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Aims Methods and results Conclusions The American Society of Clinical Oncology and College of American Pathologists HER2‐guidelines recommend repeat testing for most grade 1 mammary carcinomas that are HER2‐positive in the core biopsy. This study aimed to assess the value of repeat HER2‐testing and the histological features of HER2‐positive grade 1 carcinomas.A case‐series of HER2‐results of grade 1 carcinomas was conducted of patients with no pre‐operative systemic treatment over a 5‐year period. HER2‐positive carcinomas had histological review. Twelve HER2‐positive carcinomas were initially reported as grade 1. On review, two were reclassified as grade 2. The remaining 10 carcinomas represented 2% of the 508 grade 1 carcinomas. Eight HER2‐positive grade 1 carcinomas from other years were also studied. HER2‐positive carcinomas more often had marked nuclear pleomorphism (50 versus 6%) and were more often oestrogen receptor‐negative (17 versus 0.8%) and progesterone receptor‐negative (28 versus 8%) compared with HER2‐negative grade 1 carcinomas. Six carcinomas that were HER2 3+ in the core biopsy were also 3+ on repeat assessment. Five of seven carcinomas that were 2+ amplified in the core biopsy were also HER2‐positive in the excision.HER2‐positive grade 1 carcinomas are uncommon, and more often have marked nuclear pleomorphism and lack oestrogen receptor and progesterone receptor expression compared with HER2‐negative grade 1 carcinomas. A HER2‐poitive result in the core biopsy was confirmed in 11 of 13 tumours that had repeat testing. [ABSTRACT FROM AUTHOR]

Purpose: The goal of the study was to create a nomogram based on clinical risk factors to forecast the rate of locoregional recurrence-free survival (LRFS) in patients with esophageal squamous cell carcinoma (ESCC) who underwent radiotherapy (RT). Methods: In this study, 574 ESCC patients were selected as participants. Following radiotherapy, subjects were divided into training and validation groups at a 7:3 ratio. The nomogram was established in the training group using Cox regression. Performance validation was conducted in the validation group, assessing predictability through the C-index and AUC curve, calibration via the Hosmer-Lemeshow (H-L) test, and evaluating clinical applicability using decision curve analysis (DCA). Results: T stage, N stage, gross tumor volume (GTV) dose, location, maximal wall thickness (MWT) after RT, node size (NS) after RT, D computer tomography (CT) value, and chemotherapy were found to be independent risk factors that impacted LRFS by multivariate cox analysis, and the findings could be utilized to create a nomogram and forecast LRFS. the area under the receiver operating characteristic (AUC) curve and C-index show that for training and validation groups, the prediction result of LRFS using nomogram was more accurate than that of TNM. The LRFS in both groups was consistent with the nomogram according to the H-L test. The DCA curve demonstrated that the nomogram had a good prediction effect both in the groups for training and validation. The nomogram was used to assign ESCC patients to three risk levels: low, medium, or high. There were substantial variations in LRFS between risk categories in both the training and validation groups (p<0.001, p=0.003). Conclusions: For ESCC patients who received radiotherapy, the nomogram based on clinical risk factors could reliably predict the LRFS. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth. Case presentation: A 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45. Conclusions: G-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Mesonephric‐like adenocarcinoma (MLA) of the endometrium or ovary is a rare but distinct endometrial carcinoma which has a combination of characteristic morphological, immunohistochemical (IHC) and molecular features. SOX17 has been recently identified as a highly sensitive and specific marker for endometrial and ovarian carcinomas. In this study, we aimed to investigate SOX17 expression in MLA together with other IHCs to differentiate MLAs from other endometrial carcinomas.Seventeen previously diagnosed endometrial/ovarian MLAs were collected, and multiple IHCs were performed. Additionally, we performed SOX17, PAX8 and ER on tissue microarrays (TMAs) composed of 652 endometrial carcinomas from 2012 to 2015 when MLA diagnostic criteria were not established.All 17 MLAs showed diffuse strong positive PAX8, negative ER and variable TTF1/GATA3 staining. Notably, all MLAs showed negative (n = 10) or focal weak/moderate (n = 7) staining for SOX17, which is more diffuse and stronger than PAX8 in other endometrial carcinoma subtypes. This finding prompted us to screen TMAs with 652 endometrial carcinomas diagnosed before MLA by an approach of combined SOX17 and PAX8 IHCs, and 14 cases with positive PAX8 but negative/focal weak SOX17 were identified. We further studied the 14 cases by examining morphology and performing additional IHCs (TTF1, GATA3, ER and CD10) and would classify seven (50%) of them as MLAs based on morphological features and positive CD10, TTF1 and/or GATA3 staining.Our results suggest that a combination of SOX17 and PAX8 IHCs would aid in diagnosing MLA if the results show strong positive PAX8, but negative SOX17. [ABSTRACT FROM AUTHOR]

Purpose: In a population‐based cohort of 960 uveal melanoma (UM) patients, we describe patients with three additional malignancies, including one unique patient with four synchronous primary malignancies. Method: A descriptive presentation of the clinical course and outcome for UM patients with three additional primary malignancies. Results: After more than 20 years of follow‐up of the UM cohort, 11 patients (1.1%) were diagnosed with three additional primary malignancies before, simultaneously or after UM. Among these, one patient had four synchronous primary malignancies, detected during workup for a symptomatic UM. All diagnoses were treated during the following 4 months, firstly the breast cancer, thereafter, the lung and pancreatic cancers and finally the UM. The patient died 3 years later of abdominal carcinomatosis due to the pancreatic cancer. The family history and gene testing did not disclose any genetic predisposition for cancer. A comparison of the four synchronous tumours, morphologically and immunohistochemically, showed no similarities and the expression of antibodies was different. Conclusion: Patients with UM may be diagnosed with non‐ocular additional primary cancers. Thus, a comprehensive workup is obligatory and a further follow‐up of the UM patients seems necessary. The UM is not always the main problem. [ABSTRACT FROM AUTHOR]

