The Multifaceted Appearance of Supratentorial Ependymoma with ZFTA-MAML2 Fusion

Ependymomas are glial neoplasms with a wide morphological spectrum. The majority of supratentorial ependymomas are known to harbor ZFTA fusions, most commonly to RELA. We present an unusual case of a 9-year-old boy with a supratentorial ependymoma harboring a noncanonical ZFTA-MAML2 fusion. This case had unusual histomorphological features lacking typical findings of ependymoma and bearing resemblance to a primitive neoplasm with focal, previously undescribed myogenic differentiation. We discuss the diagnostic pitfalls in this case and briefly review the histological features of ependymoma with noncanonical gene fusions. Our report underscores the importance of molecular testing in such cases to arrive at the correct diagnosis. Supratentorial ependymomas with noncanonical fusions are rare, and more studies are necessary for better risk stratification and identification of potential treatment targets

ZC3H7B-BCOR high-grade endometrial stromal sarcoma with osseous metaplasia: Unique feature in a recently defined entity

High-grade endometrial stromal sarcoma harboring ZC3H7B-BCOR fusion is a newly defined entity in gynecologic pathology featuring a set of distinct histopathological and molecular features. It is morphologically characterized by atypical ovoid to spindle cells with a fascicular architecture, usually embedded within a myxoid stroma. Unlike high-grade endometrial stromal sarcoma associated with YWHAE-NUTM2 fusion, the neoplastic cells are consistently immunoreactive to CD10. It may be confused with myxoid leiomyosarcoma and carcinosarcoma, although the expression of myoid and epithelial markers is absent or very limited. Osseous metaplasia has not been previously described in this tumor. The presence of osseous metaplasia may raise the differential diagnosis of ossifying fibromyxoid tumor, which is also associated with ZC3H7B-BCOR fusion. The clinical prognosis is poor with disease progression in all cases described thus far. In this report, we describe a 52-year-old Singaporean woman of Chinese descent with ZC3H7B-BCOR high-grade endometrial stromal sarcoma containing focal osseous metaplasia

Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting

10.1080/2162402X.2021.1877459OncoImmunology1011-1

Identification of MET genomic amplification, protein expression and alternative splice isoforms in neuroblastomas

10.1136/jclinpath-2012-201375Journal of Clinical Pathology6611985-991JCPA

Cytokines in Pediatric Pilocytic Astrocytomas: A Clinico-Pathological Study

Pilocytic astrocytomas (PCA) are WHO Grade I tumors with a favorable prognosis. Surgical resection is usually curative. Nonetheless, progressive and/or metastatic disease occurs in 20% of patients. For these patients, treatment options are limited. The role of the immune system in PCA has not previously been reported. We hypothesize that the circulating cytokines contribute to tumorigenicity in PCA. This is an exploratory study with a focus on the identification of circulating cerebrospinal (CSF) cytokines associated with PCA. The primary objective is to demonstrate that CSF cytokines will be differentially expressed in the subset of PCAs that are difficult to treat in comparison to their surgically amendable counterparts. This is a single-institution, retrospective study of prospectively collected data. Patients with a confirmed histological diagnosis of PCA who have simultaneous intraoperative CSF sampling are included. Cerebrospinal fluid samples are subjected to multiplex cytokine profiling. Patient-derived PCA lines from selected patients in the same study cohort are cultured. Their cell culture supernatants are collected and interrogated using the sample multiplex platform as the CSF. A total of 8 patients are recruited. There were two patients with surgically difficult tumors associated with leptomeningeal involvement. Multiplex profiling of the cohort’s CSF samples showed elevated expressions of IFN-γ, IL-2, IL-12p70, IL-1β, IL-4, and TNF-α in these two patients in comparison to the remaining cohort. Next, primary cell lines derived from the same PCA patients demonstrated a similar trend of differential cytokine expression in their cell culture supernatant in vitro. Although our findings are preliminary at this stage, this is the first study in pediatric PCAs that show cytokine expression differences between the two groups of PCA with different clinical behaviors

Neuronal defects an etiological factor in congenital pelviureteric junction obstruction?

Introduction: Congenital pelviureteric junction obstruction (PUJO) is one of the most frequent causes of neonatal hydronephrosis. Obstruction at the PUJ has potential severe adverse outcomes, such as renal damage. While pyeloplasty has been established as the definitive treatment, the exact pathophysiology of congenital PUJO remains unknown. Recent research has proposed neuronal innervation defects as an etiological factor in congenital PUJO. We aim to study the expression of various neuronal markers in PUJO specimens compared with controls, and evaluate whether severity of renal disease or dysfunction pre-operatively is related to expression of neuronal markers in resected PUJO specimens. Materials and methods: All consecutive patients who underwent dismembered pyeloplasty at KK Women's and Children's Hospital, Singapore, for intrinsic PUJO from 2008 to 2012 were included. Patients with other co-occurring renal pathologies were excluded. Controls were obtained from nephrectomy patients with Wilm's tumor or other benign renal conditions during the same period. Specimens were stained immunohistochemically with neuronal markers protein gene product 9.5 (PGP9.5), synaptophysin, and S-100, and with CD-117, a marker for interstitial cells of Cajal (Table). Levels of expression of the markers were assessed semiquantitatively (decreased, increased or no change) in comparison with controls by two independent observers. Pre-operative data of patients’ renal anatomical (ultrasonography measurements of renal pelvis size) and functional parameters (differential renal function measured using MAG-3 renal scans) were obtained. Discussion: Thirty-eight PUJO specimens (38 renal units) and 20 controls were studied. Mean patient age at pyeloplasty was 25.3 months (2.9–167.6 months). Median pre-operative pelvic size was 25.0 mm (17.0–50.0 mm). Both PUJO specimens and controls showed great heterogeneity in distribution of innervation. All four immunohistochemical markers were not predictive of significant pre-operative renal pelvis dilation or pre-operative diminished renal function of the operated kidney. Conclusions: There exists marked variability in expression of neuronal markers synaptophysin, PGP9.5, and S-100, and CD-117 in PUJO specimens compared with controls. Our results show no clinical significance of the expression of neuronal markers in predicting degree of pre-operative renal pelvis dilation or differential renal function. The heterogeneity of expression of neuronal markers in PUJO specimens and controls in our population is at variance with prior studies. The etiology of PUJO is likely to be complex and multifactorial. [Table presented

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma

10.1186/s12885-020-07048-0BMC CANCER20

Primary paediatric epidural sarcomas: molecular exploration of three cases

10.1186/s12885-019-5368-zBMC CANCER19