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Simple Summary: Pregnancy-associated cancers (PACs) represent a significant clinical problem, due to their possibly delayed diagnosis, limitations of the usage of diagnostic and therapeutic methods, and often the necessity to postpone the administration of optimal treatment to the mother until after delivery to protect the health of the fetus. The purpose of this review is to summarize information on the epidemiology, proper diagnosis, and effective treatment of cutaneous malignant melanoma (CMM) during pregnancy. Moreover, our aim is to point out that there are still many topics related to pregnancy-associated melanoma (PAM) that require further research. The following article can help clinicians systematize the updated facts from various studies and case-reports as well as advise them that an interdisciplinary approach combined with broad knowledge from different fields of medicine is crucial in the treatment of PAM. Cutaneous malignant melanoma is one of the most common neoplasms among pregnancy-associated cancers (PACs). Risk factors include excessive exposure to ultraviolet radiation, the presence of benign and dysplastic nevi, and a patient or family history of melanoma. Self-examination and careful inspection of nevi are crucial, especially in the context of their progression over time. Physiological changes that occur during pregnancy, such as the darkening and enlargement of the nevi, delay the diagnosis of CMM. In the fetus, metastases are very rare, and if they do occur, they concern the placenta or fetal tissues. The choice of treatment is influenced by the cancer stage, symptoms, the time of termination of pregnancy, and the patient's decision. Essential procedures which are safe for the fetus are diagnostic biopsy, ultrasound, and the therapeutic excision of the lesion and the affected lymph nodes. Other imaging methods can be used with a safe radiation dose limit of 100 mGy. Immunotherapy and targeted treatments must be carefully considered, because of their possible adverse effects on the fetus. An interdisciplinary approach to the problem of melanoma during pregnancy is necessary, involving doctors of various specialties. [ABSTRACT FROM AUTHOR]

Background: Primary tumour biology and axillary lymph node status are key prognostic factors in breast cancer treatment. The LowMag trial introduced a magnetic sentinel lymph node biopsy procedure using a superparamagnetic iron oxide (SPIO) tracer and a handheld magnetometer as a radiation-free alternative for axillary staging. The trial aimed to assess a low-dose magnetic tracer for non-invasive preoperative evaluation of lymph node metastases and intraoperative sentinel lymph node detection. Methods: Patients with confirmed invasive breast cancer or ductal carcinoma in situ, eligible for sentinel lymph node biopsy, were included in the LowMag trial. The sentinel lymph nodes were detected perioperatively using Sentimag® and inked to maintain spatial orientation between MRI and histopathology. The amount of iron was estimated using two magnetic devices: SPaQ and Sentimag®. Additional ex vivo MRI was performed with a low-field MRI system. After being buffered in formalin, the sentinel lymph nodes were sectioned perpendicular to the MRI planes, consecutively sliced at 2 μm intervals, and stained with H&E, Perls Prussian blue, CK8/18, and CD68. Results: In an interim assessment of 20 sentinel lymph nodes, two contained metastases. The analysis revealed good concordance in uptake between the magnetic and radioactive tracers, with a median iron content of 19.21 µg. In healthy sentinel lymph nodes, iron particles were found in both the subcapsular space and sinusoids, with macrophages nearby. Healthy regions within metastatic lymph nodes showed similar behaviour to healthy nodes. In metastatic sites, iron pigment presence was reduced, especially in areas occupied by tumour cells. A healthy lymph node with low iron content displayed a large central fatty region without iron uptake but confirmed iron in sinusoidal macrophages. The metastatic lymph node had subcapsular and parenchymal tumour cells in the central region, with limited infiltration into nearby adipose tissue and no local iron enhancement. However, iron deposits were detected within the sinusoids. Discussion: The MRI images effectively distinguish between fat, nodal tissue, and the SPIO tracer, either through signal intensity or texture. This demonstrates the potential for sentinel lymph node imaging using a low-field MRI system. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma, the deadliest skin cancer, is a focus of research worldwide. This malignancy has been demonstrated to evade the immune system through several escape mechanisms. Among these, melanoma-related Dendritic Cells (DCs) alterations, particularly within the Sentinel Lymph Node (SLN), seem to play a key role. In SLNs, melanoma-related factors create a tumor microenvironment capable of impairing the immune response, inducing tolerance to tumor antigens and thus favoring SLN early metastases. The present literature review describes the interactions between Langerhans Cell (LC), a particular DC subset, and melanoma, suggesting a new potential therapeutic target. Background. Langerhans cells (LCs) are professional Dendritic Cells (DCs) involved in immunoregulatory functions. At the skin level, LCs are immature. In response to tissue injuries, they migrate to regional Lymph Nodes (LNs), reaching a full maturation state. Then, they become effective antigen-presenting cells (APCs) that induce anti-cancer responses. Notably, melanoma patients present several DC alterations in the Sentinel Lymph Node (SLN), where primary antitumoral immunity is generated. LCs are the most represented DCs subset in melanoma SLNs and are expected to play a key role in the anti-melanoma response. With this paper, we aim to review the current knowledge and future perspectives regarding LCs and melanoma. Methods. A systematic review was carried out according to the PRISMA statement using the PubMed (MEDLINE) library from January 2004 to January 2024, searching for original studies discussing LC in melanoma. Results. The final synthesis included 15 articles. Several papers revealed significant LCs–melanoma interactions. Conclusions. Melanoma immune escape mechanisms include SLN LC alterations, favoring LN metastasis arrival/homing and melanoma proliferation. The SLN LCs of melanoma patients are defective but not irreversibly, and their function may be restored by appropriate stimuli. Thus, LCs represent a promising target for future immunotherapeutic strategies and cancer vaccines. [ABSTRACT FROM AUTHOR]

Deregulation of small non-coding RNAs (sncRNAs) has been associated with the onset of metastasis. We evaluated the expression of sncRNAs in patients with early-stage breast cancer, performing RNA sequencing in 60 patients for whom tumor and sentinel lymph node (SLN) samples were available, and conducting differential expression, gene ontology, enrichment and survival analyses. Sequencing annotation classified most of the sncRNAs into small nucleolar RNA (snoRNAs, 70%) and small nuclear RNA (snRNA, 13%). Our results showed no significant differences in sncRNA expression between tumor or SLNs obtained from the same patient. Differential expression analysis showed down-regulation (n = 21) sncRNAs and up-regulation (n = 2) sncRNAs in patients with locoregional metastasis. The expression of SNHG5, SNORD90, SCARNA2 and SNORD78 differentiated luminal A from luminal B tumors, whereas SNORD124 up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (SNORD93, SNORA16A, SNORD113-6, SNORA7A, SNORA57 and SNORA18A) that distinguished patients with locoregional metastasis and predicted patient outcome. Gene ontology and Reactome pathway analysis showed an enrichment of biological processes associated with translation initiation, protein targeting to specific cell locations, and positive regulation of Wnt and NOTCH signaling pathways, commonly involved in the promotion of metastases. Our results point to the potential of several sncRNAs as surrogate markers of lymph node metastases and patient outcome in early-stage breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant sncRNAs and to validate our results in a larger cohort of patients. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs). Materials and methods: Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis. Results: One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs. Conclusion: Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making. Trial registration: This trial is registered on www.chictr.org.cn: ChiCTR2000031231. Registered March 25, 2020. Critical relevance statement: A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer. Key points: • CEUS can help identify and diagnose SLN in early breast cancer preoperatively. • Combining lymphatic and grayscale US findings can predict axillary tumor burden. • The nomogram showed a high diagnostic value in validation cohorts. [ABSTRACT FROM AUTHOR]

