Atypical Grade Research Articles

Characterization and comparison of genomic profiles between primary cancer cell lines and parent atypical meningioma tumors

BackgroundMeningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas.MethodsWe evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor.ResultsOur results were consistent with earlier studies that reported mutations in NF2, SMO, and AKT1 genes in atypical meningiomas, and we also observed mutations in MYBL2, a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient.ConclusionOur results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.

Incorporation of dermoscopy improves inter-observer agreement among dermatopathologists in histologic assessment of melanocytic neoplasms.

Histopathologic assessment of melanocytic neoplasms is the current gold standard of diagnosis. However, there are well recognized limitations including inter-observer diagnostic discordance. This study aimed to determine if integrating dermoscopy with histopathology of melanocytic neoplasms impacts diagnosis and improves inter-observer agreement. We conducted a prospective cohort study in a pigmented lesion clinic. Consecutive melanocytic lesions were identified for biopsy based on atypical gross or dermoscopic features. Standardized immunohistochemistry and levels were ordered on each specimen. The cases were randomized. Three dermatopathologists blinded to the clinical impression assessed each lesion. The cases were then re-randomized and re-assessed with addition of gross clinical and dermoscopic images. Inter-rater reliability (IRR) using Fleiss' kappa statistic revealed an increase from 0.447 without to 0.496 with dermoscopy amongst all dermatopathologists. The kappa increased from 0.495 before to 0.511 with dermoscopy in separating high-grade atypia or melanoma from moderate atypia or less. In 16 of 136 cases, at least 2 of 3 dermatopathologists favored a diagnosis of melanoma only after dermoscopy. In total, the consensus grade of atypia changed in 24.3% (33/ 136) of cases thereby representing changes to excisional margins and patient follow up. This study is limited by the cohort size. Dermoscopy significantly impacts diagnosis and improves identification of early melanomas in high risk populations and improves inter-observer agreement.

How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression.

Intestinal-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas is clinicopathologically distinctive. Our research aimed to elucidate the molecular mechanism of the development and progression of the intestinal-type IPMN. In 60 intestinal-type IPMN specimens, histological transitions from gastric-type epithelia to intestinal-type epithelia were observed in 48 cases (80%). CDX2/MUC2/alcian blue triple staining indicated that CDX2 appeared to precede MUC2 expression and subsequent alcian blue-positive mucin production. Expression of p21 and Ki-67 seemed to be accelerated by CDX2 expression (p = 6.02e-13 and p = 3.1e-09, respectively). p21/Ki-67 double staining revealed that p21 was mostly expressed in differentiated cells in the apex of papillae, while Ki-67 was expressed in proliferative cells in the base of papillae. This clear cellular arrangement seemed to break down with the progression of atypical grade and development of invasion (p = 0.00197). Intestinal-type IPMNs harbored frequent GNAS mutations (100%, 25/25) and RNF43 mutations (57%, 8/14) and shared identical GNAS and KRAS mutations with concurrent gastric-type IPMNs or incipient gastric-type neoplasia (100%, 25/25). RNF43 mutations showed emerging or being selected in intestinal-type neoplasms along with ß-catenin aberration. Activation of protein kinase A and extracellular-regulated kinase was observed in CDX2-positive intestinal-type neoplasm. These results suggest that gastric-type epithelia that acquire GNAS mutations together with induction of intrinsic CDX2 expression may evolve with clonal selection and additional molecular aberrations including RNF43 and ß-catenin into intestinal-type IPMNs, which may further progress with complex villous growth due to disoriented cell cycle regulation, acceleration of atypical grade, and advance to show an invasive phenotype.

Use of Cytology in the Diagnosis of Basal Cell Carcinoma Subtypes.

Background: Basal cell carcinoma (BCC) is the most common skin cancer in the white population. Nonsurgical treatments are first-line alternatives in superficial BCC (sBCC); therefore, differentiating between sBCC and non-sBCC is of major relevance for the clinician. Scraping cytology possesses several advantages, such as an earlier diagnosis and scarring absence, in comparison to a biopsy. Nevertheless, previous studies reported difficulties in differentiating the different BCC subtypes. The objective of this study was to determine the capability and accuracy of scraping cytology to differentiate between sBCC and non-sBCC. Methods: In this retrospective study, cytological samples of histologically confirmed BCC were examined. Select cytological features were correlated to BCC subtypes (sBCC or non-sBCC). Results: A total of 84 BCC samples were included (29 sBCC; 55 non-sBCC). An inverse correlation between the diagnosis of sBCC and the presence of mucin, dehiscence, and grade of atypia in the basal cells was observed. The presence of medium and large basal cell clusters correlated directly to a sBCC diagnosis. The presence of clear cells is strongly associated with sBCC. Therefore, Conclusion: Scraping cytology is reliable in differentiating sBCC from other BCC subtypes.

