Papillary Type Research Articles

Pediatric Thyroid Cancer in Europe: An Overdiagnosed Condition? A Literature Review.

Thyroid neoplastic pathology is the most common form of cancer associated with radiation exposure. The most common histopathological type of thyroid carcinoma is the differentiated thyroid cancer (these include papillary and follicular type), which represents over 90% of all cases, especially affecting girls rather than boys. Although patients are diagnosed in advanced stages as compared to adults, the prognosis of the disease is very good, with a 30-year survival rate of over 95% but post-therapeutic morbidity remains quite high. The treatment is based in particular on the therapeutic guidelines for adults, but as children have some histopathological and genetic characteristics of thyroid cancer, as well as different initial clinical presentations, we decided to review the literature on this pathology among the pediatric population, focusing on cases in Europe. The major interest is the impact of the Chernobyl accident.

Increasing Thyroid Cancer Incidence in Oman: A Joinpoint Trend Analysis.

ObjectivesWe sought to investigate the epidemiology of thyroid cancer and its trends in Oman over a 20-year period.MethodsWe analyzed all cases of primary thyroid cancer reported to the Oman National Cancer Registry between 1996 and 2015. Age-standardized incidence rates (ASR) were calculated using the World Standard Population. Joinpoint regression was used to assess trends and obtain annual percentage changes (APC) in incidence rates with 95% confidence intervals (95% CI) and p-values at the alpha = 0.050 level. Gender-specific APC was used to project thyroid cancer incidence rates in Oman over the next 20 years. Population attributable fraction was calculated for obesity and current non-smoking.ResultsA total of 1285 cases of primary thyroid cancer cases were registered in Oman between 1996 and 2015, with a female to male ratio of 4:1. In men, the ASR was 2.0 per 100 000 while in females it was 7.6 per 100 000 (p < 0.010). Over 80.0% of thyroid tumors were of a papillary type and 19.0% follicular type. Statistically significant trends for thyroid cancer were detected in women from 2008–2015 (APC = 14.3%, 95% CI: 8.0–20.9, p < 0.010) and among both genders (APC = 16.7%, 95% CI: 4.9–29.9, p < 0.010). If current trends continue, thyroid cancer incidence will increase to 3.1, 16.6, and 11.8 per 100 000 by 2040 in men, women, and both genders, respectively. Nearly 10.0% of thyroid cancer can be prevented by controlling obesity in the Omani population.ConclusionsOman has had moderate incidence rates of thyroid cancer with an increasing trend among women. Since projections estimate that the rates of this disease will double in women over the next 20 years, health authorities should consider providing sufficient resources to manage this condition and establish prevention programs that address obesity as part of the strategy for the prevention and control of noncommunicable diseases.

Thyroid Aspiration Overview in the Diagnosis of Suspicious Malignancy (Thyroid Papillary Carcinoma)

BackgroundThyroid carcinoma is the most common malignancy in the endocrine system. Fine Needle Aspiration Biopsy (FNAB) is a preliminaryexamination to detect thyroid neoplasms. One of FNAB diagnostic category according to Bethesda is Suspicious for Malignancy(SFM). This study was conducted to assess the cytology feature of SFM category and its concordance with histopathologic result.MethodsThis retrospective study is a descriptive categoric study with cross sectional design of 40 samples. Secondary datas were arsip inlaboratory of Anatomical Pathology of FKUI/RSCM collected on 2015 diagnosa as suspect for malignancy of tiroid based onhistopathologic result.ResultsThe histopathological results of SFM were: PTC 20 cases (50%), Hurthle cell carcinoma 2 cases (5%), adenomatous goitre withPTC focus 11 cases (27%), adenomatous goitre with atypical cell 1 case (2%), adenomatous goitre 4 cases (10%), follicularadenoma 1 case (3%), Hashimoto's thyroiditis with atypical cell 1 case (3%). Positive predictive value was 82.5% with 94% ofmalignancies were papillary type. Cytology feature of SFM specimen: cellularity moderate (57.5%), macrofollicular (67.5%), nuclearchange powdery chromatin (85%). Giant cell were 18 cases (45%, cytoplasmic were 20 cases (50%), bubble gum colloid were, 9cases (22.5%).ConclusionMost of SFM specimen have malignant histopathologic result, especially papillary type. The positive predictive value of the SFMcategory is quite high, but there is still disconcordance on histopathologic results.