Undifferentiated gastric carcinoma, characterized by anaplastic cells lacking distinct features of cytological or architectural differentiation, poses diagnostic and therapeutic challenges. Recent studies have suggested an association between this carcinoma and deficiencies in the SWI/SNF complex, particularly mutations in subunits such as SMARCA4. We herein report six cases of SMARCA4-deficient undifferentiated gastric carcinoma with molecular findings, highlighting the rarity and diagnostic pitfalls of this malignancy. Predominantly occurring in males over 50 years, these cases presented with nonspecific symptoms and were often diagnosed at an advanced stage. Histologically, the tumors exhibited a sheet-like growth pattern, reduced or absent epithelial markers, and loss of BRG-1 expression, with molecular analysis confirming SMARCA4 gene mutations. The response to conventional chemotherapy was poor, underscoring the importance of complete surgical resection and the development of alternative treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma is a rare subtype of triple‐negative breast carcinoma. These low‐grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple‐negative breast carcinomas. Solid‐variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple‐negative breast cancers. Breast adenoid cystic carcinoma exhibits MYB protein overexpression, which can be detected by immunohistochemistry (IHC). Aim: We compared the IHC expression of MYB in solid‐variant adenoid cystic carcinoma with that in other triple‐negative breast cancers. Methods: We conducted IHC staining of 210 samples of triple‐negative breast cancers, including solid‐variant adenoid cystic carcinoma (n = 17), metaplastic breast carcinoma (n = 44), basaloid triple‐negative breast cancer (n = 21), and other triple‐negative invasive ductal carcinoma (n = 128). We classified nuclear staining of MYB as diffuse/strong (3+), focal moderate (2+), focal weak (1+), or none (0). Results: All 17 solid/basaloid adenoid cystic carcinoma cases exhibited 3+ MYB expression. Of the 21 solid/basaloid triple‐negative breast cancers, one (5%) had 2+ expression, seven (33%) 1+ expression, and 13 (62%) 0 expression. Of the 44 metaplastic carcinoma cases, 39 cases (89%) had no (0) staining, and the other five cases had focal weak (1+) or moderate (2+) staining. Among the 128 triple‐negative invasive ductal carcinoma cases, 92 cases (72%) had no (0) staining, 36 cases (28%) exhibited focal weak (1+) or moderate (2+) staining. Conclusions: Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple‐negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5–4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe. [ABSTRACT FROM AUTHOR]

Introduction High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers. Methods Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as "low" or "high." Results PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]

Developing novel therapies that outperform the existing chemotherapeutic treatments is required for treatment-resistant ovarian clear cell carcinoma. We investigated the antitumor effect of metformin on ovarian clear cell carcinoma, enhancement of the antitumor effect by its combination with chemotherapy, and its molecular regulatory mechanism. First, we evaluated the viability of ovarian clear cell carcinoma lines using the water-soluble tetrazolium-1 assay and found that metformin suppressed cell viability. Cell viability was significantly suppressed by co-treatment with cisplatin and metformin. In contrast, co-treatment with paclitaxel and metformin showed no significant difference in viability compared with the group without metformin. Western blot analysis showed increased phosphorylation of AMP-activated protein kinase in some cell lines and suppressed phosphorylation of the mammalian target of rapamycin in a particular cell line. Flow cytometry analysis revealed a significant increase in the rate of apoptosis in the metformin-treated group and rate of cell cycle arrest at the G2/M phase in a particular cell line. These results indicated that metformin may be effective against cultured ovarian clear cell carcinoma cells, particularly in combination with cisplatin. [ABSTRACT FROM AUTHOR]

Background: Bladder urothelial carcinoma, is considered the 7th most common cancer in males. It is classified into luminal and basal subtypes depending on molecular markers, influencing prognosis and treatment. Identifying reliable biomarkers like GATA3, CK20, and CK5/6 through immunohistochemical methods can aid in early detection, risk stratification, and personalized treatment strategies. This study aims for evaluation prognostic role of these mentioned markers in correlation with clinicopathological parameters in urothelial carcinomas. Methods: Tumor samples of forty cases were immunohistochemically stained for GATA3, CK5/6, and CK20. A cutoff of 20% positivity was used to determine subtype classifications, with staining patterns guiding the categorization into basal, luminal, double positive, or double negative groups. Results: In this study of 40 urothelial carcinoma patients tumors were classified into basal and luminal subtypes using GATA3, CK5/6 and CK20 markers. GATA3 expression showed no significant association with clinicopathological parameters; while, CK20 was associated with tumor size, and CK5/6 with T, N classification, and lymphovascular invasion. Significant differences in clinicopathological parameters were observed when subtypes were defined by CK5/6, GATA3 or CK20, particularly in tumor grade, T and N classification, and gender. Basal molecular subtypes was correlated with poor prognostic parameters. Conclusions: This study documented that use of triple markers could define the luminal and basal subtypes of urothelial carcinoma. Basal tumors have shown to be associated with the aggressive behavior and future studies may allow the development of new therapies in the context of molecular subtypes. [ABSTRACT FROM AUTHOR]

Malignant papillary lesions, and in particular, encapsulated papillary carcinoma (EPC) of the breast, continue to present diagnostic challenges for the practising pathologist. In addition to the relative rarity of these lesions, the lack of evidence‐based diagnostic criteria, differences in the biological characteristics, and the clinical behaviour of in situ and invasive forms, variable use of immunohistochemical markers, and overlap with other tumour types including high‐grade circumscribed forms of invasive breast carcinomas has resulted in diagnostic discordance with potentially significant clinical and management implications. Pathologists should be familiar with the range of morphology observed in malignant papillary tumours, EPC, and EPC‐like tumours and the existence of tumours with overlapping features. In this review we summarize the common diagnostic pitfalls in malignant papillary tumours and provide an approach to the diagnostic evaluation and categorisation of these enigmatic entities. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is a common thyroid malignancy. The majority of thyroid lesion needs intraoperative frozen pathology diagnosis, which provides important information for precision operation. As digital whole slide images (WSIs) develop, deep learning methods for histopathological classification of the thyroid gland (paraffin sections) have achieved outstanding results. Our current study is to clarify whether deep learning assists pathology diagnosis for intraoperative frozen thyroid lesions or not. Methods: We propose an artificial intelligence-assisted diagnostic system for frozen thyroid lesions that applies prior knowledge in tandem with a dichotomous judgment of whether the lesion is cancerous or not and a quadratic judgment of the type of cancerous lesion to categorize the frozen thyroid lesions into five categories: papillary thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid tumor, and non-cancerous lesion. We obtained 4409 frozen digital pathology sections (WSI) of thyroid from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) to train and test the model, and the performance was validated by a six-fold cross validation, 101 papillary microcarcinoma sections of thyroid were used to validate the system's sensitivity, and 1388 WSIs of thyroid were used for the evaluation of the external dataset. The deep learning models were compared in terms of several metrics such as accuracy, F1 score, recall, precision and AUC (Area Under Curve). Results: We developed the first deep learning-based frozen thyroid diagnostic classifier for histopathological WSI classification of papillary carcinoma, medullary carcinoma, follicular tumor, anaplastic carcinoma, and non-carcinoma lesion. On test slides, the system had an accuracy of 0.9459, a precision of 0.9475, and an AUC of 0.9955. In the papillary carcinoma test slides, the system was able to accurately predict even lesions as small as 2 mm in diameter. Tested with the acceleration component, the cut processing can be performed in 346.12 s and the visual inference prediction results can be obtained in 98.61 s, thus meeting the time requirements for intraoperative diagnosis. Our study employs a deep learning approach for high-precision classification of intraoperative frozen thyroid lesion distribution in the clinical setting, which has potential clinical implications for assisting pathologists and precision surgery of thyroid lesions. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of thyroid nodules and malignancies in the elderly is a growing concern. Thyroid nodules in this population have unique characteristics, requiring careful treatment strategies that balance risks and benefits. Oncocytic carcinoma of the thyroid (OCA) is a rare, aggressive subtype with diagnostic challenges. Methods: This case features an 84-year-old patient who presented with a neck mass and symptoms of asphyxia. Clinical evaluation, imaging studies, and biopsy were conducted to assess the nature of the thyroid lesion. Molecular testing, including genetic analysis, was performed to identify specific mutations associated with OCA and guide treatment decisions. Results: The patient was diagnosed with oncocytic carcinoma of the thyroid. The molecular testing revealed specific genetic mutations indicative of OCA, confirming the diagnosis. The presence of these mutations guided the treatment plan, emphasizing the importance of molecular diagnostics in managing thyroid malignancies, especially in the elderly. Discussion: This case illustrates the complexities of diagnosing and treating thyroid malignancies in the elderly. Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention. [ABSTRACT FROM AUTHOR]