Molecular characteristics of meningiomas

Meningioma is the most common primary intracranial tumor in adults. The grading of meningioma is based on World Health Organization criteria, which rely on histopathological features alone. This grading system is unable to conclusively predict the clinical behavior of these tumors (i.e., recurrence or prognosis in benign or atypical grades). Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that can predict tumor behavior. This review summarizes the molecular characteristics of meningioma using genetic and epigenetic biomarkers. Molecular alterations that can predict meningioma behavior may be integrated into the upcoming World Health Organization grading system.

Ki67 labeling in CNS tumours

A study of Ki67 Labeling Index (LI) by immunohistochemistry was carried out in 47 CNS neoplasms. Astrocytic and oligodendroglial tumours were the most common group with glioblastoma, NOS and diffuse astrocytoma, NOS Grade II predominating. Ki67 LI of diffuse astrocytomas varied from 0.72 to 13.9% with a mean of 4.36%. In glioblastomas the Ki67 LIs varied from 5.96 to 22.4% with a mean of 12.3% which was comparable with various studies. 1 pleomorphic xanthoastrocytoma was reclassified as anaplastic type based on a high LI of 21.66%. All histological variants of ependymomas showed uniformly low Ki67 LIs. Grade I meningiomas show ed a mean Ki67 LI of 2.22% for benign, 5.85% for atypical Grade II and 30% in the anaplastic Grade III meningioma. Choroid plexus carcinoma and Non Hodgkins lymphomas showed very Ki67 LIs from 60 to 91%. The findings correlated well with WHO CNS tumour grade and helped to identify histologically defined lower grade tumours with potential for recurrence and progression. Keywords: CNS neoplasms, Gliomas, Proliferation markers, Ki67.

Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium

Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium

Knowledge gaps in the appendix: a multi-institutional study from seven academic centers

Appendix pathology represents uncommonly encountered specimens with unique diagnostic challenges. To delineate common knowledge gaps, extramural consults submitted to seven institutions between 2016–2017 were reviewed. All appendix consults were resections (100%, n = 43), and the majority were directed for consultation by the originating pathologist (95%, n = 41) with no additional studies performed by the consultant (65%, n = 28). This study was dominated by inquiries related to low grade appendiceal mucinous neoplasms (44%, n = 19) and goblet cell carcinoid related neoplasms (19%, n = 8). Of the 43 appendiceal consults, 19 were submitted by the contributing pathologist as low grade appendiceal mucinous neoplasm, but only half of these were diagnosed by the consultant as such (n = 9). Low grade appendiceal mucinous neoplasm-related consultation themes included diverticular disease, criteria for invasion, high grade atypia, extra-appendiceal mucin, and staging. Examples of major disagreements that were downgraded included consults submitted as low grade appendiceal mucinous neoplasm and diagnosed by the consultant as serrated polyp (n = 3), appendicitis (n = 1), and benign appendix (n = 1). Examples of major disagreements-upgraded included cases submitted as low grade appendiceal mucinous neoplasm and diagnosed by the consultant as low grade appendiceal mucinous neoplasm with high-risk features (n = 2) and mucinous adenocarcinoma (n = 2). One case contained both a major disagreement-upgrade (low grade appendiceal mucinous neoplasm changed to high grade appendiceal mucinous neoplasm) and a major disagreement-downgrade (pT3 changed to Tis). Of the 15 cases diagnosed by the consultants as low grade appendiceal mucinous neoplasm, submitted diagnoses included low grade appendiceal mucinous neoplasm (n = 9), adenocarcinoma (n = 5), and one case was submitted without a diagnosis. For goblet cell carcinoid-related consults, the usual inquiry related to distinguishing goblet cell carcinoid from goblet cell carcinoid with adenocarcinoma (adenocarcinoma ex-goblet cell carcinoid). Of the 38 overall consults with a submitted diagnosis, 53% (n = 20) were disagreements, and most of these were major disagreements-downgraded (n = 13).

