Bs Aruna Kumari

Prevalence of high-risk human papillomavirus genotypes in retinoblastoma

Background The human papillomavirus (HPV) is an important aetiological agent in cancer but its involvement in retinoblastomas (RBs) is controversial. Methods 64 formalin-fixed paraffin-embedded tissue blocks and 19 fresh-frozen specimens were subjected to multiplex PCR using PGMY09/11 primers, HPV genotyping, non-isotopic in situ hybridisation and immunohistochemistry for pRb and p16INK4a. Results 24% of RBs contained HPV DNA. 90% of HPV genotypes were of high-risk (HR) type and 10% were of intermediate-risk (IR) type. HR HPVs 45, 59, 68 and 52 were detected for the first time, as were IR HPVs 82 and 73. There was only one HPV 18-positive case. Interestingly, no low-risk genotypes were identified. Nine formalin-fixed paraffin-embedded HPV-positive cases showed nuclear HPV positivity by non-isotopic in situ hybridisation. Immunohistochemistry did not show pRb expression in 67% of cases. 34% expressed nuclear p16INK4a, of which 20 cases were also positive for HPV by multiplex PCR. A statistically significant association between HPV and pRb expression status was observed (p=0.0001).The association of HPV with p16INK4a expression was also statistically significant (p=0.0001). Conclusions While the presence of HPV in a subset of RB was demonstrated, its role in carcinogenesis needs further elucidation.

Langerhan's cell histiocytosis: A single institutional experience

Background: Langerhans cell histiocytosis (LCH) is a disease that primarily affects bone but can be associated with a clinical spectrum that ranges from a solitary bone lesion with a favorable natural history to a multisystem, life-threatening disease process. Aim: We analyzed our single institutional experience of managing children with LCH. Settings and Design: A total of 40 children of LCH, managed in tertiary cancer center in South India in the period from 2001 to 2005, were evaluated retrospectively. Materials and Methods: Clinicopathological features, laboratory findings, treatment modalities and long-term outcome were analyzed. Results: Children were aged between 2 months and 12 years, with a mean of 3 years. Majority of the children were below 5 years of age. Group B constituted a bulk of children. Disseminated cases were less (five patients). Liver function dysfunction was seen in four (10%) children. Pulmonary interstitial infiltrates were seen in two (5%) cases. Diabetes insipidus manifested in three patients. There was one death. Conclusion: A better understanding of the etiology and pathogenesis of LCH will result in more directed and efficacious treatment regimens.

Cytogenetics of Neuroblastoma : A Study Using Fine Needle Aspiration Cultures

Neuroblastoma is associated with chromosomal aberrations of 1p and 1q in a majority of cases. Some nonrandom secondary changes were observed in this study. The role of these changes in the development and progression of neuroblastoma is examined. Chromosomal analysis was performed on 33 children with neuroblastoma using fine needle aspiration cultures. Metaphases were observed in 57.5% of cases. 86.6% showed the involvement of chromosome 1. Double minutes and unidentifiable markers was also observed. The most frequent secondary changes included add(4)(q35), add(11)(p13), add(14)(q32), add(16)(q12). add(17)(p13), add(19)(q12) and add(21)(q22). Minority of cases showed deletions and translocations. Ploidy pattern ranged from diploid to hypotetraploid. The present study substantiates aberration of chromosome 1 in the form of deletions, additions, duplications and iso-chromosome with some notable secondary abnormalities.

Hepatoblastoma: Experience from a single center

BACKGROUND The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability. AIMS We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs. SETTINGS AND DESIGN Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004. MATERIALS AND METHODS Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed. RESULTS There were 9 boys and 3 girls, aged 5-60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications. CONCLUSIONS Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy.

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.

Anaplastic large cell lymphoma: A single institution experience from India

BACKGROUND Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkins lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown. OBJECTIVE To study the clinical, pathologic profile and outcome ALCL. MATERIALS AND METHODS Fifty patients who had pathologically proven diagnosis of systemic ALCL at our institute from June 2003 to May 2011 were included for retrospective analysis. This included 30 cases of anaplastic lymphoma kinase+ (ALK+), ALCL and 20 cases of anaplastic lymphoma kinase- (ALK-), ALCL. The hospital protocol for treatment of these patients included CHOP chemotherapy regimen in >15 years of age and MCP842 protocol with vinblastine for 1 year in <15 years of age. Event free survival was noted. These outcomes were correlated with ALK status, International Prognostic Index (IPI) score, and stage at presentation. RESULTS At a median follow-up of 36 months (range: 6-72 months) ALK- ALCL had a poor outcome. The 3 year event free survival in pediatric ALCL was 66.7%. In adults, this was 60% ALK+ ALCL was 60% and 20% in ALK- ALCL. CONCLUSIONS Systemic ALCL is an aggressive disease. CD3 + positivity is commonly seen in ALK- ALCL and ALK+, epithelial membrane antigen + positivity is seen in ALK+ ALCL. ALK- ALCL, advanced stage III, IV and high IPI score were associated with poor prognosis. The demographic profile and outcome in our study was similar to the world literature. With new drugs like crizotinib and brentuximab vedotin the future looks very promising.

Association between plasma homocysteine and riboflavin status in Acute Lymphoblastic Leukemia in children

Remethylation of homocysteine to methionine is dependent on an adequate supply of one or more of the B vitamins like folate, vitamin B12 and vitamin B6. Plasma total homocysteine (tHcy) is also influenced by genetic factors such as polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. MTHFR is a flavo enzyme and a key player in folate metabolism and changes in its activity could modify the susceptibility to Acute Lymphoblastic Leukemia (ALL). In this case — control study we have examined the effect of riboflavin status as measured by erythrocyte glutathione reductase activation coefficient (EGRAC) on homocysteine levels along with vitamin B12 and folate in pediatric ALL. Folate and B12 levels were significantly lower among cases as compared to controls while EGRAC and tHcy did not differ significantly among the groups. The multivariate regression analysis revealed that in the ALL group EGRAC significantly influences tHcy levels suggesting that riboflavin availability may be a predictor of tHcy levels in patients with ALL. This finding may have implications for tHcy lowering therapy.

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

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.

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.

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.