Objective: For patients with 1–2 positive sentinel lymph nodes (SLN) identified by biopsy, the necessity of axillary lymph node dissection (ALND) remains a matter of debate. The primary aim of this study was to investigate the association between postoperative pathological factors and non-sentinel lymph node (NSLN) metastases in Chinese patients diagnosed with sentinel node-positive breast cancer. Methods: This research involved a total of 280 individuals with SLN-positive breast cancer. The relationship between postoperative pathological variables and non-sentinel lymph node metastases was scrutinized using univariate, multivariate, and stratified analysis. Results: Among the 280 patients with a complete count of SLN positives, 126 (45.0%) exhibited NSLN metastasis. Within this group, 45 cases (35.71%) had 1 SLN positive, while 81 cases (64.29%) demonstrated more than 1 SLN positive. Multivariate logistic regression analysis revealed that HER2 expression status (OR 2.25, 95% CI 1.10–4.60, P = 0.0269), LVI (OR 6.08, 95% CI 3.31–11.14, P < 0.0001), and the number of positive SLNs (OR 4.17, 95% CI 2.35–7.42, P < 0.0001) were positively correlated with NSLNM. Conclusion: In our investigation, the risk variables for NSLN metastasis included LVI, HER2 expression, and the quantity of positive sentinel lymph nodes. However, further validation is imperative, including this institution, distinct institutions, and diverse patient populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: For patients with melanoma, the decision to perform sentinel lymph node biopsy (SLNB) is based on the estimated risk of lymph node metastasis. We assessed 3 melanoma SLNB risk-prediction models' statistical performance and their ability to improve clinical decision making (clinical utility) on a cohort of melanoma SLNB cases. STUDY DESIGN: Melanoma patients undergoing SLNB at a single center from 2003 to 2021 were identified. The predicted probabilities of sentinel lymph node positivity using the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center (MSK), and Friedman nomograms were calculated. Receiver operating characteristic and calibration curves were generated. Clinical utility was assessed via decision curve analysis, calculating the net SLNBs that could have been avoided had a given model guided selection at different risk thresholds. RESULTS: Of 2,464 melanoma cases that underwent SLNB, 567 (23.0%) had a positive sentinel lymph node. The areas under the receiver operating characteristic curves for the Melanoma Institute of Australia, MSK, and Friedman models were 0.726 (95% CI, 0.702 to 0.750), 0.720 (95% CI, 0.697 to 0.744), and 0.721 (95% CI, 0.699 to 0.744), respectively. For all models, calibration was best at predicted positivity rates below 30%. The MSK model underpredicted risk. At a 10% risk threshold, only the Friedman model would correctly avoid a net of 6.2 SLNBs per 100 patients. The other models did not reduce net avoidable SLNBs at risk thresholds of ≤10%. CONCLUSIONS: The tested nomograms had comparable performance in our cohort. The only model that achieved clinical utility at risk thresholds of ≤10% was the Friedman model. [ABSTRACT FROM AUTHOR]

Objective(s): Sentinel lymph node biopsy (SLNB) has been proven as a safe and efficient procedure in some cancers like breast cancer and melanoma with a reduction of complications and side effects of unnecessary lymphadenectomy in many patients. However, the diagnostic value of SLNB in gastric cancer is a point of debate. This study evaluated the diagnostic value of SLNB using radiotracer and isosulphan blue dye injection in patients with Gastric Adenocarcinomas (GA). Methods: This descriptive study was performed at Imam-Reza HOSPITAL on 39 patients diagnosed with GA with no lymphatic metastasis using two methods: the combination of radionuclide with isosulphan together (R&I) method compared with the isosulphan alone method. Lymphatic dissection was performed in all patients. The pathological results were compared between the sentinel lymph nodes (SLN) and other lymph nodes and their accordance rate was calculated. Results: In the T1 group, the sentinel lymph node biopsy detection rate was 100% for the combination of the R&I method and 60% for the isosulphan method and the false negative rate was zero. These values respectively were 88.8% and 88.8% in the T2 group with a false negative rate of 75%. In the T3 group, the values were 100% for the combination of the R&I method and 93.7% for the isosulphan method with a false negative rate of 40%. In the combination of the R&I method, the sensitivity, specificity, and positive and negative predictive values were 57.9, 100, 100, and 69.2 percent respectively. Conclusion: Based on the false negative rate (47.4%), SLNB by injection of isosulphan blue dye alone is not a diagnostic enough value for predicting lymph node metastasis in GA. Although, SLNB by combination of the R&I had better accuracy compared to the isosulphan alone, more studies with larger samples are needed to prove this result. [ABSTRACT FROM AUTHOR]

[Display omitted] As primary sites of tumor metastasis, sentinel lymph nodes (SLNs) require a highly biocompatible theranostic platform for precise localization and treatment to inhibit tumor metastasis. Herein, indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were fabricated by ICG-induced self-assembly and radiolabeled with technetuim-99 m (99mTc). The fabricated NPs were composed of hospital-available drugs and isotopes, making them highly biocompatible for in vivo applications. In a mouse model of SLN metastasis, the prepared NPs exhibited excellent capacity for preoperative planning by single-photon emission computed tomography (SPECT) imaging-enabled SLN localization, near-infrared fluorescence (NIRF) imaging-enabled intraoperative real-time monitoring, and SLN photothermal treatment. Photothermal treatment with SLN enhanced the inhibition of lung metastasis and significantly increased the survival time of mice. The prepared NPs were highly biocompatible and exhibited efficient theranostic properties for inhibiting cancer metastasis, making them promising candidates for clinical translation. [ABSTRACT FROM AUTHOR]

Background: Guidance for the management of thyroid nodules has evolved over time, from initial evaluation based predominantly on clinical grounds to now including the established role of ultrasound and fine needle aspiration cytology in their assessment. There is, however, significant variation in the management of thyroid nodules depending on which national guidelines are followed. In addition, there are certain clinical situations such as pregnancy and paediatric thyroid nodules that have differing evaluation priorities. Objectives: This review aimed to provide an overview of currently accepted practices for the initial investigation and subsequent management of patients with thyroid nodules for the non-specialist. The review also addresses areas of variance between the systems in common clinical use, as well as newer, evolving technologies, including molecular testing in the evaluation of malignancy in thyroid nodules. [ABSTRACT FROM AUTHOR]

