Extrarenal Teratoid Wilms Tumor.

Teratoid Wilms tumor (TWT) is a variant of Wilms tumor. 30 cases have been reported so far. The extrarenal TWT variant has only been 5 in number. We are reporting a case of retroperitoneal TWT in a 6-year-old female child with diagnostic and therapeutic challenges.

Unusual sites of Rosai-Dorfman disease in children: 5 years experience from tertiary care paediatric haemato-oncology centre.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder, usually presenting with massive lymphadenopathy. The involvement of extra nodal sites, bone and nodal sites like mediastinum are rare. Clinical data of three cases of extra nodal RDD who were admitted in our paediatric haemato-oncology unit were analysed in the last 5 years. The extra nodal RDD (maxillary sinus, nasal pharyngeal focus, and external auditory meatus) were diagnosed based on histopathology and positron emission tomography scan. They were treated with steroids but were refractory hence requiring salvage chemotherapy. Currently all three of them are in complete remission. Extra nodal RDD is difficult to diagnose, histopathology and radiology play an important role. Here, we present three cases, of which two were steroid-refractory which were treated with salvage chemotherapy and are in complete remission.

Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients.

PURPOSE: Pediatric acute lymphoblastic leukemia (pALL) patients have better overall survival and methotrexate (MTX) is an effective drug used in their treatment. However, the treatment-related adverse effects (TRAEs) have a bigger impact on the therapy. In this study, we have evaluated the association of polymorphisms in genes encoding proteins engaged in MTX metabolism, and the cytogenetic aberrations with TRAEs. METHODS: A total of 115 patients between the age of 1 and 18 years (average: 6.6) under maintenance therapy were selected for the study. SLC19A1 (c.80G > A), MTHFR (c.677C > T; c.1298A > C), and TYMS (c.*450_*455del) genotypes were determined using PCR techniques and Sanger sequencing. Cytogenetic and SNP findings were analyzed for any association with the reported toxicities using odds ratio, chi-square test, multifactor dimensionality reduction (MDR) analysis for synergistic effect and, multinomial logistic regression analysis for the likelihood of adverse events. RESULTS: Among the evaluated genetic variations, SLC19A1 (c.80G > A) was significantly associated with TRAEs (OR = 5.71, p = 0.002). Multinomial logistic regression analysis (chi-sq = 16.64, p < 0.001) and MDR analysis (chi-sq = 10.51 p < 0.001) confirmed the finding. On the other hand, no significant association was observed between adverse events and any specific cytogenetic aberration. CONCLUSION: SLC19A1 facilitates the import of cyclic dinucleotides and reduced folates, evaluating genotypes in this gene can help in better management of patients on methotrexate treatment. Assessing a broader gene panel can help in finding more associated markers and delivering personalized medicine to the patients.

Cytogenetics and Molecular Genetics in Pediatric Acute Lymphoblastic Leukemia (ALL) and Its Correlation with Induction Outcomes.

Arathi SrinivasanAims The aim was to study cytogenetics and molecular genetic profile in pediatric B-acute lymphoblastic leukemia (ALL) and correlate it with induction outcomes. Subjects and Methods A retrospective study of cytogenetics and molecular genetics of 98 children with B-cell ALL from January 2013 to May 2018 was done. Cytogenetics and molecular genetics were done in the bone marrow using multiplex reverse transcription polymerase chain reaction and G-banded karyotyping, respectively. Minimal residual disease (MRD) assessment was done at the end of induction by flowcytometry. Results Of the 98 children, 83 (84.6%) had evaluable cytogenetics, with 11 (13.25%) being abnormal karyotypes. Of the 11 abnormal karyotypes, seven children (8.4%) had hyperdiploidy, one had hypodiploidy, and three had miscellaneous findings. In molecular genetics, TEL-AML1 (ETV6/RUNX1)[t(12;21)] was the most common fusion gene abnormality (12.2% [12/98]), followed by E2A-PBX1 [t(1;19)] (5%), BCR/ABL1 [t(9;22)] (3%), and MLL-AF4 [t(4;11)] (1%). All the 98 children attained morphologic remission at the end of induction. All children with hyperdiploidy (7/7) attained remission and MRD negativity, but one expired during maintenance chemotherapy of disseminated tuberculosis. The child with hypodiploidy was MRD-positive. Three (25%) children with t (12;21) were MRD-positive. All children with Ph + ALL, t(1:19), and t(4;11) were MRD-negative. Fifty-two children had no detected abnormalities, six of whom had MRD positivity (11.5%). Conclusion Cytogenetic and molecular genetic subgrouping prognosticates ALL outcomes. Although 25% of TEL-AML + children had MRD positivity, larger studies are required to validate the same. End-of-induction MRD outcomes did not correlate with chromosomal aberrations.

