Immunohistological Analysis of Lichen Sclerosus of the Foreskin in Pediatric Age: Could It Be Considered a Premalignant Lesion?

BACKGROUND: A major worry of juvenile penile LS is potential malignant degeneration to spinocellular carcinoma (SCC) in adulthood. LS is characterized by increased CD8+ and CD57+ cells, dermal sclerosis, epidermal atrophy, and hyperkeratosis. p53 and Ki67 are reliable premalignant markers. Our aim was to define the LS immunohistochemical profile of foreskin in children, focusing on tissue immune response and cell proliferation. METHODS: Thirty specimens of foreskins removed from pediatric patients during circumcision were included: six from ritual operation (A), twelve from phimosis (B), and twelve from phimosis with LS (C). Formalin-fixed paraffin-embedded sections were stained for histomorphology and immunohistochemistry. A quantitative evaluation for CD8, CD57, p53, and Ki-67 and a statistical analysis were performed. RESULTS: As compared to groups A and B, the samples from group C patients showed an acanthotic epidermis, a dermal band of lymphoid infiltrate with a significant enhancement of CD8+ CD57+ lymphocytes, and a keratinocytic hyperplasia with an overexpression of Ki67+ and p53+ cells. CONCLUSIONS: Immunohistological findings confirmed an immune reaction and proliferative behavior in juvenile LS of foreskin. We believe that radical circumcision should be the first treatment of choice in pediatric patients with clinical suspicious of LS for the potential risk of transformation to SCC in adulthood.

CO2 pneumoperitoneum effects on proliferation and apoptosis in two different neuroblastoma cell lines.

PURPOSE: The proto-oncogene MYCN is considered a transcription factor involved in the regulation of neuroblastoma (NB) cell biology. Since minimally invasive-surgery represents a debated treatment of NB, we investigated CO2 effects on proliferative activity and apoptotic pathway in two NB cell lines, SH-SY5Y (MYCN-non-amplified) and IMR-32 (MYCN-amplified). METHODS: SH-SY5Y and IMR-32 were exposed to CO2 (100%) at a pressure of 15 mmHg for 4 h and then moved to normal condition for 24 h. Cell proliferation, caspase 3 activity and transcript levels of BAX, BCL-2, cyclin B, cyclin D and MMP-2 were evaluated. RESULTS: CO2 exposure caused a decrease in cell proliferation associated to increases in BAX/BCL-2 ratio and caspase 3 activity in SH-SY5Y, while opposite effects have been found in IMR-32. CO2 exposure induced a decrease of cyclin B1 in SH-SY5Y, while an increase in cyclin B1 and D1 was observed in IMR-32. A slight up-regulation of MMP-2 expression in SH-SY5Y and a significant increase of 2.2 folds in IMR-32 was observed (p < 0.05). CONCLUSIONS: Our results suggest that CO2 exposure may cause different effects on various NB cell lines, likely due to MYCN amplification status. Further in vitro and in vivo studies are needed to highlight the role of laparoscopy on NB behaviour.

Enhanced Recovery After Gastrointestinal Surgery (ERAS) in Pediatric Patients: a Systematic Review and Meta-analysis.

AIM: To systematically review literature and to assess the status of the ERAS protocol in pediatric populations undergoing gastrointestinal surgery. METHODS: Literature research was carried out for papers comparing ERAS and traditional protocol in children undergoing gastrointestinal surgery. Data on complications, hospital readmission, length of hospital stay, intraoperative fluid volume, post-operative opioid usage, time to defecation, regular diet, intravenous fluid stop, and costs were collected and analyzed. Analyses were performed using OR and CI 95%. A p value <0.05 was considered significant. RESULTS: A total of 8 papers met the inclusion criteria, with 943 included patients. There was no significant difference in complication occurrence and 30-day readmission. Differently, length of stay, intraoperative fluid volume, post-operative opioid use, time to first defecation, time to regular diet, time to intravenous fluid stop, and costs were significantly lower in the ERAS groups. CONCLUSIONS: ERAS protocol is safe and feasible for children undergoing gastrointestinal surgery. Without any significant complications and hospital readmission, it decreases length of stay, ameliorates the recovery of gastrointestinal function, and reduces the needs of perioperative infusion, post-operative opioid administration, and costs.