Diagnostic and treatment of the intraductal papillary mucinous tumor of pancreas

Adjustment of diagnostics and management of the surgical treatment of patients with intraductal papillary mucinous tumor of pancreas. From 2012 to 2018, 45 patients with intraductal papillary mucinous tumor were observed. During the observation the ultrasound examination, contrast-enhanced computed tomography and magnetic resonance tomography with contrast were used. In 29 cases radical surgery was performed, nonradical in 1 case; case follow-up is chosen for 15 patients. Intraductal papillary mucinous tumor was diagnosed and the definition of the type of tumor was made on the base of 2 types of imaging methods. Intraductal papillary mucinous tumor type 1 was founded in 5 (11%), whereas intraductal papillary mucinous tumor type 2 was founded in 20 (44,5%) and intraductal papillary mucinous tumor type 3 was observed in 20 (44,5%) cases. Intraductal papillary mucinous tumor associated with carcinoma was observed in 16 cases. Pancreaticoduodenal resection was performed in 20, distal exsection of pancreas was performed in 4 cases (2 in open manner access, 2 in robot-assisted manner), pancreatic head resection was performed in 3 cases (1 in open manner access, 2 in laparoscopic access) and in 2 cases the duodenopancreatectomy was performed. Explorative laparotomy was performed in case of intraductal papillary mucinous tumor type 2 associated with mucilaginous carcinoma and miliary metastasis in the liver. Early postoperative complications were observed in 5 cases (16, 6%): biliary fistula (n=2), postoperative wound infection (n=2), arrosive hemorrhage type B in ISGPS (n=1, was treated in an X-ray endovascular manner). Case follow-up was chosen in 15 cases of intraductal papillary mucinous tumor over the course of 6 to 74 months and disease progression was not observed. Intraductal papillary mucinous tumor is a condition associated with high risk of malignant change and demands early disease detection. The treatment should be provided in medical centers that specialize in the pancreas deceases, where a full patient examination as well as a clear-eyed understanding of diagnostic information with the execution of desirable type of surgical intervention with the guaranty of achievement R0 condition can be offered.

An insight into non transitional cell carcinoma of Bladder: A six year retrospective study

Non transitional cell carcinomas comprise 5 – 10% of all malignant bladder tumours. A retrospective study was done in 50 cases of TUR-BT (transurethral resection of bladder tumour) and radical cystectomy specimens for a period of 6 years at a tertiary care hospital. The various details analysed were the presenting complaints, age, sex, cystoscopy findings, radiological findings, urine cytology findings, gross morphology and microscopic findings. Non transitional cell carcinomas reported were squamous cell carcinoma, adenocarcinoma (papillary, mucinous and clear cell types) and sarcomatoid carcinoma.

Psychological Status and Quality of Life Associated with Radioactive Iodine Treatment of Patients with Differentiated Thyroid Cancer: Results of Hospital Anxiety and Depression Scale and Short-Form (36) Health Survey.

Purpose:The objective is to investigate psychological status and quality of life (QoL) using Hospital Anxiety and Depression Scale (HADS) and Short-Form (36) Health Survey (SF-36) questionnaires in patients with proven differentiated thyroid cancer (DTC) who are referred for radioactive iodine (RAI) ablation before, during, and after treatment.Methods:Of patients who underwent total thyroidectomy with a pathologically proven DTC (papillary and follicular types) referred for RAI treatment to our department in 2018, 150, in whom the diagnosis was newly established, were referred for the first course of RAI treatment and were consecutively enrolled in the study. The patients received an oral dose of radioiodine (3700 or 5550 MBq). For evaluation of anxiety, depression, and QoL, all patients are given two standard questionnaires, HADS, and SF-36 and are requested to answer them at four time points. First one was at 1 month before RAI, second was at the time of RAI treatment. Third and fourth ones were 1 week and 6 months later, respectively.Results:The mean age of patients was 39.17 (±12.95) years and 121 (80.7%) were female and 29 (19.3%) were male. Values of HADS and SF-36 scores at corresponding time points were significantly correlated using Pearson correlation (HADS and SF-36 scores at 1 month before RAI: r = −0.56, P < 0.001; at time of RAI: r = −0.71, P < 0.001; 6 months after RAI: r = 0.19, P = 0.021). Using paired-sample t-test, for HADS, except for difference between time points of 1 month before RAI and time of RAI, pairwise difference between scores of other time points was statistically significant after Bonferroni correction. For SF-36, pairwise difference between scores of all three time points was statistically significant. Interaction of age, gender, RAI dose, and thyroid-stimulating hormone level at the time of RAI on HADS and SF-36 scores did not show statistical significance.Conclusion:Trend in scores over several-months’ time discloses gradual improvement of QoL and merits close observation but limited psychiatric intervention.

