Risk Of Testicular Cancer Research Articles

Unemployment risk and income change after testicular cancer diagnosis: A population-based study

BackgroundAmong patients with cancer, returning to full working may serve as an indicator for return to normal lifestyle following illness, as opposed to unemployment or shifting to part-time work. The aim of the project was to clarify the association between unemployment risk and decreased income at 4 years after the diagnosis of testicular cancer (TC). Participants and methodsA case control in a cohort study includes baseline measurement of people participating in the Israeli Central Bureau of Statistics 1995 National Census, and follow-up until 2011. Cancer incidence, employment status, and income level were ascertained through the Israel Cancer Registry and Tax Authority, respectively. A matched group was sampled from the population in the census. Binary logistic regression analyses were used to assess odds ratios (ORs) for study׳s outcomes, while controlling for age, ethnicity, education, and socioeconomic and employment status at 2 years before diagnosis. ResultsA total of 113 cases of TC and 468 persons in the matched group were included in the study after excluding persons who died during the study period. No association was found between TC and subsequent risk after the 4 years of unemployment (OR = 1.12, 95% CI: 0.65–1.95) or decreased income (OR = 1.41, 95% CI: 0.84–2.36). Predictors of subsequent unemployment were unemployment 2 years before diagnosis (OR = 6.91, 95% CI: 4.39–10.86) and increasing age (OR = 1.03 per year, 95% CI: 1.01–1.06). ConclusionTC survivorship is not associated with subsequent unemployment or decreased income at 4 years after diagnosis.

Abstract 2743: Cancer risk in relatives of testicular cancer patients by histology type and age at diagnosis: a joint study from five Nordic countries

Abstract Background: None of population-based epidemiological studies to date had a large enough sample size to show familial risk of testicular cancer (TC) by patients’ and their relatives’ age at diagnosis and also by rare histological subtypes. Objective: We aimed to estimate absolute and relative risk of TC in relatives of TC patients by age at diagnosis in patients and their relatives and histology subtypes. Design: A joint population-based cohort study. Setting and Participants: A cohort of 97,402 first-degree relatives of 21,254 TC patients who were diagnosed between1955 and 2010 in five European countries was followed for cancer incidence. Outcome Measurements and Statistical Analysis: Standardized incidence ratios (SIRs) were estimated using histology-, age-, period-, and country-specific incidence rates as the reference. The lifetime cumulative risks also were calculated. Results and Limitations: The lifetime cumulative risk of TC in brothers of a patient with TC was 2.3%, which represents 4-fold increased risk (SIR = 4.1, 95%CI = 3.6-4.6) over the general population risk. TC in a father increased the risk up to 2-fold in his son (95%CI = 1.7-2.4; lifetime risk 1.2%) and vice versa. When there were ≥2 TC patients diagnosed in a family, lifetime TC risk for relatives was 10-11%. Depending on age at diagnosis, twins had 9-74% lifetime risk of TC. Family history of most of the histological subtypes of TC increased the risk for concordant and most of the discordant subtypes. There was a tendency toward concordant age at diagnosis of TC among relatives. Conclusions: This study provides clinically relevant age-specific cancer risk estimates for family members of TC patients. Familial TC cases tended to develop TC at an age close to age at diagnosis of TC among their relatives, which is the novel finding of this study. Citation Format: Elham Kharazmi, Kari Hemminki, Eero Pukkala, Kristina Sundquist, Laufey Tryggvadottir, Steinar Tretli, Jørgen H. Olsen, Mahdi Fallah. Cancer risk in relatives of testicular cancer patients by histology type and age at diagnosis: a joint study from five Nordic countries. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2743. doi:10.1158/1538-7445.AM2015-2743

A Meta-Analysis of the Relationship between Testicular Microlithiasis and Incidence of Testicular Cancer.

