A Unique Case of Primary Cutaneous Adenoid Cystic Carcinoma Associated with Aplasia Cutis Congenita in a Four-Year-Old Female: A Case Report.

INTRODUCTION: Primary cutaneous adenoid-cystic carcinoma (PCACC) is a rare malignant tumour reported in only about 450 cases in the literature, with only two adolescent cases reported. PCACC seems to occur between the fifth and seventh decade of life, and the most frequent regions involved are head and neck (46%). Aplasia cutis congenita (ACC) has an incidence of 1:10,000, and it seems to be rarely associated with neoplastic lesions. Interestingly, the association between PCACC and ACC has, so far, never been described. METHODS: We report a case of PCACC in the scalp associated with ACC in a four-year-old patient. DISCUSSION: The patient was under follow-up at the dermatology unit, but suddenly a red lesion appeared within the ACC. This red, ulcerated area increased rapidly over six months, so it was surgically removed, and the pathological examination results were suggestive for cribriform PCACC. According to the guidelines for skin tumours, the patient underwent widening resection, and an advancement-sliding skin flap was performed to recreate the scalp. After one year of follow-up, the patient has no local or widespread recurrence of the PCACC, and the surgical scar appears to have healed well. CONCLUSIONS: This clinical case is the first known patient with PCACC associated with ACC. A skin excision biopsy should be performed with wide margins to avoid a second widening resection of skin in a similar scenario. Genetic studies may help to identify the origin of this rare association.

PIK3CA-Related Overgrowth Spectrum From Diagnosis to Targeted Therapy: A Case of CLOVES Syndrome Treated With Alpelisib.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term referring to various clinical entities, which share the same pathogenetic mechanism. These conditions are caused by somatic gain-of-function mutations in PIK3CA, which encodes the 110-kD catalytic α subunit of PI3K (p110α). These PIK3CA mutations occur as post-zygotic events and lead to a gain of function of PI3K, with consequent constitutional activation of the downstream cascades (e.g., AKT/mTOR pathway), involved in cellular proliferation, survival and growth, as well as in vascular development in the embryonic stage. PIK3CA-related cancers and PROS share almost the same PIK3CA mutational profile, with about 80% of mutations occurring at three hotspots, E542, E545, and H1047. These hotspot mutations show the most potent effect on enzymatic activation of PI3K and consequent downstream biological responses. If present at the germinal level, these gain-of-function mutations would be lethal to the embryo, therefore we only see them in the mosaic state. The common clinical denominator of PROS disorders is that they are sporadic conditions, presenting with congenital or early childhood onset overgrowth with a typical mosaic distribution. However, the severity of PROS is highly variable, ranging from localized and apparently isolate overgrowth to progressive and extensive lipomatous overgrowth associated with life-threatening vascular malformations, as seen in CLOVES syndrome. Traditional therapeutic approaches, such as sclerotherapy and surgical debulking, are often not curative in PROS patients, leading to a recrudescence of the overgrowth in the treated area. Specific attention has been recently paid to molecules that are used and studied in the oncogenic setting and that are targeted on specific alterations of the pathway PI3K/AKT/mTOR. In June 2018, Venot et al. showed the effect of Alpelisib (BYL719), a specific inhibitor for the p110α subunit of PI3K, in patients with PROS disorders who had severe or life-threatening complications and were not sensitive to any other treatment. In these cases, dramatic anatomical and functional improvements occurred in all patients across many types of affected organ. Molecular testing in PROS patients is a crucial step in providing the conclusive diagnosis and then the opportunity for tailored therapy. The somatic nature of this group of diseases makes challenging to reach a molecular diagnosis, requiring deep sequencing methods that have to be performed on DNA extracted from affected tissue. Moreover, even analyzing the DNA extracted from affected tissue there is no guarantee to succeed in detection of the casual somatic mutation, since the affected tissue itself is highly heterogeneous and biopsy approaches can be burdened by incorrect sampling or inadequate tissue sample. We present an 8-year-old girl with CLOVES syndrome, born with a large cystic lymphangioma involving the left hemithorax and flank, multiple lipomas, and hypertrophy of the left foot and leg. She developed severe scoliosis. Many therapeutic approaches have been attempted, including Sildenafil treatment, scleroembolization, laser therapy, and multiple debulking surgeries, but none of these were of benefit to our patient's clinical status. She then started treatment with Rapamycin from May 2019, without significant improvement in both vascular malformation and leg hypertrophy. A high-coverage Whole Exome Sequencing analysis performed on DNA extracted from a skin sample showed a mosaic gain-of-function variant in the PIK3CA gene (p.H1047R, 11% of variant allele frequency). Once molecular confirmation of our clinical suspicion was obtained, after a multidisciplinary evaluation, we decided to discontinue Sirolimus and start targeted therapy with Alpelisib (50 mg/day). We noticed a decrease in fibroadipose overgrowth at the dorsal level, an improvement in in posture and excellent tolerability. The treatment is still ongoing.

