WHO Update Research Articles

THU540 Cribriform Morular Thyroid Carcinoma In A Young Female With Prior Exposure To Whole-Body Radiation For Metastatic Wilms’ Tumor

Abstract Disclosure: D. Caesario: None. M.S. Richardson: None. D. Carneiro-Pla: None. J.K. Fernandes: None. Introduction: Cribriform morular thyroid carcinoma (CMTC) is a rare thyroid cancer that is classically associated with familial adenomatous polyposis (FAP), but can also occur sporadically. We report a case of CMTC in a young female with history of whole-body radiation therapy (WBRT). Case Report: A 19-year-old female with past medical history of Wilms’ tumor (WT) with lung metastasis status post left nephrectomy and WBRT at the age of 6 was seen for newly diagnosed thyroid nodules. Physical exam was remarkable for thyromegaly. Thyroid function tests were normal. Thyroid ultrasound revealed 2 dominant TI-RADS 4 nodules measuring 1.9 x 1.7 x 2.1 cm on the left lobe and 0.9 x 0.8 x 0.8 cm on the right lobe. No suspicious lymphadenopathy. Fine needle aspiration biopsy on both nodules showed findings consistent with papillary thyroid carcinoma (PTC). No family history of thyroid disorders, malignancies, or FAP. She underwent total thyroidectomy with central neck node sampling. Thyroid gland surgical pathology result revealed CMTC positive for thyroid transcription factor-1 (TTF-1), β-catenin, and cytokeratins 5 and 6. It was negative for calcitonin. There was no evidence of invasion, extension, or lymph node metastasis. Genetic tests are currently pending. Discussion: CMTC was previously considered a variant of PTC, accounting for 0.2 to 6% of PTC cases. However, recent observations have challenged this view, and latest WHO update reclassified it as a distinct form of thyroid cancer. It is associated with an indolent clinical course and good prognosis. It almost exclusively affects young women. Both familial and sporadic cases are associated with mutations in the adenomatous polyposis coli (APC) gene. The APC protein is a negative regulator that controls β-catenin concentrations, which is involved in cell adhesion. Mutations in the APC gene may result in FAP and colorectal cancers. In cases associated with FAP, the tumors are usually multifocal and/or bilateral, while sporadic cases usually appear as single nodule. Tumor cells are always positive for TTF-1 and negative for calcitonin. They can also be positive for multiple cytokeratins, but strong nuclear and cytoplasmic staining for β-catenin is the hallmark of this tumor type. The case above occurred in a young female with no significant family history, but who underwent WBRT for WT as a child. Radiation is a known predisposing factor for thyroid cancer, and limited studies on early exposure to radiation revealed higher incidence of sporadic CMTC. However, even among FAP associated cases, CMTC diagnosis preceded that of FAP in up to 40% of the cases. Additionally, up to 20% of WT cases have mutations of the WT1 gene, and among these, at least half also carry acquired somatic mutations in CTNNB1, the gene encoding β-catenin. So far, there has been no reported case of CMTC in the background of WT. It will be interesting to see if she has these underlying mutations. Presentation: Thursday, June 15, 2023

Diagnostic approaches and future directions in Burkitt lymphoma and high-grade B-cell lymphoma.

Since the 2016 WHO update, progress has been made in understanding the biology of Burkitt lymphoma (BL) and the concept of high-grade B-cell lymphomas (HGBCL) that allows some degree of refinement. The summary presented here reviews in detail the discussions of the Clinical Advisory Committee and expands upon the newly published 2022 International Consensus Classification for lymphoid malignancies (Campo et al. Blood, 2022). BL remains the prototypic HGBCL and diagnostic criteria are largely unchanged. HGBCL with MYC and BCL2 and HGBCL with MYC and BCL6 rearrangements are now separated to reflect biologic and pathologic differences. HGBCL, NOS remains a diagnosis of exclusion that should be used only in rare cases. FISH strategies for diffuse large B-cell lymphoma (DLBCL) and HGBCL are discussed in detail for these diseases. Advances in integrative analysis of mutations, structural abnormalities, copy number, and gene expression signatures allow a more nuanced view of the heterogeneity of DLBCL, NOS as well as definitions of HGBCL and point to where the future may be headed for classification of these diseases.

