Clinicopathological representation of nonmetastatic Ewing sarcoma of the scapula - a case study

Ewing sarcoma (ES) is a rare type of small cell tumor of the bone and soft tissues. About 50% of ES arise in the femur and pelvis. We present a case of ES of the scapula in a seven year old female child. Because of its similarity with other small cell tumors, the diagnosis of ES is challenging and requires a combination of methods like CT scan, MRI report, histopathological evaluation and IHC, etc. The MRI report of our case has shown a consistent 5×4 cm3 mass on the left scapula. Bone marrow aspiration and biopsy of the tumor has been further analyzed. Small, round and oval cells with densely packed nuclei and scanty cytoplasm, which are characteristic to ES were observed microscopically. A positive reaction to vimentin and CD99 and negative result for the biomarkers meant for other types of tumors, favours the diagnosis of ES. The chromosomes analyzed from the peripheral blood of the patient have shown a normal karyotype. Early diagnosis of ES is very crucial for treatment. Histopathology and IHC are indispensible tools in the diagnosis of ES

A rare finding of plasma cell leukaemia with hairy-cell morphology.

The authors state that there are no conflicts of interest to disclose. This publication was funded by the CNIC. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020- 001041-S funded by MICIN/AEI/10.13039/501100011033).S

Comparative analysis of immunohistochemistry and flow cytometry in the diagnosis of acute leukaemia: a single centre study

Background: Morphological evaluation and immunophenotyping are the major diagnostic modalities of acute leukaemia (AL). Although immunohistochemistry (IHC) and flow cytometry (FCM) are necessary for lineage assessment, but in many cases the use of these modalities alone might possess a diagnostic challenge. The study was aimed to analyse the diagnostic utility of IHC and FCM in the diagnosis of AL. Methods: This cross-sectional hospital-based study was done for one year and included 55 cases. Following peripheral blood examination and bone marrow study, IHC and FCM analysis was done using CD34, anti-MPO, CD3 and CD20. Results: There were 74.5% acute myeloid leukaemia (AML) and 25.5% acute lymphoblastic leukaemia (ALL) cases. By IHC, CD34 was positive in 94.5% cases, anti-MPO in 69.1%, CD3 in 3.6% and CD20 in 12.7% cases. But by FCM, CD34 was positive in 96.2% cases, anti-MPO in 61.5%, CD3 in 3.8% and CD20 in 19.3% cases. FCM could not be done for 3 cases as there was dry tap with pancytopenia and lineage assessment was done by IHC. On comparative analysis, CD34 was found to be better expressed by FCM. Anti-MPO and CD20 were better expressed by IHC and CD3 was equally expressed by both. Conclusions: IHC is an easy and cost-effective technique which gives an accurate characterization of the lineage and subtype of AL, especially in cases where use of FCM is limited such as cases with dry tap and pancytopenia and in limited resource centers

The utility of Aspirin in Dukes C and High Risk Dukes B Colorectal cancer--the ASCOLT study: study protocol for a randomized controlled trial

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The utility of Aspirin in dukes C and high risk dukes B colorectal cancer - The ASCOLT study: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>High quality evidence indicates that aspirin is effective in reducing colorectal polyps; and numerous epidemiological studies point towards an ability to prevent colorectal cancer. However the role of Aspirin as an adjuvant agent in patients with established cancers remains to be defined. Recently a nested case-control study within the Nurses Health cohort suggested that the initiation of Aspirin <it>after </it>the diagnosis of colon cancer reduced overall colorectal cancer specific mortality. Although this data is supportive of Aspirin's biological activity in this disease and possible role in adjuvant therapy, it needs to be confirmed in a randomized prospective trial.</p> <p>Methods/Design</p> <p>We hypothesize through this randomized, placebo-controlled adjuvant study, that Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT) can improve survival in this patient population over placebo control. The primary endpoint of this study is Disease Free Survival and the secondary Endpoint is 5 yr Overall Survival. This study will randomize eligible patients with Dukes C or high risk Dukes B colorectal cancer, after completion of surgery and standard adjuvant chemotherapy (+/- radiation therapy for rectal cancer patients) to 200 mg Aspirin or Placebo for 3 years. Stratification factors include study centre, rectal or colon cancer stage, and type of adjuvant chemotherapy (exposed/not exposed to oxaliplatin). After randomization, patient will be followed up with 3 monthly assessments whilst on study drug and for a total of 5 years. Patients with active peptic ulcer disease, bleeding diathesis or on treatment with aspirin or anti-platelet agents will be excluded from the study.</p> <p>Discussion</p> <p>This study aims to evaluate Aspirin's role as an adjuvant treatment in colorectal cancer. If indeed found to be beneficial, because aspirin is cheap, accessible and easy to administer, it will positively impact the lives of many individuals in Asia and globally.</p> <p>Trials Registration</p> <p>Clinicaltrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00565708">NCT00565708</a></p

Febrile Neutropenia in Children: Etiologies, Outcomes, and Risk Factors with Prolonged Fever

