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The current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension.We reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated.Of the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P.05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P.05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568-3.609; P.001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis.Papillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

PURPOSE To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution. METHODS AND MATERIALS NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) and rENE-negative (rENE-) patients. Multivariable analysis (MVA) confirmed the prognostic importance of rENE and its grade. Staging schemas including rENE in N-classification were proposed and their performance evaluated. RESULTS A total of 274 patients were eligible (43 cN0; 231 cN-positive). rENE was identified in 83/231 (36%) cN-positive, including grade 1/2/3 rENE in 14/58/11 cases. Compared to rENE-, rENE+ patients had a lower OS (68% vs 89%, p

Purpose: Magnetic resonance imaging-detected extramural venous invasion (mrEMVI) and tumor deposits (TDs) are risk factors for the development of local recurrence and distant metastases (DMs) in rectal cancer. However, little is known about their response to neoadjuvant treatment and its relation to oncologic outcomes. This study evaluated the incidence and features of mrEMVI and TDs before and after neoadjuvant treatment in relation to the development of local recurrence and DMs.Methods and Materials: Patients with cT3/4 rectal cancer without synchronous metastases who underwent surgery in a tertiary referral hospital were retrospectively analyzed. MRI scans were re-evaluated for the presence of mrEMVI, the occurrence of TDs, and response to neoadjuvant therapy (mr-vTRG).Results: In total, 277 patients were included, of whom 163 (58.8%) presented with mrEMVI. TDs were present in 56.4% of mrEMVI-positive and 9.6% of mrEMVI-negative patients (P < .001). The 5-year DM rate was significantly higher in mrEMVI-positive patients with and without TDs (45.2% and 35.9%, respectively) compared with mrEMVI-negative patients (25.7%; P = .012). After neoadjuvant treatment, the 5-year DM rate of patients with mr-vTRG 3-5 was 46.1%, whereas good responders (mr-vTRG 1-2) had a DM rate similar to mrEMVI-negative patients (25.7% and 25.7%, respectively; P = .002). The occurrence of TDs and larger mrEMVI size resulted in a lower likelihood of regression of mrEMVI.Conclusions: The prevalence of mrEMVI and TDs in cT3-4 rectal cancer is high and is associated with worsened oncologic outcomes. mrEMVI regression (mr-vTRG 1-2), which occured in 25% of the cases, leads to oncologic outcomes similar to those in patients without mrEMVI on baseline MRI. (C) 2021 The Author(s). Published by Elsevier Inc.

Background The eighth edition of the American Joint Committee on Cancer Staging Manual includes a staging system for head and neck cutaneous squamous cell carcinoma for the first time. The pN categories for head and neck cutaneous squamous cell carcinoma and mucosal squamous cell carcinoma are identical, despite the vastly different biological behavior of these diseases. This study aimed to survey head and neck cancer specialists’ views regarding the clinical utility of the American Joint Committee on Cancer Staging Manual for head and neck cutaneous squamous cell carcinoma and to identify avenues for improvement. Design An electronic survey of 19 questions relating to the prognostic utility of the staging system was designed based on the findings of a literature review. The survey was distributed internationally to specialists managing head and neck cutaneous squamous cell carcinoma. Results Literature review identified 9 articles describing primary research relevant to the performance of the American Joint Committee on Cancer Staging Manual for head and neck cutaneous squamous cell carcinoma, which recognized a lack of homogeneity, monotonicity, and distinctiveness in the pN staging system. One hundred and five survey responses were received: 71% indicated that mucosal and head and neck cutaneous squamous cell carcinoma require different nodal staging categories; 63% indicated that immunosuppression should be included in the staging system; 70% thought that soft tissue metastases portend a worse prognosis compared with extranodal extension; 38% almost never saw pN3a tumors; and 40% felt that the N stage is a poor predictor of survival. Conclusion The views of head and neck cancer specialists across disciplines and countries align with evidence suggesting that head and neck cutaneous squamous cell carcinoma merits a staging system distinct from mucosal squamous cell carcinoma, that immunosuppression should be considered in prognostication, and that the use of extranodal extension should be modified.

Regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated extracapsular extension and tumor implants in regional lymph node metastases in dogs with mammary carcinoma. Therefore, 84 cases of mammary carcinomas with metastases in inguinal and/or axillary lymph nodes from female dogs of different breeds and a total of 139 metastatic lymph nodes were evaluated by routine histological staining. Clinical and pathological characteristics of primary tumors as well as the presence of extracapsular extension and tumor implants in the lymph nodes were analyzed, in addition to survival. One to 5 lymph nodes were evaluated in each case. Extracapsular extension and tumor implants were present in 17.9% and 39.3% of cases, respectively. The simultaneous presence of extracapsular extension and tumor implants were associated with an increased risk of death (hazard ratio 10.46). In addition, "special type carcinomas", high histological grade (grade III), and presence of extracapsular extension associated with tumor implants were related to a worse prognosis and shorter survival times (p 0.05). Based on these results, we highlight the importance of identifying extracapsular extension and tumor implants in dogs with metastatic mammary carcinomas, as they are associated with a higher risk of death and shorter survival.

The presence of tumor deposits (TDs) in colorectal cancer is associated with a poor prognosis. In patients with the concomitant presence of both TDs and lymph nodes (LNs), there is no staging option except for the number of positive LNs alone. Therefore, to determine the prognostic value of TDs in patients with stage III colorectal cancer, meta-analyses of survival outcomes of patients with TDs were performed comparing different subgroups based on the lymph node status. PubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effect models. Outcome measures were 5-year overall survival (OS) and 5-year disease-free survival (DFS). We included in the analysis 18 nonrandomized studies and 1 prospective study that examined 90,455 patients. N1c patients (TD + LN-) had worse 5-year DFS than TDs-negative stage III patients (TD-LN +) with a RR of 1.30 (95% CI 1.06–1.61, I2 = 47%). In subgroup analysis, N1c patients had worse 5-year DFS (RR = 1.60, 95% CI = 1.25–2.05, I2 = 40%) compared with TDs-negative N1 patients (TD-N1) whereas N1c patients had better 5-year OS (RR = 0.72, 95% CI = 0.62–0.83, I2 = 0%) and 5-year DFS (RR = 0.75, 95% CI = 0.57–0.99, I2 = 0%) compared with TDs-negative N2 patients (TD-N2). These results may suggest that current nodal staging for colorectal cancer needs modification. The presence of TDs may have more adverse oncologic outcomes than TDs-negative N1 patients. More studies are warranted to further verify these results.

The focus on lymph node metastases (LNM) as the most important prognostic marker in colorectal cancer (CRC) has been challenged by the finding that other types of locoregional spread, including tumor deposits (TDs), extramural venous invasion (EMVI), and perineural invasion (PNI), also have significant impact. However, there are concerns about interobserver variation when differentiating between these features. Therefore, this study analyzed interobserver agreement between pathologists when assessing routine tumor nodules based on TNM 8. Electronic slides of 50 tumor nodules that were not treated with neoadjuvant therapy were reviewed by 8 gastrointestinal pathologists. They were asked to classify each nodule as TD, LNM, EMVI, or PNI, and to list which histological discriminatory features were present. There was overall agreement of 73.5% (κ 0.38, 95%-CI 0.33–0.43) if a nodal versus non-nodal classification was used, and 52.2% (κ 0.27, 95%-CI 0.23–0.31) if EMVI and PNI were classified separately. The interobserver agreement varied significantly between discriminatory features from κ 0.64 (95%-CI 0.58–0.70) for roundness to κ 0.26 (95%-CI 0.12–0.41) for a lone arteriole sign, and the presence of discriminatory features did not always correlate with the final classification. Since extranodal pathways of spread are prognostically relevant, classification of tumor nodules is important. There is currently no evidence for the prognostic relevance of the origin of TD, and although some histopathological characteristics showed good interobserver agreement, these are often non-specific. To optimize interobserver agreement, we recommend a binary classification of nodal versus extranodal tumor nodules which is based on prognostic evidence and yields good overall agreement. Supplementary Information The online version contains supplementary material available at 10.1007/s00428-021-03197-0.

