Metastatic Nodal Disease Research Articles

Omitting Lymphadenectomy in Obese Endometrial Cancer Patients Undergoing Sentinel Lymph Node Mapping: More Is Less

Study Objective To evaluate the feasibility of sentinel lymph node (SLN) mapping in obese endometrial cancer patients. Design A retrospective study of obese patients (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, comparing surgical and oncological outcomes of two patient's cohorts. Setting Tertiary gynecology oncology center. Patients or Participants 223 patients with median BMI of 40.6 kg/m2 including: 140 patients that underwent LND (with or without SLN) and 83 patients that underwent SLN. Interventions Lymph node dissection (LND) with or without SLN versus only SLN for endometrial cancer staging. Measurements and Main Results Patients that had only SLN seemed to have more metastatic pelvic nodal disease (13.3% vs. 7.1%), though this difference did not reach statistical significance (p=0.2). Patients from the SLN only group had significantly higher rate of successful mapping (92.8% vs. 78.4%, p=0.009), bilaterally detected SLN (80.7% vs. 54.5%, p Conclusion Omitting LND from surgical staging where SLN is performed was associated with shorter operative time and minimal bleeding without affecting survival. ICG should be the dye of choice in obese endometrial cancer patients.

The prostate-specific membrane antigen (PSMA)-targeted radiotracer 18F-DCFPyL detects tumor neovasculature in metastatic, advanced, radioiodine-refractory, differentiated thyroid cancer.

Prostate-specific membrane antigen (PSMA; also termed glutamate carboxypeptidase II (GCP II)) is abundantly expressed in prostate cancer. It has been shown recently that PSMA is expressed in neovasculature of differentiated thyroid cancer. In this study, we show that 18F-DCFPyl might detect neovasculature in advanced, metastatic differentiated thyroid cancer (DTC). We first stained the preserved lymph node samples of three patients with DTC who had undergone total thyroidectomy and neck dissection for cervical lymph node metastatic disease to identify PSMA expression, with the PSMA antibody (DAKO Monoclonal). Then, we performed 18F-DCFPyl imaging in two other advanced DTC patients with elevated serum thyroglobulin (Tg), indicative of residual disease. We compared the findings with contemporaneous FDG PET/CT scan, conventional Imaging (CT,MRI) and whole-body scan performed with I123/I131. All the three lymph node samples stained positive for PSMA expression in the neovasculature. In the first imaged patient, 18F-DCFPyl detected activity within the retropharyngeal CT contrast-enhancing lymph node. Compared to FDG PET/CT, the 18F-DCFPyl scan showed a greater SUV (3.1 vs 1.8). In the second imaged patient, 18F-DCFPyl showed intense uptake in the L3 vertebra (not seen on the post treatment 131I scan or the 18F-FDG PET/CT). MRI of the lumbar spine confirmed the presence of sclerotic-lytic lesion at the location, consistent with metastatic disease. Our exploratory study is proof of principle, that the prostate cancer imaging agent 18F-DCFPyl may prove useful for the localization of metastases, in patients with metastatic RAI-refractory DTC by detecting neoangiogenesis within the tumor.

Utility of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation.

No study has evaluated the diagnostic accuracy of sonography for the depiction of metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation or determined which sonographic features are most useful. To evaluate the diagnostic accuracy of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation and to determine the most useful sonographic features. We evaluated cervical lymph node sonography and histology in children with proven thyroid carcinoma in a 10-year period. We excluded children in whom a preoperative sonogram was not available and those who did not have surgical resection of lymph nodes. We used histology as the gold standard. On sonography, we analyzed the size, shape, echotexture and vascularity of the lymph nodes and correlated these findings with the histology. We reviewed sonograms and histology of resected lymph nodes in 52 children and adolescents with proven differentiated thyroid carcinoma (33 females; ages 5-18years, mean 13.2years). Metastatic cervical lymph node disease was proved on histology in 33/52 (64%) of our patients at presentation. Sonographic findings correctly predicted whether the nodes were histologically involved with metastatic disease in 42/52 (81%). Sensitivity of sonography was 79%, specificity 84%, positive predictive value (PPV) 90%, negative predictive value (NPV) 70% and accuracy 81%. A significant association was seen between round shape (P=0.0002), abnormal echotexture (P≤0.0001) and vascularity (P≤0.0001), and abnormal lymph node histology. Importantly, in 11/26 (47%) patients with sonographic and histologically proven abnormal nodes, the nodes were normal in size and shape and the presence of metastatic involvement was recognized sonographically only on the basis of abnormal echogenicity and vascularity. Sonography has a high accuracy, specificity and PPV for identifying metastatic cervical lymph node involvement in children with differentiated thyroid carcinoma at presentation. Most of the abnormal lymph nodes were round in shape and had abnormal echogenicity and vascularity. Importantly, this paper emphasizes that in children, nodes with histologically proven metastases from differentiated thyroid carcinoma can be normal in size and shape. In these patients the presence of metastatic involvement might be recognized sonographically only on the basis of abnormal echogenicity and vascularity.