Pharmacogenetic evaluation of 6-mercaptopurine-mediated toxicity in pediatric acute lymphoblastic leukemia patients from a South Indian population.

Aim: To evaluate the variants in the genes coding for the proteins involved in thiopurine and folate metabolism with treatment related adverse effects (TRAEs). Materials & methods: Eleven variants in seven candidate genes were genotyped in 127 pediatric acute lymphoblastic leukemia patients under 6-mercaptopurine (6-MP) treatment to infer the association of selected genotypes with TRAEs. Results: Among the genotypes inspected, NUDT15 (c.415C>T) and SLC19A1 (c.80G>A) showed a significant association with the TRAEs (odds ratio = 4.01, p = 0.002 and odds ratio = 7.78, p = 0.002). Conclusion:SLC19A1 and NUDT15 play an important role in the metabolism of 6-MP and it is necessary to spot other variants in associated pathways and investigate the factors that can impact 6-MP metabolism.

Evaluation of serum procalcitonin, serum interleukin-6, and interleukin-8 as predictors of serious infection in children with febrile neutropenia and cancer.

BACKGROUND: Early diagnosis of sepsis in children with febrile neutropenia remains difficult owing to non-specific clinical and laboratory signs of infection. There is a need to assess the utility of inflammatory markers in clinical risk assessment for their ability to discriminate between low-risk and high-risk neutropenic patients since presently there is insufficient data to recommend their routine use. METHODS: This is a prospective study of children on therapy admitted with febrile neutropenia and sampled for serum procalcitonin (PCT), interleukin-6 (IL-6), and interleukin-8 (IL-8) at admission. The febrile neutropenia episodes were categorized into two groups - Group I: no focus of infection and Group II: clinically/microbiologically documented infection. Statistical analyses for comparison were performed using Z-test and receiver operating curves at various cut-off levels. RESULTS: A total of 46 episodes of febrile neutropenia in 33 children were analyzed. In total, 76% were categorized as group I and 24% as group II. The mean value of PCT in group II was higher (28.07 ng/mL) than group I (1.03 ng/mL) though there was no significant statistical difference. At a cut-off level of 2 ng/mL for PCT, sensitivity of 63%, specificity of 91%, positive predictive values (PPV) of 70%, and negative predictive value (NPV) of 88% were observed. There was no significant difference in the IL-6 and IL-8 levels between both the groups. However, at an optimal cut-off value of 50 pg/mL, IL-6 had an NPV of 80% and at a cut-off level of 130 pg/mL, IL-8 had an NPV of 73%, however, with low sensitivity and specificity. CONCLUSION: IL-6, IL-8, and PCT can be utilized to define a group of patients with a low risk of sepsis in view of their favorable NPV. The use of these biomarkers together can facilitate early discharge from the hospital, and the use of oral antimicrobial therapy, in turn, reducing the cost of supportive therapy in a developing country.

Rosette-forming Glioneuronal Tumor in the Optic Pathway of a Child.

Rosette-forming glioneuronal tumor is a rare World Health Organization grade I neoplasm, primarily involving the posterior fossa. Most cases have been reported in young adults. Although maximal surgical resection is advocated, a precise treatment modality is yet to be established. We describe an unusual presentation of rosette-forming glioneuronal tumor occurring in the optic pathway in a child. As the site of the tumor was not amenable to resection, he underwent radiotherapy and is currently well on follow-up.

Pediatric Inflammatory Myofibroblastic Tumors of the Airway: Two Case Reports with Varying Clinical Presentation.

