High Malignant Potential Research Articles

Nationwide survey of neuroendocrine carcinoma of the esophagus: a multicenter study conducted among institutions accredited by the Japan Esophageal Society.

Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare type of tumor characterized by a high malignant potential, rapid growth, and poor prognosis. Because the standard therapy for ENEC has been poorly defined, we herein aimed to attain a clear view of the current state of treatment for ENEC by performing a large-scale, multicenter study. We conducted a questionnaire-based, retrospective clinical review of 142 patients with ENEC treated at 37 hospitals accredited by the Japan Esophageal Society from January 2010 to December 2015. The most frequent main treatment performed was an operation, followed by chemoradiotherapy, chemotherapy, and endoscopic submucosal dissection. Among the 67 patients who underwent surgery, 28 (19.7%) were not accurately diagnosed with NEC or a combined NEC tumor by pretreatment biopsy. The 5-year overall survival rate of all patients was 33.2%. Among patients with Stages III and IV disease, the prognosis was significantly better in patients who underwent chemoradiotherapy than in patients who underwent other treatments. Among patients with Stages I and II disease, however, there was no difference in survival rates between those who underwent surgery and chemoradiotherapy. This nationwide survey is a valuable report of the current status of treatment of ENEC in a limited number of cases experienced at each participating institution. The survival benefit obtained from surgery was considered to be limited, especially for Stages III and IV ENEC. Accurate pretreatment histological diagnosis is essential to determine the most appropriate treatment strategy for patients with ENEC.

Characterization of anti-nuclear antibodies in patients with oral submucous fibrosis and its clinicopathologic implications - An immunofluorescence study.

Background:Oral submucous fibrosis (OSF), widespread in the Indian subcontinent, is a chronic debilitating disease of the oral cavity having a high potential for malignancy. The etiology of OSF is debatable. However, recently, autoimmunity had been suggested to play a significant role in its etiology, yet unproven. Hence, this study was conducted to explore the presence of antinuclear antibodies (ANAs) in the serum of OSF patients which is one of the serum markers of autoimmune diseases and its possible clinicopathologic associations.Materials and Methods:A total of 105 blood samples were collected from patients with OSF (n = 45), age- and sex-matched healthy controls with (n = 30) and without (n = 30) areca nut chewing habit. Serum positivity of ANA was determined by immunofluorescence and correlated with the oral habits and severity of the disease measured by maximum mouth opening (MMO) and site of involvement.Results:Significantly higher incidence of ANA (35.6%) was found in 45 OSF patients than in the healthy group (P = 0.001). Prevalence of ANA positivity was found higher in females (n = 11; 68%) than males (P < 0.001). A significantly lower MMO (P = 0.00) was found in ANA positive patients (17 ± 6.21 mm) in contrast to MMO in ANA-negative patients (28.74 ± 6.58 mm). The mean duration of habit and frequency of habit between ANA positive and negative patients was not significant. A significantly more number of sites of involvement was seen in ANA positive cases (P = 0.004). Out of 16 ANA positive OSF cases, 10 cases showed + 2 and 6 cases showed + 3 fluorescence intensity. Speckled (n = 8), homogeneous (n = 5) and nucleolar pattern (n = 3) were the fluorescence patterns observed.Conclusion:The presence of autoantibodies such as ANA, female predilection, alteration of humoral and cellular immunity justifies OSF as an autoimmune disease. This study provides broader prospective to adopt therapies that selectively target autoimmune pathways.

Curious Case of Gastrointestinal Stromal Tumor

Small bowel tumors or malignancies are relatively less common with incidence of 22.7 cases per million. Gastrointestinal stromal tumor is a subset of gastrointestinal mesenchymal tumors recognized as distinct group of mesenchymal tumors arising from interstitial cells of Cajal. It is most commonly present in the stomach followed by small intestine and colon. Small intestinal tumors have very high malignant potential. Adequate surgical resection is the only definitive treatment. We report a case which had undergone surgery for mesenchymal tumor arising from ileum and now presented with two new tumors, one in transverse colon and another in sigmoid colon.

