Updated World Health Organization Research Articles

The differential diagnosis of classical myeloproliferative neoplasms (MPN): the updated WHO criteria.

The classical myeloproliferative neoplasms (MPN), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by clonal myeloproliferation without features of myelodysplasia. The diagnostic approach proposed by the World Health Organization (WHO) uses clinical features, peripheral blood counts and smear analysis, bone marrow (BM) morphology, karyotype and molecular genetic tests to classify MPN subtypes. The detection of characteristic driver mutations like JAK2V617F, JAK2 exon 12, MPL, and calrecticulin (CALR) is a major diagnostic feature. JAK2 mutations are detected in more than 90% of patients with PV and are therefore used as highly sensitive clonal marker in this subtype. However, JAK2 mutations may also occur in ET and PMF, while CALR is virtually not seen in PV. Therefore, BM remains the central diagnostic platform and is essential for distinguishing ET from pre-fibrotic PMF and diagnosing cases which do not express JAK2, MPL or CALR ('wild-type' or 'triple-negative' MPN). The standardization of relevant BM features is mandatory to recognize characteristic and easy to assess patterns that enable an accurate discrimination between the MPN subtypes. Key parameters include cellularity, erythropoiesis and neutrophil granulopoiesis in context with specific features of megakaryocytes as well as the BM fiber content, especially in early stage MPN that present with thrombocytosis and clinically mimic essential thrombocythemia.

Application of a 5 Marker Panel to the Routine Diagnosis of Peripheral T-Cell Lymphoma With T-Follicular Helper Phenotype.

The 2017 World Health Organization update introduced a new category of nodal peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) defined by expression of at least 2 or 3 TFH markers. Our study assesses the utility of an immunohistochemical panel of 5 TFH markers (CD10, BCL6, PD-1, CXCL13, and ICOS) for identification of TFH phenotype in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS). Immunohistochemical for the 5 markers was performed on 22 cases of AITL and 29 cases of PTCL-NOS. Cases were reviewed for morphologic features characteristic of AITL. All AITL cases showed expression of ≥2 TFH markers. This panel resulted in reclassification of 41% PTCL-NOS cases to PTCL-TFH. Positive percent agreement for the TFH phenotype is 97% for PD1, 94% for ICOS, 44% for CD10 and CXCL13, and 29% for BCL6. Negative percent agreement for TFH phenotype is 100% for CD10, BCL6, and CXCL13, 82% for ICOS and 71% for PD1. AITL cases were more likely than PTCL-TFH cases to contain expanded CD21-positive follicular dendritic cell meshworks, clear cell cytology and polymorphous inflammatory background; however, there was a significant (P<0.005) Kruskal-Wallis trend in all morphologic variables between the 3 groups suggesting a continuum from PTCL-NOS to PTCL-TFH to AITL. The median number of morphologic features of AITL also correlated significantly with number of TFH markers positive (Spearman coefficient ρ=0.759). In summary, the stain panel chosen will have an impact on cases classified as PTCL-TFH. This entity may exist along a spectrum between PTCL-NOS and AITL.

Individualized breastfeeding support for acutely ill, malnourished infants under 6months old.

Reestablishing exclusive breastfeeding is the cornerstone of the 2013 World Health Organization (WHO) treatment guidelines for acute malnutrition in infants less than 6 months. However, no studies have investigated guideline implementation and subsequent outcomes in a public hospital setting in Africa. To facilitate implementation of the WHO 2013 guidelines in Kilifi County Hospital, Kenya, we developed standard operating procedure, recruited, and trained three breastfeeding peer supporters (BFPS). Between September 2016 and January 2018, the BFPS provided individual breastfeeding support to mothers of infants aged 4 weeks to 4 months admitted to Kilifi County Hospital with an illness and acute malnutrition (mid‐upper‐arm circumference < 11.0 cm OR weight‐for‐age z score < −2 OR weight‐for‐length z score < ‐2). Infants were followed daily while in hospital then every 2 weeks for 6 weeks after discharge with data collected on breastfeeding, infant growth, morbidity, and mortality. Of 106 infants with acute malnutrition at admission, 51 met the inclusion criteria for the study. Most enrolled mothers had multiple breastfeeding challenges, which were predominantly technique based. Exclusive breastfeeding was 55% at admission and 81% at discharge; at discharge 67% of infants had attained a weight velocity of >5 g/kg/day for three consecutive days on breastmilk alone. Gains in weight‐for‐length z score and weight‐for‐age z score were generally not sustained beyond 2 weeks after discharge. BFPS operated effectively in an inpatient setting, applying the 2013 updated WHO guidelines and increasing rates of exclusive breastfeeding at discharge. However, lack of continued increase in anthropometric Z scores after discharge suggests the need for more sustained interventions.

