scholarly journals Glioneuronal tumors: clinicopathological findings and treatment options

2020 ◽  
Vol 15 (3) ◽  
pp. FNL47
Author(s):  
Lidia Gatto ◽  
Enrico Franceschi ◽  
Vincenzo Di Nunno ◽  
Chiara Tomasello ◽  
Stefania Bartolini ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Treatment Options ◽  
Low Grade ◽  
Correct Classification ◽  
Aggressive Treatment ◽  
Histologic Subtype ◽  
Clinicopathological Findings ◽  
Precise Diagnosis ◽  
Cns Neoplasms ◽  
Glioneuronal Tumors

Glioneuronal tumors are very rare CNS neoplasms that demonstrate neuronal differentiation, composed of mixed glial and neuronal cells. The majority of these lesions are low grade and their correct classification is crucial in order to avoid misidentification as ‘ordinary’ gliomas and prevent inappropriate aggressive treatment; nevertheless, precise diagnosis is a challenge due to phenotypic overlap across different histologic subtype. Surgery is the standard of therapeutic approach; literature concerning the benefit of adjuvant treatments is inconclusive and a globally accepted treatment of recurrence does not exist. Targetable mutations in the genes BRAF and FGFR1/2 are recurrently found in these tumors and could take a promising role in future treatment management.

Phlegmasia cerulea dolens – an uncommon but alarming manifestation of deep vein thrombosis

VASA ◽  
2020 ◽  
Vol 49 (5) ◽  
pp. 422-426
Author(s):  
Manuela Nickler ◽  
Sebastian Haubitz ◽  
Adriana Méndez ◽  
Martin Gissler ◽  
Peter Stierli ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Treatment Options ◽  
Bleeding Risk ◽  
Venous Intervention ◽  
Aggressive Treatment ◽  
Vein Thrombosis ◽  
Prompt Treatment ◽  
Surgical Thrombectomy ◽  
Deep Vein ◽  
Phlegmasia Cerulea Dolens

Summary: In phlegmasia cerulea dolens (PCD), immediate diagnosis and prompt treatment is crucial for limb salvage. Aggressive treatment options including venous intervention, thrombolysis and/or surgical thrombectomy should be considered. Due to the lack of data, the most appropriate intervention depends upon etiology of PCD, clinical presentation and patient’s bleeding risk.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Parosteal Osteosarcoma with Pancreatic Metastasis and Multiple Relapses: A Case Report and Review of the Literature

2021 ◽  
pp. 983-988
Author(s):  
Daniel Cirotski ◽  
Jyoti Panicker
Keyword(s):  
Age Groups ◽  
Bone Cancer ◽  
Pancreatic Metastasis ◽  
Low Grade ◽  
Parosteal Osteosarcoma ◽  
Disease Course ◽  
Review Of The Literature ◽  
Histologic Subtype ◽  
Primary Bone ◽  
Multiple Relapses

Osteosarcoma is the most common primary bone cancer in all age groups. Metastasis mostly occurs with high-grade tumors disseminating to the lungs and other bones. Spread to the pancreas is rare and undocumented in the low-grade subtypes. Additionally, it is uncommon for the disease course of low-grade subtypes to involve multiple relapses. We present a 35-year-old woman with parosteal osteosarcoma who has experienced an atypical metastasis to the pancreas as well as multiple local and pulmonary relapses. The lesion was identified incidentally on routine imaging, and the patient underwent resection. We compare our case to the other reports of pancreatic metastasis in the literature. Despite being especially rare, clinicians ought to be aware of pancreatic metastasis of osteosarcoma. Furthermore, despite parosteal osteosarcoma’s less aggressive disease course, it can uncommonly lead to multiple relapses. We present a rare case exemplifying these phenomena in the prognostically favorable histologic subtype of parosteal osteosarcoma.

scholarly journals DIPG-40. TARGETING MASTER REGULATOR DEPENDENCIES IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii294-iii295
Author(s):  
Jovana Pavisic ◽  
Chankrit Sethi ◽  
Chris Jones ◽  
Stergios Zacharoulis ◽  
Andrea Califano
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Treatment Options ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Low Grade ◽  
Precision Oncology ◽  
Pontine Glioma ◽  
Convection Enhanced Delivery ◽  
Master Regulator

