Factor In Malignant Transformation Research Articles

LGG-32. MALIGNANT TRANSFORMATION OF PEDIATRIC LOW-GRADE GLIOMA TO SECONDARY HIGH-GRADE GLIOMA - REPORT FROM THE GERMAN BRAIN TUMOR STUDIES

Abstract BACKGROUND Malignant transformation (MT) of pediatric low-grade glioma (pLGG) to secondary high-grade glioma (sHGG) is a rare but momentous event. We explored its clinical, epidemiologic, and molecular characteristics and risk factors. METHODS Forty-eight pediatric patients with histology-based or radiological (n=4) diagnosis of primary LGG (median age 10.2 years [range, 0.7–16.9]) and subsequent sHGG were identified within registries of the HIT-network from 1996-2019. For 29 patients, tumor specimens of both pLGG and corresponding sHGG were available for neuropathological review and studied genetically. RESULTS MT occurred after median 4 years (range, 0.5-14) following LGG diagnosis. Its 15-year cumulative incidence was 1.6±0.4% (23/1586 SIOP-LGG-2004 patients), but 11.7±4.1% (9/100) for diffuse pLGG WHO-grade 2 (DG2). Clinical risk factors for MT were spinal location and prior dissemination. MT was accompanied by an increment of nuclear p53 accumulation (20/29 tumors), cytogenetic and molecular alterations. CDKN2A/B homozygous deletions (7/12 tumors), 1p/1q alterations (4/12) and ATRX loss (3/12) were the most common acquired alterations detected in sHGG. 8/16 tumors were unclassifiable by methylation profiling. DG2s (n=19), harboring IDH-1 mutation in 3/9 cases, progressed to diffuse WHO-grade 3 (n=8) or grade 4 HGG (n=9), two developed gliomatosis cerebri. Circumscribed LGG (PA, n=13; GG, n=7; PXA, n=4; DNET, n=1) typically harbored MAPK/ERK pathway alterations (BRAF-/NTRK-/FGFR-fusions, n=5/9; BRAFV600E mutation, n=4/12) and transformed to non-diffuse HGG (n=14), but also to diffuse grade 4 HGG. H3 K27M-/BRAFV600E co-mutation in two of these patients eventually resulted in MT to fatal diffuse midline glioma. Thirty-five sHGG patients received radio-chemotherapy. Overall survival at 5 and 10 years following MT was 49±8% and 31±8%. CONCLUSIONS Our findings underline the importance of careful long-term follow-up of patients with pLGG. Repeated resection/biopsy of recurrent/progressing or “atypical” tumors should be pursued and include molecular typing to identify patients at risk for MT and initiate appropriate treatment.

The complement regulatory protein CD46 serves as a novel biomarker for cervical cancer diagnosis and prognosis evaluation.

CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation. A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152-0.7541). Analysis of Kaplan-Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients. The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.

Contemporary diagnosis and management of gallbladder polyps

Gallbladder (GB) polyps are present in 5%–10% of the general population and consist of true neoplastic polyps (adenomas) and pseudopolyps (predominantly cholesterol, inflammatory, hyperplastic, focal adenomyomatosis). True polyps, although relatively rare neoplastic lesions (0.5%) are considered an important factor in malignant transformation and cancer development (5%) when their size is ≥ 1 cm. Given that it is essential to diagnose GB adenocarcinoma at an early stage to optimize therapeutic management, controversy exists about whether cholecystectomy is always necessary. Their imaging characteristics, size ≥ 1 cm, age > 50 years and genetic predisposition determine the indications for immediate cholecystectomy. In younger patients with polyps < 1 cm in size and without a familial history of GB carcinoma, imaging follow-up by ultrasound (US) seems to be a reasonable recommended policy. A scoring system by multivariate analysis (cross-sectional area > 123 mm2, positive blood flow signal, age > 55.5 years, alanine aminotransferase (ALT) levels > 50 U/L and an ALT/AST (aspartate aminotransferase) ratio > 0.77) can accurately predict true polyps. The widely accepted size threshold for US follow-up is 7 mm, and for intervention, it is 10 mm. Computed tomography or better magnetic resonance imaging can overcome any misdiagnosis of conventional US incidental findings alone that may lead to potentially unnecessary operations. In challenging cases, high-resolution US, novel three-dimensional US, endoscopic US or contrast-enhanced endoscopic US could be helpful. Novel microflow imaging can safely predict polyps. Risk factors for malignancy include age > 60 years, large gallstones, primary sclerosing cholangitis, Asian ethnicity and sessile polyps accompanied by focal gallbladder wall thickening > 4 mm. For polyps sized 6–9 mm, the absence of growth at recommended follow-up (6 months, one year, and two years) indicates treatment discontinuation; however, it is not required for size < 5 mm without risk factors. In addition to laparoscopic cholecystectomy, the standard management, novel interventional modalities preserving the GB in selected cases include per-oral transmural endoscopic resection of GB polyps after a bridge of endoscopic US-guided cholecystostomy or laparoscopic gallbladder-preserving polypectomy. Generally, there are still no precise and strong evidence-based guidelines; thus, the management policy of GB polyps should be individualized in ambiguous cases.