Giammusso corporoplasty for the treatment of isolated congenital ventral penile curvature: Results and long-term follow-up.

The aim was to retrospectively evaluate our experience in a large series of patients affected by isolated congenital ventral penile curvature, surgically treated using a previously described modified incisional corporoplasty. Two hundred and six patients with isolated congenital ventral penile curvature underwent a modified incisional corporoplasty. Mean age at surgery was 20.7 ± 5.5 years, and degree of ventral curvature was 60 ± 23°. After the point of maximum convexity identification, Buck's fascia was vertically opened along the deep dorsal vein, which was partially ligated, resected and removed. Tunica albuginea was then longitudinally incised and transversally closed. Post-operative follow-up examination was performed at 2 weeks, 6, 12 and 24 months and then annually. Surgical time was 79 ± 12 min. At follow-up, 189 out of 198 patients (95%) were completely satisfied, four patients (2%) complained a recurrence of penile curvature, and 6 (3%) complained about shortening of the penis. None of the patients had any interference with sexual activity. One patient (0.5%) showed erectile dysfunction 5 years after surgery, but there was no organic dysfunction during examination. The proposed technique allows correction of ventral congenital penile curvature without dorsal neurovascular bundle manipulation, resulting in minimum trauma of the erectile tissue, without injury to nerve fibres.

Stem Cell Factor Receptor Immunoexpression in Adolescent Varicocele.

PURPOSE: Stem cell factor receptor (c-kit) plays a crucial role in regulating proliferation and survival of germ cells. The aim of this study was to find the correlation between the number of c-kit positive germ cells, testicular asymmetry and histological grade in varicocele affected testis samples of adolescents. MATERIALS AND METHODS: Twenty testicular biopsy samples of adolescents affected by varicocele and eight normal control testes were included. The relationship between percentage of testicular asymmetry, number of tubular c-kit positive germ cells and severity of spermatogenic failure was assessed. RESULTS: The mean (SD; median) histological grade for spermatogenic failure in controls was 1.37(0.52; 1), while in the varicocele group, it was 2.70(1.08; 3) (P = .0052). Mean(SD; median) number c-kit positive germ cells in the control group were 20.1(2.52; 20), while in the varicocele group it was 12.35(7.16; 12.5) (P = .0059). Spearman test documented a significant positive correlation between percentage of hypotrophy and histological grade of spermatogenic failure (r = 0.5544 , 95% CI: 0.1345 to 0.8055, P = .0112) but a negative correlation with the number of c-kit positive cells (r = - 0.5871, 95% CI: - 0.8219 to -0.1817, P = .0065). Moreover, a significant negative correlation was found between grade of histological changes and number of c-kit positive germ cells (P < .0001). CONCLUSION: A significant correlation between hypotrophy, histological lesions and c-kit positive germ cells exists in varicocele testes. This finding suggests a possible role for c-kit in the pathogenesis of germ cell impairment in varicocele. Histological changes and lack of c-kit germ cells were also noted in testes not displaying hypotrophy. We believe that reliable markers should be found as better predictors of testicular function in adolescent with varicocele.

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status.

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.

Methylene blue dye for identification of processus vaginalis during hydrocele repair: experience in a teaching hospital.

BACKGROUND: The aim of this study is to investigate the use of methylene blue in perioperative identification of the patent processus vaginalis in a group of boys presenting with congenital or recurrent hydrocele where surgery was performed by junior surgeons in training. METHODS: We retrospectively reviewed the notes of 22 boys with hydrocele, of which two recurrences, who were operated via a standard inguinal approach, by trainees. Methylene blue 0.3-0.5 mL was injected into the hydrocele fluid through the scrotal wall. A processus vaginalis was identified as a blue line. RESULTS: Methylene blue injection clearly identified a patent processus vaginalis in 91% of patients. In 9% (N.=2), of which one recurrence, methylene blue injection demonstrated a hydrocele with an obliterated processus vaginalis. There were no intraoperative complications. No testicular atrophy was recorded. CONCLUSIONS: Injection of methylene blue into the hydrocele sac may be considered a useful aid for a clearer identification of a difficult patent processus vaginalis. In the present series, there were no complications, and thus we believe that this technique might be suitable and especially helpful, in cases of recurrent hydrocele, and for junior surgeons in training.

