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Cystic masses of the lateral neck are mostly benign. However, the incidence of metastatic squamous cell carcinoma (SCC) in cervical cystic masses initially diagnosed as benign is quite high in patients older than 40 years. The aim of this study was to compare the diagnostic accuracy of preoperative cytology and intraoperative frozen section (FS) in detecting malignancy in cystic masses of the neck. We reviewed 61 patients who underwent preoperative ultrasound-guided fine-needle aspiration cytology (FNAC) and neck biopsy of a cystic neck mass, and analysed the concordance between FNAC and intraoperative FS with respect to definitive histology. HPV status was also tested. Of 49 eligible cases, the accuracy of preoperative FNAC was 70.5% (weighted kappa 0.53), meaning moderate agreement between cytology and final diagnosis. Intraoperative FS consultations detected 16 cases of SCC metastasis while the remaining 33 cases were negative for SCC, showing perfect agreement with histology. Since FS results were useful in evaluating cystic neck masses, despite a moderate accuracy of cytology, we suggest intraoperative FS analysis for all cystic neck masses. This technique can allow us to switch to therapeutic neck dissection, multiple upper aerodigestive tract biopsies, tongue base mucosectomy, and bilateral tonsillectomy in the same surgical setting.

Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3–6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2–98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0–100%). PFS was reported as a crude rate in 11 studies (range 27.3–68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0–50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach.

Prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy are at higher risk of tumor recurrence and receive immediate androgen deprivation therapy (ADT). While approximately 30% of these patients do not experience recurrence, others experience disease recurrence despite ADT, and currently no biomarkers can accurately identify them. We analyzed tumors from 51 patients with node-positive prostate cancer using immunohistochemistry to investigate whether expression of the immune checkpoint ligand PD-L1 by tumor cells or the density of CD8+ or CD20+ cells are associated with clinical progression. Patients with at least 1% PD-L1+ tumor cells had shorter metastasis-free survival than those with PD-L1- tumors (p =0.008, log-rank test). Univariate Cox regression showed that patients with PD-L1+ tumors had almost four times the risk of experiencing distant metastases than those with PD-L1- tumors (hazard ratio 3.90). In addition, we found that PD-L1 expression was significantly associated with CD8+ T-cell density, but not with CD20+ B-cell density. While these results need to be confirmed in larger studies, they show that PD-L1 and CD8 may be used as biomarkers for node-positive patients at high risk of progression. The study also provides a rationale for selecting patients with node-positive PCa who might benefit the most from adjuvant immunotherapies. Patient summary: None of the available biomarkers can identify node-positive prostate cancer that will recur after surgery. We found that expression of PD-L1 by tumor cells and a high density of CD8+ T cells in tumor are associated with a higher risk of clinical progression in men with node-positive prostate cancer. Biological markers predicting tumor recurrence in node-positive prostate cancer (PCa) are currently lacking. By investigating formalin-fixed paraffin-embedded tissue sections from 51 patients with node-positive PCa, we found that patients with tumors expressing PD-L1 and/or with a higher frequency of intratumor CD8+ T cells were at the highest risk of developing PCa metastasis after surgery. These results may open new frontiers for the use of adjuvant immunotherapy in this subset of node-positive patients.

