Epidemiology and clinical features of retinoblastoma: A tertiary care center's experience in India.

INTRODUCTION: Retinoblastoma (RB) is a prototype of heritable cancers. It is more common in the lower socioeconomic strata. Delayed presentation significantly reduces the overall outcome. We have analyzed the epidemiological and clinical data of children who were diagnosed with RB between the years 2009 and 2014. AIM: RB being a disease of the poor, delayed presentation is common due to lack of awareness. We have analyzed the epidemiological profile of our patients and tried to establish the link between delayed presentation and the presence of high-risk features. High-risk features are associated with higher chance of metastasis and poor rates of vision salvage in RB. METHODOLOGY: Data were collected in a retrospective manner from the patient case files retrieved from the Medical Records Department, Kidwai cancer Institute. The data were analyzed using Excel and SPSS software (IBM Corp. released 2016, IBM SPSS statistics software for Mac OS, version 24, IBM Corp., Armonk, NY). RESULTS: A total of 53 patients were diagnosed with RB in the years 2009-2014. There was a male predominance with 1.2:1 incidence. Bilateral RB was present in 21 cases. The mean age of children with bilateral RB was 2.1 years, against 1.5 years in unilateral cases. High-risk features such as optic nerve invasion, choroidal invasion, intracranial extension, and orbital involvement were found in 12, 6, 5, and 5 eyes, respectively. Bone marrow involvement was detected in 5% and lung metastasis in 2%. Intracranial involvement was found in 10.4% and cerebrospinal fluid positivity in 15%. Children with high-risk features had a significant delay in presentation in comparison to those without high-risk features (P = 0.035). CONCLUSION: Incidence of metastatic disease and delayed presentation is still high in developing countries. Routine eye examination during vaccination visits can ensure early diagnosis and appropriate referral in many of these children.

Atypical teratoid rhabdoid tumor of the central nervous system: Case series from a regional Tertiary Care Cancer Centre in South India.

BACKGROUND: Atypical teratoid rhabdoid tumors (AT/RT) constitute a rare group of pediatric brain tumors. AIM: To study the clinical, histopathological, and immunohistochemical (IHC) profile, management and outcome of children with AT/RT of the central nervous system who presented between the years 2007 and 2015 in a regional tertiary care center in South India. MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case files. Archived slides and tissue blocks were retrieved. All cases had hematoxylin and eosin stained sections. IHC was available in all the cases. RESULTS: There were eight cases with the mean age of presentation being 4 years (range: 4 months to 15 years) and with slight male predominance (male:female = 1.66:1). Most of the presenting complaints were due to raised intra-cranial tension. The median duration of symptoms was 0.75 months. About 62.5% of the tumors were infratentorial in location. The tumors were heterogeneous showing variable expression of cytokeratin, epithelial membrane antigen, glial fibrillary acid protein, and synaptophysin. Loss of integrase interactor-1 expression was demonstrated in seven cases in which it was done. Multimodal treatment comprising surgical resection, radiotherapy and chemotherapy was tailored based on location of tumor, resectability and patient's age. The median overall survival was 2.5 months (range: 1.5-30 months). CONCLUSION: Awareness of this tumor is important as it portends a poor outcome in most patients, in spite of multi-modal treatment. Several new molecules which aim to prolong survival and improve quality of life are being developed to combat this enigmatic tumor.

A Case of Urachal Yolk Sac Tumor With Spontaneous Rupture in a Child.

Tumors arising from urachus in children are exceedingly rare and sporadically reported in literature. Being a midline structure, the urachus may harbor neoplastic germ cell elements and can occasionally present as a case of acute abdomen. A 20-month-old toddler presented with spontaneous rupture of an urachal yolk sac tumor causing hemoperitoneum. He underwent resection, received platinum-based chemotherapy and presently remains well on follow-up. Despite its rarity, urachal germ cell tumors must be considered in a child with acute abdomen and tumor markers must be measured preemptively in such cases.

