BACKGROUND/OBJECTIVES:Mucinous adenocarcinoma (MAC) is a rare and clinically problematic subtype of rectal cancer, tending to present at an advanced stage and to respond poorly to neoadjuvant therapy. The consistently worse prognosis than that of not-otherwise-specified adenocarcinoma (NOS-AC) is not fully understood, potentially owing to intrinsically more aggressive biology or specific immune evasion mechanisms. We used the IMMUNOREACT multicentre cohort, with external validation in TCGA, to investigate the clinical and immunological features of rectal MAC in detail. METHODS:Two hundred patients with rectal adenocarcinoma (16 MAC, 184 NOS-AC) from the IMMUNOREACT 1 (NCT04915326) and IMMUNOREACT 2 (NCT04917263) prospective cohorts were included. To account for the imbalance in baseline characteristics, propensity score matching (PSM) was performed on age, sex, neoadjuvant treatment and TNM stage. The immune microenvironment was characterised using immunohistochemistry (CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, CD80), flow cytometry and NanoString PanCancer IO 360™ transcriptomics of adjacent healthy mucosa. Findings were externally validated against TCGA rectal and colon adenocarcinoma datasets. RESULTS:MAC presented at significantly more advanced stage than NOS-AC across all TNM parameters: higher T stage (p = 0.006), N stage (p < 0.001), M stage (p = 0.039) and overall TNM stage (p < 0.001). In the unmatched cohort, MAC was associated with worse overall survival (HR 2.53; 95% CI 1.03-6.23; p = 0.043) and disease-free survival (HR 2.86; 95% CI 1.25-6.55; p = 0.013), but both differences became non-significant after PSM. MAC patients had higher haemoglobin after adjusting for confounders (mean difference [MD] 1.26 g/dL, 95% CI 0.30-2.31, p = 0.012), consistent with a hypothesis of reduced chronic rectal bleeding as a possible mechanism for late presentation. Transcriptomically, MAC showed suppression of HLA class II antigen presentation genes (HLA-DQA1, HLA-DQB1, HLA-DRB1) and myeloid activation genes (S100A8/A9/A12) in adjacent healthy mucosa. Loss of MMR proteins MSH6 and PMS2 in histologically normal mucosa was significantly more frequent in MAC. These findings were replicated in the TCGA cohort, which also showed lower tumour mutational burden and a distinct mucin-associated transcriptomic profile in MAC. CONCLUSIONS:The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype.

The splenic flexure of the colon is one of the least frequently affected sites by colon cancer. However, when diagnosed, it presents a significant surgical challenge primarily due to its vascular anatomical variability. In fact, the splenic flexure of the colon originates from structures embryologically derived from the midgut and hindgut, such that a careful preoperative and intraoperative evaluation of the vascular anatomy is required to perform an adequate lymphadenectomy in cases of splenic flexure colon cancer. The surgical management of splenic flexure colon cancer is currently unstandardized. In addition to the significant lack of a shared definition of splenic flexure colon cancer that would allow for comparison across studies on the topic, there is extreme variability in the type of surgical procedure and lymphadenectomy performed. The few studies in the literature on the surgical management of splenic flexure colon cancer indicate that minimally invasive segmental resection of the splenic flexure of the colon, whether laparoscopic or robotic, and a lymphadenectomy focused on knowledge of the vascular anatomy and the site of the primary colon cancer are safe and effective in ensuring good short- and long-term outcomes. However, further well-designed studies are needed to reach strong conclusions that can be used to develop recommendations regarding the surgical management of splenic flexure colon cancer.

Management of incomplete resection of rectal neuroendocrine tumours remains an open clinical question. In the issue of the World Journal of Gastroenterology , Kim et al highlighted the heterogeneous incomplete resection rates across endoscopic techniques, while analysing impact of salvage treatment in this subset of patients. We further searched for evidence favouring a specific endoscopic technique for resection and the diagnostic and therapeutic role of salvage therapy in the long term. We performed a sensitivity meta-analysis restricted to studies with ≥ 36 months follow-up (5 studies; 413 patients) to compare recurrence rates between salvage therapy and observation. Our analysis showed no significant difference in recurrence (odds ratio = 0.89; 95% confidence interval: 0.37-2.18; P = 0.80), confirming the original findings even with extended follow-up. Subgroup analysis for local and distant recurrence did not show any significant difference.