Using a population-based cohort, data from 50,598 patients treated with radical prostatectomy and pelvic lymph node dissection were used to externally validate our pathologic nodal staging score model. This model allows for quantification of the likelihood that a pathologically node-negative patient will not have lymph node metastasis after surgery. BACKGROUND: We sought to externally validate our pathologic nodal staging score (pNSS) model, which allows for quantification of the likelihood that a pathologically node-negative patient will not have lymph node (LN) metastasis after radical prostatectomy for prostate cancer (PCa) in a population-based cohort. PATIENTS AND METHODS: We analyzed data from 50,598 patients treated with radical prostatectomy and pelvic LN dissection using the Surveillance, Epidemiology, and End Results database. We estimated the sensitivity of pathologic nodal staging using a β-binomial model and developed a novel pNSS model, which represents the probability that a patient’s PCa has been correctly staged as node negative as a function of the number of examined LNs. These findings were compared against those from the original cohort of 7135 patients. RESULTS: The mean and median number of LNs removed was 6.5 and 5, respectively (range, 1–89; interquartile range, 2–8), and 96.9% of the patients (n = 49,020) had stage pN0. Similar to the original cohort, the probability of missing a positive LN decreased with the increasing number of LNs examined. In both the validation and the original cohort, the number of LNs needed to correctly stage a patient’s disease as node negative increased with more advanced tumor stage, higher Gleason sum, positive surgical margins, and higher preoperative prostate-specific antigen levels. CONCLUSION: We have confirmed that the number of examined LNs needed for adequate nodal staging in PCa depends on the pathologic tumor stage, Gleason sum, surgical margins status, and preoperative prostate-specific antigen. We externally validated our pNSS in a population-based cohort, which could help to refine decision-making regarding the administration of adjuvant therapy.

Objective This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. Methods This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). Results As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. Conclusions In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

Background: The role of lymph node dissection (LND) during nephrectomy for renal cell carcinoma (RCC) is controversial. We looked at the clinical usefulness of performing LND to stratify the risk of patients with RCC and select candidates for systemic treatment after nephrectomy. Materials and Methods: We identified 730 patients with nonmetastatic RCC treated with nephrectomy and LND at a single center. We compared the accuracy and clinical usefulness of a base model including factors defining high-risk patients according to the S-TRAC trial [(pT3 and Grade≥2 and performance status score ≥1) or pT4] relative to the base model plus pN stage for the prediction of early progression after surgery. Results: LN invasion resulted the most informative predictor of early progression (odds ratio: 6.39; 95% confidence interval [CI]: 3.26, 12.54; P < 0.0001). The accuracy was higher (P = 0.008) for the model implemented with pN (area under the curve: 0.76; 95% CI: 0.71, 0.80) as compared to the base model (area under the curve: 0.72; 95% CI: 0.68, 0.76). Performing LND to select patients for postoperative systemic treatment, resulted in a slightly higher net benefit as compared to a strategy defining risk on the base of factors other than pN. Patients with high-risk disease showed a large difference in the risk of progression according to pN-status (1-year risk: 58% [95% CI: 45, 72] for pN1; 31% [95% CI: 25, 38] for pN0; P < 0.001). Conclusions: Performing LND at the time of nephrectomy improves risk stratification, resulting into a small but nonnegligible clinical advantage for selecting high-risk patients for further treatment after surgery. Further trials should investigate whether high-risk pN1 patients would benefit from a different postoperative management.

Objectives: To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus. Patients and methods: The records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS). Multivariable Cox regression models were used to quantify the effect of multiple covariates. Results: LND was performed in 1,026 patients. In multivariable analysis, the presence of LN metastasis, the number of positive LNs, and LN density were independently associated with cancer-specific mortality (CSM). Clinical node-negative (cN-) disease was documented in 573 patients, 447 of them underwent LND with 43 cN- patients (9.6%) revealing positive LNs at pathology. LN positive cN- patients showed significantly better CSS when compared to LN positive cN+ patients. In multivariable analysis, positive cN status in LN positive patients was a significant predictor of CSM (HR, 2.923; P = 0.015). Conclusions: The number of positive nodes harvested during LND and LN density was strong prognostic indicators of CSS, while number of removed LNs did not have a significant effect on CSS. The rate of pN1 patients among clinically node-negative patients was relatively high, and LND in these patients suggested a survival benefit. However, only a randomized trial can determine the absolute benefit of LND in this setting. Copyright (C) 2018 Elsevier Inc. All rights reserved.

Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well-known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow-up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour-related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment.

