Assessment of tumoral and peritumoral inflammatory reaction in cutaneous malignant melanomas.

Skin cancer is one of the most common types of cancer, with an increasing worldwide incidence in recent decades. The main risk factor for increasing the skin cancer incidence is ultraviolet (UV) radiation. Of the two major forms of skin cancer (melanomas and non-melanotic cancers), the cutaneous melanoma (CM) is the most aggressive form, causing about 80% of the deaths resulted from this type of tumor. Malignant melanoma develops through malignant transformation of melanocytes in the skin because of prolonged exposure to solar or artificial UV. The malignant transformation of the melanocytes in the skin is accompanied by the presence of a local inflammatory reaction that, in the initial stages of carcinogenesis, would oppose to tumor development. Chronic exposure to UV or other etiopathogenic factors induces chronic inflammation, which, by producing inflammatory molecules (cytokines, chemokines, prostaglandins), constitutes a tumoral microenvironment that favors carcinogenesis, tumor invasion, metastasis, and the presence of neoplastic "mutant cells" that avoid the protective action of the immune system. Using immunohistochemistry techniques, we assessed the intra- and peritumoral inflammatory infiltrate cells in CM. The chronic inflammatory infiltrate presented more intense in the peritumoral stroma compared to the intratumoral one, heterogenous, more intensely composed of lymphocytes, plasma cells, macrophages, and mast cells (MCs), the most numerous cells in the inflammatory infiltrate being T-lymphocytes, plasma cells and macrophages; B-lymphocytes and MCs were in a small number, especially intratumorally. Inflammatory cells had a direct contact with tumor cells, blood vessels, connective matrix, suggesting that the inflammatory microenvironment plays an important role in carcinogenesis, tumor invasion, local angiogenesis, and tumor metastasis.

Retrospective Study of a Patient with Multiple de Novo Skin Tumor Formations.

In Romania, the incidence of malignant melanocytic tumors is continuously increasing. According to the World Health Organization, the incidence of melanocytic and non-melanocytic skin neoplasms has increased considerably and globally, in the last decade. We present the case of a 49-year-old patient who, over the course of 7 years, came in the Plastic Surgery Clinic of the Emergency County Hospital of Craiova for the excision of a number of 25 skin tumor formations, located on the face, cervical region, trunk and upper limbs. Treatment included complete microsurgical excision and supervision. In the end, the patient's treatment compliance decreased significantly.

Mechanisms of Altered Immune Response in Skin Melanoma.

Melanoma, a deadly form of skin cancer, poses significant challenges to the host immune system, allowing tumor cells to evade immune surveillance and persist. This complex interplay between melanoma and the immune system involves a multitude of mechanisms that impair immune recognition and promote tumor progression. This review summarizes the intricate strategies employed by melanoma cells to evade the immune response, including defective immune recognition, immune checkpoint activation, and the role of regulatory T-cells, myeloid-derived suppressor cells, and exosomes in suppressing anti-tumor immunity. Additionally, we discuss potential therapeutic targets aimed at reversing immune evasion in melanoma, highlighting the importance of understanding these mechanisms for developing more effective immunotherapies. Improved insights into the interactions between melanoma and the immune system will aid in the development of novel treatment strategies to enhance anti-tumor immune responses and improve patient outcomes.

Ductus Venosus Agenesis and Portal System Anomalies-Association and Outcome.

To evaluate the prenatal diagnosis of agenesis of ductus venosus (ADV) and portal venous system (PVS) anomalies and describe the outcome of these cases, either isolated or associated. We evaluated the intrahepatic vascular system regarding the presence of normal umbilical drainage and PVS characteristics in the second and third trimester of pregnancy. The associated anomalies and umbilical venous drainage were noted. Follow-up was performed at six months follow-up. Ultrasonography was performed in 3517 cases. A total of 19 cases were prenatally diagnosed: 18 ADV cases, seven abnormal PVS cases, and six associations of the two anomalies. We noted an incidence of 5.1‱ and 1.9‱ for ADV and PVS anomalies, respectively. Out of the 18 ADV cases, 27.7% were isolated. Five cases (26.3%) presented genetic anomalies. PVS anomalies were found in 33.3% of the ADV cases. ADV was present in 85.7% of the PVS anomalies. DV and PVS abnormalities were found with a higher than reported frequency. Normal DV is involved in the normal development of the PVS. Additional fetal anomalies are the best predictor for the outcome of ADV cases. Evaluation of PVS represents a powerful predictor for ADV cases and addresses the long-term prognosis.

Retrospective Study Over the Hypospadias Surgery in a Single Tertiary Center.

