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Context.—Like other pathology services in developing settings, pediatric pathology in Africa is faced with major challenges such as limited access to resources and few opportunities for professional advancement. Additionally, the discrepancy between the large burden of pediatric diseases, many of which individually are rare enough to prove challenging to the general pathologist, and the amount of specialized training available compounds the underlying problems and makes the provision of a high-quality service difficult. Pediatric neoplasms in particular are a chief cause for concern among general pathologists practicing in Africa.Objectives.—To provide relevant pediatric pathology information with an emphasis on pediatric malignancies to pathologists practicing in Africa, where children represent a very high proportion of the population and training in pediatric pathology is incomplete.Data Sources.—Authors' experience and relevant literature.Conclusions.—The limitations inherent in working within a low-resource setting may be reduced by thoughtful and purposeful triaging of specimens, prudent use of cytology in facilitating rapid and inexpensive diagnoses, and collaboration within and outside of the continent. Increased investment in and advocacy for child health, including the creation of additional hospitals dedicated to the care of children, are likely necessary to significantly advance children's health in the region.

Context.—Within the continent of Africa few countries have been able to practice pathology at the levels present in Europe and the Americas, and pediatric pathology does not exist as a stand-alone specialty. The author was invited by a colleague from Harvard Medical School, Boston, Massachusetts, to join a group of North American pathologists in presenting a course on the Contribution of Anatomic Pathology for advancing the health of women and children in Africa. The course was held in Ethiopia in June 2011, to review the current state of pediatric pathology in Africa and to provide resources/teaching for improving pediatric pathology services in low-resource settings. Objective.—To provide a succinct description of applicable autopsy techniques and the interpretation of gross, microscopic, and ancillary findings with respect to Africa's need to enhance the health of women and children. The author makes suggestions for obviating possible problems in anticipation of increased demands by national authorities and of public expectations of pathologists who usually have had only general training. Data Sources.—This article is based upon the author's personal experience of practicing pathology in Africa for the past 51 years, which has included visiting pathology laboratories in 9 African countries and interacting with colleagues in 18 additional African countries. The contents of this article are derived from personal observations, recent publications, and information gleaned from Internet sources. Conclusions.—Even without specific training in pediatric pathology, it is possible for pediatric autopsies to be undertaken in Africa and other resource-poor settings, in a manner that facilitates sound decision making for improving the health of women and children.

The clinicopathological spectrum of gastrointestinal (GI) smooth-muscle abnormalities associated with chronic intestinal pseudo-obstruction (CIPO) includes numerous heterogeneous conditions that are often ill-defined and poorly understood. Primary GI smooth-muscle abnormalities include familial and sporadic forms. Secondary involvement of GI smooth-muscle may result from associated GI and systemic conditions, but is less frequent than in adults. This study documents the clinicopathological findings observed in 12 South African patients with unusual forms of visceral smooth-muscle abnormalities not conforming to the diagnostic criteria of known primary visceral myopathies at the Tygerberg and Red Cross Childrens' Hospitals over a 14-year period (July 1985 through January 1999). Congenital muscle defects occurred in 5 patients where layers of bowel-wall muscle were absent or attenuated. Idiopathic fibrosis and ultrastructural features of perinuclear and mitochondrial vacuolisation were noted in 2 patients. A 21-year-old female with long-standing pseudo-obstruction demonstrated diminished immunohistochemical expression of enteric alpha-smooth-muscle actin without associated muscular degeneration or fibrosis. A secondary complication of dermatomyositis (bowel perforation) occurred twice in 1 patient. In 3 further patients (1 each with anorectal malformation, long-segment Hirschsprung's disease, and intestinal neuronal dysplasia), muscle fibrosis appeared during progression of the pre-existing disease. Visceral myopathies are poorly understood conditions that may present with CIPO. Unusual variations occur that do not conform to the usual recognised histological patterns. Secondary involvement may also be more common than anticipated in children. The challenge to further understanding these uncommon conditions lies in timely diagnosis and identification of early, subtle signs. Optimal and extensive application of various diagnostic modalities, including the development of new diagnostic tools, is of considerable importance in identifying hitherto unexplained CIPO due to GI smooth-muscle abnormalities.