Introduction: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis, is a rare disorder characterized by histiocyte proliferation. Case presentation: A 33-year-old man consulted the emergency department of a tertiary care institution in Cartagena de Indias, Colombia, due to a 6-month history of progressive deformity in the frontal right side of the face, associated with pain of slow progression, without any other symptoms or dermatological involvement. There were no other major findings on physical examination and laboratory tests performed were negative. Imaging scans obtained showed extensive inflammatory involvement of the frontal bone, which led to suspect osteomyelitis as the first diagnostic possibility. A biopsy of the lesion was performed with negative cultures for bacteria, which allowed establishing a diagnosis of extranodal Rosai-Dorfman disease with isolated bone involvement. Treatment with systemic corticosteroids was indicated with poor response, so methotrexate was added, achieving an evident improvement after 2 months. Conclusions: Little is known about the manifestations of Rosai-Dorfman disease and its treatment in the adult population. The present case report contributes to expanding the literature on this topic, which can present with rare symptoms that may pose challenges for its diagnosis. RESUMEN Introducción. La enfermedad de Rosai-Dorfman, también conocida como histiocitosis sinusal, es un trastorno poco frecuente caracterizado por la proliferación de histiocitos. Presentación del caso. Hombre de 33 años quien consultó al servicio de urgencias de una institución de tercer nivel de Cartagena de Indias, Colombia, por una deformidad de progresión lenta que apareció 6 meses atrás en el costado frontal derecho de la cara y generaba dolor. Al examen físico no hubo hallazgos mayores y los estudios paraclínicos fueron normales o negativos. Se obtuvieron imágenes que evidenciaron extenso compromiso inflamatorio/infeccioso del hueso frontal, por lo que se sospechó de osteomielitis y se realizó biopsia de la lesión que permitió establecer diagnóstico de enfermedad de Rosai-Dorfman variante extranodal con compromiso óseo aislado. El paciente recibió tratamiento con corticoide sistémico sin obtener respuesta, por lo que se adicionó metotrexato, con lo cual se logró mejoría a los 2 meses. Conclusiones. Las manifestaciones de la enfermedad de Rosai-Dorfman en población adulta son poco conocidas, además no hay mucha información sobre su tratamiento, por lo que el presente caso contribuye a ampliar la literatura sobre esta enfermedad que puede presentarse con sintomatología completamente inusual.

Background Extranodal extension (ENE) is a prognostic factor for several types of malignant tumors, including esophageal cancer. Although the prognostic value of ENE has been investigated in esophageal cancer, its clinical utility warrants further investigation. Materials and methods This retrospective single-center study evaluated 105 patients who underwent esophagectomy and had histologically node-positive metastasis between January 2007 and June 2017. The abilities of ENE to predict overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank test, as well as Cox proportional hazard models. Subgroup analyses of ENE's prognostic value were performed according to each pathological tumor-node-metastasis category. Results Significant differences according to ENE status were observed in the Kaplan-Meier analyses of OS (p = 0.001) and DFS (p = 0.001), as well as in the Cox proportional hazards models for OS (p = 0.009) and DFS (p = 0.012). Relative to patients without ENE, patients with ENE had significantly poorer OS if they also had pT3 status, pN1 status, or pathological stage III disease. However, no significant differences were observed in the subgroup analyses of pN3 status and pathological stage IV disease. Conclusions Among patients with esophageal cancer, ENE status can predict a poor prognosis and may be useful for patient stratification. However, the prognostic value of ENE status may be limited to patients with specific pathological factors.

Yun-Ming Tian,1 Lei Zeng,2 Yu-Hong Lan,1 Xia Yuan,3 Li Bai,1,* Fei Han4,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Medical Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre; State Key Laboratory of Oncology in South China; Collaborative Innovation Centre for Cancer Medicine, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li BaiDepartment of Radiation Oncology, Hui Zhou Municipal Central Hospital, No. 41 Eling North Road, Huizhou, Guangdong, People’s Republic of ChinaEmail bailihuizhou@126.comFei HanDepartment of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, People’s Republic of ChinaEmail hanfeisysucc@126.comObjective: To investigate the prognostic value of cervical node features in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and build a prognostic nomogram to predict the long-term survival.Methods: In this study, 1752 patients after IMRT from 2008 to 2011 were recruited. The clinical and laboratory characteristics and the nodal features including the nodal number, maximum dimension diameter, extranodal extension (ENE), and cervical node necrosis (CNN) were retrospective analyzed. Univariate Cox and multivariate proportional hazard regression models were used to test the prognostic value of nodal features. Prognostic nomograms were established to predict survival.Results: The 10-year distant metastases-free survival (DMFS) and disease-specific survival (DSS) rates were 86.5% and 80.8%, respectively. Multivariate analysis showed that age, sex, lactate dehydrogenase (LDH), CNN, ENE, T stage, and N stage were independent factors for DSS. Two nomograms—nomogram A (without nodal features) and nomogram B (with nodal features)—were built. The calibration curve for the probability of DSS showed good agreement between prediction by nomogram and the actual observation. The C-index of nomogram B was higher than that for nomogram A in predicting DSS (0.708 vs 0.676, P< 0.01).Conclusion: The nodal features including ENE and CNN were negative prognostic factors for NPC, and the prognostic nomogram incorporating the nodal features was more accurate in predicting survival than the nomogram without nodal features.Keywords: nodal features, extranodal extension, nodal necrosis, nasopharyngeal carcinoma, prognostic value

Tumor breaching the capsule of a lymph node is termed extranodal extension (ENE). It reflects aggressiveness of a tumor, creates anatomic challenges for disease clearance, and increases the risk of distant metastasis. Extranodal extension can be assessed on a pathology specimen, by radiology studies, and by clinical examination. Presence of ENE in a pathology specimen has long been considered a high-risk feature of disease progression and would ordinarily benefit from the addition of chemotherapy to adjuvant radiotherapy. Although the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer stage classification dichotomizes pathologic ENE according to its presence or absence, emerging evidence suggests that the extent of a pathologic ENE may provide additional value for risk stratification to guide adjuvant therapy. Recent data suggest that the prognostic importance of pathologic ENE is also applicable for HPV-associated head and neck squamous cell carcinoma. In addition, compelling data demonstrate that indisputable radiologic ENE is a powerful risk stratification tool to identify patients at high risk for treatment failure, especially distant metastasis, applicable for both HPV-positive and HPV-negative head and neck squamous cell carcinoma. However, the definition and taxonomy of radiologic ENE requires standardization. The goal of this review is to clarify the contemporary understanding of the prognostic implications of ENE in head and neck squamous cell carcinoma, present the nuances of what is presently known and unknown, and elucidate how to classify ENE pathologically and radiologically with an understanding of the strengths and weaknesses of each approach. Finally, with the development of several risk stratification methods, the relative role of ENE and other prognostic schema will be explored.