The Risk For Malignancy of the Thyroid Nodule is Modulated by Gender, Echotexture, and Intranodular Lymphocytic Thyroiditis.

Based on the American (Bethesda, 2017) or Italian (SIAPEC 2014) cytological categories of thyroid nodules, the risk of malignancy and management vary. This risk is 5-10% or<3% (benign or TIR2), 6-18% or<10% (AUS/FLUS or TIR3A), 10-40% or 15-30% (FN/SFN or TIR3B), 45-60% or 60-80% (suspicious or TIR4), 94-96% or 95% (malignant or TIR5). In 408 thyroid nodules evaluated cytologically, we computed the malignancy rate in each category considering gender (325 females, 83 males), echotexture (268 isoechoic, 140 hypoechoic), intranodular chronic lymphocytic thyroiditis (ICLT: 113 with and 295 without); histology (263 benign, 145 malignant). It was 0-1.7% for the benign categories, except hypoechoic/ICLT+ve nodules of females (25%); 0-2.3% for the AUS/FLUS category, except isoechoic/ICLT-ve nodules of males (11.1%) and hypoechoic/ICLT-ve nodules of females (22.2%). For the FN/SFN category, rate was the most variable (from 0% in isoechoic/ICLT+ve nodules of males to 100% in hypoechoic/ICLT-ve nodules of males). The 30% threshold for risk was passed in four subgroups, and the 40% threshold in two subgroups (45% in isoechoic/ICLT-ve nodules of males, 80% in hypoechoic/ICLT+ve nodules of females). For the suspicious category, rate was 100% in males, except those with isoechoic/ICLT-ve nodules (75%), and>80% in females with hypoechoic nodules. For the malignant category, rate was always 100%. In conclusion, particular groups of nodules (based on gender, echotexture, and ICLT) within the cytologically benign through the suspiciously malignant category are at risk of malignancy substantially greater (even 100%) than the standard one. Accordingly, the suggested management cannot be standardized.

Stable Ozonides with Vitamin E Acetate versus Corticosteroid in the Treatment of Lichen Sclerosus in Foreskin: Evaluation of Effects on Inflammation.

BACKGROUND: Lichen sclerosus (LS) is a disease of the skin of unclear etiology that can occur in the foreskin. Topical therapy with corticosteroids is recommended, but they can have side effects. OBJECTIVES: We aimed to compare the effects of ozonides with vitamin E acetate (OZOILE) versus topical corticosteroid in children undergoing circumcision. METHOD: Twenty children undergoing circumcision were treated before surgery: 10 children with OZOILE cream and 10 with 0.1% mometasone furoate once a day for 7 days. Ten age-matched patients with LS of the foreskin without any treatment were recruited as controls. Transcript levels of proinflammatory and anti-inflammatory cytokines and e-cadherin were evaluated in removed foreskins by qRT-PCR. RESULTS: OZOILE and steroid topical treatment produced a similar reduction of TNF-α and IL-1ß mRNA levels in foreskins from patients with LS when compared to untreated patients (p < 0.001). OZOILE and steroid treatment caused an increase in the transcript levels of IL-13 and e-cadherin in the foreskin of patients affected by LS in comparison to untreated foreskin (p < 0.001). CONCLUSIONS: On the basis of our biochemical data, a randomized clinical trial might be useful to verify the actual clinical effect of OZOILE as alternative treatment to corticosteroids in children affected by LS of the foreskin.

Gender-specific correlation of intranodular chronic lymphocytic thyroiditis with thyroid nodule size, echogenicity, and histologically-verified cytological class of malignancy risk.

