Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.

Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Defining the role of multiparametric MRI in predicting prostate cancer extracapsular extension.

OBJECTIVES: To identify the predictive factors of prostate cancer extracapsular extension (ECE) in an institutional cohort of patients who underwent multiparametric MRI of the prostate prior to radical prostatectomy (RP). PATIENTS AND METHODS: Overall, 126 patients met the selection criteria, and their medical records were retrospectively collected and analysed; 2 experienced radiologists reviewed the imaging studies. Logistic regression analysis was conducted to identify the variables associated to ECE at whole-mount histology of RP specimens; according to the statistically significant variables associated, a predictive model was developed and calibrated with the Hosmer-Lomeshow test. RESULTS: The predictive ability to detect ECE with the generated model was 81.4% by including the length of capsular involvement (LCI) and intraprostatic perineural invasion (IPNI). The predictive accuracy of the model at the ROC curve analysis showed an area under the curve (AUC) of 0.83 [95% CI (0.76-0.90)], p < 0.001. Concordance between radiologists was substantial in all parameters examined (p < 0.001). Limitations include the retrospective design, limited number of cases, and MRI images reassessment according to PI-RADS v2.0. CONCLUSION: The LCI is the most robust MRI factor associated to ECE; in our series, we found a strong predictive accuracy when combined in a model with the IPNI presence. This outcome may prompt a change in the definition of PI-RADS score 5.

Validation of a Clinical Calculator Predicting Freedom From Colon Cancer Recurrence After Surgery on the Basis of Molecular and Clinical Variables.

BACKGROUND: The Memorial Sloan Kettering clinical calculator for estimating the likelihood of freedom from colon cancer recurrence on the basis of clinical and molecular variables was developed at a time when testing for microsatellite instability was performed selectively, based on patient age, family history, and histologic features. Microsatellite stability was assumed if no testing was done. OBJECTIVE: This study aimed to validate the calculator in a cohort of patients who had all been tested for microsatellite instability. DESIGN: Retrospective cohort analysis. SETTINGS: Comprehensive cancer center. PATIENTS: This study included consecutive patients who underwent curative resection for stage I, II, or III colon cancer between 2017 and 2019. INTERVENTION: Universal testing of mircrosatellite phenotype in all cases. MAIN OUTCOME MEASURES: The calculator's predictive accuracy was assessed using the concordance index and a calibration plot of predicted versus actual freedom from recurrence at 3 years after surgery. For a secondary sensitivity analysis, the presence of a tumor deposit(s) (disease category N1c) was considered equivalent to one positive lymph node (category N1a). RESULTS: With a median follow-up of 32 months among survivors, the concordance index for the 745 patients in the cohort was 0.748 (95% CI, 0.693-0.801), and a plot of predicted versus observed recurrences approached the 45° diagonal, indicating good discrimination and calibration. In the secondary sensitivity analysis for tumor deposits, the concordance index was 0.755 (95% CI, 0.700-0.806). LIMITATIONS: This study was limited by its retrospective, single-institution design. CONCLUSIONS: These results, based on inclusion of actual rather than imputed microsatellite stability status and presence of tumor deposits, confirm the predictive accuracy and reliability of the calculator. See Video Abstract . VALIDACIN DE UNA CALCULADORA CLNICA QUE PREDICE LA AUSENCIA DE RECURRENCIA POSTQUIRURGICA DEL CNCER DE COLON SOBRE LA BASE DE VARIABLES MOLECULARES Y CLNICAS: ANTECEDENTES:La calculadora clínica del Memorial Sloan Kettering para la estimación de la probabilidad de ausencia de recurrencia del cáncer de colon sobre la base de variables clínicas y moleculares, se desarrolló en un momento en que las pruebas para la inestabilidad de microsatélites se realizaban de forma selectiva, basadas en la edad del paciente, los antecedentes familiares y las características histológicas. Se asumía la estabilidad micro satelital si no se realizaba ninguna prueba.OBJETIVO:El objetivo de este estudio fue validar la calculadora en una cohorte de pacientes a los que se les había realizado la prueba de inestabilidad de microsatélites.DISEÑO:Análisis de cohorte retrospectivo.AJUSTE:Centro integral de cáncer.PACIENTES:Pacientes consecutivos con cáncer de colon que fueron sometidos a resección curativa por cáncer de colon en estadios I, II o III entre los años 2017 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:La precisión predictiva de la calculadora fue evaluada mediante el índice de concordancia y un gráfico de calibración de la ausencia de recurrencia predecida versus la real a los 3 años tras la cirugía. A los efectos de un análisis secundario de sensibilidad, la presencia de depósito(s) tumoral(es) (categoría de enfermedad N1c) se consideró equivalente a un ganglio linfático positivo (categoría N1a).RESULTADOS:Con una mediana de seguimiento de 32 meses entre los supervivientes, el índice de concordancia para los 745 pacientes de la cohorte fue de 0,748 (intervalo de confianza del 95 %, 0,693 a 0,801), y una gráfica de recurrencias previstas versus observadas se acercó a la diagonal de 45°, indicando una buena discriminación y calibración. En el análisis secundario de sensibilidad para depósitos tumorales, el índice de concordancia fue de 0,755 (intervalo de confianza del 95 %, 0,700 a 0,806).LIMITACIONES:Diseño retrospectivo, institución única.CONCLUSIONES:Estos resultados, basados en la inclusión real del estado de estabilidad de microsatélites en lugar de imputado y la presencia de depósitos tumorales, confirman la precisión predictiva y la confiabilidad de la calculadora. (Traducción-Dr Osvaldo Gauto ).