BACKGROUND Preoperative prediction of extracapsular extension (ECE) of prostate cancer (PCa) is important to guide clinical decision-making and improve patient prognosis. PURPOSE To investigate the value of multiparametric magnetic resonance imaging (mpMRI)-based peritumoral radiomics for preoperative prediction of the presence of ECE. STUDY TYPE Retrospective. POPULATION Two hundred eighty-four patients with PCa from two centers (center 1: 226 patients; center 2: 58 patients). Cases from center 1 were randomly divided into training (158 patients) and internal validation (68 patients) sets. Cases from center 2 were assigned to the external validation set. FIELD STRENGTH/SEQUENCE A 3.0 T MRI scanners (three vendors). Sequence: Pelvic T2-weighted turbo/fast spin echo sequence and diffusion weighted echo planar imaging sequence. ASSESSMENT The peritumoral region (PTR) was obtained by 3-12 mm (half of the tumor length) 3D dilatation of the intratumoral region (ITR). Single-MRI radiomics signatures, mpMRI radiomics signatures, and integrated models, which combined clinical characteristics with the radiomics signatures were built. The discrimination ability was assessed by area under the receiver operating characteristic curve (AUC) in the internal and external validation sets. STATISTICAL TESTS Fisher's exact test, Mann-Whitney U-test, DeLong test. RESULTS The PTR radiomics signatures demonstrated significantly better performance than the corresponding ITR radiomics signatures (AUC: 0.674 vs. 0.554, P

Purpose: We investigated role of neutrophil-to-lymphocyte ratio (NLR) in the diagnosis and prediction of extracapsular extension (ECE) in clinically localized prostate cancer (PCa). Materials and methods: A total of 396 patients with clinically localized PCa who underwent open radical retropubic prostatectomy (RRP), and 260 patients with benign prostatic hyperplasia (BPH) who underwent suprapubic prostatectomy were included in the study. Preoperative NLR, prostate specific antigen (PSA), prostate specific antigen density (PSAD), free PSA, prostate volume (PV), free/total PSA (f/t PSA) in both groups, and relation of NLR with PSA, Gleason Score (GS), and pathologic stage in PCa group were investigated. Records of patients were analyzed retrospectively. Results: NLR, free PSA, f/t PSA, and PV were statistically higher in BHP, and PSAD was higher in PCa group. In PCa group, NLR was found to be higher in patients with PSA >10 ng/ml compared to those with less than ⩽10 ng/ml. NLR increases as the preoperative GS increases, and it was higher in pT3 patients than pT2 patients. NLR was statistically higher in those patients with positive lymph nodes than those without after RRP ( p = 0.029). Conclusion: NLR is not a sufficient biomarker in differentiating clinically localized PCa from BPH. NLR increases as preoperative GS and pathologic stage increases. Lymph node involved patients after RRP have statistically higher NLR. NLR can be an indicator of ECE and lymph-node involvement in clinically localized PCa.

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P

Introduction: Surgery is one of the treatment alternatives for prostate cancer, and robotic-assisted laparoscopic prostatectomy (RALP) has become the new trend in the past decade. There is no consensus yet for surgeons who will perform RALP whether they need to be trained or experienced in laparoscopy. In this study, it was aimed to investigate the effectiveness of the surgeon’s laparoscopy experience in the perioperative and postoperative results of RALP patients. Material and method: Patients who underwent RALP were retrospectively screened. The first 20 cases done by surgeons in both groups and 40 cases in total were included in the study. Surgeons with laparoscopy training were designated as group 1, and surgeons without laparoscopy training were designated as group 2. Patient’s age, preoperative prostate-specific antigen (PSA) value, prostate biopsy pathology, radical prostatectomy pathology, surgical margin positivity, extracapsular extension, and seminal vesicle invasion status, blood transfusion rate, operation time, length of hospital stay, and 1-year follow-up potency and urinary incontinence rates were compared. Results: There was no difference between the two groups in terms of age, preoperative PSA, preoperative biopsy results, blood transfusion rates, operation times, and the length of hospital stay of the patients. When the postoperative oncological and functional results of the patients were examined, there was no difference between the two groups in the prostatectomy pathology ( p = 0.895), extracapsular extension (pT3a) ( p = 0.519), positive surgical margin (pSM) ( p = 0.723), and seminal vesicle invasion (pT3b) ( p = 0.756). Potency and urinary incontinence rates were similar in both groups at the end of one year follow-up ( p = 0.327, 0.500 respectively). Conclusions: Based on our study, it is clearly seen that regardless of the surgeon’s experience of laparoscopy, it can be safely preferred when looking at the oncological and functional results of RALP.

The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.

Extranodal extension (ENE) of nodal metastasis has emerged as an important prognostic factor in many malignancies, including rectal cancer. However, its significance in patients with rectal cancer receiving preoperative chemoradiotherapy (PCRT) has not been extensively investigated. We therefore assessed ENE and its prognostic impact in a large series of consecutive rectal cancer patients with lymph node metastasis after PCRT and curative resection.Between January 2000 and December 2014, a total of 1925 patients with rectal cancer underwent surgical resection after PCRT. Medical records of 469 patients with pathologic node positivity were retrospectively reviewed.Of the 469 patients, 118 (25.2%) presented with ENE. ENE was observed more frequently in those with advanced tumor stage (higher ypT, ypN, and ypStage), lymphovascular invasion, and perineural invasion. Five-year disease-free survival rate was lower in patients with ENE-positive tumors than those with ENE-negative tumors (36.1% vs. 52.3%, P = .003). Similarly, 5-year overall survival rate was lower in patients with ENE-positive tumors than those with ENE-negative tumors (60.2% vs. 70.6%, P .001). Multivariate analysis revealed that the presence of ENE was an independent poor prognostic factor for disease-free survival (hazard ratio = 1.412; 95% confidence interval, 1.074-1.857; P = .013) and overall survival (hazard ratio = 1.531; 95% confidence interval 1.149-2.039; P = .004).The presence of ENE in patients with rectal cancer undergoing PCRT is a negative prognostic factor, reflecting poor survival outcome.

Background Matted nodes in human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPC) is an independent predictor of distant metastases and decreased overall survival. We aimed to classify imaging patterns of metastatic lymphadenopathy, analyze our classification system for reproducibility, and assess its prognostic value. Methods The metastatic lymphadenopathy was classified based on radiological characteristics for 216 patients with HPV-mediated OPC. Patient outcomes were compared and inter-rater reliability was calculated. Results The presence of ≥3 abutting lymph nodes with imaging features of surrounding extranodal extension (ENE), one subtype of matted nodes, was associated with worse 5-year overall survival, overall recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival (p ≤ 0.03). Other patterns were not significantly associated with outcome measures. Overall inter-rater agreement was substantial (κ = 0.73). Conclusion One subtype of matted nodes defined by ≥3 abutting lymph nodes with imaging features of surrounding ENE is the radiological marker of worst prognosis.

OBJECTIVE. Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENE(mi)) and role of adjuvant concurrent chemoradiation (CRT) for ENE(mi) remain unclear. This study evaluates (1) the prognostic significance of ENE(mi) in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN. Retrospective cohort study. SETTING. Commission on Cancer (CoC)–accredited facilities. METHODS. This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENE(mi) or no ENE who had undergone margin-negative surgery. The association of ENE(mi) with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENE(mi) receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS. We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENE(mi). On multivariable analysis, ENE(mi) was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENE(mi) who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION. For patients with HPV-negative HNSCC, pN+ with ENE(mi) is associated with worse OS than pN+ without ENE. However, for patients with ENE(mi), concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENE(mi) requires additional investigation.