No data are available on the cytologically and histologically demonstrated presence of intranodular chronic lymphocytic thyroiditis (ICLT) and on the ICLT relationship with thyroid nodule characteristics such as size, echotexture and nature (benign or malignant). We wished to fill this gap by analyzing data in a gender-specific fashion. We studied 408 thyroid nodules from 408 consecutive persons (325 females and 83 males). Nodules were isoechoic (n = 268) or hypoechoic (n = 140), ICLT +ve (n = 113 [27.7%]) or ICLT -ve (n = 295), cytologically low-risk (n = 197) or high-risk (n = 211), histologically benign (n = 263) or malignant (n = 145). ICLT prevailed in females (97/113) and in hypoechoic nodules (58/140 [41.4%] vs 55/268 [20.5%], P < 0.0001). Compared to males, females had (i) smaller nodules (18.5 ±â€¯9.4 vs 23.3 ±â€¯13.4 mm, P = 0.0002), a difference due to the isoechoic nodules (21.1 ±â€¯9.8 vs 26.6 ±â€¯14.1 mm, P = 0.0006), (ii) lower rates of high-risk nodules (161/325 [49.5%] vs 50/83 [60.2%], P = 0.082) and malignant nodules (110/325 [33.8%] vs 35/83 [42.2%] P = 0.16). ICLT +ve nodules were smaller than the ICLT -ve ones (15.4 ±â€¯6.9 vs 20.9 ±â€¯11.2 mm, P < 0.0001), a difference due to the isoechoic nodules (17.5 ±â€¯6.5 vs 23.6 ±â€¯11.7 mm, P = 0.0003). The smallest nodules were hypoechoic, cancerous and ICLT +ve nodules in males (9.5 ±â€¯4.0 mm); the largest were isoechoic, cytologically risky and ICLT -ve in males (29.1 ±â€¯13.2 mm). Compared to ICLT -ve nodules, malignancy prevailed in ICLT +ve nodules (55/113 [48.7%] vs 90/295 [30.5%], P = 0.0006), both in hypoechoic (37/58 [63.8%] vs 41/82 [50.0%]) and isoechoic nodules (18/55 [32.7%] vs 49/213 [23.0%]). ICLT +ve hypoechoic nodules of females and ICLT -ve hypoechoic nodules of males had the greatest rate of malignancy (67% both), while ICLT -ve isoechoic nodules of females had the lowest (19%). In conclusion, presence/absence of ICLT is associated with some sexually dimorphic characteristics of thyroid nodules. Adding the specification of ICLT positivity/negativity in cytological reports may help improving the risk of malignancy at least in some groups of thyroid nodules.

Altered Integrins Expression of Patients Affected by Cryptorchidism.

OBJECTIVES: The study aimed to investigate the expression of the integrin isoforms α7A and ß1A, expressed by myogenic precursor cells, and α7B and ß1D, expressed by mature muscle cells in the cremaster of patients affected by an undescended testis. METHODS: Fifteen samples of cremaster were obtained from patients undergoing surgery for an undescended testis. Thirty control specimens of cremaster were harvested from patients with congenital hydrocele or inguinal hernia. Immunofluorescent analysis was carried out using anti-α7A, ß1A, α7B, and ß1D integrin antibodies. Sections were observed using confocal laser scanning microscopy. RESULTS: As compared with controls, a significant loss of a α7B (p = 0.0355) and ß1D (p = 0.0069) integrins and a higher expression of α7A (p = 0.0003) and ß1A (p = 0.0150) was detected in the cremaster of patients affected by an undescended testis. CONCLUSIONS: Our data document a critical alteration of the cytoskeleton of cremasteric smooth muscle cells in patients with an undescended testis. This might explain the altered function in smooth muscle cells in cremaster implied during testicular descent. We therefore speculate that the postnatal splicing of α7A to α7B and of ß1A to ß1D integrins is delayed. This could account for the common clinical scenario of spontaneous descent of the testes in the first months of life.