There are many recent observational studies on testicular microlithiasis (TM) and risk of testicular cancer. Whether TM increases the risk of testicular cancer is still inconclusive. The objective of this updated meta-analysis was to synthesize evidence from clinical observational studies that evaluated the association between TM and testicular cancer. We identified eligible studies by searching the PubMed, Embase and Cochrane Library before March 2014. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-or fixed-model. A total of 14 studies involving 35,578 participants were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale systematic review, eleven studies were identified as relatively high-quality. TM was strong association with an increased incidence of testicular cancer (RR = 12.70, 95% CI: 8.18-19.71, P < .001), with significant evidence of heterogeneity among these studies (P for heterogeneity < .001, I2 = 82.1%). The subgroup and sensitivity analysis confirmed the stability of the results and no publication bias was detected. The present meta-analysis suggests that TM is significantly associated with risk of testicular cancer. More researches are warranted to clarify an understanding of the association between TM and risk of testicular cancer.

Cancer Risk in Relatives of Testicular Cancer Patients by Histology Type and Age at Diagnosis: A Joint Study from Five Nordic Countries

BackgroundNone of the population-based epidemiologic studies to date has had a large enough sample size to show the familial risk of testicular cancer (TC) by age at diagnosis for patients and their relatives or for rare histologic subtypes. ObjectiveTo estimate absolute and relative risks of TC in relatives of TC patients by age at diagnosis in patients and their relatives and histological subtypes. Design, setting, and participantsIn a joint population-based cohort study, 97 402 first-degree relatives of 21 254 TC patients who were diagnosed between1955 and 2010 in five European countries were followed for cancer incidence. Outcome measurements and statistical analysisStandardized incidence ratios (SIRs) were estimated using histology-, age-, period-, and country-specific incidence rates as references. Lifetime cumulative risks were also calculated. Results and limitationsThe lifetime cumulative risk of TC in brothers of a patient with TC was 2.3%, which represents a fourfold increase in risk (SIR 4.1, 95% confidence interval [CI] 3.6–4.6) compared to the general population. TC in a father increased the risk by up to twofold in his son (95% CI 1.7–2.4; lifetime risk 1.2%) and vice versa. When there were two or more TC patients diagnosed in a family, the lifetime TC risk for relatives was 10–11%. Depending on age at diagnosis, twins had a 9–74% lifetime risk of TC. Family history of most of the histologic subtypes of TC increased the risk of concordant and most discordant subtypes. There was a tendency toward concordant age at diagnosis of TC among relatives. ConclusionsThis study provides clinically relevant age-specific cancer risk estimates for relatives of TC patients. Familial TC patients tended to develop TC at an age close to the age at diagnosis of TC among their relatives, which is a novel finding of this study. Patient summaryThis joint European population study showed that sons and brothers of testicular cancer patients are at higher risk of developing this cancer at an age close to the age at diagnosis of their relatives.

Exposure to polychlorinated biphenyls and hexachlorobenzene, semen quality and testicular cancer risk.

We carried out a case-control study to investigate the possible role of occupational and environmental exposure to endocrine disruptors in the onset of testicular cancer (TC). We evaluated 125 TC patients and 103 controls. Seminal fluid examination and organochlorine analysis were performed in all subjects. Cases and controls were also interviewed using a structured questionnaire to collect demographic information, residence, andrological medical history and dietary information. We found that a higher level of reproductive tract birth defects was associated with a higher risk of TC. With regard to diet, cases reported a higher consumption of milk and dairy products than controls. Overall, there was a statistically significant increase in TC risk in cases with detectable values of total polychlorinated organic compounds against controls (14.4 vs. 1.0 %; p < 0.001). TC patients with detectable levels of organochlorines had lower mean semen parameters than those with undetectable levels, although this difference was not statistically significant. The International Agency for Research on Cancer recently included dioxin-like polychlorinated biphenyls (PCBs) in Group 1 of known human carcinogens. Our study confirmed and identified various risk factors for testicular cancer: cryptorchidism, consumption of milk and dairy products, parents' occupation and serum concentration of hexachlorobenzene and PCBs and, for the first time, we showed the correlation between semen quality and the serum concentration of these pollutants.

Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population.

BMI at diagnosis and adverse outcomes among men with malignant testicular germ cell tumors.

