WHO Classification System Research Articles

Phosphorylated mTOR and YAP serve as prognostic markers and therapeutic targets in gliomas

Glioma is the most prevalent type of tumor in the brain and is comprised of grades I–IV, according to the WHO classification system. Grade IV glioma is also known as glioblastoma multiforme (GBM), the most malignant type of glioma. Glioma is characterized by a complex molecular background, and gene profiling studies have disclosed critical genetic events in human gliomas, which make targeted therapies the most promising therapeutic strategy. However, crosstalk between the targeted signaling pathways may hinder the efficacy of targeted therapies in gliomas. Therefore, it is necessary to identify effective markers to stratify patients for specific therapeutic procedures. Although several mechanisms have been proposed based on the crosstalk between PI3K/AKT/mTORC1 and Hippo/YAP pathways, the clinical significance of the two pathways has not yet been assessed in a combinatorial manner. In this study, we evaluated the two pathways in human glioma specimens and observed the positive correlation between protein levels of p-mTORS2448 and YAP in gliomas. The findings indicated that high expression of p-mTORS2448 and YAP correlated with poor overall survival of glioma patients. As p-mTORS2448 is a specific marker of mTORC1 activation, our results reveal a potential interaction between mTORC1 and YAP, which might functionally participate in the development and progression of gliomas. In support of this hypothesis, a combination of inhibitors targeting mTORC1 and YAP showed a better inhibitory effect on growth of glioma cell lines. Altogether, our work, for the first time, reveals that p-mTORS2448 and YAP can be used as markers of PI3K/AKT/mTORC1 and Hippo/YAP pathway activity to predict prognosis and are target candidates for personalized medicine.

Rare Suprasellar Chordoid Meningioma with INI1 Gene Mutation

Background: Chordoid Meningioma is a rare brain tumour characterized genetically by loss of genetic material from chromosome 22q at cytogenetic level resulting in mutation of NF2 gene.Objectives and case report: In the present report, we described a rare case of suprasellar chordoid meningioma, which presented in a 32-year-old-woman. Her only complain was throbbing headache. Neurological examination showed left temporal hemianopia, decreased visual acuity (3/6), and no physical abnormalities related to Castleman syndrome were noted. Cranial magnetic resonance (MR) images demonstrated a 28x15 mm mass in the sellar region, which showed iso-to low intensity that enhanced vividly after gadolinium with upwards displacement of the Optic chiasm.Total surgical excision of the tumour was performed and subsequent histological examination of the tumour showed typical histology pattern of chordoid meningioma grade II according to the WHO classification system of meningiomas.Genomic DNA was extracted and mutation analysis for INI1 gene using primer of exon 4, 5, 7, and 9 showed mutation involving exon 9. DNA sequencing showedheterozygosity C­­­­­­­­­­­­­­­­­­-T mutation in exon 9 of INI1 gene leading to change of amino acid serine to phenylalanine at (codon 63). The details of this case are presented with a review of the literature.

Clinical and pathological classification of canine intraocular lymphoma.

The objectives of this retrospective study of 100 dogs with intraocular lymphoma were to describe the histomorphologic and immunohistochemical features of canine intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared to multicentric disease, and assess the clinical outcomes of these patients. Selected cases from Penn Vet Diagnostic Laboratory and Comparative Ocular Pathology Lab of Wisconsin (2004-2015) were evaluated and subtyped using the WHO classification system. Peripheral T-cell lymphoma and diffuse large B-cell lymphoma were the two most common subtypes. Questionnaires were distributed to the referring veterinarians and veterinary ophthalmologists inquiring about clinical signs at time of enucleation, staging, patient outcome, treatment, and disease progression. Cases were categorized as PSOL if only ocular involvement was noted at the time of diagnosis based on the clinical staging criteria. The majority of cases (61%) did not have systemic involvement at the time of diagnosis, and these cases did not progress postoperatively. Median survival time (MST) was significantly higher for the presumed solitary intraocular cases: 769 vs. 103days, hazard ratio of 0.23 (95% CI: 0.077-0.68). The subtype of lymphoma did not affect survival time. The results of this study suggest two significant points of clinical interest: the majority of dogs (61%) presented without signs of systemic involvement of lymphoma at the time of enucleation, and dogs with only ocular involvement showed no disease progression postenucleation.