Fattori di rischio clinici e istopatologici per metastasi a distanza in pazienti con carcinoma della testa e del collo.L’incidenza di metastasi a distanza nel carcinoma squamocellulare della testa e del collo è relativamente bassa. Sono stati descritti molteplici fattori di rischio per lo sviluppo di metastasi sistemiche, sia al momento della diagnosi che dopo il trattamento. In ogni caso, ad oggi, non esiste una meta-analisi o una revisione sistematica che indaghi i rapporti tra fattori clinico-istopatologici e la comparsa di metastasi a distanza nei pazienti con carcinoma squamocellulare della testa e del collo. Tra i 1,272 articoli utili, 23 presentavano i criteri di inclusione per un’analisi qualitativa e 6 erano adatti ad un’analisi di tipo quantitativo. La meta-analisi, condotta su un totale di 5,353 pazienti, ha mostrato come la sede ipofaringea, le categorie T3-T4, l’estensione extra-nodale, linfonodi metastatici di diametro6 cm, il fallimento loco-regionale dopo pregressi trattamenti e la scarsa differenziazione aumentino tutti in modo significativo il rischio di metastasi a distanza. In base ai nostri risultati, quindi, i pazienti con i fattori di rischio clinici e istopatologici sopra citati dovrebbero essere considerati ad alta probabilità di sviluppare metastasi a distanza e, pertanto, sottoposti ad una rigorosa valutazione pre-trattamento, così come ad un attento follow-up.The incidence of distant metastasis (DM) in head and neck squamous cell cancer (HNSCC) is relatively low. Multiple risk factors have been described for development of DM at baseline and after treatment. However, to date, there is no meta-analysis or systematic review investigating the relationships between clinical and histopathological factors and the appearance of DM in HNSCC patients. Among 1,272 eligible articles, 23 met inclusion criteria for qualitative analysis, and 6 for quantitative analysis. The meta-analysis on 5,353 patients showed that hypopharyngeal site, T3-T4 categories, extranodal extension, positive lymph node size6 cm, locoregional failure after previous treatment(s) and poor differentiation all significantly increase the risk of DM. According to our results, patients with the above-mentioned clinical and histopathological risk factors should be considered at high risk for DM and therefore submitted to strict pre-treatment assessment and undergo careful post-therapeutic follow-up.

Objectives: Advanced cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with poor outcome despite multimodality therapy. Comprehensive risk stratification may pinpoint the most suitable adjuvant treatment. This study aimed to evaluate the outcomes of surgically treated locoregional CSCCHN and to identify prognostic indicators of treatment outcomes. Methods: We retrospectively analyzed disease variables, pathologic characteristics, and management in association with treatment outcomes of all consecutive advanced CSCCHN patients who underwent surgical resection at Tel Aviv Sourasky Medical Center. Results: From 2008 to 2018, 74 patients met the inclusion criteria. Only perineural invasion (PNI) was significantly associated with worse overall survival (OS) ( P = .001). Location within the facial “mask areas” was significantly associated with pathologically negative cervical disease ( P = .001). Forty-seven patients underwent adjuvant radiation therapy (RT) which significantly improved OS and disease-free survival versus surgery alone ( P = .025 and P = 0.035, respectively). Conclusion: PNI was associated with worse OS in surgically treated advanced CSCCHN. Adjuvant RT conferred better outcomes despite high risk features.

To evaluate the diagnostic accuracy of preoperative contrast-enhanced ultrasound (CEUS) to detect extracapsular extension (ECE) and identify the relationship between ECE and nodule enhancement patterns in patients with papillary thyroid cancer (PTC). Patients with suspected thyroid cancer underwent ultrasound (US) and CEUS examinations. The US and CEUS features of the PTC nodules and thyroid capsule were recorded and classified individually. The accuracy of US and CEUS in detecting ECE was compared individually, and its relationship with various tumour enhancement patterns was analysed. The presence or absence of ECE and cervical lymph node metastasis (LNM) was confirmed pathologically. The final dataset included 119 patients with 124 PTC nodules. Seventy-two (60.5%) of these patients with PTC had no ECE (including 38 patients with single capsule invasion), while the remaining 52 had ECE. A significant difference was found in nodules with non-capsule invasion, single capsule invasion, and ECE between the cervical LNM and non-LNM groups (p < 0.01). Receiver operating characteristic curve analysis demonstrated that area under the curve (AUC) of ECE for cervical LNM was higher than that of capsule invasion (71.9% vs. 49.6%). Moreover, the CEUS images acquired to detect ECE showed higher AUC values than those of US images (79.4% vs. 65.8%) (p = 0.02). Among the PTC nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%). Compared with conventional US, CEUS is a more valuable and non-invasive imaging modality to detect ECE. • Single capsular invasion was a poor predictor of cervical lymph node metastasis, while extracapsular extension assessments were clinically significant for predicting cervical lymph node metastasis. • CEUS is better than conventional US in detecting extracapsular extension in papillary thyroid carcinoma (AUC: 79.4% vs. 65.8%) (p = 0.02). • Among the thyroid papillary carcinoma nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of single capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%).

Objectives: Despite the inclusion of extranodal extension (ENE) in the recent staging system, the presence of ENE alone is not sufficient to depict all clinical situations, as ENE is frequently found in multiple nodes. Thus, the purpose of this study was to evaluate the surgery-based treatment outcomes and clinicopathological features of oral cavity squamous cell carcinoma (OCSCC) patients with ENE found in bilateral multiple cervical metastases. Materials and methods: A retrospective single-institutional study of OCSCC patients with bilateral ENE nodes was performed from January 2011 to December 2018. OCSCC patients of different admission statuses (with primary lesions (PL), recurrent lesions (RL) and isolated neck metastases (INM)) were included for subgroup comparisons. All patients received surgical treatment with/without adjuvant therapies and had complete follow-up data. Disease-free survival (DFS) was regarded as the main outcome. Time-to-relapse data were also collected for comparison. Results: A total of 128 patients were included, of whom 97 (75.8%) were male. The mean follow-up period reached 15 months. Among the patients, 85 (66.4%) were treated for PLs, followed by 26 (20.3%) treated for RLs after failed prior therapy and 17 (13.3%) treated for INMs (concurrent or sequential). The DFS rate was merely 35.2%. Treatment-related factors such as surgical margin (p=0.003), postoperative adjuvant therapy (p=0.014) and perioperative complications (p=0.036) were significantly associated with patient outcomes. In addition, oral lesion-related variables such as oral subsites (p=0.037), T classification (p=0.026) and skull base involvement (p=0.040) were indicators of a worse prognosis. For bilateral ENE features, ENE subclassification (p=0.036), maximum size of ENE nodes (p=0.039) and arterial nodal encasement (p=0.025) tended to predict the surgery-based treatment outcomes of these patients. Conclusions: Bilateral cervical metastases with ENE features, though uncommon, are a serious regional burden, and these patients have lower-than-expected treatment outcomes, especially those with RLs or INMs. A fairly large number of OCSCC patients with advanced oral lesions gain little benefit from intensified salvage surgical treatment. Such treatment should instead be offered to select patients with smaller bilateral ENE nodes (

Hodgkin lymphoma (HL) involving the Waldeyer's ring (WR) and other extranodal head and neck sites are rare. We report our experience and PubMed literature review.Retrospective single institution cohort study using lymphoma data base and PubMed literature search using twenty-six various search terms.Twenty-nine patients were treated in our institution (1975-2018). Male:Female 22:7, median age at diagnosis 33 years (15-64), stages I-II:III-IV 25:4. Sites were nasopharynx (10), tonsil (9), parotid (5), mandible (2) and others (3). 20/29 patients received radiation therapy, 22/29 received chemotherapy. Ten years overall-survival and progression-free survival are 92% and 66% respectively. PubMed search showed 8766 citations and identified 357 patients including our patients. Male:Female 199:131, median age 45 years (5-89). Stages I-II in 286 (80%). Involvement was nasopharynx 109 (30.5%), tonsil 67 (18.8%), parotid 58 (16.2%), thyroid 45 (12.6%), adenoid 10 (2.8%), mandible 10 (2.8%) and others in 58 (16.2%). Pathology: mixed cellularity 99 (27.7%), nodular sclerosis 88 (24.6%), nodular lymphocyte-predominant 56 (15.7%), lymphocyte rich 25 (7%), classical-HL-not otherwise specified 16 (4.5%) and lymphocyte depleted 7 (2%) patients. Treatment details are available for 233 patients; 165 (46%) received radiation therapy, 137 (38%) chemotherapy. Complete remission in 208 (58%), progressive disease 14 (4%), no information 135 (38%). Overall, treatment failure in 54 (15%). Thirty (8.4%) have died; 21 disease related. KM overall-survival at 5 and 10 years was 88.5% and 77.6% respectively.This largest report showed that HL involving extranodal head and neck sites is not very uncommon and has excellent prognosis.