BACKGROUND:Primary angiosarcoma of the breast (PAB) is a rare malignancy with no standardized treatment protocol. OBJECTIVE:To quantify the impact of tumor grade on overall survival (OS) and evaluate the association of adjuvant chemotherapy and radiotherapy with survival in primary angiosarcoma of the breast (PAB). METHODS:We systematically searched PubMed, Scopus, and Cochrane Library until 27 June 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale. Kaplan-Meier curve digitization was used to reconstruct individual patient data. Random-effects meta-analysis was performed for grade comparisons and therapy associations. RESULTS:Eleven studies (436 patients) were included. Meta-analysis of six studies showed increasing tumor grade significantly predicted mortality, with homogeneous hazard ratios (HRs) of 1.2 (Grade 2 vs. 1) and 3.7 (Grade 3 vs. 1). Analysis of five studies revealed that adjuvant chemotherapy was associated with significantly improved survival (HR = 0.11, 95% CI: 0.02-0.45), while radiotherapy showed no benefit (p = 0.96). Included studies demonstrated low-moderate risk of bias. CONCLUSIONS:This first quantitative synthesis establishes histologic grade as a paramount prognostic factor in PAB and shows a strong association between adjuvant chemotherapy and survival benefit. These findings provide crucial evidence for risk stratification and support considering chemotherapy in multimodal treatment for this rare disease.

Introduction: Most rectal cancers are microsatellite-stable (MSS) and derive limited benefit from immune checkpoint inhibition. We assessed whether familial colorectal cancer aggregation defines a distinct biological context within MSS rectal cancer.Materials and Methods: We performed a prespecified analysis of two prospective multicentre cohorts conducted between 2018 and 2024. Patients with MSS rectal adenocarcinoma were classified as familial (FH⁺) or sporadic (FH⁻), with a predefined subgroup of patients with an affected first-degree relative (FDR⁺). Known hereditary colorectal cancer syndromes were excluded. Immune profiling, transcriptomic analysis and targeted sequencing were performed on tumour-adjacent histologically normal rectal mucosa and, when appropriate, tumour tissue. Analyses were stratified by neoadjuvant treatment status.Results: Among 374 patients, 92 were FH⁺ and 65 were FDR⁺. In NAT-naïve patients, FDR⁺ cases showed higher epithelial CD80⁺ cell density than FH⁻ cases. After neoadjuvant therapy, FH⁺ patients had increased activated CD8⁺CD28⁺ T cells and reduced epithelial HLA-ABC expression, whereas FDR⁺ cases showed lower CD3⁺ T-cell density. Transcriptomic analysis indicated a quiescent mucosal phenotype in FH⁺ patients, with reduced DNA repair, proliferative, metabolic, angiogenic, and immune pathway activity. Post-NAT FH⁺ and FDR⁺ patients showed higher mutational ratios. In FH⁻, but not FH⁺, higher mutational ratio was associated with improved disease-free survival and immune activation.Discussion: Familial aggregation may define a biologically distinct MSS rectal cancer subgroup, characterised by altered epithelial–immune coordination and dissociation between therapy-induced genomic stress and immune surveillance.​

The recent introduction of “molecularly defined renal cell carcinomas” in the World Health Organization classification has significantly expanded the diagnostic spectrum of renal neoplasia, highlighting entities characterized by specific genetic alterations with potential clinical and therapeutic relevance. However, the recognition of these tumors in routine practice remains challenging due to overlapping morphological features and variable access to molecular testing. In this context, immunohistochemistry (IHC) has emerged as a practical and widely available tool that can act as a surrogate for underlying molecular alterations. Depending on the biological context, IHC may reflect genetic events either through protein overexpression, as in fusion-driven tumors, or through loss of expression associated with gene inactivation in metabolically or chromatin remodeling-deficient neoplasms. Accordingly, IHC plays a central role as a screening and triage method within the diagnostic workflow of these entities. Overall, IHC remains an indispensable component in the evaluation of molecularly defined renal cell carcinomas, but its optimal use requires integration with morphological assessment and, in most cases, confirmatory molecular testing. The aim of this review is to provide a comprehensive and evidence-based overview of the main immunohistochemical surrogates used in molecularly defined renal cell carcinomas, including TFE3-, TFEB-, and ALK-rearranged tumors, as well as SDH-, FH-, and SMARCB1-deficient neoplasms, highlighting their diagnostic applications, strengths, pitfalls, and role within an integrated diagnostic workflow. For each marker, the biological rationale, expected staining patterns, diagnostic applications, and major pitfalls are discussed, with particular emphasis on variability across studies and technical limitations.