Long-term time trends in incidence, survival and mortality of lymphomas by subtype among adults in Manitoba, Canada: a population-based study using cancer registry data

ObjectiveTo examine 30-year time trends in incidence, survival and mortality of lymphomas by subtype in Manitoba, Canada.MethodsLymphoma cases diagnosed between 1984 and 2013 were classified according to the 2008 WHO...

Association of general and central obesity with hypertension

Hypertension as a risk factor for cardiovascular disease has growing prevalence. An increase in body weight is typically followed by an increase in blood pressure. This study aimed to investigate the association of general and central obesity with hypertension in Indonesian women using WHO and Indonesian classification systems. Cross-sectional study of Indonesian women aged 18 years or and more (313,714 participants), using national level Indonesia National Basic Health Research (2013). The prevalence of hypertension in Indonesian women in this study was 32.8%. Based on logistic regression analysis, hypertension was significantly associated with residential area, educational attainment, self-reported smoking status, cardiovascular disease, chronic kidney disease, diabetes mellitus, body mass index and waist circumference. Furthermore, the odds of having hypertension for general and central obesity according to WHO classification were adjusted odds ration (aOR) 2.61, 95% CI 2.52-2.70 and aOR 1.50, 95% CI 1.46-1.53. By Indonesian classification were aOR 2.21, 95% CI 2.16-2.26 and aOR 1.48, 95% CI 1.45-1.51. By using International WHO and standard Indonesia classification systems, general and central obesity were associated with hypertension in Indonesia women. Thus, not only general obesity but also central obesity should be used to assess obesity in Indonesian women.

Update From The 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Nasopharynx.

The current WHO classification system for tumors of the head and neck has made few changes from the previous edition with regards to tumors of the nasopharynx. The classification system is discussed here with particular attention to nasopharyngeal carcinoma, nasopharyngeal papillary adenocarcinoma, salivary gland anlage tumor, hairy polyp, juvenile angiofibroma, and other tumors.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Nasal Cavity, Paranasal Sinuses and Skull Base.

The sinonasal tract remains an epicenter of a diverse array of neoplasia. This paper discusses changes to the WHO classification system of tumors involving this area. In particular, seromucinous hamartoma, NUT carcinoma, biphenotypic sinonasal sarcoma, HPV-related carcinoma with adenoid cystic features, SMARCB1-deficient carcinoma, and renal cell-like adenocarcinoma are discussed.

Acute Myeloid Leukemia with Translocation (8;16)(p11;p13): A Distinct Syndrome– Case Report and Literature Review

Acute myeloid leukemia with the translocation (8;16)(p11;p13) is a rare type of acute leukemia with a number of unique features including erythrophagocytosis, extramedullary disease, and poor prognosis with high relapse rate. These cases of AML are often categorized as M4, M5a, or M5b AML under the FAB system of AML classification. However, the clinical and pathological features of AML with t(8;16) (p11;p13) do not fit into any of these French- American-British (FAB) classification system subtypes, nor is it recognized as a recurrent genetic abnormality within the WHO classification system. Here, we report the case of a 50-year-old female with a history of low-grade carcinoid tumor on surveillance who developed de novo AML with histiocytic differentiation and t(8;16)(p11;p13). Immunohistochemistry and morphology of the patient’s bone marrow biopsy was not consistent with any specific AML subtype, which resulted in diagnostic and therapeutic delays. AML with t(8;16)(p11;p13) has been described a number of times in the literature as a unique leukemic syndrome based on clinical, cytochemical, and DNA microarray features. As such, AML with t(8;16)(p11;p13) should be added to the WHO classification system list of AML with recurrent genetic abnormalities.