Is There a Need for New Classifications to Predict Prognosis in Gastroenteropancreatic Neuroendocrine Carcinomas?

Objective: Neuroendocrine neoplasms (NEN) are frequently located in the lung and gastroenteropancreatic (GEP) system organs. Neuroendocrine carcinoma (NEC) constitutes 5% of GEP NENs and has a very high malignancy potential. In this study, it is aimed to determine a new threshold value in addition to the 20% Ki-67 proliferation index that was specified as a threshold value for predicting survival in patients with grade (G) 3 tumors according to World Health Organization (WHO) 2010 classification. Method: Demographic, clinicopathologic features and survival rates of 34 patients diagnosed with GEP NEC between 2008-2015 in İzmir Katip Celebi University Atatürk Training and Research Hospital Medical Pathology Clinic were evaluated retrospectively. Results: Most of the 34 (76.5%) cases were male and the average age was 63.9 years. Median survival rates were 15, and 7 months in patients with Ki-67 indexes of ≤65% and &gt;65%, respectively (p=0.232). Conclusion: Recent studies have shown heterogeneity of high-grade NENs, identified as NEC and foreseen their subdivision into biological subgroups. The researchers suggest that the NECs should be divided into two categories as patients with Ki-67 indexes of 20-55% and &gt;55%. In our study, the most significant difference in survival rates was observed when 65% was selected as threshold value for Ki-67 index which supports the results of other studies in the literature. Since the number of our cases is limited and it is a single-center study, the findings obtained needs to be further investigated in studies with greater number of case series.

ДИАГНОСТИЧЕСКАЯ РОЛЬ МОРФОМЕТРИЧЕСКОЙ ОЦЕНКИ КОМПОНЕНТОВ ОПУХОЛЬ-АССОЦИИРОВАННОЙ СТРОМЫ СЕРОЗНЫХ КАРЦИНОМ ПРИДАТКОВ МАТКИ В ПРОГНОЗЕ ОПУХОЛЕВОЙ ПРОГРЕССИИ

The method of computer morphometry of stroma components and evaluation of stromal-parenchymal relationships in the primary tumor node of serous ovarian cancer was used. A high potential for malignancy of tumor tissue, characterized by the resumption of tumor growth after radical treatment, is observed with the predominance of the epithelial component over the stroma, with a small number of necrosis in the tumor node, low density of microcirculatory vessels in the tumor, and the predominance of fi broblastic elements in the cellular microenvironment of the tumorassociated stroma.

Molecular phenotype of high-grade endometrioid carcinoma of the endometrium.

Prognosis of the course of tumor progression is one of urgent problems of clinical oncology. A relevant specificity of endometrial cancer is its clinical polymorphism within the same histological type of the disease. The search for molecular-biological features associated with the aggressive phenotype of endometrioid carcinomas is indisputably urgent. To study molecular-biological features of endometrioid carcinoma of the endometrium (ECE) and to identify the molecular subtype of tumors with high potential of malignancy. Surgical specimens of 127patients with EC, stages I-II, aged 36-72 (the average age- 59.3± 3.2) were studied using morphological and immunohistochemical methods. The multivariant analysis with the Kullback's informative measure and PanelomiX were used to estimate the significance of the expression of specific biomarkers. The expression of a complex of multifunctional markers was evaluated in ECE cells of different malignancy stage: p53, FOXP3, p21WAF1/CIP1, р16INK4a, E2F1, cyclins Е and D1, Her2/neu, с-Myc, Е-cadherin, β-catenin, vimentin, CD44, CD24. A triad of biomarkers with threshold expression levels was determined (р53< 45%; FOXP3> 14%; с-Myc< 10%). The high expression of oncogene c-Myc and oncosuppressor p53along with the low level of FOXP3in tumor cells of ECE was associated with high proliferative potential, low differentiation grade, and deep invasion of a tumor into the myometrium. The molecular phenotype of ECE, most informative in terms of specificity and sensitivity (95%)- р5highFOXP3lowc-Mychigh, was first characterized, which would help identify a high-grade subtype of this cancer form.

Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings.

Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of ACKR2 and ACKR4 expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, ACKR2 was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, ACKR4 was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in ACKR4 expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, ACKR4 downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. ACKR4 expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration.

Non-conventional dysplasia in inflammatory bowel disease is more frequently associated with advanced neoplasia and aneuploidy than conventional dysplasia.

Several different non-conventional morphological patterns of epithelial dysplasia have been recently described in inflammatory bowel disease (IBD), but there is limited information regarding their clinicopathological and molecular features, as well as potential risk for high-grade dysplasia (HGD) or colorectal cancer (CRC) compared with conventional dysplasia developing in IBD. A total of 317 dysplastic lesions from 168 IBD patients were analysed. All lesions were re-reviewed and subtyped as either conventional [including tubular adenoma-like (n=183) and tubulovillous/villous adenoma-like (n=56)] or non-conventional dysplasia [including dysplasia with increased Paneth cell differentiation (DPD, n=40), crypt cell dysplasia (CCD, n=14), goblet cell deficient (GCD, n=10), hypermucinous (n=7), sessile serrated lesion (SSL)-like (n=4) and traditional serrated adenoma (TSA)-like (n=3)]. DNA flow cytometry was performed on 70 low-grade conventional (n=24) and non-conventional (n=46) dysplastic biopsies to determine their malignant potential and molecular pathways to HGD or CRC. Eleven sporadic tubular adenomas with low-grade dysplasia (LGD) were utilised as controls. Seventy-eight non-conventional dysplastic lesions were identified in 56 (33%) of the 168 patients, whereas 239 conventional dysplastic lesions were identified in 149 (89%) patients. Although both non-conventional and conventional dysplasias were most often graded as LGD at diagnosis (83% and 84%, respectively), non-conventional dysplasia (38%) was more likely to develop HGD or CRC in the same colonic segment than conventional dysplasia (19%) on follow-up (P<0.001). Almost half (46%) of non-conventional dysplastic samples showed aneuploidy, whereas only 8% of conventional dysplasia (P=0.002) and 9% of sporadic tubular adenomas (P=0.037) did. Also, non-conventional dysplasia more frequently presented as a flat/invisible lesion (41%) compared with conventional dysplasia (18%) (P<0.001). Among the non-conventional subtypes (n=78), DPD was the most common (n=40; 51%), followed by CCD (n=14; 18%), GCD (n=10; 13%), hypermucinous (n=7; 9%), SSL-like (n=4; 5%) and TSA-like (n=3; 4%) variants. Hypermucinous dysplasia (mean=2.1cm) was significantly larger than DPD, SSL-like, TSA-like and GCD variants (mean=1.0, 1.2, 1.2 and 1.9cm, respectively) (P=0.037). HGD or CRC was more likely to be associated with CCD (n=13; 93%), hypermucinous (n=4; 57%), GCD (n=4; 40%) and SSL-like (n=3; 75%) variants than DPD (n=6; 15%) and TSA-like dysplasia (n=0; 0%) on follow-up (P<0.001). Furthermore, the rate of aneuploidy was significantly higher in CCD (100%), hypermucinous (80%) and GCD (25%) variants than in DPD (12%), SSL-like dysplasia (0%) and TSA-like dysplasia (0%) (P<0.001). Non-conventional morphological patterns of dysplasia are not uncommon in IBD, detected in 33% of the patients. The higher frequencies of advanced neoplasia (HGD or CRC) and aneuploidy in non-conventional dysplasia, in particular CCD, hypermucinous and GCD variants, suggest that they may have a higher malignant potential than conventional dysplasia or sporadic tubular adenomas, and thus need complete removal and/or careful follow-up. Greater than 40% of non-conventional dysplasia presented as a flat/invisible lesion, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. The majority of non-conventional subtypes appear to develop via the chromosomal instability pathway, whereas an alternative serrated pathway may be responsible for the development of at least a subset of SSL-like and TSA-like dysplasias.

