Presence Of Necrosis Research Articles

IS THERE NEURAL AND FUNCTIONAL RECOVERY AFTER CLIP REMOVAL IN CERVICAL EXPERIMENTAL SYMPATHECTOMY?

ABSTRACT Background:The surgical treatment of hyperhidrosis by thoracic sympathectomy has brought, in addition to symptomatic relief for many, its main adverse effect: compensatory or reflex sweating. The clipping technique in place of the sympathetic nerve section gave rise to the hope of reversibility, but the positive results showed to be quite divergent, evidencing the academic deficiency regarding the study of this phenomenon. Aim:To observe micro and macroscopic damage caused by the polymer clip on sympathetic nerve of rabbits seven days after their clipping and the findings after three weeks of clip removal. Method:In this experimental study, 20 rabbits were divided into two groups of 10, group 1 (clipping) and group 2 (de-clipping). The right cervical sympathetic nerve of all animals was clamped with polymeric clip, and in group 2 the nerve was unclipped seven days later. Group 1 rabbits were induced to death on the 7th postoperative day, and group 2 on the 21st after removal of the polymer clip. Macroscopic variables were: clip appearance, presence of discontinuity lesion, infection and adhesions around the nerve. H&E was used in the evaluation of the phases and degree of the inflammatory process and presence of necrosis, and picrosirius red F3BA for quantification of collagen. Results:The cervical sympathetic nerve was intact, without necrosis or infection in all animals of the experiment; there were adhesions in both groups, being minimal in eight animals of each group and moderate or intense in two; the clip was completely closed in all animals at the 7th postoperative day; the inflammatory process shown was chronic, with monomorphonuclear predominance. There was no significant difference between groups regarding the intensity the inflammatory process, but the amount of collagen type I and type III was significantly higher in group 2. Conclusions:The injury caused by the polymer clip on the sympathetic nerve may be reversible, allowing functional return in the areas involved in the simulated cervical sympathectomy. Clipping of the cervical sympathetic nerve using a polymer clip does not cause discontinuity injury.

Diferentes formas de apresentação radiológica da perfuração intestinal na Enterocolite Necrosante

Objetivo: Relatar as diferentes formas de apresentação radiológica da necrose e da perfuração intestinal na Enterocolite Necrosante (ECN) em sete recém-nascidos internados em UTI neonatal. Detalhamento de Caso: Foram avaliados os RX Simples do abdome de sete RNs com ECN, sendo que todos estavam na fase 3 de Bell. Achados radiológicos: opacificação completa do abdome; bolha de ar acima do fígado; sinal da bola de futebol; imagens hipertransparentes sem o formato de víscera oca; Sinal de Rigler; e ar peritoneal livre destacando estruturas intraperitoneais. Considerações Finais: A ECN tem etiologia multifatorial, associado a três fatores principais: a imaturidade intestinal, proliferação bacteriana e dieta via oral com fórmula. O agravamento do quadro clínico, presença de sinais de instabilidade hemodinâmica, plaquetopenia e a acidose metabólica associados as alterações radiológicas específicas, podem propiciar o diagnóstico de uma ECN avançada. A indicação para a cirurgia de urgência é a presença de necrose e/ou perfuração intestinal. É fundamental reconhecer os diferentes modos de apresentação radiológica destas complicações, de forma rápida e precisa, pois, isso implicará na decisão terapêutica de uma cirurgia imediata e, consequentemente, terá impacto na qualidade de vida e na sobrevida desses neonatos.

Features of oral squamous cell carcinoma in ex vivo fluorescence confocal microscopy.

Real-time microscopic imaging of freshly excised oral squamous cell carcinomas (OSCCs) would be potentially supportive in rapid recognition of oral malignancy and an optimal and time-saving management of patients' surgical treatment. The aim of this study was to examine oral squamous cell cancer tissue in regards to the commonly known and well-described histomorphologic criteria for the diagnosis of OSCC in ex vivo confocal fluorescent microscopy and to analyze its correlation with grade of differentiation and level of invasiveness. Ex vivo confocal laser scanning microscopy (CLSM) images of 38 OSCCs were evaluated immediately after excision for presence or absence of various cytological and architectural features based on the histopathological background. Next, these features were compared to the grade of differentiation as elaborated via gold standard histologic examination. Of 38 invasive OSCCs, 14 were well differentiated, while three moderately and 19 were poorly differentiated. The presence of the commonly known cytologic and histopathologic criteria for the diagnosis of oral squamous cell carcinoma such as the destruction of the basal cell membrane, cellular and nuclear pleomorphism, anisocytosis, intraepithelial keratinization, nuclear hyperchromasia, atypical mitotic figures as well as the presence of necrosis, and mixed inflammation could be observed in ex vivo fluorescence confocal microscopy (FCM). In ex vivo fluorescence confocal microscopy pictures, cellular pleomorphism and anisocytosis were observed more often in poorly differentiated OSCCs. Intraepithelial keratinization was associated with well differentiated and moderately differentiated OSCCs. The results demonstrate the high potential of ex vivo fluorescence confocal microscopy in fresh tissue for rapid real-time diagnosis of OSCC.

