A novel coexistence of tetrasomy 8 and FLT3-ITD along with variant 3 way translocation t(4;17;15) in acute promyelocytic leukemia: Case study and literature review.

Here, we report a case of Acute promyelocytic leukemia (APL) with three way complex translocation involving chromosomes 4, 15, and 17. Although chromosome 4 is most commonly associated chromosome in three way translocation, present case is the first report with four novel co-existent findings of new break point region on chromosome 4, new cyclic mechanism with simultaneous breaks, presence of a co-existent tetrasomy 8 and FLT3 ITD positivity.; Comprehensive assessment highlight the utility of combining morphology, immunophenotyping, karyotyping, fluorescence in situ hybridization, and molecular studies for better characterization, optimal management of APL with a better understanding of the pathogenic mechanism and prognosis of the disease.

Screening of Dry Blood Spots from Newborns by Two High Performance Liquid Chromatography (HPLC) Systems: A Comparison of Their Ability to Diagnose Both Sickle and Non-sickle Hemoglobinopathies.

Screening of newborns for the presence of sickle hemoglobin (HbS) is aimed at reducing the morbidity and mortality associated with sickle cell disease in early childhood. The high cost and limited availability of dedicated high performance liquid chromatography (HPLC) systems specially designed for screening of dry blood spots (DBS), however, restrict a wider application of this preventive approach. Therefore, we examined the ability of a commonly used HPLC system for detection of hemoglobinopathies in DBS samples in order to find an alternative for the dedicated newborn screening (NBS) HPLC system. DBS samples from 7522 newborns were first examined by Variant NBS HPLC system (Bio Rad, USA) for the presence of hemoglobinopathies. Positive samples were then analysed by Variant II system (Bio Rad, USA), another platform commonly used for hemoglobinopathy screening of anticoagulated blood samples. Eighty six newborns (1.1%) showed the presence of hemoglobinopathies (HbS 28, HbE 21, HbD 27, HbQ India 9 and Hb Barts 1) by Variant NBS system-all in heterozygous state. There was 100% correlation between the two sets of results obtained by the two HPLC systems. Newborns with HbQ India showed an additional Hb peak in HPLC resulting from combination of the abnormal alpha globin chain of HbQ India with the normal gamma chain of HbF-'HbF Q India'. Variant II HPLC system, used for routine hemoglobinopathy screening in anticoagulated blood, can also be used for screening DBS samples. This obviates the need for a dedicated NBS system for hemoglobinopathy screening in newborns. We also demonstrated that both the systems are equally competent in detecting non-sickle Hb variants in DBS samples.

Diagnostic challenges posed by a rare alpha globin chain variant Hb Fontainebleau in a pregnant female and its potential effects in her children in view of multiple globin gene defects in her husband.

Alpha globin chain variants per se do not cause severe morbidity and mortality but can modify - usually ameliorate - the clinical manifestations of beta globin chain variants when co-inherited with the latter. They also pose challenges in interpretation of high-performance liquid chromatography histograms and require molecular analysis for proper characterization. Hemoglobin (Hb) Fontainebleau is a rare alpha globin chain variant [alpha 21(B2) Ala→Pro], of which only three families have been reported from India in the past. Here, we describe a case of Hb fontainebleau detected in heterozygous condition in a 19-year-old primigravida. Her husband was found to have a double heterozygous state for HbQ India and beta-thalassemia trait. This opens up the possibility of multiple combinations of hemoglobinopathies in the offspring.

Spectrum and Immunophenotypic Profile of Acute Leukemia: A Tertiary Center Flow Cytometry Experience.

BACKGROUND: For diagnosis, sub-categorization and follow up of Acute Leukemia (AL), phenotypic analysis using flow cytometry is mandatory. MATERIAL AND METHODS: We retrospectively analyzed immunophenotypic data along with cytogenetics/molecular genetics data (wherever available) from 631 consecutive cases of AL diagnosed at our flow cytometry laboratory from January 2014 to August 2017. RESULTS: Of the total 631 cases, 52.9% (n=334) were acute lymphoblastic leukemia (ALL), 43.9% (n=277) acute myeloid leukemia (AML), 2.2% (n=14) mixed phenotypic acute leukemia (MPAL), 0.5% (n=3) acute undifferentiated leukemia (AUL) and 0.5% (n=3) chronic myeloid leukemia in blast crisis (CML-BC). ALL cases comprised of 81.7% (n=273/334) B-cell ALLs (95.2%, n=260/273 common B-ALLs and 4.8%, n=13/273 Pro B-ALLs). CD13 was the commonest cross lineage antigen, expressed in B-ALL (25.6%, n=70/273), followed by CD33 (17.9%, n=49) and combined CD13/CD33 (11.3%, n=31/273) expression. T-ALLs constituted 18.3% (n=61/334) of total ALLs and included 27.9% (n=17/61) cortical T- ALLs. CD13 was commonest (32.7%, n=20/61) aberrantly expressed antigen in T-ALLs, followed by CD117 (19.1%, n=9/47). AML cases included 32.1% (n=89/277) AML with recurrent genetic abnormalities, 9.0% (n=25/277) with FLT3/NPM1c mutation and 58.9% (n=163/277) AML NOS including 14.7% (n=24/163) AML M4/M5, 1.8% (n=3/163) AML M6 and 3.7% (n=6/163) AML M7. In AMLs, CD19 aberrancy was the most common (20.2%, n=56/277) followed by CD56 (15.8%, n=42/265). CONCLUSIONS: In this study, we document the spectrum, correlate the immunophenotype with genetic data of all leukemias, especially concerning T-ALL where the data from India is scarce.