Key points Interpretation of surgical mapping is essential for postoperative radiotherapy planning. Operative and pathological reports lack comprehensive information on margins quality and tissue block mapping. Standardizing reports is essential to reduce uncertainties, aiming for less morbid poRT. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the protein expression levels of UCHL1, SNRNP200, and PAK4 in clear cell renal cell carcinoma (CCRCC) using advanced proteomic techniques. We found that UCHL1 and SNRNP200 are significantly upregulated, and PAK4 is downregulated in high-grade CCRCC, and all are involved in critical cellular pathways linked to cancer progression and poor clinical outcomes. Specifically, UCHL1 is implicated in the Akt signaling pathway, SNRNP200 plays a role in RNA splicing and cell cycle regulation, and PAK4 is associated with cell proliferation and invasion. The enhanced expression of UCHL1 and SNRNP200, and decreased expression of PAK4 correlate with shorter progression-free survival in CCRCC patients, suggesting their potential as prognostic markers and targets for therapeutic intervention. This research contributes to the understanding of CCRCC's molecular dynamics and opens new avenues for targeted treatments. Recent advancements in proteomics have enhanced our understanding of clear cell renal cell carcinoma (CCRCC). Utilizing a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation, we investigated the expression levels of UCHL1, PAK4, and SNRNP200 in high-grade CCRCC samples. Our analysis also integrated Reactome pathway enrichment to elucidate the roles of these proteins in cancer-related pathways. Our results revealed significant upregulation of UCHL1 and SNRNP200 and downregulation of PAK4 in high-grade CCRCC tissues compared to non-cancerous tissues. UCHL1, a member of the ubiquitin carboxy-terminal hydrolase family, showed variable expression across different tissues and was notably involved in the Akt signaling pathway, which plays a critical role in cellular survival in various cancers. SNRNP200, a key component of the RNA splicing machinery, was found to be essential for proper cell cycle progression and possibly linked to autosomal dominant retinitis pigmentosa. PAK4's role was noted as critical in RCC cell proliferation and invasion and its expression correlated significantly with poor progression-free survival in CCRCC. Additionally, the expression patterns of these proteins suggested potential as prognostic markers for aggressive disease phenotypes. This study confirms the upregulation of UCHL1, SNRNP200, and PAK4 as significant factors in the progression of high-grade CCRCC, linking their enhanced expression to poor clinical outcomes. These findings propose these proteins as potential prognostic markers and therapeutic targets in CCRCC, offering novel insights into the molecular landscape of this malignancy and highlighting the importance of targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology Background: Hereditary breast cancer arising in BRCA1-deficient patients is commonly diagnosed as invasive carcinoma of no special type (NST) with medullary features, while invasive lobular carcinoma (ILC) appears to be significantly under-represented in BRCA1 mutation carriers. We report a case of pleomorphic ILC arising in a 28-year-old woman harboring a germline BRCA1 c.3756_3759delGTCT p.(Ser1253Argfs*10) pathogenic variant. Case Report: A nulliparous 28-year-old woman with a family history of BRCA1 mutation presented to the symptomatic breast clinic with a several-week history of a left 80-mm breast lump. Core biopsy established a diagnosis of a poorly differentiated triple-negative breast cancer (TNBC) of pleomorphic lobular phenotype. Her clinical diagnosis was cT3, N0, M0, cStageIIB. The MDT recommended CT staging, MRI breast imaging and neoadjuvant chemotherapy (NACT). PET CT imaging showed no evidence of distant metastatic disease. The patient had a good radiological response to NACT with a FEC-T carboplatin regimen. Post-NACT imaging showed a residual cystic mass and the patient underwent a mastectomy and sentinel lymph node biopsy with plans for a delayed latissimus dorsi reconstruction following her adjuvant radiotherapy treatment. A complete pathological response was subsequently demonstrated without any evidence of metastatic disease. Conclusions: This case is the first report of pleomorphic ILC with a triple-negative receptor status and a complete pathological response in a BRCA1 mutation carrier. Our study expands the heterogeneous spectrum of TNBC and contributes to a better understanding of the molecular genetic landscape that characterizes invasive pleomorphic lobular neoplasia. [ABSTRACT FROM AUTHOR]

Background: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). Methods: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. Results: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. Conclusions: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery. [ABSTRACT FROM AUTHOR]

Background information Results Conclusions Significance Arpin, an Arp2/3 inhibitory protein, inhibits lamellipodial protrusions and cell migration. Arpin expression is lost in tumor cells of several cancer types.Here we analyzed expression levels of Arpin and various markers using Reverse Phase Protein Array (RPPA) in human mammary carcinomas. We found that Arpin protein levels were correlated with those of several DNA damage response markers. Arpin‐null cells display enhanced clustering of double stand breaks (DSBs) when cells are treated with a DNA damaging agent, in line with a previously described role of the Arp2/3 complex in promoting DSB clustering for homologous DNA repair (HDR) in the nucleus. Using a specific HDR assay, we further showed that Arpin depletion increased HDR efficiency two‐fold through its ability to inactivate the Arp2/3 complex.Arpin regulates both cell migration in the cytosol and HDR in the nucleus.Loss of Arpin expression coordinates enhanced cell migration with up‐regulated DNA repair, which is required when DNA damage is induced by active cell migration. [ABSTRACT FROM AUTHOR]