Immediate outcomes of robotic resection for hilar cholangiocarcinoma. Initial experience evaluation

Background: Outcomes of robotic resection for perihilar cholangiocarcinoma is still controversial. Aim. Estimation of outcomes after robot-assisted resection for hilar cholangiocarcinoma. Methods. Data were collected for four years (2014-2016) in a single Russian high-volume centers. All patients underwent surgery with intention to treat for hilar cholangiocarcinoma. Diagnosis was based on medical history, CT, MRI and PTBD data. The standard procedure included major liver resection with segmentectomy 1, extrahepatic bile duct resection and Roux-en-Y biliary reconstruction with D2 lymphadenectomy. In case of insufficient (<40%) volume of FLR its hypertrophy was induced by modified variant of ALPPS (PRALPPS). Results: Twelve patients were treated. Major liver resection was performed in 11 patients. In one case of papillary tumor type I according to Bismuth-Corlette classification extrahepatic bile ducts were resected without liver resection. Final histological examination confirmed hilar cholangiocarcinoma in 9 patients with exception of 2 patients with benign strictures and gallbladder sarcoma in one patient. In two patients there was conversion to open procedure due to vascular invasion required vascular resection and reconstruction. The mean operation time was 710 (490-980) min for totally laparoscopic cases. After initial period of the first 4 procedures the mean time decreased from 858 (560-980) min to 612 (490-690) min without significant differences. Mean blood loss was 420 (50-950) mL. The rate of R0/R1 resection was 9/1 in patients with malignancy. The mean number of lymph nodes harvested was 8 (4-9). Severe complications (>2 according Clavien-Dindo classification) revealed in 9 patients. In six of them IIIa,b grade morbidity was observed. One patient died due to liver failure. The mean hospital stay was 22 (11-37) days. Conclusion: The initial experience of robot-assisted resection for hilar cholangiocarcinoma suggests that robotic approach may be validated in highly selected patients. Evaluation of long-term Results is needed to clarify oncological safety.

Risk Factors for Thyroid Cancer: What Do We Know So Far?

SUMMARYThyroid cancer (TC) is the most common endocrine cancer today. The rising incidence of the differentiated papillary type cannot be entirely explained by early and meticulous diagnosis, since a proportion of large tumors has also been reported. In this review, we present the results of numerous investigations focused on possible factors causing increased TC incidence, such as chromosomal and genetic alterations, iodine intake, TSH level, autoimmune thyroid disease, gender, estrogen, obesity, lifestyle changes, and environmental pollutants. Up to now, only childhood exposure to ionizing radiation has been fully recognized as a risk factor. There is also a possibility that yet undiscovered carcinogens, especially during intrauterine life or early childhood, might be responsible for increased TC incidence as well as epigenetic changes. Therefore, more studies are necessary in order to further investigate the potential risk factors for TC and their mechanisms of action.