400 Background: Previous studies evaluating the relationship between measures of anthropometry, such as body mass index (BMI), and risk of testicular cancer have been conflicting, with most finding null or inverse associations. Methods: We conducted a retrospective review of 960 germ cell tumors among patients treated at the Dana-Farber Cancer Institute (DFCI) between 1997 and 2012 with information on BMI. BMI at diagnosis, tumor characteristics, IGCCC classification, treatment, relapse and cause of death was ascertained from electronic medical record review. We divided the men and conducted the analyses separately for two groups: 1) men who presented as clinical stage 1 (CS1), and 2) men who presented with metastases or were CS1 at diagnosis and developed metastases (lifemets). We conducted logistic regression to evaluate the association between BMI and characteristics at diagnosis, and Cox proportional hazards regression to investigate the risk of relapse and testicular cancer death. Results: 65% of men (n=628) were overweight or obese at diagnosis. We did not find an association between BMI and tumor characteristics at baseline, such as histology, lymphovascular invasion, or tumor size for either group. Among CS1 patients, men who were overweight or obese had a non-statistically significant reduced risk of relapse compared to men who were normal weight (HR: 0.83, 95% CI: 0.53-1.30). Among the lifemets group, 16% of men relapsed (n=83) and 8% died of testicular cancer (n=43). Although not statistically significant, men who were overweight or obese were less likely to present with intermediate (OR = 0.77, 95 CI: 0.39-1.52) and poor (OR = 0.66, 95% CI: 0.36-1.20) rather than good risk disease when compared to men with normal BMI. After adjusted for confounding variables, BMI was not associated with risk of relapse (HR: 0.94, 95% CI: 0.59-1.51) or risk of testicular cancer death (HR: 1.00, 95% CI: 0.54-1.84) among the lifemets group. Conclusions: We did not find an association between BMI at diagnosis and tumor characteristics at baseline, or risk of relapse or testicular cancer death among men with testicular cancer.

Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts.

Background:No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk.Methods:We conducted a population-based case–control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts.Results:The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR=1.65, 95% confidence interval (CI): 1.11–2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use.Conclusions:MBS use is a potentially modifiable risk factor that may be associated with TGCC.

Familial risk and heritability of genitourinary cancers in the Nordic Twin Cohorts.

11 Background: Twin studies estimate familial risk and heritability by leveraging the unique genetic relatedness of twins. We analyzed data from the Nordic Twin Study to investigate the genetic underpinnings of risk of genitourinary cancers. Methods: The cohort included 202,868 monozygotic (MZ) and same-sex dizygotic (DZ) twins from nationwide registries with follow-up via cancer registries. We examined cancers of the prostate, bladder, kidney and testes, and estimated familial risk, risk of a specific cancer in a twin, given that his co-twin was diagnosed with the same cancer, and heritability, the proportion of variation in cancer risk due to genetic differences. Statistical models used time-to-event analyses and accounted for censoring and competing risk of death. Results: During 32 years of follow-up, 5,041 cases of genitourinary cancer were diagnosed. The cumulative incidences in the cohort overall were 10.5% for prostate, 2.2% for bladder, 0.8% for kidney and 0.5% for testes. The strongest familial effects were found for testicular cancer. The familial risks of testicular cancer were 6% for DZ and 14% for MZ twins, i.e. a 12-fold and 28-fold higher risk for DZ and MZ twins, respectively, when their twin was also diagnosed with testicular cancer. Familial risk was also elevated for prostate, bladder, and kidney cancer and showed higher estimates among MZ than DZ twins. Statistically significant estimates of heritability were observed for prostate (57%) and kidney (38%) cancer, while testicular cancer showed evidence of both genetic (37%) and shared environmental (24%) effects. Conclusions: Familial risk estimates provide evidence of significant excess risks for individuals whose siblings develop genitourinary cancers. The higher concordance in MZ vs. DZ twins translated to strong heritability estimates for these malignancies. Results from this study have the potential to be directly translated to clinical practice and genetic counseling, and provide a context for the findings from genome wide association studies.

Undescended Testes: A Clinical and Surgical Review

Undescended testes are a common congenital disorder with potential sequelae that include infertility and malignancy. This article addresses a contemporary perspective on the pathophysiology of the undescended testis, impact on testicular function and risk of testicular cancer. Surgical management and current guidelines regarding optimal timing of surgery will also be presented.

Genetics accounts for 50% of the risk of a common testicular cancer

Genetics accounts for 50% of the risk of a common testicular cancer

Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action.

In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action.