Context Aims Materials and Methods Results Conclusion The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non‐proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories – inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system.The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters.All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated.Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non‐PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system.Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases. [ABSTRACT FROM AUTHOR]

The transformation of a benign phyllodes tumor (PT) into a malignant PT and/or carcinoma is extremely uncommon. We present a case of a 66-year-old female with a huge mass on the left breast which was successfully removed by surgical resection. The pathological diagnosis was infiltrating lobular carcinoma with pure rhabdoid features and the malignant transformation of a benign phyllodes tumor. The first time this rare case was reported, it is demonstrated a special phenomenon through the synchronous transformation of PT grades and the carcinomatous transformation of PT. [ABSTRACT FROM AUTHOR]

Thymic carcinoma (TC) is an uncommon type of thymic epithelial tumors. Patients with relapsed or refractory TCs have a poor prognosis. Immune checkpoint inhibitor monotherapy can be applied as a second-line treatment for such cases. This study reported a TC patient who did not respond to conventional chemotherapy and radiotherapy but achieved prolonged partial remission lasting 17 months following the third-line treatment with antiprogrammed cell death-1 inhibitor sintilimab. This patient did not experience any serious side effects associated with sintilimab treatment. The above results demonstrated that sintilimab could be a feasible therapeutic option for refractory TC patients. [ABSTRACT FROM AUTHOR]

Background: Poorly differentiated thyroid carcinoma (PDTC) accounts for a small portion of thyroid carcinomas but contributes to a significant proportion of thyroid carcinoma-associated deaths. The clinicopathological prognostic factors and clinical outcomes of PDTC remain unclear. We aimed to evaluate the clinical outcomes of patients with PDTC after curative treatment. Methods: A comprehensive search was performed up to September 2023. We included studies investigating treatment outcomes in patients with PDTC who underwent initial surgery. The 5-year disease-free survival (DFS) and overall survival (OS) were extracted. In this meta-analysis, the enrolled PDTC histological criteria included 3rd, 4th, and 5th World Health Organization (WHO) and Memorial Sloan Kettering Cancer Center (MSKCC) classification. A random-effects model was used for the pooled proportion analysis. Meta-regression analysis was conducted to evaluate the prognostic factors. Results: Twenty retrospective studies published between 2007 and 2023, including 1,294 patients, met all inclusion criteria. Studies that diagnosed PDTC based on various histological criteria including 3rd WHO (n=5), 4th WHO (n=12), 5th WHO (n=2), and MSKCC (n=1) were included. Overall, 5-year DFS and 5-year OS were 49.4% (95% confidence interval [CI], 42.3 to 56.4) and 73.8% (95% CI, 66.5 to 79.9), with moderate heterogeneity of 58% and 55%, respectively. In meta-regression analysis, extrathyroidal extension (ETE) was a prognostic factor for OS. Conclusion: The meta-analysis of DFS and OS in patients with PDTC show the moderate heterogeneity with a variety of histological criteria. ETE appears to have a significant impact on OS, regardless of histological criteria. [ABSTRACT FROM AUTHOR]

Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) in the caudate lobe presents surgical challenges due to the lack of distinct anatomical landmarks. This case report introduces a novel surgical approach combining Takasaki's classification and indocyanine green negative counterstaining for precise anatomical caudate lobectomy. A 78-year-old patient with hepatocellular carcinoma in the caudate lobe underwent surgery following preoperative volumetric assessment. The method involved a glissonian approach for both left and right pedicles, coupled with meticulous dissection of hepatic pedicles of the caudate lobe guided by taping of left and right glissonian pedicles, followed by indocyanine green administration for improved visualization of caudate lobe boundaries. The procedure enabled complete tumor resection with minimal blood loss. At 50 months postsurgery, the patient maintains favorable liver function and performance status. This innovative approach offers a promising solution for precise resection of caudate lobe hepatocellular carcinoma, potentially improving surgical outcomes and long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests that immunotherapy has a positive effect on non–small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, it remains unclear which type of immunotherapy is more efficient. The aim of this network meta‐analysis (NMA) was to compare the efficacy and safety of different immunotherapy types and determine the optimal option. Method: Four databases (PubMed, Cochrane Library databases, Embase, and Web of Science) and ClinicalTrial.gov were searched from inception until January 26, 2023. Randomized controlled trials (RCTs), prospective nonrandomized trials, or observational studies investigating NSCLC patients with BMs treated by immunotherapy were included. The quality of the included studies was evaluated using the Cochrane risk of bias (ROB) tool and the Newcastle‐Ottawa Scale (NOS). The efficacy of immunotherapy on NSCLC patients with BMs was evaluated using frequentist random‐effects NMA. Result: Eleven studies from 1560 citations, encompassing 1437 participants, were included in this NMA. Statistical analysis showed that pembrolizumab (SMD = 4.35, 95% CI [2.21, 6.60]) and nivolumab+ipilimumab (SMD = 3.81, 95% CI [1.21, 6.40]) could improve overall survival (OS). Pembrolizumab (SMD = 3.32, 95% CI [2.75, 3.90]) demonstrated better effects in improving the overall response rate (ORR). No significant difference in adverse event (AE) was observed between immunotherapy and chemotherapy. Conclusion: Our findings indicated that pembrolizumab was the most promising immunotherapy for NSCLC patients with BMs. Nivolumab+ipilimumab might be an alternative choice to improve OS. Limitation: Inconsistency tests were not performed because of the scarcity of direct comparison. Besides, high heterogeneity was observed in our NMA. [ABSTRACT FROM AUTHOR]

Aims: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. Methods: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000–2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. Results: The cohort comprised IPMNs with invasive tubular‐type (n = 82, 70%) and colloid‐type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS‐, AS‐, and TS‐based pT stages were not significantly associated with recurrence‐free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular‐type carcinomas, higher LS‐, AS‐, and TS‐based pT stages trended with lower RFS (based on 1‐, 3‐, and 5‐year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5‐cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. Conclusions: For invasive tubular‐type carcinomas arising in IPMN, microscopic size‐based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid‐type histology that generally portend a more favourable prognosis. [ABSTRACT FROM AUTHOR]