Utility of uroflowmetry during the follow-up of children affected by balanitis xerotica obliterans (BXO).

INTRODUCTION: To evaluate the outcome of circumcised patients with balanitis xerotica obliterans (BXO) using uroflowmetry (UF). METHODS: Between 2011 and 2013, 180 children underwent a circumcision for phimosis. The foreskin was examined on microscopy. Patients with an histological diagnosis of BXO were included in the study. Patients with BXO underwent UF two weeks after surgery and treatment with clobetasol propionate ointment. Patients were re-evaluated at 6, 12, 18 and 24 months postoperatively clinically and using UF. RESULTS: 75 of 180 circumcised patients (41.6%) were included. At two weeks, Thirtytwo of 75 patients (42.7%) displayed a pathological UF. At six months, 15 patients (20%) had pathological UF and a new cycle of clobetasol was prescribed. At one year, 10 patients (13.3%) displayed patholgocial UF and underwent progressive urethral dilatation or meatoplasty. At 18 months, 71 patients (94.7%) displayed regular UF, 3 underwent a meatoplasty and one a staged urethroplasty for a severe urethral stenosis. At two years, UF was normal in 74 out of 75 (98.7%). CONCLUSIONS: We recommend to send for hystological examination all foreskins excised after circumcision. We believe that a clinical and uroflowmetric follow-up of pediatric patients with BXO is mandatory for a prompt identification of post-voiding dysfunction.

Genetic analysis of the human insulin-like 3 gene in pediatric patients with testicular torsion.

PURPOSE: Testicular torsion (TT) mainly affects boys under 18 years old. To avoid orchiectomy, TT requires an immediate operative management. The etiology of TT is still controversial. Observed familiar recurrence suggests the presence of a genetic involvement. The INSL3 gene consists of two exons, and it is specifically expressed in fetal and adult Leydig cells. In transgenic mice, deletion of this gene was observed an increased testicular mobility and testicular torsion. We have hypothesized the possible involvement of the INSL3 gene as a predisposing factor of human TT. METHODS: We performed genetic analysis in 25 pediatric patients with unilateral and intravaginal TT (left, n = 13, 56%; right, n = 12, 48%). The age of the patients ranged from 1 to 16 years (median age n = 10.4 ± 5.46 years). In this study, we included two first male cousins affected by TT. Venous peripheral blood samples was obtained after parental written informed consent. RESULTS: The Thr60Ala polymorphism was detected in exon 1 of INSL3 gene and other 2 rarer variants (rs1047233 and rs1003887) were identified in the 3' untranslated region. These variants are prevalent in patients with TT instead of healthy subjects. CONCLUSIONS: Additional studies in a larger population are needed to better understand the clinical consequence of the INSL 3 variations founded. This would allow in the future to identify the patients at risk of TT to improve clinical management.

Anti-Inflammatory and Tissue Regenerative Effects of Topical Treatment with Ozonated Olive Oil/Vitamin E Acetate in Balanitis Xerotica Obliterans.

Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE®) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE® cream for 7 days before circumcision. We found a significant reduction in mRNA levels of IL-1ß, TNF-α, INF-γ, transglutaminase 2 and NOS2 in foreskins treated with OZOILE® in comparison to untreated ones (p < 0.001). No significant differences were observed in NF-κB activation in the specimens obtained from treated and untreated patients. Hence, OZOILE® treatment up-regulated hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF) and E-cadherin gene expression (p < 0.001). The treatment with OZOILE® showed effective results in children affected by BXO by reducing the inflammatory process and stimulating mechanisms for tissue regeneration of the foreskin. A randomized clinical trial on a large number of children affected by BXO might be useful to verify the efficacy of topical treatment with OZOILE®.

Primary monosymptomatic nocturnal enuresis and associated factors in a referral continence clinic of Abu Dhabi.