The deregulation of microRNAs (miRNAs) is associated with the various steps of the metastatic process. In addition, circulating miRNAs are remarkably stable in peripheral blood, making them ideal noninvasive biomarkers for disease diagnosis. Here, we performed a proof-of-principle study to determine whether tumor-tissue-derived miRNAs are traceable to plasma in ER-positive early breast cancer patients. We performed RNA-sequencing on 30 patients for whom plasma, sentinel lymph nodes (SLNs) and tumor tissue were available. We carried out differential expression, gene ontology and enrichment analyses. Our results show that circulating miRNAs are inversely expressed compared with tumor tissue or SLNs obtained from the same patients. Our differential expression analysis shows the overall downregulation of circulating miRNAs. However, the expression of miR-643a-3p and miR-223 was up-regulated in patients with positive SLNs. Furthermore, gene ontology analysis showed the significant enrichment of biological processes associated with the regulation of epithelial cell proliferation and transcriptional regulation commonly involved in the promotion of metastases. Our results suggest the potential role of several circulating miRNAs as surrogate markers of lymph node metastases in early breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant miRNAs and to validate our results in a larger cohort of patients. [ABSTRACT FROM AUTHOR]

A 54-year-old woman who incidentally noticed a "knot" in her left breast subsequently underwent excisional biopsy which yielded a diagnosis of malignant neoplasm with sarcomatous features. Given the broad differential diagnosis and imaging findings, the patient underwent bilateral mastectomy and intraoperative sentinel lymph node assessment. An 8.5 cm tumor that was further classified as a malignant phyllodes tumor was identified in the left breast, while the frozen section interpretation came back as positive for metastatic disease which resulted in left axillary lymphadenectomy. Two months later the patient progressed to distant metastatic disease and unfortunately passed away within 6 months after her initial diagnosis. Lymph node metastasis in phyllodes tumor is an exceptionally rare event for which patients usually do not undergo intraoperative sentinel lymph node examination; however high clinical suspicion of metastatic disease would be evidence for further investigation. [ABSTRACT FROM AUTHOR]

Sentinel lymph node (SLN) metastasis is an important promoter of distant metastasis in breast cancer. Therefore, the timely diagnosis and precise treatment are crucial for patient staging and prognosis. However, the simultaneous diagnosis of metastasis and the implementation of imaging-guided SLN therapy is challenging. Here, we report a melittin-loaded and hyaluronic acid (HA)-conjugated high-density lipoprotein (HDL) mimic phospholipid scaffold nanoparticle (MLT-HA-HPPS), which dually-target to both breast cancer and its SLN and efficiently inhibit SLN metastasis in the LN metastasis model. The melittin peptide was successfully loaded onto HA-HPPS via electrostatic interactions, and MLT-HA-HPPS possesses effective cytotoxicity for breast cancer 4T1 cells. Moreover, the effective delivery of MLT-HA-HPPS from the primary tumor into SLN is monitored by NIR fluorescence imaging, which greatly benefits the prognosis and treatment of metastatic SLNs. After paracancerous administration, MLT-HA-HPPS can efficiently inhibit primary tumor growth with an inhibition rate of 81.3% and 76.5% relative to the PBS-treated control group and HA-HPPS group, respectively. More importantly, MLT-HA-HPPS can effectively inhibit the growth of the metastatic SLNs with an approximately 78.0%, 79.1%, and 64.2% decrease in SLNs weight than those in PBS, HA-HPPS, and melittin-treated mice, respectively. Taken together, the MLT-HA-HPPS may provide an encouraging theranostic of SLN drug delivery strategy to inhibit primary tumor progression and prevent SLN metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

Aims: To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. Methods: Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). Results: TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P <.001) and multivariate (1.55 [95% CI: 1.04, 2.32], P =.030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P =.874; interaction OR: 1.04 [0.7, 1.55], P =.835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P =.180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P <.001). Conclusions: our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS. [ABSTRACT FROM AUTHOR]

In melanoma patients, surgical excision of the first draining lymph node, the sentinel lymph node (SLN), is a routine procedure to evaluate lymphogenic metastases. Metastasis detection by histopathological analysis assesses multiple tissue levels with hematoxylin and eosin and immunohistochemically stained glass slides. Considering the amount of tissue to analyze, the detection of metastasis can be highly time-consuming for pathologists. The application of artificial intelligence in the clinical routine has constantly increased over the past few years. In this multi-center study, a deep learning method was established on histological tissue sections of sentinel lymph nodes collected from the clinical routine. The algorithm was trained to highlight potential melanoma metastases for further review by pathologists, without relying on supplementary immunohistochemical stainings (e.g. anti-S100, anti-MelanA). The established method was able to detect the existence of metastasis on individual tissue cuts with an area under the curve of 0.9630 and 0.9856 respectively on two test cohorts from different laboratories. The method was able to accurately identify tumour deposits>0.1 mm and, by automatic tumour diameter measurement, classify these into 0.1 mm to −1.0 mm and>1.0 mm groups, thus identifying and classifying metastasis currently relevant for assessing prognosis and stratifying treatment. Our results demonstrate that AI-based SLN melanoma metastasis detection has great potential and could become a routinely applied aid for pathologists. Our current study focused on assessing established parameters; however, larger future AI-based studies could identify novel biomarkers potentially further improving SLN-based prognostic and therapeutic predictions for affected patients. • Deep learning algorithm establishment on histological slides in a multi-center study. • The algorithm highlights melanoma metastases on H&E stained tissue of SLN. • The method could accurately identify melanoma deposits of>0.1 mm in diameter. • Metastases detected with an AUC of 0.96 and 0.99 in two cohorts, respectively. [ABSTRACT FROM AUTHOR]

Key content: Sentinel lymph node (SLN) biopsy is an alternative to systematic lymphadenectomy in the surgical staging of gynaecological malignancy. It is recommended in the management of vulval cancer and is increasingly used in endometrial and cervical cancer.SLN failed mapping algorithms require that side‐specific lymphadenectomy should be performed in the case of failed mapping, and that suspicious lymph nodes are removed.Ultrastaging protocols improve detection of lymph‐node metastasis and should be used for the pathological processing of SLNs. Learning objectives: To understand the rationale, use and evidence for SLN biopsy in women with vulval, cervical and endometrial malignancy.To appreciate the concepts behind the technical performance of SLN biopsy.To understand the pathological processing of SLN samples and the implications this may have for the interpretation of results and adjuvant therapy. Ethical issues: How to manage adjuvant therapy decisions in the context of micrometastases or isolated tumour cells in positive pelvic SLNs in cervical or endometrial cancer when the evidence‐base is limited. [ABSTRACT FROM AUTHOR]