P-Benzoquinone initiates non-invasive urothelial cancer through aberrant tyrosine phosphorylation of EGFR, MAP kinase activation and cell cycle deregulation: Prevention by vitamin C.

According to WHO classification system, non-invasive urothelial carcinoma represents urothelial carcinoma in situ (CIS) and dysplasia. Dysplastic urothelium often progresses to CIS that further advances to urothelial carcinoma (UC). The strongest risk factor for UC is cigarette smoking. However, the pathogenesis of cigarette smoke (CS)-induced UC is poorly understood. Earlier we had shown that p-benzoquinone (p-BQ), a major toxic quinone derived from p-benzosemiquinone of CS in vivo, is a causative factor for various CS-induced diseases. Here, using a guinea pig model we showed that prolonged treatment with p-BQ led to non-invasive UC, specifically carcinoma in situ (CIS) of the renal pelvis and dysplasia in the ureter and bladder. The mechanisms of carcinogenesis were p-BQ-induced oxidative damage and apoptosis that were later suppressed and followed by activation of epidermal growth factor receptor, aberrant phosphorylation of intracellular tyrosine residues, activation of MAP kinase pathway and persistent growth signaling. This was accompanied by deregulation of cell cycle as shown by marked decrease in the expression of p21waf1/cip1 and cyclin D1 proteins as well as hyperphosphorylation of pRb. UC has been characterised by histopathology and immunohistochemistry showing aberrant CK20, increased Ki-67, and marked p53 nuclear immunopositivity with uniformly negative labelling of CD44. Oral supplementation of vitamin C (30mg/kg body weight/day) prevented CIS of the renal pelvis and dysplasia in the ureter and bladder. Since majority of non-invasive UC progresses to invasive cancer with increased risk of mortality, our preclinical study might help to devise effective strategies for early intervention of the disease.

New classification system of endometrial hyperplasia WHO 2014 and its clinical implications.

Endometrial hyperplasia (EH) is a pathological condition characterised by hyperplastic changes in endometrial glandular and stromal structures lining the uterine cavity. Endometrial hyperplasia, particularly with atypia, is a significant clinical concern because it can be a precursor of endometrial cancer. Accurate diagnosis of precancerous lesions of the endometrium and exclusion of coexisting endometrial carcinomas are absolutely required for the optimal management of patients. The classification of endometrial hyperplasia has had numerous terminology. According to the classification of WHO94, based on glandular complexity and nuclear atypia, EH is divided into four groups: non-atypical endometrial hyperplasia (simple, complex) and atypical endometrial hyperplasia (simple, complex). Estimated risk of progression of atypical hyperplasia to endometrial cancer is 8-29%. The American College of Obstetricians and Gynaecologists and the Society of Gynaecological Oncology states that endometrial intraepithelial neoplasia (EIN) classification is superior to the World Health Organisation (WHO 94) classification for histology of endometrial hyperplasia. However, the WHO classification system remains the most commonly used and reported in existing literature.The new classification, WHO 2014, accepted by the International Society of Gynaecological Pathologists, divided hyperplasia into two groups: benign hyperplasia and atypical hyperplasia/endometrial intraepithelial neoplasia (EIN). The WHO 2014 schema is more likely to successfully identify precancerous lesions than the WHO94 classification.

Retraction Note to: Improving the diagnosis, treatment, and biology patterns of feline mammary intraepithelial lesions: a potential model for human breast masses with evidence from epidemiologic and cytohistopathologic studies.

