EPEN-27. CDKN2A DELETION IN SUPRATENTORIAL EPENDYMOMA WITH RELA ALTERATION INDICATES A DISMAL PROGNOSIS – A RETROSPECTIVE ANALYSIS OF THE HIT EPENDYMOMA TRIAL COHORT

INTRODUCTION Since supratentorial RELA-fusion positive ependymomas are considered a biologically distinct disease, we aimed to identify histological and genetic predictors of outcome in a defined cohort of pediatric patients. MATERIALS AND METHODS We analyzed 54 RELA ependymomas in pediatric patients treated according to HIT2000-E protocols. All cases underwent central neuropathological review. Genome-wide copy number alterations were assessed by molecular inversion probe or SNP array. RELA alterations were detected by RT-PCR, sequencing and assessment of nuclear p65-RelA protein. Copy number alteration of the CDKN2A (cyclin dependent kinase inhibitor 2A) locus and concordant p16 protein expression were analyzed. RESULTS Fifty-two tumors were classified as WHO-grade III (96.3%) with high mitotic activity in 39 cases (72.2%), vascular proliferation in 47 (87.0%), necrosis in 43 (79.6%) and clear cell morphology in 19 (35.2%). All tumors harbored RELA alterations. Homo- or heterozygous CDKN2A deletions were detected in 9 (16.7%) and 14 (25.9%) cases, respectively. p16 protein expression was lost in all cases with homozygous deletion. Median follow-up was 5.4 years with 5-years EFS and OS of 74.1% and 92.6%. In Kaplan-Meier analysis high mitotic activity was related to shorter EFS (p=0.016) and clear cell morphology to longer OS (p=0.039); CDKN2A deletion was associated with shorter OS (homozygous deletion, p=0.009; homo-or heterozygous deletion, p=0.034). No correlation between CDKN2A deletion and high mitotic activity was found but with higher age at diagnosis (p=0.001). CONCLUSION Deletion of CDKN2A occurred in 42.6% of supratentorial ependymomas with RELA alteration and represented a genetic predictor of worse overall outcome in pediatric patients.

Unusual presentation of small bowel GIST: diffuse omental & mesenteric sarcomatosis

Gastrointestinal stromal tumors (GISTs) represent ~1% of gastrointestinal (GI) tract neoplasms. Unusual presentation of a small bowel GIST with diffuse omental and mesenteric implants in a symptomatic patient is reported. CT scan in a 68-years-old woman showed multiple processes with solid density and colliquation areas in the abdominal cavity. At surgery, an uncommon finding of multiple omental and mesenteric secondary implants was evident. The index mass with 40 cm of adjacent small bowel, omentum and all peritoneal lesions were completely removed. Definitive pathology report showed a small bowel GIST with focal areas of necrosis and high mitotic activity (35 mitosis/50 High Power Fields), with multiple metastases on mesentery and omentum. Patient was therefore submitted to adjuvant treatment with Imatinib and a close follow-up program. Small bowel GIST with high mitotic activity may present with diffuse omental and mesenteric peritoneal seedings. Complete surgical clearance remains the mainstay of treatment.

One-Step Lower Leg Reconstruction with Vascularized Functional Vastus Lateralis Muscle Flap in the Treatment of Embryonal Rhabdomyosarcoma for a Six-Month-Old Boy: A Case Report

Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in childhood, however, it is very rare in the neonatal period (0.4–2% of cases). This case depicts a boy, who presented with RMS at two weeks of age, but officially diagnosed at the age of three months. MRI and scintigraphy determined a soft tissue tumor in the soleus muscle, while biopsy confirmed embryonal RMS with high mitotic activity (Ki67 (monoclonal antibodies) ~80%). CWS (Cooperative Weichteilsarkom Studiengruppe)-2012 with I2VA (ifosfamide, vincristine, actinomycin) chemotherapy regimen was administered per protocol. Surgical treatment was performed at age of six months and 18 days. The operation consisted of radical tumor resection and total triceps surae with partial fibula resection. Immediate reconstruction of triceps muscle was accomplished using a vascularized functional musculocutaneous vastus lateralis flap. Functional outcome was measured using the Lower Extremity Functional Scale (LEFS) and the Foot and Ankle Outcome Score (FAOS) with the results of 92.5% and 99% respectively.