Cervical lymph node metastases from head and neck squamous cell cancers significantly reduce disease-free survival and worsen overall prognosis and, hence, deserve more aggressive management and follow-up. As per the eighth edition of the American Joint Committee on Cancer staging manual, extranodal extension, especially in human papillomavirus-negative cancers, has been incorporated in staging as it is important in deciding management and significantly impacts the outcome of head and neck squamous cell cancer. Lymph node imaging with various radiological modalities, including ultrasound, computed tomography and magnetic resonance imaging, has been widely used, not only to demonstrate nodal involvement but also for guided histopathological evaluation and therapeutic intervention. Computed tomography and magnetic resonance imaging, together with positron emission tomography, are used widely for the follow-up of treated patients. Finally, there is an emerging role for artificial intelligence in neck node imaging that has shown promising results, increasing the accuracy of detection of nodal involvement, especially normal-appearing nodes. The aim of this review is to provide a comprehensive overview of the diagnosis and management of involved neck nodes with a focus on sentinel node anatomy, pathogenesis, imaging correlates (including radiogenomics and artificial intelligence) and the role of image-guided interventions. • Lymph node metastasis is an important prognostic factor; survival drops by 50% with lymph node metastasis. • The prognostic importance of ENE has been known for a long time and is now incorporated in the 8th edition AJCC manual. • Imaging plays a crucial role in detecting nodal metastasis to accurately prognosticate the disease and plan the treatment. • Imaging also has a vital role in follow-up, treatment response assessment and in cervical metastasis of unknown primary. • The diagnostic accuracy of sentinel node biopsy in the assessment of node-negative neck in early oral cancers has been known for a long time; oncological adequacy has also been established. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphatic spreading is a main driver of metastasis and, thus, associated death in colon cancer. Therefore, resecting all metastatic lymph nodes is vital for cancer-free survival. Although resection within established resection lines provides a good lymph node yield, aberrant lymphatic drainage pathways may be missed. Lymphatic mapping can compensate for this shortcoming. Different methods for tracing lymphatic drainage exist, such as radiocolloid tracers, ink, and fluorescent tracers. Tracers can be applicated either during surgery or before surgery through colonoscopy, giving the tracer more time to travel through the lymphatic system and highlighting more distant tumor-draining lymph nodes. This review aims to assess which protocol best maps the lymphatic drainage pathway and thus enables an optimized, personalized approach for curative resection. An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010–0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018–0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence. [ABSTRACT FROM AUTHOR]

Aim: To gain a better understanding of the use of sentinel lymph node mapping by Chinese oncologists for endometrial cancer staging and analyze factors influencing its application. Methods: Questionnaires were collected online before and by phone after the symposium to evaluate the general characteristics of oncologists who participated in the endometrial cancer seminar and factors associated with the application of sentinel lymph node mapping in endometrial cancer patients. Results: Gynecologic oncologists from 142 medical centers participated in the survey. 35.4% of doctors employed sentinel lymph node mapping for endometrial cancer staging, 57.3% chose indocyanine green as the tracer. Multivariate analysis revealed that cancer research center (odds ratio = 4.229, 95% CI 1.747–10.237), physician familiarity with sentinel lymph node mapping (odds ratio = 126.188, 95% confidence interval 43.220–368.425) and the use of ultrastaging (odds ratio = 2.657, 95% confidence interval 1.085–6.506) were related to the doctors' selection of sentinel lymph node mapping. There was a significant difference in the surgical procedure for early endometrial cancer, the number of removed sentinel lymph node, and the reason for not adopting sentinel lymph node mapping before and after the symposium. Conclusions: The theoretical knowledge of sentinel lymph node mapping, the use of ultrastaging, and cancer research center are related to a higher acceptance of sentinel lymph node mapping. Distance learning is conducive to the promotion of this technology. [ABSTRACT FROM AUTHOR]

Background: TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging. Results: In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine. Conclusion: TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis. [ABSTRACT FROM AUTHOR]

Background: TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging. Results: In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine. Conclusion: TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis. [ABSTRACT FROM AUTHOR]

Purpose Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin-stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients. Materials and Methods A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study. Results The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis. Conclusion In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH. [ABSTRACT FROM AUTHOR]

Simple Summary: The surgical management of apparent early-stage endometrial cancer is still unclear. Nodal involvement is prognostic, but the role of retroperitoneal staging is still debated. Sentinel node mapping has been introduced and accepted as a valid alternative to full lymphadenectomy. Furthermore, ultrastaging provides a more accurate analysis of the excised lymph nodes by detecting a higher rate of low-volume metastasis. The aim of this study was to evaluate the impact of low-volume metastasis on recurrence-free survival in women with apparent early-stage endometrial cancer in a large retrospective multi-institutional collaboration. The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinically relevant information that guides further surgical management of the axilla in women with breast cancer is the distinction between non-significant (N0–N1) versus significant (≥N2) lymph node metastases. In women with newly diagnosed breast cancer, MRI is increasingly used to determine the local extent of disease in the breast. The aim of our retrospective study on 414 patients who underwent routine breast MRI for local staging of the breast was to determine whether an abbreviated protocol for regional lymph node staging is sufficient to identify patients with significant nodal disease. Our results demonstrated that a single 3 min coronal T1-weighted sequence, acquired with the system's built-in body coil, covering the chest wall, axilla, and supra- and infraclavicular region, helped rule out the presence of significant nodal disease with a NPV of 98.8% [97.0–100%]. False-positive findings were mostly caused by patients with positive, but non-significant, lymph node metastases (N1). Background: The detection of regional lymph node metastases (LNM), in particular significant LNM (≥N2), is important to guide treatment decisions in women with breast cancer. The purpose of this study was to determine whether a coronal pulse sequence as part of pre-operative breast MRI is useful to identify women without significant LNM. Material: Retrospective study between January 2017 and December 2019 on 414 consecutive women with breast cancer who underwent pre-operative breast MRI on a 1.5 T system. For lymph node (LN) staging, a coronal pre-contrast non-fat-suppressed T1-weighted TSE sequence was acquired with the system's built-in body coil, covering the chest wall; acquisition time 3:12 min. Two radiologists rated the likelihood of LNM on a 3-point scale (absent/possible/present). Validation was obtained by histology from sentinel LN biopsy, axillary LN dissection, and/or PET/CT. Results: 368/414 women were staged to have no or non-significant LNM (pN0 in 282/414, pN1 in 86/414), and significant LNM (≥pN2) in 46/414. For identification of women with significant LNM, MRI was true-positive in 42/46, false-negative in 4/46, true-negative in 327/368, and false-positive in 41/83, the latter mostly caused by women with N1-disease (38/41), yielding an NPV and PPV for significant LNM of 98.8% [95%-CI: 97.0–100%] and 50.6% [43.1–58.1%], respectively. Conclusions: A 3 min coronal T1-weighted pulse sequence covering the chest wall as part of pre-operative breast MRI is useful to rule out significant LNM with high NPV. Where MRI staging is positive for significant LNM, additional work-up is indicated to improve the distinction of N1 and N2 disease. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of obesity on melanoma has rarely been researched. Incidence of obesity is rapidly growing and melanoma is one of the most prevalent types of cancers worldwide. Several studies have shown that overweight and obese populations not only have a higher risk of developing melanoma but also tend to present with thicker melanomas at the time of diagnosis. Given that melanoma thickness is one of the main predictors of the melanoma prognosis, a worse prognosis in a patient with obesity would be expectable. However, this has not yet been demonstrated in the literature. Our study is the first to show that obese patients are twice more likely to present with lymph-node metastases. Lymph node metastases is the second most important prognosis predictor of melanoma. Our findings, therefore, raise important questions regarding the screening and treatment of obese patients with melanoma. (1) Background: While obesity is a known independent risk factor in the development of melanoma, there is no consensus on its influence on melanoma prognosis. (2) Methods: In a monocentric retrospective study, data was collected from patients who underwent sentinel lymph node (SLN) biopsy for stage IB-IIC melanoma between 2013 and 2018. Patients were divided into groups according to their body mass index (BMI). The association between BMI and melanoma features, as well as the risk factors for metastases in SLN were examined. (3) Results: Of the 1001 patients, 336 had normal weight (BMI < 25), 402 were overweight (BMI >= 25 and <30), 173 obese (BMI >= 30 and <35) and 90 extremely obese (BMI >= 35). Overweightness and obesity were associated with higher tumor thicknesses at time of diagnosis. Ulceration was not influenced by the patient's weight. Metastases in sentinel lymph node was almost twice more likely in extremely obese patients than in normal weight patients. Independent risk factors for metastases in SLN in our study were tumor thickness, ulceration, and BMI > 35. (4) Conclusions: This is the first study to show higher metastases rates in high-BMI patients with melanoma, raising important questions regarding the screening and treatment of this specific patient population. [ABSTRACT FROM AUTHOR]