Utility of the GeneXpert Mycobacterium tuberculosis/Rifampin (MTB/RIF) Assay on Paraffin-Embedded Biopsy Tissue Samples for Detecting Tuberculosis: Comparison With Histopathology.

IntroductionThe Xpert Mycobacterium tuberculosis/Rifampin (MTB/RIF) assay is a qualitative nested real-time polymerase chain reaction (PCR) performed on the GeneXpert instrument system. Although, the utility of this technique for detecting tuberculosis (TB) in sputum and pus samples is well established, however, the usefulness of GeneXpert on biopsy samples is still a matter of debate. Therefore, in this study, we evaluated the utility of GeneXpert for detecting MTB in biopsy specimens diagnosed with TB.MethodsA retrospective observational study was conducted at the Department of Pathology, Liaquat National Hospital and Medical College. The data collection period was between January 2016 and December 2018 over a period of three years. Specimens included trucut/incisional biopsies and lymph node excisions. Cases with a favoured histopathological diagnosis of TB were included in the study. The Xpert MTB/RIF assay was performed on the samples obtained from paraffin-embedded biopsy tissue material, and comparison of histological features with Xpert MTB/RIF assay was performed.ResultsA total of 114 cases were included in the study. The mean age of the patients was 40.53±16.83 years, and 57.9% of patients were male. 68.4% of cases were extra-nodal with the lung being the most common extra-nodal site. On histopathological analysis, caseation necrosis, epithelioid granulomas and Langhan's giant cells were present in 64.9%, 70.2%, and 59.6% cases, respectively. On GeneXpert PCR assay, MTB was detected in 26.3% cases. A significant association of MTB detection on Xpert PCR assay was noted with the presence of necrosis on histopathology.ConclusionIn our study, we noted that the MTB detection rate by GeneXpert assay on histopathologically diagnosed cases of TB was only 26.3%, and the detection rate was significantly increased in the presence of caseation necrosis on a biopsy tissue sample. Despite the low detection rate due to rapid turnover time, GeneXpert assay is an excellent adjunctive tool for detecting MTB in paraffin-embedded tissue samples.

Scoring model of convex probe endobronchial ultrasound multimodal imaging in differentiating benign and malignant lung lesions.

BackgroundConvex probe endobronchial ultrasound images can reflect the morphology, blood flow status and stiffness of the lesions. Endobronchial ultrasound multimodal imaging has great value for the diagnosis of intrathoracic lymph nodes. This study aimed to analyze the application of endobronchial ultrasound multimodal imaging on lung lesions.MethodsPatients undergoing endobronchial ultrasound-guided transbronchial needle aspiration in Shanghai Chest Hospital from July 2018 to December 2019 were retrospectively enrolled. Nine grayscale features (long and short axes, margin, shape, lobulation sign, echogenicity, necrosis, liquefaction, calcification, and air-bronchogram), blood flow volume and elastography five-score method were analyzed to explore the best diagnostic method. The gold standard for diagnosing lesions depends on the histological and cytopathological findings of endobronchial ultrasound-guided transbronchial needle aspiration, transthoracic biopsy, resected sample of lesions, microbiological examination or clinical follow-up of at least 6 months.ResultsEndobronchial ultrasound multimodal imaging of 97 malignant lung lesions and 19 benign lung lesions from 116 patients were analyzed. There were statistically significant differences in distinct margin, presence of lobulation sign, presence of necrosis, and elastography grading score 4–5 between malignant and benign lung lesions, among which presence of lobulation sign and elastography grading score 4–5 were independent predictors. A diagnostic scoring model was then constructed based on the above four features, and when two or more features were present, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for malignant lung lesions prediction were 92.78%, 57.89%, 91.84%, 61.11% and 87.07%, respectively.ConclusionsThe combination of endobronchial ultrasound grayscale and elastography has potential value for malignant and benign lung lesions differentiation. The diagnostic scoring model established in this study needs further validation to guide the malignant and benign diagnosis of lung lesions.