S1647 A Surprising Diagnosis of Lynch Syndrome at Age 86

INTRODUCTION: Lynch syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome and accounts for up to 6% of all CRCs in the United States. The lifetime risk of CRC is near 75% for individuals with this inheritable highly expressed gene making identification of individuals and at-risk family members important for cancer prevention and management. CASE DESCRIPTION/METHODS: 86-year-old male in excellent physical condition with history of right-sided poorly differentiated invasive stage IIa adenocarcinoma status post right hemicolectomy 12 years ago presented after 6 episodes of painless hematochezia (hemoglobin 11.9 g/dL). He chose not to undergo chemotherapy and never had a follow-up colonoscopy following his initial CRC. He reported a family history of 1 sister who recovered from breast cancer and 2 deceased younger brothers who passed from colon cancer after his original diagnosis of CRC. Both parents experienced early death from cardiovascular disease. He had 6 children. Colonoscopy revealed normal ileocolonic anastomosis but with a 3 cm ulcerated, friable mass in transverse colon, a 2.5 cm mass in rectosigmoid colon, and a large, fungating 4cm ulcerated mass 5 cm from the anal verge. CT chest/abdomen/pelvis scan demonstrated extension of the transverse colonic mass through the colon wall into the mesentery with extensive nodal and hepatic metastatic disease. Pathology revealed invasive moderately differentiated adenocarcinoma positive for MLH1, MHS2, and PMS2 suggestive of Lynch syndrome; absent MSH6 staining was noted. Family members were recommended for genetic testing. The patient ultimately opted against treatment. DISCUSSION: The average age of colon cancer diagnosis for those with LS is 44 as compared to 68 for men without the genetic syndrome. This case demonstrates a particularly unique diagnosis of Lynch syndrome in an elderly male that was not diagnosed until his second bout of CRC. Of note, both cancers occurred after age 70. Strict adherence to the revised Bethesda guidelines can miss 68% of high microsatellite instability CRCs suggesting these guidelines are inadequate for LS screening, particularly if a full multigenerational family cancer history is not available. Multiple studies have demonstrated economic feasibility and advocate for universal LS testing of CRC tumors. This case supports such a paradigm. For identifying those who may be at risk for LS, we would prefer a predictive model without an overreliance on age to determine those appropriate for screening.Figure 1.: Endoscopic view of the 3 cm transverse colon (A), 2.5 cm rectosigmoid colon (B), and 4 cm anal verge (C) masses in an 86-year-old male discovered to have Lynch syndrome.Figure 2.: CT abdomen/pelvis showing transverse colon carcinoma with direct extension through the colon wall (red arrow) and into the mesentery associated with extensive nodal, as well as hepatic (yellow arrows) metastatic disease in an 86-year-old male discovered to have Lynch syndrome.

Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer?

Objective: As sentinel lymph node (SLN) biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small-volume nodal metastatic disease. The objective of this study was to describe the management and measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells (ITC) in patients with early-stage cervical cancer at 2 high-volume centers.

Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging.

Here we have improved an existing mouse model of prostate cancer based on prostate-specific deletion of Pten and Trp53 by incorporating a Cre-activatable luciferase reporter. By coupling the deletion of those genes to the activation of a luciferase reporter, we were able to monitor tumor burden non-invasively over time. We show that, consistent with previous reports, deletion of both Pten and Trp53 on a C57BL/6 background accelerates tumor growth and results in both the loss of androgen receptor expression and castrate resistant tumors as compared with loss of Pten alone. Loss of Trp53 results in the development of sarcomatoid histology and the expression of markers of epithelial-to-mesenchymal transition Zeb1 and vimentin, with kinetics and penetrance dependent on whether one or both alleles of Trp53 were deleted. Homozygous deletion of Trp53 and Pten resulted in uniformly lethal disease by 25 weeks. While we were able to detect locally invasive disease in the peritoneal cavity in aggressive tumors from the double knockout mice, we were unable to detect lymphatic or hematogenous metastatic disease in lymph nodes or at distant sites.

