Treatment of tuberous sclerosis complex manifestations in children with mTOR inhibitors.

PURPOSE: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder that affects multiple organ systems. Mutations in the TSC1 and TSC2 genes result in the constitutive hyperactivation of the mammalian target of rapamycin (mTOR) pathway, contributing to the growth of benign tumors or hamartomas in various organs. Due to the implication of mTOR pathway dysregulation in the disease pathology, increasing evidence supports the use of mTOR inhibitors for treating multiple manifestations of TSC. METHODS: In this study, we conducted a retrospective analysis of clinical findings and treatment data from 38 patients diagnosed with tuberous sclerosis who were followed up in the Pediatric Oncology Clinic between 2010 and 2020. We collected information on patients' ages, genders, affected sites, familial history, imaging findings, presence of tumors, and treatments. RESULTS: Among the patients, nine individuals with TSC manifestations were treated with mTOR inhibitors. Specifically, everolimus was successfully administered to five patients with inborn cardiac rhabdomyoma causing hemodynamic impairment. In addition, two patients with refractory seizures received everolimus in combination with anti-epileptic drugs. A patient with renal angiomyolipomas larger than 3 cm was treated with everolimus, while a patient with extensive facial angiofibroma received topical sirolimus. All patients tolerated the mTOR inhibitors well, and the side effects were deemed acceptable. CONCLUSION: The utilization of mTOR inhibition in TSC is expected to become more prevalent in clinical practice, as current research is anticipated to provide a better understanding of the therapeutic roles of these treatments in TSC.

Isocitrate Dehydrogenase 1 and 2 Mutations in Pediatric Neuroblastoma Patients.

Objective: Neuroblastoma is one of the common tumors of childhood. The demonstration of new factors such as isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations will be important in the diagnosis and treatment. IDH1 and IDH2 mutations have been found in many types of cancer, such as malignant gliomas, acute myeloid leukemias, chondrosarcoma, and thyroid carcinoma. This study aimed to investigate the presence of IDH1 or IDH2 mutations in patients with neuroblastoma and to determine whether these mutations were different in terms of age, clinical findings, and response to treatment. Methods: Biopsy specimens of 25 patients with pediatric neuroblastoma patients were evaluated for IDH mutations. The clinical and laboratory features of the patients with/without mutation were retrospectively analyzed from a hospital database. Results: A total of 25 patients for whom genetic analysis could be performed were included in the study (60% male, n=15). The mean age was 32.2±25.9 months (3 days-96 months). IDH1 mutation was detected in 8 (32%) and IDH2 mutations in 5 (20%) patients. These mutations showed no statistically significant relationship with age, tumor localization, laboratory results, stage, and prognosis. However, in the case of IDH mutation, patients were diagnosed at the advanced stage. Conclusions: This study demonstrated the relationship between neuroblastoma and IDH mutation for the first time. Because to the fact that the mutation is very heterogeneous, it would be appropriate to conduct a larger series of patients in terms of the impact of the clinical significance of each mutation on the diagnosis and prognosis.

Evaluation of adolescents with heavy menstrual bleeding using the International Society of Thrombosis Haemostasis- Bleeding Assessment Tool and The Pediatric Bleeding Questionnaire scores.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common condition in adolescents. However, bleeding disorders are known to be one of the causes of HMB in adolescent girls, so they should be considered. Simple methods that can be used in primary health care are needed to determine whether patients have bleeding disorders. The aim of this study was to evaluate the bleeding score of patients admitted with HMB and to determine the diagnostic value of patients who were symptomatic but whose initial hemostatic tests were normal. METHODS: A total of 113 adolescents with HMB and 20 healthy adolescent girls were included in the study. The Pediatric Bleeding Questionnaire (PBQ) and the International Society of Thrombosis Haemostasis-Bleeding Assessment Tool (ISTH-BAT) were used for evaluation. RESULTS: Overall, approximately 18% (n= 20) of the adolescents in the study were diagnosed with a bleeding disorder. The cut off value for the `clinically significant bleeding score` was found to be 3.5. CONCLUSIONS: The PBQ and ISTH-BAT can help distinguish a significant bleeding history from an otherwise trivial bleeding and can be included in the algorithm for the primary care of adolescents with HMB with suspected bleeding disorders.