HIGH-GRADE ENDOMETRIAL STROMAL SARCOMA :A CASE REPORT

Uterine sarcomas are tumors of poor prognosis characterized by a great histopathological heterogeneity. High endometrial stromal sarcomas (ESS) occurring at a late age, with high mitotic activity and / or tumor necrosis, are very poorly prognostic tumors. If it is accepted that the standard treatment of uterine sarcomas is surgical, the place of adjuvant treatment remains controversial. We report a case of a high-grade ESS referred to initially on MRI and diagnosed on pathological examination of a hysterectomy performed in a 64-year-old postmenopausal woman with postmenopausal bleeding.

Neuroendocrine Neoplasm in Cecal Appendix: A Case Report

Although neuroendocrine neoplasms are relatively uncommon entities, the appendix is a site with relatively frequent emergence of this pathology and its precise diagnosis and clinical management have been a challenge for practitioners. This paper aims to present and discuss a case report of neuroendocrine neoplasia in the appendix of a patient with acute abdomen who underwent appendectomy. A 46-year-old man referred to the Emergency Department complaining of abdominal pain in the right iliac fossa and signs of peritoneal irritation. After diagnosis of acute appendicitis, the patient underwent appendectomy. In a macroscopic analysis, an area of 1.9 cm long, hardened, irregular and yellowish shapes was noted in the distal third of the appendix. Histopathological analysis showed neoplasia consisting of invasive islands of monotonous rounded epithelioid cells, large areas of necrosis, high mitotic activity, neural and angiolymphatic invasion and extension to adipose tissue compatible with invasion of the mesoappendix. Circumferential resection was compromised, suggesting the persistence of neoplasia in the patient even after the surgical approach, which would probably recommend the need for surgical approach. Therefore, the importance of sending collected materials for anatomopathological analysis is emphasized, since it helps in the clinical evaluation, in the etiological diagnosis, guides the medical conduct in the evolution of the case, as well as assisting in family mourning in cases of mortality.Keywords: Neuroendocrine tumor, Appendix, Histopathological analysis.

ХАРАКТЕРИСТИКА РЕАКТИВНИХ ЗМІН СЛИЗОВОЇ ОБОЛОНКИ ЯСЕН ЗА УМОВ РІЗНИХ ВИДІВ ОДОНТОПРЕПАРУВАННЯ ПІД МЕТАЛОКЕРАМІЧНІ КОНСТРУКЦІЇ

The issue of rehabilitation of patients with defects in hard tissues of teeth and dentition is one of the urgent problems of practical dentistry, since 65 % of the population of our country aged 35–45 years needs dental prosthetics. The traditional methods used to replace dentition defects do not always fully correspond to the aesthetic and functional requirements of patients. The aim of the study – to analyze the literature sources with the characteristic of reactive changes in the mucous membrane of the gum under conditions of various types of odontopreparation for cermet structures. In connection with the introduction of a large number of new materials into practice and the widespread prevalence of a burdensome anamnesis among the population, the issues of their biological tolerance and prevention of possible complications are especially important. The full preservation of periodontal functions after orthopedic treatment is one of the defining signs of the quality of the provided dental care. In addition to the tooth tissues, a significant influence with direct odontopreparation and prosthetics with non-removable orthopedic structures undergoes a tooth-gingival sulcus, is considered as a complex system where factors of the external and internal environment interact. Morphological integrity and functional properties of the dento-epithelial compound undergo constant tests during chewing food. Unlike multilayer flat gingival epithelium, the connective epithelium does not undergo keratinization, but due to its high mitotic activity it quickly regenerates after various injuries. With the introduction into practice of orthopedic dentistry of cast-in-one ceramic coated crowns and bridges, problems arose, the key moments of which are inflammation in the gingival margin of the supporting teeth, gum retraction, thermal injury of the pulp, periodontal overload and morpho-functional changes in the periapical tissues. Any manipulations with marginal gums during prosthetics should be carried out with the utmost care and consideration of the characteristics of the marginal gingival to avoid unpredictable periodontal reactions. The probability of a trauma of the tooth-gingival attachment increases with an irrational choice of the retraction method for various biotypes of the gums. Therefore, before the prosthetics, it is necessary to obtain data on the biotype of the gum, and additionally measure the depth of the gingival groove in order to determine its individual size, which determines the choice of the retraction method aimed at preventing gum injuries in orthopedic treatment.

