A large, locally aggressive giant cell tumour arising from the laryngeal cartilage: A Rare Case Report.

Giant cell tumour is a growth predominantly found in long bones of the body. Giant cell tumour has a rare occurrence in the head and neck. A case of a 31 year old male with no known comorbidities at the ENT Department, Shifa International Hospital, Islamabad presented with anterior neck swelling and hoarseness of voice. Patient was diagnosed as having Giant Cell Tumour of Larynx (GTCL) proven on FNA cytology and post-operative biopsy. GCTL is an uncommon entity with only 45 reported cases in the world.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

A rare case of a huge malignant pleural mesothelioma presenting in the posterior mediastinum.

We report a case of a 69-year-old woman with pleural mesothelioma presenting in the posterior mediastinum with a maximum diameter of 25 cm. She had a chronic cough and a pleural effusion was noted on chest X-ray. The examination of the effusion showed high hyaluronic acid levels, and mesothelioma was suspected. A chest computed tomography scan showed a huge mediastinal mass, which caused rapid progression of respiratory failure and compression of the heart. Sufficient tissue samples could not be obtained before death. The patient died approximately 1 month after the initial visit, and a pathological autopsy was performed. The diagnosis of malignant pleural mesothelioma was made. Malignant pleural mesothelioma with a huge posterior mediastinal mass such as in this case is considerably rare; however, it is a rapidly progressing form of the disease and is reported here as an important differential diagnosis for mediastinal tumours.

A Young Female with a Hepatic Epithelioid Hemangioendothelioma.

Background: Primary hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare tumour of vascular origin with an incidence of <0.1 cases per 100,000 people worldwide. Case description: A 29-year-old female with the history of epigastric pain and unintentional weight loss (3 kg over six months) was referred for upper endoscopy. The examination was without visual pathological findings, but a rapid urease test was positive. First-line treatment with clarithromycin-containing triple therapy for Helicobacter pylori infection was given. After completion of eradication therapy, diffuse abdominal pain developed. An abdominal computed tomography (CT) showed multiple liver nodules. Three consecutive core liver biopsies were performed and were inconclusive. A subsequent surgical liver nodule resection was performed. Histopathology of the specimen revealed grade 2 hepatocellular carcinoma; bone scintigraphy was negative for metastasis. A multidisciplinary team (MDT) recommended giving the patient sorafenib, which was poorly tolerated. The histology was reviewed using immunohistochemistry staining at the request of the oncologist, which showed expression of CD31 and CD34. Based on clinical, morphological and immunohistochemistry findings, a diagnosis of hepatic epithelioid hemangioendothelioma was made. Based on the multidisciplinary team's findings, liver transplantation was indicated as the only curative treatment. Conclusion: Because of the rarity of this disease, combining clinical, radiological and histopathological methods as well as an MDT approach can help to reach the correct final diagnosis. As demonstrated in this clinical case, it is crucial to perform immunohistochemistry of a liver biopsy to confirm a HEHE diagnosis. LEARNING POINTS: Hepatic epithelioid hemangioendothelioma is a rare vascular tumour that is often misdiagnosed and mismanaged.This case emphasises the critical importance of interdisciplinary teamwork and the use of non-invasive and invasive techniques to achieve a definitive diagnosis.

Elevated Procalcitonin Levels can Occur in Bacterial Infections and also in Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare and challenging type of thyroid cancer originating from parafollicular cells (C cells) that produce calcitonin. Diagnosing and monitoring this carcinoma can be complex due to its unique biomarkers. Procalcitonin (PCT), a precursor of calcitonin, and carcinoembryonic antigen (CEA) are important markers for MTC. Elevated PCT levels, particularly when they remain high post-infection treatment, and elevated CEA levels are significant indicators for suspecting MTC. This report emphasises the diagnostic and prognostic importance of these biomarkers in MTC, highlighting their roles in detecting and monitoring disease progression. Integrating PCT and CEA measurements into routine clinical practice can enhance detection, provide understanding of therapeutic responses and aid in the effective management of MTC. LEARNING POINTS: Procalcitonin (PCT) is a more stable and reliable biomarker than calcitonin for diagnosing and monitoring medullary thyroid carcinoma (MTC).Elevated carcinoembryonic antigen (CEA) levels effectively monitor MTC progression, especially when calcitonin levels are inconsistent.Incorporating PCT and CEA measurements into routine practice enhances MTC management, providing reliable biomarkers for diagnosis and monitoring.