Long-term analysis of multimodality treatment outcomes and prognosis of esthesioneuroblastomas: a single center results of 138 patients

BackgroundThe aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma (ENB).Materials and methodsBetween April 1984 and December 2018, 138 patients with non-metastatic ENB were retrospectively analyzed. The treatment modalities mainly included surgery alone (n = 7), radiotherapy alone (n = 33), concurrent chemoradiotherapy (n = 17), surgery combined with current chemoradiotherapy (n = 32), and surgery plus radiotherapy (n = 49).ResultsThe median follow-up time for the entire cohort was 61 months (range, 4–231 months). The 5-year overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) rate were 69.6, 78.0 and 73.9%, respectively. Surgery combined with radiotherapy elicited superior survival results, and the combination of surgery and current chemoradiotherapy achieved the best prognoses for all patients, patients with advanced Kadish disease, patients receiving intensity modulated radiation therapy and those with positive surgical margin. Univariate analysis identified orbital invasion and treatment modalities were predictors for OS, LRFFS and DMFS. Lymph node metastasis was associated with OS and DMFS, but not LRFFS. Intracranial invasion, advanced Kadish stage and not receiving concurrent chemotherapy were also predictive of lower OS. Multivariate analyses indicated that lymph node metastasis was an independent prognostic factor affecting DMFS, whereas treatment modalities was independent prognostic factors for OS and LRFFS.ConclusionOrbital invasion, intracranial invasion, lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis. Regarding the treatment modality, the optimal strategy remined surgery with radiotherapy-based multimodality treatment. The concurrent chemoradiotherapy may play a more beneficial role.

The Role of Imaging in Bladder Cancer Diagnosis and Staging.

Bladder cancer (BC) is the most common cancer of the urinary tract in the United States. Imaging plays a significant role in the management of patients with BC, including the locoregional staging and evaluation for distant metastatic disease, which cannot be assessed at the time of cystoscopy and biopsy/resection. We aim to review the current role of cross-sectional and molecular imaging modalities for the staging and restaging of BC and the potential advantages and limitations of each imaging modality. CT is the most widely available and frequently utilized imaging modality for BC and demonstrates good performance for the detection of nodal and visceral metastatic disease. MRI offers potential value for the locoregional staging and evaluation of muscular invasion of BC, which is critically important for prognostication and treatment decision-making. FDG-PET/MRI is a novel hybrid imaging modality combining the advantages of both MRI and FDG-PET/CT in a single-setting comprehensive staging examination and may represent the future of BC imaging evaluation.

Potential Receptors for Targeted Imaging of Lymph Node Metastases in Penile Cancer.

Imaging modalities using tumor-directed monoclonal antibodies may be of value to improve the pre- and intraoperative detection and resection of lymph node (LN) metastatic disease in penile squamous cell carcinoma (PSCC). We investigated the expression of prostate-specific membrane antigen (PSMA), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) to analyze their potency for diagnostic applications. Antigen expression was determined in primary tumors and LNs with and without metastases of 22 patients with PSCC. The total immunostaining score (TIS, 0–12) was determined as the product of a proportion score (PS, 0–4) and an intensity score (IS, 0–3). EGFR and VEGF expression were high in primary tumor (median TIS 8) and LN metastases (median TIS 6 and 8, respectively). No EGFR expression was seen in LNs without metastases. However, LNs without metastases did show VEGF expression (median TIS 6). No EpCAM or PSMA expression was seen in PSCC. This study shows that VEGF and EGFR expression is moderate to high in LN metastases of PSCC. Both VEGF and EGFR warrant further clinical evaluation to determine their value as a target for pre- and intraoperative imaging modalities in the detection of LN metastases in PSCC.

