Revised World Health Organization Classification Research Articles

A case of branch duct type intraductal papillary neoplasm of the bile duct treated by open surgery after 11 years of follow-up

The intraductal papillary neoplasm of the bile duct (IPNB) is a novel disease concept that was recently classified as a biliary cystic tumor by the revised World Health Organization classification. This is the case report of a 70-year-old female patient who experienced repeated episodes of obstructive jaundice and cholangitis since 2000, attributed to a mucus-producing hepatic tumor. Surgery was advised due to the repeated episodes; however, the patient refused. In May, 2011, the patient developed jaundice and fever and was treated with antibiotics. Since there was no improvement, the patient was admitted to the Tokyo Rosai Hospital. Abdominal computed tomography (CT) revealed a 50-mm cystic mass with an internal septum in the left hepatic lobe. Although the tumor size had remained almost unchanged compared to the initial CT scan performed in 2000, intra- and extra-hepatic bile duct dilation was more prominent on the second CT scan. Following admission, endoscopic retrograde cholangiopancreatography was performed and revealed an expanded papilla of Vater due to a mucous plug. A balloon catheter was inserted into the bile duct to remove the mucous plug, resulting in the drainage of copious amounts of mucus and infected bile. The patient finally consented to surgery and left hepatic lobectomy was performed. Consequently, the diagnosis of low-grade IPNB was made. Branch duct type IPNB, which is characterized by imaging appearance of a cystic mass and slow progression, is attracting increasing attention. In the present case, a cystic mass was identified in the left hepatic lobe, with no significant change in size after 11 years of follow-up, leading to the diagnosis of branch duct type IPNB. Considering the fact that IPNB is usually treated surgically at the time of diagnosis, the present case, due to the long-term follow-up, provides valuable insight into the natural history of the tumor.

Prognosis based on the revised histological classification by the World Health Organization (2010) for pancreatic neuroendocrine tumors

Background/aim: Pancreatic neuroendocrine tumors (PNETs) are a rare subgroup of tumors, for which the factors predictive of survival and prognosis are not well known. Recently, the European Neuroendocrine Tumors Society (ENETS) proposed the TNM staging and the World Health Organization (WHO) revised its histological classification in 2010. This study aimed to evaluate whether the ENETS staging and the revised WHO classification can predict survival after surgical resection of PNETs. Methods: Twenty consecutive curative resections for PNETs were performed at our institute from 1998 to 2012. The prognostic factors based on the revised WHO histological classification (2010) for survival were retrospectively evaluated using the Kaplan–Meier method. Results: The mean patient age was 60.3 10.9 years. Twelve patients (60%) were diagnosed with functioning tumors and 8 (40%) with nonfunctioning tumors. Surgical methods comprised pancreatoduodenectomy (n 1⁄4 3), distal pancreatectomy (n 1⁄4 5), enucleation (n 1⁄4 9), and central pancreatectomy (n 1⁄4 3). Hepatectomy was performed for 2 patients with synchronous liver metastasis. According to the ENETS staging, 14 (70%), 2 (10%), 2 (10%), and 2 (10%) had stage I, II, III, and IV tumors, respectively. According to the revised WHO histological classification (2010), 13 (65%), 5 (25%), 1 (5%), and 1 (5%) patient was diagnosed with neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC), and mixed adenoneuroendocrine carcinoma (MANEC), respectively. Univariate analysis revealed that both the ENETS staging and the revised WHO histological classification (2010) significantly predicted survival after surgical resection for PNETs. Conclusions: The ENETS staging and the revised WHO histological classification (2010) may be useful to predict survival in PNETs. However, because PNETs represent a rare tumor subgroup, more time and a sufficient number of cases are required to confirm its prognostic reliability.