Stromal lymphocytes are associated with upgrade of B3 breast lesions.

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade. A higher number of lymphocytes in the surrounding specialised stroma was observed in upgraded ductal and papillary B3 lesions than non-upgraded (p < 0.01, negative binomial model, n = 307). We developed a model using lymphocytes combined with age and the type of lesion, which was predictive of upgrade with an area under the curve of 0.82 [95% confidence interval 0.77-0.87]. The model can identify some patients at risk of upgrade with high sensitivity, but with limited specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic, but additional predictive features are needed.

The immunomodulatory ballet of tumour-derived extracellular vesicles and neutrophils orchestrating the dynamic CD73/PD-L1 pathway in cancer.

Head and neck squamous cell carcinoma (HNSCC) is a global cancer burden with a 5-year overall survival rate of around 50%, stagnant for decades. A tumour-induced immunosuppressive microenvironment contributes to HNSCC progression, with the adenosine (ADO) pathway and an upregulated expression of inhibitory immune checkpoint regulators playing a key role in this context. The correlation between high neutrophil-to-lymphocyte ratio (NLR) with advanced tumour staging suggests involvement of neutrophils (NØ) in cancer progression. Interestingly, we associated a high NLR with an increased intracellular PD-L1 localization in primary HNSCC samples, potentially mediating more aggressive tumour characteristics and therefore synergistically favouring tumour progression. Still, further research is needed to harness this knowledge for effective treatments and overcome resistance. Since it is hypothesized that the tumour microenvironment (TME) may be influenced by small extracellular vesicles (sEVs) secreted by tumours (TEX), this study aims to investigate the impact of HNSCC-derived TEX on NØ and blockade of ADO receptors as a potential strategy to reverse the pro-tumour phenotype of NØ. UMSCC47-TEX exhibited CD73 enzymatic activity involved in ADO signalling, as well as the immune checkpoint inhibitor PD-L1. Data revealed that TEX induce chemotaxis of NØ and the sustained interaction promotes a shift into a pro-tumour phenotype, dependent on ADO receptors (P1R), increasing CD170high subpopulation, CD73 and PD-L1 expression, followed by an immunosuppressive secretome. Blocking A3R reduced CD73 and PD-L1 expression. Co-culture experiments with HNSCC cells demonstrated that TEX-modulated NØ increase the CD73/PD-L1 axis, through Cyclin D-CDK4/6 signalling. To support these findings, the CAM model with primary tumour was treated with NØ supernatant. Moreover, these NØ promoted an increase in migration, invasion, and reduced cell death. Targeting P1R on NØ, particularly A3R, exhibited potential therapeutic strategy to counteract immunosuppression in HNSCC. Understanding the TEX-mediated crosstalk between tumours and NØ offers insights into immunomodulation for improving cancer therapies.

SMARCB1/INI1-deficient undifferentiated tumour of the thorax: a case report and review of the literature.

The 5th WHO classification of thoracic tumours includes thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) among the "other epithelial tumours of the lung" chapter. Herein, we present a case of undifferentiated thoracic neoplasm with retention of SMARCA4 expression, lack of NUT fusion protein and loss of SMARCB1/INI1 expression. After presenting the clinical and pathological features of the tumour, we carried out a review of the literature on the same topic. Albeit very rare, we believe this entity should be included in the heterogeneous group of undifferentiated neoplasms of the thorax.

Tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma.

Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.