// Serena Bonin 1, * , Alessia Parascandolo 2, * , Cinzia Aversa 1 , Renzo Barbazza 1 , Nobuo Tsuchida 3 , Maria Domenica Castellone 4 , Giorgio Stanta 1 and Giancarlo Vecchio 5, 6, 7 1 Dipartimento di Scienze Mediche, Universita di Trieste-Cattinara, Trieste, Italy 2 IRCSS SDN, Naples, Italy 3 Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan 4 Istituto di Endocrinologia e Oncologia Sperimentale G.Salvatore, CNR, Naples, Italy 5 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita di Napoli Federico II, Naples, Italy 6 Istituto Superiore di Oncologia, Naples, Italy 7 Istituto Superiore di Oncologia, Genoa, Italy * Co-first authors Correspondence to: Giancarlo Vecchio, email: vecchio@unina.it Keywords: breast cancer; luminal B; lymph node metastasis; α-L-Fucosidase-1; immunohistochemistry Received: October 06, 2017 Accepted: February 01, 2018 Epub: February 07, 2018 Published: March 16, 2018 ABSTRACT Background: The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Results: Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. Conclusions: This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. Methods: We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

Prophylactic central neck dissection in clinically node-negative patients remains controversial. The aim of this multicenter retrospective study was to determine the rate of metastases in the central neck in clinically node-negative differentiated thyroid cancer patients, to examine the morbidity, and to assess the risk of regional recurrence in patients treated with total thyroidectomy with concomitant bilateral or ipsilateral central neck dissection compared with those undergoing total thyroidectomy alone. 258 consecutive clinically node-negative patients were divided into three groups according to the procedures performed: total thyroidectomy only (group A), total thyroidectomy with concomitant ipsilateral central neck dissection (group B), and total thyroidectomy combined with bilateral central neck dissection (group C). Mean operative time and postoperative stay were shorter in Group A (p < 0.01). The incidence of postoperative transient hypoparathyroidism was lower in Group A (p = 0.03), whereas no differences in the incidence of permanent hypoparathyroidism and nerve palsy were present. Postoperative radioactive iodine administration was higher in group B and particularly C (p = 0.03) compared with group A. There were no statistically significant differences in terms of regional recurrence. Differentiated thyroid cancer has a high rate of central lymph node metastasis even in clinically node-negative patients; in the present study there was no statistically significant difference in the rates of locoregional recurrence between the three modalities of treatment. Total thyroidectomy appears to be an adequate treatment for clinically node-negative differentiated thyroid cancer. Prophylactic central neck dissection might be considered for differentiated thyroid cancer patients with large tumor size or extrathyroidal extension.

Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of submucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the postsurgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post–endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than 5 cancer cells at the tumor invasive front, among the variables that must be included in histologic reports. In Western countries, however, no authoritative endorsements recommend the inclusion of TB in the histology report because of the heterogeneity of definitions and measurement methods as well as its apparent poor reproducibility. To assess the prognostic value of TB in pT1 CRCs, this meta-analysis evaluated 41 studies involving a total of 10137 patients. We observed a strong association between the presence of TB and risk of nodal metastasis in pT1 CRC. In comparing TB-positive (684/2401; 28.5%) versus TB-negative (557/7736; 7.2%) patients, the prevalence of nodal disease resulted in an odds ratio value of 6.44 (95% confidence interval, 5.26-7.87; P&nbsp