Thiol disulfide homeostasis in ionizing radiation and chemotherapeutic drug exposure.

OBJECTIVE: This study aims to reveal the oxidant and antioxidant status in nurses with chemotheropathic drug exposure and radiology unit workers exposed to ionizing radiation (IR). METHODS: Nineteen radiology unit workers, 14 nurses, and 15 controls were included the study. All of the participants using antioxidants, vitamin supplements, smokers, any therapeutic drugs, and exposed therapeutic or diagnostic X-ray or chemotherapeutic drugs in 12 months were excluded from the study. Total and native thiols, disulfide/native thiol percent ratios (SS/SH), disulfide/total thiol percent ratios, disulfide amounts, and native thiol/total thiol percent ratios, ischemia-modified albumin (IMA) were determined. RESULTS: Disulfide levels, disulfide/total thiol ratio, and disulfide/native thiol ratio of serum samples of both radiology unit workers and nurses were significantly higher and ratio of native thiol/total thiol was lower than the control group. The radiation dose in radiology unit workers was mean±SD: 0.02±0.009, median (min-max): 0.02 (0.001-0.04). Thiol-disulfide homeostasis was disturbed and the balance shifted in the direction of oxidant damage, even at low-dose IR exposure and normal range. CONCLUSION: As far as we know, the current findings first demonstrate an apparent chronic oxidative stress in the subjects who were occupationally exposed to antineoplastic drugs and radiation even if annual radiation exposure dose measurements are normal.

Evaluation of the Attitude of Parents in Pediatric Oncology Towards COVID-19 Vaccine.

Severe acute respiratory syndrome, coronavirus (SARS, COVID-19) has been declared a pandemic by the World Health Organization since March 2020. Patients with active cancer should be considered especially for priority access to the COVID-19 vaccine. Therefore, our study aimed to learn parents' opinions of cancer-diagnosed patients about the COVID-19 vaccine. Between December 2021 and January 2022, 76 people were willing to answer the questionnaire from the parents of outpatient/inpatient patients at the Pediatric Hematology and Oncology Clinic of Dr. Sami Ulus Obstetrics, Child Health and Diseases Education Research Hospital were included. In our study, 18 parents (23.7%) did not get vaccinated. Among the reasons for not getting vaccinated, the most common answer for "I fear from the vaccine's side effects.", "Do you think oncology patients are at risk for COVID-19?", "Do you think the COVID-19 pandemic affects cancer treatment?" were 90.7%, 89.5% and 21% yes, respectively. Would your opinion of the vaccine be positive if the domestic vaccine was produced?"-67.4% answered yes. Vaccine hesitation and public misinformation put cancer patients at risk. Increasing awareness of the rejection of COVID-19 vaccines is important for public health and the fight against the pandemic. In addition, the doctors' recommendations for conducting oncology treatment will significantly impact parents' compliance with the COVID-19 vaccine.

Sirolimus treatment of a PTEN hamartoma tumor syndrome presenting with melena.

BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. One of the disorders in PHTS spectrum, CS is characterized by macrocephaly, mucocutaneous findings, gastrointestinal system (GIS) polyposis and an increased lifetime risk of GIS, breast, thyroid and other cancers. CASE: In this study, we report an adolescent patient presenting with recurrent life-threatening upper GIS bleeding as a result of hamartomatous polyposis. Genetic studies revealed a known pathogenic nonsense mutation confirming the initial diagnosis of CS. CONCLUSIONS: Additionally, we describe our therapeutic intervention to improve the patient`s clinical symptoms with sirolimus, which its use is infrequently addressed in the literature for pediatric age group harboring PTEN mutations.

Dynamic Thiol-Disulfide Homeostasis in Children With ß-Thalassemia Trait.