Extended Right Hepatectomy by Liver Hanging Maneuver in an Infant with Hepatoblastoma.

Liver hanging maneuver (LHM) is now a safe, accurate, and well established technique for various kinds of hepatic resections. But because of technical difficulty and limited experience, there have been very few reports of hepatic resection using LHM in children as compared to adults. We hereby report a case of extended right hepatectomy with part of caudate lobectomy using LHM in an 8-month-old infant for a large hepatoblastoma in Kidwai Memorial Institute of Oncology, a regional cancer center in south India. LHM facilitates major hepatectomy with "anterior approach," reducing several risks caused by liver mobilization: bleeding, rupture of the tumor, tumor cell dissemination, hemodynamic instability, and post op liver failure. This technique is very useful and safe for bulky pediatric hepatic tumors.

Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

CONTEXT: There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. AIMS: The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). SETTINGS AND DESIGN: In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. MATERIALS AND METHODS: Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. RESULTS: Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. CONCLUSIONS: Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

Histological diversity and clinical characteristics of Ewing sarcoma family of tumors in children: A series from a tertiary care center in South India.

BACKGROUND: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a Tertiary Care Center in South India. MATERIALS AND METHODS: This retrospective descriptive study includes 51 cases of ES in children aged below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic, primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ hybridization (FISH). RESULTS: Fifty-three percent were female and 47% were male with mean age of 10 years. The most common site of involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow-up in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%). All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical histomorphology. CONCLUSION: ESFT had wide histological variation which required confirmation by ancillary studies.

Complications of chemoport in children with cancer: Experience of 54,100 catheter days from a tertiary cancer center of Southern India.

BACKGROUND: Chemoport is an essential part of the management of children with cancer and provides long-term venous access. There are few studies from resource poor countries reporting complications of chemoport. AIMS: This study was aimed at describing the complications of chemoport in patients with cancer. MATERIALS AND METHODS: This retrospective observational study analyzed 200 patients <15 years of age who underwent chemoport insertion. The medical records of these patients were reviewed for the patient characteristics, diagnosis, nature of port use, port-related complications and their management. RESULTS: A total of 209 ports were implanted in 200 patients and 24 ports were removed due to port-related complications. There were 122 boys and 78 girls whose ages ranged from 4 months to 13 years (median age 2.5 years). About72% of patients were <2 years old. The cumulative duration of catheterization was 54,100 days. Of 209 ports, there were 36 complications that led to the removal of 21 ports. Port-related infection was the most common infection observed in our study (0.66/1000 catheter days and 11.9%). Mechanical complications were seen in 9 patients. Venous thrombosis and skin necrosis occurred in one patient each. CONCLUSIONS: Use of chemoport is safe and is a boon for children with cancer in developing countries with incidence of complications similar to Western countries. Although use of chemoport is associated with complications, they are easily managed. With stringent catheter care by trained personnel, some complications can be prevented.

Posterior reversible encephalopathy syndrome in pediatric acute leukemia: Case series and literature review.

Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state coupled with a unique radio imaging appearance. We describe this rare, mostly reversible condition in five cases undergoing similar treatment under preset protocol (MCP-841) for acute lymphoblastic leukemia (ALL) at our centre. Hypertension is a well-known adverse effect of high-dose corticosteroid therapy primarily mediated by its effects on the mineralocorticoid receptor especially in pediatric population and we hypothesize that this may be the etiology of PRES in two of these patients.