Background and aim: Head and neck nuclear protein of testis carcinoma (HN‐NUT) is a rare form of carcinoma diagnosed by NUT immunohistochemistry positivity and/or NUTM1 translocation. Although the prototype of HN‐NUT is a primitive undifferentiated round cell tumour (URC) with immunopositivity for squamous markers, it is our observation that it may assume variant histology or immunoprofile. Methods: We conducted a detailed clinicopathological review of a large retrospective cohort of 30 HN‐NUT, aiming to expand its histological and immunohistochemical spectrum. Results: The median age of patients with HN‐NUT was 39 years (range = 17–86). It affected the sinonasal tract (43%), major salivary glands (20%), thyroid (13%), oral cavity (7%), larynx (7%), neck (7%) and nasopharynx (3%). Although most cases of HN‐NUT (63%) contained a component of primitive URC tumour, 53% showed other histological features and 37% lacked a URC component altogether. Variant histological features included basaloid (33%), differentiated squamous/squamoid (37%), clear cell changes (13%), glandular differentiation (7%) and papillary architecture (10%), which could co‐exist. While most HN‐NUT were positive for keratins, p63 and p40, occasional cases (5–9%) were entirely negative. Immunopositivity for neuroendocrine markers and thyroid transcription factor‐1 was observed in 33 and 36% of cases, respectively. The outcome of HN‐NUT was dismal, with a 3‐year disease specific survival of 38%. Conclusions: HN‐NUT can affect individuals across a wide age range and arise from various head and neck sites. It exhibits a diverse spectrum of histological features and may be positive for neuroendocrine markers, potentially leading to underdiagnosis. A low threshold to perform NUT‐specific tests is necessary to accurately diagnose HN‐NUT. [ABSTRACT FROM AUTHOR]

Purpose: The goal of our study was to better characterize new CT diagnoses of peritoneal carcinomatosis (PC) in the ED, and to evaluate how to best identify the primary lesion. Prompt identification of the source of the carcinomatosis may allow for the patient to receive early initial care from the correct clinical service. Methods: All new CT cases of PC-like appearance identified on CT in the ED from January 2017 through July 2020. Each report and corresponding medical record were manually reviewed. Patient demographics, presence/absence of intravenous contrast, source organ predicted by the radiologist in the CT scan report, pathologic diagnosis, and amount of ascites were tabulated. Chi-tests were used to test the statistical significance of differences between groups. Results: Of the 131 CT cases of new PC-like appearance which received workup, 108 cases had pathologically proven PC and 23 cases had no underlying malignancy yielding a positive predictive value for actual PC of 82%. The most common cause of new PC in women was gynecological (66%), and in men was of GI tract origin (57%). Concordance between radiologist prediction and final pathology was higher with intravenous contrast (58%) compared to without contrast (40%); although this difference was not statistically significant (p = 0.19). A moderate or large amount of ascites was found in more than half of GYN primaries and in adenocarcinoma of unknown primary and there was a statistically significant difference in amount of ascites between cancer primaries (p = 0.01). Conclusion: A PC-like appearance on CT in the ED will likely be in patients with known malignancy, but of the new cases, there is a high PPV for it to represent new peritoneal carcinomatosis. Gynecological and GI malignancies are the most common cause in women and men, respectively, and this may help in focusing the radiologist's search pattern. Usage of intravenous contrast may help in identifying a primary lesion, and the presence of high-volume ascites should suggest a GYN primary or adenocarcinoma of unknown primary when there is no other obvious primary lesion. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of tyrosine kinase inhibitor (TKI)combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, from January 2018 to December 2022, and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to secondline TKI with or without immune checkpoint inhibitor. The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group, and the 31 patients receiving second-line TKI alone were enrolled as single treatment group. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response, and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events. The Kaplan-Meier method was used to calculate median overall survival (mOS)and median progression-free survival (mPFS)for the two groups, and the two groups were compared in terms of objective response rate (ORR)and disease control rate (DCR). The chi-square test was used for comparison of baseline data and follow-up results between groups. Results The median follow-up time was 16.5(3.2 — 53.4)months for the 63 patients. The combination group had an mOS of 24.3(95% confidence interval ［CI］：20.0—28.6)months and an mPFS of 9.8(95%CI：7.5—12.1)months, while the single treatment group had an mOS of 15.8(95%CI：11.4—20.1)months and an mPFS of 4.1(95%CI：3.2—4.9)months, and there were significant differences in mOS and mPFS between the two groups (P=0.029 and 0.038). The combination group had an ORR of 47% and a DCR of 84%, while the single treatment group had an ORR of 19% and a DCR of 65%； there was a significant difference in ORR between the two groups (P=0.021), but with no significant difference in DCR between the two groups (P= 0.070). As for adverse events, 4 patients (12.5%)in the combination group and 3(10.0%)in the single treatment group experienced grade Ⅲ — Ⅳ serious adverse events, with no fatal drug reactions in either group, and there was no significant difference in the incidence rate of adverse events between the two groups (P=0.783). Conclusion Compared with TKI alone, TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC, without increasing serious adverse reactions [ABSTRACT FROM AUTHOR]

The mainstay of successful treatment for parathyroid carcinoma remains complete surgical excision. Although intraoperative parathyroid hormone (ioPTH) monitoring is a useful adjunct during parathyroidectomy for benign primary hyperparathyroidism, its utility for parathyroid carcinoma remains unclear. A retrospective review of 796 patients who underwent parathyroidectomy with ioPTH monitoring for primary hyperparathyroidism revealed 13 patients with parathyroid carcinoma on final pathology from two academic institutions. A systematic review yielded 5 additional parathyroid carcinoma patients. Complete excision of malignancy, or operative success (eucalcemia ≥6 mo. after parathyroidectomy); operative failure (persistent hypercalcemia <6 mo. after parathyroidectomy); and perioperative complications were evaluated. Comparison of the >50% ioPTH decrease alone to >50% ioPTH decrease into normal reference range was analyzed using Chi-squared, Kolmogorov–Smirnov, Kruskal–Wallis tests. All 18 parathyroid carcinoma patients achieved a >50% ioPTH decrease, and 14 patients also had a final ioPTH level decrease into normal reference range. 93% of patients who met normal parathyroid hormone reference range had operative success, whereas only two of the four (50%) patients with parathyroid carcinoma with a >50% ioPTH decrease alone demonstrated operative success. Parathyroidectomy guided by a >50% ioPTH decrease into normal reference range may better predict complete excision of malignant tissue in patients with parathyroid carcinoma compared to >50% ioPTH decrease alone. IoPTH monitoring should be used in conjunction with clinical judgment and complete en bloc resection for optimal treatment and success. • There are minimal intraoperative adjuncts to guide resection of parathyroid cancer. • >50% intraoperative parathyroid hormone decrease into normal reference predicts complete surgical excision. • Intraoperative parathyroid hormone monitoring with complete en bloc excision should be completed. [ABSTRACT FROM AUTHOR]

Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5–20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5–100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Maxillary sinus carcinomas usually present as a locally advanced disease at the time of diagnosis and it is extremely unusual to have a second primary maxillary carcinoma on the contralateral side after many years of completion of treatment of the first malignancy. We present here a case report of a sphenopalatine artery (SPA) pseudoaneurysm mimicking the second primary maxillary carcinoma. Methods: We reviewed the literature for SPA pseudoaneurysm. Results/case report: This report describes the case of a 90-year-old man with a background of adenoid cystic carcinoma of the right maxillary sinus, diagnosed and treated with surgery and radiotherapy 14 years ago, who presented with a history of multiple episodes of epistaxis. The radiological evaluation showed a heterogeneously enhancing mass with a central hemorrhagic component and surrounding bony erosions in the left maxillary sinus and the patient was planned for biopsy from the suspicious mass along with SPA ligation. However, on opening the maxillary antrum there was excessive bleeding and it was determined unsafe to proceed further. The patient was subsequently taken to interventional radiology for diagnostic angiography which revealed an SPA pseudoaneurysm that was subsequently embolized successfully. Conclusions: Sphenopalatine artery pseudoaneurysms should be considered as a differential for recurrent epistaxis in patients with a history of sinonasal malignancy. In such cases, endovascular embolization is a viable management option. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Epithelial‐myoepithelial carcinoma of the breast is an extremely rare biphasic tumor. This report documents the first case of epithelial‐myoepithelial carcinoma presenting in the location of a previously treated ductal carcinoma in order to increase the awareness of this entity as a potential differential for recurrent breast lesions. Epithelial‐myoepithelial carcinoma of the breast is an exceedingly rare biphasic tumor, seldom documented in medical literature. This report describes the first known case of this entity at the site of a previously treated neoplasm in a 75‐year‐old female with a history of high‐grade ductal carcinoma in situ who presented with a new breast mass. Imaging demonstrated an oval shaped mass with microlobulated borders and hypoechoic echogenicity on ultrasound. Following multidisciplinary discussion, she underwent a mastectomy, revealing epithelial‐myoepithelial carcinoma with metaplastic squamous cell carcinoma. The patient began chemotherapy but discontinued due to poor tolerance and neurological complications. Generally, prognosis for epithelial‐myoepithelial carcinoma (World Health Organization Classification of Breast Tumors 2019, 8562/3) is highly variable, with limited available data suggesting that epithelial‐myoepithelial carcinoma may follow a course similar to that of breast adenocarcinomas with both hematogenous and lymphatic spread. Treatment typically involves curative excision, though the role of axillary lymph node sampling remains under discussion. This case underscores the need for vigilance in post‐treatment surveillance for breast cancer and highlights the importance of recognizing this entity in recurrent breast pathology. [ABSTRACT FROM AUTHOR]

Skin cancer is the most common cancer type in the USA, with over five million annually treated cases and one in five Americans predicted to develop the disease by the age of 70. Skin cancer can be classified as melanoma or non-melanoma (NMSC), the latter including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC). Development of BCC and SCC is impacted by environmental, behavioral, and genetic risk factors and the incidence is on the rise, with the associated number of deaths surpassing those caused by melanoma, according to recent reports. Substantial morbidity is related to both BCC and SCC, including disfigurement, loss of function, and chronic pain, driving high treatment costs, and representing a heavy financial burden to patients and healthcare systems worldwide. Clinical presentations of BCC and SCC can be diverse, sometimes carrying considerable phenotypic similarities to benign lesions, and underscoring the need for the development of disease-specific biomarkers. Skin biomarker profiling plays an important role in deeper disease understanding, as well as in guiding clinical diagnosis and patient management, prompting the use of both invasive and non-invasive tools to evaluate specific biomarkers. In this work, we review the known and emerging biomarkers of BCC and SCC, with a focus on molecular and histologic biomarkers relevant for aspects of patient management, including prevention/risk assessments, tumor diagnosis, and therapy selection. [ABSTRACT FROM AUTHOR]

• Bartholin gland carcinomas are rare, accounting for 5.8% of all vulvar cancers. • Misdiagnosis leads to significant diagnostic delays of up to 19 months. • Surgery was the preferred treatment modality for early-stage Bartholin gland carcinoma. • Primary chemoradiation ± surgical nodal assessment was favoured for stage II/III tumors. • Five-year recurrence free and overall survival were 76% and 64%, respectively. To evaluate the management and outcomes of Bartholin gland cancer at a single tertiary institution. A single institution retrospective review of 9 cases of BGC between 2004 and 2022 was conducted. Demographics, pathological characteristics, treatment, follow up and oncologic outcomes were extracted from clinical records. Data are summarised using descriptive statistics and survival probabilities are presented with Kaplan Meier graphs. Ten cases of BGC were identified at our institution over a period of 18 years. Nine out of ten clinical records were available for analysis. Eight patients presented with vulval swelling and four were treated initially for Bartholin cyst or abscess. One patient had a histological diagnosis of adenoid cystic carcinoma while the remaining were squamous cell carcinomas. With the exception of stage I disease chemoradiation was the primary mode of treatment. Adverse events included skin desquamation (4/9), venous thrombo-embolism (2/9), gastro-intestinal (1/9) and neurotoxicity (1/9). Median follow up was 60 months with a 5-year recurrence free and overall survival at 76 % and 64 % respectively. BGC may present after a long duration of symptoms and at advanced stages. Primary chemoradiation appears to be a feasible treatment option in advanced disease with the benefit of decreased morbidity. [ABSTRACT FROM AUTHOR]

Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8–22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. The median hospital stay after BNCT was 2 days (1–6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required. [ABSTRACT FROM AUTHOR]