Accuracy and applicability of the revised WHO classification (2009) of dengue in children seen at a tertiary healthcare facility in northern India

Revised case definitions of dengue into dengue with/without warning signs (DWS/D) and severe dengue (SD) was proposed by the World Health Organization (WHO)/Tropical Disease Research (TDR) in 2009. To date, there has been no Indian study that has applied this classification. To assess the accuracy and applicability of the revised WHO classification (2009) of dengue in children seen at a tertiary healthcare facility in India. Over a period of 1 year children from the pediatric ward and Out Patient Department (OPD) of the King George Medical University Hospital, Lucknow were enrolled in the study according to predefined criteria and tested for dengue. Each dengue-positive patient was classified according to both the older system [dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS)] and the new system (D, DWS, and SD). The severity of dengue was compared to the level of treatment received. A total of 56 patients tested positive for dengue--51 from the pediatric ward and five from the OPD. According to the older WHO classification, 42 (75 %) patients were classified as DF and 13 (23.2 %) as DHF/DSS; one patient was unclassifiable. Five patients (8.9 %) received level 1 treatment, ten (17.8 %) received level 2 treatment, and 41 (73.2 %) received level 3 treatment. According to the new WHO/TDR classification, 46 (82.1 %) patients were classified as SD, nine (16 %) as DWS, and only one (1.7 %) as D. Many of the severe manifestations (encephalopathy, shock, mucosal bleed, platelet count <20,000, respiratory distress, liver enzymes >1,000 U/L) were seen in patients who were classified as DF according to old classification, whereas these patients were mostly classified as SD by the new classification. Sensitivity of the older and new classifications was 24.8 and 98 %, respectively. The revised WHO/TDR (2009) classification has very high sensitivity for identifying severe dengue and is easy to apply.

Usefulness of World Health Organization (WHO) dengue case classifications in a Sri Lankan clinical setting

Background: Dengue viral infections are a major public health problem in many tropical and sub-tropical countries of the world. Early diagnosis and appropriate therapeutic interventions are critical for reducing both morbidity and mortality. The WHO has proposed a revised classification based on warning signs as the validity and usefulness of the WHO 1997 dengue classification has been questioned in recent times. The objective of this study was to assess the usefulness and applicability of these guidelines in the clinical setting. Methods: Clinical and laboratory findings were recorded in a standard format and cases were classified using the two classifications. Presence of warning signs in clinical DF and DHF groups were compared. Results: One hundred and six patients with clinically suspected dengue between January and July 2010 were studied. Seventy eight (75.7%) had dengue fever (DF) and 28 (26.4%) had dengue haemorrhagic fever (DHF) according the clinical parameters. Of the patients with DHF, only five (17.9%) fulfilled all four WHO criteria for DHF. Application of the revised WHO classification revealed 19 (17.9%) dengue without warning signs, 82 (77.4%) dengue with warning signs and 5 (4.7%) severe dengue. Presence of warning signs was compared in clinical DF and DHF groups. In total, 60 (76.9%) DF and 26 (92.9%) DHF patients developed warning signs, and 1 (3.6%) DHF patient did not have any warning signs. Thirty three (42.3%) DF patients had 2 or more warning signs while 22 (78.5%) DHF patients had two or more warning signs. Conclusion: There were limitations in applying the WHO 1997 classification in making a diagnosis of DHF. We were able to classify all patients using the revised WHO 2009 classification and is more compatible with observed clinical findings and user-friendly to the practicing physician. DOI: http://dx.doi.org/10.4038/jccp.v42i1-2.4550 Journal of the Ceylon College of Physicians, 2011, 42 , 21-27

Clinicopathological Features and Outcomes of T- and NK-Cell Lymphomas in European Russia

With the introduction of the revised World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues in 2001, many patients had to be re-evaluated for the correct diagnosis of T- and NK-cell lymphomas. Because some T-cell malignancies are associated with poor outcome, it is important to identify subsets of patients that may benefit from novel or more intensive therapies. The purpose of this study was to determine, for the first time, the relative frequencies, pathological features and outcomes of patients with T- and NK-cell lymphomas in a predominantly Russian Slavic population. We identified 291 patients with a diagnosis of T- and NK-cell malignancies treated at our Center between 2000-2008. In applying the revised WHO classification, we confirmed the diagnosis and had complete clinical follow up and pathological information on 264 cases that were included in the analysis. We found some differences in frequency of several subsets as compared with previously published reports, including younger age of onset and relatively higher incidence of T-LGL in our patients. We also confirm that intensive treatment regimens of advanced stage PTCL and ALK—ALCL led to considerable improvement in response rates, but not in the overall survival.