Risk of hepatitis B infection in pediatric acute lymphoblastic leukemia in a tertiary care center from South India.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high in Asian countries. Little is known about outcome of leukemia in HBV infected patients in these regions. Hence, we conducted this study in two cohorts of patients. PROCEDURE: We retrospectively evaluated mortality, reduction in dose intensity and duration of therapy (intensive phase and maintenance phase) in children with acute lymphoblastic leukemia (ALL) who developed HBV infection. Sixty-three patients with ALL were included in the retrospective cohort of the study. These were followed up for a minimum of 5 years. We prospectively investigated the prevalence of anti-HBc antibodies in 105 treatment naïve pediatric patients with ALL and negative for HbsAg. RESULTS: Twenty of the 63 patients developed hepatitis, of which 10 were attributed to HBV. All the 10 patients with HBV hepatitis had significantly reduced dose intensity during maintenance therapy with an average delay in completion of therapy of 140 ± 83 days and also a high mortality (40%). In the prospective cohort of the study, 39% of treatment naive patients who were HBsAg negative were anti-HBc positive at presentation, possibly reflecting occult HBV infection. CONCLUSIONS: HBV infection poses a serious problem in patients with ALL. Hence we propose that in India, in addition to screening for HBsAg, patients with leukemia should also be screened for anti-HBc. Improved hepatitis B vaccine coverage in the community under the universal immunization programme and introduction of HBV nucleic acid test (NAT) for blood donations should also help in addressing the problem.

Spectrum of pediatric brain tumors: a report of 341 cases from a tertiary cancer center in India.

Brain tumors are the second most common cancers after hematological malignancies accounting for approximate 21% of all childhood malignancies in children between ages of 0 and 14 y. The present study was undertaken to determine the spectrum of the brain tumors diagnosed in a tertiary cancer center in South India. A retrospective analysis of the data of pediatric brain tumors diagnosed between 2003 and 2009 was done and data was classified according to the age, gender and histology types. Out of 2,844 pediatric patients, 341 (11.99%) were diagnosed as having brain tumors. Most of the patients were in the age group of >5-14 y. Male to female ratio was 1.58:1. The most common pediatric brain tumor was medulloblastoma followed by astrocytoma and ependymoma. Glioblastoma multiforme was the most common subtype of astrocytoma. Other common tumors were glioma, oligodendroglioma, periphereral neuroectodermal tumor and germ cell tumor. As compared to western data, incidence of brain tumors in children was found to be less in the present study.

A single center experience in 266 patients of infantile malignancies.

INTRODUCTION: The diagnosis and management of cancer in infantile age group is a significant challenge to pediatric oncologists. Malignancies occurring in infants often have different clinical and biological behavior in comparison to older children. This study was performed with an aim to find out the profile of infantile cancers at a tertiary care cancer center in South India. METHODS: The present study was a retrospective analysis of infants presenting with malignancy between 2003 and 2012 to our center in South India. RESULT: A total of 4588 pediatric patients were registered in the Department of Pediatric Oncology at our institute between 2003 and 2012. Among those, 266 (5.79%) of the patients were infants (0-1 years). There were 65.75% males and 34.25% females. Solid tumors were the most common malignancy in this age group (72.56%). Leukemias were observed in 67 (25.19%) infants. ALL was the most common hematological malignancy (17.29%) followed by AML (5.64%). Common solid tumors in descending orders were neuroblastoma, soft tissue sarcoma, renal tumors, germ cell tumors, retinoblastoma and hepatoblastoma. Thirteen (4.89%) neonates were seen in our study. The most common malignancy in neonates was neuroblastoma. CONCLUSION: The distribution of malignancy in infants is quite different from that which is found in older children. Although neuroblastoma is the most common infantile tumor in western countries, in our study leukemia is the most common infantile malignancy. Embryonal tumors such as neuroblastoma, Wilms tumor, retinoblastoma, and hepatoblastoma were more prevalent in infants. Solid tumors were the most common malignancy in infants which is followed by leukemia.

An unusual case of pulmonary granulocytic sarcoma treated with combined chemotherapy and radiation.