INTRODUCTION: An inflammatory myofibroblastic tumor (IMT) is a rare tumor of intermediate malignant potential. It may occur in a wide range of anatomical locations. One-third are found in the respiratory tract. We report two cases of IMT of the airway diagnosed at our institution. CASE REPORT: Case 1: A 6-year-old male child presented with a 1-month history of hoarseness of the voice. On evaluation, a polypoid nodule was noted in the right vocal cord which was excised through the endolaryngeal route. Histopathology was suggestive of anaplastic lymphoma kinase (ALK)-negative IMT. He presented with recurrence after 4 months, for which he underwent endolaryngeal reexcision and tracheostomy for airway protection. A third recurrence after 6 months was managed with laser excision, and the patient was started on oral celecoxib. After 1.5 years of follow up, endoscopic examination showed no recurrence, and celecoxib was continued. Case 2: A 7-year-old male child presented with cough and respiratory distress. Bronchoscopy and high resolution computed tomography showed a polypoidal lesion with calcification arising from the left anterolateral wall of the trachea with significant narrowing of the lumen. The patient underwent biopsy followed by endoscopic excision, and was diagnosed with IMT. Currently the patient is under follow up with no recurrence. CONCLUSION: IMT indicates a proliferative myofibroblastic growth. Surgical resection should be recommended for all lesions if not prohibited by anatomic location or morbidity. Patients should be followed up closely for recurrence. In most cases, complete surgical excision will suffice; however multiple recurrences can be managed with chemotherapy. These two cases highlight the importance of a multidisciplinary approach in rare tumors in difficult anatomical locations.

Profile and Outcome of Pediatric Brain Tumors - Experience from a Tertiary Care Pediatric Oncology Unit in South India.

CONTEXT: Tumors of the central nervous system (CNS) constitute the second most common pediatric cancers. Unlike leukemia, management of CNS tumors requires a good multidisciplinary team. Higher rates of treatment abandonment are documented in view of complexity of the treatment with long duration, involving neurosurgery, radiation, chemotherapy, and high cost of treatment. Morbidity associated with CNS tumors may be significant in terms of physical deficits as well as neuropsychological and neuroendocrine sequelae. Pediatric neurooncology is still at a very nascent stage in the developing countries. There are only a few reports on the multidisciplinary approach and outcomes of pediatric brain tumors in developing countries. AIMS: The aim of this study is to identify the clinicopathological profile of Pediatric CNS tumors in a tertiary care center located in South India in comparison with reports from other low-and middle-income Countries. SETTINGS AND DESIGN: A retrospective analysis of medical records of all children diagnosed with brain tumors from January 2012 to November 2016 at our institute was done. SUBJECTS AND METHODS: A retrospective study of clinical, pathological profile, and outcomes of children <18 years diagnosed with brain tumors at our institute from January 2012 to November 2016 was done. Histopathological categorization was done as per the WHO classification 2007. The multidisciplinary treatment with respect to surgery, radiation, and chemotherapy was noted and the outcomes were recorded. STATISTICAL ANALYSIS USED: R for Statistical Computing (Version 3.0.2; 2013-09-25). RESULTS: A total of 52 children were diagnosed with male preponderance of 66.6%. Highest incidence was noted in the age group of 0-4 years (50%). Majority of them were supratentorial (59.6%). CNS embryonal tumors contributed to 48% of all our brain tumors. 73% of them underwent either resection or biopsy. Eight (15.3%) of them died due to the progression of disease, but 44% abandoned treatment due to the progression/recurrence of disease. Those lost to follow-up were mostly among the high-risk groups with poor prognosis such as pontine glioma, medulloblastoma (high risk), and primitive neuroectodermal tumor. CONCLUSIONS: Although brain tumors constituted 30% of all our solid tumors, only 56% of them received appropriate treatment and 25% abandoned treatment. High rates of abandonment were a consequence of late diagnosis, complex multidisciplinary treatment involved, high treatment cost, lack of uniformity in management between different oncology centers and poor prognosis of the tumor subtype.

A Rare Case of Perinatal Intrarenal Neuroblastoma.

Perinatal neuroblastoma is the most common solid malignant tumor in infancy which comprises one fifth of all neuroblastomas. Most of them are of adrenal origin and extra-adrenal neuroblastoma is uncommon. We present a rare case of perinatal intrarenal neuroblastoma in a neonate who presented with an incidentally detected abdominal mass. These tumors cause diagnostic and therapeutic dilemma because of its uncommon location. Although very rare, neuroblastoma should be considered in the differential diagnosis of perinatally detected renal tumors.

ABVE-PC and modified BEACOPP regimen in Indian children with Hodgkin lymphoma: Feasibility and efficacy.