Characterization of adherent primary cell lines from fresh human glioblastoma tissue, defining glial fibrillary acidic protein as a reliable marker in establishment of glioblastoma cell culture.

BackgroundPrimary adherent glioblastoma cell lines are an important tool in investigating cellular and molecular tumor biology, as well as treatment options for patients.AimThe phenotypical and immunocytochemical characterization of primary cell lines from glioblastoma specimens during establishment is of great importance, in order to reliably identify these cell lines as primary glioblastoma cell lines.Methods and ResultsSixteen primary adherent cell lines out of 34 glioblastoma samples (47%) were established and further characterized. For phenotypical characterization, morphology and growth characteristics of the cells were classified. The cell lines had a high growth rate with a doubling time of 2 to 14 days. Morphologically, the cells displayed spindle‐form or polygonal to amorphous shapes and grow as monolayer or in foci without evidence of contact inhibition. The cells were able to migrate and to form colonies. For further characterization, the protein expression of the astrocyte‐specific protein glial fibrillary acidic protein (GFAP), the glial marker S100B, the neuronal marker TUBB3, and malignancy marker VIM, as well as the progenitor markers NES and SOX2, the proliferation marker MKI67, and the fibroblast marker TE7 were determined. Based on the immunocytochemical validation criterion of a coexpression of GFAP and S100B, 15 out of these 16 cell lines (94%) were defined as primary glioblastoma cell lines (pGCL). All 15 pGCL expressed TUBB3 and VIM. NES and SOX2 were stained positively in 13/15 and 6/15 pGCL. MKI67 was expressed in 11/15 and TE7 in 2/15 pGCL.ConclusionThese results point out that in self‐established primary adherent glioblastoma cell lines, the expression of the specific astrocytic and glial markers GFAP and S100B and of the malignancy and progenitor markers VIM, NES, and SOX2 has to be validated. These data show that primary cell lines of glioblastoma origin with high malignant potential are reliably to establish using standardized validation criteria.

Endocytoscopic observation with methylene blue staining for duodenal neoplasms associated with familial adenomatous polyposis

Duodenal cancer is a leading cause of death after colectomy in patients with familial adenomatous polyposis (FAP). Detailed endoscopic evaluation of duodenal lesions with potential for carcinoma development is therefore mandatory. Here we investigated the features of duodenal lesions in FAP patients using an endocytoscopy system (ECS). We retrospectively reviewed duodenal lesions in 15 cases of FAP using an ECS (GIF-H290EC) with methylene blue (MB) as the vital dye. With reference to the Spigelman classification, we investigated the number of lesions using white light (WL), narrow-band imaging (NBI), and MB staining. Using the maximum magnification power of the ECS we investigated the histology (duct openings or finger-like projections) and grade of dysplasia (presence or absence of enlarged oval-shaped nuclei) of the lesions. The number of duodenal lesions increased in ascending order of WL, NBI, and MB (P < 0.05). Among 51 MB-unstained lesions, 46 (90.2%) were proven to be duodenal neoplasms histologically. Duct openings were seen in 90.2% of tubular adenomas and tubulovillous adenomas. Finger-like projections were seen in 33.3% of tubular adenomas and in 88.2% of tubulovillous adenomas. Enlarged oval-shaped nuclei were observed in 100% of duodenal cancers, 33.3% of high-grade adenomas, and 9.4% of low-grade adenomas. MB staining allows more accurate detection of duodenal neoplasms in comparison to conventional WL and NBI observation. In cases of FAP, use of the maximum magnification power of the ECS may allow selection of lesions with high malignant potential.

Comprehensive Assessment of Diet Quality and Risk of Precursors ofEarly-Onset Colorectal Cancer.