Background: Anastomotic leaks (ALs) remain a critical complication after rectal cancer surgery. Emerging evidence suggests that local immune dysregulation may play a key role in anastomotic healing. We investigated the immune microenvironment of histologically normal, tumor-adjacent rectal mucosa-a tumor-conditioned field-as a potential substrate for AL predisposition. Methods: IMMUNOREACT 4 is a sub-analysis of the IMMUNOREACT project (clinicaltrials.gov NCT04915326 and NCT04915326), a multicenter translational study evaluating immune features of histologically normal, tumor-adjacent rectal mucosa of patients undergoing colorectal anastomosis. A prospective cohort (n = 121) was analyzed using flow cytometry, in addition to a retrospective cohort (n = 262) using immunohistochemistry. Immune markers of epithelial activation and lymphocyte subsets were compared between patients with and without postoperative ALs. Exploratory predictive models combining immune and clinical variables were developed and evaluated using discrimination, calibration and decision curve analyses. Results: At flow cytometry, the CK+HLAabc+ MFI (AUC 0.66, 95% CI 0.52-0.80), CD8+CD38+ cell rate (AUC 0.65, 95% CI 0.52-0.78) and CD3+CTLA4+ cell rate (AUC 0.65, 95% CI 0.51-0.80) showed moderate predictive potential for ALs. In immunohistochemistry, CD3+ (AUC 0.57, 95% CI 0.54-0.60), CD8+ (AUC 0.57, 95% CI 0.52-0.62), CD8β+ (AUC 0.59, 95% CI 0.53-0.65) and Tbet+ (AUC 0.60, 95% CI 0.56-0.64) showed some predictive ability for ALs. The model including CD8β+, the BMI, neutrophile/lymphocyte ratio and tumor location had an AUC of 0.67 (95% CI 0.62-0.72). Conclusions: Immune activation within histologically normal, tumor-adjacent rectal mucosa-characterized by epithelial HLA upregulation and cytotoxic or Th1 T cell infiltration-is associated with postoperative ALs. Although predictive accuracy is limited, these findings support the concept that a tumor-conditioned immune microenvironment may predispose patients to impaired anastomotic healing. Integration of mucosal immune profiling with clinical variables represents a promising exploratory approach that warrants further prospective validation.

PURPOSE:Immunohistochemistry (IHC) is a crucial step in the diagnostic and therapeutic management of colorectal carcinoma (CRC). This study aimed to explore the feasibility and diagnostic accuracy of general-purpose vision-language models (VLMs), specifically Gemini (2.5 Pro) and ChatGPT-4.0, for the automated classification of MMR status using immunohistochemical whole-slide images (WSIs). METHODS:A retrospective cohort of 50 CRC cases, stratified by reference MMR phenotype, was analyzed, with models performing a dual assessment: individual IHC evaluation and an overall result (Proficient Mismatch Repair, pMMR, or Deficient Mismatch Repair, dMMR). RESULTS:The AI models achieved 100% specificity in correctly classifying cases with retention of all four MMR proteins as pMMR (20/20 cases). However, the overall sensitivity for detecting dMMR cases was 65% (13/20 cases), with lower concordance observed for MSH2/MSH6 loss (60%) compared to MLH1/PMS2 loss (70%). CONCLUSIONS:This drop in sensitivity was attributed to the models' reluctance to confirm true protein loss, often categorizing the result as "Indeterminate" or "Inadequate". Crucially, the diagnostic certainty of the AI models increased dramatically only when a clear Internal Positive Control (IPC) was visible in the image, establishing the IPC as an indispensable feature for robust dMMR identification and differentiating true biological loss from technical artifacts.