Tumour deposits are independently associated with recurrence in colon cancer.

AIM: Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. METHOD: Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. RESULTS: Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. CONCLUSION: Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.

Imaging Characteristics Predictive of Cervical Extranodal Tumor Extension in Patients With Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: The aims of the study were to determine the predictive imaging findings of extranodal extension (ENE) in metastatic cervical lymph nodes of head and neck squamous cell carcinoma and to investigate the interobserver agreement among radiologists with different experience levels. MATERIALS AND METHODS: Patients with cervical lymph node dissection and who had metastatic lymph nodes and preoperative imaging were included. Three radiologists evaluated nodal necrosis, irregular contour, gross invasion, and perinodal fat stranding. They also noted their overall impression regarding the presence of the ENE. Sensitivity, specificity, odds ratios based on logistic regression, and interobserver agreement of ENE status were calculated. RESULTS: Of 106 lymph nodes (that met inclusion criteria), 31 had radiologically determined ENE. On pathologic examination, 22 of 31 nodes were positive for ENE. The increasing number of metastatic lymph nodes was associated with the presence of the ENE ( P = 0.010). Irregular contour had the highest sensitivity (78.6%) and gross invasion had the highest specificity (96%) for the determination of the ENE. The radiologists' impression regarding the presence of the pathlogical ENE had 39.3% sensitivity and 82% specificity. Metastatic lymph nodes with a perinodal fat stranding and with the longest diameter of greater than 2 cm were found to be strong predictors of the ENE. The gross invasion demonstrated the highest κ value (0.731) among the evaluated imaging criteria. CONCLUSIONS: In the assessment of ENE, the gross invasion had the highest specificity among imaging features and showed the highest interobserver agreement. Perinodal fat stranding and the longest diameter of greater than 2 cm in a metastatic lymph node were the best predictors of the ENE.

Utility of positive core number on MRI-ultrasound fusion targeted biopsy in combination with PI-RADS scores for predicting unexpected extracapsular extension of clinically localized prostate cancer.

OBJECTIVES: To evaluate the utility of magnetic resonance imaging (MRI) and MRI-ultrasound fusion targeted biopsy (TB) for predicting unexpected extracapsular extension (ECE) in clinically localized prostate cancer (CLPC). METHODS: This study enrolled 89 prostate cancer patients with one or more lesions showing a Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 but without morphological abnormality in the prostatic capsule on pre-biopsy MRI. All patients underwent TB and systematic biopsy followed by radical prostatectomy (RP). Each lesion was examined by 3-core TB, taking cores from each third of the lesion. The preoperative variables predictive of ECE were explored by referring to RP specimens in the lesion-based analysis. RESULTS: Overall, 186 lesions, including 81 (43.5%), 73 (39.2%), and 32 (17.2%) with PI-RADS 3, 4, and 5, respectively, were analyzed. One hundred and twenty-two lesions (65.6%) were diagnosed as cancer on TB, and ECE was identified in 33 (17.7%) on the RP specimens. The positive TB core number was ≤2 in 129 lesions (69.4%) and three in 57 lesions (30.6%). On the multivariate analysis, PI-RADS ≥4 (p = 0.049, odds ratio [OR] = 2.39) and three positive cores on TB (p = 0.005, OR = 3.07) were independent predictors of ECE. Lesions with PI-RADS ≥4 and a positive TB core number of 3 had a significantly higher rate of ECE than those with PI-RADS 3 and a positive TB core number ≤2 (37.5% vs. 7.8%, p < 0.001). CONCLUSIONS: Positive TB core number in combination with PI-RADS scores is helpful to predict unexpected ECE in CLPC.

The prognostic effect of radiological extranodal extension in HPV-positive oropharyngeal squamous cell carcinomas: a retrospective cohort analysis.

PURPOSE: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. METHODS: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). RESULTS: A non-significant trend towards better outcomes in the rENE- group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. CONCLUSIONS: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE.

The significance of the presence of extranodal extension in the metastatic node of differentiated thyroid cancer: a proposal for modification in the American Thyroid Association (ATA) risk stratification.

BACKGROUND: Multiple factors contribute to recurrences in differentiated thyroid cancers (DTC). Though the nodal size and number of positive nodes along with the presence of extranodal extension (ENE) have been mentioned in the present ATA risk stratification, the weightage given for ENE seems inadequate compared to the former two. METHODOLOGY: Factors predicting recurrences were analysed in this retrospective study of patients with DTC operated in a tertiary care centre. Based on our findings, we propose a modification in the present risk stratification. We have done so by comparing with existing risk stratification for fit and discrimination of this system. RESULTS: Out of 1428 patients, 859 (60.2%) patients had pathological nodal metastases (pN +) with ENE being present in 26.8% of these. The recurrence rate was 6.4% (92 patients). Recurrence rates in patients with ≤ 5 nodes without ENE, > 5 nodes without ENE, ≤ 5 nodes with ENE and > 5 nodes with ENE were 2.7%, 1.3%, 8.3% and 10.3%, respectively. Recurrence rates in patients with 0.2-3 cm without ENE, 0.2-3 cm with ENE and > 3 cm with/without ENE were 1.8%, 8.5% and 13.4%, respectively. A modified risk stratification incorporating ENE and excluding the number of metastatic nodes was proposed. The modified risk stratification had a better fit than the present system in terms of higher C index and lower AIC. CONCLUSIONS: Extranodal extension in differentiated thyroid cancer had the maximum influence on recurrence risk (recurrence-free survival) in our cohort. The prognostic impact of ENE supersedes the number of positive nodes in the risk of recurrence.

[Clinical characteristics and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region].

Objective: To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region. Methods: We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis. Results: The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history (HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status (HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits (HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy (HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits (HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy (HR=5.002, 95% CI: 2.300-10.880) and radiotherapy (HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade (HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression (HR=0.399, 95% CI: 0.168-0.945), HER-2 expression (HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy (HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions: The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

The 8th AJCC classification is inferior to a new neck stage based on intraparotid lymph node in parotid gland cancer.

BACKGROUND: Lymph node (LN) status is an important prognostic factor for parotid gland cancer (PGC). This study aimed to analyze the impact of extranodal extension (ENE) of intraparotid LN and LN metastasis burden on survival in PGC. METHODS: Patients with surgically treated PGC and at least one metastatic cervical LN were retrospectively enrolled. Primary outcome variables were distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). The impact of ENE and LN metastasis burden was assessed using the Cox model. RESULTS: A total of 292 patients were included. ENE in cervical or intraparotid LN was not associated with DMFS, DSS, or OS. Intraparotid LN metastasis had a significant impact on prognosis, and the presence of only one metastatic intraparotid LN offered an approximately 1.5-fold risk of distant metastasis. Prognostic models based on the number of positive LNs (1 vs. 2-3 vs. 4+) were superior to the AJCC N stage in terms of DMFS, DSS, and OS. CONCLUSIONS: ENE of cervical or intraparotid LN has a limited effect on the prognosis of PGC, and the number of positive LNs is better than the AJCC N stage in LN status evaluation.

Lymphoma and Other Lymph Node Pathologies Among Adult Patients with Lymphadenopathy in Abakaliki, Nigeria.

INTRODUCTION: Lymphadenopathy is usually due to benign or malignant conditions. It can also be local or systemic in distribution and can involve peripheral or deep-seated lymph nodes. This study aimed to determine the prevalence of lymphoma and the distribution pattern of lymph node pathologies among adult patients who presented with lymphadenopathy and its relationship with age and sex. METHODS: A retrospective study was conducted, and a record of all cases of lymphadenopathy with histological diagnosis over 5-year period (January 2017 to December 2021) was extracted from Departments of Anatomical Pathology of Alex Ekwueme Federal University Teaching Hospital, Abakaliki. The data generated were analyzed using Statistical Package for Social Sciences (SPSS) software, version 26. RESULTS: One hundred and ninety results were extracted with an age range of 18 to 94 years and a mean age of 41 ± 16 years. They were made up of 75 (39.5%) males and 115 (60.5%) females, with a male-to-female ratio of 1:1.5. The prevalence of lymphoma was 50.0% (95/190). Thirty-five (18.4%) were Hodgkin's lymphoma (HL), while 60 (31.6%) were non-Hodgkin's lymphoma (NHL). Other pathologies manifested by cases of lymphadenopathy include metastatic tumor deposits (38 (20%)), reactive lymphoid hyperplasia (29 (15.3%)), and tuberculous lymphadenitis (18 (9.5%)). Others include sinus histiocytosis (4 (2.1%)), dermatopathic lymphadenitis (5 (2.6%)), and Castleman's disease (1 (0.5%)). CONCLUSION: About half of all patients who presented with lymphadenopathy were lymphoma with a high prevalence of 50%, and the majority were NHL. Other major causes of lymphadenopathy were metastatic tumor deposits, reactive lymphoid hyperplasia, and tuberculous lymphadenitis. Any case of lymphadenopathy should be properly investigated early for effective management.

Revised Nodal Staging Integrating Tumor Deposit Counts With Positive Lymph Nodes in Patients With Stage III Colon Cancer.

OBJECTIVE: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging. SUMMARY BACKGROUND DATA: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered. METHODS: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared. RESULTS: Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2. CONCLUSIONS: Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with high-risk stage III colon cancer staged as N3.

Negative Prognostic Impact of Tumor Deposits in Rectal Cancer: A National Study Cohort.

OBJECTIVE: To investigate whether tumor deposits (TDs) in rectal cancer are associated with increased recurrence risk and decreased survival. BACKGROUND: Tumor deposits (TDs) are considered a risk factor for recurrence after colon cancer resection, and the presence of TDs prompts adjuvant chemotherapy. The prognostic relevance of TDs in rectal cancer requires further exploration. METHODS: All patients treated with abdominal resection surgery for rectal cancer in Sweden between 2011 and 2014 were eligible for inclusion in this retrospective cohort study based on prospectively collected data from the Swedish Colorectal Cancer Registry. The primary endpoint was local recurrence or distant metastasis. Secondary outcomes were overall and relative survival. RESULTS: Five thousand four hundred fifty-five patients were identified of which 3769 patients were analyzed after exclusion. TDs were found in 404 (10.7%) patients, including 140 (3.7%) patients with N1c-status. In TD-positive patients, local recurrence and distant metastasis rates at 5 years were 6.3% [95% CI 3.8-8.8%] and 38.9% [95% CI, 33.6-43.5%] compared with 2.7% [95% CI, 2.1-3.3%] and 14.3% [95% CI, 13.1-15.5%] in TD-negative patients. In multivariable regression analysis, the risk of local recurrence and distant metastasis were increased; HR 1.86 [95% CI, 1.09-3.19; P =0.024] and 1.87 [95% CI, 1.52-2.31; P =<0.001], respectively. Overall survival at 5 years was 68.8% [95% CI, 64.4-73.4%] in TD-positive patients and 80.7% [95% CI, 79.4-82.1%] in TD-negative patients. pN1c-patients had similar outcomes regarding local recurrence, distant metastasis, and survival as pN1a-b stage patients. TD-positive pN1a-b patients had significantly worse outcomes whereas TDs did not affect outcomes in pN2a-b patients. CONCLUSION: This study suggests that TDs have a negative impact on the prognosis in rectal cancer. Thus, efforts should be made to diagnose TD-positive rectal cancer patients preoperatively.

Prognostic Value of Tumor Deposits in Stage III Colorectal Cancer Patients with Different N Stages: A Population-Based, Retrospective, Cohort Study.

PURPOSE: Tumor deposits (TDs) seem to be associated with the prognosis of patients with colorectal cancer (CRC). The goal of this study was to investigate the prognostic value of TDs among patients with stage III CRC at different N stages. METHODS: A retrospective analysis was performed on two independent cohorts of stage III CRC patients from the Surveillance, Epidemiology, and End Results (SEER) database (n = 8232) and the First Affiliated Hospital of Wenzhou Medical University (n = 423). Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). RESULTS: Of 8232 patients in the SEER cohort, the presence of TDs revealed poorer 5-year OS rates and 5-year CSS rates in all N-stage subgroups. X-tile software identified 5 (5-year OS: P = 0.004; 5-year CSS: P < 0.001) as the optimal cutoff value for TD count in the TD-positive subgroup at the N2 stage. The OS (5-year OS: 62.0% vs. 42.0%, P < 0.001) and CSS (5-year CSS: 66.0% vs. 43.8%, P < 0.001) of patients with five or more TDs were significantly worse than those with one to four TDs in the N2 stage subgroups. Of 423 patients in the Wenzhou cohort, the 3-year OS rate for patients in the positive group was worse than that for patients in the negative group (88.7% vs. 94.3%, P = 0.015). CONCLUSIONS: TD count should be considered when evaluating the prognosis of patients with the N2 stage. Those with higher TD counts (≥ 5) might have a worse prognosis.

Reappraisal of Tumor Deposit as a Prognostic Factor in Pancreatic Cancer.

PURPOSE: Tumor deposits (TDs) are discrete tumor nodules within the lymphatic drainage area of the primary tumor without histological evidence of lymph node tissue or identifiable vascular or neural structure. This study aims to analyze the prognostic impact of TDs in patients with pancreatic ductal adenocarcinoma (PDAC) and explore their potential role in staging system. METHODS: The prospectively maintained database from the Fudan University Shanghai Cancer Center was queried for patients undergoing resection for PDAC. Patients with TDs were matched by propensity score with those without TDs. The cumulative prevalence of recurrence was estimated using the cumulative incidence function. Overall survival was estimated using Kaplan-Meier curves. RESULTS: A total of 123 patients (9.7%) had TDs, of whom 108 were matched at a 1:3 ratio with 324 patients without TDs. The cumulative incidence of recurrence was significantly higher for TD-positive patients than TD-negative patients (P = 0.04). The median overall survival was significantly shorter for patients with TDs than for those without TDs (15.9 versus 21.8 months, P < 0.001). The presence of TDs attenuated the effect of lymph node metastasis on survival, with no significance between node-negative and node-positive subpopulations (P = 0.165). Patients with TDs had comparable survival to N2 patients without TDs (15.9 versus 17.1 months, P = 0.383). CONCLUSIONS: TD is an important prognostic factor for recurrence and survival in patients undergoing resection for PDAC. We suggest that patients presenting TDs be classified into the stage III category in the next edition of the staging system.

Is the N2A Category Still Necessary for Oral Cancer Patients After Extranodal Extension Upgrade?

BACKGROUND: The presence of single-node metastasis (Ns) sometimes could be encountered in patients with oral squamous cell carcinoma (OSCC). The survival outcome for different Ns should be worthy of discussion. METHODS: Patients diagnosed with OSCC at the National Taiwan University Hospital between January 2007 and December 2018 were reviewed. All patients with Ns were classified into two groups: with and without extranodal extension (ENE). RESULTS: We analyzed 311 OSCC patients with Ns: 77 (24.76%) with and 234 (75.24%) without ENE. Lymph node (LN) >3 cm was the only significant factor associated with ENE (odds ratio 17.21, p < 0.001). The 5-year, disease-free survival of N1/N2A and N3B patients was 60.5% and 49.4%, respectively (p = 0.04), and the 5-year overall survival was 63.1% and 33.6%, respectively (p = 0.0001). Four fifths of Ns patients with LN >3 cm were upgraded to N3B category as ENE+. Postoperative radiotherapy (PORT) could provide significant benefit in regional control for Ns patients with (p = 0.03) and without (p = 0.0004) other adverse features. After multivariant Cox analysis, ENE+ was a modest and significant risk factor for disease-free (p = 0.08) and overall survival (p = 0.001). By contrast, the LN>3cm and N2A category were not significant risk factors for disease-free and overall survival. CONCLUSIONS: For OSCC patients with Ns, the survival outcome between N3B category and N1/N2A category was significantly different. After ENE+ upgrades (>80%), there were fewer N2A patients, and these patients became more comparable to N1 patients. PORT could significantly improve regional control for Ns patients.

MMP14 expression levels accurately predict the presence of extranodal extensions in oral squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Extranodal extension (ENE) is an adverse prognostic factor for oral squamous cell carcinoma (OSCC), and patients with OSCC along with ENE require neck dissection. In this study, we developed a novel ENE histology-based pathological predictor using MMP14 expression patterns in small biopsy specimens. METHODS: A total of 71 surgically resected tissue, 64 dissected lymph node (LN), and 46 biopsy specimens were collected from 71 patients with OSCC. Immunohistochemical analyses of total MMP14 expression in the tumour nest and cancer-associated fibroblasts (CAFs) were performed using the MMP14 co-scoring system (high- or low-risk). The association analysis of MMP14 expression in metastatic LNs was performed with respect to the presence and absence of ENE. Clinicopathological analyses and multivariate examinations were performed to assess the risks of metastasis and ENE presence. The predictive value of ENE and the impact of ENE and MMP14 expression on 5-year overall survival were examined. RESULTS: High-risk MMP14 expression was detected in metastatic LN specimens with ENE. MMP14 expression in tumour nests and CAFs and its overexpression at the tumour-stromal interface significantly correlated with the presence of ENE. The MMP14 co-scoring system was an independent risk predictor for ENE, with sensitivity, specificity, and accuracy of over 80% in biopsy samples; patients with a high risk in the MMP14 co-scoring system had significantly worse prognoses in both resections and biopsies. CONCLUSION: The MMP14 co-scoring system accurately predicted ENE presence and poor prognosis via immunohistochemical evaluation of small biopsies. This system is a simple, accurate, and inexpensive immunohistochemical approach that can be used in routine pathological diagnosis for effective treatment planning.

Long-term oncological results in penile cancer treated by inguinal lymphadenectomy.

PURPOSE: In 95% of cases, penile cancer is a squamous cell carcinoma whose specificity is lymphatic spread with the inguinal lymph nodes as the first relay route. Inguinal lymph node dissection is a primordial part of the treatment. The objective was to assess the oncological results of inguinal lymph node dissection in penile cancer at our centre. METHODS: We retrospectively included all patients having undergone inguinal lymph node dissection at our centre between 1 January 2004 and 1 January 2020 for the treatment of penile cancer. Patients for whom lymphadenopathy was palliative were excluded. Depending on indications, the procedures consisted in either dynamic sentinel node biopsy, modified lymphadenectomy or radical lymphadenectomy. All cancers were reclassified using the 2016 TNM classification system. Survival was analysed according to the Kaplan-Meier method. RESULTS: 242 inguinal lymph node dissections were performed in 122 patients. There were 71 pN0 (58%), 9 pN1 (7%), 4 pN2 (3%) and 38 pN3 (31%). Mean follow-up was 51 ± 45 months. The 3-year recurrence-free survival rate was 76% in pN0 patients and 17% in pN3 patients. The 5-year specific and overall survival rates were, respectively, 82% and 73% for pN0 stages, and 14% and 17% for pN3 stages. Extracapsular extension on an inguinal lymphadenopathy appeared as a highly negative prognostic factor. CONCLUSION: Inguinal lymph node dissection is essential in the treatment of penile cancer. Recurrence-free, specific and overall survival are closely linked to the lymph node stage. Extracapsular extension and pelvic lymph node invasion are highly negative prognostic factors.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.