Rate of Malignant Transformation Differs Based on Diagnostic Criteria for Oral Lichenoid Conditions: A Systematic Review and Meta-Analysis of 24,277 Patients.

This systematic review and meta-analysis aims to evaluate the evidence on the malignant potential of oral lichenoid conditions (OLCs) including oral lichen planus (OLP), oral lichenoid lesions (OLL), and lichenoid mucositis dysplasia (LMD). In addition, it aims to compare the rate of malignant transformation (MT) in OLP patients diagnosed according to different diagnostic criteria, and to investigate the possible risk factors for OLP MT into OSCC. A standardized search strategy was applied across four databases (PubMed, Embase, Web of Science, and Scopus). Screening, identification and reporting followed the PRISMA framework. Data on MT were calculated as a pooled proportion (PP), subgroup analyses and possible risk factors for MT were pooled as odds ratios (ORs). Among 54 studies with 24,277 patients, the PP for OLCs MT was 1.07% (95% CI [0.82, 1.32]). The estimated MT rate for OLP, OLL and LMD was 0.94%, 1.95% and 6.31%, respectively. The PP OLP MT rate using the 2003 modified WHO criteria group was lower than that using the non-2003 criteria (0.86%; 95% CI [0.51, 1.22] versus 1.01%; 95% CI [0.67, 1.35]). A higher odds ratio of MT was observed for red OLP lesions (OR = 3.52; 95% CI [2.20, 5.64]), smokers (OR = 1.79; 95% CI [1.02, 3.03]), alcohol consumers (OR = 3.27, 95% CI [1.11, 9.64]) and those infected with HCV (OR = 2.55, 95% CI [1.58, 4.13]), compared to those without these risk factors. OLP and OLL carry a low risk of developing OSCC. MT rates differed based on diagnostic criteria. A higher odds ratio of MT was observed among red OLP lesions, smokers, alcohol consumers, and HCV-positive patients. These findings have implications for practice and policies.

Comparative Longitudinal Analysis of Malignant Transformation in Pleomorphic Adenoma and Recurrent Pleomorphic Adenoma.

Background: Recurrence in pleomorphic adenoma (PA) has been debated as a risk factor for malignant transformation (MT). In this study, we investigated whether recurrence is a risk factor for MT, by longitudinally analyzing cases with recurrent PA (RPA), and carcinomas from PA (CXPA) or RPA (CXRPA). Methods: The study population included 24 CXPA, 24 RPA, 6 CXRPA, and 386 PA cases (study period 2010–2018). Time and event data were collected from the medical documents to identify the time–event sequences. Results: The time interval to MT in CXRPA was significant longer than that of benign recurrence (median 342.0 vs. 109.5 months). In CXRPA, the recurrence intervals were not shorter than those in RPA according to recurrence frequency. Crudely, the MT rate was 5.9% among primary cases and 20.0% among recurrent cases. However, the time-adjusted MT rates increased up to 11.4% (incubation time > 60 months) and 20.0% (>120 months) in primary cases, which were not different from recurrent cases. Conclusion: In these longitudinal analyses, we did not find any clinical evidence that recurrence facilitates MT in the background of PA. Instead, a long incubation time seems to be a key factor for MT of underlying RPA.