Glioma-related epilepsy in patients with diffuse high-grade glioma after the 2016 WHO update: seizure characteristics, risk factors, and clinical outcomes.

The aim of this study was to investigate the epidemiological characteristics, associated risk factors, and prognostic value of glioma-related epilepsy in patients with diffuse high-grade gliomas (DHGGs) that were diagnosed after the 2016 updated WHO classification was released. Data from 449 patients with DHGGs were retrospectively collected. Definitive diagnosis was reaffirmed according to the 2016 WHO classification. Seizure outcome was assessed using the Engel classification at 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors associated with preoperative and postoperative glioma-related epilepsy. Lastly, the prognostic value of glioma-related epilepsy was evaluated by Kaplan-Meier and Cox analysis. The incidence of glioma-related epilepsy decreased gradually as the malignancy of the tumor increased. Age < 45 years (OR 2.601, p < 0.001), normal neurological function (OR 3.024, p < 0.001), and lower WHO grade (OR 2.028, p = 0.010) were independently associated with preoperative glioma-related epilepsy, while preoperative glioma-related epilepsy (OR 7.554, p < 0.001), temporal lobe involvement (OR 1.954, p = 0.033), non-gross-total resection (OR 2.286, p = 0.012), and lower WHO grade (OR 2.130, p = 0.021) were identified as independent predictors of poor seizure outcome. Furthermore, postoperative glioma-related epilepsy, rather than preoperative glioma-related epilepsy, was demonstrated as an independent prognostic factor for overall survival (OR 0.610, p = 0.010). The updated WHO classification seems conducive to reveal the distribution of glioma-related epilepsy in DHGG patients. For DHGG patients with high-risk predictors of poor seizure control, timely antiepileptic interventions could be beneficial. Moreover, glioma-related epilepsy (especially postoperative glioma-related epilepsy) is associated with favorable overall survival.

Staging and Classification of Primary Musculoskeletal Bone and Soft-Tissue Tumors According to the 2020 WHO Update, From the AJR Special Series on Cancer Staging.

Staging of primary musculoskeletal bone and soft-tissue tumors is most commonly performed using the AJCC and the Enneking or Musculoskeletal Tumor Society (MSTS) staging systems. Radiologic imaging is integral in achieving adequate musculoskeletal neoplastic staging by defining lesion extent and identifying regional lymph node involvement and distant metastatic disease. Additional important features in surgical planning, though not distinct components of the staging systems, include cortical involvement, joint invasion, and neurovascular encasement; these features are optimally evaluated by MRI. In 2020, the WHO updated the classification of primary musculoskeletal tumors of soft tissue and bone. The update reflects the continued explosion in identification of novel gene alterations in many bone and soft-tissue neoplasms. This growth in gene alteration identification has resulted in newly designated lesions, reclassification of lesion categories, and improved specificity of diagnosis. Although radiologists do not need to have a comprehensive knowledge of the pathologic details, a broad working understanding of the most recent update is important to aid accurate and timely diagnosis given that histologic grading is a component of all staging systems. By using a multidisciplinary approach for primary musculoskeletal neoplasms involving colleagues in pathology, orthopedic oncology, radiation oncology, and medical oncology, radiologists may promote improved diagnosis, treatment, and outcomes.

