Hepatic perivascular epithelioid cell tumors:Benign,malignant,and uncertain malignant potential

In 2013,the World Health Organization defined perivascular epithelioid cell tumor(PEComa)as“a mesenchymal tumor which shows a local association with vessel walls and usually expresses melanocyte and smooth muscle markers.”This generic definition seems to better fit the PEComa family,which includes angiomyolipoma,clear cell sugar tumor of the lung,lymphangioleiomyomatosis,and a group of histologically and immunophenotypically similar tumors that include primary extrapulmonary sugar tumor and clear cell myomelanocytic tumor.Clear cell tumors with this immunophenotypic pattern have also had their malignant variants described.When localizing to the liver,preoperative radiological diagnosis has proven to be very difficult,and most patients have been diagnosed with hepatocellular carcinoma,focal nodular hyperplasia,hemangioma,or hepatic adenoma based on imaging findings.Examples of a malignant variant of the liver have been described.Finally,reports of malignant variants of these lesions have increased in recent years.Therefore,we support the use of the Folpe criteria,which in 2005 established the criteria for categorizing a PEComa as benign,malignant,or of uncertain malignant potential.Although they are not considered ideal,they currently seem to be the best approach and could be used for the categorization of liver tumors.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential

BACKGROUND Up until now,no research has been reported on the association between the cli-nical growth rate of multilocular cystic renal neoplasm of low malignant potential(MCRNLMP)and computed tomography(CT)imaging characteristics.Our study sought to examine the correlation between them,with the objective of distin-guishing unique features of MCRNLMP from renal cysts and exploring effective management strategies.AIM To investigate optimal management strategies of MCRNLMP.METHODS We retrospectively collected and analyzed data from 1520 patients,comprising 1444 with renal cysts and 76 with MCRNLMP,who underwent renal cyst decom-pression,radical nephrectomy,or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution.Detection of MC-RNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology.RESULTS Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP.Precisely,it comprises 1.48%of all cases involving simple renal cysts,5.26%of those with complex renal cysts,and a noteworthy 12.11%of renal tumors coexisting with renal cysts,indicating a statistically significant difference(P=0.001).Moreover,MCRNLMP constituted a significant 22.37%of the patient po-pulation whose cysts demonstrated a rapid growth rate of≥2.0 cm/year,whereas it only represented 0.66%among those with a growth rate below 2.0 cm/year.Of the 76 MCRNLMP cases studied,none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis.In the remaining 67 patients,who were actively monitored over a 3-year postoperative period,only one showed suspicious recurrence on CT scans.CONCLUSION MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators.In treating MCRNLMP,partial nephrectomy is preferred,while radical nephrectomy should be minimi-zed.After surgery,active monitoring is advisable to prevent unnecessary nephrectomy.

Preoperative prediction of malignant potential of 2-5 cm gastric gastrointestinal stromal tumors by computerized tomography-based radiomics

BACKGROUND The use of endoscopic surgery for treating gastrointestinal stromal tumors(GISTs)between 2 and 5 cm remains controversial considering the potential risk of metastasis and recurrence.Also,surgeons are facing great difficulties and challenges in assessing the malignant potential of 2-5 cm gastric GISTs.AIM To develop and evaluate computerized tomography(CT)-based radiomics for predicting the malignant potential of primary 2-5 cm gastric GISTs.METHODS A total of 103 patients with pathologically confirmed gastric GISTs between 2 and 5 cm were enrolled.The malignant potential was categorized into low grade and high grade according to postoperative pathology results.Preoperative CT images were reviewed by two radiologists.A radiological model was constructed by CT findings and clinical characteristics using logistic regression.Radiomic features were extracted from preoperative contrast-enhanced CT images in the arterial phase.The XGboost method was used to construct a radiomics model for the prediction of malignant potential.Nomogram was established by combing the radiomics score with CT findings.All of the models were developed in a training group(n=69)and evaluated in a test group(n=34).RESULTS The area under the curve(AUC)value of the radiological,radiomics,and nomogram models was 0.753(95%confidence interval[CI]:0.597-0.909),0.919(95%CI:0.828-1.000),and 0.916(95%CI:0.801-1.000)in the training group vs 0.642(95%CI:0.379-0.870),0.881(95%CI:0.772-0.990),and 0.894(95%CI:0.773-1.000)in the test group,respectively.The AUC of the nomogram model was significantly larger than that of the radiological model in both the training group(Z=2.795,P=0.0052)and test group(Z=2.785,P=0.0054).The decision curve of analysis showed that the nomogram model produced increased benefit across the entire risk threshold range.CONCLUSION Radiomics may be an effective tool to predict the malignant potential of 2-5 cm gastric GISTs and assist preoperative clinical decision making.