We report an unusual case of a 6-year-old male child who presented with fever and a cough of one month's duration. A bone marrow aspiration and cytogenetics were suggestive of acute myeloid leukaemia with t(8;21)(q22;q22). A chest x-ray and computed tomography of the thorax showed a soft tissue lesion in the right lung. The fine needle aspiration cytology (FNAC) of this lesion was suggestive of pulmonary granulocytic sarcoma. The patient was successfully treated with induction chemotherapy (cytosine arabinoside + daunomycin), followed by consolidation with high-dose cytosine arabinoside. In view of the persistent lesion in the right lung, the patient was given external beam radiotherapy (EBRT), which resulted in near total resolution of the lung granulocytic sarcoma. We report this case in view of its rarity and clinical importance, and to highlight the treatment options in this scenario.

G-banding and fluorescence in situ hybridization in childhood acute myeloid leukemia from South India.

BACKGROUND: The current WHO classification of hematologic malignancies defines distinct entities of myeloid disorders based on the presence of recurrent cytogenetic abnormalities. Diagnostic clonal chromosomal abnormalities provide important prognostic information and are among the most important factors in predicting initial response to chemotherapy, duration of remission and overall survival.  METHODS: This study analyzed chromosomal abnormalities in bone marrow aspirates of 50 children diagnosed with acute myeloid leuckemia (AML).  RESULTS: The culture success rate was 94%, clonal chromosomal abnormalities constituted 62% and recurrent chromosomal abnormalities were 56%. In the favorable prognostic category, there were 51.6% of cases with t(8;21)(q22;q22), 16.1% had t(15;17)(q22;q21), and a total of 12.9% had chromosome 16 rearrangement. The adverse risk category showed a low frequency of t(9;11)(p22;q13); t(1;22)(p13;q13); inv(3)( q21q26); add 4(q35) and ring chromosome. According to fluorescent in situ hybridization (FISH) results in 16 cytogenetically normal patients, there were no CBFß/MYH11 fusion genes observed in chromosome 16 rearrangements.  DISCUSSION: Larger studies of this kind may provide more information about chromosome 16 rearrangements in cytogenetically normal patients. The present analysis suggests that both age and cytogenetics are important strategies for risk stratification (outcome). Additional laboratory parameters should also be considered in childhood AML.

Primary pulmonary rhabdomyosarcoma in children: Report of three cases with review of literature.

Primary pulmonary rhabdomyosarcoma in children is rare. Three children aged three, nine and three years were evaluated for abnormal shadows on radiological examination with pneumothorax in two cases. Resection and histopathological examination revealed embryonal rhabdomyosarcoma in all and cystic malformation in first case. All the three children were treated with surgery and first two received adjuvant chemotherapy. The disease free duration was 160 months, 19 months and seven months respectively. The literature on primary pulmonary rhabdomyosarcoma in children was reviewed.

Cell-free epstein-barr viral loads in childhood hodgkin lymphoma: a study from South India.

Cell-free Epstein-Barr viral (EBV) DNA is detectable in plasma of patients with EBV-related lymphomas. The aim of this study was to evaluate the utility of plasma EBV DNA as a biomarker of EBV association in childhood Hodgkin lymphoma (HL). Furthermore, an attempt was made to evaluate the effectiveness of viral quantitation for assessing response to chemotherapy. Thirteen cases of childhood HL were included in this study. All 13 cases were EBV associated as reflected by expression of EBV LMP1 in the tumor specimen. Eighty-five percent had detectable EBV DNA levels; viral loads ranging from 2.9 to 156.2 × 10³ copies/ml (mean 29 × 10³ copies/ml); while in 2 patients and 30 controls tested, viral DNA was undetectable. In four patients, follow-up samples were available after three cycles of chemotherapy; all had EBV DNAemia prior to chemotherapy but undetectable EBV DNA posttherapy. This corroborated with complete response in these four patients. Plasma EBV viral load quantification maybe a useful tool for detecting EBV association with lymphomas and in monitoring response to treatment in childhood HL in centers with limited resources, more so in India where majority of childhood HL is likely to be EBV associated. This is the first Indian study estimating plasma EBV viral loads in HL.

Wilms' tumor: single centre retrospective study from South India.

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.