The aim of the present study was to investigate the prevalence of primary monosymptomatic nocturnal enuresis (PMNE) and its associated factors in a major referral centre for nocturnal enuresis in the City of Abu Dhabi. Children referred to the Pediatric Continence Clinic of Department of Pediatric and Urology Surgery at Al Noor Hospital, Abu Dhabi (UAE), between January 2014 and January 2016 for the suspected diagnosis of NE were considered. The inclusion criteria of our study were: age 5-14 years; full medical history and physical examination; urine dipstick to exclude glycosuria and proteinuria; completion of diagnostic urological work-up; final diagnosis of PMNE. Parents were encouraged to follow a program on urotherapy. All children underwent renal and bladder ultrasound, abdominal X-ray and uroflowmetry with electromyography. Constipation was treated, if present. 39 patients had a diagnosis of PMNE. A constipation was present in 17 children (43.6%). Statistical analysis documented a higher incidence of PMNE in the male groups. 38 out of 39 children (97.4%) resolved PMNE, 14 following urotherapy and 24 required medical therapy with desmopressin. Our experience clearly confirms a higher prevalence rate of PMNE in boys than in girls. In the study population, the large intake of dry and reducedin- fibers foods, the excessive intake of carbonated drinks and the hot climatic condition might negatively influence the incidence of fecal retention and the subsequent PMNE. A multi-modal assessment seems to be effective in the management of PMNE, showing a very high rate of resolution.

Premedication with melatonin vs midazolam: efficacy on anxiety and compliance in paediatric surgical patients.

Preoperative anxiety is a major problem in paediatric surgical patients. Melatonin has been used as a premedicant agent and data regarding effectiveness are controversial. The primary outcome of this randomized clinical trial was to evaluate the effectiveness of oral melatonin premedication, in comparison to midazolam, in reducing preoperative anxiety in children undergoing elective surgery. As secondary outcome, compliance to intravenous induction anaesthesia was assessed. There were 80 children undergoing surgery randomly assigned, 40 per group, to receive oral midazolam (0.5 mg/kg, max 20 mg) or oral melatonin (0.5 mg/kg, max 20 mg). Trait anxiety of children and their mothers (State-Trait Anxiety Inventory) at admission, preoperative anxiety and during anaesthesia induction (Modified Yale Pre-operative Anxiety Scale), and children's compliance with anaesthesia induction (Induction Compliance Checklist) were all assessed. Children premedicated with melatonin and midazolam did not show significant differences in preoperative anxiety levels, either in the preoperative room or during anaesthesia induction. Moreover, compliance during anaesthesia induction was similar in both groups. CONCLUSIONS: This study adds new encouraging data, further supporting the potential use of melatonin premedication in reducing anxiety and improving compliance to induction of anaesthesia in children undergoing surgery. Nevertheless, further larger controlled clinical trials are needed to confirm the real effectiveness of melatonin as a premedicant agent in paediatric population. What is Known: • Although midazolam represents the preferred treatment as a premedication for children before induction of anaesthesia, it has several side effects. • Melatonin has been successfully used as a premedicant agent in adults, while data regarding effectiveness in children are controversial. What is New: • In this study, melatonin was as effective as midazolam in reducing children's anxiety in both preoperative room and at induction of anaesthesia.

Mixed Botryoid and Spindle Cell Bladder Rhabdomyosarcoma: An Outstanding Pediatric Case.

We report a case of a 3-year-old North African child, initially assessed for nonspecific urinary symptoms such as haematuria and burning urination. The ultrasound evaluation showed a vegetating mass occupying the lumen with weak vascular signs at the Colour-Doppler evaluation. An explorative cystoscopy was performed and it revealed a nonbleeding lesion, white in colour, pedunculated, projecting into the lumen, and associated with a brown satellite formation. Histological examination showed a mixed Botryoid and Spindle Cell Rhabdomyosarcoma. This mixed histology has not been described before and no statistical data are reported in literature so far. Despite the Embryonal Rhabdomyosarcoma variant being the most common, the association characterized by two histological Rhabdomyosarcoma subtypes such as Botryoid and Spindle Cell is rarely observed and it is important to get an accurate histological diagnosis in order to immediately start the correct treatment protocol.