Vascular endothelial growth factor and epithelial cell adhesion molecule immunoexpression in enzootic nasal adenocarcinoma of goats

Enzootic nasal adenocarcinoma (ENA) is a contagious and viral disease in sheep and goats. The disease leads to the death of the affected animals and causes economic losses in infected small ruminant flocks. Epithelial cell adhesion molecule (EpCAM) is a newly discovered tumor antigen, commonly expressed by several tumors occurring in humans. Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulate the formation of blood vessels and plays an important role in angiogenesis, essential for tumor development. In this study, ENA originating from the nasal mucosa is detected on histopathological and cytopathological examinations, with transmission electron microscopy confirming viral particles in the tumoral cells. The aim of this study was to examine VEGF and EpCAM immunoexpressions using streptavidin–biotin complex immunoperoxidase technique in 24 naturally ENA-affected goats. Sneezing, dyspnea, seromucous or purulent nasal discharge, exophthalmos, and weight loss were commonly observed clinical symptoms. The tumors located in the nasal cavity were generally unilateral and were bilateral in only two cases. Cytological examination of the tumoral masses revealed uniform epithelial cell clusters and abundant inflammatory reaction. On histopathological examination, tubular, papillary, or mixed types of ENA were diagnosed. On ultrastructural examination, intracytoplasmic, spherical, retrovirus-like particles were demonstrated. Immunohistochemically, strong positive reactions were reported for both EpCAM and VEGF in the cytoplasm of the tumor cells. Thus, this study showed that EpCAM and VEGF may have an important role in ENA pathogenesis.

A Case of Type 1 Papillary Renal Cell Cancer with Pelvic Tumor Thrombus Masquerading as Urothelial Cancer with Review of Literature

Background: Adult renal tumors vary from renal cell carcinoma (RCC) to upper tract urothelial cancer (UTUC). Tumor characteristics such as renal vein and inferior vena cava tumor thrombus are usually seen with RCC, but tumor thrombus into pelvicaliceal system (PCS) is a rare entity in RCC. At present only 11 cases have been reported in the literature. Case Presentation: We report an unusual case of papillary type 1 RCC in a young Muslim man mimicking as UTUC radiologically and found to have free tumor thrombus in PCS. At follow-up of 6 months after right nephroureterectomy with bladder cuff excision, he is doing well clinically and radiologically without any recurrence. Conclusion: RCC with tumor thrombus into PCS is an uncommon entity. It can give similar appearance as an urothelial cancer of the pelvis on radiologic imaging. Pelvic tumor thrombus is now considered as a factor of poor prognostic importance and rarely encountered with pure papillary type of RCC.

Innovative ultrasound-based diagnosis of renal tumors

In Germany, renal tumours are detected earlier also due to advancing technology within ultrasound devices and its more widespread application. Ultrasound diagnosis is usually the first imaging procedure available to urologists. For all renal lesions larger than 1 cm in diameter, fat content can be revealed by quantitative measurements within CT/MRI diagnostic modalities to confirm the suspected diagnosis of angiomyolipoma, or in patients with potentially malignant renal lesions referral (with all the their imaging data) to the multidisciplinary tumour team. As afurther step, biopsy may be indicated, especially in the case of inflammatory lesions or suspected lymphoma; otherwise patients with asolid tumour are treated within atumour stage-appropriate urological therapy regime. Contrast-enhanced ultrasonography (CEUS) is currently unable to distinguish between benign and malignant renal tumours. Nevertheless, this noninvasive method is useful in everyday clinical practice: in excluding renal pseudolesions, in inflammatory lesions, for follow-up of traumatic pseudolesions, and for the differential diagnosis of atypical renal cyst diagnosis versus renal cancer. Contrast-enhanced sonography also reveals the microperfusion of kidney tumors, providing clues for distinguishing between clear cell and papillary types of renal cell carcinoma. The method is also utilised in CEUS-controlled biopsy procedures of renal lesions. Contrast-enhanced sonography augments CT/MRI imaging with real-time information on the perfusion of the kidney tumour and can be atherapy-relevant aid for the multidisciplinary cancer conference with the ultrasound examinations being presented as video clips for comment thereon.