Evaluation of the Traditional and Revised WHO Classifications of Dengue Disease Severity

Dengue is a major public health problem worldwide and continues to increase in incidence. Dengue virus (DENV) infection leads to a range of outcomes, including subclinical infection, undifferentiated febrile illness, Dengue Fever (DF), life-threatening syndromes with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. The long-standing World Health Organization (WHO) dengue classification and management scheme was recently revised, replacing DF, Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) with Dengue without Warning Signs, Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure). We evaluated the traditional and revised classification schemes against clinical intervention levels to determine how each captures disease severity using data from five years (2005–2010) of a hospital-based study of pediatric dengue in Managua, Nicaragua. Laboratory-confirmed dengue cases (n = 544) were categorized using both classification schemes and by level of care (I–III). Category I was out-patient care, Category II was in-patient care that did not meet criteria for Category III, which included ICU admission, ventilation, administration of inotropic drugs, or organ failure. Sensitivity and specificity to capture Category III care for DHF/DSS were 39.0% and 75.5%, respectively; sensitivity and specificity for SD were 92.1% and 78.5%, respectively. In this data set, DENV-2 was found to be significantly associated with DHF/DSS; however, this association was not observed with the revised classification. Among dengue-confirmed cases, the revised WHO classification for severe dengue appears to have higher sensitivity and specificity to identify cases in need of heightened care, although it is no longer as specific for a particular pathogenic entity as was the traditional schema.

Clinicopathologic features and outcome of acute erythroid leukemia based on 2008 revised World Health Organization classification

We report 67 patients with acute erythroid leukemia (erythroleukemia) based on the World Health Organization (WHO) 2008 classification. Reviewing the clinicopathologic features, cytogenetics and outcomes, the characteristics of erythroleukemia resembled myelodysplastic syndromes (MDS). Patients with poor performance status, advanced anemia and poor-risk cytogenetics had significantly inferior outcomes. The International Prognostic Scoring System (IPSS) for MDS is useful to differentiate the prognosis of erythroleukemia.

Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p=.96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p=.02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p=.44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p=.005). The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the published data for future treatment decision-making remains difficult when the histologic diagnosis has not been based on the new improved classification system.

High-grade malignant glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

High-grade malignant glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up R. Stupp, J.-C. Tonn, M. Brada & G. Pentheroudakis On behalf of the ESMO Guidelines Working Group* Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, and Department of Oncology-Hematology Riveria-Chablais, Vevey, Switzerland; Department of Neurosurgery, Universitatsklinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany; Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, Sutton, UK; Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

BENZENE 2009—Health effects and mechanisms of bone marrow toxicity: Implications for t-AML and the mode of action framework

This overview of the Symposium and its organization includes a historical survey of the scientific literature in which the relationship of benzene exposure to the development of aplastic anemia and other bone marrow diseases, including acute myeloid (myelogenous) leukemia, is described. Previous conferences on the health effects of benzene are summarized. The important role of the revised World Health Organization classification of tumors of the hematopoietic and lymphoid tissues in clarifying the specific diseases related to benzene exposure is emphasized.

Myeloid Sarcoma

Myeloid sarcoma (MS), also termed extramedullary acute myeloid leukemia, extramedullary myeloid tumor, and granulocytic sarcoma or chloroma, is a rare manifestation that is characterized by the occurrence of 1 or more tumor myeloid masses occurring at an extramedullary site. The wide spectrum of this disorder and the conditions that it overlaps diagnostically were well reflected in the 25 cases submitted to the Society for Hematopathology/European Association for Haematopathology Workshop held in Indianapolis, IN, in November 2007. This review, on the one hand, focuses on the definition and most recent achievements on the pathobiology of MS, and on the other, also in the light of the revised World Health Organization classification, summarizes the main features of a representative series of this condition aiming to provide readers a useful document for daily practice.