The relationship between Stroma AReactive Invasion Front Areas (SARIFA), Warburg-subtype and survival: results from a large prospective series of colorectal cancer patients.

BACKGROUND: Stroma AReactive Invasion Front Areas (SARIFA) is a recently identified haematoxylin & eosin (H&E)based histopathologic biomarker in gastrointestinal cancers, including colorectal cancer (CRC), defined as direct contact between tumour cells and adipocytes at the tumour invasion front. The current study aimed at validating the prognostic relevance of SARIFA in a large population-based CRC series as well as at investigating the relationship between SARIFA-status and previously established Warburg-subtypes, both surrogates of the metabolic state of the tumour cells. METHODS: SARIFA-status (positive versus negative) was determined on H&E slides of 1,727 CRC specimens. Warburg-subtype (high versus moderate versus low) data was available from our previous study. The associations between SARIFA-status, Warburg-subtype, clinicopathological characteristics and CRC-specific as well as overall survival were investigated. RESULTS: 28.7% (n=496) CRC were SARIFA-positive. SARIFA-positivity was associated with more advanced disease stage, higher pT category, and more frequent lymph node involvement (all p<0.001). SARIFA-positivity was more common in Warburg-high CRC. 44.2% (n=219) of SARIFA-positive CRCs were Warburg-high compared to 22.8% (n=113) being Warburg-low and 33.1% (n=164) being Warburg-moderate (p<0.001). In multivariable-adjusted analysis, patients with SARIFA-positive CRCs had significantly poorer CRC-specific (HRCRC-specific 1.65; 95% CI 1.41-1.93) and overall survival (HRoverall survival 1.46; 95% CI 1.28-1.67) independent of clinically known risk factors and independent of Warburg-subtype. Combining the SARIFA-status and the Warburg-subtype to a combination score (SARIFA-negative/Warburg-high versus SARIFA-positive/Warburg-low versus SARIFA-positive/Warburg-high, and so on) did not improve the survival prediction compared to the use of SARIFA-status alone (SARIFA-negative + Warburg-high: HRCRC-specific 1.08; 95% CI 0.84-1.38; SARIFA-positive + Warburg-low: HRCRC-specific 1.79; 95% CI 1.32-2.41; SARIFA-positive + Warburg-high: HRCRC-specific 1.58; 95% CI 1.23-2.04). CONCLUSIONS: Our current study is the by far largest external validation of SARIFA-positivity as a novel independent negative prognostic H&E-based biomarker in CRC. In addition, our study shows that SARIFA-positivity is associated with the Warburg-high subtype. Further research is warranted to provide a more mechanistic understanding of the underlying tumour biology. Based on our data, we conclude SARIFA-status should be implemented in pathologic routine practice to stratify CRC patients.

Keloid of Pinna Revealed a Chondroid Syringoma in Disguise.

Cutaneous mixed tumor or chondroid syringoma is a rare benign, skin appendageal tumor prevalent in areas of the head and neck. It represents the cutaneous counterpart of the pleomorphic adenoma of salivary glands. Its clinical presentation often misguides the clinician to underdiagnose it as a reactive lesion. We report the case of a 94-year-old male admitted for excision of cutaneous carcinoma concurrently with a chondroid syringoma of the pinna provisionally misdiagnosed as a keloid.

A detailed insight into macrophages' role in shaping lung carcinogenesis.