The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. In a prospective cohort study (Nurses' Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14). Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

линико-патологические особенности уротелиальной карциномы в педиатрической практике

Introduction. This review of the literature presents the results of the analysis of studies on the etiology, pathogenesis, methods of diagnosis and treatment of urothelial carcinoma in persons under 20 years of age. Worldwide, the number of such patients is small, and special programs of treatment and diagnostic measures, as well as molecular genetic panels for these patients have not yet been developed. Materials. Relevant publications indexed in PubMed, Web of Sciences Core Collection, and Journal Citation Reports were searched. Data on risk factors and molecular-genetic changes that contribute to malignancy of the urinary epithelium, early clinical manifestations, as well as features of radiation, endoscopic, morphological diagnostics and treatment of this class of tumors are analyzed. Results. Risk factors for urothelial carcinoma in patients younger than 20 years and older age groups are similar, however, there is a smaller role of occupational factors in young patients. Differences in the molecular subtype of tumors were found in these age groups with a predominance of urothelium-like subtype A among young patients, which leads to a more favorable prognosis of the disease and a lower rate of recurrence in individuals under 20 years of age. The main method of treatment of these neoplasms in both age groups remains transurethral resection of the bladder (TURMP), which allows radical removal of the tumor. Adjuvant treatment involving intra – bubble or systemic chemo-or immunotherapy in the postoperative period is indicated when detecting tumors with a high malignant potential, due to the risk of its metastasis and the high probability of the need for organ-carrying surgery. In clinical practice, recommendations developed for the treatment of cancer patients in the older age group are used, since there are no special guidelines for the diagnosis, treatment, and follow-up of younger patients. Conclusions. The development of methods for the timely diagnosis, treatment and Rehabilitation of children's patients with verified bladder tumors by representatives of the medical community (oncologists, oncologists, pediatricians) remains an urgent task in the near future.

Thymic carcinoma metastasize to the small intestine: a case report

BackgroundThymic carcinoma is a rare mediastinal neoplasm with a high malignant potential. It often shows pleural invasion and distant metastasis. The metastasis of thymic carcinoma to the small intestine is rarely reported and difficult to distinguish from other gastrointestinal tract tumors.Case presentationAn elderly man presented with lower abdominal pain for 2 months. Abdominal CT showed a mass communicated with the small intestinal lumen. After radical resection of the small intestinal tumor, resected specimens showed moderately differentiated squamous-cell carcinoma with lymph nodes metastases. The patient received chest CT and was found to have a mass in anterior mediastinum. Biopsies of the mass revealed thymic squamous-cell carcinoma.ConclusionsWe highlighted the metastasis of thymic carcinoma to the small intestine is rare and easily misdiagnosed. In patients with a mass communicated with the small intestinal lumen, a suspicion of thymic carcinoma metastasis should not be overlooked and we should make accurate differential diagnosis from the other small intestinal tumors.

Lipoma or Liposarcoma? Robotic Resection of a Retroperitoneal Mass

Study Objective Demonstrate robotic-assisted resection of a large retroperitoneal lipomatous mass. Design Surgical video Setting Tertiary-care operating room using DaVinci Xi system with four 8 mm trocars, and a 12 mm assistant port. Patients or Participants A 48-year-old female with a multi-fibroid uterus and seven centimeter lipomatous mass in her right hemipelvis Interventions The patient underwent robotic-assisted excision of the right retroperitoneal mass, total hysterectomy, right salpingo-oophorectomy, left salpingectomy, and cystoscopy. Measurements and Main Results Although superficial lipomas are common and most likely benign, retroperitoneal lipomatous tumors are rare. Tumors greater than ten centimeters have a higher malignant potential and are typically found in the deep retroperitoneal space. Robotic-assisted laparoscopy revealed a large lipomatous mass in the right retroperitoneal space consistent with radiographic imaging. The surgeon divided the round ligament and extended the incision parallel to the infundibulopelvic ligament to enter the right retroperitoneum. He then carefully dissected and resected the lipomatous tumor from the pararectal space and performed the remainder of the procedures without complication. Benign lipomas and low grade liposarcoma are difficult to differentiate. The latter has a high rate of local recurrence if incompletely resected, therefore complete resection should be the surgical goal. Pathology revealed partially encapsulated mature adipose tissue consistent with lipoma with negative fluorescent in situ hybridization (FISH) analysis using a dual color MDM2/CEN12 probe set confirming the likely benign behavior of the mass. Conclusion Retroperitoneal lipomatous tumors are rare. Distinguishing between lipomas and liposarcomas is a diagnostic challenge both radiographically and intraoperatively. Confirmatory histopathology, and often molecular pathology, is necessary for the final diagnosis. Knowledge of the pathology of retroperitoneal lipomatous masses and the related surgical anatomy and goals are imperative to optimal management.