Cost–Utility Analysis of Nivolumab in Adjuvant Treatment of Melanoma in France

IntroductionThe aim of the current study is to estimate the cost-effectiveness of adjuvant treatment with nivolumab relative to clinically relevant comparators in adult patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection from a French societal perspective.MethodsThe comparators were observation, low-dose interferon and pembrolizumab. A subgroup analysis was carried out in patients with BRAF mutation, adding dabrafenib plus trametinib. A three-state partitioned survival model was developed to project costs and health benefits over a 20-year time horizon. Extrapolation for recurrence-free survival (RFS) and overall survival (OS) was carried out using spline-based models. Because of the immaturity of OS data in pivotal trials for nivolumab and pembrolizumab, a predictive model of OS treatment effect based on RFS effect was developed using a correlation equation. Health state utilities and adverse events disutilities were derived from the CheckMate 238 trial and literature. Costs were estimated in 2019 euros. The model’s primary outcome was efficiency frontier. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results.ResultsObservation, low-dose interferon and nivolumab were on the efficiency frontier. The incremental cost–utility ratio of nivolumab versus low-dose interferon (closest therapy on the efficiency frontier) was €37,886/quality-adjusted life year (QALY). Probabilistic sensitivity analysis reported an 80% probability of nivolumab being a cost-effective strategy for a willingness-to-pay threshold of €52,000/QALY. In the subgroup with BRAF mutation, the efficiency frontier was not changed by the addition of dabrafenib plus trametinib.ConclusionsNivolumab is a cost-effective strategy as adjuvant treatment in adult patients with surgically resected melanoma in France.Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00446-z) contains supplementary material, which is available to authorized users.

Extraskeletal myxoid chondrosarcoma: A high incidence of metastatic disease to lymph nodes.

Extraskeletal myxoid chondrosarcoma (ESMC) is a rare type of soft-tissue sarcoma with limited series reporting outcome of treatment. Currently there is limited data on the incidence and impact on patient outcome in those with metastatic disease to lymph nodes in ESMC. Thirty (21 males, 9 females) patients, mean age 50 ± 16 years, with ESMC were reviewed. The tumors were most commonly located in the lower extremity (n = 23, 77%) and the mean tumor size and volume were 9 ± 5 cm and 490 ± 833 cm3 . Mean follow up was 7 ± 4 years. Six (20%) patients either presented (n = 3, 10%) or developed (n = 3, 10%) lymph node metastatic disease. When comparing patients without, with lymph node metastasis and metastasis elsewhere, patients with lymph nodes metastasis had worse survival than those without metastasis, however better 10-year disease specific survival than those with metastasis elsewhere (100% vs 62% vs 0%; P < .001). There is a high incidence of lymph node metastatic disease in patients with ESMC. Although survival in these patients is worse compared to those without metastasis, their survival is better than those with metastasis elsewhere. Due to the high incidence of lymph node metastatic disease, preoperative staging of the lymph node should be considered.

Sentinel lymph node biopsy predicts systemic recurrence in digital papillary adenocarcinoma.

Digital papillary adenocarcinoma (DPA) is a rare, aggressive neoplasm of sweat gland origin. It can recur at local, regional, or distant sites. There is limited knowledge about the role of sentinel lymph node biopsy (SLNB) in predicting recurrence in these patients. We present our experience with this uncommon tumor to evaluate the role of SLNB in predicting outcome. Medical records of all patients who underwent surgical treatment for biopsy-proven upper extremity DPA at the study institution were reviewed. Descriptive statistics and Fisher's exact test were used to analyze data. Twenty-one patients were identified. Most patients were male (71%), and the median age was 51 years. SLNB was performed in 18 patients; three were positive for nodal metastatic disease (17%). At a median follow-up of 53 months, there were no local recurrences and two cases of systemic recurrence. No patient with a negative sentinel lymph node has evidence of metastasis or recurrence. Fisher's exact test demonstrated a significant association between a positive SLNB and recurrence (P = .02). SLNB revealed metastatic disease in 17% of patients with DPA and appears to predict systemic recurrence in this small series.

Well-differentiated rectal neuroendocrine tumors: analysis of histology, including insulinoma-associated protein 1 expression, and biologic behavior, involving a large cohort of 94 cases