A PROSPECTIVE STUDY ABOUT THE SURGICAL MANAGEMENT OF THYROID CARCINOMA

INTRODUCTION : Thyroid cancer is one of the most common endocrine cancer and has the highest mortality among endocrine neoplasms. In India, its incidence is between 0.8–2 per 1,00,000 population. Early diagnosis and treatment remain the cornerstone of management to decrease the mortality rates. lack of prospective randomized trials, the management of these cancers generates tremendous controversy. study was planned to assess &amp; evaluate the management of various thyroid carcinomas. METHODS: A total of 40 patients were selected which were pathologically / histologically proven cases of Thyroid carcinoma in this Prospective study design in 2.5 years. Detailed Clinical Examination was done &amp; Prior to surgery all the patients went through investigations. Subjects included both the genders , all age groups including pediatric and geriatric age group and all classes of socio economic strata. RESULTS: No of female patients were 30 and male patients 10.Male :female ratio in this study was 1:3.FNAC / Biopsy / Cytology detected papillary carcinoma in 26 patients (65%) ,follicular neoplasm in 11 patients (27.5%) ,2 (5%) patients of anaplastic and one (2.5%) of medullary carcinoma. 86.6% of the patients had a firm gland &amp; hard gland and rest presented with a soft gland on palpation.Total Thyroidectomy with cervical block dissection was performed in 32 (80%) cases .Rest of the 20 % were dealt with Sub total Thyroidectomy with cervical block dissection. CONCLUSION: Most of the cancers present as a slow growing goiter for few months to few years duration.Most of the cancers are of papillary carcinoma type , FNAC detects the majority of the cancers and is an important diagnostic test.Thyroid cancers have a good prognosis as most of the patients present as Stage I disease &amp; most of the patients require total thyroidectomy with or without lymph node dissection followed by radio iodine ablation as treatment.Thyroid cancer,irrespective of the extent of disease,has good prognosis

PRMT1 expression in renal cell tumors- application in differential diagnosis and prognostic relevance

BackgroundProtein arginine methyltransferase-1 (PRMT1) is associated with the progression of various tumor types and the process of epithelial to mesenchymal transition (EMT). However, the expression of PRMT1 in renal cell tumors (RCT) is unknown.MethodsWe evaluated PRMT1 immunohistochemical (IHC) expression on tissue microarray (TMA) of 208 specimens of RCT, including clear cell renal cell carcinomas (ccRCC), papillary RCC type I and II (pRCC I and II), chromophobe RCC (chRCC), renal oncocytomas (RO), collecting duct carcinomas - Bellini (CDC) and multilocular cystic renal cell neoplasms of low malignant potential (MLCRN-LMP). Moreover, a subset of ccRCC, pRCC, chRCC, RO were also studied using conventional sections. PRMT1 expression in tumor tissue was compared to the IHC expression of EMT-related transcription factors (ZEB1, RUNX1, and TWIST1) and cell surface markers (ß-catenin, N- and E-cadherin). Additionally, qRT-PCR expression of PRMT1 in ccRCC, pRCC, and chRCC was evaluated and the results were compared to the mRNA PRMT1 transcript profiling data in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) cohort.ResultsPRMT1 immunoreactivity was observed in the majority of ccRCC, RO, all MLCRN-LMP, but in a minority of chRCC (p = 0.044), and it was associated with low grade and low stage ccRCC (p = 0.014; p = 0.044, respectively). ZEB1 immunoreactivity was noted in all RO, in minority of chRCC and neither of MLCRN-LMP (p < 0.001). The majority of PRMT1-negative ccRCC was negative to ZEB1 and showed cytoplasmic expression of TWIST1 (p = 0.028; p < 0.001, respectively). PRMT1 positive ccRCC mostly expressed RUNX1 (p = 0.019). PRMT1 and ZEB1 expression were associated with better cancer-specific survival in patients with ccRCC (p = 0.029; p = 0.009, respectively). In multivariate analysis, ZEB1 expression was an independent prognostic factor for cancer-specific survival (hazard ratio [HR], 0.367; p = 0.026). Significant IHC heterogeneity was observed in PRMT1, ZEB1 and TWIST1 expression (p < 0.001). Homogenous loss of PRMT1 was associated with high grade and high stage ccRCC, while the homogenous loss of PRMT1 and ZEB1 was more frequent in patients who died of ccRCC (p = 0.017; p = 0.040; p = 0.044; p = 0.009, respectively). Relative mRNA-PRMT1 expression in both cohorts was down-regulated in tumor tissue compared to non-tumor parenchyma (p = 0.009). Unlike in our samples, mRNA-PRMT1 expression in the TCGA cohort was not correlated to ccRCC tumor stage or grade. PRMT1, ZEB1, and TWIST1 expression were not associated with EMT related aberrant ß-catenin expression, a gain of N-cadherin or loss of E-cadherin expression. Only RUNX1 was associated with a gain of N-cadherin (p = 0.003).ConclusionsIHC expression of PRMT1 may be characteristic for low grade and low stage ccRCC, while the homogenous loss of PRMT1 may be significant for high grade and high stage ccRCC. Both, PRMT1 and/or ZEB1 expression, could be associated with better survival of the patients with ccRCC.