Abstract Diffuse intrinsic pontine glioma (DIPG) remains a fatal disease with no effective drugs to date. Mutation-based precision oncology approaches are limited by lack of targetable mutations and genetic heterogeneity. We leveraged systems biology methodologies to discover common targetable disease drivers—master regulator proteins (MRs)—in DIPG to expand treatment options. Using the metaVIPER algorithm, we interrogated an integrated low grade glioma and GBM gene regulatory network with 31 DIPG-gene expression signatures to identify tumor-specific MRs by differential expression of their transcriptional targets. Unsupervised clustering identified MR signatures of upregulated activity in RRM2/TOP2A in 13 patients, CD3D in 5 patients, and MMP7, TACSTD2, RAC2 and SLC15A1/SLC34A2 in individual patients, all of which can be targeted. Notably, intratumoral administration of etoposide by convection enhanced delivery was effective in murine proneural gliomas in which TOP2 was identified as a MR while RRM2—targetable by drugs such as cladribine—has been shown to be a positive regulator of glioma progression whose knock-down inhibits tumor growth. We also prioritized drugs by their ability to reverse MR-activity signatures using a large drug-perturbation database. Patients clustered by predicted drug sensitivities with distinct groups of tumors predicted to respond to proteasome inhibitors, Thiotepa or Volasertib all of which have early evidence in treating gliomas. We will refine this analysis in a multi-institutional study of >100 patient gene expression profiles to define MR signatures driving known biological/molecular disease subtypes, use DIPG cell lines recapitulating common MR architectures to optimize therapy prioritization, and validate our findings in vivo.

scholarly journals COVD-01. VINBLASTINE MONOTHERAPY INDUCTION FOR LOCALISED CNS GERMINOMA DURING THE COVID-19 PANDEMIC

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii282-iii282
Author(s):  
Rafael Moleron ◽  
Sara Stoneham ◽  
Thankamma Ajithkumar ◽  
Justin Cross ◽  
James Nicholson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Treatment Options ◽  
Single Agent ◽  
Germ Cell Tumour ◽  
Research Priorities ◽  
Tumour Volume ◽  
Cell Tumour ◽  
Low Grade ◽  
Testicular Seminoma

Abstract INTRODUCTION Patients with localised CNS-germinoma have excellent survival. More recently, intensive inpatient chemotherapy (carboPEI=carboplatin/etoposide/ifosfamide in Europe) has been effectively employed to reduce radiotherapy fields and/or dose. Current research priorities focus on reducing treatment burden and long-term sequelae. Of note, outpatient-based single-agent carboplatin chemotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology) [Alifrangis,EJC,2020]. Recently, successful vinblastine monotherapy was reported in localised CNS-germinoma [Murray,Neurooncol-Adv,2020]. METHODS Due to the COVID-19 pandemic, adapted UK guidelines for germ-cell-tumour management were distributed, including potential non-standard treatment options that would reduce hospital visits/admissions. A 30-year-old patient presented with a 32mmx30mmx35mm diameter solid+multi-cystic localised pineal CNS lesion, consistent radiologically with a germ-cell-tumour with prominent teratoma component. Investigation revealed negative AFP/HCG markers and biopsy-proven pure germinoma. After appropriate consent, the patient commenced 12-week induction with weekly vinblastine monotherapy (low-grade-glioma dosing [Lassaletta,JCO,2016]), with wk6&12 MRI re-assessment prior to definitive radiotherapy. RESULTS Vinblastine was well-tolerated. After initial 4mg/m2 test-dosing (wk1), standard 6mg/m2 was delivered for wk2, but resulted in asymptomatic neutropenia (nadir 0.3x10^9/l) and missed dosing at wk3. Subsequent doses were 4mg/m2, with no further neutropenia. As expected, MRI showed moderate 40% tumour volume reduction by wk12. Surgical resection of the residual presumed teratoma component was undertaken prior to radiotherapy. CONCLUSION Patients with CNS-germinoma have excellent outcomes and reduction of treatment-effects remains a priority. The exquisite chemosensitivity of germinoma, excellent results from monotherapy for metastatic testicular disease, and early promise of vinblastine monotherapy lend itself to further exploration for CNS-germinoma.

scholarly journals A Case of Atypical Bartonellosis in a 4-Year-Old Immunocompetent Child

2021 ◽  
Vol 9 (5) ◽  
pp. 950
Author(s):  
Chiara Sodini ◽  
Elena Mariotti Zani ◽  
Francesco Pecora ◽  
Cristiano Conte ◽  
Viviana Dora Patianna ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Bartonella Henselae ◽  
Delayed Diagnosis ◽  
Mitral Valve Regurgitation ◽  
Low Grade ◽  
Systemic Involvement ◽  
Mild Disease ◽  
Precise Diagnosis ◽  
Major Illness ◽  
The Right

In most cases, infection due to Bartonella henselae causes a mild disease presenting with a regional lymphadenopathy frequently associated with a low-grade fever, headache, poor appetite and exhaustion that spontaneously resolves itself in a few weeks. As the infection is generally transmitted by cats through scratching or biting, the disease is named cat scratch disease (CSD). However, in 5–20% of cases, mainly in immunocompromised patients, systemic involvement can occur and CSD may result in major illness. This report describes a case of systemic CSD diagnosed in an immunocompetent 4-year-old child that can be used as an example of the problems that pediatricians must solve to reach a diagnosis of atypical CSD. Despite the child’s lack of history suggesting any contact with cats and the absence of regional lymphadenopathy, the presence of a high fever, deterioration of their general condition, increased inflammatory biomarkers, hepatosplenic lesions (i.e., multiple abscesses), pericardial effusion with mild mitral valve regurgitation and a mild dilatation of the proximal and medial portion of the right coronary artery, seroconversion for B. henselae (IgG 1:256) supported the diagnosis of atypical CSD. Administration of oral azithromycin was initiated (10 mg/kg/die for 3 days) with a progressive normalization of clinical, laboratory and US hepatosplenic and cardiac findings. This case shows that the diagnosis of atypical CSD is challenging. The nonspecific, composite and variable clinical features of this disease require a careful evaluation in order to achieve a precise diagnosis and to avoid both a delayed diagnosis and therapy with a risk of negative evolution.

scholarly journals CBIO-16. SUPPRESSION OF HISTONE H3.3 MITOTIC PHOSPHORYLATION DRIVES DEVELOPMENT OF H3K27M-MUTANT DIFFUSE MIDLINE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii18-ii19
Author(s):  
Charles Day ◽  
Alyssa Langfald ◽  
Florina Grigore ◽  
Leslie Sepaniac ◽  
Jason Stumpff ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Treatment Options ◽  
Chromosome Instability ◽  
Pericentromeric Heterochromatin ◽  
Low Grade ◽  
High Grade ◽  
Chromosome Missegregation ◽  
Mitotic Phosphorylation ◽  
Chk1 Kinase

Abstract Pediatric midline gliomas – including DIPG – are lethal brain tumors in children, with poor prognosis and limited treatment options that provide only short-term benefits. The majority have a lysine-to-methionine substitution at residue 27 (H3K27M) in genes expressing histone H3 – predominantly in the H3.3 variant. This causes a global reduction in H3 Lys27 tri-methylation (H3K27Me3), comprehensive epigenetic reprogramming, and is a key driver in gliomagenesis. We show that the H3.3K27M mutation also induces chromosome segregation defects, which in high-grade tumors, results in extensive copy number alterations (CNAs). Ser31 is one of five amino acid substitutions differentiating H3.3 from canonical H3.1. Mitotic phosphorylation of H3.3 Ser31 by Chk1 kinase is restricted to pericentromeric heterochromatin, where it plays a role in chromosome segregation. We show that the K27M mutation affects neighboring Ser31 phosphorylation and pericentromeric heterochromatin organization. We demonstrate that (i) H3.3 K27M protein is defective for Ser31 phosphorylation by Chk1 kinase in vitro; (ii) DIPG cell lines have significantly decreased mitotic Ser31 phosphorylation, and are chromosomally unstable; and (iii) CRISPR-reversion of H3.3K27M to Lys27 restores phospho-Ser31 (and Lys27 tri-methylation) and significantly decreases chromosome instability. Expression of H3.3K27M or non-phosphorylatable H3.3S31A mutants in WT cells results in chromosome missegregation; this is suppressed by co-expression of phospho-mimetic H3.3K27M/S31E. In normal cells, chromosome missegregation stimulates p53-dependent cell cycle arrest in G1 to prevent the proliferation of aneuploid daughters. However, cells expressing H3.3 K27M or S31A failed to arrest following missegregation - despite having WT p53. Finally, in a novel mouse model of glioma, mean survival of mice with tumors induced with H3.3K27M and H3.3S31A was 81 and 68 days: 100% of H3.3S31A mice developed high-grade tumors. H3.3 WT controls developed only low-grade tumors and all survived 100 days. H3.3S31A is WT for Lys27 tri-methylation and thus, loss of Ser31 phosphorylation alone is oncogenic.

Rectal Granular Cell Carcinoma Requiring Abdominoperineal Resection

2021 ◽  
pp. 000313482198904
Author(s):  
Michaelia S. Sunderland ◽  
Anthony Dakwar ◽  
Sowsan Rasheid
Keyword(s):  
Abdominoperineal Resection ◽  
Tumor Invasion ◽  
Granular Cell Tumor ◽  
Treatment Options ◽  
Granular Cell ◽  
Cell Tumor ◽  
Low Grade ◽  
Anal Sphincters ◽  
Transrectal Biopsy ◽  
Laparoscopic Abdominoperineal Resection

Background Granular cell tumors, derived from neural crest cells, are rare tumors infrequently located in the colon or rectum. We will discuss a patient with a rectal granular cell tumor invading the anal sphincters requiring an abdominoperineal resection. Methods A 56-year-old male, with anal pain, was found to have a perirectal mass. Pathology from ultrasound-guided transrectal biopsy demonstrated low grade granular cell tumor. The patient underwent a laparoscopic abdominoperineal resection with perineum reconstruction. Results Pathology demonstrated a granular cell tumor of 4.5 centimeters with tumor invasion of the anal sphincters. Surgical margins were free of neoplasm. Discussion This is the only documented case of a colorectal granular cell tumor that has required an abdominoperineal resection. On histology, it was considered low grade but its behavior was more consistent with a malignant process. Additional research on malignant granular cell tumors is necessary to help improve treatment options, prevent recurrence, and improve overall survival. His medical course will be followed for disease progression or metastasis.

Relationship between Immunophenotype and Clinicopathological Findings for Superficial Nonampullary Duodenal Epithelial Tumor

Digestion ◽  
2021 ◽  
pp. 1-8
Author(s):  
Shigeki Fukusada ◽  
Takaya Shimura ◽  
Hiroyasu Iwasaki ◽  
Yusuke Okuda ◽  
Takahito Katano ◽  
...  
Keyword(s):  
Malignant Potential ◽  
Low Grade ◽  
Negative Group ◽  
Epithelial Tumor ◽  
Endoscopic Findings ◽  
Intestinal Phenotype ◽  
Oral Side ◽  
Clinicopathological Findings ◽  
Gastric Phenotype ◽  
The Relationship

<b><i>Introduction:</i></b> The natural history and prognosis of superficial nonampullary duodenal epithelial tumors (SNADETs) remain uncertain. We elucidated the relationship between immunophenotype and clinicopathological features. <b><i>Materials and Methods:</i></b> A total of 98 SNADETs were divided into 3 groups according to immunohistochemical findings: gastric phenotype (G type), gastrointestinal phenotype (GI type), and intestinal phenotype (I type). Cellular dysplasia was divided into low-grade dysplasia and high-grade dysplasia/adenocarcinoma (≥HGD). White opaque substance (WOS) deposition was categorized into diffuse WOS, partial WOS, and no WOS, based on endoscopic findings. <b><i>Results:</i></b> Of the 98 SNADETs, 4 lesions (4.1%) were G type, 32 lesions (32.7%) were GI type, and 62 lesions (63.2%) were I type. All G-type SNADETs were located in the oral side of the papilla including the bulb, and the rate of bulbar lesions was significantly higher in the G type than in the GI and I types (<i>p</i> = 0.004). The most frequent type of WOS was no WOS (4/4, 100%) for G type, partial WOS (19/32, 59.4%) for GI type, and diffuse WOS (34/62, 54.8%) for I type (<i>p</i> &#x3c; 0.001), and loss of intestinal character was significantly correlated with WOS deficiency. GI/I-type SNADETs with partial or no WOS and G-type SNADETs were associated with ≥HGD. Additionally, the frequency of ≥HGD lesion was significantly higher in the CD10-negative group than in the CD10-positive group (57.1 vs. 19.8%, <i>p</i> = 0.043). <b><i>Conclusion:</i></b> Pathological intestinal character was correlated with the presence of WOS, and CD10 loss was associated with malignant potential of SNADETs.

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