For dogs with oral tumors, cervical lymph node (LN) metastasis alters treatment and prognosis. It is therefore prudent to make an accurate determination of the clinical presence (cN+ neck) or absence (cN0 neck) of metastasis prior to treatment. Currently, surgical LN extirpation with histopathology is the gold standard for a diagnosis of metastasis. Yet, recommendations to perform elective neck dissection (END) for staging are rare due to morbidity. Sentinel lymph node (SLN) mapping with indirect computed tomography lymphangiography (ICTL) followed by targeted biopsy (SLNB) is an alternative option to END. In this prospective study, SLN mapping followed by bilateral END of all mandibular LNs (MLNs) and medial retropharyngeal LNs (MRLNs) was performed in 39 dogs with spontaneously occurring oral neoplasia. A SLN was identified by ICTL in 38 (97%) dogs. Lymphatic drainage patterns were variable although most often the SLN was identified as a single ipsilateral MLN. In the 13 dogs (33%) with histopathologically confirmed LN metastasis, ICTL correctly identified the draining lymphocentrum in all (100%). Metastasis was confined to the SLN in 11 dogs (85%); 2 dogs (15%) had metastasis beyond the SLN ipsilaterally. Contrast enhanced CT features had good accuracy in predicting metastasis, with short axis measurements less than 10.5 mm most predictive. ICTL imaging features alone were unable to predict metastasis. Cytologic or histopathologic SLN sampling is recommended prior to treatment to inform clinical decision-making. This is the largest study to show potential clinical utility of minimally invasive ICTL for cervical LN evaluation in canine oral tumors. [ABSTRACT FROM AUTHOR]

The objective of this study was to gain our initial experience in one-step nucleic acid amplification (OSNA) for detecting sentinel lymph node (SLN) metastasis as compared to standard pathological staging in patients with breast cancer. Fifteen patients with preoperatively confirmed early breast cancer eligible for breast-saving therapy and sentinel lymph node biopsy (SLNB) were enrolled in the study. Lymphatic mapping and SLNs detection were performed through the magnetic method. Excised SLNs were intraoperatively examined through OSNA and frozen-section methods. All lymph nodes were postoperatively examined through histopathology and immunohistochemistry. The results of latter methods were correlated. Our initial experience proved OSNA to be a sensitive and efficient alternative to intraoperative assessment of metastases in SLN in breast cancer patients. Moreover, the information obtained by the OSNA method provides the surgeon with the possibility of assessing a more accurate prognosis during the initial surgery. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer. Materials and methods: We prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves. Results: A total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1–2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001). Conclusions: CEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer. Key Points: • The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis. • The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV). • Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis. [ABSTRACT FROM AUTHOR]

The sentinel lymph node (SLN) concept hypothesizes that metastatic cancer cells will spread through the lymphatic system to the SLN being the first one in the lymphatic chain to receive the metastatic cells, indicating that if the SLN is free of cancer cells the rest of the lymphatic chain is also without metastatic disease. Diagnostic ultrasound imaging (US) has been used to evaluate lymph nodes (LN) to determine level of suspicion and to guide LN biopsies. However, conventional US cannot be used for lymphatic mapping, which requires administration of a tracer. This has been changed with the use of contrast-enhanced US (CEUS) to detect lymphatic channels and SLNs after subcutaneous injections of microbubble-based US contrast agents (UCAs). The aim of this review is to examine the clinical evidence on the role of subcutaneous injection of UCA, known as lymphosonography, to be used as preoperative identification of SLNs in patients with breast and other cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: The rate of positive parametrial lymph nodes in a series of apparent early-stage cervical cancer patients undergoing bilateral sentinel lymph node mapping was 3.1%. After ultrastaging of parametrial tissue, no occult micrometastasis was detected. Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1–IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu–Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the "sentinel" of the sentinel lymph node. [ABSTRACT FROM AUTHOR]

Simple Summary: Contrary to the common belief that prostate cancer is an immune desert, our study shows tumor-associated B-cell responses in prostate cancer. We demonstrate mature and activated phenotypes of B cells with an increased frequency of effector plasmablasts in tumor-draining sentinel lymph nodes. These findings indicate a B-cell-specific antitumor immune response, emphasizing the importance of further trials targeting B cells in prostate cancer immunotherapy. B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate–high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Indicators of a potential recurrence of melanoma in patients after the detection of lymph node metastasis are needed in order to not treat patients unnecessarily with a systemic therapy. Blood parameters such as the number of white blood cells and ratios of different white blood cell subtypes are collected in the clinical routine and could be useful indicators of a possible disease relapse. The aim of our present study was to identify blood parameters which predict the recurrence of melanoma in melanoma patients with microscopic sentinel lymph node metastasis. We identified the lymphocyte-to-monocyte ratio (LMR) and C-reactive protein (CRP) to be the strongest predictors for melanoma recurrence. Although adjuvant therapies with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors improve recurrence-free survival (RFS) in stage III melanoma patients significantly, prognostic factors are needed to identify patients with a high risk of disease recurrence. Therefore, the aim of our study was to investigate the prognostic potential of routinely collected blood parameters for stage III melanoma patients with microscopic sentinel lymph node (SLN) metastasis. Altogether, we retrospectively analyzed 138 stage III melanoma patients who were diagnosed with microscopic SLN metastasis at the skin cancer center of the University Hospital Cologne between 2011 and 2020 and who did not receive prior adjuvant therapy with ICI or BRAF/MEK-inhibitors. Univariate and multivariate Cox regression analyses, Kaplan–Meier survival analyses and receiver operating characteristic (ROC) curves were performed to assess the impact of preoperatively collected blood parameters and blood ratios on recurrence-free survival (RFS; primary endpoint) and overall survival (OS). A high neutrophil-to-lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR) and high C-reactive protein (CRP) value were significantly associated with shorter RFS in multivariate analysis. For LMR (cut-off 3.5) and for CRP (cut-off 3.0) this effect remained after dichotomization. CRP showed a stronger association with RFS than NLR or LMR, with the highest association being detected for the combination of low LMR and high CRP. Additionally, derived NLR ≥ 2.0 was significantly associated with shorter OS in multivariate analysis. In summary, our data suggest that CRP in combination with LMR should be considered as a marker for melanoma recurrence in stage III melanoma patients with microscopic SLN metastasis. [ABSTRACT FROM AUTHOR]

AIMS: To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. METHODS: Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). RESULTS: TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P < .001) and multivariate (1.55 [95% CI: 1.04, 2.32], P = .030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P = .874; interaction OR: 1.04 [0.7, 1.55], P = .835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P = .180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P < .001). CONCLUSIONS: our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS. [ABSTRACT FROM AUTHOR]