Transverse colon cancer, which accounts for approximately 10

Non-muscle invasive bladder cancer (NMIBC) accounts for the majority of bladder cancer diagnoses and remains a clinical challenge due to its high recurrence and progression rates despite intravesical Bacillus Calmette–Guérin (BCG) therapy. In recent years, tumor-infiltrating lymphocytes (TILs) have emerged as promising biomarkers, reflecting the interplay between the tumor and host immune system. However, the evidence regarding their prognostic and predictive role is still conflicting, largely due to methodological heterogeneity, lack of standardized evaluation criteria, and limited prospective validation. This narrative review summarizes the current knowledge on TILs in NMIBC, focusing on their compartmental distribution (stromal, intraepithelial, and tumor–stroma interface), compositional diversity (CD4+, CD8+, Treg, B cells), and spatial dynamics. Special attention is given to their role in predicting response to BCG immunotherapy, the contribution of tumor-associated macrophages and tertiary lymphoid structures, and the emergence of immune escape pathways, including Programmed Death-Ligand 1 (PD-L1) and the HLA-E/NKG2A axis. Advances in digital pathology, spatial transcriptomics, and integrated immunoscore models provide more accurate metrics compared to simple cell counts, highlighting the importance of functional and spatial signatures. Despite encouraging progress, TILs are not yet ready for routine incorporation into histopathological reporting. Future directions include standardized assessment, integration with molecular biomarkers, and prospective multicenter validation to enable their translation into risk stratification and personalized therapeutic decision-making.

Gastric cancer (GC) is one of the most frequent malignancy worldwide. Laparoscopic total gastrectomy (LTG) has been used in early and advanced gastric cancer. YouTube® is the most widely used online video platform used as training tool for surgical procedure. The COVID-19 pandemic worsened this educational trend. This study aims to evaluate the educational quality of LTG YouTube® video on by using the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool. A YouTube ® search was conducted using “laparoscopic total gastrectomy.” Videos were rated by two investigators using the LAP-VEGaS video assessment tool. The association between the scores and the video characteristics (e.g., video authors, year of uploading and length of video) was assessed. The LAP VEGaS Score median was 6.00 (range 2–17, IQR (4–9)) and mean of 6.79 SD (± 3.38). According to LAP VEGaS Score, 18 videos were ≥ 11, while 89 ones were < 11. Correlation between LAP VEGaS Score, views (rs = 0.317, p < 0.001) and video time (rs = − 0.338, p < 0.001) turned out week. No association between score and upload time (rs = 0.03, p = 0.761) was recorded. No statistically significant discrepancy was detected between years of upload (< 2020, ≥ 2020) (p = 0.781). LAP VEGaS scores were significantly higher for videos lasting less than 10 min (p < 0.001) and for videos uploaded by Surgical Scientific Societies (p < 0.05). Educational quality turned out to be low. The COVID-19 pandemic and publication of LAP-VEGaS guidelines did not seem to have affected video quality. Paper’s main novel aspects: - This is the first study to evaluate the educational quality of YouTube video on laparoscopic total gastrectomy using the LAP-VEGaS tool. - A number of evaluated cases and an analysis of all videos available on YouTube, in comparison to other studies, represent strong points in our study.

Episiotomy is a perineal incision enlarging the vaginal opening during labor, preventing severe perineal/vaginal/ano-rectal lacerations. We performed a systematic literature review (PRISMA guidelines; Pubmed, Scopus and Web of Science databases) of primary malignant tumors arising from the episiotomy site. Thirteen primary carcinomas were reported, mainly endometriosis-related histotypes (77%) (nine clear cell, CCC; one endometrioid, EC) with only two vulvar invasive squamous cell carcinomas and one adenoid cystic carcinoma of Bartholin’s gland. No sarcomas, melanomas or malignant trophoblastic tumors were described. Endometriosis was associated with tumors or reported in history (62%). Malignant transformation occurred 3 to 27 (mean 16) years after diagnosis of endometriosis. Patients were usually post-/peri-menopausal (eight cases, 61%) (age range: 31–70 years, mean 50). Imaging should exclude distant (0% in our series) or lymph node metastases (three cases, 23%), looking for potential invasion of vagina (five cases, 39%), anus (including sphincter) (four cases, 31%) and/or other deep pelvic soft tissues (five cases, 39%). All patients underwent surgery, except for a CCC-patient (only chemoradiation) subsequently progressing and dying of disease. Adjuvant chemotherapy and/or radiotherapy were administered to five (39%) cases, neoadjuvant therapy to four cases (31%). Globally, three (23%) cases recurred or progressed, and two-thirds (15%) died of disease (1 CCC, 1 EC). Radical surgery with lymph node status evaluation and eventual excision should be performed when possible. Chemotherapy and/or radiotherapy can be considered in an adjuvant and/or neoadjuvant setting (or as only treatment in inoperable patients). However, the role of different treatments should be studied in further larger multicenter series.

