the molecular level and the immune environment within tumors of various thyroid cancer subtypes in order to identify potential targets for therapy and provide precise treatment for patients with thyroid adenocarcinoma.
METHODS
First, we analyzed the expression of IRX5 in pan-cancer and papillary thyroid carcinoma by bioinformatics methods and collected paired samples from our center for validation. Subsequently, we analyzed the significance of IRX5 on the prognosis and diagnosis of PTC. Next, we explored the possible mechanisms by which IRX5 affects the prognosis of thyroid cancer patients by GO/KEGG enrichment analysis, and further investigated the effect of IRX5 on immune infiltration of thyroid cancer. Ultimately, by conducting experiments on cells and animals, we were able to show how IRX5 impacts the aggressive characteristics of thyroid cancer cells and its influence on macrophages within the immune system of thyroid cancer.
RESULTS
In 11 malignant tumors, including PTC, IRX5 is overexpressed and associated with a poor prognosis. IRX5 may affect the prognosis of PTC through embryonic organ development, ossification, mesenchyme development, etc. Increased IRX5 expression decreases the presence of cytotoxic and Th17 cells in papillary thyroid cancer. IRX5 was highly expressed in different PTC cell lines, such as K-1 and TPC-1. Silencing IRX5 effectively halted the growth and movement of PTC cells while also decreasing M2 polarization and enhancing M1 polarization in tumor-associated macrophages.
CONCLUSION
IRX5 could impact the outlook of individuals with PTC by stimulating the shift of macrophages to M2 in the immune surroundings of thyroid cancer growths, suggesting a potential new focus for treating thyroid cancer, particularly through immunotherapy.
PubMed: 38868535
DOI: 10.3389/fonc.2024.1399484 -
Practical Laboratory Medicine May 2024While recent studies have demonstrated several genetic alterations are associated with pathogenesis of RCC, the significance of cyclin-dependent kinase inhibitor 2A and...
OBJECTIVES
While recent studies have demonstrated several genetic alterations are associated with pathogenesis of RCC, the significance of cyclin-dependent kinase inhibitor 2A and cyclin-dependent kinase inhibitor 2B in tumorigenesis of RCC is less clear. We investigate the distribution of and mutations in patients with RCC and analyze the impact of and mutations on RCC.
METHODS
A pathological examination was conducted using thirty fresh renal tissue samples with renal masses that had undergone partial or radical nephrectomy. Multiplex ligation-dependent probe amplification (MLPA) was used to detect genetic aberrations of and in genomic DNA isolated from samples. Subsequently, and mutations were confirmed using chromosomal microarray technique.
RESULTS
Twenty-one patients were diagnosed with RCC, eight with benign diseases, including angiomyolipoma (AML) and oncocytoma, and one with mucinous adenocarcinoma of renal pelvis. Two of twenty-one patients (9.5 %) with clear-cell RCC were positive for and gene deletions. Interestingly, patients with and mutations were associated with sarcomatoid patterns of RCC (2 out of 4, 50 %). In contrast, no or deletions were detected in samples from benign renal tumors, papillary RCC, or other kidney cancers.
CONCLUSIONS
This study demonstrated the potential use of and as biomarkers for the prognostic and molecular classification of renal cancer. and mutations may be associated with RCC development and sarcomatoid changes. Further research is needed to understand the underlying molecular mechanisms of and in the pathogenesis of RCC.
PubMed: 38867760
DOI: 10.1016/j.plabm.2024.e00410 -
Hereditary Cancer in Clinical Practice Jun 2024Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing...
Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient's family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A > G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient's screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.
PubMed: 38867252
DOI: 10.1186/s13053-024-00281-9 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2024To investigate cyclin D2 (CCND2) expression in papillary thyroid carcinoma (PTC) and its association with the clinicopathological features.
OBJECTIVE
To investigate cyclin D2 (CCND2) expression in papillary thyroid carcinoma (PTC) and its association with the clinicopathological features.
METHODS
The public databases TCGA, TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues, and its diagnostic value for PTC was analyzed using ROC curves. GO enrichment analysis of CCND2-related differentially expressed genes (DEGs) in PTC was performed, and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source. RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP. CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry, and its correlation with clinicopathological features of the patients were analyzed.