In children with ß-thalassemia (ß-thal) trait, tissue damage occurs with oxidative stress due to oxygen free radicals and reactive oxygen species (ROS) production. Dynamic thiol-disulfide homeostasis (DTDH) is one of the most important indicators showing the pro-oxidant/antioxidant status in the body. In this study, we aimed to examine the status of DTDH by measuring native thiol, disulfide, and total thiol levels in children with ß-thal trait. The study included 40 children with ß-thal trait and 30 healthy controls (matched by age and gender). The DTDH parameters were measured by an automated method and results were compared between the groups. The levels of native thiol, total thiol, and disulfide in children with ß-thal trait group were statistically significantly higher than the control group (p < 0.001). There was no significant difference in disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol levels between the groups. In addition, there was no correlation between hemoglobin (Hb) and serum ferritin levels with the markers of DTDH in children with ß-thal trait. In our study, a significant increase was found in native thiol, total thiol, and disulfide levels in response to oxidative stress in children with ß-thal trait compared to the healthy control group. Disulfide levels of the children with ß-thal trait were higher than the control group, showing oxidative stress is high in ß-thal trait. Accordingly, it increases the native thiol and total thiol capacity as compensation.

Intrauterine Growth Retardation is a Risk Factor for Anthracycline Toxicity.

BACKGROUND: Anthracycline chemotherapy is used to treat a variety of cancers. However, late cardiac effects of anthracycline chemotherapy, such as subclinical left ventricular dilatation and/or dysfunction, have been observed in more than half of long-term survivors of childhood cancers. A major risk factor for anthracycline cardiotoxicity is intrauterine growth restriction (IUGR). We assessed the significance of IUGR as an important risk factor for late cardiotoxic effects of anthracycline therapy in asymptomatic long-term survivors of childhood cancers. MATERIALS AND METHODS: The study included 61 survivors of childhood cancers. Cardiac functions were prospectively studied using both conventional and non-conventional echocardiographic methods (two-dimensional speckle tracking echocardiography) after completion of the treatment. The patients were divided into two groups based on their birth weights: Group 1 (patients with IUGR) and Group 2 (patients with normal birth weight). RESULTS: Conventional echocardiography revealed a similar and normal range of left ventricle systolic and diastolic functions in both groups. However, global longitudinal and circumferential strain values demonstrated subclinical left ventricular systolic dysfunction in both groups as compared with normal reference strain values. Furthermore, Group 1 patients had significantly lower global longitudinal and circumferential strain and strain rate values than those in Group 2 patients. CONCLUSION: Asymptomatic long-term survivors of childhood cancers with a history of IUGR may have an increased risk of anthracycline cardiotoxicity due to the low content of mitochondrial DNA (mtDNA). IUGR is a risk factor for late anthracycline cardiotoxicity.

Acute haemorrhagic pericarditis: an unusual presentation of Chlamydophila pneumoniae pneumonia infection.

CHLAMYDOPHILA PNEUMONIAE: , a common cause of respiratory tract infections, rarely leads to serious conditions. A 13-year-old boy with serologically confirmed C. pneumoniae infection presented with pneumonia complicated by pericardial and bilateral pleural effusions. He had a large haemorrhagic pericardial effusion from which 1000 ml of fluid was aspirated over 10 days and a right haemorrhagic pleural effusion which required a chest drain and the removal of 700 ml over 5 days. The addition of clarithromycin to ceftriaxone appeared to enhance recovery. As far as we are aware, this is the first report in the English literature of massive haemorrhagic pericardial and pleural effusions in children owing to C. pneumoniae infection.

Evaluation of long-term cardiac side effects of anthracycline chemotherapy by conventional and non-conventional echocardiographic methods in childhood cancer survivors.

OBJECTIVE: Anthracycline chemotherapeutic agents carry the well-recognised risk of cardiac toxicity. The aim of this study was to determine the long-term effect of anthracycline chemotherapy on the biventricular function in childhood cancer survivors using tissue Doppler imaging and two-dimensional speckle tracking echocardiography. PATIENTS AND METHODS: The study included 45 survivors of childhood cancers and 50 healthy age-matched control patients. Cardiac function was prospectively studied with conventional echocardiography, tissue Doppler imaging, and speckle tracking echocardiography after completion of treatment. The same analysis was performed on matched controls. RESULTS: There was no difference in age, gender, height, and weight between the study and control groups. The mean anthracycline dose was 240 ± 106 mg/m2 and the mean remission duration was 8.2 ± 5 years (1-20 years) in the study group. Conventional echocardiography showed similar ejection fraction, shortening fraction, and left ventricle end-diastolic diameter in both groups. Mitral lateral and septal tissue Doppler imaging showed normal but according to control group relatively sub-normal systolic and diastolic function in patient group. The global longitudinal and circumferential strain and strain rates were significantly lower in the patient group compared to control group. Correlation analysis revealed a negative and significant correlation between total anthracycline dose and global longitudinal and circumferential strain and strain rates. CONCLUSION: Sub-clinical systolic and diastolic dysfunction may not be detected by conventional echocardiographic methods which are frequently used in daily practice. Sub-clinical systolic and diastolic dysfunction may be detected more sensitively by echocardiographic method such as speckle tracking echocardiography in childhood cancer survivors.