Despite significant advancements in cancer treatment in recent decades, the high mortality rate associated with lung cancer remains a significant concern. The development and proper execution of new targeted therapies needs more deep knowledge regarding the lung cancer associated tumour microenvironment. One of the key component of that tumour microenvironment is the lung resident macrophages. Although in normal physiological condition the lung resident macrophages are believed to maintain lung homeostasis, but they may also initiate a vicious inflammatory response in abnormal conditions which is linked to lung cancer development. Depending on the activation pathway, the lung resident macrophages are either of M1 or M2 sub-type. The M1 and M2 sub-types differ significantly in various prospectuses, from phenotypic markers to metabolic pathways. In addition to this generalized classification, the recent advancement of the multiomics technology is able to identify some other sub-types of lung resident macrophages. Researchers have also observed that these different sub-types can manipulate the pathogenesis of lung carcinogenesis in a context dependent manner and can either promote or inhibit the development of lung carcinogenesis upon receiving proper activation. As proper knowledge about the role played by the lung resident macrophages' in shaping the lung carcinogenesis is limited, so the main purpose of this review is to bring all the available information under the same roof. We also elaborated the different mechanisms involved in maintenance of the plasticity of M1/M2 sub-type, as this plasticity can be a good target for lung cancer treatment.

A Case of Traumatic Distal End Radius Fracture With a Hemorrhagic Volar Wrist Ganglion Cyst.

Wrist ganglion cysts are the most common benign soft tissue swelling in the hand and wrist. They may arise from flexor and extensor tendon sheaths, interphalangeal joints, wrist joints, and even the neural tissues around the hand and wrist. Some volar wrist ganglion cysts arise from the radiocarpal joint and scaphotrapezial joint. It is uncommonly encountered as an incidental finding during the fixation of a distal radius fracture. In our case, a volar wrist hemorrhagic ganglion cyst was incidentally found during the fixation of the fracture. Prior to the injury, the patient had no complaints of swelling over her right wrist. The cyst was removed using microscopic magnification.

Predicting the response to neoadjuvant chemoradiation for rectal cancer using nomograms based on MRI tumour regression grade.

PURPOSE: This study aimed to develop nomograms that combine clinical factors and MRI tumour regression grade to predict the pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. METHODS: The retrospective study included 204 patients who underwent neoadjuvant chemoradiotherapy and surgery between January 2013 and December 2021. Based on pathological tumour regression grade, patients were categorized into four groups: complete pathological response (pCR, n=45), non-complete pathological response (non-pCR; n=159), good pathological response (pGR, n=119), and non-good pathological response (non-pGR, n=85). The patients were divided into a training set and a validation set in a 7:3 ratio. Based on the results of univariate and multivariate analyses in the training set, two nomograms were respectively constructed to predict complete and good pathological responses. Subsequently, these predictive models underwent validation in the independent validation set. The prognostic performances of the models were evaluated using the area under the curve (AUC). RESULTS: The nomogram predicting complete pathological response incorporates tumour length, post-treatment mesorectal fascia involvement, white blood cell count, and MRI tumour regression grade. It yielded an AUC of 0.787 in the training set and 0.716 in the validation set, surpassing the performance of the model relying solely on MRI tumour regression grade (AUCs of 0.649 and 0.530, respectively). Similarly, the nomogram predicting good pathological response includes the distance of the tumour's lower border from the anal verge, post-treatment mesorectal fascia involvement, platelet/lymphocyte ratio, and MRI tumour regression grade. It achieved an AUC of 0.754 in the training set and 0.719 in the validation set, outperforming the model using MRI tumour regression grade alone (AUCs of 0.629 and 0.638, respectively). CONCLUSIONS: Nomograms combining MRI tumour regression grade with clinical factors may be useful for predicting pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. The proposed models could be applied in clinical practice after validation in large samples.

DNA Methylation and Its Effects on TRIM29 Gene Expression in the Equine Sarcoid Tissue.

Sarcoids are the most frequently diagnosed dermatological tumour in horses. It is a disease that can affect various species of equids, such as donkeys, mules and zebras. This type of tumour can develop in all horse breeds, regardless of age and gender. Treatment options depend on many factors, such as the type of lesion, location, extent, owner preference and financial considerations. In the present study, we investigated the TRIM29 expression, the methylation status of its first exon and its involvement in the formation of equine sarcoids. Bisulfite sequencing PCR (BSP) was used to determine DNA methylation at CpG sites and real-time quantitative polymerase chain reaction (qPCR) was used to detect TRIM29 expression level. Our results showed that TRIM29 is significantly downregulated in lesional samples (FC = -3.72; p < 0.001). Furthermore, TRIM29 expression was significantly correlated (R = -0.73; p < 0.001) with hypermethylation of its specific CpG sites in the first exon of this gene. Our research has demonstrated that the identification of increased methylation of CpG sequences in horse sarcoids, along with the decreased expression of the TRIM29 gene, is an important step towards understanding the molecular mechanisms underlying the disease. These findings can serve in the future as a diagnostic biomarker for horse sarcoids and help in detecting the disease.