AIMS: To study the toxicity of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide) and modified-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in intermediate-risk and high-risk Hodgkin lymphoma patients. METHODS: High-risk patients received 4 cycles of modified-BEACOPP (m-BEACOPP) plus 4 cycles of ABVD. Intermediate-risk patients received 4 cycles of ABVE-PC plus 2 cycles of ABVD. RESULTS: From 2010 to 2014, 17 patients received 66 cycles of m-BEACOPP and 9 patients received 40 cycles of ABVE-PC. In the m-BEACOPP and ABVE-PC courses, respectively, significant thrombocytopenia (<50,000/mm(3)) occurred in 10.6% vs 0% of courses; anemia (Hb. <8 gm/dl) in 27.3% vs 15%; neutropenia (ANC<500/mm(3)) in 46.9% vs 32.5%; and febrile neutropenia in 33.3% vs. 22.5%. Only episode of documented infection (hepatic abscess) occurred in ABVE-PC. There were no episodes of sepsis, typhlitis or pneumonia in either group. All 26 patients are in remission with a median follow-up of 35 months (range, 17-61); and there have been no relapses. Two of 26 (7.7%) patients failed to achieve rapid early response after 2 cycles and complete remission after 4 cycles of chemotherapy; both achieved remission with more intensive regimens followed by radiation. The remaining 24 patients did not receive radiation therapy. CONCLUSIONS: Both m-BEACOPP and ABVE-PC regimens have acceptable toxicity; and thus can be used in most centres with optimum supportive care facilities. They offer promising response rate and relapse free survival without the need for radiation therapy in most patients; and thus may be considered for children with high-risk and intermediate-risk Hodgkin lymphoma.

Two Uncommon Paraneoplastic Neurological Syndromes in a Child With Hodgkin Lymphoma.

Paraneoplastic neurological syndromes (PNS) are rare, remote effects of cancer that are usually caused by an altered immune response to the tumor and not due to the tumor mass, metastasis, infection, ischemia, or metabolic derangements. PNSs can affect any area of the central, the peripheral, and the autonomic nervous systems. These are rare in lymphomas compared with solid tumors attributed to their presentation even in late stages and the absence of onconeural antibodies. We present a child with stage IIB Hodgkin lymphoma who presented with dual PNS, achalasia cardia, and Holmes Adie pupil occurring synchronously with the cancer.

Impact of cancer support groups on childhood cancer treatment and abandonment in a private pediatric oncology centre.

AIMS: To analyze the impact of two cancer support groups in the treatment and abandonment of childhood cancer. MATERIALS AND METHODS: This is a retrospective review of children with cancer funded and non-funded who were treated at Kanchi Kamakoti CHILDS Trust Hospital from 2010 to 2013. A total of 100 patients were funded, 57 by Ray of Light Foundation and 43 by Pediatric Lymphoma Project and 70 non-funded. RESULTS: The total current survival of 80%, including those who have completed treatment and those currently undergoing treatment, is comparable in both the groups. Abandonment of treatment after initiating therapy was not seen in the financially supported group whereas abandonment of treatment after initiation was seen in one child in the non-funded group. CONCLUSIONS: Besides intensive treatment with good supportive care, financial support also has an important impact on compliance and abandonment in all socioeconomic strata of society. Financial support from private cancer support groups also has its impact beyond the patient and family, in reducing the burden on government institutions by non-governmental funding in private sector. Improvement in the delivery of pediatric oncology care in developing countries could be done by financial support from the private sector.

Primary pulmonary diffuse large B-cell non-Hodgkin's lymphoma in a child.

A 3-year-old girl presented with a history of intermittent fever of six months duration associated with respiratory symptoms consisting of recurrent cough, fever, wheeze and a suspected history of contact with tuberculosis (TB). Chest radiograph revealed pulmonary infiltrates mimicking miliary TB. She was started on anti-tuberculous treatment, but in view of clinical deterioration, a further work-up including a lung biopsy revealed non-Hodgkin's lymphoma (NHL). This case documents the extremely rare occurrence of pulmonary involvement and miliary infiltrates on the chest radiograph in NHL.

Inflammatory demyelinating disorders of childhood: experience with six children.

Demyelinating disorders of the central nervous system (CNS) in children pose diagnostic and prognostic difficulties in clinical practice. In this report, we describe our experience with inflammatory demyelinating disorders of CNS in six children, classified as per the proposed criteria by the Pediatric Multiple Sclersois Study Group. We emphasize the importance of appropriate diagnosis and follow-up to distinguish transient inflammatory demyelinating diseases from chronic inflammatory demyelinating diseases.