In this study, the frequency of different types of mammary masses and their relationship with cytohistopathologic changes was investigated and data on history, macroscopic description, clinical examination and treatment were collected. To determine the prevalence and types of cytohistopathologic changes, mammary glands from 12 female cats were evaluated. The mean age of cats at the time of diagnosis was 11.5 ± 1.9 years (range 4–14 years), the mean gross size of the masses was 3.1 ± 2.4 cm, 4/12 (33.3 %) masses were ≤3.0 cm in diameter, and the maximum diameter of the largest mass had a median of 5 cm, with a range of diameter of 6 × 5 × 4 cm. Moreover, the preferential localization of mammary masses was the abdominal lobes (%50) and thoracic lobes (%33.3), and inguinal lobes (%16.7 of cases). Furthermore, two cases of the inguinal masses affected the caudo-inguinal lobe, six cases caudo-abdominal lobe, and thoracic masses were found in four cases. Eventually, six cases (%50) of masses were found in the right mammary lobes and six cases (%50) in the left mammary lobes. The majority of the masses revealed elastic (%50 of cases), hard (%25 of cases), or soft (%25 of cases) consistency. In the present study, according to the criteria of the veterinary and the medical WHO classification system, of the 12 cats with the cytohistopathological features of six (50 %) cases qualified abscess, 3 (25 %) cases as cystic hyperplasia and 3 (25 %) cases were called situ carcinoma. Whereas, all hyperplastic lesions (case nos. 7–9 and ranging in size from, 1 to >4 cm3) and carcinomas in situ lesions (case nos. 10–12 and ranging in size from, 1 to >3 cm3) were found incidentally upon routine cytohistology. Other lesions were observed grossly and removed either at surgery (case nos. 1–6). Finally, the cats were treated with unilateral lumpectomy (3 cases) and also, nine (75 %) cases had subsequent drainage, 3 (25 %) of which showed cystic hyperplasia and 6 (50 %) showed abscess on subsequent histopathological evaluation. Therefore, a correct diagnosis must be established quickly, and treatment must be instituted rapidly when alteration is noted in the mammary glands.

Surgical management of ventrally located spinal meningiomas via posterior approach.

Spinal meningioma is a relatively common tumor among intradural extramedullary spinal tumors. When the locus of the meningioma is located on the ventral side, tumor removal, dura mater resection, and reconstruction via a posterior approach safety become technically difficult. Twelve patients, who received surgical treatment for ventral spinal meningioma via a posterior approach, were included. There were three male and nine female patients, with an average age of 66.3years (47-88years). The average observation period was 55.4months (22-132months). In these cases, we analyzed the spinal level of tumor position, histopathological type (subtype), the grade of tumor resection (Simpson grade), pre- and post-operative walking state (Nurick grade), perioperative neurological complications, and the recurrence. Spinal meningioma occurred in the cervical spinal cord in three cases, with a further nine cases in the thoracic spinal cord. Histopathologically, all 12 tumors were assessed as grade I on the WHO classification system (eight cases of meningothelial type and four cases of psammomatous type). The level of tumor resection was Simpson grade I resection for two cases and Simpson grade II resection for the remaining ten cases. The average of Nurick grade improved from 3.3 preoperatively to 1.3 postoperatively. In all cases, we identified no neurological complications. One incident of tumor recurrence was identified 11years after an operation involving a Simpson grade II resection CONCLUSION: Posterior approaches provide adequate exposure to safely remove ventrally located meningioma. Posterior exposures with lateral bone resection, dentate ligament division, provide also adequate exposure for safe removal.

Micropapillary: A component more likely to harbour heterogeneous EGFR mutations in lung adenocarcinomas.

The micropapillary (MP) subtype has recently been established to be a distinct marker of poor prognosis in lung adenocarcinomas (LACs). According to the 2015 WHO classification system, LAC constituents are required to be precisely reported. T790M mutation and an insertion in exon 20 (E20ins) are associated with EGFR-TKI resistance. A total of 211 LAC patients were involved in this study, and EGFR mutations were determined using an amplification refractory mutation system (ARMS). Sex, smoking history, lymph node status, and clinical stage differed significantly between the EGFR wild type and mutant groups (p < 0.05). The EGFR mutation occurred more frequently in female, non-smokers, ACs with papillary (85.7%) or MP components (91.4%) (p < 0.001). Twenty ACs with naïve T790M or E20ins were microdissected. The AC constituents metastasizing to lymph nodes exhibited a phenotype and EGFR status that was consistent with the primary loci constituents. Glomerulus-like solid components exhibited the same EGFR status as the surrounding T790M-mutated MP components. The MP and glomerulus-like portions in AC tumours exhibited a congenial EGFR status, but the acinar cells with papillary cells were heterogeneous. The naïve T790M mutants, although minor in the MP component, dramatically increased after EGFR-TKI therapy and indicate that the MP components feature intrinsic heterogeneity.