Neuronal Vacuolization in Feline Panleukopenia Virus Infection

Feline panleukopenia virus (FPV) infections are typically associated with anorexia, vomiting, diarrhea, neutropenia, and lymphopenia. In cases of late prenatal or early neonatal infections, cerebellar hypoplasia is reported in kittens. In addition, single cases of encephalitis are described. FPV replication was recently identified in neurons, although it is mainly found in cells with high mitotic activity. A female cat, 2 months old, was submitted to necropsy after it died with neurologic deficits. Besides typical FPV intestinal tract changes, multifocal, randomly distributed intracytoplasmic vacuoles within neurons of the thoracic spinal cord were found histologically. Next-generation sequencing identified FPV-specific sequences within the central nervous system. FPV antigen was detected within central nervous system cells, including the vacuolated neurons, via immunohistochemistry. In situ hybridization confirmed the presence of FPV DNA within the vacuolated neurons. Thus, FPV should be considered a cause for neuronal vacuolization in cats presenting with ataxia.

Clinicopathological features and prognosis of primary GISTs with tumor rupture in the real world.

e22510 Background: Ruptured GIST has poor prognosis and patients (pts) with ruptured GISTs are recommended for imatinib adjuvant therapy, however, their clinicopathological features and the prognosis in the era of imatinib are unknown. Using data obtained from two different registry studies in Japan, we examined ruptured GIST patients in clinical practice. Methods: The study cohort registered 665 pts (339 male and 326 female; median age 66 yrs) with histologically-proven primary GISTs who underwent R0 or R1 surgery between 2003 and 2007. The validation cohort included 172 pts (100 and 72; median age 62.5) between 2000 and 2014. Pathological Dx was done with H&E, KIT- and DOG1-IHC. Results: Disease located in the stomach (n = 506), small intestine (n = 119), large intestine (n = 26), or others (n = 14) in the study cohort and it was 120, 37, 14 or 2 in the validation, respectively. Median tumor size was 4.0 and 5.0 cm, median mitosis 2.6 and 5.0 /50HPF, and tumor rupture was seen in 21 pts (3.2%) and 5 pts (2.9%) in the study and validation cohorts, respectively. Rupture occurred preoperatively in 12 pts and intraoperatively in 9 of the study cohort. Ruptured GISTs showed high mitotic activities (median mitosis 13.0 vs 2.5 /50HPF; P < 0.0001), larger tumor (median size 9.6 vs 4.0 cm; P = 0.0008), and were more symptomatic than non-ruptured in the study cohort. Ruptured GIST pts had more frequent relapses (P < 0.0001) and showed shorter RFS (estimated RFS = 2.4 yrs; P < 0.0001) than non-ruptured (8.4 yrs). There were no difference in age, gender, location, surgical approach, cell type, preoperative and postoperative imatinib use between two groups.These results were confirmed in the validation cohort. Ruptured GISTs showed more frequnent relapses in the peritoneum. Multivariate analysis indicated that location (HR = 1.6), size (1.07), mitosis (1.01), and rupture (4.5) were independent prognostic factors of RFS. Rupture was not always prognostic for OS, and age (1.03), gender (2.3), and mitosis (1.01) were independent prognostic factors of OS. Conclusions: Ruptured GISTs were symptomatic larger tumors with high mitotic activity and showed frequent relapses, however, it was not independently prognostic for OS in the era of imatinib.

Ossifying Fibromyxoid Tumor of the Retromolar Trigone: A Case Report and Systematic Review of the Literature

Ossifying fibromyxoid tumor (OFMT) is a mesenchymal neoplasm of uncertain lineage and intermediate biologic behavior. Involvement of the head and neck area is infrequent (10% to 15%) and intraoral presentation is very rare. An OFMT developing in the retromolar trigone of a 13-year-old male is presented, along with a comprehensive review of oral OFMT cases. Among 12 oral OFMTs (including the present case), most patients were male (72.7%), with a mean age of 30.3 (13-67) years. The tumors generally appeared as painless masses of firm or hard consistency (mean diameter 27.7 mm), most commonly located in the soft tissues of the mandible (50%). Common microscopic features included ossification, lack of atypia or high mitotic activity, and immunohistochemical positivity for S100 (5/7), vimentin (6/6), GFAP (3/6), and SMA (2/6). Recurrence was reported only in one case. Further characterization of this rare entity is needed to increase our understanding of its distinct clinical and histopathologic features.