Magnetic resonance severity index assessed by T1-weighted imaging for acute pancreatitis: correlation with clinical outcomes and grading of the revised Atlanta classification-a narrative review.

Acute pancreatitis (AP) is a common disease that may involve pancreas and peripancreatic tissues with a prevalence of up to 50 per 100,000 individuals for year. The Atlanta classification was assessed for the first time in 1992 and modified in 2012 in order to describe morphological features of AP and its complications. AP can be morphologically distinguished in two main types: interstitial edematous pancreatitis (IEP) and necrotizing pancreatitis (NEP). This classification is very important because the presence of necrosis is directly linked to local or systemic complications, hospital stays and death. Magnetic resonance (MR) is very useful to characterize morphological features in AP and its abdominal complications. Particularly we would like to underline the diagnostic, staging and prognostic role of T1-weighted images with fat suppression that could be significant to assess many features of the AP inflammatory process and its complications (detection of the pancreatic contour, pancreatic necrosis, presence of haemorrhage). Signs of inflammatory and edema are instead observed by T1-weighted images. MR cholangiopancreatography (MRCP) is necessary to study the main pancreatic duct and the extrahepatic biliary tract and contrast-enhancement magnetic resonance imaging (MRI) allows to assess the extent of necrosis and vascular injuries.

NCOG-62. CNS SARCOMA IN A TODDLER WITH NOVEL BALANCED TRANSLOCATION OF t(8;11)(q13;q13)

Abstract A CASE REPORT A 23-month-old boy was noted to have a brain tumor after being evaluated for chronic global developmental delay. The initial neurological exam was concerning for left leg circumduction and drag. Further investigation with MRI demonstrated a 7 x 9.3 x 7.4 cm supratentorial cystic encapsulated mass identified in the right lateral ventricle with heterogeneously enhancing mural nodule measuring 0.9 x 2.7 x 3.3 cm in diameter. Capsular enhancement was also noted after contrast administration. No diffusion restriction was seen. Mass effect on septum pellucidum was seen along with an increase in size of the left lateral ventricle. Following which the patient underwent right posterior parietal craniotomy and gross total resection of the tumor. Pathology report based on the cellular appearance, cell density, presence of necrosis, and the proliferative activity classified the tumor as likely intermediate grade undifferentiated sarcoma, mostly mesenchymal in origin. Tumor cytogenetics showed balanced translocation (8;11) (q13; q13) in all metaphase cells. Cytogenetics performed on the blood sample showed normal karyotype, suggesting that the translocation seen in tumor cells was somatic in nature rather and not a germline mutation. As the radiological signs and the long clinical course of the disease (evidenced by global developmental delay noted more than a year prior to a presentation and no signs of disseminated disease) suggested it to be a low-grade tumor a decision was made not to treat aggressively with further chemo and radiotherapy. However, the pathology of the tumor was suggestive of a primary malignant undifferentiated sarcoma of the brain. The patient continued to do well with no signs of recurrence on MRI and/or clinical picture for 4 years after the initial surgery. DISCUSSION Primary CNS sarcoma is rare. Balanced translocation (8;11) (q13; q13) has not been described in the literature before.

Pulmonary neuroendocrine neoplasms with well differentiated morphology and high proliferative activity: illustrated by a case series and review of the literature

ObjectivesPulmonary neuroendocrine neoplasms (NENs) are subdivided in carcinoids and neuroendocrine carcinomas (small cell lung carcinoma and large cell neuroendocrine carcinoma (LCNEC)), based on the presence of necrosis and mitotic index (MI). However, it is unclear if tumors with well differentiated morphology but high proliferation rate should be regarded as LCNEC or as high grade carcinoids. In previous case series, a longer overall survival then expected in LCNEC has been suggested. We describe 7 of those cases analyzed for pRb expression and overall survival. Material and methodsCases with well differentiated morphology, but MI > 10/2mm2 and/or Ki-67 proliferation index >20% were selected based on pathology reports of consecutive NENs in our university medical center (Maastricht UMC+, 2007-2018) and confirmed by pathological review. Immunohistochemistry was performed to assess pRb expression. ResultsSeven stage IV cases were included in this study. Median overall survival was 8 months (95% confidence interval 5-11 months). Cases with well differentiated morphology and preserved pRb expression (4/7) had a median overall survival of 45 months. ConclusionA subgroup of pulmonary NENs with well differentiated morphology but high proliferation rate likely exists. pRb staining might be helpful to predict prognosis, but clinical relevance remains to be studied.