Well-differentiated rectal neuroendocrine tumors (R-NETs) are increasingly being detected by screening colonoscopy, commonly manifesting as polyps. Chromogranin A is frequently negative in R-NETs. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently shown excellent sensitivity and specificity for neuroendocrine (NE) differentiation in various anatomic sites but has not been systematically evaluated in R-NET. A retrospective histologic review of all available R-NETs was performedand stained for INSM1 immunohistochemistry, as well as for Ki-67 and chromogranin A, if not already available. Clinical and follow-up information was obtained from the medical chart. A total of 94R-NETs were included in our cohort. Of these, 82 (87%) were <10mm in greatest dimension, and submucosal involvement was noted in 70 patients (74%). The tumors displayed a variety of histologic patterns, and the majority of the cases had intratumoral fibrosis (61%). Synaptophysin and INSM1 were reactive in 100% cases, whereas chromogranin A was reactive in 45% cases. The mean Ki-67 proliferative index was 1.6% (range: 0.5-5%). The median follow-up of the cohort was 30 months (80 cases, range: 3-226 months). Only three patients were identified with regional lymph node metastasis, all of which showed a tumor size ≥10mm and had lymphovascular invasion (LVI). R-NETs in our fairly large cohort display an indolent biologic behavior without distant metastasis. Metastatic disease in lymph nodes was associated with tumor size and the presence of LVI, but not with the Ki-67 proliferative index. This is also the first systematic study documenting INSM1 as a highly sensitive NE marker in R-NET.

Controversial Role of Adjuvant Therapy in Node-Negative Invasive Intraductal Papillary Mucinous Neoplasm.

Adjuvant chemotherapy and/or chemoradiation [chemo(radiation)] is considered the standard of care for resected patients with pancreatic adenocarcinoma. However, invasive carcinoma arising from an intraductal papillary mucinous neoplasm (IPMN) seems to have different biologic behavior and prognosis. Retrospective data suggest a survival benefit of adjuvant chemo(radiation) for resected invasive IPMNs with metastatic nodal disease; however, it is unclear whether this remains valid for node-negative patients. To compare the outcome of patients with invasive IPMNs who received adjuvant chemo(radiation) with that of those treated with surgery alone, we queried the National Cancer Database regarding data of patients who underwent pancreatic resection for invasive IPMN between 2006 and 2015. A propensity score analysis was conducted to balance covariates between treatment groups. For the study, 492 patients were eligible, of whom 267 (54.3%) received adjuvant chemo(radiation). Estimated 1- and 3-year overall survival rates were 88.9% and 73.5% versus 93.2% and 72.8% for patients who did or did not receive adjuvant chemo(radiation), respectively. Among patients with negative nodal stage, there was no difference in overall survival between patients who received versus patients who did not receive adjuvant chemo(radiation) (P = 0.973). In contrast, among patients with positive nodal disease, those who received adjuvant chemo(radiation) had significantly better OS compared with those who did not (P = 0.001). In patients with resected invasive IPMNs, adjuvant chemo(radiation) was associated with significantly improved overall survival only in presence of nodal metastases. This finding can help clinicians to select adjuvant treatment in a patient-tailored fashion.

Impact on colorectal cancer pathology reporting practice of migration from TNM 5 to TNM 8.

The introduction of TNM 8 into UK pathology practice in January 2018 considers tumour deposits in colorectal cancer staging for the first time. The impact of this new classification on pathology reporting practices has yet to be evaluated. A clinical audit was conducted, comparing consecutive colorectal cancer resection specimens reported under TNM 5 classification guidelines in 2017 (n=177) and TNM 8 guidelines in 2018 (n=234). Tumour features (venous invasion, perineural invasion, lymph node metastatic disease, tumour deposits) and changes in reporting practices were evaluated among four specialist gastrointestinal pathologists working within a large pathology department. Adoption of TNM 8 practice led to an approximate doubling in the use of ancillary stains (41.0% of TNM 8 versus 22.0% of TNM 5 cases, P<0.001) to help evaluate tumours. A narrowing of the range between pathologists was observed in reporting cases as having one or more form of regional, extramural, discontinuous tumour (TNM 5 range=50.0-79.0%, TNM 8 range=57.8-65.7%), with no change in the overall proportion of cases reported as such (62.7% versus 62.4%, P=0.95). However, significant interobserver variation in reporting rates for individual parameters remained. TNM 8 colorectal cancer staging offers potentially greater reproducibility in pathology reporting of regional, extramural, discontinuous disease with similar proportions of patients reported as having one or more of these forms of tumour spread compared with TNM 5. Further guidance in defining individual features is required to reduce interobserver variation in pathology assessments and to help elucidate the clinical significance of each parameter.

Expression of Ki67 and p53 Proteins: Breast Cancer Aggressivity Markers in Brazilian Young Patients.