Identification of "Double Hit" Lymphomas Using Updated WHO Criteria: Insights From Routine MYC Immunohistochemistry in 272 Consecutive Cases of Aggressive B-Cell Lymphomas.

Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89% sensitivity, 38% specificity, 92% negative predictive value, and 29% positive predictive value. Three of 15 (20%) of DHL were MYC IHC negative. One case contained a MYC translocation detectable IGH/MYC fusion probes but not MYC break-apart probes. A subset of DHL lack MYC protein expression, and recognition of this subset of cases requires FISH testing. These results provide an appropriate diagnostic algorithm for implementation of 2016 WHO diagnostic criteria.

Opportunities to improve vaccination coverage in a country with a fledgling health system: Findings from an assessment of missed opportunities for vaccination among health center attendees—Timor Leste, 2016

IntroductionSince its independence in 2002, Timor Leste has made significant strides in improving childhood vaccination coverage. However, coverage is still below national targets, and children continue to have missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. Timor Leste implemented the updated World Health Organization methodology for assessing MOV in 2016. MethodsThe MOV data collection included quantitative (caregiver exit interviews and health worker knowledge, attitudes, practices surveys (KAP)) and qualitative arms (focus group discussions (FGDs) with caregivers and health workers and in-depth interviews (IDIs) with health administrators). During a four-day period, health workers and caregivers with children <24 months of age attending the selected eight facilities in Dili Municipality were invited to participate. The researchers calculated the proportion of MOV and timeliness of vaccine doses among children with documented vaccination histories (i.e., from a home-based record or facility register) and thematically analyzed the qualitative data. ResultsResearchers conducted 365 caregiver exit interviews, 169 health worker KAP surveys, 4 FGDs with caregivers, 2 FGDs with health workers, and 2 IDIs with health administrators. Among eligible children with documented vaccination histories (n = 199), 41% missed an opportunity for vaccination. One-third of health workers (33%) believed their knowledge of immunization practices to be insufficient. Qualitative results showed vaccines were not available at all selected health facilities, and some facilities reported problems with their cold chain equipment. ConclusionThis study demonstrates that many children in Timor Leste miss opportunities for vaccination during health service encounters. Potential interventions to reduce MOV include training of health workers, improving availability of vaccines at more health facilities, and replacing unusable cold chain equipment. Timor Leste should continue to scale up successful MOV interventions beyond Dili Municipality to improve vaccination coverage nationally and strengthen the health system overall.

Design and Validation of a Gene-Targeted, Next-Generation Sequencing Panel for Routine Diagnosis in Gliomas.

The updated 2016 World Health Organization (WHO) classification system for gliomas integrates molecular alterations and histology to provide a greater diagnostic and prognostic utility than the previous, histology-based classification. The increasing number of markers that are tested in a correct diagnostic procedure makes gene-targeted, next-generation sequencing (NGS) a powerful tool in routine pathology practice. We designed a 14-gene NGS panel specifically aimed at the diagnosis of glioma, which allows simultaneous detection of mutations and copy number variations, including the 1p/19q-codeletion and Epidermal Growth Factor Receptor (EGFR) amplification. To validate this panel, we used reference mutated DNAs, nontumor and non-glioma samples, and 52 glioma samples that were previously characterized. The panel was then prospectively applied to 91 brain lesions. A specificity of 100% and sensitivity of 99.4% was achieved for mutation detection. Orthogonal methods, such as in situ hybridization and immunohistochemical techniques, were used for validation, which showed high concordance. The molecular alterations that were identified allowed diagnosis according to the updated WHO criteria, and helped in the differential diagnosis of difficult cases. This NGS panel is an accurate and sensitive method, which could replace multiple tests for the same sample. Moreover, it is a rapid and cost-effective approach that can be easily implemented in the routine diagnosis of gliomas.