Malignant glioma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up

Malignant glioma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up

Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system

Although some studies have validated the 2001 World Health Organization (WHO) classification of acute myeloid leukemia (AML), including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics but has no independent impact on prognosis. In 2008, the revised WHO classification has expanded this category into "AML with myelodysplasia-related changes" (AML-MRC). We evaluated the clinical, pathologic, cytogenetic, and molecular features of 100 AML patients using the 2008 WHO criteria. Patients underwent genetic screening for NPM1, FLT3-ITD, FLT3-D835, and CEBPA mutations. Compared with patients with AML, not otherwise specified, patients with AML-MRC were significantly older (P= .014), presented with a lower hemoglobin (P= .044), more frequently expressed CD14 (P= .048), and exhibited a decreased frequency of CEBPA mutations (P= .001). Multivariate analysis indicated that patients with AML-MRC had a significantly worse overall survival, progression-free survival, and complete response compared with AML-not otherwise specified (all P< .001). These data support the clinical, morphologic, and cytogenetic criteria for this 2008 WHO AML category.

The Need for Standardization of Methods for Worldwide Infant Hearing Screening: A Systematic Review

No uniform case definition presently exists for infant hearing screening programs worldwide especially for minimal hearing loss (HL). This article systematically reviewed the current practices in developing countries for programs aimed at early detection of "disabling" congenital and early-onset HL and found significant variations which undermine comparability of key findings in the reported studies. Implications for the exclusion of minimal HL are explored within the context of the International Classification of Functioning, Disability and Health (ICF) of the World Health Organization and its adapted version for children and youth (ICF-CY). A revised World Health Organization classification that accounts for all categories of HL based on ICF-CY may provide a suitable framework for improved uniformity in reporting standards.

WHO Classification of Tumours of the Central Nervous System, Fourth Edition

WHO Classification of Tumours of the Central Nervous System, Fourth Edition D.N. Louis, H. Ohgaki, O.D. Wiestler, W.K. Cavenee, editors IARC, Lyon, France Copyright © 2007 312 pages. CHF 122.00 / US $109.80. Representing the first volume in the fourth edition series of the World Health Organization (WHO) Classification of Tumours , this book provides a welcome mix of old and new. Similar to prior versions, it opens with a summary of the recently revised WHO Classification of Tumours of the Central Nervous System (CNS), the remainder of the book being dedicated to a comprehensive yet succinct presentation of …

Y1-01: Toward A New Histological Classification Of Lung Tumors

Y1-01: Toward A New Histological Classification Of Lung Tumors

Re: Pulmonary arterial hypertension in connective tissue diseases

SIR, In their review of pulmonary arterial hypertension in connective tissue diseases, Kahler and Colleselli [1] discuss the epidemiology, pathophysiology, diagnostic tools and treatment options of this disease. However, in their first table, there seems to be confusion between the terms ‘pulmonary arterial hypertension’ and ‘pulmonary hypertension’. The revised World Health Organization classification of pulmonary hypertension [2, 3], is based upon the underlying pathophysiological processes involving the pulmonary blood vessels. Five classes are distinguished (Table 1). In the first ‘class, referred to as pulmonary arterial hypertension, the pulmonary arteries are the real site of pathology (hence the name of pulmonary arterial hypertension). The second class comprises those forms of pulmonary hypertension that afflict the veins and is hence called pulmonary venous hypertension. The third and fourth class consist of forms of pulmonary hypertension associated, respectively, with hypoxic lung disease and thromboembolic disease. The fifth class includes other rare causes of pulmonary hypertension and is referred to as the ‘miscellaneous’ class. So, in contrast to the terminology applied by Kahler and Colleselli in their first table (in which also class 2, 3 and 4 are referred to as pulmonary arterial hypertension), only the first class can truly be referred to as pulmonary arterial hypertension. For the clinician, it is important to realize that not all forms of pulmonary hypertension do represent pulmonary arterial hypertension. This distinction has also therapeutical consequences. Indeed, some drugs can be used to treat pulmonary arterial hypertension (e.g. vasodilators like calcium antagonists; prostaglandins; endothelin receptor antagonists), but not to treat the other forms of pulmonary hypertension. To illustrate this, vasodilator therapy, which may be helpful for patients with pulmonary arterial hypertension (class 1), could actually worsen the hypoxaemia in patients with class 3 pulmonary hypertension. Similarly, the non-appropriate use of vasodilators in patient with pulmonary venous hypertension (class 2) may actually increase signs of left heart failure.