In attempting to advance the health of women and children in Africa, practitioners should be cognizant of the history of health care delivery in the continent and the nature of the existing systems. Although autopsies began in Africa several millennia ago, traditional healers have held sway for many centuries and continue to do so for most of Africa's people. The role of laboratory medicine in advancing modern health care has been impeded by its ever-increasing high cost, lack of confidence in the system, lack of adequately trained personnel, and inadequate provision of facilities and training opportunities. This is partly caused by the continent having the highest proportion of young children in the world, an exceptionally heavy disease burden, and a low proportion of tax payers. For laboratory medicine to have its intended effect in making accurate diagnoses, national, minimal standards for certification and practice should be formulated. There should be periodic inspections, rewards for excellence, and opportunities for professional development. It is recommended that laboratory medicine be practiced in a 4-tier system, with the highest in teaching hospitals, and the lowest in primary health care clinics. For the practice of anatomic pathology to advance, an effective referral system and an equitable minimal and maximal workload for each pathologist are needed. The changing dynamics of urbanization, with massive unemployment rates, unhealthy life styles, and the continued role of traditional healers calls for gifted leaders to come to the fore and facilitate internal and external cooperation with diverse health care agencies.

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.

Five childhood malignant ectomesenchymomas are reported from three centers in three countries. The children were all younger than 3 years (four less than 12 months), four were boys, and four tumors were sited in the pelvis or external genitalia. All tumors had distinctive light microscopic features of rhabdomyosarcoma and three also demonstrated small numbers of included neuronal cells. Immunohistochemical studies and transmission electron microscopy revealed the additional presence of neurogenic components in the remaining two patients. An additional epithelial component was found by immunohistochemistry in one tumor, which suggests a pluripotential origin that still requires karyotypic investigation. Aggressive chemotherapy and adequate surgical excision have thus far been effective in providing disease-free follow-up for periods of 7 to 50 months. It is implied that because the biological behavior and morphology closely resemble those of rhabdomyosarcoma and because the neurogenic component is often in...

As the incidence of childhood Castleman's disease (CD) is reported to be rare in Western communities, the recent occurrence of three cases in non-HIV infected prepubertal children stimulated a 10-year (1983-1993) retrospective investigation into the conditions at a children's hospital that serves a predominantly developing community. Retrospective histologic examination revealed six cases of CD among children 3-11 years of age and another five probable cases having histological features of CD without adequate clinical and laboratory data. Three CD cases were associated with malignancy (Kaposi's sarcoma in two and a gastric B cell lymphoma in the other). Two CD cases were plasma cell type, one hyaline vascular, and three intermediate. One child with recurrent plasma cell-type features in a groin node had a Kaposi's sarcoma in the thigh. The five probable cases of CD all had intermediate histological features. Four of the 11 cases being reported came from a geographic locality that provides about 3% of the laboratory's case material and these included both cases that developed Kaposi's sarcoma. All patients who developed malignancy had the plasma cell variant. As all cases have been identified in developing communities, where the disease may often be misdiagnosed as nonspecific reactive lymphadenopathy, and there is an evident association with malignancy, it is recommended that children in these areas with the plasma cell variant of CD be closely monitored for subsequent malignancy.

The significance of dysplastic features in the surgical pullthrough segment of bowel in patients with Hirschsprung's disease (HD) has not yet been clarified. The aim of this study was to evaluate prospectively the ganglionated proximal bowel in 26 patients with HD (January 1988 through January 1991). The significance of dysplastic features and their influence on post operative outcome were evaluated by means of a newly devised histological scoring system based on the morphological features. Functional outcome was assessed clinically at follow-up interview. Comparison was with control specimens from 22 patients undergoing unrelated bowel surgery and a further 5 patients with neuronal intestinal dysplasia (NID). Results indicated a wide spectrum of histologically identified dysplastic features in patients with NID, the ganglionated bowel of HD and controls. Although individual abnormal features were noted in the control group, significant degrees of dysplasia were absent. The overall degree of dysplasia was less striking than that observed in NID and in the 5 patients in whom NID co-existed with HD. Dysplasia of the ENS in residual bowel could be correlated with postoperative dysfunction in 4 out of 5 patients (80%) with HD and features of co-existing NID. In addition, milder symptoms were noted in 50% of patients having a borderline score (5-6/12). This study emphasizes the relationship between clinical obstructive symptoms and a high degree of dysplasia within the ENS. A histological grading system is of value in evaluating the spectrum of abnormal findings and prospectively identifying those with functional significance in patients with NID co-existing with HD.