Advancements in research and development to combat COVID-19 using nanotechnology

The whole world is currently facing a global health crisis due to the coronavirus disease (COVID-19) pandemic caused by SARS coronavirus 2, which started in Wuhan City, China, in December 2019. The pandemic has affected 235 countries, areas or territories and infected over 42 million people across the globe as per WHO update on 27 October 2020. More than 1.1 million people have died and the numbers are increasing daily. However, some drugs have been authorized for emergency treatment of patients, medication and vaccines with proven efficacy to prevent and treat the disease is still under various phases of development. The entire world is consistently making efforts to address three major challenges related to COVID-19 including prevention of its spread, prompt and early diagnosis and treatment of patients to save lives. Touted as one of the game-changing technologies of the century, nanotechnology has huge potential to develop solutions against these three major challenges of the disease. Nanotechnology comprises of multidisciplinary prospects encompassing diverse disciplines including medicine, material science, artificial intelligence, environment, virology, physical sciences, chemistry and biology. The numerous challenges can be addressed through the engineering of the various physicochemical properties of materials presents in abundance in nature. Various claims, studies and reports on research and development to combat these challenges associated with COVID-19 have been collectively discussed in this article from the perspectives of nanotechnology.

Covid-19 Demographics from a Tertiary Care Center: Does It Depreciate Quality-of-Life?

Novel Coronavirus-disease-2019 (Covid-19) caused by the severe-acute-respiratory-syndrome coronavirus-2 (SARS-CoV-2) shows a rapid spread all over the world. It’s still an ongoing pandemic with greater morbidity and mortality. In our study, we describe clinical features, and demographics of patients presenting to our tertiary care center with Covid–19 infection. Global burden was around 14 million Covid-19 positive cases with .5 million deaths and rising as per WHO update. A descriptive analytical cross-sectional study was carried out from June 1st to 30th, 2020 in a tertiary care center. Patients who tested positive by Reverse Transcriptase-Polymerase chain reaction were included in the study and clinical characteristics and outcome of the patients were analyzed along with impact on quality-of-life. Sample size was 250. Mean age was around 41 years, with age range from 15 to 75 years. Gender ratio was 1:2.4, with male preponderance. Most common presenting symptom was throat pain (60%). Rhinorrhea and sneezing complaints were not recorded. Clinical categorization was done and scored accordingly. Clinical outcomes of above patients showed complication rate 5.2%, mortality rate .8%, with discharge and recovery rate being rate 94.8% and 96% respectively. Fear of COVID-19 scale was used to assess quality-of-life impact. We found throat pain was the most common symptom in our study. No cases reported with rhinorrhea/sneezing. Good recovery rate noted. Quality-of-life impacted.

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Middle East Respiratory Syndrome (MERS) Infection in Hematological and Oncological Patients: A Case Series from a Tertiary Care Center in Saudi Arabia

We present the largest to date of a case series of nine patients with hematological and oncological malignancies who were infected with Middle East Respiratory Syndrome Coronavirus (MERS-CoV). MERS-CoV is a novel beta-coronavirus with a high fatality rate in comorbid patients. The majority of MERS cases globally were reported from Saudi Arabia (1983 cases, including 745 related deaths with a case-fatality rate of 37.5%) according to the WHO update of February 2019. All were clinically stable before acquiring the virus.Most of the cases had an active disease as relapse or refractory with three cases being neutropenic. The clinical presentation and radiological features of the patients were variable and inconsistent (Table 1). Diagnosis was confirmed with RT-PCR assays targeting upstream of the E gene and the open-reading frame gene 1a which had to be done repeatedly and required an average of 3 (with max. of 7) samples for a test to be positive (Table 2). All the patients developed respiratory failure, were admitted to the critical care unit (ICU) and required mechanical ventilation. The length of hospital stay ranged from 15 - 48, with an average of 24 days. Unfortunately, all nine patients died within days after admission to the ICU. In addition, the time from diagnosis to death has an average of 9 days ranging from 2-24 days, respectively.In conclusion, MERS CoV infection in hematology/oncology patients has a very poor prognosis regardless of the status of the underlying disease. The clinical presentation is not distinctive and confirming the diagnosis requires numerous respiratory samples. Measures to prevent nosocomial outbreaks should include proper compliance with personal protection equipment by health-care workers when managing patients with suspected and confirmed MERS-CoV infection and prompt isolation of infected patients. Future research is required to enhance our understanding of the disease and to evaluate superior diagnostic and therapeutic options.DisclosuresNo relevant conflicts of interest to declare.