Simple Summary: Pseudo-H&E (p-H&E) imaging using a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) is a novel microstructural technique for assessing en face optical sections of ex vivo specimens. In this study, the comparison of p-H&E, frozen-sectioned H&E, and paraffin-sectioned H&E images was intraoperatively realized through ex vivo sentinel lymph node (SLN) biopsy for breast cancer metastasis assessment. The results revealed that OCMIS is a useful tool for intraoperative breast cancer metastasis assessment through SLN biopsy in patients requiring surgery. Frozen-sectioned hematoxylin–eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images. [ABSTRACT FROM AUTHOR]

Metastasis is a major cause of death in patients with cancer. The two main routes for cancer cell dissemination are the blood and lymphatic systems. The underlying mechanism of hematogenous metastasis has been well characterized in the past few decades. However, our understanding of the molecular basis of lymphatic metastasis remains at a premature stage. Conceptually, cancer cells invade into lymphatic capillary, passively move to collecting lymphatic vessels, migrate into sentinel lymph node (SLN;, the first lymph node to which cancer cells spread from the primary tumor), and enter the blood circulatory system via the subclavian vein. Before arriving, cancer cells release specific soluble factors to modulate the microenvironment in SLN to establish a beachhead for successful colonization. After colonization, cancer cells inhibit anti-tumor immunity by inducing the recruitment of regulatory T cell and myeloid-derived suppressor cells, suppressing the function of dendritic cell and CD8+ T cell, and promoting the release of immunosuppressive cytokines. The development of novel strategies to reverse cancer cell-triggered SLN remodeling may re-activate immunity to reduce beachhead buildup and distant metastasis. In addition to being a microanatomic location for metastasis, the SLN is also an important site for immune modulation. Nanotechnology-based approaches to deliver lymph node-tropic antibodies or drug-conjugated nanoparticles to kill cancer cells on site are a new direction for cancer treatment. Conversely, the induction of stronger immunity by promoting antigen presentation in lymph nodes provides an alternate way to enhance the efficacy of immune checkpoint therapy and cancer vaccine. In this review article, we summarize recent findings on the reprogramming of SLN during lymphatic invasion and discuss the possibility of inhibiting tumor metastasis and eliciting anti-tumor immunity by targeting SLN. [ABSTRACT FROM AUTHOR]

Simple Summary: Radio-guided sentinel lymph node (SLN) detection techniques are utilized in many malignancies, including breast and penile cancer. In the setting of prostate cancer (PCa), SLNs identification had low specificity and sensitivity in available studies, and extended pelvic lymph node dissection (ePLND) remains the gold standard in the assessment of nodal invasion. Our study is the first to detect SLNs pre- and intraoperatively while performing 'whole-pelvis' modified-extended lymphadenectomy (mePLND), including lymph nodes (LNs) from the ePLND template, as well as the presacral and Marcille's fossa areas. The aim of this study was to assess the efficacy of single-photon emission computed tomography (SPECT-CT) and the gamma-probe in the SLN detection, as well as to map lymphatic drainage patterns in the prostate. Results showed that the SLN detection technique has very low specificity and relatively high sensitivity and remains a poor nodal staging tool in intermediate- and high-risk PCa patients. Background. In many malignancies, sentinel lymph node dissection (SLND) is being used as a nodal staging tool. We prospectively evaluated the diagnostic value of radio-guided sentinel lymph node (SLN) detection in patients with prostate cancer (PCa). This study aimed to investigate the reliability of the radio-guided SLN detection technique for perioperative localization of LNs metastases as well as to map lymphatic drainage patterns of the prostate. Methods. Forty-three patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging underwent radical prostatectomy with modified-extended pelvic lymph node dissection (mePLND). A day before the planned surgery, a Tc-99m nanocolloid was injected into the prostate under the control of transrectal ultrasonography (TRUS). Preoperative single-photon emission computed tomography (SPECT-CT) imaging and intraoperative gamma-probe were used to identify SLNs. All positive lesions were excised, followed by mePLND. The excised lymph nodes (LNs) were then submitted for histopathological examination, which was used as a reference for the calculation of diagnostic parameters of the SLN technique for SPECT-CT and the intraoperative gamma-probe. Results. In total, 119 SLNs were detected preoperatively (SPECT-CT) and 118 intraoperatively (gamma-probe). The study revealed that both SLN detection techniques showed a sensitivity of 90% and a specificity of 6.06%. The negative predictive value (NPV) was 66.67%. SLN technique would have correctly staged nine of 10 patients, which is the same result as in the case of limited LND. However, it allowed the removal of all metastatic nodes only in four of them. SLND would have comprised 69.7% of preoperatively detected LNs, and removed 13 out of 19 positive LNs (68.42%), respectively. Conclusions. Radio-guided SLND has a low diagnostic rate and is a poor staging tool. ePLND remains the gold standard in nodal metastases assessment in PCa. Our study indicates that lymphatic drainage of the prostate and actual metastasis routes may vary significantly. [ABSTRACT FROM AUTHOR]

• Contralateral groin metastases or recurrences in patients with unilateral SN metastasis are rare. • Unilateral groin treatment is sufficient in patients with unilateral SN metastases. • In near-midline vulvar cancer, unilateral SN detection is sufficient when the lymphoscintigram shows unilateral lymph flow. • These findings offer further opportunity to safely reduce treatment-related morbidity in early-stage vulvar cancer. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%–4.5%]) had a contralateral groin recurrence. The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary sarcomas of the parotid gland are rare malignancies of mesenchymal origin for which there is no generally well-defined treatment guideline. The aim of this study was to analyze, through the review of the literature, the factors affecting the prognosis of patients with primary sarcoma of the parotid gland. Size/extension at the diagnosis and the sarcoma's histotype were the most important prognostic factors. Multivariate analysis showed that surgery performed on the tumor was the only parameter affecting long-term survival. In particular, total parotidectomy with preservation or, in the most advanced cases, with the sacrifice of facial nerve should be performed at any age independently of tumor histology. The aim of this study was to systematically review the literature of sarcoma of the parotid gland in order to analyze the main factors affecting survival rate. A systematic literature review was performed between January 1990 to November 2021, and 88 patients affected by parotid gland sarcomas were included. The most common histological types were Rhabdomyosarcoma and Synovial Sarcoma. From our review, it emerges that primary sarcomas of the parotid glands are locally aggressive but show low tendency to metastasize to the lymph nodes of the neck and that surgery (i.e., total or radical parotidectomy) is the main approach for their treatment. The global overall survival (OS) is 52% at 5 years and 34.1% at 10 years. The OS for T1, T2, T3, T4 tumor at 5 years of follow up is 80.0%, 66.5%, 56.7% and 33.3%, respectively. Size/extension at the diagnosis and the sarcoma's histotype are the most important prognostic factors. Multivariate analysis showed that surgery (total or radical parotidectomy) performed on the tumor (p = 0.0008) was the only parameter that significantly affected the OS. Among the other variables, age (younger), use of adjuvant therapy and lymph node metastasis showed borderline significative values (p = 0.05). Our analysis suggests that, when a primitive parotid sarcoma is diagnosed, total or radical parotidectomy should be performed at any age independent of tumor histology. Because regional lymph node metastases from parotid sarcomas are uncommon, alternative strategies (e.g., close follow-up by imaging and evaluation of sentinel lymph nodes) should be pursued before lymph node (selective/radical) dissection. [ABSTRACT FROM AUTHOR]