Nuclear shape, architecture and orientation features from H&E images are able to predict recurrence in node-negative gastric adenocarcinoma

BackgroundIdentifying intestinal node-negative gastric adenocarcinoma (INGA) patients with high risk of recurrence could help perceive benefit of adjuvant therapy for INGA patients following surgical resection. This study evaluated whether the computer-extracted image features of nuclear shapes, texture, orientation, and tumor architecture on digital images of hematoxylin and eosin stained tissue, could help to predict recurrence in INGA patients.MethodsA tissue microarrays cohort of 160 retrospectively INGA cases were digitally scanned, and randomly selected as training cohort (D1 = 60), validation cohort (D2 = 100 and D3 = 100, D2 and D3 are different tumor TMA spots from the same patient), accompanied with immunohistochemistry data cohort (D3′ = 100, a duplicate cohort of D3) and negative controls data cohort (D5 = 100, normal adjacent tissues). After nuclear segmentation by watershed-based method, 189 local nuclear features were captured on each TMA core and the top 5 features were selected by Wilcoxon rank sum test within D1. A morphometric-based image classifier (NGAHIC) was composed across the discriminative features and predicted the recurrence in INGA on D2. The intra-tumor heterogeneity was assessed on D3. Manual nuclear atypia grading was conducted on D1 and D2 by two pathologists. The expression of HER2 and Ki67 were detected by immunohistochemistry on D3 and D3′, respectively. The association between manual grading and INGA outcome was analysis.ResultsIndependent validation results showed the NGAHIC achieved an AUC of 0.76 for recurrence prediction. NGAHIC-positive patients had poorer overall survival (P = 0.017) by univariate survival analysis. Multivariate survival analysis, controlling for T-stage, histology stage, invasion depth, demonstrated NGAHIC-positive was a reproducible prognostic factor for poorer disease-specific survival (HR = 17.24, 95% CI 3.93–75.60, P < 0.001). In contrast, human grading was only prognostic for one reader on D2. Moreover, significant correlations were observed between NGAHIC-positive patients and positivity of HER2 and Ki67 labeling index.ConclusionsThe NGAHIC could provide precision oncology, personalized cancer management.

Long-term efficacy of a new medical device containing Fernblock® and DNA repair enzyme complex in the treatment and prevention of cancerization field in patients with actinic keratosis.

Actinic keratosis (AKs) are part of the cancerization field, a region adjacent to AKs containing subclinical and histologically abnormal epidermal tissue due to Ultraviolet (UV)-induced DNA damage. The photoproducts as consequence of DNA damage induced by UV are mainly cyclobutane pyrimidine dimers (CPDs). Fernblock® demonstrated in previous studies significant reduction of the number of CPDs induced by UV radiation. Photolyases are a specific group of enzymes that remove the major UV-induced DNA lesions by a mechanism called photo-reactivation. A monocentric, prospective, controlled, and double blind interventional study was performed to evaluate the effect of a new medical device (NMD) containing a DNA-repair enzyme complex (photolyases, endonucleases and glycosilases), a combination of UV-filters, and Fernblock® in the treatment of the cancerization field in 30 AK patients after photodynamic therapy. Patients were randomized into two groups: patients receiving a standard sunscreen (SS) andpatients receiving the NMD. Clinical, dermoscopic, reflectance confocal microscopy (RCM) and histological evaluations were performed. An increase of AKs was noted in all groups after three months of PDT without significant differences between them (p=0.476). A significant increase in the number of AKs was observed in SS group after six (p=0.026) and twelve months of PDT (p=0.038); however, this increase did not reach statistical significance in the NMD group. Regarding RCM evaluation, honeycomb pattern assessment after twelve months of PDT showed significant differences in the extension and grade of the atypia in the NMD group compared to SS group (p=0.030 and p=0.026, respectively). Concerning histopathological evaluation, keratinocyte atypia grade improved from baseline to six months after PDT in all the groups, with no statistically significant differences between the groups. Twelve months after PDT, p53 expression was significantly lower in the NMD group compared to SS group (p=0.028). The product was well-tolerated, with no serious adverse events reported. Our results provide evidence of the utility of this NMD in the improvement of the cancerization field and in the prevention of the development of new AKs.&#x0D;

Long-Term Efficacy of a New Medical Device Containing Fernblock® and DNA Repair Enzyme Complex in the Treatment and Prevention of Cancerization Field in Patients with Actinic Keratosis