Cost-effectiveness analysis of infant feeding modalities for virally suppressed mothers in Canada living with HIV.

The aim of the study was to determine whether exclusive breastfeeding or exclusive formula feeding is more cost-effective when a Canadian mother with HIV is adherent to antiretroviral therapy and has full virologic suppression. Current Canadian guidelines recommend that mothers with HIV practice exclusive formula feeding. This contradicts the updated World Health Organization (WHO) guidelines which recommend that mothers with HIV should breastfeed for ≥12 months while receiving support for antiretroviral therapy adherence. Due to the economic and health risks and benefits associated with each modality, there remains expert disagreement on whether the WHO recommendations should be adopted in high-income countries. A microsimulation model was developed to estimate lifetime costs and effectiveness (i.e., infant's quality-adjusted life years) of a hypothetical group of 1,000,000 initially healthy, HIV-negative infants, if the mother with HIV was on antiretroviral therapy with full virologic suppression and either exclusive breastfeeding or exclusive formula feeding. The model was developed from the economic perspective of the Ontario Ministry of Health, taking into account direct costs associated with infant feeding modality as well as related indirect costs born out of the child's lifetime health outcomes. Uncertainties related to model parameters were evaluated using one-way and probabilistic sensitivity analyses. In comparison to exclusive formula feeding, exclusive breastfeeding was the dominant feeding modality (i.e., less costly and more effective) yielding cost-savings of $13,812 per additional quality-adjusted life year gained. Neither one-way nor probabilistic sensitivity analyses altered the conclusions. Despite the risk of HIV transmission, exclusive breastfeeding was more cost-effective than exclusive formula feeding. These findings merit review of current infant feeding guidelines for mothers with HIV living in high-income countries.

Real world data as a key element in precision medicine for lymphoid malignancies: potentials and pitfalls.

Molecular genetic studies of lymphoma have led to refinements in disease classification in the most recent World Health Organization update. Nevertheless, a 'one-size-fits-most' treatment strategy based on morphology remains widely used for lymphoma despite significant molecular heterogeneity within histopathologically-defined subtypes. Precision medicine aims to improve patient outcomes by leveraging disease- and patient-specific information to optimise treatment strategies, but implementation of precision medicine strategies is challenged by the biological diversity and rarity of lymphomas. In this review, we explore existing and emerging real-world data sources that can be used to facilitate the development of precision medicine strategies in lymphoma. We provide illustrative examples of the use of real-world analyses to refine treatment strategies, provide comparators for clinical trials, improve risk-stratification to identify patients with unmet clinical needs and describe long-term and rare toxicities.

Next Generation Sequencing in AML—On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation?

Acute myeloid leukemia (AML) is a clonal disease caused by genetic abberations occurring predominantly in the elderly. Next generation sequencing (NGS) analysis has led to a deeper genetic understanding of the pathogenesis and the role of recently discovered genetic precursor lesions (clonal hematopoiesis of indeterminate/oncogenic potential (CHIP/CHOP)) in the evolution of AML. These advances are reflected by the inclusion of certain mutations in the updated World Health Organization (WHO) 2016 classification and current treatment guidelines by the European Leukemia Net (ELN) and National Comprehensive Cancer Network (NCCN) and results of mutational testing are already influencing the choice and timing of (targeted) treatment. Genetic profiling and stratification of patients into molecularly defined subgroups are expected to gain ever more weight in daily clinical practice. Our aim is to provide a concise summary of current evidence regarding the relevance of NGS for the diagnosis, risk stratification, treatment planning and response assessment in AML, including minimal residual disease (MRD) guided approaches. We also summarize recently approved drugs targeting genetically defined patient populations with risk adapted- and individualized treatment strategies.

Newer Drugs for Tuberculosis Prevention and Treatment in Children.