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Simple SummaryThyroid cancer incidence is increasing, with overdiagnosis being the major driver of the thyroid cancer “epidemic”. Papillary thyroid carcinoma, usually with excellent prognosis, sometimes has an aggressive metastatic pattern. This heterogeneity in progression makes it difficult to tailor treatment strategies for an individual patient. We aimed to identify clinicopathological factors associated with papillary thyroid carcinoma recurrence, persistence, and specific mortality. Our study supports that both pre-surgical factors, such as male gender, presence of psammoma bodies, gross extra-thyroidal extension, and lateral compartment lymph node metastases, as well as lymph vessel invasion, venous invasion, presence of necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of PTC patients. The same is true when analysis is restricted to stage I patients. The importance of this report is to emphasize clinical and imaging pre-surgical thyroid cancer patients’ evaluation for an appropriate surgical treatment and patient prognosis.Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients’ files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient’s surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.

S2690 You Cannot Ignore Abdominal Dropsy: A Rare and a Fateful Presentation

INTRODUCTION: Angiosarcoma (AS) is a rare soft tissue sarcoma known to be one of the aggressive malignancies which carry a poor prognosis with 5- year overall survival reported at <43%. AS mainly originates from the breast (35%) and skin (20%), followed by soft tissue (13%) involvement. Hepatic AS accounts for only 0.5%–2% of primary hepatic malignancies. CASE DESCRIPTION/METHODS: A 56-year-old male presents with abdominal pain and 20-pound weight loss for the past two months. His abdomen appeared tense and distended. Results showed a hemoglobin 6.1 gm/dL, platelet count 63 × 103 /mm3, total bilirubin of 3.2 mg/dL, ALP 315 IU/L, AST 305 IU/L, ALT 209 IU/L, and albumin of 2.6 gm/dL. A CT of the abdomen showed multiple hypodense lesions in the liver, and spleen with the peripheral enhancement of the contrast [Figure 1A] suggestive of metastatic lesions. Colonoscopy was normal and EGD demonstrated multiple erythematous nodular lesions in the gastric body [Figure 1B] and duodenum [Figure 1C], biopsies of which were inconclusive. A CT guided liver biopsy showed small aggregates of anastomosing vascular channels with highly atypical cells suggestive of AS [Figure 2A]. Tumour cells were positive for CD-34 [Figure 2B] and focally positive for Factor VIII [Figure 2C]. The patient deteriorated very rapidly and died 2 weeks later due to cardiac arrest. DISCUSSION: Hepatic AS is more commonly seen in males (3:1) with a median age of the presentation around the 5th- 6th decade. Use of anabolic steroids, oral contraceptives, exposure to radiation, and chemicals like arsenic, vinyl chloride, and thorium dioxide are certain risk factors for the development of hepatic angiosarcoma. Often patients report non-specific symptoms such as abdominal pain, anemia, weight loss, fever, fatigue, however, can present with jaundice and ascites in case of advanced disease. Rare but spontaneous rupture of the liver and intraabdominal bleeding can also occur in patients with hepatic AS. Tumor size, visceral tissue involvement, the presence of necrosis, and metastatic disease at the initial presentation are some of the poor prognostic factors. CT angiography is the preferred imaging modality. Pathological diagnosis is often required. Median survival is approximately 6 months without any treatment. Surgery can be considered if they are localized to a lobe. Chemotherapy can be offered for palliation in cases of advanced and multifocal disease. Because of a high recurrence rate, liver transplant is generally not recommended for hepatic AS.Figure 1.: A. (From top to bottom) CT of the abdomen showed multiple hypodense lesions in the liver. B. EGD demonstrated multiple erythematous nodular lesions in the gastric body. C. EGD demonstrated multiple erythematous nodular lesions in theduodenum.Figure 2.: A: Liver biopsy showed small aggregates of anastomosing vascular channels with highly atypical cells suggestive of AS. B: Tumour cells positive for CD-34. C: Focally positive for Factor VIII.