THE EXPRESSION OF NFATC1 IS MORE PREDOMINANT IN TRIPLE NEGATIVE BREAST CARCINOMA PATIENTS

Breast carcinoma is the most common malignancy among women in developed and developing countries. Invasive breast carcinomas are classified into 4 subtypes i.e. luminal A and B, human epidermal growth factor receptor 2 (HER2)-enriched and triple negative, the latter has the worst prognosis. Nuclear factor of activated T cell (NFATc)1 is an important transcription factor in malignant transformation and progression. Therefore, NFATc1 expression may determine prognosis of breast carcinoma. This study aimed to determine the roles of NFATc1 inbreast carcinoma progression. Materials and Methods Fifty-two paraffin blocks were selected and prepared to assess NFATc1 expression by immunohistochemistry. These data were taken from medical records: i.e. molecular classification, patient age, tumor size, lymphovascular invasion and grade of tumor were recorded. Results: Positive NFATc1 expression was observed in 4 samples i.e. in the nuclei of luminal A (1 out of 12; 8.8%), luminal B (1 out of 15; 6.7%), and triple negative (2 out of 12; 16.7%), but no NFATc1 expression was detected in HER2-enriched samples. Clinicopathologically, more of these patients were in the fifth decade (38.5%), with larger tumor size (?2 cm; 90%), lymphovascular invasion positive (80.8%), and high degree (3; 59.6%). Conclusion: NFATc1 expression is more predominant in triple negative breast carcinoma.

Malignant transformation of endometriosis on vaginal cuff after hysterectomy: a case report

Objective. Endometriotic tissue implants rarely transform to malignant tissue, especially in a patient with a hysterectomy and bilaterally salpingo-oophorectomy. However, several cases with cancer arising from endometriosis after hysterectomy were reported in the literature. Hormone replacement therapy only with estrogen is a crucial risk factor for malignant transformation of persistent endometriotic tissue. Case Report. The present case demonstrates an endometrioid adenocarcinoma arising from persistent endometriosis tissue in a patient who was performed hysterectomy with bilateral salpingectomy 3 years ago. The histopathologic specimens of the previous surgery did not include any malignant tissue. After 3 years, she applied to the hospital with abnormal vaginal bleeding, and her histopathologic examination result found an ulcerated mass at the upper one-third of the vagina that is compatible with endometrioid adenocarcinoma. Conclusion. It is crucial to keep in mind the endometriosis history of the patient, to be able to diagnose cancer arising from endometriosis while evaluating the patient with a hysterectomy.

Expression of p53, p63, podoplanin and Ki-67 in recurring versus non-recurring oral leukoplakia

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank, p = 0.036; multivariate Cox, HR: 2.48 (1.13–5.44; p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.

Transient Inhibition of the JAK1/3-STAT5 Pathway By Ruxolitinib Is Insufficient to Produce Clinical Benefit in Patients with Indolent Adult T-Cell Leukemia

