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.

Acute promyelocytic leukemia with unusual karyotype.

Acute myeloid leukemia (AML-M3) is associated with the translocation t(15;17)(q22;q12-21) which disrupts the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. We report a two-year-old patient with AML-M3 without the usual translocation t(15;17). Cytogenetic studies demonstrated normal appearance of chromosome 15 while the abnormal 17 homologue was apparently a derivative 17, der(17)(17qter-cen-q21:), the rearrangement distinctly shows deletion at 17q21 band and the morphology corresponding to an iso chromosome i(17q-). This case report is a rare cytogenetic presentation of acute promyelocytic leukemia (APML).

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.

Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children.

Introduction: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children. Materials and Methods: Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) method. Results: Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A→C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48- 2.45, p = 0.851) and OR for A1298C was 1.29(95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p =0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58 -6.52, p = 0.286). Conclusion: The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C→T and 1298 A→C gene polymorphisms and risk of ALL, which may be due to the small sample size.

Homocysteine, vitamin B12 and folate status in pediatric acute lymphoblastic leukemia.

OBJECTIVE: The cause of majority of acute leukemias is unknown, but likely to involve interaction of environment, hematopoitic development and weak susceptibility loci within an individual's genetic constitution. The present study evaluates the association between plasma levels of homocysteine, folate and vitamin B12 and acute lymphoblastic leukemia. METHODS: Plasma levels of homocysteine, folate and vitamin B12 were compared between cases of acute lymphoblastic leukemia and age and sex matched normal controls. Homocysteine levels were measured by solid immunoassay, while folate and vitamin B12 levels were determined by radioassay. RESULTS: Folate levels were significantly among cases as compared to control group (8.56 +/- 4.35) vs (14.04 +/- 2.62) ng/ml, P< 0.001). Although individually vitamin B12 and homocysteine were not significant different between cases and controls, the combined effect of all three parameters was significantly different (P< 0.001), with 83.3% of correct classification of cases and controls was obtained by discriminate function analysis. CONCLUSION: The data provide evidence for the role of folate, vitamin B12 and homocysteine levels in acute lymphoblastic leukemia, suggesting that gene-environment interaction may be an important factor in the development of acute lymphoblastic leukemia.

Bone marrow involvement at presentation in pediatric non-haematological small round cell tumours.

Pediatric small round cell tumors (SRCT) are a group of neoplasms occurring in children, which have in common a cytomorphology of groups of small round cells with scanty cytoplasm. The common SRCT encountered are neuroblastoma, retinoblastoma, Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), rhabdomyosarcoma and lymphoma which show varying degrees of bone marrow involvement and bone marrow evaluation forms a part of the initial staging procedure. This study was undertaken to evaluate marrow involvement at presentation in pediatric non hematological SRCT. 7833 bone marrow aspirates done over a period of three years in different malignancies were analysed and of these 180 aspirates were performed in patients of pediatric non hematological SRCT at presentation. These cases were evaluated in detail for incidence of marrow involvement. Thirty two (17.7%) cases showed marrow involvement and these cases have been analysed with respect to the primary tumor. The SRCT showing involvement of bone marrow included neuroblastoma (48.8%), retinoblastoma (11.1%), Ewing's sarcoma/PNET (8.6%) and rhabdomyosarcoma (3.2%).These findings are discussed in the light of available world literature.

Childhood hepatic angiosarcoma--a case report.

Hepatic angiosarcoma (HAS) is an extremely rare liver tumor in children. We report a case of childhood HAS in a six year old girl who presented with acute abdominal pain and fever with a mass in epigastrium. Left hepatic lobectomy was performed with a clinical diagnosis of hepatoblastoma. Histopathological examination revealed features typical of hepatic angiosarcoma. The case is presented for its rarity and to discuss the interrelation between infantile hemangioendothelioma (IHE) and HAS.

Mixed exocrine-endocrine pancreatic carcinoma in childhood.

A 7-year-old boy with mixed exocrine-endocrine pancreatic cancer is presented. This may be the second reported case of such a tumor in childhood.

Fusarium solani fungemia in a patient with acute lymphoblastic leukemia.

A patient with ALL on anticancer chemotherapy developed fever which was later attributed to be due to Fusarium fungemia. The details of the case & a review of literature follows.

Pneumocystis carinii pneumonia in two patients with Hodgkin's disease.

The incidence of Pneumocystis carinii pneumonia (PCP) in immunocomprOMised patients is on the increase. We describe two patients with Hodgkin's disease who were proved to have P. carinii pneumonia by toluidene blue "O" (TBO) staining of their induced sputa. To the best of our knowledge, there are no reports from our country regarding P. carinii infection in patients with malignancy.

Extranodal sinus histiocytosis with massive lymphadenopathy--a case report.

Sinus histiocytosis with massive lymphadenopathy involving organs other than the lymph nodes is a rare event. A case of SIIML presenting with multiple skin and subcutaneous nodules and multiple osteolytic lesions is described. A search of the Indian literature revealed many cases of nodal SIIML, but none of the reported cases had prominent extranodal involvement.