Children suffer a huge and often an unrecognized burden of tuberculosis (TB) in endemic countries like India. Better data have improved the visibilityof childhood TB, but the establishment of functional TB prevention and treatment programs for children remains challenging. Barriers to TB prevention include: 1) non-implementation of existing guidelines, 2) perceived inability to rule out active TB with fear of creating drug resistance and 3) limited local guidance on the use of preventive therapy after close contact with drug resistant TB. Barriers to TB treatment include: 1) diagnostic challenges in resource-limited settings, 2) presentation to maternal and child health (MCH) services with poor linkage to the TB control program and 3) limited local guidance on the treatment of children with likely drug resistant TB. The authors provide an overview of newer drugs used for TB prevention and treatment in children. They discuss new options for the treatment of latent TB infection (LTBI) and new or repurposed drugs used in the treatment of children with multidrug resistant (MDR)-TB. The background information provided describes the benefits, risks and feasibility of various treatment options, which should assist treatment decisions until updated World Health Organization (WHO) guidance becomes available.

Beyond health care providers\u2019 recommendations: understanding influences on infant feeding choices of women with HIV in the Eastern Cape, South Africa

BackgroundDespite the array of studies on infant feeding practices of HIV-infected women, gaps still exist in the understanding of the underlying reasons for their infant feeding choices. Potential for behavioural change exists, especially in the light of the 2016 updated World Health Organization guideline on HIV and infant feeding. The aim of this paper is to determine the rate of adoption of exclusive breastfeeding in this cohort, examine the determinants of infant feeding choices of HIV-infected women and assess the underlying reasons for these choices.MethodsThis was a mixed methods study conducted between September 2015 and May 2016. It analyses the quantitative and qualitative data of 1662 peripartum women enrolled in the East London Prospective Cohort Study across three large maternity services in the Eastern Cape. Women with HIV reported their preferred choices of infant feeding. In addition, participants explained the underlying reasons for their choices. Descriptive and inferential statistics summarised the quantitative data, while thematic content analysis was performed on qualitative data.ResultsOf the 1662 women with complete responses, 80.3% opted to exclusively breastfeed their babies. In the adjusted model, up to grade 12 education level (AOR: 1.81; 95% CI: 1.14, 2.86), rural/peri-urban residence (AOR:1.44; 95% CI: 1.05, 1.96), alcohol use (AOR: 1.65; 95% CI: 1.25, 2.18), negative or unknown HIV status at booking (AOR:1.85; 95% CI:1.27, 2.70), currently married (AOR:1.43; 95% CI:1.01, 2.02) and WHO Clinical Stage 2–4 (AOR:1.77; 95% CI: 1.15, 2.72) were significantly associated with the decision to exclusively breastfeed. Health care providers’ recommendations, perceived benefits of breastfeeding, unaffordability of formula feeding, and coercion were the underlying reasons for wanting to breastfeed; while work/school-related demands, breast-related issues, and fear of infecting the baby influenced their decision to formula feed.ConclusionThe majority of HIV-infected women chose to breastfeed their babies in the Eastern Cape. Following up on these women to ensure they breastfeed exclusively, while also addressing their possible concerns, could be an important policy intervention. Future studies should focus on how early infant feeding decisions change over time, as well as the health outcomes for mother and child.

Current criteria for the diagnosis of adrenocortical carcinoma

Adrenocortical carcinoma is a rare malignant tumor of the adrenal cortex with an unfavorable prognosis. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) published the 4th edition of the WHO Classification of Tumors of Endocrine Organs. The updated classification reflects a multidisciplinary experience in diagnosing and predicting the course of adrenal cortex tumors, obtained on the basis of current studies. This paper highlights the key provisions of the updated WHO classification for adrenocortical carcinoma.

Up-regulation of EMT-related gene VCAN by NPM1 mutant-driven TGF-β/cPML signalling promotes leukemia cell invasion.

Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) is acknowledged as a distinct leukemia entity in the 2016 updated World Health Organization (WHO) classification. NPM1-mutated AML patients are correlated with higher extramedullary involvement. Epithelial-mesenchymal transition (EMT) is one of the key steps which cause distant metastasis in tumor. However, whether EMT-related programs contribute to cell invasion in NPM1-mutated AML remains unclear. In this study, we identified the EMT-related gene versican (VCAN) in NPM1-mutated AML across three patient datasets. Further experiments validated the elevated VCAN expression in NPM1-mutated AML primary blasts and OCI-AML3 cells with NPM1 mutation. Mechanistic studies revealed that increased VCAN expression was at least partially regulated by NPM1 mutant via TGF-β/cPML/Smad signalling. Functional evaluations showed that silencing VCAN by shRNA significantly suppressed cell migration and invasion capacity, whereas increased VCAN by overexpressing NPM1-mA enhanced migration and invasion ability of leukemia cells. Finally, we found that high expression of VCAN was associated with poor prognosis in AML patients. These findings provide insights into the involvement of EMT-related gene VCAN in the pathogenesis of NPM1-mutated leukemia, which suggests that VCAN is an attractive target for novel diagnostic and therapeutic strategies in NPM1-mutated AML.

Heterogeneity of genomic alterations and clinical aspects in peripheral T-cell lymphoma: future perspectives

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphoid malignancies. Several recent comprehensive genomic studies characterize the genomic alterations of each PTCL type and reveal the complexity and heterogeneity. The updated World Health Organization classification has precisely distinguished "lymphoma" from "lymphoproliferative disorder" and has included a new entity based on the tumor phenotypes. Although establishing the classifications based on genomic alterations has been difficult because of heterogeneity, the genomic alterations may support the diagnosis. Establishing genomic alterations that act as predictive markers for clinical courses and/or therapeutic targets is needed in future studies using genomic alteration information. Since patients with PTCL generally have poor prognosis, establishing the target and standard therapies is one of the major issues to be addressed. In addition to clinicopathological and genomic analyses, patient-derived xenograft models can provide these therapeutic strategies. Integration of analyzed data is considered to promote future PTCL studies, leading to improved PTCL prognosis.

Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups.

With the updated World Health Organization (WHO) 2016 neuropathological diagnostic criteria, radiographic prognostic associations in lower-grade gliomas (LGG, WHO grade II and III) are undergoing re-evaluation. We identified 316 LGG patients (151 grade II and 165 grade III) for a combined cohort from three independent databases. We analyzed the preoperative axial FLAIR, axial T2-weighted and post-gadolinium volumetric T1-weighted MR images. The molecular data collected included the status of IDH1/2, TP53, TERT promoter and ATRX mutations, in addition to 1p/19q co-deletions. In a subset of cases (n = 133), we assessed the "T2-FLAIR mismatch" sign. Gliomas were assigned to one of the three molecular groups: Group O (IDH-mutant, 1p/19q co-deleted oligodendrogliomas, n = 95), Group A (IDH-mutant, ATRX inactivated astrocytomas, n = 175) and Group G (IDH wild-type, GBM-like, n = 46). A contrast-enhancing tumor was seen in 98 patients (31%), most frequently in Group G (n = 28/45, 57%), when compared to Group A (n = 49/175, 28%) and Group O (n = 24/95, 25.3%) tumors (p = 0.008 and p = 0.0011, respectively). Consistent with previous reports, T2-FLAIR mismatch was preferentially found in Group A tumors (73.1%, 60 of 82), although its presence was not associated with survival, after controlling for molecular group. False positive mismatch sign was noted in 28.5% (12/42) Group O tumors, but none of the tumors in Group G. A combination of all three factors: age under 40years at first diagnosis, a tumor size larger than 6cm and T2-FLAIR mismatch was highly specific for IDH mutant astrocytoma (Group A). We identify radiographic correlates of molecular groups in lower-grade gliomas, which join clinical demographic features in defining the characteristic presentation of these tumors. Radiographic correlates of prognosis in LGG require re-evaluation within molecular group.

Tubular brain tumor biopsy improves diagnostic yield for subcortical lesions.