Thyroid paraganglioma accompanied by lymph node metastasis or trachea invasion: A case report.

Thyroid paraganglioma (TP) is an uncommon neuroendocrine tumor with potential for misdiagnosis. Case 1 (male; 44 years old) presented with hoarseness for 3 months. A 2.5-cm gray nodule in the left thyroid was diagnosed as TP by immunohistochemistry. Lymph node metastasis was confirmed by H&E staining and immunohistochemistry. The patient was followed-up for 3 years without any signs of recurrence or metastasis. Case 2 (female; 39 years old) presented with an asymptomatic but rapidly growing thyroid nodule. The patient underwent thyroidectomy 8 years ago (2008) and was diagnosed with TP postoperatively. The patient was diagnosed with recurrence and exhibited trachea invasion. Thyroidectomy and partial trachea resection were performed. A literature review revealed that 62 other cases of TP have been reported, and most of them exhibited low malignant potential. However, the two cases presented in the current case report exhibited a high malignant potential, accompanied by lymph node metastasis or trachea invasion, and these features imply that the choice of treatment for patients should be based on their different degrees of malignancy.

Circulating extracellular vesicle-encapsulated microRNA as screening biomarkers for intraductal papillary mucinous neoplasm.

Since intraductal papillary mucinous neoplasms (IPMNs) occasionally contain pancreatic malignancies, it is vital to develop a screening program that can detect IPMNs in the general population and that can identify IPMNs with high malignant potential. The present study investigated whether microRNAs (miRNAs/miRs) in the blood may be diagnostic markers for IPMN screening. Initially, extracellular vesicle-encapsulated miRNAs (EV-miRNAs) in the serum with altered expression between IPMN, IPMN-derived carcinoma (IPMC) and control samples, were identified using microarray analysis. To validate the microarray results, the expression levels of selected EV-miRNAs were detected. Briefly, serum EV-miRNAs were extracted from 38 patients with IPMN (11 patients with IPMC and 27 patients with benign IPMN) and 21 non-tumor controls. The results of the microarray analysis revealed that the expression levels of EV-miR-22-3p, EV-miR-4539 and EV-miR-6132 were higher in the IPMN and IPMC serum samples compared with those in the control samples. With regards to discriminating IPMNs from controls, only miR-4539 exhibited a significant difference (P=0.004). In the comparison between IPMN and IPMC, carcinogenic antigen 19-9 (CA19-9) and EV-miR-6132 exhibited significant differences (P=0.01 and P=0.007, respectively). Receiver operating characteristic (ROC) curve analysis demonstrated that EV-miR-4539 could discriminate patients with IPMNs from control patients, with an area under the curve (AUC) of 0.72. Additionally, ROC analysis indicated that the markers could discriminate patients with IPMC from benign IPMN, with AUC values of 0.77 for EV-miR-6132 and 0.74 for CA19-9. In conclusion, the present study suggested that EV-miRNAs may be used as diagnostic markers for the detection of IPMNs in the general population as well as for identifying IPMNs with high malignant potential.

Mixed epithelial endocrine neoplasms of the colon and rectum - An evolution over time: A systematic review.

BACKGROUNDMixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIMTo provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases.METHODSA comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms [“mixed tumors colon” OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis.RESULTSIn total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified proposal for a new, simple, clinically relevant, non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms (MEENs).CONCLUSIONMEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high, intermediate or low grade malignant potential. This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.