▪ INTRODUCTIONAdult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of regulatory T cells caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Viral protein Tax is a key factor in malignant transformation. Peripheral blood mononuclear cells (PBMCs) collected from patients with smoldering and chronic-subtype ATL exhibited ex vivo spontaneous proliferation associated with Tax-dependent transactivation of two autocrine loops (IL-2/IL-2Rα, IL-15/1L-15Rα), and one paracrine loop (IL-9/IL-9Rα). Accordingly, antibodies directed against IL-2Rα, IL-9, and IL-15 inhibited proliferation of ATL cells. As the three cytokine/cytokine receptor loops act through downstream activation of the JAK1/3 and STAT5 signaling pathways, addition of the pan-JAK inhibitor tofacitinib and JAK1/2 inhibitor ruxolitinib also inhibited proliferation. Furthermore, ruxolitinib, when administered by continuous intravenous infusion, inhibited ATL cell proliferation in NOG mice. METHODSThese observations led to a phase 2 open-label trial evaluating the safety and efficacy of ruxolitinib in patients with smoldering, chronic, or clinically indolent acute subtype ATL. Ruxolitinib was given at the FDA-approved dose of 20 mg orally twice daily for 28 days. Patients who responded to initial treatment could restart at the time of progression and be treated until progression. Primary objective was the clinical response rate per Revised Cheson Criteria and the International Consensus Meeting Criteria for ATL. Secondary objectives were 1) safety profile, 2) time to progression, 3) overall survival, and 4) duration of response off treatment. RESULTS5 patients with smoldering, 3 with chronic, and 2 with previously treated acute ATL were enrolled between October 2012 and July 2016. There were no grade 3/4 toxicities attributable to the study drug. Cytopenias were the most commonly reported adverse events, including two grade 3 neutropenias (table 1). One patient had a partial response lasting 2.4 months. Median time to progression was 1.6 months and median overall survival was 22.3 months. Three patients with partial or near-partial response were re-treated after a median of 5.7 months. To determine the time course of inhibition of the JAK-STAT pathway the concentration of phosphorylated STAT3 or STAT5 in ex vivo PBMCs was determined after an oral dose of 20 mg of ruxolitinib. Levels of phosphorylated STAT5 returned to baseline after 3-6 hours following the oral dose (figure 1), indicating that the pathway remained active for up to 18 hours per day when the drug was given twice daily. DISCUSSIONBoth of ruxolitinib's FDA approvals-for polycythemia vera and myelofibrosis-were based on reduction in spleen size. Its inhibitory effect on JAK2-mediated thrombopoietin signaling lead to thrombocytopenia as the main dose-limiting toxicity and precluded aggressive dose titration. In our study, single-agent ruxolitinib at the FDA-approved dose was safe but not effective in patients with indolent subtypes of ATL, likely due to lack of persistent JAK1/STAT5 inhibition. Further studies should therefore focus on 1) combinations of ruxolitinib with agents showing synergy on high-throughput screens, such as the Bcl-XL inhibitor navitoclax, and 2) more potent inhibitors of JAK1/3, like baricitinib, which was not associated with significant anemia or thrombocytopenia in a phase 3 trial. Ultimately, the future of indolent ATL treatment may lie in a multidrug combination that includes a specific JAK1 or JAK3 inhibitor. Considering the pervasive activation of the gamma cytokine JAK/STAT pathway in all T-cell malignancies, with up to 86% of patients manifesting pSTAT in the nucleus, the future of all T-cell malignancies may involve a specific JAK1 or JAK3 inhibitor. [Display omitted] DisclosuresMiljkovic:Pfizer Oncology: Research Funding.

Unclassified hepatocellular adenoma with beta-catenin mutation: a case report

BackgroundHepatocellular adenoma (HCA) subtypes are considered as risk factors for malignant transformation; thus, an accurate diagnosis is important. We report a case of resected HCA previously diagnosed as unclassified HCA using immunohistochemistry, subsequently discovered to harbor a mutation in exon 3 of the beta (β)-catenin gene using deoxyribonucleic acid (DNA) sequencing.Case presentationThe patient was a 26-year-old woman who was referred to our hospital because of a 150-mm tumor in the right lobe of the liver. Considering the possibility of malignancy, we performed right lobe hepatectomy. Based on the histopathological and immunohistochemical findings, the tumor was diagnosed as an unclassified HCA. Next, we performed sequencing of DNA isolated from the tumor and identified a mutation in exon 3 of β-catenin, suggesting that the tumor contained an activating mutation of the β-catenin gene.Conclusionβ-Catenin mutations in HCA cannot be detected by immunohistochemistry alone, and molecular analysis is required to accurately diagnose and evaluate its prognosis.

A systematic review on the complications and management of hepatic adenomas: a call for a new approach.

Hepatic adenomas are benign hepatic lesions with heterogeneous characteristics. Awareness of complications, including haemorrhage and malignant transformation, has improved alongside a concurrent rise in their detection. Monitoring and management guidelines, however, remain inconsistent. This systematic review analyses the natural history of hepatic adenomas, and existing and novel risk factors associated with haemorrhage and malignant transformation. Results of this systematic review commonly identified male sex, and the beta-catenin histopathological hepatic adenoma subtype, as risk factors for malignant transformation, whilst those associated with haemorrhage included lesion size and number, exophytic nature, and recent hormone use. Overall, females demonstrated higher rates of haemorrhage, whilst males exhibited a higher risk of hepatocellular carcinoma development. This systematic review highlights that tumour size and subtype may not be as characteristically linked with complications as previously thought. We have additionally reported novel risk factors contributing to development of hepatic adenoma-related complications. We conclude by highlighting the risk of taking a conservative approach to seemingly low-risk lesions and suggest revised practice guidelines.

Determination of Ki-67 expression in oral leukoplakia in snuff users and non-users in Khyber Pakhtunkhwa province of Pakistan.