Divergent Metastatic Patterns Between Subtypes of Thyroid Carcinoma Results From the Nationwide Dutch Pathology Registry.

BackgroundMetastatic disease is the main cause of cancer-related mortality in thyroid carcinoma (TC) patients. Clinical studies have suggested differences in metastatic patterns between the different subtypes of TC. This study systematically evaluates the metastatic patterns of different subtypes in TC patients.MethodsA nationwide review of pathological records of all 650 patients diagnosed with a primary malignancy in the thyroid who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA).ResultsMetastatic disease was present in 228 (35.1%) patients and was found in 38.7%, 17.3%, 75.4%, and 47.8% of patients with follicular, papillary, anaplastic, and medullary types of TC, respectively (P < .0001). The majority of patients had more than 1 metastasis. The most common site of metastatic disease was the lung for papillary (79.7%), follicular (72.9%), and anaplastic (92.1%) carcinoma but not for medullary carcinoma (56.3%), P < .0001. Medullary carcinoma patients most frequently had metastases to the liver (81.3%). The combination of metastases also differed between subtypes.ConclusionThere are major differences in metastatic patterns between different subtypes of TC. The patterns and frequencies identified in this autopsy study may reflect the underlying biology of metastatic thyroid cancer and have potential to influence future monitoring and treatment strategies depending on clinical correlations.

1275 Intestinal-Type Intracholecystic Papillary Tubular Neoplasm (ICPN) Presenting as Acute Hemorrhagic Cholecystitis

INTRODUCTION: The term Intracholecystic Papillary Tubular Neoplasm (ICPN) was coined by Adsay et al (2012). ICPN includes mass-forming (papillary or polypoid), intramucosal and preinvasive gallbladder neoplasms larger than one cm in size. CASE DESCRIPTION/METHODS: A 73-year-old man presented with acute and sharp right upper quadrant abdominal pain for one day. He denied nausea, vomiting, diarrhea, fever or chills. Past medical history included COPD, non-Hodgkin lymphoma in remission and hypertension. He was not receiving anticoagulants or antiplatelet medications. On abdominal examination, there was marked tenderness in the right upper quadrant area with a positive Murphy's sign. Laboratory testing revealed leukocytosis of 22,000/µL with neutrophilia and normal liver chemistry tests and a serum lipase level. Abdominal ultrasonography showed a markedly distended gallbladder with mural thickening of up to 1.0 cm and numerous gallstones with a positive sonographic Murphy's sign. Non-contrast CT showed mixed attenuation suggesting hemorrhage into the gallbladder lumen and suggestive of acute hemorrhagic cholecystitis. He underwent open cholecystectomy. Surgical findings were a distended gallbladder with a thickened and inflamed wall. Half of the gallbladder lumen was occupied by stones and the remainder was filled with detached, friable, tan-red hemorrhagic material. Microscopic examination of several of detached fragments and intact mucosa showed an abundant ICPN of intestinal-type origin and a tubular-papillary growth pattern. There was marked acute and chronic inflammation of the gallbladder wall without mural perforation. DISCUSSION: ICPNs are usually seen in middle-aged individuals, with a 2- fold higher prevalence in women. Macroscopically, ICPNs are exophytic tumors: tubular/lobulated types are soft, friable and can get easily detached appearing as sludge or debris, while granular or papillary types are sessile and feathery filling the gallbladder lumen. ICPN exhibits a variety of cell lineages such as biliary (50%), gastric (25%), intestinal (8%, as in our patient), oncocytic (6%) and mixtures of lineages (∼10%). In our patient, the two most plausible pathogenic processes are either diagnosis of an incidental ICPN due to the associated acute calculus hemorrhagic cholecystitis or acute “acalculous” cholecystitis from tumor shedding and bleeding into the gallbladder lumen and causing cystic duct obstruction associated with asymptomatic (incidental) cholelithiasis.