Stathmin destabilizing microtubule dynamics promotes malignant potential in cancer cells by epithelial-mesenchymal transition

BACKGROUND： Stathmin is a ubiquitous cytosolic regulatory phosphoprotein and is overexpressed in different human malignancies. The main physiological function of stathmin is to interfere with microtubule dynamics by promoting depolymerization of microtubules or by preventing polymerization of tubulin heterodimers. Stathmin plays important roles in regulating many cellular functions as a result of its microtubuledestabilizing activity. Currently, the critical roles of stathmin in cancer cells, as well as in lymphocytes have been valued. This review discusses stathmin and microtubule dynamics in cancer development, and hypothesizes their possible relationship with epithelial-mesenchymal transition（EMT）.DATA SOURCES： A PubMed search using such terms as ＂stathmin＂, ＂microtubule dynamics＂, ＂epithelial-mesenchymal transition＂, ＂EMT＂, ＂malignant potential＂ and ＂cancer＂ was performed to identify relevant studies published in English.More than 100 related articles were reviewed.RESULTS： The literature clearly documented the relationship between stathmin and its microtubule-destabilizing activity of cancer development. However, the particular mechanism is poorly understood. Microtubule disruption is essential for EMT, which is a crucial process during cancer development. As a microtubule-destabilizing protein, stathmin may promote malignant potential in cancer cells by initiating EMT.CONCLUSIONS： We propose that there is a stathminmicrotubule dynamics-EMT（S-M-E） axis during cancer development. By this axis, stathmin together with itsmicrotubule-destabilizing activity contributes to EMT, which stimulates the malignant potential in cancer cells.

Retroperitoneal Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): Case Report

Retro peritoneal smooth muscle tumors of uncertain malignant potential (STUMP) are rare and often misdiagnosed as leiomyosarcoma. We hereby report the case of a retroperitoneal STUMP diagnosed on a surgical specimen in a 44-year-old woman without any history of disease.

Betel quid chewing and oral potential malignant disorders and the impact of smoking and drinking:A meta-analysis

BACKGROUND Oral potential malignant disorders(OPMDs)are a precancerous condition of oral disease.Several studies have found that betel quid chewing,smoking and alcohol drinking might be the risk factors of OPMDs.But the relationships of them,especially their interaction are still inconclusive.AIM To evaluate the relationship between betel quid chewing and OPMDs and to explore the interaction of smoking and alcohol drinking on the relationship.METHODS We searched Pub Med,Web of Science,Embase and the Cochrane Library databases with items complete until January 2021 for relevant studies.The research data were extracted according to the inclusion criteria.The pooled odds ratios(ORs)and 95%confidence intervals(CIs)were used to evaluate the effect size.Subgroup analysis was performed to assess interactions between exposures and OPMDs.Relative excess risk of interaction(RERI)was used to estimate the size of interaction.RESULTS Nine articles were selected in the final meta-analysis.The results showed that betel quid chewing(pooled OR:8.70,95%CI:5.18-14.61),alcohol consumption(pooled OR:1.95,95%CI:1.5-2.55),and smoking(pooled OR:4.35,95%CI:3.06-6.2)could significantly increase the risk of OPMDs compared to individuals without these behaviors.Smoking and alcohol drinking synergistically increased the association between betel quid chewing and OPMDs(pooled OR;:14.38,95%CI:7.14-28.95;pooled OR;:11.12,95%CI:8.00-15.45,respectively).The RERI;and RERI;were 2.33 and 1.47,respectively.CONCLUSION The synergistic effects between smoking/drinking and betel quid highlights the importance of focusing on individuals with multiple exposures.Further study should be conducted to confirm these interactions.