FxCycle™ Based Ploidy Correlates with Cytogenetic Ploidy in B-Cell Acute Lymphoblastic Leukemia and Is Able to Detect the Aneuploid Minimal Residual Disease Clone.

BACKGROUND: Flow cytometry (FCM) is a simple, sensitive, and specific technique that can potentially determine DNA ploidy in B-cell precursor ALL (BCP-ALL) and is complementary to cytogenetics. METHODS: A prospective FCM DNA ploidy analysis using FxCycle™ Violet (assay sensitivity 0.01%) was done in 125 consecutive new cases of BCP-ALL (90 cases <15 years of age) and compared with corresponding cytogenetic ploidy (karyotyping and/or FISH) data wherever available. This assay was also subsequently evaluated for detection of residual aneuploid clone in few BCP-ALL cases. RESULTS: Of the total 125 BCP-ALL cases evaluated, flow ploidy analysis revealed diploidy (DI 0.96-1.05) in 44.8% (n = 56), low-hyperdiploidy (DI 1.06 to 1.15) in 13.6% (n = 17), high-hyperdiploidy (DI 1.16-1.39) in 32.8% (n = 41) and near-tetraploidy (DI ≥ 1.80) in 2.4% (n = 3) cases. The high risk sub-group of low-hypodiploidy (DI 0.70 to 0.88)/near-triploidy (DI 1.40 to 1.79) constituted 5.6% (n = 7) cases while there was only one case with haploidy (DI 0.58). Overall, high concordance of 90.4% (n = 113) was noted between the combined cytogenetics ploidy and FCM ploidy. Of the total discordant cases (n = 12), the maximum discordance was seen in the low-hyperdiploid DI subgroup (n = 10), which included seven cases with low DNA index high hyperdiploidy (LDI-HHD). FCM DNA ploidy assay was able to detect the residual clone in all six MRD positive aneuploid cases evaluated. CONCLUSIONS: FxCycle™ based DNA ploidy ascertains strong correlation with cytogenetic profiles and yields complementary information that can be used by the cytogenetics laboratories or otherwise. © 2019 International Clinical Cytometry Society.

Mixed-phenotypic acute leukemia series from tertiary care center.

INTRODUCTION: Mixed-phenotype acute leukemias (MPALs) are a heterogeneous group of rare leukemias constituting approximately 2%-5% of all leukemias, in which assigning a single lineage of origin is not possible. They are diagnosed by either the presence of antigens of more than one lineage or by the presence of dual population of blasts belonging to two or more lineages. We highlight the clinicopathological, immunophenotype, and genetic data of a cohort (n = 14) of patients diagnosed and treated at our center. MATERIALS AND METHODS: We retrospectively analyzed consecutive cases of MPAL diagnosed in our flow cytometry laboratory from May 2012 to August 2015. These cases were diagnosed based on immunophenotyping of peripheral blood/bone marrow aspirates and morphology/genetics wherever available as per the World Health Organization (WHO) 2008 guideline. RESULTS: Among 628 consecutive acute leukemia (AL) cases diagnosed and evaluated during this period, we identified 14 (2.2%) patients with MPAL fulfilling WHO 2008/EGIL criteria for immunological characterizing of AL criteria. Majority of these were males (n = 8, male:female ratio 1.3:1) and adults (n = 11, 78.5%). The median age of this cohort was 41 years (range 2-80). These cases were further classified as: B/myeloid (n = 9), T/myeloid (n = 4), and B/T MPAL (n = 1). Cytogenetics was available in 12 out of 14 cases, out of which, three cases had normal karyotype, three with t(9;22)(q34;q11), and two cases with complex karyotype. We also came across a rare case of B + T lymphoid MPAL who had mixed-lineage leukemia gene t(v; 11q23) rearrangement. CONCLUSION: MPAL is a complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and molecular features. Multiparametric flowcytometry by using comprehensive antibody panels is a valuable tool for diagnosis. Subsequent cytogenetic and molecular analysis for further prognostic stratification and treatment modalities are important.

Anatomical relationship between mental foramen, mandibular teeth and risk of nerve injury with endodontic treatment.