Birthweight and risk of thyroid cancer and its histological types: A large cohort study

BackgroundThe aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk. ObjectiveTo investigate if birthweight is associated with the later risk of thyroid cancer and its histological types. Methods246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936–1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). ResultsDuring follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03–1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07–2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90–1.59] per kilogram). ConclusionA heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.

Papillary Renal Neoplasm With Reverse Polarity: A Morphologic, Immunohistochemical, and Molecular Study.

We evaluated the clinicopathologic and chromosomal characteristics of a distinct subset of papillary renal tumors and compared them to a control series of papillary renal cell carcinoma types 1 and 2. Of the 18 patients, 9 were women and 9 were men, ranging in age from 46 to 80 years (mean, 64 y; median, 66 y). The tumors ranged in diameter from 0.6 to 3 cm (mean, 1.63 cm; median, 1.4 cm). Fourteen tumors were WHO/ISUP grade 2 and 4 were grade 1. All were stage category pT1. The tumors had branching papillae with thin fibrovascular cores, covered by cuboidal to columnar cells with granular eosinophilic cytoplasm, smooth luminal borders, and mostly regular and apically located nuclei with occasional nuclear clearing and inconspicuous nucleoli. Tubule formation and clear cytoplasmic vacuoles were observed in 5 and 9 tumors, respectively. Ten tumors had pseudocapsules. Psammoma bodies, necrosis, mitotic figures and intracellular hemosiderin are absent from all tumors. In contrast, papillary renal cell carcinoma type 1 consisted of delicate papillae covered by a single layer of cells with scanty pale cytoplasm with nuclei generally located in a single layer on the basement membrane of the papillary cores, while type 2 tumors had broad papillae covered by pseudostratified cells with eosinophilic cytoplasm and more randomly located nuclei. Both had occasional psammoma bodies, foamy macrophages and intracellular hemosiderin. Immunohistochemically, all were positive for pancytokeratin AE1/AE3, epithelial membrane antigen, MUC1, CD10, GATA3, and L1CAM. Cytokeratin 7 was positive in 16 tumors (1 had <5% positivity). CD117 and vimentin were always negative. α-methylacyl-CoA-racemase (AMACR/p504s) showed variable staining (range, 10% to 80%) in 5 tumors. However, all tumors in the control group were negative for GATA3 and positive for AMACR/p504s and vimentin immunostains. Fluorescence in situ hybridization analysis of the study group demonstrated chromosome 7 trisomy in 5 tumors (33%), trisomy 17 in 5 tumors (33%), and trisomy 7 and 17 in 3 tumors (20%). Chromosome Y deletion was found in 1 of 7 male patients and chromosome 3p was present in all tumors. No tumor recurrence or metastasis occurred. In summary, we propose the term papillary renal neoplasm with reverse polarity for this entity.

Papillary architecture of the Leopardus pardalis tongue.

The ocelot (Leopardus pardalis) is a Felidae of wide geographical distribution and food flexibility; therefore, it is essential to understand the morphology of the species. Thus, we aimed to describe its lingual morphology in order to gain information regarding the anatomy of this carnivore's digestive system. The tongues ​​were removed for ex situ macroscopic and morphometric analyses, as well as for light microscopy and scanning electron microscopy, of fragments of the different lingual regions. The tongue of L.pardalis had an elongated form that was subdivided into the apex, body and root, in which four papillary types were observed: filiform, fungiform, circumvallate and conical. It presented with a stratified, keratinized squamous epithelium, followed by loose and dense connective tissues, as well as a skeletal striated musculature that comprised most of the organ. In addition, in scanning electron microscopy the filiform papillae showed a complex with multiple layers of keratin with triangular shape projected caudally in oral cavity. The fungiform papillae were distributed among the filiform and showed a rounded shape with some gustatory pores, and are keratinized but in a lower intensity if compared with filiform. The vallate papillae, located in lingual root, showed an oval format, had a deep groove surrounded the papillae and some gustatory pores. The conical papillae are located in lingual root and are similar to the filiform. The tongue of L.pardalis resembles other carnivorous species, mainly among felids. However, it differed in relation to the quantity of vallate papillae and the absence of foliate papillae.