TB CONSIDERED: DERAILING THE HIGHLY VIRULENT XDR-TB

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Worldwide, there are 25,000 cases of extensively drug resistant tuberculosis (XDR-TB) diagnosed yearly. Between 1993-2017, 65 cases of XDR-TB were reported in the US. When XDR TB first came to public attention in 2006 it was portrayed as an incurable disease. However, with novel diagnostic tests and medication, XDR-TB can be cured. We present a case of XDR-TB in a native Chinese lady. CASE PRESENTATION: A 37-year-old Chinese woman presented with worsening shortness of breath, weight loss, subjective fevers, and hemoptysis for six months. She was treated for TB 10 years ago in China with a 2-drug regimen for 10 months. Physical exam revealed a resting tachycardia and crackles in both lungs. CBC showed a WBC of 10,300 with a normal differential. CT scan of chest revealed consolidations and multiple cavitary regions in the bilateral upper lobes with prominent hilar lymph nodes. HIV testing was negative and cultures were positive for Mycobacterium TB and drug sensitivities revealed XDR-TB. Sputum smear revealed 4+ acid fast bacilli (AFB)(>30 bacilli/HPF). She was placed in isolation on a cocktail of 8 antibiotics and observed for drug tolerance and side effects. Baseline electrolytes, liver enzymes and ECG were normal. Due to rarity of the disease and public health concern, she was transferred to an NIH facility and is currently responding well to bedaquiline, clofazimine, linezolid, amikacin, meropenem and cycloserine. Two months into therapy, she no longer has hemoptysis and sputum smears remain negative for AFB. DISCUSSION: XDR-TB is resistant to first line drugs: isoniazid and rifampin, second line fluoroquinolones, and at least 1 injectable drug. Current XDR-TB treatment is long, toxic, complicated, expensive and essentially ineffective. Research is thriving in the field of TB treatment. A 2018 WHO update designated bedaquiline, a drug proven to reduce mortality, treatment duration and increase treatment success, as the core component in XDR-TB management. The Nix-TB, ZeNix and SimpliciTB are clinical trials testing bedaquiline, pretomanid and linezolid; a regimen removing injectables, expected to treat XDR-TB in 6-9 months. However, a 6-month course of bedaquiline costs $30,000 in US and $513,000 is required to treat XDR-TB. Petty politics, lack of organization and responsibility among state legislature denied our patient appropriate treatment for more than two months. CONCLUSIONS: Due to extensive travel and immigration from TB-endemic areas, 70.1% of TB cases in the US occur among non-U.S.-born persons. The mortality rate of XDR-TB is 50% and although rare, suitable treatment must be provided, because TB somewhere, is TB everywhere. Unfortunately, our patient’s son succumbed to XDR-TB. Our country and world must come together to eliminate this global threat that we are currently inadequately equipped to tackle. Reference #1: Brigden, Grania et al. “New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid” Infection and drug resistance vol. 8 367-78. 30 Oct. 2015 Reference #2: “Fact Sheets | Drug-Resistant TB | Extensively Drug-Resistant Tuberculosis (XDR TB) | TB | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/tb/publications/factsheets/drtb/xdrtb.htm. Reference #3: Companion Handbook to the WHO Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis. Geneva: World Health Organization; 2014. 5, Treatment strategies for MDR-TB and XDR-TB.Available from: tps://www.ncbi.nlm.nih.gov/books/NBK247431/ DISCLOSURES: No relevant relationships by Leonard Berkowitz, source=Web Response no disclosure on file for Ozana Lipka; No relevant relationships by Meghana Parsi, source=Web Response