Phospho-histone-H3 immunostaining for pulmonary carcinoids: impact on clinical appraisal, interobserver correlation, and diagnostic processing efficiency

Lung carcinoid tumors are classified as either typical or atypical based on the presence of necrosis and the maximum mitotic count per 2mm2 area. Determining the mitotic count, which is manually conducted on slides stained with hematoxylin and eosin (HE), is time-consuming and subject to high interobserver variability. The objective of this study was to test the sensitivity and specificity of a surrogate mitosis marker, phospho-histone-H3 (PHH3) immunostaining, in the processing of pulmonary carcinoids as compared with the standard HE evaluation. Carcinoid tissue blocks that were available from lung resection specimens were analyzed using HE and PHH3 stains. Two thoracic pathologists and two residents determined the mitotic count on HE and PHH3 stains in accordance with the 2015 WHO guidelinesand recorded the time required to complete this task. For both methods, the interobserver agreement among raters for the mitotic count/2mm2 was assessed by conducting intraclass correlation analyses. We found that for both pathologists and residents, the time required to determine the mitotic count using the PHH3 method was reduced compared with the traditional HE method. Furthermore, residents detected more mitoses/2mm2 using the PHH3 stain compared with the HE method. More importantly, the PHH3 method yielded better interobserver agreement than the HE method in terms of mitoses/mm2 detection. Overall, our data confirmed that histologic assessments of carcinoid tumors using PHH3 staining provides practical benefits in terms of scoring times, mitosis detection, and reproducibility of mitotic counts. In addition, we found that the benefit was even greater for less experienced pathologists.

Analysis of RPL37A, MTSS1, and HTRA1 expression as potential markers for pathologic complete response and survival.

Non-metastatic locally advanced breast carcinoma (LABC) treatment involves neoadjuvant chemotherapy (NCT). We evaluated the association of clinical-pathological data and immunoexpression of hormone receptors, HER2 and Ki67, and new biomarkers, RPL37A, MTSS1 and HTRA1, with pathological complete response (PCR) or tumour resistance (stable disease or disease progression), disease-free survival (DFS) and cancer-specific survival (CSS). This is a retrospective study of 333 patients with LABC who underwent NCT. Expression of MTSS1, RPL37A and HTRA1/PRSS11 was evaluated by immunohistochemistry in TMA slides. Cutoff values were established for low and high tumour expression. ROC plotter evaluated response to NCT. Chi-square test for factors related to PCR, and Kaplan-Meier test and Cox model for factors related to DFS and CSS were prformed. The mean follow-up was 70.0months and PCR rate was 15.6%. At 120months, DFS rate was 32.5% and CSS rate was 67.1%. In multivariate analysis, there was an association between: (1) necrosis presence, intense inflammatory infiltrate, ER absence, HER2 molecular subtype and high RPL3A expression with increased odds of PCR; (2) lymph node involvement (LNI), high Ki67, low RPL37A and high HTRA1 expression with increased risk for NCT non-response; (3) LNI, high proliferation, necrosis absence, low RPL37A and high HTRA1 expression with increased recurrence risk; (4) advanced LNI, ER negative tumours, high HTRA1, low RPL37A expression and desmoplasia presence with higher risk of cancer death. RPL37A is a potential biomarker for response to NCT and for prognosis. Additional studies evaluating HTRA1 and MTSS1 prognostic value are needed.

Predictive Indicators of Survival in Patients With Surgically Resected Lung Carcinoid Tumors at a Greek Medical Center.

IntroductionLung carcinoid tumors are neuroendocrine neoplasms, less frequent than other lung tumors. They are subdivided into typical carcinoids (TC) and atypical carcinoids (AC), according to the rate of mitosis and the presence of necrosis. Lung carcinoids are often asymptomatic and only discovered incidentally. They may also present with cough, wheezing, asthma, and chronic obstructive pulmonary disease, chest pain, and hemoptysis depending on the location of the tumor and, less commonly, present with carcinoid syndrome. In our study, we describe the clinical and pathological features of patients with surgically resected lung carcinoids at our institution over a period of 14 years. We also examine if these features, including age, gender, tumor size, type of carcinoid, stage, nodal involvement, and Ki-67 expression are associated with patients' survival.Materials and methodsWe retrospectively reviewed patients that underwent surgery with a final histologic diagnosis of a pulmonary carcinoid tumor from March 2005 to March 2019. The evaluation included history, physical examination, chest radiographs, computerized tomography of the chest, upper abdomen, and brain, and bone scintiscan. All specimens resected during the surgical procedures were sent for pathological examination, including mediastinal and hilar lymph nodes. The patients' age, gender, tumor size, type of carcinoid, nodal involvement, stage, and Ki-67 expression were recorded and correlated to the patients' survival rates.ResultsThe study included 108 patients - 52 males and 56 females - with a mean age of 51.5 years (range 11-80 years). Atypical carcinoid was the diagnosis in 28 patients (16 males and 12 females) and 80 patients had the diagnosis of typical carcinoid (36 males and 44 females). Tumor size was ≤3.7 cm in 84 patients (68 with TC and 16 with AC) and >3.7 cm in 22 patients (12 with TC and 10 with AC). Sixteen patients had nodal deposits, 12 in N1 nodes and four in N2 nodes. Eighty patients were classified in stage I, 18 patients in stage II, and 10 patients in stage III. None of the patients had distant metastases. The Ki-67 proliferation index was examined in 84 specimens and Ki-67 was <2.5 in 50 patients and ≥2.5 in 34 patients. Of the 108 patients, eight died, all with disease-related death. According to the Cox regression univariate analysis, four factors were correlated to shorter survival: atypical histology, tumor size >3.7 cm, nodal involvement, and advanced stageConclusionsIn conclusion, we found that histological type, tumor size, nodal involvement, and stage are associated with survival in patients with surgically resected lung carcinoids without distant metastases. Other parameters, such as age at operation, gender, and Ki-67 index, did not have a role in survival in these patients according to the Cox regression univariate analysis.