Hypoxia affects tumor aggressiveness and activates pathways associated with epithelial mesenchymal transition (EMT) which are crucial for tumor progress. In this study, the correlation of hypoxia and EMT with sentinel lymph node status and tumor-specific survival was investigated in primary melanomas. CD34 for capillary count and Hypoxia inducible factor-1α (HIF-1α) as hypoxia indicators as well as Ezrin and L1-Cell Adhesion Molecule (L1CAM), both critical proteins contributing to EMT, were analyzed using immunohistochemistry in 49 melanoma patients with long follow-up (F/U, mean 110 months; range 12–263 months). We found a significant correlation between Breslow tumor thickness and Ezrin expression (p = 0.018). L1CAM expression in primary melanoma was significantly associated with HIF-1α expression (p < 0.0001) and sentinel lymph node metastasis (p = 0.011). Furthermore, low capillary count, reflecting hypoxic condition, was significantly associated with Ezrin expression (p = 0.047) and decreased tumor-specific survival (p = 0.035). In addition, patients with high Ezrin expression in their primary melanoma had a dramatic loss of life early in their F/U period (mean survival time 29 months; range 15–44 month). Our results highlight the relevance of Ezrin, L1CAM and HIF-1α as prognostic markers in melanoma patients. Additionally, we demonstrate that hypoxia in primary melanoma affects EMT and is at least partly responsible for early metastatic dissemination. [ABSTRACT FROM AUTHOR]

In canine cutaneous mast cell tumours (cMCTs), histologic grade and clinical stage are the most important prognostic factors, with high‐grade tumours and metastatic lymph nodes (LNs) significantly influencing the evolution of disease. However, it is uncertain whether histologic grade and clinical stage should be given equal weighting value in patient prognostication and management. Dogs with low‐ and high‐grade cMCTs and at least one overtly metastatic sentinel LN undergoing standardized treatment, consisting of surgical excision of the cMCT, lymphadenectomy and chemotherapy, were retrospectively included. The aim was to determine whether, at the same clinical stage, histologic grade retained prognostic relevance. Sixty dogs were included: 26 had a high‐grade cMCT tumour and 34 had a low‐grade cMCT. Median follow‐up was 367 days (range, 187–748) in the high‐grade group, and 1208 days (range, 180–2576) in the low‐grade group. Median time to progression was significantly shorter in the high‐grade group than in the low‐grade group (214 days versus not reached; p <.001), as well as tumour‐specific survival (545 days versus not reached; p <.001). On multivariable analysis, a high histologic grade and incomplete margins retained prognostic significance for both tumour progression and tumour‐specific death. In dogs with cMCT and at least one overtly metastatic LN undergoing multimodal treatment, histologic grade significantly correlated with outcome. Overall prognosis was not unfavourable, even in the high‐grade group, further supporting that a multimodal therapeutic approach, addressing primary tumour and sentinel LN, should be offered. Whether chemotherapy should be incorporated in the therapeutic planning of low‐grade cMCTs remains to be defined. [ABSTRACT FROM AUTHOR]

Objective. To analyze and discuss the influencing factors of sentinel lymph node metastasis in breast cancer. Methods. A total of 469 breast cancer patients admitted in the Department of Pathology of Guangdong Women and Children Hospital from October 2016 to December 2021 were retrospectively analyzed. The general information, immunohistochemical expression, tumor molecular subtype, tumor size, histological grade, pathological type, and tumor location were collected and the relationship with sentinel lymph node metastasis was analyzed. Results. For patients with different age, Ki-67 and Human epidermal growth factor receptor-2 (HER-2) immunohistochemical expression level (invasive cancer), molecular subtype (invasive cancer), tumor size, histological grade (invasive cancer) and pathological type. The results of multivariate logistic regression analysis showed that the age was less than or equal to 40 years; the molecular subtype was Luminal B and HER-2 overexpression (invasive cancer); tumor was larger; the histological grade (invasive cancer) was higher; the pathological type was invasive carcinoma, there were independent risk factors for sentinel lymph node metastasis in breast cancer. The sentinel lymph node metastasis rates of invasive lobular carcinoma, invasive micropapillary carcinoma, and metaplastic carcinoma (all met the criteria for squamous cell carcinoma and histological grade III) were higher than 50% in special invasive carcinomas. Conclusion. Age, expression level of Ki 67 and HER-2, molecular typing, tumor volume and histological grade are all high-risk factors related to sentinel lymph node metastasis of breast cancer. When one or more of the above factors are involved in an examination, pathologists should be more cautious in making a sentinel lymph node frozen diagnosis. By standardizing the sampling and increasing the number of frozen sections (slicing more frozen tissue layers), the section quality can be improved. This may be conducive to reducing the false negative rate and reducing the pain and risk of secondary surgery. [ABSTRACT FROM AUTHOR]

Objective: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC).Methods: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0.Results: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC.Conclusion: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III). [ABSTRACT FROM AUTHOR]

Objective: Sentinel lymph-node biopsy (SLNB) is now as alternative to pelvic and para-aortic lymph-node dissection (PPALND) for managing endometrial cancers. These data have been largely published from high-volume specialized institutions, but complete PPALND is still performed by many surgeons at smaller nonspecialized centers. The aim of this research was to demonstrate that SLNB is feasible, reproducible, and sensitive without affecting cancer-specific outcomes when implemented at nonspecialized centers. Materials and Methods: Cases of patients with clinical stage-I endometrial cancer were retrospectively reviewed from September 2016 through February 2020. Endometrioid, uterine papillary serous (UPSC), malignant mixed-mesodermal tumor (MMMT), and clear-cell (CC) histologies were included. All patients had undergone either robot-assisted or laparoscopic hysterectomies with SLNB. Indocyanine green was injected into the cervix bilaterally. Per the algorithm, patients with suboptimal lymph-node mapping or nodes suspicious for metastasis underwent a side-specific pelvic lymph-node dissection (LND). Para-aortic LND was performed at the discretion of the surgeon. In addition to SLNB, PPALND was performed for patients with MMMT, UPSC, or CC. Sentinel lymph nodes (SLNs) were evaluated using ultrastaging protocols with serial sectioning and cytokeratin staining. The medical records were queried for clinical or radiographic evidence of recurrences. Results: A total of 92 cases were included: 69 stage IA; 12 stage IB; 3 stage II; and 8 stage III (2 IIIA, 2 IIIC1, 4 IIIC2). The majority of cancers were endometrioid (73%), followed by UPSC (15.0%), MMMT (5.0%), and CC (4%). At least 1 SLN was detected in 95.4% of cases. The rate of bilateral SLN detection was 74.3% and improved over time from 2017 to 2019: 70% (2017); 74.4% (2018); and 80% (2019). Twenty patients underwent PPALND. Non-SLNs were positive in 3 patients, all with high-risk histologies. No other patients had false–negative SLNs. No recurrences occurred in this cohort with a median follow-up of 22 months. Conclusions: SLNB is a sensitive and specific method for assessing lymph-node involvement in patients with clinical stage-I endometrial cancers. These results are comparable to the rates reported in the literature and shows that, in nonspecialized centers, this approach is safe and reproducible without affecting cancer-specific outcomes. (J GYNECOL SURG 38:305) [ABSTRACT FROM AUTHOR]