Objectives: The aim of the article was to evaluate Ki-67 expression in oral leukoplakia in snuff users and non-users. Study Design: Descriptive Cross sectional study. Setting: At different hospitals of Khyber Pakhtunkhwa province. Period: From August 2016 –March 2017. Material & Methods: Clinically diagnosed and histopathologically confirmed cases of oral leukoplakia in snuff users and non-users 30 cases each were immunohistochemically examined and percentage expression of nuclear Ki-67 was evaluated by a semi quantitative method in basal, parabasal and suprabasal layers of the lining epithelium. Results: The relationship of expression of Ki-67 in parabasal and suprabasal layers of affected epithelium in snuff users was found to be statistically significant with a p value of 0.007 and 0.002 respectively. Conclusion: The present study concludes that the proliferative index is high in snuff users as compared to non-users which can be a factor for malignant transformation.

Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma

Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG. We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus. Among the included 486 adults with molecularly classified LGG, median agewas 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDHmut1p/19qcodel in 169 (35%), IDHmut1p/19qintact in 125 (26%), and IDHwt in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDHmut1p/19qcodel patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDHmut1p/19qintact (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDHwt classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008). MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG.

Comparison of Coding Transcriptomes in Fibroblasts Irradiated With Low and High LET Proton Beams and Cobalt-60 Photons

To identify differential cellular responses after proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type. A panel of primary dermal fibroblast cultures was irradiated with low and higher linear energy transfer (LET) proton beams. Cobalt-60 photon irradiation was used as reference. Dose was delivered in 3 fractions of 3.5Gy (relative biological effectiveness) using a relative biological effectiveness of 1.1 for proton doses. Cells were harvested 2hours after the final fraction was delivered, and RNA was purified. RNA sequencing was performed using Illumina NextSeq 500 with high-output kit. The edgeR package in R was used for differential gene expression analysis. Pairwise comparisons of the transcriptomes in the 3 treatment groups showed that there were 84 and 56 differentially expressed genes in the low LET group compared with the Cobalt-60 group and the higher LET group, respectively. The higher LET proton group and the Cobalt-60 group had the most distinct transcriptome profiles, with 725 differentially regulated genes. Differentially regulated canonical pathways and various regulatory factors involved in regulation of biological mechanisms such as inflammation, carcinogenesis, and cell cycle control were identified. Inflammatory regulators associated with the development of normal tissue complications and malignant transformation factors seem to be differentially regulated by higher LET proton and Cobalt-60 photon irradiation. The reported transcriptome differences could therefore influence the progression of adverse effects and the risk of developing secondary cancers.

Epstein-Barr virus infection of mammary epithelial cells and risk of associated malignancy

The human tumor virus, Epstein-Barr virus (EBV), is a γ-herpesvirus associated with human epithelial and B-cell malignancies. The association of EBV infection with breast cancer has been reported in many recent studies (1). EBV can be divided into two major types, EBV type 1 and EBV type 2. Type 1 is dominant throughout most of the world, but the two types are equally prevalent in Africa (2). The EBV infection pattern is classified as either lytic, or latent 0, I, II and III (3). LMP1 is the well-documented oncoprotein of the EBV latent gene products (4). EBV strongly constitutes a risk factor for malignant transformation because it can infect mammary epithelial cells “MECs” and its DNA fragments can induce immortalization in these cells (5,6). EBV is incriminated as a carcinogenic agent by the World Health Organization (7) so; a childhood immunization against EBV might have a great impact on public health. This editorial is on a research article by Hu et al. (8) entitled “Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation”. This editorial will focus on the evidence that delayed EBV infection causes latent infection of “MECs” leading to phenotypic changes which is a part of a multistep process of breast carcinogenesis together with other genetic and environmental factors.

Malignant transformation arising in mature cystic teratoma

Background: The prognosis of patients with malignant transformation arising within mature cystic teratoma is poor. However, preoperative diagnosis is dif cult due to its rarity. The aim of this study was to evaluate the clinical and histopathological characteristics of such malignancies. Materials and Methods: A retrospective cross sectional study on a series of cases was performed in the Department of Pathology, Patan Academy of Health Sciences, Patan Hospital, Lalitpur, Nepal from April 2011 to March 2016. Data from the histopathology database were analyzed using SPSS version 16.0. Results: Mature cystic teratoma comprised 230 cases (57.6%) out of total 399 cases of ovarian neoplasms. Malignant transformation was noted in 7 (3%) of the mature cystic teratoma. The mean age at diagnosis of patients with malignant transformation of mature cystic teratoma was 47.57 years. The size of the tumors ranged from 7-14cm. The mean diameter of tumor was 10.28cm. There was signi cant difference in age between mature cystic teratoma and malignant transformations arising within mature cystic teratoma. No signi cant association was noted in tumor size. Torsion was noted in a single case. Squamous cell carcinoma was the most common malignant tumor seen in 5 cases. The TNM stage distribution was T1aNx for 4 cases, T2aNx for one case and T3aNx for 2 cases. Conclusion: Squamous cell carcinoma is the most common malignancy arising in mature cystic teratoma. Advanced age is a signi cant risk factor for malignant transformation in mature cystic teratoma.