Background: The increase in breast cancer (BC) cases in young women is of great importance since the tumor behavior in this group is generally more aggressive than in their older counterparts, and strategies for early diagnosis and prognostication are needed. Therefore, this work sought to investigate prognostic markers associated with young (<44 years old) BC patients. Methods: Two hundred thirty-six primary tumor tissues from 232 BC patients, of which 44 had less than 44 years at diagnosis were evaluated regarding the expression of estrogen and progesterone receptors (ER and PR), human epidermal growth factor receptor 2 (HER2), Ki67, and p53 (used as an indicator of p53 mutations) through immunohistochemistry. Also, data regarding tumor size, histopathological grade (HG), lymph node metastasis disease stage, and patients' survival status were collected. Results: Early age tumors had higher Ki67 expression and p53 mutations, and these markers were positively correlated with each other and associated worse prognosis parameters, such as negativity for ER and PR and positivity for HER2, and with higher HG, tumor size, and disease stage. In young patients, Ki67 correlated with ER, PR, and HG, whereas p53 correlated with HER2 and disease stage. Also, Ki67 associated with BC death independently of time from diagnosis, patients age, tumor size, and disease stage, and showed a trend toward a positive correlation with death in young patients, but not in the older group. Conclusion: Young BC patients were more likely to have intensely proliferative tumors with p53 mutations and these markers may hold prognostic relevance in BC, especially in this subgroup of patients.

Management of Appendiceal Neuroendocrine Tumors: Metastatic Potential of Small Tumors.

Appendiceal neuroendocrine tumors (ANETs) are rare neoplasms usually discovered incidentally during appendectomy. ANETs < 2cm were thought to have no metastatic potential, and this dogma has driven management. Our aim is to evaluate the metastatic potential of ANETs < 2cm. A retrospective review was performed in a series of patients with ANETs who presented to our tertiary referral center from 1998 to 2019. Demographics, tumor characteristics, treatment, and clinical outcomes were evaluated. In total, 114 patients were included. Median follow-up was 3.3years (range, 21days-15years). At last follow-up, 34 (30%) patients had positive regional lymph nodes and 20 (18%) patients had metastatic disease. Of the 20 patients with metastatic disease, 11 (55%) had primary ANETs < 2cm. Patient age > 40years at diagnosis and ANETs with serosal invasion, lymphovascular invasion, intermediate tumor grade, or positive lymph nodes were features significantly more likely to present with metastatic disease. We found no difference in the rate of lymph node positivity, metastatic disease, or overall survival when patients were stratified by tumor size or type of resection (appendectomy vs. right hemicolectomy). On multivariate analysis, patients with metastatic disease at diagnosis had worse overall survival (HR = 24.4, p = 0.008). In our cohort, tumor size was not a significant risk factor for metastatic disease or worse outcome as many patients with ANETs < 2cm developed metastatic disease. Appendectomy alone was sufficient surgical management for most ANETs. Patients with risk factors for metastatic disease, regardless of primary ANET size, should be evaluated thoroughly and counseled for further management and surveillance.

External evaluation of the Briganti nomogram to predict lymph node metastases in intermediate-risk prostate cancer patients.

The Briganti nomogram can be used with a threshold of 5% to decide when to offer lymph node dissection during radical prostatectomy. The objective of the study was to assess the accuracy of the Briganti nomogram on intermediate-risk prostate cancer patients managed in a single academic department. We retrospectively reviewed the files of all patients managed by radical prostatectomy (RP) and bilateral pelvic lymph node dissection (BPLND) in our center between 2005 and 2017. The overall accuracy of the model in predicting metastatic lymph node disease was quantified by the construction of a receiver-operator characteristic (ROC) curve. A calibration plot was drawn to represent the relationship between the predicted and observed frequencies. We included 285 patients, among whom 175 (61.4%) were classified as intermediate risk as defined by D'Amico. The median follow-up was 60 (34-93) months. Twenty-seven patients (9.5%) were diagnosed with lymph node metastases. The median number of lymph nodes removed was 10 (7-14). The mean Briganti score was 19.3% in patients with lymph node involvement (LNI) and 6.3% in patients without LNI. Focusing on intermediate-risk patients, 91(52%) and 84 (48%) had a Briganti score < 5% and ≥ 5%, respectively, among whom 6 (6.6%) and 7(8.3%) had lymph node metastases. The accuracy of the score was low for intermediate risk patients with an area under the curve (AUC) of 53.1% (95% CI 0.45-0.61). The Briganti nomogram in our retrospective cohort showed low accuracy for the prediction of lymph node involvement in an intermediate-risk prostate cancer population.