Introduction: Actinic keratosis (AKs) are part of the cancerization field, a region adjacent to AKs containing subclinical and histologically abnormal epidermal tissue due to Ultraviolet (UV)-induced DNA damage. The photoproducts, “as consequence of DNA damage induced by UV”, are mainly cyclobutane pyrimidine dimers (CPDs). Fernblock® demonstrated in previous studies significant reduction of the number of CPDs induced by UV radiation. Photolyases are a specific group of enzymes that remove the major UV-induced DNA lesions by a mechanism called photo-reactivation. Methods: A monocentric, prospective, controlled, and double blind interventional study was performed to evaluate the effect of a new medical device (NMD) containing a DNA-repair enzyme complex (photolyases, endonucleases and glycosilases), a combination of UV-filters, and Fernblock® in the treatment of the cancerization field in 30 AK patients after photodynamic therapy (PDT). Patients were randomized into two groups: patients receiving a standard sunscreen (SS) and patients receiving the NMD. Clinical, dermoscopic, reflectance confocal microscopy (RCM) and histological evaluations were performed. Results: An increase of AKs was noted in all groups after three months of PDT without significant differences between them (p=0.476). A significant increase in the number of AKs was observed in SS group after six (p=0.026) and twelve months of PDT (p=0.038); however, this increase did not reach statistical significance in the NMD group. Regarding RCM evaluation, honeycomb pattern assessment after twelve months of PDT showed significant differences in the extension and grade of the atypia in the NMD group compared to SS group (p=0.030 and p=0.026, respectively). Concerning histopathological evaluation, keratinocyte atypia grade improved from baseline to six months after PDT in all the groups, with no statistically significant differences between the groups. Twelve months after PDT, p53 expression was significantly lower in the NMD group compared to SS group (p=0.028). The product was well-tolerated, with no serious adverse events reported. Conclusion: Our results provide evidence of the utility of this NMD in the improvement of the cancerization field and in the prevention of the development of new AKs.

Endoscopic and clinicopathological features of intramucosal, histologically mixed-type, low-grade, well-differentiated gastric tubular adenocarcinoma with the potential for late-onset lymph node metastasis

BackgroundIntramucosal, histologically mixed-type, low-grade (LG), well-differentiated gastric tubular adenocarcinomas (tub1s; LG-tub1s) have larger mean diameters and exhibit a higher frequency of the gastric mucin phenotype (G-phenotype) than pure LG-tub1s. In proportion to their increases in diameter, G-phenotype differentiated-type early gastric cancer (EGC) tumours reportedly grow to eventually contain (an) undifferentiated-type component(s) and LG-tub1s, which are included in differentiated-type EGCs, reportedly exhibit changes in their glandular architectural and cytological atypia grades from LG to high-grade (HG) and can grow to contain a moderately differentiated tubular adenocarcinoma (tub2) component and undifferentiated components. Because they generally show a higher frequency of malignancy relative to tumours with a higher atypia grade and lower differentiation degree, it is suggested that, among mixed-type LG-tub1s, G-phenotype LG-tub1s containing an HG-tub2 component (LG-tub1s > HG-tub2) with undifferentiated components might lead to late-onset metastasis to lymph nodes even after a successful endoscopic submucosal dissection (ESD). We aimed to clarify the endoscopic and clinicopathological features of these G-phenotype LG-tub1s > HG-tub2.MethodsOf the 13,217 oesophagogastroduodenoscopies performed at our institutions between September 2008 and March 2016, 185 EGC lesions were evaluated in this retrospective observational study. Among these EGC lesions, 60 intramucosal LG-tub1s were divided into 53 tub1 (44 pure LG-tub1s and nine LG-tub1s containing HG-tub1) lesions and seven LG-tub1 > tub2 (LG-tub1 containing LG- and HG-tub2) lesions.ResultsThe frequencies of the superficial depressed type (P = 0.026), reddish colour (P = 0.006), HG of contained tub2s (P = 0.006), and G-phenotype (P = 0.028) were significantly higher in the LG-tub1 > tub2 group than those in the tub1 group. However, the largest lesion of the LG-tub1 > tub2 group had a superficial flat appearance, an isochromatic colour, an HG-tub2 and an undifferentiated component, and a large diameter greater than 30 mm, and it exhibited a G-phenotype.ConclusionsIntramucosal G-phenotype LG-tub1s > HG-tub2 are potential premalignant stomach neoplasms that may have specific endoscopic and clinicopathological features. However, G-phenotype LG-tub1s > HG-tub2 with undifferentiated component, which potentially show higher malignancy than those without undifferentiated components might change from a reddish to isochromatic colour. Accurately diagnosing, treating, and following-up G-phenotype LG-tub1s > HG-tub2 might decrease the number of patients who experience late-onset metastasis after ESD.