Malignancy Risk in Brazilian Women with Endometrial Polyps

Abstract Background: Endometrial polyps are generally benign, but can turn into premalignant or malignant lesions. Advanced age, menopausal status, abnormal uterine bleeding, polyp size, obesity, hypertension, diabetes, hormone therapy, breast cancer, and tamoxifen use are risk factors. Objective: The aim of this study was to determine the prevalence of malignant lesions on endometrial polyps with resection by hysteroscopy in both pre- and postmenopausal women, and risk factors for malignant transformation. Materials and Methods: This was a retrospective study with 303 women who underwent hysteroscopy-guided polypectomy in 2012 at the hospital of the University of Campinas (UNICAMP), Brazil. Polyps were classified as either benign or malignant. The variables analyzed were age, parity, body mass index, symptoms (asymptomatic, bleeding) associated pathologies (arterial hypertension, diabetes mellitus, breast cancer), endometrial line, and size of the polyp. Frequency, medians, and standard deviation of the ...

Direct Immunofluorescence in Clinically Diagnosed Oral Lichen Planus

Purpose: Oral lichen planus (OLP) is relatively common mucosal disease in clinical dentistry. OLP is intractable and regarded having malignant potential. Until now, there is some debate on how far OLP can be malignant, and which characteristics can be a risk factor for malignant transformation. Clinician need to know some differences between OLP and lesions similar to OLP to manage properly and suppose prognosis correctly. Therefore, the aim of this study was to divide clinical OLP into two groups and to compare the results of direct immunofluorescence (DIF) between two groups. Methods: This study was conducted on outpatients who visited at the department of Oral Medicine in Chonbuk National University Hospital from January 2007 to November 2015. Patients with DIF result were retrospectively reviewed. The selected patients were classified ‘clinical typical of OLP’ (CTO) or ‘clinical compatible with OLP’ (CCW) by modified World Health Organization diagnostic criteria of OLP and oral lichenoid lesion. Results: DIF were classified by deposition intensity or pattern of anti-human antibody and fibrinogen. The classification of fluorescence pattern in each specimen was graded as positive, possibly positive or negative. Conclusions: Both CTO and CCW had positive and possibly positive pattern. Prevalence of positive pattern was 68.8% in CTO and 52.6% in CCW and that of possibly positive pattern was 9.4% in CTO and 5.3% in CCW. Prevalence of negative was 21.8% in CTO and 42.1% in CCW.

Carcinoma ex-pleomorphic adenoma derived from recurrent pleomorphic adenoma shows important difference by array CGH compared to recurrent pleomorphic adenoma without malignant transformation

IntroductionA key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. ObjectiveWe analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. MethodsDNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. ResultsNo somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. ConclusionThe occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation.

Superficial Spreading Melanoma „Slumbered“ Behind the Shadow of Onychomycosis

Summary Malignant melanoma is the most aggressive form of cutaneous cancer. Due to the continuously increasing rate of newly detected cases each year and because of its particular low survival rate, the scientific interest in this type of neoplasia is constantly growing. Sun exposure is identified as the major etiologic factor for malignant transformation of the melanocytes. According to the WHO, malignant melanoma is divided into four main groups, as the superficial spreading form is defined as the most “gentle” among them. The name of this subspecies does not have to “drowse” the attention of dermatologists considering the possible metastasic risk, even at a later stage. Due to lack of subjective complaints, patients do not seek active consultation on this occasion, as this type of lesions often remain missed within the clinical examination. Early diagnosis, however, as well as early surgical removal is the key to increasing the survival rate of the patients. We present a case of a 88 year-old female patient consulted with dermatologist on occasion of severe onychomycosis, as a pigment lesion on the anterior surface of the right leg. Clinically and dermatoscopically suspected superficial spreading melanoma was detected within the examination.