BACKGROUNDS Pathologic features of oropharyngeal squamous cell carcinoma (OPSCC) treated with trans-oral robotic surgery predict prognosis and adjuvant therapy. We hypothesized that pathologic muscle invasion (pMI) is associated with poor pathological markers. METHODS Retrospective review of surgically treated OPSCC to identify pMI and its association with poor pathologic markers. RESULTS pMI was present in 12/37 patients, and compared to non-pMI, was associated with higher rates of lymphovascular invasion (75% vs. 36%, p = 0.03), perineural invasion (16.7% vs. 0%, p = 0.04), extranodal extension (66.7% vs. 20%, p

The presence of Lymph node metastasis with extranodal extension (ENE) is considered to be an important adverse prognostic factor for survival in patients with head and neck cancer. The aim of this study was to determine the prognostic significance of ENE in patients with laryngeal squamous cell carcinoma (LSCC). Three hundred and fifty-five patients with LSCC who underwent surgical resection and neck dissection were included. The status of cervical lymph node was classified into three groups: pathological negative nodal (pN-), pathological positive nodal without ENE (ENE-), and pathological positive nodal with ENE (ENE+). A total of 85 of 355 (23.9%) LSCC were pathological nodal positive, and ENE was detected in 22/355 (6.2%) patients. ENE was associated with drinking (p=0.005), T stage (p=0.000), tumor location (p=0.000), and differentiation degree (p=0.000). The number of lymph node metastasis in ENE+ group was associated with almost twice compared to ENE- group (p=0.005). The 5-year overall survival rates for patients in the pN-, ENE-, and ENE+ groups were 86.4±2.6%, 75.9±6.3%, and 53.7±12.7%, respectively (p=0.000). After adjusting for confounding variables, ENE+ was associated with more than five times the hazard of death than pN- cases (p=0.000), and more than twice the hazard of death than ENE- cases (p=0.036). Compared to N2-3/ENE- cases, N2-3/ENE+ cases had the poorest survival rate (p=0.013). ENE+ was associated with worse outcomes compared to pN - or ENE- status. ENE is an independent prognostic factor in LSCC, and could be an indicator of the need for adjuvant treatment.

Background Rapid recurrence, defined as gross tumor recurrence after primary operation but prior to initiating postoperative radiation therapy (PORT), is underappreciated in head and neck cancer (HNC). Methods CT simulation images in patients with HNC managed surgically with adjuvant therapy at a single center between 2010 and 2017 were retrospectively reviewed. Results A total of 194 patients with HNC were included. Rapid recurrence occurred in 39 patients (20%) with a median time from operation to CT simulation of 37 days. On multivariable analysis (MVA), extranodal extension (ENE) was the only predictor of rapid recurrence (P = .03). While rapid recurrence, ENE, and perineural invasion were all associated with poor overall survival (OS) on MVA, rapid recurrence was the strongest predictor (hazard ratio [HR] 5.47). Conclusion Rapid recurrence occurs at an underappreciated rate and is associated with poor survival outcomes. Patients with ENE are at highest risk and may benefit from diagnostic imaging evaluations immediately prior to PORT.

MRI assessment of rectal cancer not only assesses tumor depth and surgical resectability but also extramural disease which affects prognosis. We have observed that nonnodal tumor nodules (tumor deposits; mrTDs) have a distinct MRI appearance compared to lymph node metastases (mrLNMs).We aimed to assess whether mrTDs and mrLNMs have different prognostic implications and compare these to other known prognostic markers.This was a retrospective cohort study of 233 patients undergoing resection for rectal cancer from January 2007 to October 2015. Data were obtained from electronic records and MRIs blindly rereported. Survival was determined using Kaplan-Meier method. Prognostic markers were evaluated using Cox regression and competing risks analysis. Inter-observer agreement for mrTD was measured using Cohen Kappa.On multivariable analysis, baseline mrTD/mrEMVI (extramural venous invasion) status was the only significant MRI factor for adverse survival [hazard ratio (HR) 2.36 (1.54-3.61] for overall survival, 2.37 (1.47-3.80) for disease-free survival (both P0.001), superseding T and N categories. mrLNMs were associated with good prognosis (HR 0.50 (0.31-0.80) P = 0.004 for overall survival, 0.60 (0.40-0.90) P = 0.014 for disease-free survival). On multivariable analysis, mrTDs/mrEMVI were strongly associated with distant recurrence (HR 6.53 (2.52-16.91) P ≤ 0.001) whereas T and N category were not. In a subgroup analysis of posttreatment MRIs in postchemoradiotherapy patients, mrTD/mrEMVI status was again the only significant prognostic factor; furthermore those who showed a good treatment response had a prognosis similar to patients who were negative at baseline. Inter-observer agreement for detection of mrTDs was k0.77 and k0.83.Current MRI staging predicting T and N status does not adequately predict prognosis. Positive mrTD/mrEMVI status has greater prognostic accuracy and would be superior in determining treatment and follow-up protocols. Chemoradiotherapy may be a highly effective treatment strategy in mrTD/mrEMVI positive patients.

Background The treatment of advanced oral squamous cell carcinoma (OSCC) is a clinical challenge because it is unclear which therapeutic approaches are the best for this highly heterogeneous group of patients. Because TP53 mutations are the most common genetic event in these tumors, the authors investigated whether they could represent an ancillary biomarker in the management of advanced OSCC. Methods The TP53 gene was sequenced in 78 samples from patients with advanced OSCC who received treatment at 2 institutions located in the United States and Brazil. TP53 mutations were classified according to an in-silico impact score (the evolutionary action score of p53 [EAp53]), which identifies mutations that have greater alterations of p53 protein function (high-risk). Associations between TP53 mutation status/characteristics and clinicopathologic characteristics were investigated. The relevant findings were validated in silico by analyzing 197 samples from patients with advanced OSCC from The Cancer Genome Atlas. Results No differences in clinical outcomes were detected between patients with TP53-mutant and wild-type TP53 disease. However, patients who had tumors carrying high-risk TP53 mutations had a significantly increased risk of developing extranodal extension (ENE) compared with those who had wild-type TP53-bearing tumors. The increased chances of detecting ENE among patients who had high-risk TP53 mutations was validated among patients with advanced OSCC from The Cancer Genome Atlas cohort. Conclusions High-risk TP53 mutations are associated with an increased chance of detecting ENE in patients with advanced OSCC. Because ENE is 1 of the major factors considered for OSCC patient management, TP53 mutation status may represent a potential ancillary biomarker for treatment decisions regarding postoperative adjuvant therapy.

Highlights • Molecular prognostication lags behind for head and neck squamous cell carcinoma. • Analysis of wound drainage fluids after neck dissection has prognostic potential. • Expression of CXCL-12 may predict minimal residual disease after radical surgery., Aim In a pilot prospective study, we aimed to test the feasibility and report on the preliminary results on the expression of molecular biomarkers in wound drainage fluids (WDFs) of operated head and neck squamous cell carcinoma (HNSCC) patients. Material and methods Nineteen patients undergoing primary tumor resection with en-block neck dissection were enrolled. In postoperative days 1–3, the expression of several biomarkers in WDFs was measured using enzyme-linked immunosorbent assay (ELISA) kits and correlated with clinical and histopathologic features. Results The expression of stromal cell-derived factor 1 (CXCL-12) was significantly increased in WDFs in presence of lymph node metastases, extranodal extension (ENE), and in case of close resection margins. In addition, Osteopontin expression was significantly increased in presence of ENE, whereas transforming growth factor beta (TGF-β) detection was significantly reduced. At multivariate analysis, CXCL-2 levels in both day 1 and 3 post-surgery were the only factor which retained significance in the prediction of close surgical margins (p = 0.028 and 0.025 for day 1 and day 3, respectively). Both CXCL-2 and Ostepontin assays were significantly correlated with ENE (p = 0.018 and 0.035 for day 1; 0.052 and 0.025 for day 3, respectively) whereas TGF- β expression was significant at day 1 only (p = 0.038) Conclusions Our pilot study showed that WDFs could qualify as a potential source of relevant postoperative information. Further studies are needed to confirm the prognostic impact of CXCL-12, Osteopontin and TGF-β expressed in WDFs on the personalized management of HNSCC.