Development and validation of a risk model for noninvasive detection of cancer in oral potentially malignant disorders using DNA image cytometry

Objective:To elucidate whether DNA aneuploidy was an independent discriminator for carcinoma within oral potentially malignant disorders(OPMDs),and further establish and validate a risk model based on DNA aneuploidy for the detection of oral cancer.Methods:A total of 810 consecutive patients with OPMD were prospectively enrolled from March 2013 to December 2018,and divided into a training set(n=608)and a test set(n=202).Brushing and biopsy samples from each patient were processed by DNADNA image cytometry and histopathological examination,respectively.Results:DNA aneuploidy of an outside DNA index≥3.5 in OPMD was an independent marker strongly associated with malignant risk[adjusted odds ratio:13.04;95%confidence interval(CI):5.46-31.14].In the training and test sets,the area under the curve(AUC)was 0.87(95%CI:0.82-0.91)and 0.77(95%CI:0.57-0.97),respectively,for detecting carcinoma in OPMD patients.The independent risk factors of lateral/ventral tongue and non-homogenous type combined with a risk model built with a multivariate logistic regression revealed a more favorable diagnostic efficacy associated with the training set(AUC:0.93;95%CI:0.91-0.96)and test set(AUC:0.94;95%CI:0.90-0.98).The sensitivity and specificity of carcinoma detection within OPMD was improved to 100%and 88.1%,respectively.Conclusions:This large-scale diagnostic study established a risk model based on DNA aneuploidy that consisted of a noninvasive strategy with lateral/ventral tongue and non-homogenous features.The results showed favorable diagnostic efficacy for detecting carcinoma within OPMD,irrespective of the clinical and pathological diagnoses of OPMD.Multicenter validation and longitudinal studies are warranted to evaluate community practices and clinical applications.

RELATIONSHIP BETWEEN PROLIFERATING CELL NUCLEARANTIGEN EXPRESSION AND ITS MALIGNANCY POTENTIAL IN COLORECTAL CARCINOMA

Objective: To study the relationship between proliferating cell nuclear antigen expression and its malignancy potential in colorectal carcinoma. Methods: Paraffin sections of 86 patients with advanced colorectal carcinoma were assessed by immunohistochemical study, using a mouse monoclonal antibody (pc-10, DAKO Co. USA) to check proliferating cell nuclear antigen (PCNA). To compare PCNA with conventional clinicopathologic factor, including p53 overexpression, tissue carcinoembnyonic antigen immunoreactivity pattern and flow cytometric DNA ploidy for assessing tumor malignancy potential. In addition, recurrence and survival of patients with advanced colorectal carcinoma after curative resection were analyzed in accordance with degree of PCNA expression. Results: PCNA-labeling index (PCNA-LI) increased significantly as the tumor stage advanced (p=0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P=0.0027), lymphatic invasion (P=0.0001), vascular invasion (P=0.0001), lymph node metastasis (P=0.0001), and liver metastasis (P=0.0036). Mean PCNA-LI was also significantly higher in tumor with DNA aneuploidy (P=0.0006) and negative (P=0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; Recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P<0.01), and three-year survival rates for curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P<0.005). Conclusion: There were correlations between PCNA-LI and various pathologic parameters, PCNA-LI increased significantly as the tumor stage advanced in colorectal carcinoma, the rates of recurrence and death got higher as PCNA-LI increased after curative resection for colorectal carcinoma.