Most studies of children with prolonged fever and neutropenia (PFN) have focused on invasive fungal disease (IFD) as the etiology of fever and not on other causes. Data are lacking regarding risk factors and adverse outcomes in pediatric cancer patients with PFN compared with those whose fevers resolve more rapidly. Retrospective medical record review was performed for all cancer patients with febrile neutropenia (FN) in the pediatric oncology unit at University of Chicago Medicine Comer Children’s Hospital from March 2009 to July 2016. Resolving febrile neutropenia (RFN), lasting less than 96 hours, and PFN episodes (≥ 96 hours) were compared to identify risk factors and outcomes associated with PFN. A total of 572 FN episodes were identified in 265 patients. PFN occurred in 119 (21%) FN episodes (50 patients) and RFN occurred in 453 (79%) FN episodes (215 patients). In multivariable analysis, autologous stem cell transplant (odds ratio [OR] 6.5, P 39°C at the time of presentation (OR 2.4, P<0.01) and absolute monocyte count (AMC) <100 cells/m3 (OR 2.7, P=<0.01) were independently associated with PFN. Pneumonia, neutropenic enterocolitis and IFD were more common etiologies of fever in PFN compared with RFN. Patients with PFN were more likely to be admitted to the pediatric intensive care unit [OR 3, (95%CI, 1.66%-5.28%), P<0.001] and had a trend toward higher 30-day mortality [OR 3.8, (95%CI, 0.52%-29.32%), P=0.07]. Patients with PFN are at increased risk for serious illness and death. A better understanding of the etiologies of PFN other than IFD is needed to be able to appropriately diagnose and treat this high-risk group

An Immunohistochemical study of Androgen Receptor and Beta-Catenin in Triple Negative Breast Cancers

BACKGROUND: Breast cancer is the most common cancer worldwide and remains an important global health issue. Triple negative breast cancer accounts for 15% of breast cancers. The median survival of woman with advanced triple negative breast cancer is 13 months. Improved understanding is urgently required to advance our treatment approach to triple negative breast cancer. AIMS AND OBJECTIVES: 1. To evaluate the status of androgen receptor and beta-catenin in triple negative breast cancers. 2. To correlate the immunohistochhemical expression of these markers with histological grade. 3. To correlate the relation between androgen receptor and beta catenin. MATERIAL AND METHODS: This is a prospective and retrospective study of expression of androgen receptor and beta catenin in triple negative breast carcinomas conducted in the Institute of Pathology, Madras Medical College and Rajiv Gandhi Government General hospital, Chennai for a period of 2 years with 40 cases. The expressions are correlated with clinicopathological parameters. RESULTS: Androgen receptor evaluation in triple negative breast cancer which has a poor prognosis could help better understanding of these lesions and the possibility of specific targeted therapy. Beta catenin activity is required for many of the tumorigenic characteristics of triple negative breast cancer. Thus targeting beta catenin may have important implications in triple negative breast cancers therapy. CONCLUSION: In this study, the incidence of IBC-NOS type forms the highest among triple negative breast cancers. AR is expressed in 22.5% of cases and beta catenin 52.5% of cases. This study shows no statistically significant association between AR and beta catenin expression with histopathological parameters as the study sample is less and detection methods of these markers are yet to be validated. AR is significantly expressed in 22.5% of tumours which implicate the use of androgen related targeted therapy in these cases. AR could be an independent prognostic marker and additional AR related targeted therapies can be done if its methods of detections are validated and outcome is established. Beta catenin will have both prognostic and therapeutic significance if the signaling pathways are targeted and outcome established. Further studies are needed on the molecular characteristics of certain histologic types and it will improve our understanding of their prognostic implications and contribute to the tailored treatment

Contribución de la optimización de la dosis de imatinib al tratamiento integral del paciente con Leucemia Mieloide Crónica

[ES] Imatinib es un inhibidor de tirosina quinasa, utilizado como estándar de tratamiento en pacientes con Leucemia Mieloide Crónica en fase crónica, a una dosis estándar de 400 mg/día. La amplia variabilidad farmacocinética interindividual que caracteriza a imatinib, y la conocida relación entre las concentraciones mínimas del fármaco en estado estacionario, y la probabilidad de consecución de la respuesta óptima al tratamiento, hace de la monitorización farmacoterapéutica de sus niveles plasmáticos, una herramienta objetiva de ayuda al clínico a la hora de realizar modificaciones posológicas de imatinib. Por tanto, el objetivo de la tesis ha sido evaluar la contribución de la optimización de dosis de imatinib, mediante la determinación de las concentraciones plasmáticas y de los parámetros farmacocinéticos, al tratamiento integral del paciente con Leucemia Mieloide Crónica en la práctica clínica diaria. Para realizar el proceso de monitorización farmacoterapéutica de manera fiable, se ha desarrollado un método analítico de HPLC asociada a un detector UV para la determinación de las concentraciones de imatinib. Además, se ha realizado la validación externa de los modelos farmacocinéticos poblacionales ya existentes en la bibliografía, desarrollados principalmente en población adulta y caucásica, para seleccionar el modelo más adecuado para su incorporación en la práctica clínica diaria. Finalmente se ha creado un algoritmo de monitorización para el ajuste de dosis de imatinib, en pacientes con Leucemia Mieloide Crónica en la práctica clínica diaria, siguiendo los criterios de evaluación de la respuesta al tratamiento de las principales guías clínicas