American Joint Committee for Cancer (AJCC) staging manual has been recently updated with 8th edition which led to an immense shift in the tumor, node, and composite stages, in comparison to the previous staging. This was mainly due to the incorporation of depth of invasion (DOI) and extranodal extension (ENE) in staging. The impact of new staging system is widely studied as combined subsites in oral cancer. This study is to focus on a single subsite of oral cavity which is known for its poor prognosis. We evaluated 109 patients who had buccal mucosal squamous cell carcinomas (BSCC) who underwent treatment, with a curative intend, between 2014 and 2015. Clinical records were reviewed and the tumors were re-staged as per 8th edition of AJCC; disease-free survival (DFS) was also analyzed. Our study population had a mean age of 54.5 ± 10.35 years and male to female ratio of 4:1. During a median follow-up of 41 months, 35 patients (32.1%) developed recurrence. There was a statistically significant shift in stages between AJCC 7th edition against AJCC 8th edition leading to 34% upshift in T-stage, 43.1% upshift in N-stage, eventually leading to a 23.9% upshift in the composite stage. Tumors which got upgraded due to upshift in nodal stage had a poor survival (p = 0.002). Newer staging system is easy to use in clinical practice. Around a quarter of the BSCC got upstaged with the introduction of the newer staging system. But it was surprising to note that there were no statistically significant differences in DFS between the tumors of the same composite stages with regard to the two staging systems.

Pathologic extranodal extension (pENE) impacts treatment planning and is an important prognostic indicator for patients with head and neck squamous cell carcinoma (HNSCC). Computed tomography (CT) is a commonly used modality for assessment of radiographic ENE (rENE). To determine the predictive value of CT-identified rENE in predicting pENE, we performed a systematic review through a search of 4 databases (PubMed, Scopus, Cochrane, and OVID). Meta-analysis of diagnostic performance based on human papillomavirus (HPV) status was conducted. For HPV-negative HNSCC, pooled sensitivity, specificity, and accuracy were 60.6%, 93.3%, and 82.6%, respectively. Overall positive predictive value (PPV) was 82.7%. For HPV-positive HNSCC, pooled sensitivity, specificity, and accuracy were 77.7%, 72.2%, and 63.8%, respectively. Overall PPV was 68.6%. Significant differences were observed in diagnostic performance parameters between the two cohorts. The radiographic characteristics of HPV-positive and HPV-negative nodal metastases in HNSCC differ and radiographic evaluation of ENE in HPV-positive nodes is challenging. Development of refined imaging characteristics of HPV-positive nodes is needed to improve diagnostic performance.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated the safety of omitting axillary lymph node dissection (ALND) in T1–T2cN0 patients with fewer than three positive sentinel nodes (SLNs) undergoing breast-conservation therapy. While microscopic extracapsular extension (mECE) > 2 mm is associated with increased nodal burden, the significance of extranodal tumor deposits (ETDs) in the axillary fat is uncertain. Consecutive patients with T1–T2cN0 breast cancer undergoing sentinel node biopsy and ALND for SLN metastases from January 2010 to December 2018 were identified. ETDs were defined as intravascular tumor emboli or metastatic deposits in the axillary fat. Clinicopathologic characteristics and nodal burden were compared by ETD status. Among 1114 patients, 113 (10%) had ETDs: 81 (72%) were intravascular tumor emboli and 32 (28%) were soft tissue deposits. Patients with ETDs had larger tumors (median 2.2 vs. 2.1 cm; p = 0.033) and more often had mECE (83% vs. 44%; p

Purpose Combined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL. Methods We reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis. Results Extranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects. Conclusion The real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.

PURPOSE Extranodal extension (ENE) is a well-established poor prognosticator and an indication for adjuvant treatment escalation in patients with head and neck squamous cell carcinoma (HNSCC). Identification of ENE on pretreatment imaging represents a diagnostic challenge that limits its clinical utility. We previously developed a deep learning algorithm that identifies ENE on pretreatment computed tomography (CT) imaging in patients with HNSCC. We sought to validate our algorithm performance for patients from a diverse set of institutions and compare its diagnostic ability to that of expert diagnosticians. METHODS We obtained preoperative, contrast-enhanced CT scans and corresponding pathology results from two external data sets of patients with HNSCC: an external institution and The Cancer Genome Atlas (TCGA) HNSCC imaging data. Lymph nodes were segmented and annotated as ENE-positive or ENE-negative on the basis of pathologic confirmation. Deep learning algorithm performance was evaluated and compared directly to two board-certified neuroradiologists. RESULTS A total of 200 lymph nodes were examined in the external validation data sets. For lymph nodes from the external institution, the algorithm achieved an area under the receiver operating characteristic curve (AUC) of 0.84 (83.1% accuracy), outperforming radiologists’ AUCs of 0.70 and 0.71 ( P = .02 and P = .01). Similarly, for lymph nodes from the TCGA, the algorithm achieved an AUC of 0.90 (88.6% accuracy), outperforming radiologist AUCs of 0.60 and 0.82 ( P < .0001 and P = .16). Radiologist diagnostic accuracy improved when receiving deep learning assistance. CONCLUSION Deep learning successfully identified ENE on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists with specialized head and neck experience. Our findings suggest that deep learning has utility in the identification of ENE in patients with HNSCC and has the potential to be integrated into clinical decision making.

OBJECTIVE To comprehensively examine the prognostic significance of extranodal extension (ENE) in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). METHODS Retrospective cohort of cases diagnosed with HPV-positive OPSCC from 2010 to 2015 in the National Cancer Database. Inclusion of all OPSCC HPV-positive cases with appropriate International Classification of Diseases-0-3 codes that received surgery with a neck dissection. Univariate and multivariable analyses were conducted. Hazard ratios (HR) for the independent effects of ENE and N stage on overall survival were estimated by Cox proportional hazards regression. RESULTS Cases that were ENE-negative had the highest 5-year survival (92.6%; 95% confidence interval [CI]: 90.5%-94.7%). ENE-positive cases had the lowest 5-year survival (84.0%; 95% CI: 80.7%-87.4%). After adjusting for confounding variables, ENE-positivity was associated with almost twice the hazard of death (HR = 1.90; 95% CI: 1.35-2.67) compared to ENE-negative cases. Nodal (N) category 1, ENE-positive status was associated with an increased risk of death (HR = 1.88; 95% CI: 1.26-2.80) compared with N1, ENE-negative status. Compared to N1/ENE-negative cases, N2/ENE-positive cases had the poorest survival (HR: 2.93; 95% CI: 1.94-4.43). Both microscopic and macroscopic ENE were associated with worse outcomes compared to node-positive/ENE-negative status. CONCLUSION The implementation of the American Joint Committee on Cancer 8th edition staging system provides a much-improved framework to develop and discuss treatment plans for HPV-positive OPSCC. We feel that careful consideration should be given to the importance of ENE in patients with HPV-positive OPSCC. LEVEL OF EVIDENCE 4 Laryngoscope, 130:939-945, 2020.