Economic and psychosocial problems experienced by pediatric with cancer patients and their families during the treatment and follow-up process.

AIM: To identify the psychosocial and economic problems of the pediatric patients with cancer who were treated at the Dr. Sami Ulus Obstetrics and Gynecology and Child Health and Diseases Training and Research Hospital's Pediatric Oncology Department and their relatives during this process. MATERIAL AND METHODS: We interviewed a total of 100 patients who were treated at Dr. Sami Ulus Obstetrics and Gynecology and Child Health and Diseases Hospital's Pediatric Oncology Department between 1996 and 2015, and were now followed up without treatment and their relatives using survey questions on the psychosocial and economic problems they experienced. RESULTS: Most of patients were from provinces outside Ankara. The average monthly income was below the level that would meet the family needs in 80% of the families and only 16% had extra income. Additional economic support had been received by 93% of the families in the patient group. Twenty-five families (25%) had been forced to sell property during the treatment. Forty-nine (49%) families had borrowed money from acquaintances and relatives or had taken out a bank loan. Serious psychological problems were experienced during and after the treatment by 46% of the mothers; 41% of the families had used religious procedures more commonly during the treatment period to cope with the psychological problems. Education was subject to a 1-2 year pause in 83% of the patients. CONCLUSION: Childhood-age patients with cancer and their families experience significant psychosocial and economic problems during and after the treatment process. Providing medical treatment and psychosocial support in harmony is an important factor that increases the success of cancer treatment. The patient and the family will require psychosocial support mechanisms throughout life, starting from the moment they face the disease. Developing national social support programs and legal regulations to form a basis for such programs are required in our country.

AMAÇ: Dr. Sami Ulus Kadin Dogum ve Çocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi Çocuk Onkoloji Klinigi'nde tedavi edilmis kanserli çocuk hastalarin ve yakinlarinin bu süreçte karsilastiklari psikososyal ve ekonomik sorunlari belirlemek. GEREÇ VE YÖNTEMLER: Dr. Sami Ulus Çocuk Sagligi ve Hastaliklari Hastanesi Çocuk Onkoloji Klinigi'nde 1996­2015 yillari arasinda tedavi görmüs ve su anda hastaliksiz olarak izlemde olan toplam 100 hasta ve yakini ile görüsülerek yasadiklari psikososyal ve ekonomik sorunlara iliskin anket sorulari yönlendirildi. BULGULAR: Hastalarimizin çogu Ankara disi illerden gelmekte idi. Hasta ailelerinin %80'inin ortalama aylik gelirinin ailenin gereksinimlerini karsilama düzeyinin altinda oldugu ve sadece %16'sinin ek geliri oldugu saptandi. Hasta grubunda ailelerimizin %93'ü ek ekonomik destek almislardi. Yirmi bes aile (%25) tedavi süresince sahip olduklari bazi mal varliklarini satmak zorunda kalmisti. Kirk dokuz (%49) aile tanidik ve akrabalarindan borç almisti ya da bankadan kredi çekmisti. Annelerin %43'ünün tedavi sirasinda ve sonrasi ciddi psikolojik sorunlar yasadigi, psikolojik sorunlarla basa çikabilmek için ailelerin %40'inda tedavi döneminde dini ibadetlere egilimde artis oldugu gözlendi. Hastalarimizin %83'ünün egitimlerinde 1­2 yil gibi bir kayip yasandigi görüldü. ÇIKARIMLAR: Çocukluk çagi kanser hastalari ve aileleri tedavi sürecinde ve sonrasinda önemli oranda psikosoyal ve ekonomik sorunlar yasamaktadir. Kanserde, tibbi tedavi ile psikososyal destegin bir uyum içerisinde yürütülmesi tedavi basarisini artiran önemli bir etmendir. Hastanin ve ailesinin hastalikla tanistigi ilk andan baslayarak tüm hayat boyunca psikososyal destek mekanizmalarina gereksinim vardir. Ülkemizde ulusal olarak bu yönde gelistirilecek sosyal destek programlari ve bu programin yürütülecegi zemini olusturacak yasal düzenlemelere gereksinim vardir.