The Hounsfield unit density value (HUDV) is a relative quantitative measurement of radio density used by radiologists in the interpretation of computed tomography (CT) images. Our aim is to investigate the role of HUDV in evaluating pre-epiglottic space (PES) involvement of laryngeal carcinoma. Seventy-four patients treated for laryngeal carcinoma in our clinic between 2014 and 2019 were included in the study. The invasion status of PES was determined radiologically and pathologically. HUDV was measured with a circular selected region of interest, with a constant size of 10 mm2 for PES. The relationship between patological PES invasion, radiological PES invasion, and HUDV was evaluated. Measuring HUDV to determine PES invasion (74.3 %) was significantly higher than​​ conventional CT evaluation (59.5 %) (p = 0.001). The agreement coefficient (kappa value) of the conventional CT evaluation and the HUDV regarding PES involvement was 0.673, which was interpreted as 'good'. HUDV could be used as an additional tool in diagnosing pre-epiglottic space invasion in laryngeal cancer. [ABSTRACT FROM AUTHOR]

Small mammals are very popular companion animals, and the incidence of particular tumour types in these animals is the subject of extensive research. We carried out a retrospective and comparative analysis of the incidence of reproductive tract and mammary tumours and tumour-like lesions collected from 103 pet rabbits, 75 pet rats, 71 guinea pigs, 12 mice, 11 hamsters, eight African pygmy hedgehogs, four ferrets and two chinchillas. The results indicate that uterine tumours and tumour-like lesions are common in pet rabbits, guinea pigs and African pygmy hedgehogs. In pet rabbits, the most common uterine tumour was endometrial adenocarcinoma, while in guinea pigs benign lesions predominated (ie, leiomyoma, endometrial adenoma, cystic endometrial hyperplasia and deciduoma). Uterine tumours in African pygmy hedgehogs included adenosarcomas and endometrial polyps. Ovarian lesions were found only in guinea pigs (ovarian rete adenomas, rete cysts) and African pygmy hedgehogs (mostly granulosa cell tumours), while testicular tumours were diagnosed in pet rabbits, one pet rat and one guinea pig. Mammary tumours were common in pet rabbits, pet rats, guinea pigs, mice, hamsters and African pygmy hedgehogs. In pet rats, the most common mammary tumour was fibroadenoma, while in other animals carcinomas predominated. In guinea pigs and, to a lesser extent, in pet rats, a significant percentage of mammary tumours occurred in males. Guinea pigs seem to be predisposed to mammary tumours of ductal origin. This study describes for the first time uterine angioleiomyoma in the pet rabbit and mammary spindle cell carcinoma in the Djungarian hamster and chinchilla. [ABSTRACT FROM AUTHOR]

Background Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts. Methods We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype. Results Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort. Conclusions The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes. [ABSTRACT FROM AUTHOR]

Background Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. Methods The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. Results Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. Conclusion This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy. [ABSTRACT FROM AUTHOR]

Bowens disease is a rare condition, considered a precursor to squamous cell carcinoma. Because of its similarity to several other skin conditions, accurate diagnosis can be challenging. There are multiple risk factors and several treatment options. This article has hoped to give an overview of risk factors, signs and symptoms, treatment, and complications with the aim of giving nurses and non-medical prescribers increased confidence in recognising this disease. Bowen's disease is a rare condition thought to affect approximately 15 per 100,000 people in the UK each year. Because of the similarity with other skin conditions, diagnosis can be challenging for clinicians. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a gluten-sensitive immune-mediated enteropathy. This proof-of-concept study used a convolutional neural network (CNN) to classify hematoxylin and eosin (H&E) CD histological images, normal small intestine control, and non-specified duodenal inflammation (7294, 11,642, and 5966 images, respectively). The trained network classified CD with high performance (accuracy 99.7%, precision 99.6%, recall 99.3%, F1-score 99.5%, and specificity 99.8%). Interestingly, when the same network (already trained for the 3 class images), analyzed duodenal adenocarcinoma (3723 images), the new images were classified as duodenal inflammation in 63.65%, small intestine control in 34.73%, and CD in 1.61% of the cases; and when the network was retrained using the 4 histological subtypes, the performance was above 99% for CD and 97% for adenocarcinoma. Finally, the model added 13,043 images of Crohn's disease to include other inflammatory bowel diseases; a comparison between different CNN architectures was performed, and the gradient-weighted class activation mapping (Grad-CAM) technique was used to understand why the deep learning network made its classification decisions. In conclusion, the CNN-based deep neural system classified 5 diagnoses with high performance. Narrow artificial intelligence (AI) is designed to perform tasks that typically require human intelligence, but it operates within limited constraints and is task-specific. [ABSTRACT FROM AUTHOR]

Introduction: It is not known if the nature, number and duration of presenting symptoms at diagnosis of hepatocellular carcinoma impact on overall survival. This study examines whether the presenting symptoms of hepatocellular carcinoma have a significant impact on prognosis. Methods: The study cohort comprised 725 patients with symptomatic hepatocellular carcinoma seen in our department since October 1983. Another 545 patients were diagnosed on surveillance or from incidental findings. Presenting symptoms at diagnosis were documented. A survival census was performed on 31 October 2015 with the national registry of deaths. Presenting symptoms were examined for association with overall survival using multivariable Cox regression analysis. Survival analysis was done by Kaplan-Meier method with log-rank testing. Bivariate Pearson correlation was used to look for any association between duration of symptoms and overall survival. Results: Patients with symptomatic hepatocellular carcinoma had a significantly shorter survival than those diagnosed incidentally or on screening (94.0 vs. 786.0 days, P < 0.001). Survival was shorter in patients presenting with fluid retention (56.0 vs. 118.0 days, P < 0.001), jaundice (48.0 vs. 94.0 days, P = 0.017) and two or more symptoms (P = 0.010). Pain was associated with better survival (P < 0.001). On multivariable Cox regression analysis, only fluid retention (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.30-1.87) and jaundice (HR 1.36, 95% CI 1.07-1.74) were independently associated with shorter survival. There was no significant relationship between the duration of symptoms and overall survival. Conclusion: Patients with hepatocellular carcinoma who present with fluid retention or jaundice have significantly shorter overall survival. This is useful in assessing patients at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background and aims: Second‐generation direct‐acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV‐associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC. Methods: Participants underwent full HLA class I/KIR typing and long‐term HCV follow‐up. Results: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow‐up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA‐treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell‐mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK‐cell‐mediated immunity did not predict HCC. Conclusion: Cirrhosis is the main risk state predisposing to HCC, but weak NK‐cell‐mediated immunity may predispose to post‐2G DAA HCC more than intermediate or strong NK‐cell‐mediated immunity. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions A Serous Tubal Intraepithelial Carcinoma (STIC) without concomitant invasive carcinoma is occasionally identified and associated with a high risk of subsequent peritoneal carcinomatosis. Management needs optimisation. This study explores professionals' opinions and clinical practices regarding the diagnosis, counselling, treatment and follow‐up of isolated STIC to facilitate clinical decision making and optimise the direction of future research. A secondary aim is to assess international clinical guidelines.Focus group study.Four online sessions.International panel (n = 12 countries) of gynaecologists, gynaecologic oncologists, pathologists and medical oncologists (n = 49).A semi‐structured interview guide was used. Two independent researchers analysed transcripts by open and axial coding. Results were organised in domains. Relevant (inter)national guidelines were screened for recommendations regarding isolated STIC.Professionals' opinions and clinical practices regarding isolated STIC management.Regarding pathology, most professionals identified the SEE‐FIM protocol as standard of care for high‐risk patients, whereas variation exists in the histopathological examination of fallopian tubes in the general population. Confirmation of STIC diagnosis by a specialised pathologist was recommended. Regarding work‐up and follow‐up after STIC diagnosis, there was variety and discordance. Data on outcomes is limited. As for treatment, chemotherapy and PARP inhibitors were not recommended by most. Eleven guidelines provided limited recommendations.We identified recommendations and highlighted knowledge gaps in the diagnosis and management of isolated STIC. Moreover, recommendations in clinical guidelines are limited. There is an agreed need for international collaboration for the prospective registration of isolated STIC. [ABSTRACT FROM AUTHOR]