Subtyping of IPMN.

Intraductal papillary mucinous neoplasms (IPMNs) characteristically consist of mucin-filled dilated ducts lined with neoplastic cells forming papillae with a diverse range of morphologies and varying grades of atypia. Based on morphological characteristics and immunohistochemical reaction against mucin proteins, IPMNs are classified into four distinct subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. In this chapter, histomorphological criteria and techniques of immunohistochemical staining and its evaluation for subtyping IPMNs are described.

Papillary lesions of the breast

Papillary lesions of the breast comprise a heterogeneous group. These lesions are characterised by the presence of papillary projections of variable length and thickness composed of central fibrovascular cores covered by epithelium. The distinction among intraductal papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), papillary DCIS, and papillary carcinoma can be challenging. An assessment of the presence and distribution of myoepithelial cells in the lesion is one of the most helpful features in arriving at the correct diagnosis. Benign intraductal papillomas and papillomas with atypia (ADH or DCIS) have myoepithelial cells both within and surrounding the involved space. Papillary DCIS and papillary carcinomas lack myoepithelial cells within the papillary proliferation; DCIS retains a myoepithelial cell layer at the periphery and encapsulated and solid papillary carcinomas may lack a peripheral myoepithelial cell layer. Evaluation of the epithelial component is the next step. Benign papillomas have an epithelial component that is heterogeneous with variability in nuclear size, shape and cell placement. Atypia and/or carcinoma usually manifest as a monomorphic proliferation of epithelial cells with low nuclear grade atypia and areas of polarisation. Morphological features and use of adjunctive immunostains to guide diagnosis will be discussed.

Targeted therapies for the treatment of patients with advanced, recurrent or relapsed thymic epithelial tumours

Thymic epithelial tumours (TETs) are rare neoplasms of the anterior mediastinum with a reported incidence of 0.15 per million person-year in the United States (1). They are classified into thymomas and thymic carcinomas on the basis of morphological features, the grade of atypia of epithelial cells and their relative proportion to lymphocytes.

The diffusing capacity of the lung for carbon monoxide is associated with the histopathological aggressiveness of lung adenocarcinoma†

The diffusing capacity of the lung for carbon monoxide (DLCO) is an indicator of lung damage. We sought to determine whether DLCO is associated with the aggressiveness of lung adenocarcinoma using histopathological indexes, such as tumour differentiation, scar grade, nuclear atypia and the mitotic index. Fifty-seven patients with low DLCO (≤80% of predicted) and 466 patients with normal DLCO (>80% of predicted) who underwent R0 resection of lung adenocarcinoma between 2005 and 2012 were retrospectively reviewed. The relationships between the DLCO status and each histopathological index as well as the overall survival were evaluated. Low DLCO had significant relationships with moderate/poor differentiation (79% vs 57% [low DLCO vs normal DLCO]), scar grade 3/4 (37% vs 18%), nuclear atypia 3 (65% vs 30%) and the mitotic index 3 (26% vs 8%). After adjusting for the age, sex, forced expiratory volume in 1 s, smoking status and tumour size, a low DLCO still showed a significant correlation with the histopathological indexes. These histopathological indexes were all significant factors for the overall survival on log-rank tests. In a multivariable Cox regression analysis with 13 clinicopathological variables, moderate/poor differentiation and nuclear atypia Grade 3 were significant histopathological factors for the overall survival (hazard ratios: 2.16 and 1.84; 95% confidence intervals: 1.10-4.51 and 1.06-3.21; P = 0.024 and 0.029, respectively). Our findings regarding the relationship between DLCO and the histopathological indexes of lung adenocarcinoma suggest that lung damage may be associated with carcinogenesis and progression.

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors).

ObjectiveEpithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors.Materials and methodsAmong duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO) 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands.ResultsAs for patient characteristics, there were 76 men (75.2%) and 25 women (24.8%), with a median age of 65 years (range, 34 to 84). The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1%) and gastric-type tumors (12 lesions, 10.9%). Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7%) and tubulovillous-type tumors (7 lesions, 6.4%). Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7%) and pyloric gland-type (PG) tumors (9 lesions, 8.2%). The grade of atypia was significantly higher in gastric-type tumors (p<0.01). PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands.ConclusionsAbout 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

Long-term follow-up study of gastric adenoma; tumor-associated macrophages are associated to carcinoma development in gastric adenoma.

Some gastric adenomas may progress to adenocarcinoma in a short time, but others remain as adenoma for a long time. Among 1138 cases diagnosed as adenoma by biopsy at Kure Medical Association Hospital between 1990 and 2010, 51 adenomas were enrolled. Of these, 28 adenomas (group A) were followed for 60months or longer with no progression to adenocarcinoma within 60months, and the other 23 adenomas (group B) were upgraded to carcinoma by consecutive biopsies performed within 1year after the first biopsy. These adenomas were compared clinicopathologically and immunohistochemically. Macroscopically, the mean size of group B adenomas was significantly larger than that of group A adenomas (18.6 vs. 9.9mm) at the first biopsy. The frequency of a depressed area in the adenoma was significantly higher in group B than group A. Microscopically none of group A but 7 (30.4%) of 23 group B adenomas showed severe atypia. Each of a highly proliferative gland measured by Ki-67 labeling, cellular atypical grade, gastric phenotype defined by MUC5AC and MUC6 and CD204-positive tumor-associated macrophage (TAM) was a significant risk factor for adenocarcinoma development in gastric adenoma by univariate analysis. Only moderate or severe atypia of adenoma cells and the TAM number in the stroma of adenomas were independent risk factors by multivariate analysis. As independent risk factors, cellular atypia may reconfirm the importance of morphological analysis, and the TAM number may indicate the significance of TAM function in gastric adenoma.

Melanomas vs. nevi in high‐risk patients under long‐term monitoring with digital dermatoscopy: do melanomas and nevi already differ at baseline?

What lesions to select for a most efficient dermatoscopic monitoring of patients with multiple nevi remains an unresolved issue. To compare the grade of atypia of melanomas and nevi of the same patient at baseline. Prospective observational study using 236 dermatoscopic baseline images (59 quartets from 59 patients, each including one melanoma detected during follow-up and three nevi). Dermatologists (n = 26) were asked to assess the 'grade of dermatoscopic atypia' on a numerical scale and to identify the melanomas. On average, each dermatologist identified 24 of 59 melanomas (40%, range: 11-37). The number of correct picks was greater for dermatologists with moderate (mean: 28) or high (mean: 28) experience compared to beginners (mean 17; P < 0.001). In three of the 59 sets, none of the 26 dermatologists identified the melanoma. The mean grade of dermatoscopic atypia was 2.5 for nevi (95% CI: 2.4-2.6) and 3.0 for melanomas (95% CI: 2.9-3.1, P < 0.001). Rating dermatologists were informed that each quartet of images included one melanoma creating substantial deviation from a real-life situation. A significant proportion of melanomas detected during follow-up cannot be differentiated from nevi at baseline. This necessitates the additional inclusion of less atypical lesions for monitoring.

Endovaskularna priprema za delikatnu operaciju meningeoma - prikaz slučaja

Introduction: Embolization prior to surgery can make tumor resection less complicated by reducing blood loss during surgery and shortening the time of the operation. Case report: In this paper, we presented a case of a sixty-three-year-old woman who was admitted to the Clinic of Neurosurgery, Clinical Center Niš, Serbia, at November 2016, after she underwent a CT brain scan that showed a large tumor of the left cerebellopontile angle. Digital subtraction angiography presented a large, highly vascularized tumor lesion that compressed the brain stem. The patient underwent endovascular procedure, and complete embolization of the tumor vessels was established. The radiologist delivered embolization material via the left ascending pharyngeal artery. In the next 24 hours, an operation was performed i.e. radical extirpation surgery (Simpson grade I). Postoperatively, the patient's GCS was 15, with no new neurological deficit. Postoperative brain CT scan showed neither rest tumor nor blood clot inside the tumor bed. Pathohistological finding revealed atypical meningioma grade II. Conclusion: Despite some clinicians' dilemma considering the utility of preoperative embolization of meningioma vessels, we believe that a team of educated and dedicated radiologist and neurosurgeon could achieve great results in resection of large and inaccessible cranial tumors.