Background/Aim: Radiotherapy is a treatment option for both adjuvant and neo-adjuvant settings for biliary tract cancer. Guidelines on the delineation of the target volume of lymph nodes are lacking; only generic indications are available, without specific recommendations for different primary tumour locations (e.g. intrahepatic, extrahepatic biliary tract or gallbladder cancer). The aim of this study was to systematically review available literature to provide recommendations on lymph node target volume delineation in patients with unresectable biliary tumour. Materials and Methods: A systematic search of electronic databases was performed up to July 2016. The primary outcome measure was the rate of lymph node involvement according to the location of primary biliary tumour. Sites with ≥5% of nodal metastases were considered in the clinical target volume for radiotherapy planning. Results: Twelve studies (1075 patients) were included. The most frequent site of lymph node metastasis in intrahepatic biliary tree carcinoma was retroportal (61.1%, 95% confidence interval (CI)=50.7-70-6%). Other frequently involved lymph nodes were along the hepatoduodenal ligament [frequency=38.7%, 95% CI=31.0-47.0%], those along the common hepatic artery (17.0%, 95% CI=8.2-31.9%) and the hilar nodes (16.9%, 95% CI=13.2-21.4%). In extrahepatic biliary tree cancer, the most frequently involved lymph nodes were the pericholedochal (42.7%, 95% CI=33.8-52.1%) and those along the hepatoduodenal ligament (40.3%, 95% CI=32.4-48.8%). Other commonly involved nodal regions included retroportal lymph nodes (30.9%, 95% CI=23.0-40.1%), pancreaticoduodenal anterior and posterior nodes (30.1%, 95% CI=12.2-57.1%), those along the common hepatic artery (19.7%, 95% CI=11.8-31.0%) and para_aortic nodes (15.2%, 95% CI=8.0-27.0%). The most common site of metastases in gallbladder cancer were the pericholedochal nodes (25.2%, 95% CI=18.6-33.2%), those along the cystic duct (23%, 95% CI=16.6-30.8%), and retroportal nodes (17.1%, 95% CI=11.6-24.5%). Conclusion: Biliary tract cancer has a high propensity for regional lymphatic metastases. An evidence-based nodal target definition of biliary tract cancer based on primary tumour location was proposed.

Background Central neck dissection (CND) remains controversial in clinically node-negative differentiated thyroid carcinoma (DTC) patients. The aim of this multicenter retrospective study was to determine the rate of central neck metastases, the morbidity and the rate of recurrence in patients treated with total thyroidectomy (TT) alone or in combination with bilateral or ipsilateral CND. Methods The clinical records of 163 clinically node-negative consecutive DTC patients treated between January 2008 and December 2010 in three endocrine surgery referral units were retrospectively evaluated. The patients were divided into three groups: patients who had undergone TT alone (group A), TT with ipsilateral CND (group B), and TT with bilateral CND (group C). Results The respective incidences of transient hypoparathyroidism and unilateral recurrent nerve injury were 12.6% and 1% in group A, 23.3% and 3.3% in B, and 36.7% and 0% in C. Node metastases were observed in 8.7% in group A, 23.3% in B, and 63.3% in C. Locoregional recurrence was observed in 3.9% of patients in group A and in 0% in B and C. Conclusions We found no statistically significant differences in the rates of locoregional recurrence between the three groups. Therefore, TT appears to be an adequate treatment for these patients; CND is associated with higher rates of transient hypoparathyroidism and cannot be considered the treatment of choice even if it could help for more appropriate selection of patients for RAI. Ipsilateral CND could be an interesting option considering the lower rate of hypocalcemia to be validated by further studies.

The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT.

Coexistence of metastasis from squamous cell carcinoma and tuberculosis within lymph nodes is rare. We report a case of 86 years old woman with a mass in the left laterocervical region. The patient had undergone excision of a poorly differentiated squamous cell carcinoma from the mucosa of the left cheek, a few months before. Histological examination of a mass of few fused lymph nodes, isolated from left laterocervical lymphadenectomy, showed metastatic squamous cell carcinoma with concomitant granulomatous inflammation. A diagnosis of tuberculosis associated with malignancy was posed. The suspect was confirmed by a positive anamnestic finding of a previous tuberculosis infection. The granulomatous reaction may be associated with many types of tumor, and can be found in the draining lymph nodes. The possibility that this reaction is also due to a tuberculosis infection should be kept in mind for elderly oncology patient.