Enucleated globes with choroidal melanoma: A retrospective histopathological study and correlation with cytogenetic profile in 2 eye centers

BackgroundUveal melanoma is the commonest intraocular malignant tumor in adults and the choroid is the commonest involved location. It is more prevalent in Caucasians; however, the demographics are widely variable based on ethnicity. Histopathological features have been correlated to the cytogenetic profile, which we intend to report through the study of enucleated eyes with choroidal melanoma (CM). Materials and MethodsA retrospective review of 28 enucleated globes with CM in 2 tertiary eye centers (January 2000-December 2017). The tumors were histopathologically classified based on the 8th edition of the American Joint Committee on Cancer (AJCC). The histopathological risk factors and the AJCC classifications were correlated with Fluorescence in situ hybridization (FISH) for chromosomes 3 and 8 available results in 18/28 eyes. ResultsWe have included 28 patients with a mean age of 56 years, 13 males (46.4%) and 15 females (53.6%). None had lymph node involvement or metastatic disease. The tumor size was categorized as 3 and 4 in 68% of eyes. Half tumors were of spindle cell type and were associated with absent cytogenetic abnormality in chromosomes 3 and 8 (P=0.005). Closed vascular loops presence was significantly associated with abnormal chromosomes 3 and 8 (P=0.027). ConclusionPatients in our area presented late with larger tumor size. The spindle cell CM was the commonest and correlated with negative FISH results, while the presence of closed vascular loops was a risk factor for abnormal FISH results hence expected worse prognosis. AJCC classification did not correlate well with our FISH results.

CD3 and CD20 immune cell densities in primary tumors, lymph node metastasis, and recurrent disease samples of head and neck squamous cell carcinoma.

6551 Background: Immune cell (IC) infiltrates in primary tumors (PT) have been identified as prognostic markers in head and neck squamous cell carcinoma (HNSCC). IC densities may differ among PT, lymph node metastasis (LNM) and recurrent disease (RD) and by primary disease site (oral cavity- OC, oropharynx- OP, hypopharynx- HP, larynx- L). Here, we compare CD3 and CD20 IC densities in PT, LNM and RD in paired samples from different disease sites and determine the prognostic impact of IC infiltrates. Methods: Tissue microarrays with 425 PT, 198 LNM and 46 RD samples--each in triplicate--were stained immunohistochemically for CD3 and CD20 in the same slide. Immune cell densities per mm2 were determined using a digital image analysis software (QuPath). Individual means were calculated from triplicates of each sample. IC infiltrates from different sample types (PT, LNM, RD) and primary tumor sites were compared using Kruskal-Wallis and Mann-Whitney-U tests. Paired samples were compared using Wilcoxon signed rank test. IC densities were classified as CD3 high/low and CD20 high/low for each primary tumor site using the individual median as a cut-off. Overall survival (OS) was calculated using the Kaplan-Meier method. P-values for each hypothesis were corrected using a false discovery rate of 5%. Results: CD3 and CD20 IC densities differed significantly by sample type (both p&lt;0.0001) and primary site (CD3: p=0.012, CD20: p=0.0017). CD3 and CD20 densities were significantly lower in PT compared to LNM or in RD compared to PT and LNM. Paired samples (n=172) revealed a significantly higher CD3 and CD20 density (both p&lt;0.0005) in LNM compared to PT, but no significant differences between PT and RD (n=28, p&gt;0.05). CD3 densities were significantly higher than CD20 densities in all sample types. CD3high patients had the best prognosis in all sites except for OC (q&lt;0.05) independent of CD20 status. In OC, CD3 density was not prognostic, but CD3low/CD20high patients had the worst OS compared to CD3low/CD20low and CD3high/CD20high or even CD3high/CD20low patients (p=0.018) who had the best prognosis. Conclusions: IC densities of CD3 and CD20 vary by sample type and primary site. Except for OC, in all sites the prognostic impact is determined by CD3high, whereas in OSCC only the combination of CD3 and CD20 IC densities achieves a good prognostic value. Interestingly, CD3low/CD20high patients have the worst overall survival in OC patients. Further work is needed to understand the interaction of B- and T cell infiltrates in the tumor, especially in OC.