An accurate histopathological evaluation of radical cystectomy (RC) specimens is crucial for optimal tumor staging, prognosis, and therapeutic decision making. The increasing demand for precision medicine and multidisciplinary oncological management emphasizes the necessity for standardized protocols in the handling and sampling of bladder cancer specimens. The effective processing of RC specimens begins with the integration of clinical and anamnestic data, along with appropriate formalin fixation methods to meet diagnostic needs. The pathologist must meticulously document the macroscopic characteristics and dimensions of the surgical specimen, especially in post-neoadjuvant chemotherapy (post-NAC) cases where the primary tumor may not be macroscopically visible. Sampling strategies should ensure a comprehensive assessment of the primary tumor and any extra-organ or metastatic involvement. Despite international guidelines, variability in pathology practices persists, particularly concerning prostate sampling in RC and the use of frozen sections for margin assessment. Addressing these challenges necessitates a consensus-driven, standardized approach to improve the reproducibility and quality of histopathological data. By addressing gaps in current pathology practices, this review advocates for uniform protocols that enhance diagnostic accuracy, ultimately improving patient care and clinical decision making.

Background/Objectives: Duodenal stump fistula (DSF) is one of the most feared postoperative complications in gastric cancer surgery. It has a 1.6–5% incidence rate and correlates with potentially high rates of morbidity (75%) and mortality (16–20%). The absence of duodenal stump reinforcement is considered one of the main risk factors. Our meta-analysis aimed to provide updated evidence by comparing DSF rates among patients who underwent distal or total gastrectomy for malignant gastric disease with or without reinforcement of the duodenal stump. Methods: We performed a systematic review following the PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library databases were used to identify articles of interest. Meta-analysis was performed by using RevMan Version 5.4. Results: The six included comparative studies (19,527 patients: 11,545 reinforcement group versus 7982 control group) covered an approximately 20-year study period (2005–2023). All the studies included were observational in nature. Meta-analysis of pooled results showed that, compared to the control group, the reinforcement group recorded a statistically significant lower DSF rate (OR: 0.32, 95% CI: 0.17, 0.60, p = 0.0004). Considering secondary outcomes, no statistically significant differences were identified between the two groups in terms of operative time, EBL, overall postoperative complications, and length of hospital stay. Just major postoperative complications were considerably lower in the reinforcement group compared to the control group (OR: 0.66, 95% CI: 0.43, 0.99, p = 0.04). Conclusions: Duodenal stump reinforcement appears to reduce the rate of DSF after distal or total gastrectomy for malignant gastric disease. Given the significant biases among meta-analyzed studies, our results require careful interpretation. Further randomized, possibly multicenter trials may turn out to be of paramount importance in confirming our results.

Invasive lobular carcinoma (ILC) is the most common special type of breast carcinoma, accounting for 5–15% of all breast carcinoma cases. Its metastatic pattern differs from that of invasive breast carcinoma of no special type, with ILC metastases to the peritoneum, gastrointestinal tract, and female genital tract being more frequent. This literature review focuses on ILC cases with metastasis to the female genital tract (FGT). Searches were conducted in medical databases including PubMed, Scopus, and Web of Science, using specific keywords. Inclusion criteria centered on studies presenting one or more cases of patients with ILC metastasis to the FGT and English language publications. Exclusion criteria included articles that did not present original research findings, studies with insufficient data, and publications in languages other than English. A thorough analysis of 154 results from PubMed, 56 from Scopus, and 173 from Web of Science after the application of inclusion and exclusion criteria resulted in the inclusion of 54 manuscripts describing 61 cases. The demographic, clinicopathological, and therapeutic aspects of ILC metastases to the FGT were reviewed and the differential diagnosis and prognosis for each anatomic location in the FGT were discussed separately. Our analysis of the data showed that the restricted mean survival time was 186 ± 30.7 months and that a negative ER on a secondary tumor was found to be linked to worse patient survival rates. Also of note is the fact that in 37.7% of cases there was involvement of multiple FGT anatomic locations and in 36% of cases there were metastases in organs or anatomic locations other than the FGT. To our knowledge, our study is the only one to describe the features of patients with secondary FGT involvement from ILC.

Background and Objectives: Post-Operative Pancreatic Fistula (POPF) is reported among 13% to 64% of cases following a distal/left pancreatectomy (D/LP). Many efforts aim to prevent the onset of POPF or reduce its clinical impact. This meta-analysis sought to provide data by assessing POPF rates among patients undergoing D/LP for benign or malignant pancreatic diseases, with or without pancreatic stump mesh wrapping. Materials and Methods: We undertook a systematic review following the PRISMA guidelines, alongside the Cochrane Handbook for Systematic Reviews of Interventions. We evaluated the certainty in the evidence using the GRADE approach for the following key outcomes: overall POPF and clinically relevant POPF. PubMed/MEDLINE, Web of Science, and Scopus were employed to retrieve relevant papers. Pooled analysis was carried out employing RevMan Version 5.4.1. Results: Among the 8 comparative studies considered (1042 subjects: 430 Wrapping Mesh Group (WMG) versus 612 control group (CG)), seven were retrospective observational studies and one was a randomized controlled trial. Polyglycolic acid (PGA) mesh was used in 7 studies, except for one, who used a polyglactin mesh. Regarding the primary outcomes, meta-analysis showed lower rates of Overall POPF (Ov-POPF) (OR: 0.57, 95% CI: 0.37, 0.88; p = 0.01) and clinically relevant POPF (CR-POPF) (OR: 0.33, 95% CI: 0.21, 0.50; p < 0.00001) in the WMG. Moreover, the WMG also showed a decrease in Estimated Blood Loss (EBL) (MD: −43.11, 95%, CI: −63.20, −23.02, p < 0.0001), a shorter period with surgical drain (MD: −9.66, 95% CI: −17.99, −1.34, p = 0.02) and a decreased length of hospital stay (MD: −4.60, 95%, CI: −7.83, −1.36, p = 0.005). Conclusions: Our meta-analysis showed that wrapping the pancreatic stump with mesh is associated with lower rates of overall POPF and clinically relevant POPF, lower EBL, a shorter period with the surgical drain and reduced hospital stay duration. There is a need for high-quality methodological research to identify the risk factors for the onset of POPF and to evaluate and compare the results of various surgical approaches used to reduce its rate and associated morbidity.

Eosinophilic esophagitis (EoE) has emerged as a distinct clinicopathological entity and a major cause of upper gastrointestinal morbidity worldwide. Once misinterpreted as a variant of Gastroesophageal Reflux Disease (GERD), its unique identity as an immune-mediated inflammatory disease was solidified by foundational studies in the early 1990s. This discursive review synthesizes key findings from peer-reviewed literature to outline the evolution of EoE’s diagnosis and management. The review highlights that a definitive diagnosis is now a multidisciplinary process that integrates clinical symptoms, characteristic endoscopic findings, and, most critically, a comprehensive histopathological evaluation of esophageal biopsies. It emphasizes the limitations of relying on a single eosinophil count and underscores the value of ancillary histological features and the Histologic Scoring System, which provides a more nuanced and predictive assessment of disease activity. The review also discusses the evolving understanding of PPI-responsive esophageal eosinophilia as a subtype of EoE, streamlining the diagnostic approach. In conclusion, while EoE is a chronic condition that can lead to significant esophageal remodeling if untreated, a robust diagnostic framework and a range of effective therapies are now available to manage the disease, though a continued lack of clinical awareness remains a key challenge.

Clear cell renal cell carcinoma is the most common histological type of renal cancer, which is a common cancer type usually associated with a long clinical course. During this course, various metastatic sites can be observed. In this review, we have focused on metastases to the thyroid gland. We conducted research in three medical databases, including PubMed, Scopus, and Web of Science, using the same search algorithm. Our inclusion criteria focused on case reports and case series studies since 2011, covering therapeutic strategies for the primary and/or metastatic disease, as well as subsequent follow-up data. Studies with insufficient or uncertain data, or written in a language other than English, were excluded. An analysis of 510 articles from PubMed, 1729 from Scopus, and 649 from Web of Science, after application of inclusion and exclusion criteria, resulted in 77 reports, analyzing 189 patients. A description of the clinical, pathological, ancillary, and follow-up data, in the light of recent therapeutic schemes, was attempted. Our results suggest that metastases' imaging features comprised more commonly a solitary nodule with a median size of 3.5 cm and worrisome features in ultrasonography, such as heterogeneity, hypoechogenicity, partially solid configuration, and variable internal vascularization. Histological and immunohistochemical examination of the lesion is necessary because these findings are not specific. Common non-thyroid metastases are seen in the urogenital system, lungs, and pancreas. We calculated the restricted mean survival from primary diagnosis at 274.6 months (95% CI: 264.3-285.0 months) and the restricted mean survival from thyroid metastases treatment at 93.9 months (95% CI: 65.3-122.4 months). Results regarding how patient characteristics affect these survival numbers were statistically nonsignificant (p > 0.05).