S&T-39 CONCORDANCE OF URETEROSCOPIC BIOPSY GRADE TO RADICAL NEPHROURETERECTOMY GRADE AND STAGE BASED ON THE 1973 AND 2004 WHO CLASSIFICATION SYSTEMS FOR UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyScience & Technology Posters1 Apr 2016S&T-39 CONCORDANCE OF URETEROSCOPIC BIOPSY GRADE TO RADICAL NEPHROURETERECTOMY GRADE AND STAGE BASED ON THE 1973 AND 2004 WHO CLASSIFICATION SYSTEMS FOR UPPER TRACT UROTHELIAL CARCINOMA Ryuta Tanimoto, Scott G Hubosky, Kelly A Healy, Ruth Birbe, Marluce Bibbo, and Demetrius H Bagley Ryuta TanimotoRyuta Tanimoto More articles by this author , Scott G HuboskyScott G Hubosky More articles by this author , Kelly A HealyKelly A Healy More articles by this author , Ruth BirbeRuth Birbe More articles by this author , Marluce BibboMarluce Bibbo More articles by this author , and Demetrius H BagleyDemetrius H Bagley More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2868AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Upper tract urothelial carcinoma (UTUC) is relatively rare with diagnostic and treatment strategies usually originating from long term single institutional experiences which report pathological findings using the antiquated 1973 WHO classification system for grading urothelial carcinoma. Given the challenges with preoperative staging of UTUC, ureteroscopic biopsy grade frequently influences treatment decisions. The aim of this study was to compare the correlation of ureteroscopically derived UTUC biopsies and subsequent radical nephroureterectomy (NU) grades using the 1973 and 2004 WHO classification systems for grading urothelial carcinoma. Ureteroscopically derived grade was also correlated to NU stage using both classification systems. METHODS A retrospective review was performed of 170 consecutive patients who underwent NU for suspected UTUC at our institution over a 14-year period. After applying exclusion criteria, we had 97 patients with both ureteroscopic and NU grade available. Ureteroscopic biopsy specimens were then compared to the final NU specimen to determine grade and stage concordance using both the 1973 and 2004 WHO classification systems. The 1973 Grade 1 lesions and grade 3 lesions were considered low grade and high grade, respectively, according to the 2004 system. A cytopathologist applied the 2004 classification to all 1973 grade 2 lesions. RESULTS When the 2004 system was applied to 1973 grade 2 ureteroscopic biopsies, 16/34 (47%) were noted to be high grade. When considering ureteroscopic biopsy grades 1, 1-2, and 2 in the 1973 system, 58% of these cases correlated to ≤grade 2 on NU specimen while 60% of low grade cases using the 2004 system were found to be low grade on NU. Both grading systems showed significant association between NU grade and pathological stage. The 2004 system found better correlation with low-grade disease on ureteroscopic biopsy to superficial stage (<pT2) on NU (62%) compared to the 1973 system (53%) (κ coefficient 0.32 vs. 0.18, respectively). CONCLUSIONS Similar to urothelial carcinoma of the bladder, our findings suggest that grade heterogeneity exists in UTUC. When the 2004 WHO classification system was utilized, ureteroscopic biopsy grade could predict the final NU grade and pathological stage more accurately than the 1973 WHO classification system. Caution must be exercised when interpreting the results of UTUC studies exclusively using the 1973 WHO grading system, given the apparent heterogeneity of 1973 grade 2 lesion. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e324 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ryuta Tanimoto More articles by this author Scott G Hubosky More articles by this author Kelly A Healy More articles by this author Ruth Birbe More articles by this author Marluce Bibbo More articles by this author Demetrius H Bagley More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinicopathological study of cutaneous adnexal tumors in a tertiary hospital of South India