OBJECTIVES: The objective of the present study was to evaluate the anatomical relationship between mental foramen (MF), including the incidence of the anterior loop of the inferior alveolar nerve (AL), and roots of mandibular teeth in relation to risk of nerve injury with endodontic treatment. MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) images, which included teeth either side of the MF, were randomly selected. The anonymised CBCT images were reconstructed and examined in coronal, axial and sagittal planes, using three-dimensional viewing software, to determine the relationship and distance between MF and adjacent mandibular teeth. The actual distance between the root apex and MF was calculated mathematically using Pythagoras' theorem. If present, the incidence of an AL in the axial plane was also recorded. RESULTS: The root apex of the mandibular second premolar (70 %), followed by the first premolar (18 %) and then the first molar (12 %), was the closest to the MF. Ninety-six percent of root apices evaluated were >3 mm from the MF. An AL was present in 88 % of the cases. CONCLUSIONS: With regards to endodontic treatment, the risk of nerve injury in the vicinity of the MF would appear to be low. However, the high incidence of the AL highlights the need for clinicians to be aware and careful of this important anatomical feature. CLINICAL RELEVANCE: The risk of injury to the MN with endodontic treatment would appear to be low, but given the high incidence, it is important to be aware and be careful of the AL.

The effects of device position on the operator's radiation dose when using a handheld portable X-ray device.

INTRODUCTION: Handheld X-ray devices are now offered in dental practice. Handheld X-ray units challenge the concept of a restricted access to the "controlled area" as they are held by the operator. Although an integral lead shield is provided, the distance from the body is variable, dependent on how the device is held. The aim of this article was to investigate the level of operator dose when using a handheld X-ray device in various positions. MATERIAL AND METHODS: A NOMAD Pro™ Handheld X-ray system (Aribex Inc., Charlotte, NC) fitted with a remote control and mounted on a tripod was used in this study. A maxillofacial phantom ATOM(®) Max Dental and Diagnostic Phantom, model 711 HN (CIRS Inc., Norfolk, VA) was used to simulate the patient's head position. A mannequin was used to represent the operator. Pre-calibrated thermoluminescent dosemeters (TLDs) (Qados, Agar Scientific, Stansted, UK) were placed on the mannequin close to the eyes and at the level of thyroid, trunk, waist, hand (right finger + left palm) and feet, and three TLDs were used for background radiation. Three test scenarios were investigated; Position 1, close to operators' body and parallel to the ground; Position 2, away from the body with the arms fully extended (approximately 40 cm distance) and parallel to the ground; Position 3, perpendicular to the ground while the arms are partially extended. 30 exposures each of 1 s were performed in each test. RESULTS: Background radiation was measured at 0.0110 mGy. The highest exposure after subtracting background radiation was recorded on the palm of the left hand (0.0310 mGy) at Position 3. The estimated dose to the operator was calculated based on an average workload of 100 intraoral radiographs weekly for a dental practitioner working 46 weeks a year. CONCLUSIONS: There is a negligible increase in operator exposure levels using handheld X-ray devices which remain well below the recommended levels of the Ionizing Radiation Regulations 1999. They could however represent an increase from what should be a nil exposure when using a wall-mounted machine. The position of the device relative to the operator has a significant effect on the overall operator's radiation exposure. The use of personal dosemeters is highly recommended to ensure a continuity of low radiation dose exposure. Furthermore, guidance, training and protocols on usage must be in place, strictly adhered to and regular audits are necessary to ensure compliance.

Canine Gouging: A Taboo Resurfacing in Migrant Urban Population.

Cosmopolitan cities have become a pool of migrants from different parts of the world, who carry their cultural beliefs and superstitions with them around the globe. Canine gouging is a kind of infant oral mutilation (IOM) which is widely practiced among rural population of Africa where the primary tooth bud of the deciduous canine is enucleated. The belief is that the life threatening illnesses in children like vomiting, diarrhoea, and fevers are caused by worms which infest on tooth buds. This case report is of a 15-year-old Somalian born boy, who presented at the dental institute with intermittent pain in his lower right permanent canine which was associated with a discharging intra oral buccal sinus. The tooth was endodontically treated and then restored with composite. General dental practitioners need to be vigilant when encountered with tooth presenting unusual morphology, unilateral missing tooth, and shift in the midline due to early loss of deciduous/permanent canines. Identification of any such dental mutilation practice will need further counselling of the individual and family members. It is the duty of every dental professional to educate and safeguard the oral and dental health of general public.

Digital radiography in the dental practice: an update.

The implementation of digital imaging in dental practice should be considered. The vast number of advantages of digital imaging include time saving and image manipulation. Dose reduction is a big attraction but in practical terms this might not be fully taken advantage of, as a number of studies suggest. Challenges of images storage, back-up and exchange should be taken into account. Careful planning and integration with practice software should lead to a smooth transition. Remember, computer systems sometimes fail and contingency plans should be in place to avoid disruption to the workflow of the practice.