P11.53 Genotype trumps phenotype: Oligodendroglioma and oligodendroglioma like tumors- A 1p19q fluorescence in situ hybridization based study at a tertiary referral centre in north India

Abstract BACKGROUND The 2016 WHO update of CNS tumours defines oligodendroglioma as a diffusely infiltrating glioma with IDH 1 or IDH 2 mutation and co-deletion of chromosomal arms 1p and 19q. We evaluated the role of 1p19q testing by Fluorescence in situ hybridization (FISH) in the diagnosis and correct classification of CNS tumours in accordance with WHO 2016 classification and exclusion of morphological mimickers of oligodendrogliomas. MATERIAL AND METHODS A retrospective analysis of CNS tumours was carried out that were tested for 1p19q co-deletion by FISH over a period of fourteen months at our institute. Correlation with tumour morphology as well as other molecular tests (IDH mutation and MGMT) where available was then done. A tumour was considered to have 1p or 19q deletion when the 1p probe to 1q probe ratio (1p/1q) or the 19q probe to 19p probe ratio (19q/19p) was &lt;0.80. RESULTS A total of 125 cases underwent FISH testing for 1p19q co-deletion over a period of last fourteen months at our institute with 74 male patients and 51 women. Thirty-eight of the 125 evaluated patients demonstrated 1p19q co-deletion on FISH. These included 25 oligodendrogliomas, 9 astrocytomas (Grade II/III) and 4 cases of oligoastrocytomas by morphology. Out of these cases, 21 cases had a co-existent IDH mutation, while two cases were IDH wild type and for 15 cases the status was unknown. Rest of the 87 patients were negative for 1p19q co-deletion and included cases of oligodendroglioma, other gliomas (pilocytic astrocytoma, oligoastrocytoma, glioblastoma) and few glioneuronal tumours (ganglioglioma, dysembryoplastic neuroepithelial tumour and central neurocytoma). CONCLUSION 1. Analysis of 1p19q co-deletion by FISH plays an important role in correctly identifying cases of oligodendroglioma as shown in our study. This is important as it is both a predictive as well as prognostic biomarker 2. In cases with co-deletion but IDH wild type status, the 1p19q status should be confirmed by other methods such as comparative genomic hybridization to confirm the presence of whole chromosome loss.3. FISH analysis also helps in excluding morphologic mimics of oligodendroglioma such as glioneuronal tumours and pilocytic astrocytomas in young patients. 4. However, in a resource limited country like ours, a good morphological diagnosis should still form the basis for FISH and other molecular tests to avoid unnecessary testing.

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PB2009 PERIPHERAL BLOOD INVOLVEMENT BY FLOW CYTOMETRY IS NOT AN UNUSUAL FEATURE IN IGM MGUS/WALDENSTRÖM MACROGLOBULINEMIA WITH MYD88 L265P MUTATION.

Background:The IgM monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum IgM paraprotein concentration &lt;30 g/L, bone marrow (BM) lymphoplasmacytic infiltration by clonal population &lt;10% and no symptoms or end‐organ damage. Waldenström Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma (LPL) with BM involvement and an IgM monoclonal gammopathy of any concentration. Patients fullfilling criteria for WM and not requiring inmediate treatment are classified as smoldering WM. More than 90% of LPL/WM cases and 60% of IgM MGUS display the MYD88 L265P mutation (MYD88mut), suggesting that IgM MGUS is closer to mature B‐cell neoplasms than to plasma cell myeloma according to 2016 WHO update. From the immunophenotypic point of view, clonal B cells are reported in 75% of IgM MGUS in BM on multiparameter flow cytometry (FC). However, data about peripheral blood (PB) involvement in IgM MGUS/WM are scarce.Aims:To analyze the incidence of PB involvement detected by FC in a series of IgM MGUS/WM with MYD88mut in BM consecutively diagnosed in a single institution.Methods:69 patients (47 male/22 female; median age 77 years, range 38‐92) diagnosed with IgM MGUS/WM MYD88mut between 2000 and 2019 with PB FC availability were selected. The diagnosis was made in BM in all cases. For FC analysis, 100,000 events were acquired in a FACSCanto II (BD) cytometer and were analyzed with the Infinicyt software (Cytognos). The study of the MYD88 L265P mutation was performed in PB by allele‐specific qPCR and the analysis of the IGH gene rearrangement by PCR.Results:Monoclonal gammopathy was detected in routine blood tests in asymptomatic patients in 52/69 (75%) cases. Median lymphocyte count was 2.04x109/L (0.77‐8.81). Only 3/69 (4.3%) patients presented with ≥4x109/L lymphocytes. Leukemic involvement by FC was detected in 36/69 (52%) patients (see Table 1). The phenotype of clonal lymphocytes was the usually described in WM (CD19dimCD22dimCD25dim) in most cases. In those patients, the median percentage of B‐cells from the total lymphocytes was 8% (0.6‐40%) with only 5 (7%) patients presenting ≥20% B‐lymphocytes. The median percentage of clonal B‐cells in respect of the total number of B‐cells was 60% (3‐100%). However, in 9 patients the clonal B‐lymphocytes could not be quantified because of the minor representation of this abnormal population with non‐specific phenotype. In 5 (7%) patients an additional abnormal B‐cell population was detected, 4/5 being phenotypically consistent with chronic lymphocytic leukemia. PB involvement was most frequently observed in patients displaying ≥30% lymphocytes in BM (15/20, 75% vs. 21/48, 44% in patients with &lt;30% lymphocytes, P = 0.032). No differences were observed with regard to the amount of serum monoclonal component (PB involvement: 12/24 cases with ≥15 g/L vs. 24/45 patients with &lt;15 g/L, P = NS). MYD88mut was detected in 31/34 (91%) cases with leukemic expression. In 13/31 (42%) patients without PB involvement by FC, molecular data were consistent with circulating disease (only MYD88mut 2/31, only clonal IGH rearrangement 5/29, both 6/29).Summary/Conclusion:In our series, PB involvement by FC was not unusual in patients with IgM MGUS/MW MYD88mut. However, nearly all patients had a normal lymphocyte count and a percentage of B‐cells within the normal ranges. Leukemic expression by FC correlated with the degree of BM infiltration. Finally, PB involvement could be detected by molecular techniques (MYD88 L265P mutation and/or clonal IGH rearrangement) in almost half of the patients with negative FC.image

TM1-2 Diffuse low grade glioma after the 2016 WHO update, seizure characteristics, imaging correlates and outcomes

ObjectivesSeizures are a common presenting symptom in patients with low grade glioma (LGG). Exact mechanisms of epileptogenesis are unknown and the influence of radiological and histological characteristics are not well studied, particularly after the 2016 WHO reclassification of gliomas. We aimed to define predictors of seizure development and outcome in patients with LGG.DesignRetrospective single institution case series.Subjects63 patients who underwent resection of supratentorial LGG in a single institution, 45 presented with seizures.MethodsRetrospective analysis of patient records to assess seizure outcome and other demographics including radiological variables, tumour characteristics, type of surgery and histology based on the 2016 WHO update.ResultsAfter surgery, 33 patients (73%) who presented with seizures were Engel class I at median follow up of 43 months. Complete and near total resection were associated with improved Engel class compared to subtotal resection. Awake craniotomy gave improved seizure outcomes compared to under general anaesthesia (84% vs 65%). Molecular genetics did not predict seizure outcome. Updated histology did not predict seizures at diagnosis, only tumour heterogeneousity on initial MRI (p=0.043). Tumour volume at presentation impacted EOR but not seizure outcome.ConclusionsSeizure outcome is directly related to EOR. Tumour histology based on molecular genetics did not predict seizure development or outcome. Use of awake craniotomy results in greater EOR and improved Engel class.