Expression levels of specific microRNAs are increased after exercise and are associated with cognitive improvement in Parkinson's disease.

There is a consensus regarding the efficacy of physical exercise in maintaining or improving human health; however, there are few studies examining the effect of physical exercise on the expression levels of microRNAs (miRNA/miRs) in Parkinson's disease (PD). The aim of the present study was to investigate the effects of an interval training program on a cycle ergometer on the expression levels of miR­106a­5p, miR­103a­3p and miR­29a­3p in serum samples from men with PD. This was a quasi­experimental study with pre­ and post­testing and with a non­equivalent group design. The participants were selected based on the eligibility criteria and subsequently classified into two groups: Experimental group and control group. The evaluations were performed at the beginning of the study (week 0) and after 8 weeks of the intervention program (week 9). The interval training program was performed on a cycle ergometer for 30 min, three times a week during an 8­week period. The expression levels of miR­106a­5p, miR­103a­3p and miR­29a­3p in the experimental group were increased after physical exercise and were associated with cognitive improvement in men with PD. However, further studies are required to clarify the potential use of these circulating miRNAs as markers of adaptation to physical exercise. Collectively, the present results indicated that these three miRNAs may be associated with the exercise response and cognitive improvement in men with PD.

Aplasia pura adquirida crônica da série vermelha secundária à quimioterapia em paciente com adenocarcinoma endometrioide invasivo / Chronic acquired pure aplasia of the red series secondary to chemotherapy in a patient with invasive endometrioid adenocarcinoma

O presente relato de caso descreve a apresentação atípica de uma paciente com adenocarcinoma endometrioide invasivo que evoluiu com aplasia pura adquirida crônica da série vermelha secundária à quimioterapia. Paciente de 71 anos, sexo feminino, procurou atendimento médico por quadro de metrorragia com três meses de evolução. A curetagem uterina evidenciou adenocarcinoma endometrioide invasor moderadamente diferenciado. Iniciou-se uma abordagem com esquema quimioterápico composto por Carboplatina e Paclitaxel interrompido ao quinto ciclo para evitar progressão de aplasia medular constatada por biópsia de medula óssea. A possível hematotoxicidade do protocolo Paclitaxel e Carboplatina foi observada na conduta terapêutica da paciente, por sua progressão para uma apresentação atípica de aplasia pura adquirida crônica da série vermelha após administração desta associação de drogas.

The present case report describes the atypical presentation of a patient with invasive endometrioid adenocarcinoma that evolved with chronic acquired pure aplasia of the red series secondary to chemotherapy. A seventy-one-yearold patient, female, sought medical care for a three-month-old metrorrhagia evolution. The uterine curettage showed moderately differentiated invasive endometrioid adenocarcinoma. It was initiated an approach with chemotherapy regimen consisting of Carboplatin and Paclitaxel interrupted at the fifth cycle to prevent progression of spinal aplasia found by bone marrow biopsy. The possible hematoxicity of the patient, for its progression to an atypical presentation of chronic acquired aplasia of the red series after administration of this combination of drugs.

Thyroglossal duct cyst: Factors affecting cosmetic outcome and recurrence.

BACKGROUND: Thyroglossal duct cyst (TDC) is the most common congenital abnormality in the neck in children. The purpose of this study was to perform a comprehensive review of all cases of TDC surgically treated at a single institution and to evaluate the factors that influence the rate of recurrence, and the aesthetic outcome of the surgery on follow up. METHODS: All cases of TDC surgically treated at the Department of Pediatric Surgery at Meyer Hospital from January 2005 to December 2016 were selected. Charts from 248 patients were reviewed and risk factors for recurrence evaluated. A questionnaire was submitted to the patients' parents to determine if postoperative complications were present  and standardized neck pictures were requested, to evaluate the cosmetic result . Microsoft Office Excel 2007 for Windows and Graphpad Prism 6 were used for data management and statistical analysis. RESULTS: Simple cyst excision and post-inflammatory fibrosis (P < 0.05) were assessed as important risk factors for the recurrence of TDC. Recurrence rate on Sistrunk procedure was 5%. Variables such as post-inflammatory fibrosis before surgery (P < 0.001), the positioning of a drain (P < 0.01) and the development of recurrence (P < 0.001), negatively influenced the cosmetic result. No thyroglossal duct cyst carcinoma and no long-term postoperative complications were observed. CONCLUSIONS: Recurrence rates were higher in patients who underwent simple cyst excision instead of the Sistrunk procedure, as already reported in literature. Presence of post-inflammatory fibrosis and positioning of the drain at surgery were associated with higher rates of recurrence, as well as worse cosmetic outcome.

Giant Ovarian Lymphangioma: Case Report and Review of the Literature.

INTRODUCTION: Lymphangiomas are benign tumors/malformations, characterized by proliferation of the lymphatic vessels. They may arise anywhere, although the most common localizations are the head-neck region and the axilla. To date, only 21 cases of lymphangioma of the ovary in a 60-year literature survey have been reported. CASE REPORT: A 16-year-old female patient with long standing abdominal distension had 40 cm × 15 cm × 29 cm ovarian lymphangioma. CONCLUSIONS: Our case highlights that lymphangiomas can occur in the adolescent population and should be added to the differential diagnosis of ovarian masses in this age group.

A Novel Objective Approach to the External Measurement of Pectus Excavatum Severity by Means of an Optical Device.

BACKGROUND: Current approaches to quantifying the severity of pectus excavatum require internal measurements based on cross-sectional imaging. The aim of this study is to exploit a novel index evaluated on the external surface of the chest with a three-dimensional (3D) optical scanner. METHODS: Fifty-one children (41 male, 10 female) between 2 and 17 years of age were evaluated with a 3D optical scanner. Pectus excavatum severity was calculated by using an ad hoc instant 3D scanner and defining an automatic procedure to generate an optical 3D correction index (CI3D). For the latter, an ideal threshold was derived from a statistical analysis, and five blind surveys were collected from pediatric specialists on chest wall deformities. The CI3D was then correlated with blind clinical assessments of PE severity. RESULTS: The cutoff thresholds were determined to optimally discriminate between six degrees of severity of PE patients by a correlation analysis. The correlation coefficient obtained by matching the CI3D with the average subjective severity shows that the proposed method outperforms traditional approaches. CONCLUSIONS: The optical 3D index has a good match with the average subjective assessment in distinguishing patients with mild to severe PE. This innovative approach offers several advantages over existing indices, as it is repeatable and does not require cross-sectional imaging. The index might be particularly suitable for monitoring the efficacy of nonoperative treatment and, in the future, for designing an optimal personalized usage of therapeutic devices.

Regenerative Surgery in the Treatment of Cosmetic Defect Following Nuss Procedure.

BACKGROUND: In the past decade, the minimally invasive repair of pectus excavatum (MIRPE) has become the treatment of choice for severe pectus excavatum (PE), proving acceptable to excellent cosmetic results. Recently, autologous fat grafting (FG) has been identified in aesthetic and reconstructive surgery to ideally handle volume and contour defects. We report our experience about FG in the treatment of residual minor defects after MIRPE and a proposal for a new indication of this largely adopted technique. MATERIALS AND METHODS: From April 2012 to April 2015, 127 patients underwent bar removal. At outpatient check, a questionnaire was adopted to investigate aesthetic outcome prior and after surgery (3 months postoperation); scoring options varied from 4 to 0 [4, excellent; 3, very good; 2, good; 1, acceptable; and 0, unacceptable]. In patients scoring less than "good," we proposed FG at the same operating session of bar removal. The donor areas were the abdomen, trochanteric region, and inner thigh. The tissue was gently collected through a thin cannula, filtrated, and then promptly injected into the defect. RESULTS: Eleven patients (8.8%) have been selected for FG. No complications have been detected during the follow-up period (range 1-36 months). In three cases, we performed further FG procedure to achieve an optimal result. Questionnaire reported an increased mean score from 1.8 to 2.7. CONCLUSION: In our early experience, FG has provided satisfactory cosmetic results. With the present report we advocate FG as a minimally invasive "tool" to achieve better defect correction after MIRPE. These preliminary results suggest that FG could be a worthwhile resource in treating chest wall malformations.

Scoliosis and Pectus Excavatum in Adolescents: Does the Nuss Procedure Affect the Scoliotic Curvature?

BACKGROUND: Pectus excavatum (PE) is known to be associated with adolescent idiopathic scoliosis (AIS). The correction of severe PE requires a mini-invasive procedure (MIRPE), with a metal bar positioned and left in the chest for 3 years. Adolescence seems to be the more appropriate time not only for MIRPE but also for AIS peak progression. This study was designed to answer the question whether, in adolescents, MIRPE could affect mild/moderate AIS. METHODS: We carried out a meta-analysis focused on defining the natural progression of untreated AIS. Inclusion criteria were as follows: AIS patients -age 10-18 years old -Cobb angle <40°-none treated as orthotics/electrostimulation/surgery. The expected outcome was the percentage of patients who improved, worsened, or hold steady of their condition at follow-up. Between 2008 and 2014, we followed up a cohort of 67 adolescents with severe PE treated with MIRPE, assessing whether AIS underwent a modification in the period between bar insertion and removal. RESULTS: Meta-analysis included 9 studies with 1641 AIS patients. Although heterogeneous (I(2) = 99.5%, P < .0001), the overall percentage of progression for untreated AIS was 42.5% (CI 18.2%-72.2%). In our follow-up group who underwent MIRPE, 34 out of 67 patients had concurrent AIS with a Cobb angle >10° (range 10°-45°). We demonstrated that MIRPE had a favorable effect on AIS, with a mean improvement of 1.5° (CI 0.64-2.44; P = .0011). CONCLUSION: In our PE patients with AIS, MIRPE had a beneficial effect also on the spine. From our preliminary results, it seems that MIRPE should be offered during puberty as a timely option for treating PE and stabilizing mild/moderate scoliosis progression, when concurrent.

Role of thoracoscopy in traumatic diaphragmatic hernia.

Thoraco-abdominal trauma can in rare cases involve diaphragmatic rupture and subsequent herniation of intra-abdominal contents. We report a case of this complication in a 5-year-old boy who was injured in a car crash, and who manifested respiratory distress and hemodynamic instability after 48 h of being monitored in the pediatric intensive care unit. Multiple radiologic investigations were inconclusive and the definite diagnosis was established only on thoracoscopic exploration.

Unique case of epidermoid cyst located in the omentum.

Cystic lesions deriving from the omentum are rare benign clinical conditions of uncertain etiopathogenesis. In this report we describe a case of antenatal diagnosed intra-abdominal cystic mass, which, due to the absence of symptomatology and constant ultrasound morphology over time, did not require immediate treatment. The present patient was followed up until surgery, which was performed at 4 years of age: on laparoscopy a cyst within the greater omentum was identified and excised. Histopathology indicated a cyst with epidermoid structure, which is unusual among the omental cysts reported in the literature.

Cervical thymic cyst in childhood: a case report.

Cervical thymic cysts are rare cervical masses which usually present in the first decade of life accounting for 0.3% - 1% of all congenital neck masses. Due to its rarity thymic cysts are seldom included in the differential diagnosis of cystic cervical mass and are often mistaken for more common conditions such as branchial cleft cyst or cystic hygroma. Herein we present a case of a 6-year-old girl with a right lateral cervical cystic mass with multiple septae extended from mandibular angle along the neurovascular bundle of the neck which revealed to be a thymic cyst at histopathology.

Treatment of ovarian lesions in children and adolescents: a retrospective study of 130 cases.

In this study, we analyze the management of ovarian masses in a total of 130 children surgically treated for 137 ovarian lesions (7 bilateral). The most frequent symptoms were chronic (52.3%) and acute (25.4%) abdominal pain. Histological examination revealed 64 (46.7%) functional lesions, 59 (43.1%) benign neoplasms, 5 (3.7%) malignant ones, and 7 (6.6%) torsed normal ovaries. Ovarian torsion occurred in 36 cases (26.27%). A conservative treatment was performed in 81 (59.1%) girls: 61 (75.3%) treated in nonemergency and 20 (24.7%) in emergency surgery; laparoscopic approach in 35 cases (43.2%); and open surgery in 46 (56.8%). The remaining 56 (40.9%) ovarian masses underwent nonconservative surgery: 40 cases (71.4%) nonemergency and 16 (28.6%) emergency; laparoscopy in 20 patients (35.7%); and open surgery in 36 (64.3%). Fertility preservation should be a goal in the surgical treatment. The management of ovarian torsion should include adnexal detorsion and recovery of the ovarian tissue. In case of benign neoplasms, laparoscopic tumorectomy should be the gold standard; in early stage malignant tumors, fertility-sparing surgery with accurate staging is preferred.

Splenogonadal fusion: exceptional association with Moebius syndrome and intestinal intussusception.

We present an exceptional association of splenogonadal fusion, Moebius syndrome, and intestinal intussusception. At the age of 1 year, the patient presented with vomiting, bloody stools, and abdominal distension. He underwent a laparotomy that revealed an ileo-ileal intussusception. Three days later, he underwent a new surgery for the reduction of a suspected inguinal hernia. A dark-red tubular structure consisting of splenic tissue was seen passing down through the processus vaginalis and attaching onto the left testicle. Owing to the rarity of the splenogonadal fusion, each case should be reported for a better knowledge of its etiopathogenesis, clinical characteristic and associations.

The role of testicular volume in adolescents with varicocele: the better way and time of surgical treatment.

PURPOSE: We report varicocele prevalence in adolescents. Surgical treatment has been proposed in adolescents with relevant testicular disproportion to avoid fertility problems in adulthood. We prospectively analyzed the testicular volume variation in adolescents with varicocele and hypoplastic testis. MATERIALS AND METHODS: In a 2-year period we selected 54 consecutive pediatric patients with a median age of 14.5 years (range 13 to 16) who had left varicocele using certain criteria, including testicular volume discrepancy greater than 20%, no previous inguinal-testicular surgery and no symptoms. Adolescents were divided into 2 groups, including 27 who underwent surgical correction with lymphatic sparing microsurgical varicocelectomy (intervention) and 27 who were only observed (control). After surgery or at first observation patients were evaluated clinically and by ultrasound at 3, 6 and 12 months. Testicular volume was estimated by the prolate ellipsoid formula. RESULTS: We noted significant improvement in testicular volume with less than 20% disparity between the 2 gonads in 23 patients (85.2%) in the intervention group and in 8 controls (29.6%). Two recurrences (7.4%) were reported in the intervention group, each in an adolescent with increased testicular volume. CONCLUSIONS: Our study confirms significantly increased testicular volume in many surgically treated boys and shows that physiological catch-up growth occurs in adolescents with varicocele without treatment. Considering critically results in each group, in select cases clinical and ultrasound followup is indicated before intervention due to a possible spontaneous decrease in testicular asymmetry. Further histopathological studies are needed to identify the relationship between testicular hypoplasia, irreversible damage and future fertility problems to determine which adolescents should be treated.

Calcified cystic lymphangioma of the mesentery: case report.

Mesenteric cysts are rare and are associated with heterogeneous pathological conditions. We describe an extraordinary case of mesenteric calcified cystic lymphangioma in a 10-year-old boy. To the best of our knowledge only 6 mesenteric calcified cystic lymphangioma have been reported. The patient was admitted with abdominal pain and vomiting. Abdominal X-ray and computed tomography scan documented a calcified cyst which dislocated and compressed the ileum. Laparatomy revealed that the cyst arose in the mesentery at 100 cm from the ileocecal valve. The cystic wall was composed of fibrosclerotic calcified tissue and had an endothelial lining. In the adjacent fibrofatty stroma there were distended hemolymphatics. Postoperative recovery was uneventful. At follow-up 6 months after surgery the patient is well. Calcified cystic lymphangioma of the mesentery should be considered in the differential diagnosis of an intra-abdominal calcified cyst in children.

Teratoid hepatoblastoma.

We present the case of a Middle Eastern child, diagnosed and treated at 8 months of age for a hepatic neuroblastoma. After surgical removal of a 7 cm mass of the left liver lobe at our institution when the child was 15 months of age, the tumor was reclassified as a teratoid hepatoblastoma. The tumor was composed of fetal and embryonal hepatic tissue, undifferentiated tissue, and a teratoid background of loose mesenchymal tissue containing osteoid, squamous, and mucinous epithelium. We speculate on the histogenesis of teratoid hepatoblastoma and discuss its association with chemotherapy.

Multidisciplinary surgical approach to a surviving infant with sirenomelia.

Sirenomelia is an extremely complex and rare malformation with different degrees of lower-extremities fusion associated with gastrointestinal, musculoskeletal, vascular, cardiopulmonary, and central nervous system malformations. In the English literature, there are only 5 reports of infants surviving with this condition. In our case, a 2540-g female infant was born with normal vital signs, no facial dysmorphism, and a complete soft tissue fusion of the lower limbs, from perineum to ankles. Radiologic examinations revealed an intestinal atresia and a single pelvic kidney, with a unique ureter, 2 femurs, 2 tibias, 2 fibulas, and 2 feet (simpus dipus). At 7 months of age, a multidisciplinary surgical team achieved complete separation of the lower limbs, with independent vascular and nerve supplies. At the time of this writing, the infant was 28 months old and had a regular growth curve. Many future reconstructive surgeries have been planned to achieve an acceptable quality of life for this infant.