Pattern of scrotal examination by physicians in the Eastern Province of Saudi Arabia

Introduction: A wide variety of pathological lesions affect the scrotal contents. They include both benign and malignant lesions. Missed or delayed diagnosis of such lesions can lead to compromised fertility, cosmetic deformities, testicular loss or even death. Early diagnosis of scrotal lesions can prevent the possible development of such complications. Objectives: The pattern of scrotal examination by physicians in the Eastern Province of Saudi Arabia was evaluated in this study to assess the extent of efficacy for early diagnosis. Materials and methods: In this cross-sectional study of scrotal pathology, self-administered questionnaires regarding scrotal evaluation were answered by physicians of different disciplines, including emergency care, internal medicine, paediatric surgery, family medicine and general practitioners. The questionnaires included direct questions on clinical examination of the scrotum as well as clinical scenario quizzes. Collected data were analysed with SPSS (Statistical Product and Service Solutions) version 17 (SPSS Inc., Chicago, IL, USA). The chi-squared test was used to analysis categorical variables, while the t -test was used for continuous variables. Factors affecting scrotal evaluation were assessed by logistic regression. Results: 257 questionnaires were analysed. Routine evaluation of the scrotum was performed by only 14% of respondents. Among the physicians who did not perform routine scrotal examination, 64.2% restricted it to cases with scrotal complaints and 16% considered the conservative cultural nature of their patients a hindering factor. Forty-five per cent did not perform scrotal examination in the standing position. Only 27.8% advised patients with high risk of testicular cancer to perform routine self-examination of their testicles. Conclusions: This study revealed a significant deficiency of early detection of scrotal disease by physicians in the Eastern Province of Saudi Arabia with a high probability of development of complications. We recommend that all physicians be advised to follow a well-structured protocol for scrotal examination during routine practice.

Increased Risk of Cancer in Infertile Men: Analysis of U.S. Claims Data

Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Data suggest a higher risk of testicular cancer in infertile men. However, the relationship between infertility and other cancers remains uncertain. We analyzed subjects from the Truven Health MarketScan®claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups were created of men who underwent vasectomy and a control cohort of men who were not infertile and had not undergone vasectomy. The incidence of cancer was compared to national U.S. estimates. Infertile men were also compared to men who underwent vasectomy and the control cohort using a Cox regression model. A total of 76,083 infertile men were identified with an average age of 35.1 years. Overall 112,655 men who underwent vasectomy and 760,830 control men were assembled. Compared to age adjusted national averages, infertile, vasectomy and control subjects in the study cohorts had higher rates of all cancers and many individual cancers. In time to event analysis, infertile men had a higher risk of cancer than those who underwent vasectomy or controls. Infertile men had a higher risk of testis cancer, nonHodgkin lymphoma and all cancers than the vasectomy and control groups. Consistent with prior reports, we identified an increased risk of testicular cancer in infertile men. The current data also suggest that infertile men are at an increased risk of all cancers in the years after infertility evaluation. Future research should focus on confirming these associations and elucidating pathways between infertility and cancer.

International testicular cancer incidence trends: generational transitions in 38 countries 1900-1990.

Rapid increases in testicular cancer incidence have marked the second half of the last century. While these secular rises, observed mainly in countries attaining the highest levels of human development, appear to have attenuated in the last decade, rates continue to increase in countries transiting toward high developmental levels. The purpose of our study was to provide a comprehensive analysis and presentation of the cohort-specific trends in testicular cancer incidence rates in 38 countries worldwide. We used an augmented version of the Cancer Incidence in Five Continents series to analyze testicular cancer incidence in men aged 15-54 in 38 countries, via age-period-cohort analysis. In many European countries, the USA, Canada, Australia, and New Zealand, there is a continuation of the increasing risk among successive generations, yet rates are attenuating in male cohorts born since the 1970s in several Northern European countries, in contrast to the steeply increasing trends in recent cohorts in Southern Europe. Incidence rates have also been increasing in the populations traditionally at rather low risk, such as in the Philippines, Singapore, China, and Costa Rica. The attenuation of testicular cancer risk in younger generations (in the most developed countries) alongside concomitant increases (in countries undergoing developmental change) is indicative of a global transition in the risk of testicular cancer. While identifying the underlying causes remains a major challenge, increasing awareness and adapting national healthcare systems to accommodate a growing burden of testicular cancer may prevent future avoidable deaths in young men.