The role of EBUS-TBNA in lung cancer restaging and mutation analysis

In recent years, several molecules targeting specific genetic aberrations were released for the treatment of patients affected by locally advanced and metastatic non-small cell lung cancer (NSCLC), leading to an improvement in survival. Moreover, inhibitors of PD-1 and PD-L1 immune checkpoints showed to improve survival, and they are now indicated as first-line treatment in selected patients. Hence, the collection of adequate samples for diagnosis, staging, genotyping and immunohistochemical analysis is a fundamental step in NSCLC treatment planning. When feasible, EBUS-TBNA is suggested as the first-choice diagnostic tool by most of the guidelines. Several studies demonstrated that mutation analysis is viable with high levels of accuracy on both cytological and histological samples obtained by EBUS-TBNA. No technical factor (type of needle, number of passes, use of rapid-on-site-examination, material processing, detection method) has been identified as uniquely influencing the diagnostic yield of molecular analysis. EBUS-TBNA demonstrated to be useful for the restaging of patients affected by locally advanced NSCLC who underwent induction chemotherapy or chemo-radiotherapy, as well as in those who show acquired resistance to targeted therapy and immunotherapy. Nevertheless, most authors agree that a high number of false negative results should be expected due to the likely presence of necrosis and fibrosis induced by neoadjuvant treatments. Therefore, in case of EBUS-TBNA negative sample, pathologic confirmation by surgical biopsy is recommended for the planning of definitive treatment. As suggested by a few preliminary experiences, a wide application of next-generation sequencing (NGS) on EBUS-TBNA specimens will lead to the development of better tailored treatments with simultaneous identification of a large number of gene alterations on a single sample at the time of diagnosis.

Histological Evaluation of Human Pulp Response to Direct Pulp Capping with MTA, CEM Cement, and Biodentine.

Statement of the Problem: Direct pulp capping (DPC) is an established method in which the exposed pulp is coated with a suitable material to prevent further damage and to help its repair and healing. Different proposed materials may have different impact on pulp response during this treatment.Purpose: The purpose of this study was to compare the response of human dental pulp after DPC with calcium-enriched mixture (CEM), mineral trioxide aggregate (MTA) cement, and Biodentine.Materials and Method: In this clinical trial study, class V cavities were prepared on the buccal surfaces of 30 human premolar teeth, until the pulps were mechanically exposed. Then, teeth were randomly pulp capped with MTA, CEM cement and Biodentine, followed by resin modified glass ionomer filling. The fourth group was the control group (n= 10), in which the teeth were extracted without any prior intervention. Six weeks after the intervention, the teeth were extracted and prepared for histological evaluation in terms of the type and degree of pulp inflammation, dentin bridge formation and the presence of necrosis. Data were analyzed using Kruskal-Wallis and Mann Whitney U tests.Results: In all groups, necrosis was not observed and inflammation was chronic. The Biodentine group exhibited significantly more pulpal inflammation compared with the other groups (p= 0.001). There were no significant differences among CEM cement, MTA and Biodentine in terms of the dentine bridge formation. The thickness of the dentin bridge formed in the Biodentine group was significantly higher than MTA and control group (p= 0.035 and p= 0.011, respectively).Conclusion: Although the dentin bridge formation and the thickness of dentin bridge formed in the Biodentine group were higher than the other groups, pulp showed greater inflammation compared to CEM cement and MTA. The results of this study suggested that MTA and CEM cement performed better when employed as the direct pulp capping material.

Intrastromal implantation of chicken corneal grafts into the cornea of rabbits for corneal thickening: an experimental study.