Acquired Hirschsprung's disease is a rare and controversial form of colonic aganglionosis. Little is known about its aetiology and pathogenesis. We report five cases encountered amongst 173 long-term follow-up patients treated for classical Hirschsprung's disease between 1957 and 1990 at the Red Cross Children's Hospital, Cape Town, and review the current literature. The clinical and pathological findings of the cases have been studied to explore possible aetiological mechanisms. Our cases, like most of those previously reported, developed obstructive symptoms and acquired aganglionosis in pulled-through bowel which had been previously confirmed as ganglionated. Two patients had histological evidence of hyaline fibrosis of blood vessels in the segment of bowel with acquired aganglionosis. Such fibrosis and other features attributable to regional hypoxia were not found in the other three cases. It is suggested that ischaemia with fibrosis may have a pathogenetic role in some, but not all, cases of acquired Hirschsprung's disease. A plea is made for patients developing recurrent symptoms of Hirschsprung's disease, after adequate surgical correction, to be fully studied with repeated sequential biopsies in order to gain a better understanding of the entity.

Primary pulmonary tumors are infrequent in childhood, therefore an accurate diagnosis and treatment is often delayed. We review the English language literature and report the clinical and pathological features of eight tumors arising in the lungs of pre-adolescent children, accessioned between 1960 and 1991 in the pathology department of a children's hospital in South Africa. The ratio of pulmonary primary tumors to secondary neoplasms and to non-neoplastic lesions of the lung examined during this period was 1:5:60. Over the last 31 years we received three plasma cell granulomas, two pleuro-pulmonary blastomas, a mucoepidermoid carcinoma, an endobronchial fibrosarcoma, and a hemangioma. All patients presented with cough unresponsive to medical treatment. The incidence and spread of primary lung tumors in children was similar to that reported from other centers. Plasma cell granuloma is the most common primary tumor in the lungs of children. Aggressive behavior is most frequently encountered with pleuro-pulmonary blastoma and rhabdomyosarcoma, and because of their association with cystic lesions careful examination of lungs is required in such cases. Most other malignant neoplasms, such as muco-epidermoid carcinoma and primary fibrosarcoma, are usually of a low grade of malignancy. A decreasing incidence of bronchogenic carcinoma seems to be reported during the first two decades of life.

The clinicopathologic features of three examples of mesenchymal hamartoma of the chest wall are described. The entity has been recorded under a number of names including osteochondroma, osteochondrosarcoma, benign chondroblastoma, mesenchymoma, and chondromatous hamartoma. The condition is manifest at birth or shortly thereafter with deformity of the chest wall and respiratory distress. Radiographic examination reveals a well-defined, partly calcified mass involving one or more ribs. The tumor is composed predominantly of chondroid tissue with large endothelium-lined blood spaces and immature mesenchyme with osteoclastic giant cells and osteoid. We review the literature and suggest that the lesion should be distinguished from aneurysmal bone cyst, chondroma, and other mesenchymal neoplasms. In order to avoid local recurrence the recommended treatment is complete surgical resection.

Two fatal childhood cases of the rare pulmonary blastoma are reported. One was associated with a congenital cystic adenomatoid malformation. Both neoplasms extended to involve visceral pleura and were entirely composed of blastemal and mesenchymal elements without recognizable neoplastic epithelial components. The mesenchymal component in both instances consisted of malignant rhabdomyoblasts, undifferentiated mesenchyme, and differentiated, apparently benign, cartilage. Review of the literature suggests that these features may be specific for the childhood forms of pulmonary blastoma. It is further suggested that pulmonary blastoma, malignant mesenchymoma of the lung, and primary pulmonary rhabdomyosarcoma may have a common pathogenetic origin.

Fifteen light for dates infants and their placentae were compared to 15 well-grown infants and their placentae. The former were born to thin, underweight women while the latter were born to women of normal weight. The light for dates infants were symmetrically growth retarded but not wasted at delivery and their placentae had a reduced weight, volume, chorionic surface area, percentage parenchyma and total villous surface area. The peripheral villous surface area and volume of peripheral villous trophoblast, fetal capillaries and connective tissue was also reduced in the placentae of light for dates infants, suggesting retarded placental growth in the latter half pregnancy. In contrast, the stem villous surface area and volume of stem villous trophoblast, fetal capillaries and connective tissue was similar in both groups of placentae, suggesting the same rate of growth in early pregnancy. There were no differences in the volume of fibrin or infarcts. The ratio of total villous surface area to infant weight, length and head circumference was reduced in the light for dates infants. This may restrict the materno-fetal oxygen exchange, and thereby increase the risk of fetal hypoxia during labour. It is concluded that the placentae of light for dates infants born at term to underweight women are both absolutely and relatively small with a reduced villous surface area.

Background/purpose The aim of this study was to retrospectively evaluate and compare the clinical features, treatment strategy, pathology, and outcome of all patients with hepatoblastoma treated at an African hospital over a 31-year period (1970 to 2001). Methods Forty patients with hepatoblastoma were divided into 3 groups according to the treatment given. Group I (1970 to 1983, 14 patients) had no protocol therapy; group II (1984 to 1988, 6 patients) received protocol treatment according to Children's Study Group (CCSG) guidelines; group III (1989 to 2001, 20 patients) received SIOPEL protocol therapy. All available clinical, surgical, radiologic, and pathologic data were reviewed and analyzed. Results Overall patient survival was as follows: group I, 14%; group II, 50%, and group III, 80%. Deaths in group II were caused by chemotherapy-induced immunosuppression only. Prognostic data for group III showed that all tumor-related deaths could be predicted by identifying multifocal disseminated growth patterns ( P = .001) or vascular invasion ( P = .001) in resected tumors. Of the 40 diagnostic tumor biopsies performed, 2 significant complications (1 death, 1 intraperitoneal tumor seeding) occurred. Histologic criteria evaluating these biopsies were not predictive of overall survival. Conclusions The introduction of protocol therapy has resulted in a marked improvement in survival. Immunosuppression-related sepsis in our setting resulted in unacceptable mortality in patients treated according to CCSG guidelines. A diagnostic biopsy in hepatoblastoma is of value but not without complications. Preoperative chemotherapy followed by complete surgical excision according to International Society of Paediatric Oncology guidelines yields excellent results with a current survival rate of 80%.

Intestinal obstruction and bleeding are uncommon complications of congenital syphilis (CS). A VDRL-positive infant developed incomplete intestinal obstruction and rectal bleeding. Despite conservative management, his symptoms continued. At laparotomy, terminal ileal inflammation and stenosis were demonstrated. He underwent ileal resection and primary end-to-end anastomosis with resolution of his symptoms. Histopathological examination demonstrated heavy plasmacytic infiltration of the lamina propria and submucosa with ulceration of the mucosa, consistent with syphilitic ileitis. This report documents for the first time bleeding from ileal ulcers associated with intestinal obstruction in CS and highlights an unusual presentation of the disease.

The prognosis for patients with adult Wilms' tumor is poor in contrast to pediatric Wilms' tumor. A 23-year-old patient with Wilms' tumor is described who relapsed twice; initially after adjuvant treatment with abdominal irradiation, vincristine, and actinomycin and again after treatment with high dose doxorubicin. The patient was treated with cisplatin and etoposide and is clear of disease 75 months after presentation. She has given birth to a healthy baby.

Sixty-six solid neoplasms occurring in neonates treated at the Red Cross Childrens Hospital over a 34-year period (1957–1991) were reviewed and recalled for long-term follow-up (mean 10.4 years). Associated congenital abnormalities were rare, but chromosomal abnormalities were detected in 3 patients, one of which was familial. Teratomatous germ-cell tumours predominated, followed by neuroblastomas and soft-tissue tumours; 23 had malignant morphologic appearances and 43 were morphologically non-malignant. Seventy-nine per cent presented within the 1st week of life, 41% of these within the first 24 h. Although most sacrococcygeal teratomatous germ-cell tumours were benign, malignancy was present in 2 patients (1 of these presented during the 1st week of life). A further 11 sacrococcygeal teratomas were found on light microscopy to include immature elements and had unpredictable clinical behaviour; 2 of these later metastasized despite adequate surgical clearance.

Protein energy malnutrition of childhood is the most prevalent form of malnutrition in the tropics and throughout the world. Intercurrent infection, particularly gastroenteritis, measles, pneumonia, malaria and schistosomia-sis are known to precipitate overt disease. Associated subclinical vitamin and trace element deficiencies have been found to have an important additional role in augmenting morbidity and mortality attributed to protein energy malnutrition. A state of good health requires an adequate and balanced intake of nutrients. Minimal requirements for essential nutrients are dependent upon diverse physiological and climatic factors such as growth, pregnancy, lactation, illness, exercise, temperature and humidity. In addition individual responses to nutritional deprivation are quite variable. In tropical areas a high proportion of the population subsists on a marginal diet where carbohydrate provides 80%–90% daily energy requirements as compared with 35%–50% of the diet amongst prosperous people in temperate climates. It is widely recommended that dietary protein should approximate 1 g/kg body weight in adults while young children require two to three times this amount. In addition to contributing an average 10% of daily energy requirements, proteins contain essential amino acids that are important in metabolic processes. Tryptophan occurs in very limited quantities in white maize, the staple diet in much of Africa, where pellagra often accompanies protein energy undernutrition. In Asia, where thiamine deficient polished rice is the staple diet, beriberi tends to be associated with protein energy undernutrition.

A familial occurrence of Hirschsprung's disease and neuronal intestinal dysplasia (NID) is reported. Familial occurrence of NID in a parent and long-segment Hirschsprung's disease in two children in a family as well as a further report of NID in monozygotic twins is described. The linkage of these neurodevelopmental conditions is explored and a common etiologic mechanism for the two conditions is postulated.

A retrospective study of the pathology in 86 consecutive autopsies of fatal meningococcal infection in children, performed at the Red Cross War Memorial Children's Hospital during the 19-year period from 1973 to 1991, was undertaken. The most prominent pathological changes found at autopsy were those of an overwhelming bacterial infection with evidence of disseminated intravascular coagulopathy in many organs of the body. The skin, adrenal glands and central nervous system were most commonly involved. Acute myocarditis occurred in 23 cases (27%) and was diagnosed almost exclusively histologically. In only one case was it diagnosed clinically. In addition, the nutritional status and the morphological expression of immune reactivity of our hospital population was better than expected.

The syndrome of degenerative leiomyopathy (DL) causing intestinal obstruction clinically manifests in young indigenous African children as massive megacolon without aganglionosis. We report on a clinico-pathologic study of 18 children seen over a 15-year period. All patients came from the same geographic area. Mean age at presentation was 9.5 years with mean duration of symptoms 4.3 years. The youngest infant was 6 months old. Eighteen children presented with progressive abdominal distention and infrequent stooling; 11 had intermittent diarrhoea and 9 colicky abdominal pain. Gross colonic gaseous distention was noted with proximal extension into the small bowel in 9 and into the stomach and oesophagus in 4. The rectosphincteric reflex was present in all 7 patients studied with anorectal manometry. The diagnosis, confirmed on full-thickness rectal biopsy, showed characteristic features distinguishing it from chronic idiopathic intestinal pseudo-obstruction, progressive systemic sclerosis, and mixed connective-tissue disease of childhood. The bowel was dilated, thin-walled, and on microscopy showed smooth-muscle degeneration and necrosis with replacement fibrosis of muscular layers, displacement of ganglion cells, mild increase in numbers and thickness of nerve fibres, mild inflammatory change, and medial fibrosis of small muscular arteries. Immunohistochemical studies were within normal limits. One child died; 14 have been maintained with a combination of prokinetic agents, low-residue diet, laxatives, and enemas; and 3 patients did not respond to this medical therapy on short-term follow-up. Nine children required surgical intervention — 2 diagnostic laparotomies, 4 volvulus, and 3 adhesive bowel obstructions. Four of these required subsequent surgical procedures. DL is a distinctive entity with a classical clinical and histologic picture whose exact etiology is still obscure, Exploratory laparotomy should be avoided.

The colon in kwashiorkor was investigated by means of rectal biopsy and sigmoidoscopy in 20 children, followed by barium enema in 10 of the children. The colon during the acute phase of the disease showed a surface epithelial atrophy, with infiltration of plasma cells and congestion of small vessels. Viewed under the dissecting microscope, a disorganized vascular pattern was seen in all cases. On recovery from kwashiorkor after 3 to 4 weeks, the abnormal vascular pattern and epithelial atrophy of the colon had returned to normal in most children.

Fifty-seven primary gastrointestinal lymphomas, seen over the 17-year period, 1952 to 1969, have been investigated. Nineteen of the lymphomas arose in the stomach, 34 in the small bowel and 4 in the large bowel. Small-bowel lymphomas in adults occurred almost exclusively in nonwhite patients and 33% of these patients presented as a malabsorption syndrome. Lymphomas of the stomach had a better prognosis (29% survived 5 years) than those of the small bowel (6% survived 5 years). The problems in histologic differentiation from carcinoma and pseudolymphoma are discussed.

Arteriography was performed in 13 children with suspected Wilms' tumour to establish the diagnosis before pre-operative radiotherapy. The characteristic tumour circulation showed thin, elongated and attenuated “spider-leg” vessels and tortuous “corkscrew” vessels in all cases. Abrupt changes of calibre and direction with micro-aneurysms at the bends were common, as were areas of avascularity and delayed emptying of tumour vessels. These appearances successfully differentiated cases of Wilms' lumour from other conditions giving similar urographic findings. An exception was a case of multilocular cystic kidney which had similar arteriographic findings to those noted in Wilms' tumour.