Morphological patterns of paediatric solid cancer in Lagos, Nigeria

With successful implementation of the Expanded Programme on Immunisation (E.P.I.), many Nigerian children are protected against the common infections of childhood which claim their lives within the first decade of existence. Recent observations tend to show that paediatric cancer may start to play a significant role in childhood morbidity and mortality. Therefore, this study analyses 372 cases of paediatric solid malignant tumours received at the Department of Morbid Anatomy, Lagos University Teaching Hospital (L.U.T.H) from 1974 to 1988. Considering all the age groups together, the commonest malignant tumour is lymphoma (32.8%), of which Burkitt's lymphoma accounts for 19.6%. Retinoblastoma and Wilms' tumour represent second and third commonest solid cancers respectively. There is, however, slight variation in the different age groups. For example, in the age group 1-4 years, malignant lymphoma is an uncommon disease representing only 11.0% of all cancers whilst retinoblastoma (34.5%) and nephroblastoma (24.0%) together account for 58.6%. Epithelial cancer although rare in children, represents 12.6% in the 10-14 year age group. There is a higher incidence of this tumour when compared to the other age groups (less than 1 year, 1-4 years and 5-9 years). Intracranial neoplasia are uncommon, representing only 2.0%. The overall incidence of solid malignant tumours in children aged 0-14 years in Lagos is estimated to be 22 per million person years.     

Treatment of acute thrombosis of the system of the inferior vena cava

Burkitt's lymphoma in Africa may be curable by chemotherapy alone; in nonendemic regions results are reportedly less favorable. Fifty-four Americans with Burkitt's lymphoma were treated with two sequential combined treatment regimens that incorporated therapeutic approaches from clinical trials in Africa. Four patients died during induction therapy, and 48 of the remaining 50 achieved complete remissions. Twenty-two relapsed at a median of three months from the start of therapy. The overall two-year actuarial survival was 54 percent: younger patients ( less than 12 years old) and patients with minimal tumor burden (stages A, B and AR) had significantly better survivals than older patients (P less than 0.02) and patients with advanced abdominal tumors (stages C and D) (P less than 0.01). No differences in survival were detected between patients treated at the National Institutes of Health and those treated in regional institutions on either protocol. Complete response rates, relapse frequency and survival in American patients are similar to results in Africa.     

Burkitt-type lymphoma in France among non-Hodgkin malignant lymphomas in Caucasian children

In a retrospective analysis of 87 cases of Caucasian childhood non-Hodgkin malignant lymphoma (NHML) from Lyon, France, all the case were diffuse lymphomas, but 47 were diagnosed as monomorphic small non-cleaved NHML, pathologically indistinguishable from Burkitt's lymphoma (BL). BL could then be the most frequent childhood lymphoma in France. This homogeneous series allows better definition of the characteristics of BL within NHML. Age distribution is similar to that of endemic BL, with a sex ratio of 3.7/1. Abdominal masses are initially present in 68% of the cases, whereas jaw is involved in only 4%. The disease is characterized by its overwhelming evolution in the absence of therapy. However, complete remission (CR) is usually obtained after the first chemtherapy regimen. Most relapses occur at 3-8 months. Death could be related to cerebrospinal fluid (CSF) involvement, local recurrence or secondary marrow involvement. Ninety per cent of the patients alive with no evidence of disease (NED) 8 months after CR can be considered as definitely cured. Our study on Caucasian children with NHML indicates that, from histological and clinical criteria, nearly half the cases are very similar to African BL. Even though EBV rarely associated with our cases, BL could be a worldwide lymphoma.     

Witzel gastrostomy in gynecologic surgery

From 1965 to 1990, 46 cases of malignant nasopharyngeal tumours were diagnosed in Iceland. The incidence rate is as low as in other Western countries, 0.6/100,000 per year. Histo-pathological diagnosis were as follows: Undifferentiated carcinoma 45%; squamous cell carcinoma 30%; non-keratinizing carcinoma 7%; and plasmacytoma 9%; lymphoma 7%; rhabdomyosarcoma 2%. Four per cent were diagnosed at stage I, 13% at stage II, 29% at stage III and 54% at stage IV. The overall crude survival at 10 years from diagnosis was 28.3%. The following factors were found to have a prognostic value: Stage of disease, size of tumour (T-classification) and age at diagnosis. Nodal stage (N-classification) alone and sex were not found to be prognostic factors. There was no difference in survival among the different WHO types of cancer. Patients with carcinoma were all treated with radiotherapy. The survival of those who received more than 60 Gy was better than of those who received 60 Gy or less (p = 0.04).     

Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid

To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse.     

The imaging of Burkitt's and Burkitt-like lymphoma

We describe the radiological findings at presentation and follow up in 24 adult patients with Burkitt's and Burkitt-like lymphoma, age range 17-67 years. This is an older age group than previously described in North American series, but the clinical and imaging characteristics appear similar. Disease confined to the abdomen was seen in 12 (50%) at presentation, of whom 11 had bowel or mesenteric tumours. Of those with bowel involvement, five patients had disease that had arisen in the ileocaecal region. Intra-abdominal disease was large volume (greater than 5 cm) in the majority of patients. Four patients (17%) had small isolated masses in the head and neck region, two (8%) had isolated unilateral axillary lymphadenopathy. Six (25%) patients presented with disseminated disease, all with hepatic and/or splenic involvement, intra-abdominal and peripheral lymphadenopathy. Three of these patients with disseminated disease were human immunodeficiency virus (HIV) positive. Neurological symptoms were present in a total of five patients at presentation or relapse but positive imaging findings were present in only two patients who had MRI. Computed tomography (CT) head scans performed in four patients were normal. Disease recurrence most commonly occurred within the abdomen.     

Dural sinus thrombosis in children with cancer

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.     

The so-called white Burkitt's lymphoma

A case of histopathologically proven Burkitt's lymphoma is described with special reference to clinical, serological and immunological features. This case report is followed by a review of the literature on the problem of American and African Burkitt's lymphoma. We can state that there is good correspondence between the white and black Burkitt's lymphomas with regard to epidemiology, histopathology, therapy and some immunological aspects. The two groups differ from each other in age, primary tumor manifestation, involvement of the bone marrow at time of diagnosis and quantitatively in the positive EBNA-test. It is therefore suggested that black and white Burkitt's lymphoma are not different diseases but different patterns of one disease.     

Burkitt's lymphoma in adults with and without human immunodeficiency virus infection: a single-institution clinicopathologic study of 75 patients

BACKGROUND: Burkitt's lymphoma (BL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma (NHL) in the general population and for 35-40% in the setting of human immunodeficiency virus (HIV) infection. The authors report a 9-year single-institution experience with 75 adult BL patients (46 with and 29 without HIV infection) and compare the clinical and pathologic features of the disease in the two groups of patients. METHODS: Between May 1987 and June 1995, 131 patients with HIV infection and systemic NHL were diagnosed and treated at the National Cancer Institute in Aviano, Italy. In 46 cases (35%), the diagnosis was BL. During the same period, 29 of 1004 HIV negative NHL patients (2.8%) were diagnosed with BL and treated at the same institution. RESULTS: No statistical differences were found in the general characteristics of the two groups at the time that BL was diagnosed. Complete response rate was significantly lower for patients with HIV infection than for those without HIV infection (40% vs. 65%, P = 0.03). The median overall survival was significantly shorter for patients with HIV infection (7 months vs. not yet reached, P = 0.0001). However, the disease free survival (DFS) at 4 years was identical for the two groups of patients (74% for HIV positive patients vs. 73% for HIV negative patients, P = 0.70). CONCLUSIONS: The data from this study show that patients with BL with and without HIV infection share similar clinicopathologic characteristics at presentation. Although the median overall survival is significantly shorter for patients with HIV infection, the DFS is identical for both groups.     

Indications and relative indications for stem cell transplantation in non-Hodgkin's lymphoma

High dose chemotherapy with or without total body irradiation and autologous stem cell rescue has proven to be effective treatment to cure patients with relapsed intermediate grade and high grade non-Hodgkin's lymphoma. Important factors for selection of candidates most likely to do well with these approaches include patients whose disease is responsive to conventional therapy and those who have minimal disease volume at the time of transplant. The treatment-related mortality of autologous stem cell transplantation has diminished from 20% to less than 5% with improved supportive care and selection of patients with less advanced disease. Although the treatment-related mortality of allogeneic stem cell transplantation may be as high as 20-40%, a graft versus lymphoma effect may decrease relapse with the result that overall survival is not substantially different between autologous and allogeneic transplantation. The definitive indications for stem cell transplantation include patients who have relapsed with intermediate or high grade NHL. Relative indications include intermediate/high grade non-Hodgkin's lymphoma patients, "high risk" first complete remission (CR), resistant relapse; low grade non-Hodgkin's lymphoma in sensitive or resistant relapse, advanced disease (sensitive or resistant relapse, transformation), first CR (younger patients). Relative contraindications include specific patient profiles such as bulky high grade lymphoma which progresses on appropriate conventional therapy, poor performance status, active serious infection, serious cardiac, renal, pulmonary or liver dysfunction, active, central nervous system (CNS) disease unresponsive to cranial irradiation/intrathecal therapy. For patients with previous marrow involvement or active marrow involvement at the time of harvest or transplant, "purged" autografts, peripheral blood stem cell transplantation and allografts have been used successfully.     

Correlation of renal images on bone scan and intravenous pyelogram

In a controlled study in Ghana, the hemoglobin electrophoretic pattern in 112 patients with Burkitt's lymphoma was compared to that of their nearest neighbor controls of the same age, sex, and tribe, as well as their sibling controls. Analysis of the data obtained did not show any statistically significant protective advantage for sickle cell trait against Burkitt's lymphoma. Hemoglobin C trait appeared to offer a slight protective advantage (p less than 0.1), but this did not reach statistical significance. These results do not disprove the malaria co-factor hypothesis in the etiology of 0urkitt's lymphoma, but deprive it of an additional indirect evidence in its favor.     

An aggressive case of Burkitt's lymphoma with t(8;14) and c-myc rearrangement transformed from CD5+ B-cell lymphoma

We experienced a case of Burkitt's lymphoma showing an unusual surface phenotype, CD5 expression, at an early stage of the disease. Initially, this patient showed massive abdominal para-aortic lymph node swelling which rapidly developed into leukemic change. Based on the clinical course and cytogenetic features of lymphoblasts in the bone marrow, which showed t(8;14) and c-myc gene rearrangement, the patient was diagnosed with Burkitt's lymphoma. Combination chemotherapy induced short-term remission, but central nervous system (CNS) involvement developed, followed by a regrowth of lymphoma cells in the bone marrow. The bone marrow at the end stage showed monotonous expansion of large cells with conspicuous vacuolation in the basophilic cytoplasm. The initial lymphoma cells showed pan-B markers and were CD5 positive but weakly CD10 positive; however, the lymphoma cells obtained from the bone marrow at the terminal stage did not express CD5. The chromosomal t(8;14) was seen, and identical rearrangement of immunoglobulin heavy chain joining gene and c-myc gene were detected by Southern blot analysis in the bone marrow lymphoblasts throughout the clinical course. This case is evidence that remarkable transformation of CD5-positive lymphoblasts to CD5-negative lymphoblasts occurred in an identical clone of Burkitt's lymphoma.     

Anorexia and lycanthropy ++: grandiosity and fall

Epstein-Barr virus (EBV) is linked to a spectrum of human diseases including epithelial and lymphoid malignancies in which it exists predominantly in a latent state. EBV is capable of establishing replicative infection at oropharyngeal and genital sites. Replicative EBV infection also occurs in oral hairy leukoplakia, in EBV associated lymphoproliferative disorders, and to a minor degree in nasopharyngeal carcinomas. Recent evidence also suggests that EBV replication, also, may be associated with AIDS related lymphomas and Hodgkin's disease. However it is widely believed that virus in circulating B-lymphocytes and in B-cell malignancies is stringently latent. We now show that by Southern blot analysis we can detect replicative forms of virion DNA in 14.5% (8 of 55) of EBV-positive Burkitt's lymphoma biopsies. This may be the explanation for the elevation of the titres of lytic cycle EBV antigens that is associated with presentation and relapse of EBV associated Burkitt's lymphoma.     

Epstein-Barr virus and associated diseases. Course of Medical Virology, Institut Pasteur, 1995/1996

The Epstein-Barr virus (EBV) is an ubiquitous virus infecting nearly the entire adult human population. The EBV is closely associated with rhinopharyngeal cancer in Southern China and Northern Africa. Three geographic subtypes of EBV have been identified to date. They differ by their nuclear antigene EBNA2. The EBNA2 AC strains predominate in Asia; EBNA2 AD strains predominate in the United States; EBNA2 B strains have all been identified in black Africa. Burkitt's lymphoma is the most frequent tumor in children aged 5 to 9 years in equatorial Africa. A prospective study in 42,000 children in Ouganda demonstrated that children who develop Burkitt's lymphoma have severe EBV infection during the first months of life. Very early EBV infection observed in North or equatorial Africa increases the risk of Burkitt's lymphoma by 20-times that in Europe. Hyperendemic malaria observed in the equatorial zone increases the incidence of tumors by a factor of 20. An association between EBV and rhinopharyngeal cancer is a constant feature only in South China, in North and East Africa, as well as in arctic regions as cases of carcinoma not associated with EBV infection have been reported in Greece. Surveys in the Democratic Republic of China concerning several hundred thousand persons have shown that serum IgA/VCA allows early diagnosis of cancer. It is estimated that the risk of rhinopharyngeal cancer is 20% in Chinese with high levels of IgA/VCA.     

Serum lactate-dehydrogenase isoenzymes in HIV positive children. A longitudinal study

The impairment of humoral immunity with rapid turn-over of cellular B clones in children with HIV infection is known as well as the conduct of LDH isoenzymes in B cell lymphoproliferative diseases like Burkitt's lymphoma. Therefore, serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes have been evaluated twice (within 12 months) in 11 children with HIV infection with respect to a control group (30 subjects). Furthermore, the relationship between those and other clinical and immunologic parameters (total lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta CDC 1987) has been studied. HIV infected children have shown a significant decrease in LD1 rates, which was directly correlated to CD4/CD8 values. After the follow-up, this correlation became even more significant. Thus, these findings may suggest the usefulness of LDH isoenzymes evaluation as a marker of disease activity in children with HIV infection.     

Tumors of childhood in Ibadan, Nigeria (1973-1990)

Childhood neoplasms provide a fertile field for epidemiological research and afford a unique opportunity for studying possible mechanisms of carcinogenesis. The present study reviews 1881 malignant childhood neoplasms in children less than 15 years of age seen in the University College Hospital, Ibadan during an 18-year period. The male-to-female ratio was 1.4:1 and modal age of occurrence was 10 years. The most common childhood neoplasms were lymphomas (45.4%), retinoblastomas (9.7%), and malignant renal neoplasms (8.5%). Burkitt's lymphoma constituted 92% of all lymphomas and 37% of all childhood tumors. Comparison of two clinicopathological studies of childhood cancer in Ibadan between 1960-1972 and 1973-1990 revealed a dramatic upsurge in the relative frequencies of intracranial neoplasms, leukemias, renal neoplasms, and retinoblastomas, with a decline in the relative frequencies of bone neoplasms and Burkitt's lymphoma during the latter period. Whether these changes reflect actual changes in the distribution of childhood cancer in the local population will require further study.     

Hodgkin's disease in patients older than 70 years of age: a registry-based analysis

Between 1973 and 1993, 529 patients aged 15 years and over with Hodgkin's disease (HD) were entered into a lymphoma registry. Twenty-eight cases (1 only diagnosed at autopsy) of histologically proven HD in patients aged 70 years or older were identified. The distribution of sex, 'B' symptoms, histology and stage was not significantly different from that of younger patients, except for the fact that there were no patients aged 70 years or older with lymphocyte predominant HD. Nineteen patients were treated radically, 5 patients palliatively and 4 patients received no radiotherapy or chemotherapy. Three of the 14 patients treated with chemotherapy achieved the planned dose intensity. The cause-specific 5-year survival was 75% for patients aged 15-69 years and 28% for patients aged 70 years and over (logrank chi(2) = 43.7, P < 0.00001). The younger and older groups treated with radical intent had complete response rates of 97% and 74%, respectively (logrank chi(2) = 17.91, P < 0.00001) and relapse rates at 5 years of 27% and 56%, respectively (logrank chi(2) = 4.86, P = 0.0275). The main reason for the poorer prognosis of patients aged 70 years and over was the increasing difficulty of chemotherapy delivery associated with advancing age.     

Burkitt's lymphoma mimicking an acute dentoalveolar abscess

Burkitt's lymphoma is a monoclonal proliferation of B lymphocytes classified histologically as a poorly differentiated lymphocytic lymphoma. The jaw and retroperitoneal structures are the most commonly involved sites. Prognosis is highly dependent on the stage of the disease. In some cases, the first manifestation of Burkitt's lymphoma is in the jaws, and symptoms may be misdiagnosed as infection. Dental radiographs can play an important role in the diagnosis. A case of a peculiar Burkitt's lymphoma involving the mandible that was misdiagnosed as an acute dentoalveolar abscess is presented.     

Outcomes and failure patterns in childhood craniopharyngiomas

Past studies of craniopharyngiomas in children have shown overall survival (OS) up to 95% at 5 years and 80% progression-free survival (PFS) at 5 years, although many of these series predate modern neuroimaging and current therapeutic management. Moreover, little mention has been made of failure patterns for craniopharyngioma in children. To obtain a contemporary assessment of outcome among pediatric craniopharyngioma patients, and also to determine the failure patterns for this tumor, we completed a retrospective study of a consecutive cohort of all children with craniopharyngioma diagnosed at the Johns Hopkins Hospital from 1980 to 1996. Resection was performed in 30 children, in 8 of whom gross total resection (GTR) was achieved. Initial treatment took the form of GTR followed by observation for 8, subtotal resection (STR) plus observation in 11, and STR followed immediately by radiotherapy in 8. The timing of radiotherapy following STR was unclear for 3. OS was 95.2% (SE= 4.7%) at 5 years, with only 2 children dying after 4 years from diagnosis. Five-year PFS was 59.4% (SE=10.2%). Before surgery, 19 children had visual loss and 15, endocrine deficits; after surgery, 21 children had visual loss and 29, endocrine deficits. Median time to relapse was 0.98 years (SD=2.5 years). Radiographic (n=4) and clinical (n=7) relapses did not differ in time to progression (P=0.32), but radiographic relapses were significantly associated with age at diagnosis less than 5 years (P=0.02). Degree of resection was not significantly associated with PFS (P=0.32) or with postoperative visual or endocrine deficits. Absence of calcification on diagnostic neuroimaging (n=8) was significantly associated with improved PFS [5-year PFS 100% vs. 42.9% (SE=14.7%), P=0.02], even when adjusted for extent of resection (P=0.03). Preoperative visual loss was predictive of postoperative visual loss (P=0.03). Survival for children diagnosed with craniopharyngioma in the current era is outstanding, even with relapse, although postoperative visual and endocrinological morbidities are high. Failures occurred both radiographically and clinically, typically in the first 3-4 years after surgery, suggesting a need for close surveillance initially with neuroimaging, particularly in younger children, and also clinical examination. The short times to relapse observed here may stem from a tendency to delay radiotherapy until recurrence. Lack of calcification at diagnosis is associated with a tendency to remain free of relapse.     

Testicular lymphoma: a population-based study of incidence, clinicopathological correlations and prognosis. The Danish Lymphoma Study Group, LYFO

In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens (orchiectomy and/or radiotherapy) was 63.6% (P < 0.05). Median relapse-free survival was 28 and 14 months, respectively. Overall 5-year survival for all cases was 17%. Adverse prognostic factors at the univariate level were stage IV, constitutional symptoms, serum lactic dehydrogenase elevation and performance score (WHO 3-4). It is suggested that the treatment of stage IE/IIE TL should include early CCT and CNS prophylaxis.