Kontrastmittelgestützte Sonographie (CEUS) bei Patienten/Patientinnen mit Hyposplenie: eine retrospektive Analyse

There are a range of different diseases which may impact the spleen functionality negatively. Especially if a spleen is described as “small” on ultrasound, computer tomography or magnet resonance imaging, a functional examination should be carried out to exclude a possible underlying splenic dysfunction resulting in immune deficiency. If such a condition exists, preventative vaccination is paramount to protect the patient from life threatening illness. An analysis of retrospective collected data was performed to investigate if “contrast enhanced ultrasonography” has a role in the functional diagnostic workup of the small spleen. Method: The data of n = 66 subjects with a reduced spleen size (hyposplenia) was analysed for the presence of underlying diseases, occurrence of Howell-Jolly-Bodies and splenic function using nuclear radioisotope scan (scintigraphy). Each spleen was examined using standardised B-mode sonography followed by contrast enhanced ultrasound (CEUS). Results: 26 patients (39,4 %) demonstrated a striking contrast agent behaviour (arterial and/or parenchymal). Of all patients who underwent functional diagnostic testing (34 persons), 27 indeed had a proven functional hyposplenia/asplenia. In 16 of these cases, striking contrast enhancement was found. The number of patients showing no signs of underlying splenic dysfunction was seven. All these demonstrated inconspicuous enhancement on CEUS. Sensitivity was calculated as 59,3 %, specificity as 100 %. The positive predictive value was also 100 % and the negative predictive value was 38,9 % (The results of the radioisotope scan (scintigraphy) and the presence of Howell- Jolly-Bodies were used as reference). Conclusion: Judging by the results of this analysis, CEUS could represent a suitable new method to detect possible splenic malfunctions. However splenic dysfunction cannot be reliably excluded if the contrast uptake pattern proves to be inconspicuous. In these cases, other diagnostic tools should be used. Conventional Howell-Jolly bodies or pitted erythrocytes were determined. If necessary, the diagnostic workup can be completed using radioisotope scanning.Viele Grunderkrankungen unterschiedlicher Genese können mit Funktionsstörungen der Milz einhergehen. Insbesondere wenn bereits sonographisch, computer- tomografisch oder im Rahmen eines MRTs eine verkleinerte Milz beschreiben wurde, ist eine Funktionsdiagnostik der Milz klinisch relevant. Bei Funktionseinschränkungen sollte bei gleichzeitigem Vorliegen eines Immundefektes präventiv entgegengewirkt werden. Die Auswertung retrospektiv erhobener Daten sollte zeigen, ob ein Nutzen in der Funktionsdiagnostik der Milz via kontrastmittelgestützten Ultraschall besteht. Methode: Die Daten von n = 66 Probanden/Probandinnen mit verkleinerter Milz (Hyposplenie) wurden hinsichtlich einer Grunderkrankung, dem Vorhandensein von Howell-Jolly-Körpern und einer Funktionsstörung via Szintigraphie analysiert. Jede/r Patient/in wurde zunächst B-Bild-sonographisch und anschließend mit Kontrastmittel (CEUS) untersucht. Ergebnisse: 26 Personen (39,4 %) hatten ein auffälliges Kontrastmittelverhalten (arteriell und/oder parenchymal). Von allen Patienten/Patientinnen mit Funktionsdiagnostik (34 Personen) hatten 27 Studienteilnehmende eine funktionelle Hyposplenie/Asplenie. Für 16 dieser Personen zeigte sich ein auffälliges Enhancement. Es gab sieben Patienten/Patientinnen, die keine funktionelle Milzstörung hatten. Diese hatten allesamt ein unauffälliges Enhancement. Die Sensitivität wurde mit 59,3 %, die Spezifität 100 % berechnet. Der positiv prädiktive Wert lag bei 100 % und der negativ prädiktive Wert bei 38,9 % (Szintigraphie und Howell-Jolly-Körperchen als Referenzstandard). Fazit: Als neue Diagnostik, um mögliche Milzfunktionsstörungen zu detektieren, ist nach den Ergebnissen der vorliegenden Arbeit die CEUS ein geeignetes und nützliches Verfahren. Bei einem unauffälligem CEUS mit milztypischer Kontrastmittelverteilung kann eine Funktionsstörung jedoch nicht ausgeschlossen werden, sodass eine weitere Diagnostik in Betracht gezogen werden sollte. Herkömmlich werden dazu Howell- Jolly Körper oder pitted-Erythrozyten bestimmt. Wenn nötig, sollte gegebenenfalls eine Szintigraphie durchgeführt werden

The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated&nbsp;with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission