L Appaji

Cytogenetic characterization of Ewing tumors using fine needle aspiration samples: a 10-year experience and review of the literature

Chromosomal analysis was performed in fine needle aspiration samples of 98 primary Ewing tumors (ETs) prior to treatment. Among the 58 (59.18%) successful cultures, t(11;22)(q24;q12) was observed in 87.9% and 6.8% had abnormalities other than t(11;22), viz., del(22)(q12), der(16)t(1;16)(q12;q11), and variant t(8;22)(q24;q12). Involvement of breakpoints 1q21, 1q22, 3p14, 16q22, and 17p13 was also observed. Numerical abnormalities such as trisomies 8 and 12 were found in 29.3% and 20.6% and trisomy 18 in 17.2%. An attempt was made to evaluate the role of these additional changes in the process of tumor development, metastasis, and progression of the disease. This is the largest cytogenetic study on ET from a single center using a simple and reliable technique of fine-needle aspiration culture. The literature on cytogenetics of ET is reviewed.

Descriptive epidemiology of childhood cancers in Bangalore, India

While fairly complete and reliable incident data on childhood cancers are available from the registries in India, mortality and survival information is not. Information concerning the latter was obtained by the Bangalore cancer registry through active follow-up involving visits to homes of patients. Between 1982 and 1989, 617 cases of cancers in childhood were registered, giving an age-standardized incidence rate of 84.8 and 48.4 per million in male and female children, respectively. Active follow-up provided mortality/survival information in 532 or 86.2 percent of these cases. Overall, observed five-year survival was 36.8 percent (both genders combined) with a relative survival of 37.5 percent when childhood mortality in the general population was taken into account. The five-year relative survival was best for thyroid carcinoma (100 percent) followed by Hodgkins disease (73 percent) and retinoblastoma (72.9 percent). Survival was comparatively low, being 9.9 percent in acute nonlymphatic leukemia and less than 20 percent in rhabdomyosarcoma and the category grouped as ‘other malignant neoplasms.’ Survival in Hodgkins disease was influenced by clinical stage at presentation, but was not statistically significant possibly due to small numbers.

Association of Burkitt's Lymphoma with the Epstein-Barr Virus in Two Developing Countries

The clinical presentation of Burkitts lymphoma (BL) and its association with the Epstein-Barr virus (EBV) varies in different geographic areas, BL in developing countries being “intermediate” between the sporadic and endemic types, both in its clinical presentation and its association with EBV, which varies from 25-80%. In this study we have analysed the clinical features, EBV association, subtype and prevalence of the deleted variant of the Latent Membrane Protein-I (LMP-1) of EBV in forty-two cases from two developing countries- India (n=25) and Argentina (n=17). In both countries the abdomen was the site most commonly involved while jaw involvement was rare. EBV was detected by in-situ hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of cases from India were EBER positive. EBV typing using EBNA-3C primers showed a predominance of Type A in both countries (India-13/16 and Argentina-7/8). The 30bp deletion of the LMP-I gene was detected in all evaluated cases from Argentina while the wild type of the gene was seen in all the evaluable Indian cases. Our study highlights the similarities and differences in the clinical presentation and EBV association of BL in two developing countries and also indicates that the subtype of EBV and prevalence of the LMP-I deletion may reflect the predominant subtype in a particular population.

Rhabdomyosarcoma: cytogenetics of five cases using fine-needle aspiration samples and review of the literature

Cytogenetic analyses of fine-needle aspiration samples were performed on five cases of which three were alveolar rhabdomyosarcomas (RMS), one was embryonal RMS and one was RMS of mixed alveolar and embryonal histology. Three cases of alveolar RMS and one case of embryonal RMS showed t(2;13). A del(1)(p11) in a mixed alveolar and embryonal RMS was observed without the presence of t(2;13). add(17)(q25) was present in one of the alveolar RMS along with a t(2;13). Modal number of chromosome in the five cases ranged from hyperdiploid to hypertetraploid. Clinical, cytological, histopathological and cytogenetic findings are correlated. The role of additional abnormalities is discussed with a review of appropriate literature.

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.

Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate

Abstract Chronic myeloid leukemia (CML) is a rare disease in children, accounting for 2–3% of leukemias in this age group. Few studies have reported on efficacy of imatinib in childhood CML. The purpose of this retrospective study was to determine the efficacy of imatinib in children. A total of 43 patients from age 7 years to 20 years with newly diagnosed CML received imatinib daily at 260 mg/m2. Response rates, survival and toxicity were evaluated. The median follow-up was 43 months. All patients achieved a complete hematological response. Twenty-five (58.1%) patients achieved a complete cytogenetic response and 18 (41.9%) achieved a major molecular response at any time during their follow-up period. Both overall survival and progression-free survival at 43 months’ median follow-up were 100%. Event-free survival was 92.8%. Imatinib was well tolerated. We conclude that imatinib is effective in children and adolescents with CML.

Cytogenetic study of non-Hodgkin lymphoma from South India: histologic and geographic correlations

Cytogenetic analysis of fine needle aspiration cultures was performed on 189 patients with non-Hodgkin lymphoma from South India. Successful karyotyping was possible in 97 patients (51.3%). Burkitt lymphoma constituted 56% of the cases studied followed by diffuse type 20%, follicular 8.8%, lymphoblastic 6.6%, and unclassified 6.6%. Characteristic chromosomal translocations were t(8;14)(q24;q32) [32.2%], t(8;22)(q24;q11) [10%], t(2;8)(p12;q24) [2.2%], t(14;18)(q34;q21) [3.3%], and t(11;14)(q23;q32) [2.2%]. Notable geographical variation of some structural abnormalities was the finding in the present study such as, lower frequency of t(14;18) in follicular lymphomas and higher frequency of t(8;14) in Burkitt lymphomas when compared with the Western studies.

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.

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.