Wilms' tumor is the most common malignant renal tumor in paediatric age group, and is classically managed by multimodal treatment which involves surgery, radiotherapy and chemotherapy. The last few decades have seen a dramatic change in the prognosis of this disease, which once was a uniformly lethal malignancy. While there is plenty of data in world literature on the outcome of Wilms' tumor, there is paucity of data from India. Hence, we conducted the present study to analyze the outcome of Wilms' tumor at our institute. To study the clinicopathologic profile and outcome of Wilms' tumor with NWTS (National Wilms' Tumor Study Group) IV protocol. Sixty-one patients with histopathological proven diagnosis of Wilms' tumor and had received treatment at our institute from Jan 2003 through Dec 2010 were included for analysis. Patients received treatment based on NWTS IV protocol. Patients were analysed for overall survival and event free survival and these outcomes were correlated with age, sex, stage at presentation and histology. Favourable histology which included focal anaplasia was found in 80.3 % while unfavourable histology was elicited in 19.7 % of the cases. The estimated 5 year event-free survival was 83.3 % and overall survival was 85.2 %. Tumour histology was the single most important factor predicting the survival. Patients with childhood Wilms' still present very late in our setting, this poses management challenges as large tumor are technically difficult to deliver at surgery. Histology has a crucial role in outcome of this disease. With multidisciplinary approach, similar survival rates to National Wilms' Tumor Study Group seems to be achievable even in Indian scenario.
Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The MAb604.107 exhibited higher affinity for the “Gain-of-function” mutants of Notch1 NRR associated with T Acute lymphoblastic Leukemia (T-ALL). Modeling of the mutant NRR with 12 amino-acid insertion demonstrated “opening” resulting in exposure of the S2-cleavage site leading to activated Notch1 signaling. The MAb, at low concentrations (1–2 μg/ml), inhibited elevated ligand-independent Notch1 signaling of NRR mutants, augmented effect of Thapsigargin, an inhibitor of mutant Notch1, but had no effect on the wild-type Notch1. The antibody decreased proliferation of the primary T-ALL cells and depleted leukemia initiating CD34/CD44 high population. At relatively high concentrations, (10–20 μg/ml), the MAb affected Notch1 signaling in the breast and colon cancer cell lines. The Notch-high cells sorted from solid-tumor cell lines exhibited characteristics of cancer stem cells, which were inhibited by the MAb. The antibody also increased the sensitivity to Doxorubucinirubicin. Further, the MAb impeded the growth of xenografts from breast and colon cancer cells potentiated regression of the tumors along with Doxorubucin. Thus, this antibody is potential immunotherapeutic tool for different cancers.
FISH is one of the most sensitive molecular methods to detect genetic abnormalities with DNA probes. When cytogenetic studies are normal or insufficient, FISH may detect cryptic rearrangements, rare or slowly proliferative abnormal populations in non-mitotic cells. We cytogenetically evaluated 70 childhood ALL -67.1% were found to have an abnormal karyotype. The 23 patients (32.9%) with a normal karyotype were analyzed by FISH applying two probes; TEL/AML1 and MYB which detect cryptic rearrangements of t(12;21)(p13;q22) and deletion of (6q) respectively, associated with a good prognosis. Out of 23 patients, one was positive for t(12;21)(p13;q22) (4.3%). None of our patients were positive for MYB del(6q). Two patients showed an extra signal for MYB on chromosomes other than 6 (8.6 %) indicating amplification or duplication. Findings were compared with the available literature. Our study clearly indicated the integrated FISH screening method to increase the abnormality detection rate in a narrow range. FISH is less useful for diagnostic study of patients with suspected del(6q) but it helps in detecting known cryptic rearrangements as well as identification of new abnormalities(translocation , duplication and amplification) at the gene level.
Chediak Higashi Syndrome (CHS) is a rare autosomal recessive disease, characterized by partial oculocutaneous albinism, frequent pyogenic infections, and the presence of abnormal large granules in leukocytes and other granule containing cells. The abnormal granules are readily seen in blood and marrow granulocytes. About 50% to 85% of patients eventually enter an accelerated phase, manifested by fever, lymphadenopathy, anemia, jaundice, neutropenia, thrombocytopenia, and widespread lymphohistiocytic organ infiltrates. The first accelerated phase of CHS may occur shortly after birth or several years later. Most patients undergo a variable period of recurrent infections before going into the accelerated phase. Therefore, primary presentation in the accelerated phase is unusual. This case was referred to our institution that is a tertiary care cancer centre, with a clinical diagnosis of lymphoma/leukemia. Hence this interesting case of CHS in accelerated phase at presentation is described. The child had 1-month history of fever, bilateral neck swellings, and loss of appetite. On the basis of the clinical presentation, hematologic, and histopathologic findings, a diagnosis of accelerated phase of CHS was made. The child was treated with antipyretics, antibiotics, and stem cell transplantation was suggested to him. When the child presents to a hospital with oculocutaneous albinism and recurrent infections, careful examination of the peripheral blood smear by an experienced morphologist cannot be overemphasized. A high degree of awareness and early recognition of the syndrome, could lead to the institution of the only possible curative treatment, bone marrow transplant, before the accelerated phase supervenes.
A 7-year-old boy was referred with a provisional diagnosis of bilateral Wilms tumor. Peripheral smear revealed elevated leukocyte count with 90% blasts. Bone marrow aspiration and biopsy were hypercellular with sheets of blasts. Immunohistochemistry on paraffin sections showed a pre-B phenotype of acute lymphoblastic leukemia. Computerized tomographic scan of the abdomen showed moderate bilateral renal enlargement. Ultrasound-guided fine needle aspiration cytology of both kidneys showed blasts similar to those seen in the bone marrow. Finally, a diagnosis of pre-B acute lymphoblastic leukemia infiltrating both the kidneys was made. This case is being presented because of its rarity.
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