Hypospadias surgery is a common activity in every department for pediatric surgery, increased incidence of this condition contributing this aspect. For this purpose permanent review of the data of cases is probably necessary, in order to promptly evaluate short and long term results. MATERIAL AND METHODS: The authors are presenting this retrospective clinical and statistical study, enrolling 149 patients, hospitalized and operated in the Department of Pediatric Surgery and Orthopedics, between 2009 and 2018. several parameters were taken into consideration: moment of conception, type of hypospadias, associated malformations, use of meatoplasty, age at meatoplasty, age at urethroplasty, type of urethroplasty, postoperative incidents and complications. RESULTS: Most of the patients included in the study were classified as anterior type of hypospadias, associated malformations were present in 20,13% of the patients, and 80% of the associated malformations belonged to the urogenital system. Over 60% of the cases underwent meatoplasty as a tactical procedure. Mathieu was the most appreciated procedure (74,5%) for urethroplasty and over a half of the patients were operated after the age of 3 years. Early and late postoperative fistula formation was noted in 18,12% of cases. CONCLUSIONS: Better parameters to assess the exact type of hypospadias are needed to be introduced. Also, clear protocols for preoperative work-up in detection of other abnormalities, especially genito-urinary. Meatoplasty as a tactical procedure is having unclear influence for urethroplasty. Decreasing the age at urethroplasty should be the next goal. Some surgeons should really get overspecialized for this type of surgery.

Prenatal findings and pregnancy outcome in fetuses with right and double aortic arch. A 10-year experience at a tertiary center.

OBJECTIVE: Our objective was to evaluate the accuracy of the prenatal diagnosis and the relation between the type of right aortic arch (RAA) with other intra- or extracardiac (EC) and chromosomal anomalies. METHODS: A retrospective, observational study was conducted between 2011-2020 in a Romanian tertiary center. All RAA cases, including double aortic arch (DAA), were extracted from the databases and studied thoroughly. RESULTS: We detected 18 RAA cases: five (27.78%) type I (mirror image, "V" type), 11 (61.12%) type II ("U" type), and two (11.10%) DAA cases. Heart anomalies were associated in 38.89% (overall), 60% (type I), 36.37% (type II), and 0% (DAA) cases. Tetralogy of Fallot represented the most prevalent cardiac malformation (in 22.23% of cases). EC anomalies were present in 44.44% of fetuses (20% of type I, 54.55% of type II, and 50% of DAA cases). Genetic abnormalities were found in 41.17% of pregnancies, with 22q11.2 deletion in 23.53%. 55.55% of the cases had a good neonatal evolution and 44.45% of the pregnancies were terminated. An overall good outcome of pregnancy was noted in 40% of type I RAA, 63.64% of type II RAA, and 50% of DAA cases. All RAA cases examined in the first trimester were correctly diagnosed. CONCLUSIONS: RAA can be accurately diagnosed and classified by means of prenatal ultrasound since early pregnancy. A detailed anatomy scan and genetic testing, including 22q11 deletion, should be offered to all pregnancies when RAA is discovered. When isolated, RAA associates a good outcome, indifferently the anatomical type.

Peripheral adenopathies in children - an attempt of clinical morphological profile.

AIM: The authors have proposed to assess peripheral adenopathies in a series of hospitalized children in order to identify and define clinical and morphological profiles of different types of lymph node (LN) diseases. MATERIALS AND METHODS: The studied group consisted of 58 patients less than 18 years of age. The investigation algorithm included: gender, age, site, involvement, side, extension and histopathological (HP) type of LN lesions. Tissue fragments were processed using classical histological techniques (formalin fixation and paraffin embedment) and stained with Hematoxylin-Eosin (HE). In some cases (tuberculous lesions and lymphomas), special stainings (Ziehl-Neelsen) and immunohistochemistry were used. Stratification scales of cases were defined according to each parameter in order to compare the data. All obtained data were assessed individually, compared to each other and with similar data from the literature with the help of a statistical apparatus [χ² (chi-squared) test and analysis of variance (ANOVA) test] in some cases. RESULTS: The young patients were slightly more frequently boys, of all ages but with a mean age of 10 and half years. The affected LNs belonged most often to neck region, either on the left or on the right side but sometimes bilateral or even on the midline; usually, more than one LN was involved in the area. In most of the cases, the lesions were localized in only one LN area. HP picture was dominated by the inflammatory processes, firstly the nonspecific ones, followed by tuberculosis. DISCUSSIONS: Our observations fitted, for each parameter, with the wide ranges found in the literature. Comparisons between parameters' variations revealed differences, sometimes significant that we tried to organize in clinical and morphological profiles. CONCLUSIONS: The assessment of our data allowed us to define some clinical and morphological profiles of different types of adenopathy that, by improvement on studies including larger series, could be of real use in daily pediatric practice.