Evaluation of the effectiveness of testicular cancer and testicular self-examination training for patient care personnel: intervention study.

Testicular cancer (TC) is the most common malignancy among men aged 15-35 years. Testicular self-examination (TSE) is an important tool for preventing late-stage TC diagnoses. This study aimed to assess health beliefs and knowledge related to TC and TSE and the effectiveness of TC and TSE training for patient care staff in a hospital. This was a prospective, randomized, controlled intervention study. The study included 96 patient care staff divided into two groups of 48 participants each: Group I, the interactive education group, and Group II, the pamphlet education group. The results demonstrated that TSE practice and TC knowledge significantly increased in both Group I and Group II. Significant differences were observed between the groups pre and post education. TSE and TC knowledge levels were higher for participants in Group I than those in Group II. There was a significant difference in the performance of TSEs between groups: the rates were 83.3% in Group I and 54.2% in Group II. Perceived confidence and perceived barriers increased significantly for both groups. Interactive education sessions should be used to train men at risk for TC to perform TSEs.

The genetics of human migrations

When our human ancestors began to migrate from the African savannahs across the Alps into Northern Europe and Asia between 200,000 and 60,000 years ago, they encountered a colder climate, different food sources and new predators. Inevitably, evolution began to work on those wandering tribes: their skin became lighter, their metabolism adapted to new food sources, and their immune system had to handle different pathogens. Modern Homo sapiens began to evolve into slightly different subspecies or, as they are referred to in the common vernacular, different races. This shallow notion of race—that differences in our appearance have deep‐seated consequences for who and what we are as human beings—is the root of racism, which has led to slavery, discrimination, murder and genocide throughout the millennia. With the emergence of modern genetics and genomics, scientists had hoped that a better understanding of genetic differences and similarities among humans would eventually help to overcome the controversial and toxic notion of race as having anything to do with a person's ability, intelligence or humanity. As J. Craig Venter, then head of the Celera Genomics Corporation in Rockville, MD, USA, put it in 2000, when the first draft of the human genome was published: “Race is a social concept, not a scientific one”. Since the publication of the human genome, further advances in genomic sequencing and statistical analysis are now yielding new insights into the link between past human migrations and today's variety of genetic differences that govern disease resistance, skin pigmentation, tolerance to cold, and ability to digest or metabolize various nutrients. Such findings are contributing to discussions around the delicate issues of race, ethnicity and identity, but they are also having a significant impact on biomedical research and personalized health care. Furthermore, genetic analysis is shedding light on the migrations themselves, along with …

Androgen receptor polymorphisms and testicular cancer risk.

Testicular cancer (TC) is currently the most common malignant solid tumour in Caucasian males aged 15-39years. Epidemiological evidence suggests that its onset may be due to an imbalance in the action of steroidal sex hormones and their receptors. A faulty androgen receptor signalling pathway can, in fact, cause various male reproductive disorders. The androgen receptor (AR) gene has two polymorphic segments consisting of CAG and GGC repeats. The length of CAG repeats has been shown to affect the regulation of AR activity. In our study, we used fragment analysis to evaluate the AR gene repeats of 302 TC patients and 322 controls, to establish if there is any association between repeat number and TC. This study of the largest Italian caseload investigated to date highlighted three particularly significant aspects. First, a CAG repeat number of ≥25 may be considered a risk factor for the onset of TC, given its greater frequency in patients in comparison with controls. This difference became significant for the non-seminoma group. Second, men with CAG repeats below 21 or above 24 were found to have a, respectively, 50 and 76% higher risk of TC than those with CAG 21-24, suggesting that these too can be considered a risk factor for TC. Finally, stage II patients were more likely to have a CAG repeat number <21 or >24 than stage I patients.

Risk of Testicular Cancer Following Childhood Cancer Testicular Radiation

Risk of Testicular Cancer Following Childhood Cancer Testicular Radiation

Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients.

Klinefelter syndrome (KS) is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KS patients, enrolled from December 2009 to January 2013. Lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and beta-human chorionic gonadotrophin subunit (β-HCG) serum levels assays and testicular ultrasound (US) with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance (MR) was performed in KS when testicular US showed micro-calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro-calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules <1 cm, but none had nodules >1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and β-HCG levels and in US pattern have been detected during follow-up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions.