An interinstitutional review of the value of FNAB in pediatric oncology in resource-limited countries.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as a reliable diagnostic modality in the general pediatric population, but its role in pediatric oncology still remains elusive. With new treatment protocols subscribing to preoperative chemotherapy, the need for a quick, minimally invasive, and accurate diagnostic procedure has arisen. This study assesses the feasibility of FNAB in childhood malignancies to render a specific diagnosis on which treatment can be initiated. An 11-year retrospective study was done on FNABs in patients 19 years and under referred for clinically malignant mass lesions. Cases were confirmed with histology, immunocytochemistry, flow cytometry, or clinical follow-up. Of the 357 patients referred for FNABs, 36 patients were lost to follow-up and 31 FNABS were inadequate. A total of 290 cases were included in the study, of which 68 (23%) cases were benign and 222 (77%) were malignant. The most frequently occurring tumors were nephroblastoma (68), non-Hodgkin's lymphoma (39), rhabdomyosarcoma (22), Hodgkin's lymphoma (22), and neuroblastoma (22). The sensitivity of the procedure for neoplasia was 96.6%, the specificity 97.0%, positive predictive value 99.0%, and negative predictive value 90.1%, with a diagnostic accuracy of 96.7%. The ability of FNAB to enable a specific diagnosis to be made, that is correct and accurate subtyping of the tumor on which chemotherapy or radiotherapy could be commenced was 75.7%. This study shows that FNAB can be used with confidence to confirm malignancy in children. With clinicoradiological correlation and the aid of ancillary techniques, FNAB allows a rapid and accurate preoperative diagnosis for definitive therapy commencement in most cases.

Infection with human immunodeficiency virus-1 (HIV) among children with cancer in South Africa.

UNLABELLED: BACKGROUND IN ADULTS,: HIV increases the risk of certain cancers known, or thought, to have an underlying infectious etiology; the impact on the risk of cancer in children is less clear. METHODS: Here, we report results of an on-going study at four pediatric oncology centers in South Africa in which children diagnosed with cancer are tested routinely for HIV. Odds ratios (OR) for the prevalence of various malignancies were calculated (with adjustment for age, sex, and center) for the children infected with HIV using all children with cancer and non-malignant conditions, but not infected with HIV, as a comparison group. RESULTS: Of 882 children with cancer, 38 were HIV infected (for 12 the HIV status was unknown). HIV was associated with Kaposi sarcoma (all 10 cases were HIV infected; P < 0.001) and with Burkitt lymphoma (OR = 46.2, 95% confidence interval (CI) 16.4-130.3; 13/33). For non-Burkitt non-Hodgkin lymphoma (NHL), 2/39 were HIV infected (OR = 5.0, 95% CI 0.9-27.0). No other cancer type was significantly associated with HIV, including lymphoid leukemias (OR = 0.4, 95% CI 0.04-2.9; 1/172). CONCLUSIONS: Only Kaposi sarcoma and Burkitt lymphoma were significantly associated with HIV infection although results for non-Burkitt NHL were suggestive. Notably, we did not identify an association between infection with HIV and lymphoid leukemias, for which an underlying infectious etiology has been suggested.

Catastrophic intracerebral hemorrhage in a young infant with Wilms tumor.

We present a 7-month-old male infant with stage I Wilms tumor who unexpectedly died from a catastrophic intracerebral hemorrhage, 4 months after completion of chemotherapy and complete surgical resection of the tumor. The precise etiology underlying the fatal event remains unclear as postmortem was refused, but we postulate spontaneous hemorrhage from an underlying cerebral vascular malformation as the most likely cause, which led to the child's unfortunate demise. Although extremely rare, cerebral vascular anomalies have previously been reported in children with Wilms tumor. The coexistence of the 2 uncommon disorders may be related to their congenital origin. Wilms tumor diagnosed in very young infants have clinical and morphologic attributes that do not pertain in older children and the risk of associated congenital anomalies is also much higher among those discovered in the first year of life. This raises the question whether routine magnetic resonance imaging should not be performed in infants less than a year with Wilms tumor, as part of the initial evaluation, to exclude cerebral metastases and underlying vascular malformations.

Perspectives of the management of childhood lymphoma: experience at Tygerberg Hospital, Western Cape, South Africa.

Hodgkin's disease (HD) in children corresponds to a large degree to HD in adults. Non-Hodgkin's Lymphoma (NHL) in children, however, differs from NHL in adults with respect to the classification, natural history, management and course. For practical reasons clinicians generally classify and treat NHL in children as either B-cell or T-cell disease. Over the past 22 years, the Paediatric Oncology Unit of the Tygerberg Hospital has treated HD with three different regimens. Use of the CLVPP and MOPP/ABVD regimens resulted in late relapses that adversely affected event free survival (EFS). For the last four years HD has been treated according to the regimen suggested by Schellong with good short term survival rates. Lymphoblastic or T-cell NHL is treated with regimens normally used for acute lymphoblastic leukaemia (e.g. BFM protocols) or modified leukaemia treatments for leukaemia-lymphoma syndromes (e.g. LSA2L2). We lately use a modified BFM regimen with a 70% EFS for all stages. Three consecutive regimens have been used to treat B-cell NHL over the past 22 years. The first was a COMP regimen, followed by the LMB-89 and LMB-96 regimens. Although toxicity has increased with the increased intensity of the treatment regimen, EFS has improved from 25% to 87% for all B-cell NHL. The majority of patients had stage III and IV disease. Although the LMB regimens are toxic, the implementation is manageable provided good laboratory back up and supportive facilities are available.

The 2000 Burkitt lymphoma trial in Malawi.

BACKGROUND: We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity. METHODS: All Malawian children admitted to Queen Elizabeth Central Hospital, from 03/08/2000 to 12/03/2002 with confirmed BL were eligible. A fine needle aspirate, bone marrow aspirate, cerebrospinal fluid cytology, haemoglobin (Hb), white cell count (WCC), malaria smear, ELISA for HIV, and abdominal ultrasound were performed routinely. Murphy staging was used. The first dose of chemotherapy (COP1) consisted of 300 mg cyclophosphamide (CPM), 1 mg vincristine, and 60 mg prednisone given on day 1 and followed by COP2 on day 8 (only for patients with larger tumour volumes, stage III or IV disease). The vincristine dose in COP2 was 2 mg. COMP1 and 2 given on days 22 and 36 consisted of 500 mg CPM, 2 mg vincristine, 60 mg prednisone, and 2 g methotrexate. All doses were calculated per body surface area. Intrathecal methotrexate and hydrocortisone were given with COP1 and 2. RESULTS: Forty-two patients, 30 boys and 12 girls median ages 6 and 7.5 years, respectively, had Murphy stage I(n5), II(n8), III(n21), and IV(n8) disease. The face was involved in 74%, abdomen in 55%, bone marrow in 14%, kidneys in 24%, and 12% had paraplegia. Fourteen children died during or shortly after completion of chemotherapy. Three of these were disease related. Twelve patients suffered a local relapse after 57-328 days, and one a CNS relapse at 76 days. The projected EFS at 12 months is 50% in stage I, 50% in stage II, 24% in stage III, 25% in stage IV, and 33% for all patients. The cumulative mean dose of CPM was 62 mg/kg in survivors and 64 mg/kg in children who relapsed. One third of patients experienced significant marrow suppression, and infections after COMP1. CONCLUSIONS: Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.

Hepatocellular carcinoma and liver tumors in South African children: a case for increased prevalence.

BACKGROUND: The high regional incidence of hepatocellular carcinoma (HCC) in South Africa also may be present in children of the region, although the link to hepatitis B (HBV) appears less clear. The objective of this study was to assess the incidence and probable causes of HCC in South African children. METHODS: Data were obtained from seven participating pediatric oncology units and from the tumor registry to review hepatic tumors in children in South Africa. RESULTS: One hundred ninety-four children (ages 0-14 years) presented with malignant primary hepatic tumors (1988-2003). One hundred twelve tumors (57%) were hepatoblastoma (HB), 68 tumors (35%) were hepatocellular carcinoma (HCC) (including 9 patients with the fibrolamellar variant, 6 of which occurred in black children), 10 tumors (5%) were sarcoma of the liver, and 4 tumors were lymphoma. The ratio of HB to HCC (1.67) was markedly lower compared with other reports, suggesting a greater prevalence of HCC. Correlation with population statistics indicated an incidence of 1.066 malignant liver tumors per year per 10(6) children age < 14 years (HB, 0.61 per 10(6) children; HCC, 0.39 per 10(6)). Two-thirds of patients with HCC were positive for HBV surface antigen (HBsAg), and HCC occurred mostly in black African patients (93%). The mean age of onset was 1.47 years for HB and 10.48 years for HCC. A preponderance of males (3.5:1.0) was noted in the HBsAg-positive group that was not reflected elsewhere. Serum alpha-fetoprotein (AFP) levels were raised both in patients with HB (100%; most AFP levels were very high) and in patients with HCC (69%), although 15% of patients with HCC had low or normal AFP levels. CONCLUSIONS: It appeared from the current results that HCC is more prevalent among children in South Africa compared with the children in more developed countries, although their rates were lower that the rates noted in adults. A collaborative approach will be required to improve their diagnosis and management.

Malawi pilot study of Burkitt lymphoma treatment.

BACKGROUND: Burkitt lymphoma (BL) accounts for 50% of childhood cancer in Malawi. Lack of resources precludes the use of new successful treatment approaches such as the LMB 89 group B protocol, which cures >80% of children with stage III BL with high dose chemotherapy and matching supportive care. Our objective was to achieve a good cure rate in Murphy stage I-III BL with manageable toxicity in Malawi at a drug cost of <1000 US dollars per patient. PROCEDURE: The intensity and toxicity of the LMB 89 group B protocol was reduced and adapted to Malawi realities. All stages received the same treatment. Children with suspected BL in the period July 1997-November 1999 were subjected to abdominal ultrasound, a tumor biopsy and/or fine needle aspirate (FNA) and bone marrow (BM), cerebrospinal fluid (CSF), and peripheral blood examination. HIV seropositive children were excluded. Endpoints are projected event free survival (EFS) at minimum 1 year, blood and gastro-intestinal tract toxicity, and risk for and severity of infections. RESULTS: Forty-four children were eligible for treatment and analysis. Their median age was 7.2 years, M:F ratio 1.4:1 with 10 stage I, 5 stage II, and 29 stage III patients. Projected Kaplan-Meier EFS for all was 57% (CI 41-73) at 1 year with 90% EFS in stage I and 52% EFS in stage III. The survival curve remained stable at 500 days. Toxicity and delays in appropriate supportive care contributed to ten deaths during treatment. Local recurrent tumor caused five and CNS recurrence one death. Two children died from progressive disease. The incidence of severe (grade 3 and/or 4) hematologic toxicity varied from 13% to 36%, gastro-intestinal toxicity (GIT) from 2% to 17%, and infections from 7% to 41% per chemotherapy module. CONCLUSIONS: It is possible to administer less intense and less costly multiagent chemotherapy to children with BL in a developing society with acceptable EFS rates. Adequate supportive care of the at-times associated severe toxicity must be made available to better the results.