Role of hygienic factors in the etiology of allergic disorders in children.

BACKGROUND/AIM: We investigated the role of body flora and chronic inflammatory infections in the etiology of allergic disorders in Turkish children. MATERIALS AND METHODS: Forty pediatric asthma patients with positive skin prick tests and 40 age-matched healthy subjects with negative skin prick tests were enrolled in this cross-sectional study. Serum H. pylori IgG, viral hepatitis serology, IL-10, and TGF-beta levels were measured. Stool and throat cultures were taken and tested for occurrence of microorganisms. RESULTS: A significantly higher percentage of nonatopic subjects tested positive for anti-H. pylori antibodies compared to atopic subjects (60% vs. 20%). Serum IL-10 levels were also significantly higher in nonatopic subjects. No significant differences in direct microscopy and culture specimens of stools were observed. Examination of throat flora showed significantly higher occurrences of Neisseria and beta-hemolytic Streptococcus in nonatopic subjects, but higher occurrences of gram-positive bacilli in atopic subjects. CONCLUSION: Higher prevalence of anti-H. pylori antibody and higher serum levels of IL-10 in nonatopic subjects suggest that chronic infection and inflammation may protect against atopic disease. Higher occurrences of Neisseria and beta-hemolytic Streptococcus in throat cultures from nonatopic subjects are novel findings that lend further support to the hygiene hypothesis.

Vitamin D receptor polymorphisms in immune thrombocytopenic purpura.

BACKGROUND: Vitamin D receptor (VDR) polymorphisms have been studied in immune-mediated disorders, but not yet in immune thrombocytopenic purpura (ITP). We investigated whether VDR variants were associated with ITP in children. METHODS: The study included 44 children with a diagnosis of ITP and 100 healthy controls. Five VDR polymorphisms (Cdx-2, FokI, BsmI, ApaI and TaqI) were genotyped and used to evaluate the association of VDR variants with ITP. RESULTS: The distribution of the three Cdx-2 genotype groups (GG, GA, and AA) was significantly different between ITP patients and controls (P = 0.025); the homozygous GG genotype of Cdx-2 was overrepresented in ITP patients. The frequency of the A allele of Cdx-2 was significantly different between patients and controls (P = 0.01). The A allele of Cdx-2 was associated with a decreased risk of ITP (OR, 0.343; 95% CI: 0.150-0.782). No statistically significant difference was found between the ITP group and control group for Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P > 0.5). CONCLUSION: There appears to be an interaction between the Cdx-2 variant of VDR and childhood immune thrombocytopenia.

Vitamin D Receptor (VDR) Polymorphisms in Pediatric Patients Presenting With Hodgkin's Lymphoma.

Vitamin D receptor (VDR) polymorphisms are found more commonly in some tumor types than in healthy individuals, suggesting that some polymorphisms (Cdx2, Fok1, Bsm1, Apa1, Taq1) contribute to tumor development. There is no previous report on VDR polymorphism in Hodgkin's lymphoma (HL) patients. VDR polymorphism patterns in 95 pediatric HL cases with 100 healthy controls were compared. No statistically significant difference was found between the patient group and control group in terms of Cdx2, Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P>0.5). Our findings suggest that VDR polymorphisms may not play a role in HL development.

Are the methylenetetrahydrofolate reductase 1298 and 677 gene polymorphisms related to optic glioma and hamartoma risk in neurofibromatosis type 1 patients?

The methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in carcinogenesis through its effects on DNA synthesis and methylation and also has a significant role in the etiology of many disorders, such as diabetes, migraine, and cardiovascular disease. Neurofibromatoses (NF) are autosomal dominant inherited diseases that can affect tissues such as bone and skin and predispose individuals to tumor development in various parts of the nervous system or body. Optic nerve glioma and brain tumors are common in children with NF, and leukemia and lymphoma incidence is also higher than normal. We therefore aimed to investigate the possible relationship between the MTHFR gene polymorphism and accompanying tumors such as neurofibroma, hamartoma, and optic glioma in children with NF1 found to have the MTHFR 677 and MTHFR 1298 gene polymorphism in this study. We included 55 pediatric patients diagnosed with NF1 between 2005 and 2014 in the study group. The control group included 44 healthy subjects without acute or chronic disease findings. A significant relationship was found between the MTHFR A1298C polymorphism and the incidence of optic glioma (p=0.014) (AA vs. AC: OR 11, 95% CI 1.27-95.17; AA vs. CC: OR 7.33, 95% CI 0.35-150.70). We also found a significant relationship between the MTHFR C1298C polymorphism and the incidence of hamartoma (p=0.019) (AA vs. AC: OR 2.12, 95% CI 0.662-6.809; p=0.203). Epilepsy incidence was high in subjects with MTHFR C677C. The MTHFR A1298C, C1298C, and C677C gene polymorphisms can be associated with a higher optic glioma, hamartoma, and epilepsy incidence, respectively, in patients diagnosed with neurofibromatosis type 1.

Single-center experience with sirolimus therapy for vascular malformations.

Vascular malformations (VMs) are described as congenital malformations of the vasculature derived from capillaries, veins, lymphatic vessels, arteries, or a combination of these vessels. They can cause significant morbidity resulting from soft tissue hypertrophy-related disfiguration, bony abnormalities, and even organ compromise. They are usually treated with various interventional procedures to achieve local control; however, the chance of success decreases as the anatomical distribution of the malformation widens. Unfortunately, medical treatment options have been quite limited in these patients. Sirolimus is an antiangiogenetic and antiproliferative pharmacologic agent that has been used for the management of VM in the last decade. We report 6 pediatric patients (4 with capillary lymphaticovenous malformations, 1 with lymphaticovenous malformation, and 1 with venous malformation) seen at our clinic within the last 2 years with lesions covering wide anatomical areas. After the patients had unsuccessfully undergone various treatments at various centers, they were treated at our facility with peroral sirolimus. The mean duration of treatment was 13 months, but in 3 patients, tapered dosing continues. Five patients achieved partial responses. The response to sirolimus treatment increased as the lymphatic component of the VM increased. All patients tolerated sirolimus well; side effects were acceptable. Sirolimus is a safe and effective medical treatment for widely distributed VMs with significant lymphatic components and no further local treatment option.

How should we monitor boys with testicular microlithiasis?

Testicular microlithiasis (TM), a rare condition characterized by calcification within the seminiferous tubules, is associated with benign and malignant disorders of the testis. We review current practices of following up pediatric patients diagnosed TM incidentally on scrotal ultrasonography (US). We analyzed retrospectively patient characteristics, family history, indications for US, pathological features, US findings, outcome, and follow-up. At our institution, 2875 scrotal US examinations were performed on 2477 children with various scrotal complaints from 2008 to 2015. Testicular microlithiasis was detected in 81 patients (i.e., an incidence of 3.27%). Every 6 months, each patient underwent a clinical and ultrasonographic evaluation as well as serum tumor markers determination to detect a potential malignancy. Seventy-eight patients who had undergone scrotal US at least twice were included in this study. We evaluated the US studies for the type of TM (diffuse and focal) and change in follow-up studies. Testicular microlithiasis was typically diffuse (n = 56, 71.8%) and bilateral (n = 45, 57.7%), and it was detected the most frequently in the 9-11-year age group (27 patients, 34.6%). The most common comorbid conditions included undescended testes (31 patients, 39.7%) and hydrocele (11 patients, 14.1%). We found that serum tumor markers were within normal limits both at diagnosis and upon follow-up. No testicular tumors or new abnormal symptoms developed during the clinical follow-up. There is no convincing evidence that TM alone is premalignant in a pediatric population. In terms of follow-up, we advise regular self-examinations and annual US in the absence of risk factors.