Pathological fractures of humerus in children. Therapeutic and pathological considerations.

INTRODUCTION: A pathological fracture appears after a low-energy trauma or minor trauma on bones with a modified histological structure; sometimes, the patient reports shoulder pain antedating the fracture. The most common benign bone tumors that cause pathological fractures in children are simple bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. This type of bone tumors is usually asymptomatic until they reach a large size and cause a pathological fracture after minor trauma. The optimal treatment remains controversial. Our objective was to describe our modern treatment strategies of the large benign osseous tumors of the humerus complicated by pathological humerus fractures and histological aspects in these cases. PATIENTS, MATERIALS AND METHODS: The study was prospective and included patients who were diagnosed with pathological humeral fractures, which required surgically orthopedic treatment. We selected three cases of pathological fractures of humerus in children each with its particularities, treated in the Department of Pediatric Surgery and Orthopedics, Emergency County Hospital, Arad, Romania. Treatment included curettage of the cyst, sampling for histopathological (HP) examination, bone substitution and titanium elastic nails (TEN) osteosynthesis. RESULTS: No complications and no recurrence were seen in the early postoperative period. CONCLUSIONS: Osteosynthesis with TEN and bone substitution is a viable option for treatment of pathological fracture of humerus, secondary to the osseous benign tumors, which required surgically treatment, despite the different HP aspects. By using a combined treatment in these cases, we eliminate the disadvantages of isolated use of the described techniques in the literature.

Clinico-imaging and morphological aspects of the benign serous ovarian epithelial tumors in children and adolescents.

Benign serous ovarian epithelial tumors represent a major area of interest in pediatric pathology through the incidence and the hormonal and reproductive implications that they induce. In this study, we analyzed 24 tumors diagnosed and surgically operated in children and adolescents, in relation to clinical, histological and immunohistochemical parameters, which can provide information on the potential for growth of lesions. The average age of diagnosis was 13.2 years, the majority of tumors being present in patients over 10 years (75%), with accompanying symptoms (83.3%), unilateral (91.7%) and dimensions of maximum 10 cm (66.7%). The histopathological aspect indicated a cystic growth pattern, sometimes papillary, and in three cases, the presence of atypical focal areas of the tumor epithelium. The Ki67 proliferation index values were higher in the case of tumors larger than 10 cm, those with papillary pattern, and in those with atypical areas, while p53 reactions were present only in cases with atypical proliferation areas. The parameters investigated in this study are useful both for assessing the risk of tumor growth and progression, as well as for stratifying patients for active clinical surveillance.

A rare case of a Wilms tumor: case report.

The nephroblastoma or Wilms tumor (WT) is the most common renal tumor in childhood, representing approximately 6-7% of all pediatric cancers, with a yearly incidence of 10 cases in one million children less than 15 years old, and continues to arouse interest by remarkable actual therapeutic successes, consecutive to the multidisciplinary approach. Its maximum incidence is around the age of 3-3.5 years old, having an equal frequency in males and females. We present the case of a child, aged three years and five months, who was diagnosed with WT (nephroblastoma) with triphasic pattern, stage II tumor, and admitted to the Department of Oncopediatry for chemotherapeutic treatment and clinico-biological investigations.

The importance of perinatal autopsy. Review of the literature and series of cases.

Perinatal autopsy remains the gold-standard procedure used to establish the fetal, neonatal or infant abnormalities. Progressively, perinatal pathology has become a specialized field with important roles of audit for fetal prenatal diagnostic tools, in parents counseling regarding future pregnancies, in scientific research, for epidemiology of congenital abnormalities and teaching. The differences between prenatal ultrasound and autopsy reports represent a strong argument for the autopsy examination following termination of pregnancy. The reasons for such discrepancies are related to the ultrasonographic or pathological examination conditions, the type of the anomalies, the expertise and availability of the operators. Several facts led to an undesirable increase of refusals from parents to consent to a conventional invasive autopsy: the centralization of pathology services, the poor counseling provided by non-experts in fetal medicine and the clinicians' over-appreciation of the importance of the ultrasound diagnostic investigation. Although non-invasive alternatives have been tested with promising results, conventional autopsy remains the gold standard technique for the prenatal diagnosis audit. We report and analyze several cases of prenatally diagnosed malformed fetuses with different particularities that underline the necessity of perinatal autopsy. We discuss the antenatal findings and management and post-mortem autopsies in the respective pregnancies.

