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.     

Eyelid tumors anmd renal transplantation

The high incidence of malignant neoplasms in renal transplant recipients and other immunosuppressed patients is well recognized. A large proportion of these neoplasms are skin cancers. The frequent occurrence of other ocular complications, such as cataract, elevated intraocular pressure, hypertensive retinopathy, cytomegalovirus retinitis, and herpetic keratitis in patients after kidney transplant, has also been described. This report presents the clinical and histopathologic features of eyelid involvement by keratoacanthoma and squamous cell carcinoma in two patients after renal transplantation and alerts ophthalmologists to the potential for this association.     

Familial jejunal atresia with renal dysplasia

Although jejunal atresia occasionally may occur with a familial pattern, an association with renal disease has not been described. The authors report on three family members treated over two generations, all of whom had both proximal jejunal atresia and renal dysplasia. This association was most likely inherited as an autosomal dominant trait.     

Inherited diseases of the glomerular basement membrane

The inherited diseases of the glomerular basement membrane include Alport's syndrome (AS), nail-patella syndrome, and thin basement membrane nephropathy. Classical AS is inherited in an X-linked manner and accounts for approximately 85% of the cases. Its manifestations include hematuria, sensorineural hearing loss, ocular defects, and a progression to renal failure. A defect(s) in the alpha 5 (IV) chain of type IV collagen is believed to be the etiology of classic AS, and alterations in its encoding gene localized to the X-chromosome have been elucidated. Although isolated cases of anti-glomerular basement membrane glomerulonephritis have been reported following renal transplantation in patients with AS, it is considered an effective form of renal replacement therapy. Less is known regarding the genetic basis of the autosomal-dominant form of AS, which apparently accounts for the remaining 15% of the cases. Nail-patella syndrome is characterized by nail dysplasia, patellar hypoplasia or aplasia, and nephropathy. It is inherited in an autosomal-dominant fashion with the gene locus assigned to the long arm of chromosome 9. Possible linkage between the COL5A1 gene and the gene for nail-patella syndrome has been suggested. Approximately 30% of the patients progress to end-stage renal failure. Renal transplantation has been successful in treating patients who progress to end-stage renal failure. Thin basement membrane nephropathy is an autosomal dominant trait that accounts for approximately 30% of the cases presenting as persistent, asymptomatic hematuria. The cause of thin basement membrane nephropathy is unknown at present. No decline in renal function is associated with thin basement membrane nephropathy.     

Sarcomatoid renal carcinoma with angiosarcomatoid component. Light microscopic and immunohistochemical study

We describe a case of primary renal pelvic carcinoma which showed an unusual histologic pattern of anastomosing blood-filled channels lined by atypical cells. This angiosarcomatoid pattern merged with solid areas typical of renal carcinoma. Immunoperoxidase stains for cytokeratin and epithelial membrane antigen were positive in both the angiosarcomatoid and typical carcinomatous areas, while stains for factor VIII-related antigen and desmin were negative. Since primary renal angiosarcomas are rare neoplasms, the diagnosis of sarcomatoid renal carcinoma should be considered in primary renal neoplasms which show this angiosarcomatoid pattern.     

Detection of anti-lipoarabinomannan antibodies for the diagnosis of active tuberculosis

Patients with acquired cystic kidney disease (ACKD) are at an increased risk of renal neoplasms. Frequent tumors are adenomas and renal cell carcinomas. However, renal oncocytomas may occur in patients with ACKD. Little is known about oncocytomas of the native kidney following renal transplantation. By means of B scan ultrasonography, a solid and echo-inhomogeneous renal mass was incidentically observed in the right native kidney of a 28-year-old female patient with ACKD 4 years following renal transplantation. A nephrectomy was performed. The histological examination revealed a renal oncocytoma. The increased prevalence of neoplasms in the case of ACKD and following renal transplantation requires careful monitoring of the patients concerned. In very rare cases a renal oncocytoma may develop in the native kidney after renal transplantation.     

Low density lipoprotein of synovial fluid in inflammatory joint disease is mildly oxidized

The histologic diagnosis of adult renal epithelial neoplasms with prominent eosinophilic cytoplasm (renal oncocytoma, chromophobe renal-cell carcinoma (RCC), eosinophilic variant of clear-cell RCC, eosinophilic variant of papillary RCC, and collecting duct carcinoma), could be problematic in some cases because of overlapping morphologic features. Precise diagnosis is essential, however, because it often connotes a distinct biologic behavior. Proliferative activity has not been specifically investigated in this spectrum of renal tumors, so we studied the MIB-1 proliferation index in 20 renal oncocytomas, 12 chromophobe RCCs, 9 eosinophilic variants of papillary RCCs, and 13 eosinophilic variants of clear-cell RCCs. Our purpose was to identify the biologic potential of these renal tumors on the basis of MIB-1 tumor proliferation index and to ascertain whether that index had diagnostic value. Overall, nuclear grade correlated with MIB-1 tumor proliferation index (P=.03). The mean proliferation index progressively increased from renal oncocytomas (0.3) to chromophobe RCCs (0.8) to eosinophilic variants of papillary RCCs (2.2) to eosinophilic variants of clear-cell RCCs (4.1) (P=.002). None of the renal oncocytomas or chromophobe RCCs had an index greater than 2, whereas 8 of 13 eosinophilic variants of clear-cell RCCs had an index greater than 2; in 5 of these, it was more than 3. Thus, in the differential diagnosis between renal oncocytoma/chromophobe RCC and eosinophilic variant of RCC, an MIB-1 index of greater than 3 with appropriate morphologic correlation would strongly support the diagnosis of the latter. We also concluded that the progressive increase in MIB-1 tumor proliferation index across the spectrum of granular renal-cell neoplasms parallels the emerging data in the current literature concerning the biologic potential of adult renal epithelial tumors and justifies histologic categorization of adult renal epithelial neoplasms.     