Intraoperative frozen section evaluation of ovarian sex cord-stromal tumours and their mimics: a study of 121 cases with emphasis on potential diagnostic pitfalls.

Ovarian sex cord-stromal tumours (SCSTs) present diagnostic difficulties during frozen section (FS) consultations due to their diverse morphology. This study aimed to evaluate the accuracy of FS evaluation of SCSTs in our institution, as well as to examine the reasons leading to incorrect FS diagnosis. Cases mimicking SCSTs and diagnosed as such during FS were also highlighted. We analysed 121 ovarian SCST cases and their mimics which underwent FS consultations over a 10-year period, to evaluate FS accuracy, reasons for deferrals and discrepancies. FS diagnoses were concordant, deferred and discrepant compared to the final diagnosis in 50 (41.3%), 39 (32.2%) and 32 (26.5%) cases, respectively. Major discrepancies (9/121, 7.4%) were mostly related to the diagnosis of adult granulosa cell tumour (AGCT). A fibromatous AGCT was misinterpreted as fibroma on FS, while a cystic AGCT was called a benign cyst. Conversely, a mesonephric-like adenocarcinoma, a sertoliform endometrioid carcinoma and a thecoma were misinterpreted as AGCT on FS. Another discrepant case was a Krukenberg tumour with prominent fibromatous stroma in which malignant signet ring cells were overlooked and misinterpreted as fibroma. Minor discrepancies were primarily associated with fibroma (21/23, 91.3%), wherein minor but potentially impactful details such as cellular fibroma and mitotically active cellular fibroma were missed due to sampling issues and misinterpretation as leiomyoma. FS evaluation for ovarian SCSTs demonstrated an overall accuracy of 78.5%, 81.0% and 81.8% for benign, uncertain/low malignant potential and malignant categories, respectively. There was no FS-related adverse clinical impact in all cases with available follow-up information (120/121 cases). Intraoperative FS evaluation of ovarian SCSTs is challenging. A small number of cases were misinterpreted, with AGCTs being the primary group where errors occur. Awareness of common diagnostic pitfalls and difficulties, alongside application of a stepwise approach, including (1) obtaining comprehensive clinical information, (2) thorough macroscopic examination and directed sampling, (3) meticulous microscopic examination with consideration of pitfalls and mimics, (4) effective communication with surgeons in difficult cases, and (5) consultation of subspecialty colleagues in challenging cases, will enhance pathologists' reporting accuracy and management of such cases in the future.

Congenital hepatoblastoma: Expanding knowledge, improving outcomes.

Hepatoblastoma (HB) is a rare liver tumour, and its congenital counterpart (CHB) is even less frequent. CHB has a clinically challenging management and a generally perceived worse outcome. This study aims to review the literature on CHB to better define presentation, diagnosis, available treatments and management options. The analysis of outcomes suggests that a significant portion of mortality is unrelated to the malignant nature of the tumour. Key factors influencing overall outcomes were identified: mortality linked to the 'mass effect' during both the prenatal (22%) and perinatal (32%) stages, as well as 'oncological' mortality encompassing tumour and/or treatment-related factors (46%). Overall, after birth, CHB does not seem to confer a worse oncological prognosis per se, and should be managed similarly to older children, if patients are stable enough to undergo proper staging and treatment. A deeper knowledge and better outcomes would come from a large, homogeneous, collection of data possibly allowing a global protocol, focusing on a comprehensive management of CHB.