The pathology of urinary bladder lesions with an inverted growth pattern

Inverted lesions in the urinary bladder have been the source of some difficulty in urological pathology. The two common ones are von Brunn＇s nests and cystitis cystic/cystitis glandularis, which are considered normal variants of urothelium. Apart from them, a number of other rare urothelial lesions with inverted growth pattern occur in the urinary bladder. Some of them are only reactive conditions, just as pseudocarcinomatous hyperplasia. Some are benign tumors, namely inverted papilloma. Whereas others are malignant neoplasms, including inverted papillary urothelial neoplasm of low malignant potential （PUNLMP）, non-invasive inverted papillary urothelial carcinoma （low-grade and high-grade）, and invasive urothelial carcinoma （inverted, nested and big nested variants）. Because of the overlapping morphological features of all the inverted lesions mentioned above, even between high-grade invasive carcinoma and psendoearcinomatous hyperplasia which are only a kind of reactive conditions, it is very important for the surgical pathologist to recognize and be familiar with these inverted lesions in urinary bladder. In this article, we review these spectrums of inverted lesions of the urinary bladder. Emphasis is placed on histogenesis, morphology, differential diagnosis of these lesions, and the pathologic grading of the non-invasive inverted neoplasms, such as inverted papilloma, inverted PUNLMP, non-invasive inverted papillary urothelial carcinoma with low-grade, and non-invasive inverted papillary urothelial carcinoma with high-grade.

Clinical characteristics and outcomes of patients with hepatic angiomyolipoma:A literature review

First reported in 1976,hepatic angiomyolipoma(HAML)is a rare mesenchymal liver tumor occurring mostly in middle-aged women.Diagnosis of the liver mass is often incidental on abdominal imaging due to the frequent absence of specific symptoms.Nearly 10%of HAMLs are associated with tuberous sclerosis complex.HAML contains variable proportions of blood vessels,smooth muscle cells and adipose tissue,which renders radiological diagnosis hazardous.Cells express positivity for HMB-45 and actin,thus these tumors are integrated into the group of perivascular epithelioid cell tumors.Typically,a HAML appears on magnetic resonance imaging(or computed tomography scan)as a hypervascular solid tumor with fatty areas and with washout,and can easily be misdiagnosed as other liver tumors,particularly hepatocellular carcinoma.The therapeutic strategy is not clearly defined,but surgical resection is indicated for symptomatic patients,for tumors showing an aggressive pattern(i.e.,changes in size on imaging or high proliferation activity and atypical epithelioid pattern on liver biopsy),for large(>5 cm)biopsy-proven HAML,and if doubts remain on imaging or histology.Conservative management may be justified in other conditions,since most cases follow a benign clinical course.In summary,the correct diagnosis of HAML is challenging on imaging and relies mainly on pathological findings.

The Prevalence of Oral Lesions among Palestinian Dental Patients Attending Oral Medicine Dental Clinics at Al-Quds University

Objectives: In Palestine, there are no data about the prevalence of oral lesions or their associated risk factors. Thus, this study came to assess the prevalence and the risk factors of oral lesions among adult dental patients visiting Al-Quds University (AQU) Dental Clinics. Materials and Methods: Three hundred Twenty patients were diagnosed clinically for the presence of oral lesions at oral medicine clinics at Al-Quds University in the period between 2015 to 2016. Their age ranged from 21 to 60 years old (mean age: 40.2 ± 17.6). Senior students were trained to conduct the oral exam under the direct supervision of Oral Medicine specialist. Trained students also collected data on patients’ demographics, dental history, medical history and other health related habits. Descriptive and bivariate analyses were generated to describe lesions prevalence and associations with other suggested factors. Results: A total of 68 lesions were found in this study (29.4% of study’s sample). Recurrent aphthous ulcer, traumatic ulcer and geographic tongue were the most common oral lesions. Ten oral potentially malignant lesions were diagnosed (8 cases were Leukoplakia, 2 cases were erythroplakia). Non filtered smoking cigarettes were associated with reported lesions. Oral lesions were noticed to increase with age. Oral lesions were more common on the Tongue, labial and buccal mucosain this study. Conclusions: This study revealed high prevalence of apthous and traumatic ulcer while potentially malignant lesions like leucoplakia and erythroplakia were also seen in patients who were smokers. Dentists should have a high level of awareness during oral examination and intervention should be performed to raise awareness among the population about the harmful effects of smoking on oral health.