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors

BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.     

Genetic testing in presymptomatic diagnosis of multiple endocrine neoplasia

Multiple endocrine neoplasias (MEN) are familial diseases characterized by endocrine neoplasms and transmitted in an autosomal dominant manner. In MEN type 1, the major lesions affect parathyroid glands, pancreatic islet cells and anterior pituitary. The MEN-1 gene has been mapped to chromosome 11q13 and a set of DNA-polymorphic markers localized close to this region provides a useful tool for presymptomatic diagnosis in MEN-1 families. MEN type 2 refers to the inherited forms of medullary thyroid carcinoma (MTC) associated or not with pheochromocytoma and hyperparathyroidism. In MEN-2, germinal mutations of the C-RET proto-oncogene which is localized on chromosome 10q11 have been found in the three clinical and allelic forms of the syndrome respectively, MEN-2 type A, B and familial isolated MTC. Mutations of C-RET are found in more than 90% of MEN-2 patients and genetic screening leads to accurate risk evaluation in families and consequently a preventive treatment of MTC and adrenal neoplasms. Recent discoveries on MEN syndromes and related familial endocrine disorders have a major clinical impact and allow a better understanding of the physiological pathways involved in familial as well as in sporadic endocrine tumor pathogenesis.     

A comparison of A103 and inhibin reactivity in adrenal cortical tumors: distinction from hepatocellular carcinoma and renal tumors

Distinguishing adrenal cortical neoplasms from either hepatocellular carcinomas or renal tumors can be difficult. Two recently described antibodies, A103 and inhibin A, are most often reported to be reactive with adrenal cortical neoplasms but with neither hepatocellular carcinoma nor renal cell carcinoma. To compare the sensitivity and specificity of these two antibodies in the diagnosis of adrenal cortical tumors, we stained 22 adrenal cortical adenomas, 4 adrenal cortical carcinomas, 25 hepatocellular carcinomas, and 43 renal tumors, including 33 renal cell carcinomas and 8 oncocytomas, with the A103 and inhibin A using an avidin-biotin complex technique. Fifteen (68%) of 22 adrenal adenomas and 2 (50%) of 4 adrenal cortical carcinomas were reactive with A103. Nineteen (86%) of 22 adrenal adenomas and 3 (75%) of 4 adrenal cortical carcinomas were reactive for inhibin A. None of the renal tumors or hepatocellular carcinomas reacted with A103, but 1 (4%) of 25 hepatocellular carcinomas (a high-grade pleomorphic tumor) and 1 (2%) of 43 renal tumors (a clear-cell renal cell carcinoma) were reactive with inhibin A. The cytoplasmic reactivity for A103 in adrenal tumors was coarsely granular and most common in clear-cell areas. Reactivity for inhibin was either cytoplasmic or membranous and stained both clear-cell and granular areas. We conclude that both antibodies are useful in the immunohistochemical diagnosis of adrenal cortical neoplasms and that A103 is slightly more specific and inhibin slightly more sensitive.     

Renal tubular acidosis and deafness: report of a large family

The syndrome of distal renal tubular acidosis (dRTA) and sensorineural deafness has been reported in consanguineous families and is believed to be inherited in an autosomal recessive pattern. All affected patients also have nephrocalcinosis. We report here a family with 6 of 12 children affected with this syndrome. The parents are unaffected and are not blood related. This is the largest family described to date with distal renal tubular acidosis and sensorineural deafness.     

Molecular genetic insights into cardiovascular disease

The recent application of molecular genetic tools to inherited forms of cardiovascular disease has provided important insight into the molecular mechanisms underlying cardiac arrhythmias, cardiomyopathies, and vascular diseases. These studies point to defects in ion channels, contractile proteins, structural proteins, and signaling molecules as key players in disease pathogenesis. Genetic testing is now available for a subset of inherited cardiovascular diseases, and new mechanism-based therapies may be available in the near future. This remarkable progress and the implications it may have for more common forms of cardiovascular disease are reviewed here.     

Inhibition of epithelial Na+ currents by intracellular domains of the cystic fibrosis transmembrane conductance regulator

Mucormycosis historically has caused substantial morbidity with high mortality in renal transplant patients with disseminated and/or rhinocerebral infection and in patients with gastrointestinal illness regardless of predisposing conditions. We report the first successful treatment of gastric mucormycosis in a renal transplant recipient and review presumed pathogenic mechanisms of mucormycosis in renal transplant recipients as well as historical data.     

Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.     

Mokken scaling of the Epworth Sleepiness Scale items in patients with the sleep apnoea/hypopnoea syndrome

Jeune syndrome (asphyxiating thoracic dystrophy) is a rare inherited disease which is fatal in early childhood in 70% of cases. Severe renal involvement may occur and lead to chronic renal insufficiency in patients who survive respiratory failure. Therefore the opportunity to perform kidney transplantation is quite rare. We report a successful cadaver renal transplantation in a 10-year-old boy with Jeune syndrome type 2.     

Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance

We describe a familial form of renal Fanconi syndrome characterized by hypercalciuria, low-molecular-weight proteinuria, nephrocalcinosis and slowly progressive renal failure. Males are much more severely affected than females. The patients studied included 15 males and 10 females, and five families with up to three generations involved. Studies of the two largest families described here have already shown that their disease is inherited on the X-chromosome. The series contains the two unrelated patients originally described by Dent and Friedman in 1964 as 'hypercalcuric rickets'.     

Complications of percutaneous ethanol ablation

Percutaneous ethanol injection therapy performed with sonographic visualization is a steadily growing therapeutic method that can be used in the ablation of solid and cystic masses in a variety of anatomic locations. Ethanol has been used for many years as an angiographically administered agent for vascular embolization of tumors such as hepatic and renal neoplasms. It was first used as a percutaneously injected agent for the sclerosis of renal cysts. Local infiltration or intravascular injection of ethanol leads to cell death by causing cell membrane lysis, protein denaturation, and vascular occlusion. Because of the initial success in the sclerosis of renal cysts, percutaneously injected ethanol is now used in the ablation of hepatic cysts and solid tumors, such as hepatocellular carcinomas. As a treatment agent, ethanol combines the benefits of being widely available, inexpensive, efficacious, and relatively easy to administer. Optimal results require that the radiologist have considerable experience in ultrasonographic scanning techniques and facility with percutaneous needle insertion under real-time visualization. Alternatively, the radiologist may choose CT as a method to visualize needle placement. Percutaneous ethanol injection therapy usually is an effective alternative to conventional surgical resection of liver lesions and has a low complication rate. We present two patients in whom hypotensive complications occurred during percutaneous ethanol injection therapy and discuss the likely causative mechanisms.     

Abdominal sonography in asymptomatic executives: prevalence of pathologic findings, potential benefits, and problems

Abdominal ultrasonography was performed on 1000 asymptomatic executives over a period of 6 months as part of a comprehensive health examination. The use of ultrasonography in these persons was evaluated with regard to the prevalence and variety of pathologic conditions detected as well as potential benefits, risks, and use as a screening tool. Significant sonographic diagnoses included renal cell carcinoma in four patients (0.4%) and abdominal aortic aneurysm in four patients (0.4%). Abdominal sonography performed on 7925 asymptomatic executives over a subsequent 2 1/2 year period led to detection of 23 (0.3%) additional renal cell carcinomas. The prevalence of renal cell carcinoma in this population is substantially greater than that of the general population. Abdominal sonography facilitates detection of occult renal neoplasms and aortic aneurysms. The cost effectiveness and potential use of sonography as a screening tool remains to be determined, however, given the relatively low overall prevalence of these pathologic conditions.     

Environmental tobacco smoke exposure in the home and worksite and health effects in adults: results from the 1991 National Health Interview Survey

It is generally accepted that genetics play a significant role in the pathogenesis of hypertension. Since hypertension often follows kidney transplantation, candidate genes have been sought and found in the kidneys of rats and humans. One well-recognized, inherited influence on blood pressure (BP) occurs via abnormal renal sodium handling in vivo. Further, abnormal renal sodium handling is seen in isolated kidneys of genetically hypertensive rats. People who have a relative inability to handle a sodium load properly, and retain it inappropriately, often develop high BP and are referred to as "salt-sensitive". More than half of patients diagnosed with essential hypertension are salt-sensitive. In contrast to the deleterious effects associated with high sodium intake, many believe that ingestion of more potassium, calcium, and magnesium may influence BP favorably. The beneficial effects of these ions work, at least in part, through an effect on sodium balance, i.e. a diuretic influence. In support of this concept, they lower BP more effectively in salt-sensitive hypertensives. Refined carbohydrates and saturated fats are also associated with salt retention and hypertension. Thus, dietary factors, working directly on their own and/or indirectly via effects on genetic mechanisms, may alter BP favorably or unfavorably.     

Charcot-Marie-Tooth disease: a new paradigm for the mechanism of inherited disease

Recent work has identified the genes and mutational mechanisms that underlie several inherited diseases of the peripheral nervous system and has provided both the first genetic rationale for classification of these disorders and an insight into their biological basis. These studies have yielded some surprising findings, including the discovery that two very different mutational mechanisms (duplication and point mutation) can result in a similar clinical phenotype in Charcot-Marie-Tooth disease type 1A, and that mutations involving the same gene can give rise to different clinical phenotypes.