RESULTS
Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues ( < 0.001) in close correlation with tumor stage, gender, age, pathological subtype, and lymph node involvement ( < 0.05). ROC curve analysis showed that at the cutoff value of 4.983, the diagnostic sensitivity, specificity, and accuracy of CCND2 expression for PTC was 83.6%, 94.9%, and 78.5%, respectively. CCND2 expression was positively correlated with B cells, CD4 T cells, and macrophages ( < 0.001) and negatively with CD8 T cells ( < 0.01), and also correlated with memory B-cell infiltration, CD4 T-cell memory activation, M2 macrophages, resting mast cells, and mast cell activation ( < 0.05). RT-qPCR, Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells ( < 0.01) and also in clinical PTC tissues than in the adjacent tissues ( < 0.05) in correlation with tumor size, lymph node metastasis and TNM stage ( < 0.05).
CONCLUSION
CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..
Topics: Humans; Cyclin D2; Thyroid Cancer, Papillary; Thyroid Neoplasms; Cell Line, Tumor; Female; Male; ROC Curve; RNA, Messenger; Gene Expression Regulation, Neoplastic; Lymphatic Metastasis
PubMed: 38862457
DOI: 10.12122/j.issn.1673-4254.2024.05.21 -
Cureus May 2024Urachal carcinoma is an uncommon malignancy with a peculiar biomolecular characterization and therefore a complex approach. It was incorporated by the World Health...
Urachal carcinoma is an uncommon malignancy with a peculiar biomolecular characterization and therefore a complex approach. It was incorporated by the World Health Organization in 2004 in the tumors of the urinary system classification. This neoplasm is generally diagnosed in advanced stages. The standard treatment is surgical, however, due to the rarity and relatively late clinical manifestation of urachal carcinomas, the survival data are mostly case reports, as well as information about medical-surgical treatment based on evidence. The data used were extracted from both the physical and electronic clinical records. Among atypical presentations reported in the literature, we report a case of urachal adenocarcinoma with simultaneous glomerulonephritis as a paraneoplastic syndrome of which there is no report to date. Surgery was carried out in our patient, unfortunately with lifetime morbidity from kidney function replacement secondary to kidney function damage by glomerulonephritis, despite previous immunosuppression treatment for rapidly progressive glomerulonephritis. It is worth mentioning that if the initial diagnosis represents a clinical challenge, treatment is even more complex, given the little information that currently exists about it. Urachal carcinoma is a diagnostic and treatment challenge. Up to now, surgery has been the treatment of choice in localized or locally advanced disease, however, with a high morbidity for the patient.
PubMed: 38860075
DOI: 10.7759/cureus.60106 -
American Journal of Cancer Research 2024lncRNA PTCSC3, which stands for Papillary Thyroid Carcinoma Susceptibility Candidate 3, has been found to play a role in various cellular processes, including cell...
Human bone marrow mesenchymal stem cell-driven LncRNA PTCSC3 upregulation within lung adenocarcinoma cells reduces erlotinib resistance by mitigating Wnt/β-Catenin pathway.
lncRNA PTCSC3, which stands for Papillary Thyroid Carcinoma Susceptibility Candidate 3, has been found to play a role in various cellular processes, including cell proliferation, apoptosis, and migration, acting as either an oncogene or a tumor suppressor depending on the context. This study investigates the influence of lncRNA PTCSC3, derived from human bone marrow mesenchymal stem cell (hBMSC), on the efficacy of erlotinib (Er)-resistant lung adenocarcinoma (LUAD) cells and elucidates underlying mechanism. The hBMSCs and LUAD (PC9 and A549) cells were employed to establish an Er-resistant LUAD cell model. It was observed that exposure to hBMSCs reduced the viability of A549-Er and PC9-Er cells and increased their rate of apoptosis. Further investigations revealed that in the presence of hBMSCs-containing medium, PTCSC3 expression was significantly upregulated, concomitantly with a suppression of the Wnt/β-Catenin pathway. Conversely, silencing PTCSC3 led to enhanced A549-Er and PC9-Er activities, reduced cell apoptosis, and activated Wnt/β-Catenin pathway. The effects of PTCSC3 modulation were also examined by transfecting LUAD cells with different PTCSC3 expression vectors and treating them with XAV939, a Wnt/β-Catenin pathway inhibitor, which similarly decreased cell viability. In the rescue experiment, the effect of hBMSCs on LUAD cells could be counteracted by down-regulation of PTCSC3, and the effect of PTCSC3 down-regulation on cells was mitigated by XAV939. This study revealed that hBMSCs promote the up-regulation of PTCSC3 in LUAD cells, thus inhibiting Wnt/β-Catenin pathway and reversing Er resistance, offering a potential novel strategy to enhance the efficacy of chemotherapy in LUAD.
PubMed: 38859830
DOI: 10.62347/BOFP2157