PROLIFERATIVE VERRUCOUS LEUKOPLAKIA: A CASE REPORT

Proliferative verrucous leukoplakia (LVP) is a rare type of oral leukoplakia with slow growth and high potential for malignancy, with female predilection in the sixth decade of life. The aim of this report is to describe the clinical and histopathologic findings of a case of LVP. A 52-year-old male patient, an alcoholic since 12 years old, sought the health service because of an asymptomatic lesion with a 1-year evolution. The intraoral examination revealed multiple bilateral whitish plates with clear borders and verrucous surface located in jugal mucosa and labial commissure. The initial diagnostic hypothesis was verrucous carcinoma. An incisional biopsy was performed, and the histologic slices revealed fragments of mucosa coated by hyperkeratinized squamous epithelium with a verrucous surface corresponding to LVP. The patient is stable and under follow-up. The importance of early diagnosis and routine follow-up of patients because of the high rates of malignant transformation is emphasized.

The SLAMF3 rs509749 polymorphism correlates with malignant potential in multiple myeloma

The signaling lymphocytic activation molecule family 3 (SLAMF3) is highly expressed on plasma cells from patients with multiple myeloma (MM) and induces high malignant potential by ERK signaling mediated via the interaction with adaptor proteins SHP2 and GRB2. This study focused on the single-nucleotide polymorphism (SNP) of the SLAMF3 gene (rs509749, 1804A>G, M602V) in MM. The SNP G allele was a major type, and the frequencies of the GG, GA, and AA genotypes were 61.8%, 29.4%, and 8.8%, respectively, in patients with MM, which was almost the same as in healthy the control group in the Japanese population. Interestingly, patients with GG genotypes had significantly shorter overall survival times than patients with GA/AA genotypes. Consistent with those results, SLAMF3-overexpressing KMS-34 cells with the G allele (V602) had higher cell proliferation potential and were more resistant to anti-MM agents than those with the A allele (M602). When those cells were subcutaneously inoculated into NOG mice, tumor sizes in mice receiving V602 cells rapidly increased, and survival was significantly shorter than in mice injected with M602 cells. Furthermore, SLAMF3 V602 molecules bound more tightly to SHP2 and GRB2, with increased SHP2 and ERK phosphorylation compared with M602 cells. The mRNA expression of cell cycle-related genes (CCND1 and CCNE1) and anti-apoptotic genes (BCL2L and p21) was increased in V602 cells compared with M602 cells. The results thus suggested that the G allele of SLAMF3 SNP rs509749 may be associated with MM disease progression.

Impact of Knowledge and Risk Perceptions on Older Adults' Intention for Surveillance Colonoscopy.

The authors aimed to characterize older adults' intentions for future surveillance colonoscopy, knowledge of polyps, and predictors of colonoscopy plans. Guidelines recommend that the decision to continue or stop surveillance colonoscopy in older adults with colon polyps be "individualized." Although older adults want to be included in decision making, how knowledge regarding polyps influences decisions is unknown. In collaboration with a rural family medicine practice, the authors invited adults aged 65 years and older with a history of colon adenomas to complete a 14-item survey regarding intention for colonoscopy and knowledge of colon polyps. Sixty-seven of 105 (63%) patients completed the survey. The mean age was 72 years. Regarding future surveillance, 53% planned to return, 25% were unsure, and 22% did not plan to return. There were no significant differences in baseline characteristics on the basis of the intention for future colonoscopy. Regarding polyp knowledge, 73% had correct knowledge around how common polyps are; 50% thought that more than half of untreated polyps would become cancerous-an inaccurately elevated perception by 10 folds. Respondents who perceived polyps to have a high malignant potential were more likely to report plans for surveillance colonoscopy (68% vs. 39%; P=0.03). In this survey of older adults with a history of polyps, many had a falsely elevated perception of polyps' potential for cancer that was associated with a higher intention for future colonoscopy. Ensuring older adults have an understanding of the risks of polyps is an essential step toward improving decision making around surveillance colonoscopy.