To evaluate the feasibility and effects of the intrastromal implantation of chemically modified corneal stroma obtained from chicken into the corneas of rabbits for corneal thickening. Chicken corneas were cut, debrided, treated with cross-linking and implanted in an intrastromal pouch created in the cornea of 10 white New Zealand rabbits with femtosecond laser. Slit-lamp biomicroscopy and optical coherence tomography were performed immediately, 7, 30 and 90days postoperatively. Corneas were removed at 90daysand cut in two halves. One half was sent to histological analysis for the presence of necrosis, polymorphonuclear inflammatory cells, blood vessels and fibrosis, while the other half was evaluated with transmission electron microscopy to verify tissue organization and the presence of keratocytes and inflammatory cells. Corneal thicknesses were comparatively analyzed over time with Wilcoxon test (p ≤ 0.05). The chicken grafts were incorporated into the cornea of all animals over time. Mean rabbit cornea thickness increased from 338µm preoperatively to 538µm (p < 0.0077) at 90days, while mean chicken graft thickness decreased from 350 to 215µm (p < 0.0077). No clear signs of rejection attributable to the xenograft were observed in any of the implanted eyes. However, some macroscopic and histological events were observed in some of the eyes, probably due to procedural issues during implantation. The intrastromal implantation of chicken grafts was shown to be feasible and predictable to thicken the recipient rabbit cornea without apparent rejection. However, before being considered in humans, further meticulous clinical trials are required to establish the clinical utility, safety and efficacy of xenografts for the treatment of patients with advanced keratoconus.

Abstract 3525: Epidemiology and clinicopathology prognostic factors of TFEB translocation renal cell carcinoma (TBRCC): Analysis of updated pooled database

Abstract Renal cell carcinomas harboring the t(6;11) (p21;q12) translocation with a specific Alpha(MALAT1)-TFEB gene fusion is a recognized rare subtype of the Microphthalmia Transcription factor (MiT) family of translocation RCC. TBRCC is an indolent disease that occurs at a younger age. Though it may take on a wide spectrum of morphology, TBRCC has been classically characterized by distinctive biphasic morphology with larger epithelioid cells and smaller cells clustered around eosinophilic spheres formed by basement membrane material. This analysis was conducted to update and expand our existing knowledge of this rare disease. In order to study the demographic characteristics, cytogenetic and molecular signatures, survival, and prognostic factors, we compiled a pooled database of 140 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on survival. The median age was 32 (3-78) years with a peak incidence between ages 17 and 30 years. Males and females were afflicted equally. The median overall survival (OS) of the whole group was not reached with more than 78% alive at 10 years. The group's median disease-free survival (DFS) was 96 months. Six percent of this cohort recurred. Among patients who recurred, the median time to recurrence was 24(6-75) months. Sex did not impact OS or DFS. Similarly, the molecular partner of the TFEB gene fusion, Alpha (MALAT1) versus others, did not seem to impact OS or DFS. The presence of necrosis seemed to adversely impact OS (HR:14.3, p&amp;lt;0.0001) and DFS (HR:14.4, p&amp;lt;0.0001). Nuclear grade negatively impacted DFS, the higher the grade the worse the DFS. The presence of eosinophilia, psammoma bodies, and pigmentation did not affect OS or DFS. Similarly, the histologic morphology, biphasic vs others, did not affect OS or DFS. Multivariate analysis revealed older age (HR:1.08, p=0.01) and larger tumor size (HR:10.12, p=0.002) adversely impacted OS. This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with TBRCC. Age, size, and necrosis were found to adversely impact the OS. However, higher nuclear grade only adversely impacted the cohort's DFS. Citation Format: Philip A. Haddad, Dalia Hammoud, Kevin Gallagher. Epidemiology and clinicopathology prognostic factors of TFEB translocation renal cell carcinoma (TBRCC): Analysis of updated pooled database [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3525.