BACKGROUND/AIM We evaluated the diagnostic value of functional imaging with [18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (PET/CT) for the identification of extranodal extension (ENE) in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS In this study, 94 patients with HNSCC who underwent FDG-PET/CT were enrolled. We recorded the maximum standardized uptake value (SUVmax), compared the results with pathologic findings, and evaluated the diagnostic performance of using a SUVmax cut-off value for ENE. RESULTS Of the 566 dissected levels examined, 53 (9.4%) exhibited ENE. The mean SUVmax of LN with and without ENE were 6.67 and 1.64, respectively (p

BACKGROUND This study compared our proposed N classification including the addition of the number of positive lymph node (LN+) and extranodal extension (ENE) with the current and previous American Joint Committee on Cancer (AJCC) N classifications in salivary gland cancer (SGC). METHODS This study involved 172 SGC patients who underwent surgery. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS In multivariate analyses, LN+ number, LN ratio, and ENE were associated with OS and DFS outcomes (all P

This study examines outcome heterogeneity and potential to refine the TNM-8 cN-classification using radiologic extranodal extension (rENE) in a contemporary HPV-positive (HPV+) oropharyngeal carcinoma (OPC) cohort.All HPV+ OPC treated with definitive IMRT from 2010-2015 were included. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist for rENE. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) vs rENE-negative (rENE-). Multivariable analysis (MVA) for OS confirmed the prognostic value of rENE. Refined cN-classifications for new TNM staging proposals were evaluated against TNM-8 using established criteria.A total of 517 cN+ (rENE+: 97; rENE-: 420) and 41 cN0 cases were identified. The rENE+ proportion increased with rising N-category (N1/N2/N3: 11%/19%/84%, p 0.001). Median follow-up was 5.1 years. Compared to rENE-, rENE+ patients had a lower 5-year OS (56% vs 85%) and DFS (46% vs 83%) overall, and in N1 (OS: 57% vs 89%; DFS: 51% vs 87%) and N2 subsets (OS: 45% and 76%; DFS: 33% vs 74%) (all p 0.001). MVA confirmed the prognostic value of rENE for OS (HR = 3.86, p 0.001) and DFS (HR = 3.89, p 0.001). We proposed two new cN-classifications: Schema1 reclassified any N_rENE+ as New_N3; Schema2 reclassified N1_rENE+ as New_N2 and N2_rENE+ as New_N3. Stage incorporating either Schema1 (ranked 1st) or Schema2 (ranked 2nd) cN-categories outperformed TNM-8.This study confirms that rENE is prognostically important and facilitates understanding of known outcome heterogeneity within TNM-8 in HPV+ OPC patients. rENE is a promising parameter to refine the TNM-8 cN-classifications.

Purpose of review The level of evidence for current (adjuvant) treatment strategies after node positive inguinal lymphadenectomy is relatively low because of a paucity of prospective studies and controversy exist between the two major guidelines. The present review aims to provide a review of current literature on the available treatment options of patients after a tumor positive inguinal lymph node dissection. Recent findings Patients without inguinal extranodal extension or less than two tumor positive inguinal nodes are at low risk of ipsilateral pelvic nodal disease. Patients with pN1 disease are unlikely to benefit from adjuvant treatment, whereas patients with pN2 disease might benefit from adjuvant radiotherapy. For patients with high risk of pelvic nodal disease, prophylactic pelvic lymph node dissection (PLND) is advised by current guidelines. The InPACT study investigates whether adjuvant chemoradiotherapy could be used instead of prophylactic PLND. Subgroup analyses of retrospective cohorts suggest that patients with pN3 disease based on tumor positive pelvic nodes may benefit from adjuvant radiotherapy or chemotherapy. Given the weak level of evidence and substantial toxicity associated with current regimens, adjuvant chemotherapy cannot be generally recommended. Summary Despite current treatment strategies, patients with pN2-pN3 disease still have a poor prognosis. Prospective international multicenter studies are necessary to identify the best treatment options for patients with advanced node positive penile squamous cell carcinoma.

The clinical characteristics of stage III colon cancer and the prognostic significance of tumor deposits were investigated, to construct a prognostic nomogram.The data of patients were retrieved from the Surveillance, Epidemiology, and End Results database. Patients were randomized to a training or validation cohort. The Kaplan-Meier method was used to analyze survival rates. In the training cohort, a prognostic nomogram was established via Cox regression and then tested in the validation cohort. The accuracy and discrimination of the nomogram were assessed using concordance indices (C-indices) and calibration curves.Of the 9246 patients meeting the inclusion criteria, 1788 (19.3%) had tumor deposits. Patients with tumor deposits only showed similar survival rates to those with lymph node metastases only (P = 0.83). Compared with these, patients with both tumor deposits and lymph node metastases exhibited significantly worse survival (P 0.01). In the multivariate Cox regression analyses, the following were identified as independent prognostic indicators and adopted to formulate the nomogram: tumor deposits, age, ethnicity, T stage, the number of positive regional lymph nodes, grade, and carcinoembryonic antigen. In the training cohort, the calibration curve showed good consistency, and the concordance index of the nomogram for predicting overall survival reaches 0.727 (95% CI: 0.71524-0.73876), superior to the concordance index of the American Joint Committee on Cancer staging system (0.594, 95% CI: 0.58224-0.60576). These results are supported in the validation cohort.Tumor deposits may be an independent prognostic factor for patients with stage III colon cancer after colectomy. The nomogram constructed herein accurately predicted overall survival.

Background Lymph node yield (LNY) was implemented in the stratification of papillary thyroid cancer (PTC) patients. The effect of LNY may be related to the extent of surgery. This study aims to identify influencing factors for LNY in central compartment neck dissection (CND). Methods Data of 13 712 consecutive PTC patients were analyzed retrospectively. Risk factors for LNY in CND and distribution characteristics of LNY were evaluated. Its relationship with prognosis was studied in another cohort of 136 cases. Results LNY in therapeutic CND was significantly higher than prophylactic CND (Unilateral: 5.55 ± 3.79 vs 3.41 ± 2.77; Bilateral: 8.90 ± 5.10 vs 6.47 ± 4.17, P, Lymph node yield (LNY) in central compartment neck dissection (CND) of papillary thyroid cancer (PTC) is related to preoperative and intraoperative assessment of the disease. Inadequate LNY may lead to poor prognosis.

To develop a machine learning–based ultrasound (US) radiomics model for predicting tumour deposits (TDs) preoperatively. From December 2015 to December 2017, 127 patients with rectal cancer were prospectively enrolled and divided into training and validation sets. Endorectal ultrasound (ERUS) and shear-wave elastography (SWE) examinations were conducted for each patient. A total of 4176 US radiomics features were extracted for each patient. After the reduction and selection of US radiomics features , a predictive model using an artificial neural network (ANN) was constructed in the training set. Furthermore, two models (one incorporating clinical information and one based on MRI radiomics) were developed. These models were validated by assessing their diagnostic performance and comparing the areas under the curve (AUCs) in the validation set. The training and validation sets included 29 (33.3%) and 11 (27.5%) patients with TDs, respectively. A US radiomics ANN model was constructed. The model for predicting TDs showed an accuracy of 75.0% in the validation cohort. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and AUC were 72.7%, 75.9%, 53.3%, 88.0% and 0.743, respectively. For the model incorporating clinical information, the AUC improved to 0.795. Although the AUC of the US radiomics model was improved compared with that of the MRI radiomics model (0.916 vs. 0.872) in the 90 patients with both ultrasound and MRI data (which included both the training and validation sets), the difference was nonsignificant (p = 0.384). US radiomics may be a potential model to accurately predict TDs before therapy. • We prospectively developed an artificial neural network model for predicting tumour deposits based on US radiomics that had an accuracy of 75.0%. • The area under the curve of the US radiomics model was improved than that of the MRI radiomics model (0.916 vs. 0.872), but the difference was not significant (p = 0.384). • The US radiomics–based model may potentially predict TDs accurately before therapy, but this model needs further validation with larger samples.

In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). Median patient age was 58 years, and median tumor size was 1.7 cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41 months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Differentiated thyroid carcinomas make up most thyroid malignancies. The AJCC staging system and the ATA risk prediction system are the best predictors of mortality and recurrence, respectively. Key factors to be identified and reported by pathologists are reviewed in this article and include: (1) aggressive histologic variants of papillary thyroid carcinoma (including tall cell, columnar cell, and hobnail variants); (2) presence of gross extrathyroidal extension (into skeletal muscle or adjacent organs); (3) angioinvasion (including number of foci); (4) number, anatomic level, and size of lymph node metastases; (4) extranodal extension; (5) genetics (especially BRAF V600E or TERT promoter mutation).