Molecular data has become an essential part of the updated World Health Organization (WHO) grading of central nervous system tumors. However, stereotactic needle biopsies provide only small volume specimens and limit the extent of histologic and molecular testing that can be performed. We assessed the use of a tubular retractor-based minimally invasive biopsy technique to provide improved tissue yield and diagnostic data compared to needle biopsy. Eighteen patients underwent an open transtubular biopsy compared to 146 stereotactic biopsies during the years of 2010-2018. Tubular biopsies resulted in a higher volume of tissue provided to the pathologist than needle biopsies (1.26cm3 vs. 0.3cm3; p < 0.0001). There was a higher rate of non-diagnostic sample with stereotactic compared to transtubular biopsy (13% vs. 0%; p = 0.13). Six patients who underwent stereotactic biopsy required reoperation for diagnosis, while no transtubular biopsy patient required reoperation in order to obtain a diagnostic specimen. Postoperative hematoma was the most common post-operative complication in both groups. Stereotactic transtubular biopsies are a viable alternative to stereotactic needle biopsies with excellent rates of diagnostic success and acceptable morbidity relative to the needle biopsy technique. As molecular data begins to increasingly drive treatment decisions, additional biopsy techniques that afford large tissue volumes may be necessary to adapt to the new needs of pathologists and treating oncologists.

Mucinous Cystadenoma of the Urachus and Review of Current Classification of Urachal Mucinous Cystic Neoplasms.

Urachal neoplasms are uncommon and represent a minor portion of bladder tumors. According to the recently updated World Health Organization classification (2016), these tumors are classified as adenomas, adenocarcinomas, nonglandular neoplasms, and mixed carcinomas. The mucinous cystic neoplasms represent a small percentage of urachal tumors with morphologic spectrum ranging from benign mucinous cystadenoma to borderline mucinous cystic tumor of low malignant potential and to malignant mucinous cystadenocarcinoma. Benign urachal mucinous cystic adenomas are exceedingly rare, and only a few cases have been reported in the literature to date. The goal of this review is to summarize the clinical features, histopathologic characteristics, treatment, and prognosis of urachal mucinous cystadenoma in light of differentiating them from mucinous cystic tumor of low malignant potential and mucinous cystadenocarcinoma.

Clinical implications of molecular markers in acute myeloid leukemia.

The recently updated World Health Organization (WHO) Classification of myeloid neoplasms and leukemia reflects the fact that research in the underlying pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable advances in our understanding of the disease. Gene mutations now allow us to explore the enormous diversity among cytogenetically defined subsets of AML, particularly the large subset of cytogenetically normal AML. Despite the progress in unraveling the tumor genome, only a small number of recurrent mutations have been incorporated into risk-stratification schemes and have been proven to be clinically relevant, targetable lesions. We here discuss the utility of molecular markers in AML in prognostication and treatment decision making, specifically highlighting the aberrations included in the current WHO classification.

Variability and Lack of Prognostic Value Associated With Atypical Pituitary Adenoma Diagnosis: A Systematic Review and Critical Assessment of the Diagnostic Criteria.

Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology. To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence. A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth. Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression. Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.

Prevalence of underweight and overweight among young adolescents aged 12-15years in 58 low-income and middle-income countries.

The co-existence of underweight and overweight is a great challenge for public health in low-income and middle-income countries (LMICs). The objective of the study is to report the prevalence of underweight, overweight and obesity among young adolescents in 58 LMICs. Data were from the Global School-based Student Health Survey (2007-2013) in 57 LMICs and from the Chinese National Surveys on Students' Constitution and Health (2010). A total of 177325 young adolescents aged 12-15years from 58 LMICs were included. Weight status was defined based on both the updated International Obesity Task Force (IOTF) and World Health Organization (WHO) criteria. Based on the IOTF/WHO criteria, the overall prevalence of weight categories among young adolescents in LMICs was 13.4%/4.7% for underweight, 15.4%/17.3% for overweight and 5.6%/8.6% for obesity. However, the prevalence varied largely across countries and regions. Based on the IOTF criteria, the prevalence of underweight ranged from 0.0% in Niue to 48.8% in Sri Lanka and obesity ranged from 0.1% in Vanuatu to 35.0% in Niue; a prevalence exceeding 10.0% for both underweight and excess weight (overweight and obesity combined) was found in 29.3% of these countries. Underweight was more prevalent in Southeast Asia and Africa, while obesity was more frequent in Central and South Americas. There were no age and sex differences in the prevalence of weight categories for most countries. Our data confirm the continued dual burden of underweight and overweight in young adolescents in many LMICs and the need for policy and programmes to address both conditions.