Pattern of disease recurrence and treatment after surgery for nonfunctioning well-differentiated pancreatic neuroendocrine tumors

BackgroundThe risk of recurrence after curative surgery for pancreatic neuroendocrine tumors is reported to be between 10% and 30%. Among the available locoregional and systemic treatments, there are no specific recommendations regarding the best option for treating recurrent disease. The aims of this study were to evaluate the pattern of recurrence after surgery performed with curative intent for nonfunctioning pancreatic neuroendocrine tumors and to analyze the impact of treatment on disease progression. MethodsAll patients submitted to curative surgery for sporadic, well-differentiated, nonfunctioning pancreatic neuroendocrine tumors at 2 Italian centers between 2001 and 2018, with evidence of disease recurrence during follow-up, were included (n = 46). ResultsThe most frequent type of recurrence was distant metastases (n = 38, 83%), located in the liver in 100% of cases, whereas 8 patients (17%) had an isolated local recurrence. Therapy for first disease recurrence included both locoregional (n = 14) and systemic treatments (n = 32). A second disease recurrence/progression occurred in 28 patients (61%). Patients who underwent systemic treatment after the first disease recurrence had better progression-free survival (1-year progression-free survival 78%) compared with those submitted to a locoregional procedure (1-year progression-free survival 50%; P = .007). Independent predictors of shortened progression-free survival after the first disease recurrence were the type of treatment (locoregional, hazard ratio 4.452, P = .001), the presence of necrosis (hazard ratio 2.732, P = .022) and age (>60 year, hazard ratio 2.494, P = .040). ConclusionUpfront locoregional treatment of the first recurrence of nonfunctioning pancreatic neuroendocrine tumors after curative surgery should be avoided in favor of systemic therapy.

Do morphologic characteristics play a role in nodal metastatic progression of well-differentiated pancreatic neuroendocrine tumors?

Pancreatic neuroendocrine neoplasms (NENs) are tumors with histopathologic and prognostic heterogeneity that pose difficulties in establishing standards for diagnosis, classification, and treatment. Among NENs, well-differentiated neuroendocrine tumors (NETs) have been classified as grade 1, 2, and 3 in the most recently released World Health Organization classification. Although well-differentiated NETs are associated with relatively better prognosis, they have a potential for malignant behavior such as extrapancreatic spread, metastasis, or recurrence. The present study aimed to evaluate clinical and histomorphologic findings of patients with well-differentiated pancreatic NETs and to identify histopathologic findings effective in predicting nodal metastatic progression. The study group consisted of 54 patients diagnosed with well-differentiated NET. All preparations and blocks of the patients were examined for the following histopathologic parameters: tumor diameter, microscopic tumor growth pattern (solid, trabecular, acinar, and mixed), cellular features (clear, eosinophilic, oncocytic, peliotic, and pseudopapillary), stromal changes (calcification, lymphocytic infiltration, and stromal hyalinization), presence of necrosis, perineural invasion, lymphovascular invasion, mitotic activity, and Ki67 proliferative index. Lymph node metastasis was present in 7 patients. Lymph node metastasis was significantly associated with tumor diameter of >2 cm (p = 0.012), Ki67 proliferative index of >20% (p = 0.022), grade 3 tumors (p = 0.002), presence of dense stromal hyalinization (p = 0.034), and mild lymphocytic infiltration (p = 0.041). The present study revealed that the new findings such as presence of dense stromal hyalinization and absence of remarkable lymphocytic infiltration could be predictive morphologic findings for the development of lymph node metastasis.

Ipsilateral and Concurrent Breast Cancer and Atypical Ductal Hyperplasia: Does Atypia Also Need Surgical Excision?

Standard-of-care management of atypical ductal hyperplasia (ADH) is surgical excision. Multiple studies have identified features of ADH in patients at low risk for upgrade who may benefit from omission of surgical excision. Patients with an ipsilateral breast cancer have been excluded from studies investigating observation for the management of ADH. This was a retrospective review of women with both a breast cancer and an ipsilateral separate site of ADH diagnosed on percutaneous biopsy, who underwent excision of both sites from 2008 to 2018. Radiographic and pathologic features of ADH and cancer were analyzed, including imaging size, biopsy modality, distance between sites, cancer subtype, grade, prognostic markers, ADH foci, and presence of necrosis or micropapillary features. Final pathology at the ADH site was used to determine upgrade. Multivariable logistic regression was performed to identify variables significantly associated with ADH upgrade to malignancy. Among 62 women meeting the inclusion criteria, 11 (17.7%) upgraded to malignancy [9 ductal carcinoma in situ (DCIS), 2 invasive cancer] at the site of ADH. Upgrade was significantly higher with ipsilateral DCIS (p = 0.03), ultrasound biopsy at the ADH site (p = 0.01), and ADH with necrosis (p = 0.04). The group at lowest risk for upgrade had stereotactic biopsy and ADH without necrosis (0% upgrade). The presence of breast cancer does not significantly increase the likelihood for upgrade at a separate site of ipsilateral concurrent ADH above contemporary reported upgrade rates of ADH alone (10-30%). When considering breast conservation for breast cancer, omitting excision of the site of ADH can be considered when low-risk features are present.