Introduction: Tumors of the cutaneous appendages are uncommon. They are categorized into sweat gland tumors, hair follicle tumors and sebaceous gland tumors. Benign adnexal neoplasm’s are more common than the malignant tumors. Aim: To study the spectrum of adnexal tumors of skin with respect to age, sex, site and histopathological pattern. Methodology: We conducted a retrospective analysis of 40 histopathologically confirmed cases of cutaneous adnexal tumors in a tertiary hospital of South India during three years. All the specimens of cutaneous adnexal tumors received during this period were analysed and lesions were categorized according to WHO classification system for Skin Adnexal Tumors. Result: 40 cases of Skin adnexal tumors were diagnosed during the study period. 21 cases (55%) were benign, while 19 cases (45%) were malignant. Skin adnexal tumors were most common in the age group of 31-50 years (35%), with equal sex distribution. The head and neck region was the most common site affected (37.5%) with 45% located on the face. The sweat gland tumors formed the largest group involving 55% cases followed by the hair follicle tumors (25%), followed by 10% each of apocrine gland and sebaceous gland tumors. Pilomatricoma was the most common benign tumor and malignant nodular hidradenoma was the most frequent malignant adnexal tumor in our study. Conclusion: Histopathological examination is the gold standard in the diagnosis of cutaneous adnexal tumors due to their wide spectrum and frequency of differentiation along two different lines within the same lesion. Keywords: Adnexal tumors, Histopathology, Skin, Pilomatricoma, syringocystadenoma

Mucinous Neoplasms Of The Appendix And Peritoneum: Virtual Microscopy For Histomorphologic Assessment And Interobserver Diagnostic Reproducibility

Introduction/ Background Among gastrointestinal (GI) tumours, pseudomyxoma peritonei (PMP) from appendiceal origin has unique clinical and morphologic features. Due to the relative paucity of patients and the absence of therapeutic consensus, evaluation and refinement of the morphologic criteria used for assessment of the disease are still difficult. As a result, a uniformly accepted classification is still lacking. In collaboration with NJ Carr, who initiated the conference consensus process, in Basingstoke, and on behalf of the French group RENA-PATH, 11 experienced GI pathologists agreed to participate to a virtual workshop, in order to assess inter-observer variability in PMP diagnosis and staging. Aims The goal of the study was to evaluate, for appendiceal and peritoneal mucinous neoplasms, the degree of concordance in the identification of diagnostic histological criteria by experienced pathologists, and to assess the degree of inter-individual variation in the application of WHO classification (2010) and TNM staging system (7th edition). Methods A single section stained with hematoxylin and eosin from 9 resected cases of mucinous neoplasms was selected by members of RENA-PATH. All digitalized at a maximum resolution (X40) using an HAMMAMATSU scanner system, to ensure that all participants evaluate exactly the same tumour areas; 1 to 16 questions were prepared for each case. On Teleslide web platform, interactive services provided by TRIBVN. All submitted cases were then reviewed by a panel of 11 pathologists with specific expertise and interest in PMP. Data were analyzed using SAS program. Results Whole slide set evaluated by all participants; no abstention or “unknown diagnosis” for any submitted case. Agreement for classification, WHO 2010: Appendiceal mucinous neoplasms: LAMN 83 %; mucinous adenocarcinoma 92%. Peritonei mucinous carcinoma: Low grade 91.7%; high grade 91.7%. Disagreement on the concept of High Grade AMN defined by low power architecture of LAMN + high grade cytology. Agreement for using pTNM classification (82%) in PMP. Pushing Invasion (PI) and dissection by acellular mucin (DAM) in appendix wall are not reproducible criteria and need to be better defined. Criteria need to be redefined to use HAMN according to a majority of participants. The identification of signet ring cells is not reproducible; the lesion needs to be better defined. Invasion of organs and pattern of invasion (broatfront invasion / classic by irregular glands or single cells with desmoplasia) are not reproducible criteria. Improvement in staging assessment is needed Conclusion: Although histopathological features of peritoneal disease are significant prognostic factors requiring pathologists to classify mucinous carcinoma peritonei (pseudomyxoma peritonei), reproducibility in interpretation must be improved. This international collaborative project allows pathologists worldwide to share their expertise and knowledge through a dedicated interactive workshop session. It is expected an improvement in the management of mucinous neoplasms of the appendix and peritoneum.

Epidemiology and Clinical Features of Adults Myelodysplastic Syndromes in Algeria: A Population-Based Study. Review of the Algerian Myelodysplastic Syndromes Study Group

BACKGROUND: In Algeria, the incidence of hematologic malignancies has been difficult to estimate for many years and MDS incidence is unclear because of historical lack of population-based registration and possibly because of under diagnosis. Today, many hematological centers, including 17 university hospitals, have been developed in the entire north and have useful epidemiological data pertinent to MDS. We studied the incidence of MDS and its subtypes, age distribution, geographic distribution and trends in the rate of diagnosis over the last 5 years in Algeria.DESIGN AND SETTING: Retrospective analysis of nationwide survey of all adult cases of MDS (>16 years) diagnosed between January 2010 and 31 December 2014.PATIENTS AND METHODS: Patients diagnosed with MDS and referred to all departments of hematology at the 17 participating centers between 2010-2014 were identified. Complete demographic and clinical data, laboratory results, treatment modalities were collected and analyzed.RESULTS: Between 2010 and 2014, a total of 243 patients with newly diagnosed MDS have been identified. The sex ratio (M/F) is: 1:08, and the median age is 64.3 years (16 - 82 years). Globally, 27% of MDS are diagnosed in the whole Western region of the country, 56% in the Centre, 14% in the East and 3% in the south. The crude mean annual incidence rate of MDS was 0.07 per 100,000 inhabitants aged ≥15 years old. 11.2% patients were less than 45 years and 42% were older than 70 years.4.3% patients were from rural areas and 6, 2 % were cigarette smokers.Mean hemoglobin level was 7.8 g/dl, mean WBC level was 6134/µl, mean platelets level was 134907/µl, mean VGM level was 92.7 fl and mean ferretin level was 739.31 ng/ml. The mean blood transfusion units were 13.5 units. 36.3% patients had RCMD, 15.9% had RAEB2 and 13.2% had RAEB1. 34.4% patients had cytogenetic abnormalities, and del-5q was more commonly encountered in 22.7%. The IPSS-R was very low in 18.3%, low in 18.3%, intermediate in 11.8%, high in 7.5% and non-specified in 36.6%. Treatment regimens were supportive care (transfusion RBC with chelation, and platelets) and growth factors (EPO, Romiplostine, and G-CSF). At the date of end point, 44% of patients were alive, 26% were death and 31% were lost of follow up.CONCLUSION: Epidemiologic features of our patients are different from the occidental ones. Mean age of presentation of MDS in Algeria is lower than developed countries. The relatively younger age of patients compared to the Western countries may be due to the demographic composition of our population. The annual incidence is still low, but a continuously increasing incidence rate of MDS has been observed throughout the study period and an overall increase in the number of MDS patients diagnosed nationwide over the last five years indicates a need for additional health care resources including curative and therapy-intense strategies, such as stem cell transplant facilities to optimize outcome. Refractory anemia was the most common subtype in both FAB and WHO classification systems and in both genders. The best supportive care was used in all patients in first line treatment and the Iron overload is a permanent feature of MDS. DisclosuresNo relevant conflicts of interest to declare.

A36: The TP53 mutations in the Russian patients with de novo DLBCL

Background TP53 dysfunction is implicated in lymphomagenesis and disease progression. Information about the frequency and spectrum of TP53 mutations in the Russian pathients with diffuse large B-cell lymphoma (DLBCL) in the current version of the IARC TP53 Mutation Database R17 is not represented. The goal of this work was to study the frequency, spectrum and functional significance of TP53 mutations in Russian patients with DLBCL. Material and methods At the present time the pilot group of 14 patients were included in the study. Diagnosis was assessed according to the criteria of the WHO classification system. Genomic DNA was isolated from formalin-fixed, paraffin embedded tissue blocks. Direct sequence analysis of gene TP53 was performed according to the IARC protocol, 2010 update. Results In two patients were identified single nucleotide substitutions that are not described in the current version of the PubMed database. All of mutations occurred in the DNA-binding domain of p53. The nonsense mutation Arg196Ter was detected in one patient. Previously it was shown that formation of this premature stop codon might activate the nonsense-mediated RNA decay pathway. The second patient had two missense mutations – Leu130Phe and Arg156Cys. The first of them leads to p53 inactivation according to the analysis of the functional importance of amino acid substitutions using service PolyPhen-2. Conclusion We detected TP53 mutation in 14% cases. The mutational rate in our study is in good agreement with other studies where the frequency of the TP53 mutations in patients with DLBCL ranged mostly from 13% to 23%.

The Incidence and Survival of Rare Cancers of the Thyroid, Parathyroid, Adrenal, and Pancreas.

With the exception of papillary and follicular thyroid cancer, malignant cancers of the thyroid, parathyroid, adrenal, and endocrine pancreas are uncommon. These rare malignancies present a challenge to both the clinician and patient, because few data exist on their incidence or survival. We analyzed the incidence and survival of these rare endocrine cancers (RECs), as well as the trends in incidence over time. We used the NCI's SEER 18 database (2000-2012) to investigate incidence and survival of rare cancers of the thyroid, parathyroid, adrenal, and endocrine pancreas. Cancers were categorized using the WHO classification systems. We collected data on incidence, gender, stage, size, and survival. Time trends were evaluated from 2000-2002 to 2010-2012. We identified 36 types of rare cancers in the endocrine organs captured in the SEER database. RECs of the thyroid had the highest combined incidence rate (IR8.26), followed by pancreas (IR 3.24), adrenal (IR 2.71), and parathyroid (IR 0.41). The incidence rate for all rare endocrine organs combined increased 32.4 % during the study period. The majority of the increase was attributable to rare cancers of thyroid, which increased in not only microcarcinomas, but in all sizes. The mean 5-year survival for RECs is 59.56 % (range 2.49–100 %). This study is a comprehensive analysis ofthe incidence and survival for rare malignant endocrine cancers. There has been an increase in incidence rate of almost all RECs and their survival is low. We hope that our data will serve as a source of information for clinicians as well as bring awareness regarding these uncommon cancers.

Prognostic significance of substage and WHO classification systems in T1 urothelial carcinoma of the bladder.

Treatment of T1 urothelial bladder cancer (T1-BC) is challenging as risk assessment criteria for progression are lacking. Histological grade and T1 substage have been identified as important prognostic factors. Currently, no consensus exists regarding the optimal sub-staging and grading systems for T1-BC. We reviewed recent advances in the various grading and sub-staging systems and their clinical applicability. Stratification by muscularis mucosae invasion is the most explored sub-staging system. Its prognostic value was established by 12/23 (52%) available studies. Importantly, muscularis mucosae identification varied substantially among pathologists. Sub-staging based on diameter of invasive carcinoma [T1 microinvasive and T1 extensive-invasive (T1m/e)] proved a more reproducible system with at least equal prognostic value. However, more study is needed to investigate interobserver variation. For nonmuscle-invasive bladder cancer grading, the 1973 and 2004 WHO classifications both provide independent prognostic information. However, remarkably few studies have investigated their applicability in T1-BC only. The available reports suggest that the 1973 WHO classification is superior to WHO 2004. If multicenter studies confirm the promising results of T1m/e sub-staging, it may be incorporated in the Internation Union Against Cancer TNM classification system for urinary bladder cancer. More studies are warranted to define the optimal classification system for grade in T1-BC.