Background: Extranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). Identifying ENE by clinical and/or radiological examination is difficult, thereby leading to unnecessary neck dissections. Currently, no definitive predictors are available for ENE. Thus, we aimed to determine the histological predictors of ENE by routine histopathological examination using biopsy and surgically resected specimens.Methods: This retrospective study included 186 surgically resected OSCC and 83 matched biopsy specimens. Clinical features associated with the tumor microenvironment, including desmoplastic reaction (DR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs), were evaluated using hematoxylin and eosin-stained primary OSCC and neck dissection specimens. These histological features were divided into two groups: DR-immature (DR-I) and DR-mature (DR-M); TB-high (TB-H) and TB-low (TB-L); and TILs-low (TILs-L) and TILs-high (TILs-H). Clinical depth of invasion (cDOI) and pathological DOI (pDOI) were adapted for biopsies and resections, respectively; DOI was evaluated as DOI >10 mm and DOI ≤10 mm. The clinicopathological relationships between these histopathological features and ENE and the independent risk factors for ENE were analyzed. The histological predictors of ENE were evaluated.Results:The histological status of DR, TILs, and TB present in biopsy and resection specimens showed high accuracy with that of ENE. DR-I, TILs-L, and TB-H were significantly associated with lymph node metastasis, cDOI, and pDOI. Bivariate and multivariate analyses revealed that TB-H and pDOI >10 mm in resections were independent factors for the presence of ENE (ENE+). The combination of TB-H/pDOI >10 mm in resection specimens showed high specificity (91%) and accuracy (83%) regarding ENE+. Although there proved to be no independent factors in biopsies, DR-I and TILs-L were significantly associated with ENE+ (p<0.001). The combination of DR-I/TILs-L/cDOI >10 mm in biopsies exhibited high sensitivity and specificity with ENE+ (70% and 77%, respectively, p<0.001). These histological predictors could detect even minor ENE (Conclusions:The tumor microenvironment status in primary OSCC was significantly associated with that of ENE, and TB-H was an independent risk factor for ENE. The histological status of DR-I/TILs-L/cDOI >10 mm in biopsy specimens and TB-H/pDOI >10 mm in resection specimens is a useful predictor of ENE.

PurposeTo investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC).MethodsSeven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan–Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC.ResultsThirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS.ConclusionsAge ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.

Importance Understanding patient-specific risk of adverse histopathologic findings after primary surgery for human papillomavirus (HPV)-positive oropharynx squamous cell carcinoma (OPSCC) may help guide patient consultations. Objective To determine the likelihood of adverse histopathologic features that may indicate adjuvant radiotherapy or chemoradiotherapy after primary surgery for HPV-positive OPSCC according to 2021 National Comprehensive Cancer Network guidelines. Design, Setting, and Participants This retrospective cohort study was performed at a single academic tertiary care center. Of 258 patients who underwent transoral robotic surgery (TORS) from March 1, 2012, to March 1, 2021, 136 consecutive, treatment-naive patients with HPV-positive OPSCC without obvious clinical extranodal extension (ENE) who underwent definitive TORS and neck dissection were included in the analysis. Indications for surgical treatment included non–deeply infiltrative oropharynx tumors, minimal soft palate involvement, and low suspicion for pathologic ENE. Exposures Primary site TORS with neck dissection. Main Outcomes and Measures The primary outcomes were the adverse histopathologic features of pathologic ENE and positive surgical margins (PSM) that are indications for possible adjuvant chemoradiotherapy. Outcomes were compared among varying American Joint Committee on Cancer 7th edition (AJCC-7) T and N categories and patient clinical characteristics. Results Of the 136 patients included in the analysis (113 men [83.1%]; median age, 63 [interquartile range, 55-70] years), 109 (80.1%) had at least 1 indication for possible adjuvant radiotherapy. Twenty-seven patients (19.9%) had pathologic ENE and 10 (7.3%) had PSM. Thirty-four patients (25.0%) had pathologic ENE and/or PSM, whereas 3 (2.2%) had both. Age, smoking history, history of alcohol consumption, and clinical T category were not associated with pathologic ENE, PSM, lymphovascular invasion, perineural invasion, or pN2 category or greater. The proportion of pathologic ENE varied by clinical N category: 0 of 16 for cN0, 8 of 48 (16.7%) for cN1, 3 of 23 (13.0%) for cN2a, and 16 of 45 (35.6%) for cN2b. Compared with patients with cN1-cN2a disease, patients with cN2b disease had higher odds of pathologic ENE (odds ratio, 3.01; 95% CI, 1.14-8.10). Clinical and pathologic N category were concordant in 77 patients (56.6%), whereas 42 (30.9%) were upstaged and 17 (12.5%) were downstaged. Conclusions and Relevance In this cohort study, approximately one-quarter of carefully selected patients with HPV-positive OPSCC without obvious clinical ENE undergoing primary surgery had pathologic ENE and/or PSM. Patients with AJCC-7 cT0-cT2 cN0-cN2b disease, especially cN0-cN2a, without signs of clinical ENE may represent appropriate candidates for primary surgery when avoidance of adjuvant chemotherapy and/or reduction of adjuvant radiotherapy dose/extent are the goals.

Purpose: There is a sex disparity in papillary thyroid cancer (PTC). Male sex is associated with a higher likelihood of advanced stage disease. This study aimed to examine the significance of sex for extranodal extension (ENE) in PTC. Patients and Methods: We reviewed the data of PTC patients who had undergone initial surgical resection from July 2012 to December 2014 (N = 1531). The effects of sex and other clinicopathological factors on ENE were investigated.Results: Of 1531 patients identified, 377 (24.6%) were male, 816 (53.3%) had positive nodes, and 256 (16.7%) had ENE. Compared with female patients, male patients had a higher risk of ENE (P < 0.001). Multivariable analysis of clinicopathological factors revealed that male sex (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.37 - 2.87; P < 0.001), age older than 60 years (OR, 1.93; 95% CI, 1.08 - 3.35; P = 0.023), extrathyroidal extension (OR, 3.52; 95% CI, 2.42 - 5.14; P < 0.001), bilateral multifocality (OR, 2.18; 95% CI, 1.53 - 3.13; P < 0.001), and more positive nodes were significantly associated with increased risk of ENE. Patients with 6-10 positive nodes were 16.45-fold higher to have ENE than patients with 5 positive nodes or less (95% CI, 11.07 - 24.68; P < 0.001).Conclusion: Male PTC patients had a higher risk of ENE than female. Sex was an independent predictor of ENE. The underlying mechanism needs to be investigated further.

Background In gastric cancer (GC), extracapsular growth (ECG) pattern of lymph node metastases is associated with decreased overall survival rates compared to intracapsular lymph node metastases (ICG). Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in hematogenous metastatic spread. Aim of the present study was to analyze if EMT related genes are involved in the growth pattern of lymph node metastases in GC. Methods Out of our prospective database with 529 patients who underwent surgical resection for GC between 2002 and 2014 forty lymph node positive patients were identified (20 ECG, 20 ICG). The expression of 84 EMT-associated genes were analyzed by RT2 Profiler PCR Array (n=20). Results were validated by Real-Time PCR (n=20). Results GC with ECG showed differently expressed EMT related genes. GC leading to ECG showed an upregulation of three and downregulation of eleven genes. Those differences, however, could not be confirmed in PCR analysis. Conclusions This study demonstrates that EMT related genes are not responsible for the different growth patterns of lymph node metastases in GC. Further studies are required to evaluate the underlying mechanisms of ECG in GC as it might provide a potential therapeutic target for this subgroup of more aggressive tumors in the future.