Hirschprung's disease in different settings - a series of three cases from a tertiary referral center.

Failure of neural crest cells to migrate from neural crests during intrauterine development result in partial or total aganglionosis of the colon in newborn. Hirschprung's disease (HD) represents the clinical manifestation of this pathogenic process, currently accounting for the majority of lower intestinal obstruction in the first period of life. Our aim was to present a series of three cases presenting to our tertiary care center with a range of symptoms, all benefiting from surgery and consequent pathology examination of biopsy or resection pieces. The first case was of a male newborn that presented several years ago with common symptoms for HD (abdominal distension, vomiting and the total lack of intestinal passage for feces). Coming from young healthy parents after normal labor, the newborn displayed signs of Down's disease after physical examination. After abdominal radiography, the patient underwent surgery and consecutive pathology revealed notable signs of Crohn's disease (CD): massive stasis in the serosa and submucosa, chronic inflammatory infiltrate and lack of nervous cells in both plexuses and mucosa. Immunohistochemistry revealed low intensity CD34 membrane staining for fibroblast-like ganglion cells while CD117 staining showed few nervous cells within the mucosa. The second case presented before one year of age with an infectious background, already being operated upon with colostoma. We performed corrective surgery of the colostoma and consecutive pathology showed low CD117 cytoplasmic staining and intensely positive NSE (neuron specific enolase) staining within myenteric plexuses. Finally, the third and most recent case was that of a 4-year-old boy with an early diagnosis of megacolon and no previous surgery, who we evaluated by laparoscopy with five biopsies and consecutive S100 staining revealed a small number of nervous cells within nervous plexuses. In conclusion, an early diagnosis of HD is essential for successful therapeutic measures. Histology and, more recently, immunohistochemistry, represent the gold-standard procedures needed to objectify the diagnosis.

Prenatal diagnosis and perinatal outcome in congenital diaphragmatic hernia. Single tertiary center report.

PURPOSE: To evaluate the perinatal results for fetuses and neonates with left-sided congenital diaphragmatic hernia (CDH) and the role of the prenatal diagnosis in the pregnancy outcome. MATERIALS AND METHODS: We reviewed data from fetuses and neonates with left-sided CDH, managed from January 2009 and December 2013 in the University Clinic Hospital, Craiova, Romania. The following data were analyzed: the gestational age at the time of diagnosis, fetal karyotyping, presence of associated structural malformations, ultrasound (US) data (circumference and area of right lung, lung-to-head ratio - LHR, observed/expected LHR, hepatic herniation), the type of antenatal care, the pregnancy outcome, the place of birth and the conventional autopsy data, if performed. Perinatal outcomes were obtained by reviewing hospital documents. RESULTS: Twenty-one cases were identified. No fetal surgery was performed in our series. Mean gestational age at time of diagnosis was 29 weeks of amenorrhea (WA) (range, 16-37 WA). Associated structural malformations were noticed in nine (42.8%) cases, in which three fetuses had a normal karyotype and two had chromosomal abnormalities, and four fetuses were not investigated. Isolated congenital diaphragmatic hernia was confirmed in 12 (57.1%) cases. All early second trimester diagnosed cases were terminated. The overall mortality rate was 61.9%. Rates of fetal deaths, early neonatal deaths, late neonatal deaths, and survival were 28.5%, 19%, 14.2%, and 38%, respectively. The perinatal mortality rate was 19% in cases with isolated congenital diaphragmatic hernia. CONCLUSIONS: The overall and perinatal mortality rate in congenital diaphragmatic hernia was still high in our series. Early perinatal deaths are associated with early diagnosis and with the presence of other structural defects. The prevalence of chromosomal abnormalities in perinatal death could not be determined from these data. In isolated congenital diaphragmatic hernia, mortality is related to the presence of herniated liver and severe pulmonary hypoplasia, this being well correlated with antenatal ultrasound parameters used for the estimation of fetal lung volumes. The antenatal diagnosis allowed better counseling of the parents, description of associations and improving the neonatal care.

Gastrointestinal stromal tumor, jejunal atresia and stenosis in a neonate.

Gastrointestinal stromal tumors could rise in different areas of the digestive tract, at any age, but very rarely in neonates. We present the case of a 5-day-old male, with intestinal stenosis and atresia (type II) operated for peritonitis. On the resected specimen, the histopathological examination revealed a small gastrointestinal tumor of 8 mm. The immunohistochemical analysis indicated a low malignant potential. He is currently at two years of oncologic follow-up with no evidence of disease.