Incidence of testicular tumor subtypes according to the updatedWHO classification, North Rhine-Westphalia, Germany, 2008-2013.

In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors. The aim of this study was to provide up-to-date population-based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification. We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine-Westphalia for the years 2008-2013. We used population counts to estimate age-standardized incidence rates per million person-years (EUROSTAT revised European Standard Population). The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non-seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non-seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age-standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person-years) and embryonal carcinoma plus teratoma (4.9 per million person-years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31years) than those that did not include seminoma (28years). Population-based incidence time trends for seminomatous and non-seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non-seminomatous TGCTs are examined.

Diffuse low grade glioma after the 2016 WHO update, seizure characteristics, imaging correlates and outcomes

ObjectivesThe majority of patients with supratentorial diffuse grade II glioma present with seizures, which adversely affect quality of life. The exact mechanism of epileptogenesis is unknown and the influence of tumour characteristics, radiological and histological, are not well studied, particularly following the introduction of molecular genetics in the 2016 WHO reclassification of gliomas. We sought to define predictors of seizure development and outcome in low grade glioma. Patients and MethodsA retrospective review of patients who underwent resection of a supratentorial grade II glioma in a single institution. All patients underwent surgery at initial presentation with the aim of maximal safe resection. Presenting symptoms and radiological variables were recorded, including eloquent location, cortical involvement, tumour margins and tumour volume. Extent of resection (EOR), surgery type (awake vs asleep) and seizure outcome were analysed. Using molecular genetics data the original histology was reclassified according to the 2016 WHO update. Results63 patients were included, 45 (71%) presented with seizures. 36 (57%) had oligodendroglioma and 27 astrocytoma. IDH-1 mutation was present in 53 (84%). 18 (29%) had tumour in an eloquent location. 33 (73%) were Engel class I following surgery at median follow up of 43 months. 6 patients were Engel II, 6 class III. Complete and near total resection were associated with improved Engel class compared to subtotal resection. No factors such as age, tumour location, tumour margins or tumour molecular genetics (including IDH-1 mutation) predicted better seizure outcome. Updated histological subtype did not predict the presence of seizures at initial diagnosis, only tumour heterogeneousity on initial MRI (p = 0.043). More patients who underwent awake craniotomy with intraoperative mapping were Engel class 1 post-operatively than those operated under general anaesthetic (84% vs 65%). Tumour volume at presentation did not correlate with seizure outcome but impacts on the EOR. ConclusionSeizure outcome is directly related to EOR in low grade glioma, which can be predicted by the initial tumour volume. Tumour histological subtype, including updated molecular genetic classification did not predict seizure development or outcome in this series. The use of awake craniotomy results in greater EOR and improved Engel Class following surgery.

A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria

AbstractThe 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5–93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9–41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid predominance is a heterogeneous group and that erythroid richness has no impact on overall survival.

Treatment of aggressive B-cell lymphomas.

Treatment of aggressive B-cell lymphomas.

Commentary on the WHO 2008 classification of immunodeficiency-associated lymphoproliferative disorders

The 2008 WHO update of Classification of Tumours of Hematopoietic and Lymphoid Tissues revised the classification of immunodeficiency-associated lymphoproliferative disorders with the aim to better define these heterogeneous entities to better distinguish between reactive and neoplastic lesions, further refine some entities (plasmablastic lymphoma, monomorphic post-transplant lymphoproliferative disorders and other iatrogenic immunodeficiency-associated lymphoproliferative disorders), and introduce a new lymphoma entity (large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease). The purpose of this review is to highlight the changes in the 2008 WHO classification of immunodeficiency-associated lymphoproliferative disorders.

Global Development

WHO Update on Avian Influenza A (H5N1) in Humans. American Military Allowed to Continue Vaccination against Anthrax.