Background: Periampullary adenocarcinomas typically exhibit either intestinal or pancreatobiliary (PB) differentiation, and the type of differentiation may be prognostically more important than the anatomic site of origin. This study aimed to evaluate prognostic significance of histological type of periampullary carcinomas. Methods: Microscopic slides from 110 consecutive pancreatoduodenectomies performed between 2010 and 2020 were reviewed and classified as intestinal or PB type. Clinicopathological factors were compared between PB-(n=93) and intestinal-type (n=17) differentiation. Results: The intestinal type included significantly more patients with welldifferentiated histology (35.3% vs. 11.8%, p=0.001) and fewer patients with perineural invasion (41.2% vs. 76.4%, p=0.029), advanced T stage (> T3; 41.2% vs.74.2%, p=0.007), and systemic recurrence (71.4% vs. 92.9%, p=0.005) than PB type. The 5-year-overall survival rate of intestinal-type was significantly higher than that of PB-type (58.8% vs. 20.4%, p=0.003). When pancreatic cancer was separately analyzed, the intestinal type showed the best 5-year-overall survival rate, with no significant difference between the PB types excluding PDAC and PDAC (39.4% vs. 19.2%, p=0.148). In multivariate analysis, curative resection (hazard ratio, 0.417; 95% CI, 0.219-0.792, p=0.008) was the only significant prognostic factor. Conclusion: Although intestinal histologic phenotype was not an independent prognostic factor on multivariate analysis, it showed pathologic features associated with better survival, while the PB type showed more aggressive tumor biology and consequently worse survival. Further studies are needed to demonstrate the prognostic significance of histologic phenotype. [ABSTRACT FROM AUTHOR]

Introduction: Icaritin (ICT), a promising anti-hepatocellular carcinoma (HCC) prenylated flavonoid, is hindered from being applied due to its low water solubility and high lipophilicity in poorly differentiated HCC which is associated with upregulation of CD44 isoforms. Thus, hyaluronic acid (HA), a natural polysaccharide with high binding ability to CD44 receptors, was used to formulate a modified liposome as a novel targeted ICT-delivery system for HCC treatment. Methods: The ICT-Liposomes (Lip-ICT) with and without HA were prepared by a combined method of thin-film dispersion and post-insertion. The particle size, polydispersity (PDI), zeta potential, encapsulation efficacy (%EE), drug loading content (%DLC), and in vitro drug release profiles were investigated for physicochemical properties, whereas MTT assay was used to assess cytotoxic effects on HCC cells, HepG2, and Huh7 cells. Tumor bearing nude mice were used to evaluate the inhibitory effect of HA-Lip-ICT and Lip-ICT in vivo. Results: Lip-ICT and HA-Lip-ICT had an average particle size of 171.2 ± 1.2 nm and 208.0 ± 3.2 nm, with a zeta potential of −13.9 ± 0.83 and −24.8 ± 0.36, respectively. The PDI resulted from Lip-ICT and HA-Lip-ICT was 0.28 ± 0.02 and 0.26 ± 0.02, respectively. HA-Lip-ICT demonstrated higher in vitro drug release when pH was dropped from 7.4 to 5.5, The 12-h release rate of ICT from liposomes increased from 30% at pH7.4 to more than 60% at pH5.5. HA-LipICT displayed higher toxicity than Lip-ICT in both HCC cells, especially Huh7with an IC50 of 34.15 ± 2.11 μM. The in vivo tissue distribution and anti-tumor experiments carried on tumor bearing nude mice indicated that HA-Lip- ICT exhibited higher tumor accumulation and achieved a tumor growth inhibition rate of 63.4%. Discussion: The nano-sized Lip-ICT was able to prolong the drug release time and showed long-term killing HCC cells ability. Following conjugation with HA, HA-Lip-ICT exhibited higher cytotoxicity, stronger tumor targeting, and tumor suppression abilities than Lip-ICT attributed to HA-CD44 ligand-receptor interaction, increasing the potential of ICT to treat HCC. [ABSTRACT FROM AUTHOR]

Head and neck squamous carcinoma (HNSC) is a prevalent malignant disease, with the majority of patients being diagnosed at an advanced stage. Endoplasmic reticulum stress (ERS) is considered to be a process that promotes tumorigenesis and impacts the tumor microenvironment (TME) in various cancers. The study aims to investigate the predictive value of ERS in HNSC and explore the correlation between ERS-related genes and TME. A series of bioinformatics analyses were carried out based on mRNA and scRNA-seq data from the TCGA and GEO databases. We conducted RT-qPCR and western blot to validate the signature, and performed cell functional experiments to investigate the in vitro biological functions of the gene. We identified 63 ERS-related genes that were associated with outcome and stage in HNSC. A three-gene signature (ATF6, TRIB3, and UBXN6) was developed, which presents predictive value in the prognosis and immunotherapy response of HNSC patients. The high-risk group exhibited a worse prognosis but may benefit from immunotherapy. Furthermore, there was a significant correlation between the signature and immune infiltration. In the high-risk group, fibroblasts were more active in intercellular communication, and more T cells were observed at the end of the sequential phase. The genes in the ERS-related signature were overexpressed in HNSC cells, and the knockdown of TRIB3 significantly inhibited cell proliferation and migration. This study established a novel ERS-related signature that has potential implications for HNSC therapy and the understanding of TME. [ABSTRACT FROM AUTHOR]