Large cell neuroendocrine carcinoma of the uterine cervix with cytogenetic analysis by comparative genomic hybridization: a case study

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a newly introduced category of the revised World Health Organization classification. We reported a case of cervical LCNEC with cytogenetic analysis by comparative genomic hybridization (CGH). The cervical tumor showed moderately increased mitotic activity (8-14 mitotic figures per 10 high-power fields) and focal necrosis, which made it problematic to differentiate from atypical carcinoid. CGH analysis failed to detect chromosome 11q loss that has been reported to be characteristic of pulmonary atypical carcinoids. Furthermore, chromosome 3q amplification, which has been detected frequently in pulmonary small cell carcinomas and LCNECs but not in pulmonary typical and atypical carcinoids, was the most remarkable chromosomal aberration. Although CGH reports are extremely rare in neuroendocrine tumors of the uterine cervix, specific chromosomal aberrations may be useful in their distinction.

Extraskeletal myxoid chondrosarcoma: Updated clinicopathological and molecular genetic characteristics

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma characterized by distinctive morphological and cytogenetical features. As its name implies, EMC was believed to represent a variant of soft-tissue chondrosarcoma owing to its histological resemblance to chondroblastic tissue in the early stages of cartilage development or chondroid tumors such as skeletal chondrosarcoma. However, the chondroid nature has been a subject of controversy, and its line of differentiation remains to be determined. Consequently, the tumor is provisionally classified into a group of tumors of uncertain differentiation in the revised World Health Organization classification of tumors of soft tissue and bone. Moreover, immunohistochemical and ultrastructural features of neural or neuroendocrine differentiation have been recently reported in a subset of EMC, providing a new insight into their histogenetic nature. Chromosomal rearrangements involving 9q22, such as t(9;22)(q22;q12), and resultant NR4A3 fusion genes are tumor-type specific or pathognomotic for this entity and are assumed to play an important role in the development of EMC. Although the biological mechanisms and functions are largely unknown, the NR4A3-related pathway is considered a potential molecular target for future therapeutic intervention. Because of its protracted but resilient nature, a tenacious and long-term follow up is necessary for any patient.

Bronchioloalveolar Carcinoma of the Lung 3 Centimeters or Less in Diameter: A Prognostic Assessment

Background Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of adenocarcinoma for which the incidence is actually rising, but the histologic definition of BAC has been recently changed by the revised World Health Organization (WHO) classification in 1999. The clinical features of patients with BAC diagnosed according to the recently revised WHO classification have not yet been clarified. In this retrospective study, we investigated the pattern of recurrence and survival outcome for patients with resected BAC by pathology review, compared with those in patients who had adenocarcinoma other than BAC. Methods From 1985 through 2002, 108 patients underwent surgical resection for pulmonary adenocarcinoma 3 cm or less in diameter at the University of Yamanashi, Japan. All of the resected specimens of these 108 patients were pathologically reviewed again to confirm the diagnosis as BAC or adenocarcinoma other than BAC. The tumor was defined as BAC when the adenocarcinoma lesion had a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion according to the WHO classification (third edition). Results Twenty-five patients (23%) had a diagnosis of BAC, and 83 (77%) had a diagnosis of other adenocarcinoma. There was a female predominance among both patients with BAC and those with other adenocarcinoma. Lymph node involvement was seen for 30 lesions (36%) of adenocarcinoma other than BAC, but not for any BAC lesions. The median duration of follow-up after surgery was 5.1 years. There was no recurrence in the postoperative course in patients with BAC for a 5-year disease-free survival rate of 100%, whereas the 5-year disease-free survival rate for other adenocarcinoma was 63.5%. Conclusions The patients with resected BAC, which is defined as a noninvasive adenocarcinoma by the revised WHO classification, had an excellent prognosis. However, these results may depend on a strictly accurate pathology diagnosis as BAC. Limited resection might be curative in patients with focal BAC based on evidence of pathologic noninvasive features.