Abstract 2632: Increased recurrence and clinical grade in renal cell carcinomas associated with novel EGFR splice variants

Abstract Background: It is well established that alterations of epidermal growth factor receptor (EGFR) are associated with the development and progression of epithelial tumors across several cancer types. Alternative splicing and alterations of EGFR splice sites can cause translational changes and EGFR alterations have historically demonstrated associations with clinical and therapeutic outcomes in lung cancer. Objectives: To evaluate the prevalence and clinical significance of recently identified novel ΔEGFR-TKF splice variant in 102 renal cell carcinoma (RCC) tumors Methods: The majority of the RCC samples were RNA sequenced through the Orien AVATAR™ pipeline, and 7 additional cases were analyzed through Moffitt STAR™. Moffitt STAR™ and AVATAR™ are next generation targeted sequencing assay that include both DNA and RNA analyses. Frequency tables were generated using the data collected. The Grehan-Breslow-Wilcoxon test was used to compare recurrence free survival (RFS) due to the higher weight given to survival difference at earlier time points. The rationale being that the majority of recurrence events occurred earlier than 25 months in EGFR ≥5% cases and 50 months in the EGFR &amp;lt;5% cases compared to the follow-up times of 75 months and 125 months in the study cohort. Results: We identified a EGFR gene splice variant, predominantly c.2470-188_c.2470-2, between exons 20 and 21 in RCCs subjected to the sequencing assay. Of 1075 solid tumors analyzed, the presence of the EGFR gene splice variant was observed, in any amount, within 74 of 102 RCC cases (72.5%), with the only exceptions being one multiple myeloma and sarcoma case. Using an EGFR slice variant cutoff of ≥5%, 33 of 102 (32.4%) RCC were chosen to be further investigated. Upon further analysis, 32 EGFR slice variant tumors were clear cell RCC, while 1 was papillary type II RCC. Thirty cases involving ≥5% slice variants were clinically staged revealed 6 T1, 8 T2, and 16 T3/4 cases compared to tumors with &amp;lt;5% of the splice variants which were staged 28 T1, 10 T2, 21 T3/4, and 8 Tx (p=.011). The RFS curve trended to worse outcomes for patients with ≥5% EGFR splice variants compared to &amp;lt;5% EGFR splice variants (p=.0315). All variants were identified at the RNA level without obvious corresponding DNA alterations. There was an average of 106 unique reads (average of 7.7% of all reads) for these cases supporting this variant. Conclusion: EGFR splice variants in RCC are a relatively frequent and specific molecular alteration. This novel splice variant may prove to be significant as a druggable target or as part of a kidney cancer screening protocol. Citation Format: George A. Coba, Saif Zaman, Jamie K. Teer, Timothy Robinson, Roger Li, Jingsong Zhang, Todd C. Knepper, Philippe E. Spiess, Wade Sexton, Matthew A. Smith, Mayer N. Fishman, Julio M. Pow-Sang, Michael A. Poch, Scott M. Gilbert, Anthony M. Magliocco, Theresa A. Boyle, Brandon J. Manley. Increased recurrence and clinical grade in renal cell carcinomas associated with novel EGFR splice variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2632.

Remarkable effect of presurgical nivolumab on originally inoperable papillary renal cell carcinoma with tumor thrombus in inferior vena cava.

For the long-term survival of a patient with renal cell carcinoma and a vena cava tumor thrombus, total resection is desired: inoperable patients are sometimes treated with drugs. The effect of the presurgical use of nivolumab, an anti-programmed cell death 1 (PD-1) antibody drug, has been described. Our patient had inoperable renal cancer with an inferior vena cava tumor thrombus. We were able to downsize the tumor to operable size by administrating nivolumab. The patient underwent a nephrectomy and thrombectomy safely. Pathological findings revealed papillary renal cell carcinoma type 2. No viable cells were identified in the removed thrombus. Anti-programmed cell death ligand 1 was expressed on the cell membrane in approximately 20% of the tumor cells, and PD-1 positive tumor-ifiltrating immune cells had infiltrated particularly at the edge of the tumor. This case indicates the positive effect of the presurgical use of nivolumab for advanced papillary renal cell carcinoma.