To evaluate the locations of metastatic pelvic sentinel nodes (SLN) and the proportion of SLNs outside and within defined typical anatomical positions along the upper paracervical lymphatic pathway (UPP). Consecutive women with endometrial cancer (EC) of all risk groups underwent pelvic SLN-detection using cervically injected indocyanine green (ICG). A strict anatomically based algorithm and definitions of SLNs was adhered to. The positions of ICG-defined SLNs were intraoperatively depicted on an anatomical chart. All SLNs were examined using ultrastaging and immunohistochemistry. The proximal third of the obturator fossa and the interiliac area were defined as typical positions. The parauterine lymphovascular tissue (PULT) was separately removed. The proportions of metastatic SLNs, overall and isolated, typically, and atypically positioned were analyzed per woman. A median of two (range 1–12) SLN metastases along the UPP including the PULT were found in 162 women. 41 of 162 women (25.3 %) had isolated metastases in the obturator fossa harboring 49.1 % of all SLN metastases. Three women (1,9 %) had isolated PULT metastases. SLN metastases outside typical positions were identified in 28/162 women (17.3 %); isolated metastases were seen in seven women (4.3 %), so 95.7 % of pelvic node positive women had at least one metastatic SLN located at a typical position. A selective removal of lymph nodes at typical proximal obturator and interiliac positions and the PULT can replace a full side specific pelvic LND when SLN mapping is unsuccessful. The obturator fossa is the predominant location for metastatic disease. • An anatomically based nodal sampling is an alternative when SLN mapping fails. • The obturator fossa harbored 49.1 % of all SLN metastases. • Isolated obturator metastases in 25.3 % of node positive women. • A full lymphadenectomy can be omitted. [ABSTRACT FROM AUTHOR]

Patients with cutaneous melanoma routinely undergo sentinel lymph node (SLN) biopsy. If this first lymph node is clear, the entire lymph node basin is very likely to be free from the metastatic disease. Lymph node analysis is therefore of great importance with respect to prognostication and further management. Various cell types, including benign nevoid rests, can mimic metastatic melanomatous cells in the SLN. There is no standardized method to differentiate naevoid rests from metastatic melanoma. Diagnosis is based on cell location, morphology and multiple immunohistochemical techniques, with no single test being completely diagnostic. We present a patient with Lentigo Maligna melanoma, who was found to have benign nevoid rests on SLN biopsy, and discuss the diagnostic tests and considerations in differentiating benign nevoid rests from metastatic melanoma. [ABSTRACT FROM AUTHOR]

Introduction. Technetium-labeled sulfur colloid (TSC) is a radiolabeled mapping agent commonly used for sentinel lymph node biopsy (SLNBx). Tilmanocept, a CD206 receptor-targeted mapping agent, has gained recent popularity due to potential advantages of rapid and quick uptake to the SLNs. The objectives of this study were to assess (1) the difference in the number of SLNs harvested using tilmanocept versus TSC and (2) the difference in time to transcutaneous localization when using an intraoperative injection approach. Methods. Patients undergoing breast conservation and SLNBx were consented and randomized to receive either 0.5 mCi of filtered TSC or 0.5 mCi of tilmanocept injected intradermally immediately after induction of anesthesia. Axillary transcutaneous gamma detector probe counts were taken at 1-minute intervals until a hot spot was identified. SLNs were then identified and excised. Additional nodes were excised if their counts per second (cps) were greater than 10% of the cps of the hottest SLN. The number of SLNs was based on both number of nodes collected intraoperatively and the number recorded in the final pathology report. Results. The study population consisted of 86 patients, 48 randomized to tilmanocept and 38 to TSC. There were no significant differences in patient or tumor characteristics between the two groups. Localization rates were 100% for both cohorts. The mean number of SLNs identified and removed was not significantly different (p = 0.34 , intraoperatively; p = 0.57 , pathology reported). Time to transcutaneous localization was 3.3 ± 2.0 minutes for tilmanocept and 3.9 ± 2.3 minutes for TSC (p = 0.19). The average cps for the hottest node was 2,180.0 ± 2,460.5 in the tilmanocept group compared to 2,679.3 ± 2,687.5 in the TSC group (p = 0.94). Conclusion. There was no significant difference in the number of SLNs harvested or in the time to transcutaneous localization when using tilmanocept versus TSC as the radiolabeled mapping agents for intraoperative injection and mapping. Either agent can be used without any significant difference in performance. [ABSTRACT FROM AUTHOR]

Objective: To develop a predictive model for additional inguinal lymph node metastases (LNM) at inguinal lymph node dissection (ILND) after positive dynamic sentinel node biopsy (DSNB) using DSNB characteristics to identify a patient group in which ILND might be omitted. Patients and Methods: We conducted a retrospective study of 407 inguinal basins with a positive DSNB in penile cancer patients who underwent subsequent ILND from seven European centres. From the histopathology reports, the number of positive and negative lymph nodes, presence of extranodal extension and size of the metastasis were recorded. Using bootstrapped logistic regression, variables were selected for the clinical prediction model based on the optimization of Akaike's information criterion. The area under the curve (AUC) of the receiver‐operating characteristic curve was calculated for the resulting model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. Results: Of the positive DSNBs, 64 (16%) harboured additional LNM at ILND. Number of positive nodes at positive DSNB (odds ratio [OR] 2.19, 95% confidence interval (CI) 1.17–4.00; P = 0.01) and largest metastasis size in mm (OR 1.06, 95% CI 1.03–1.10; P = 0.001) were selected for the clinical prediction model. The AUC was 0.67 (95% CI 0.60–0.74). The DCA showed no clinical benefit of using the clinical prediction model. Conclusion: A small but clinically important group of basins harbour additional LNM at completion ILND after positive DSNB. While DSNB characteristics were associated with additional LNM, they did not improve the selection of basins in which ILND could be omitted. Thus, completion ILND remains necessary in all basins with a positive DSNB. [ABSTRACT FROM AUTHOR]

A 53-year-old woman with a plantar malignant melanoma lesion was referred to our tertiary clinic for sentinel lymph node mapping. Lymphoscintigraphy with 99Tc-Phytate detected ipsilateral inguinal and popliteal sentinel nodes. After total resection of nodes, the pathology report confirmed that all specimens were involved by the tumor. As part of an institutional study evaluating somatostatin receptor avidity of melanoma by 99Tc-HYNIC-TOC scan, she also underwent a whole-body octreotide scan, which surprisingly showed intense tracer uptake in the right cervical region, confining in SPECT/CT images to a mass at the C2 spinal level, adjacent to the right carotid bifurcation. Neck surgery with gamma probe after injection of another dose of 99mmTc-HYNIC-TOC was performed successfully, and the pathology report was consistent with a carotid body tumor. To best our knowledge, our case is the first one in the literature, which reports an incidental paraganglioma with 99Tc-HYNIC-TOC scan which resected via radio-guided surgery, again with 99mmTc-HYNIC-TOC tracer. [ABSTRACT FROM AUTHOR]

Background: The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients.Methods: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model.Results: The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS.Conclusion: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization. [ABSTRACT FROM AUTHOR]