Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease.

We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation of hepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes.

Subdermal fibrous hamartoma of infancy: pathology of 40 cases and differential diagnosis.

Forty subdermal fibrous hamartomas of infancy occurred in 29 males and 11 females who were 7 months to 4 years of age at surgery. At least 4 were congenital. The lesions were situated in axilla, chest wall, and breast (17 cases); abdominal wall, inguinal region, and scrotum (8); buttock and lower limb (6); upper limb (4); neck and scalp (3); and low back (2). They were 0.7 to 10 cm, ill defined, and five underwent reexcision, which was curative in all. All had the characteristic mixture of fibrous and adipose tissue and nests of immature mesenchyme in different proportions, and nearly all showed lymphocytes and thick patent capillaries in the mesenchyme. However, the fibrous component varied considerably in amount, pattern, and cellularity, so that lesions that were typical in some areas, in others resembled collagenizing vascular granulation tissue, deep fibrous histiocytoma, or fibromatosis. Those in which adipose tissue predominated were distinguished from fibrolipoma by foci of immature mesenchyme and from lipoblastoma by their lack of a capsule and of a lobular pattern.

Pathology of osseous and genitourinary lesions of Proteus syndrome.

A male patient followed from the age of 3 to 25 years was eventually diagnosed as having Proteus syndrome. He was born with linear epidermal nevi of the neck and forearm and presented with macrodactyly of the right hand and progressive hemihypertrophy of the right lower limb recurring after multiple reduction operations. The bone ends showed disorderly overgrowth of hyaline and fibrocartilage mixed with collagen and bone, and early differential diagnoses included Ollier's disease. The child also had vertebral anomalies, scoliosis, a bony protrusion of the cranial vertex, and strabismus. In the second decade he developed gyriform swelling of the soles, retinopathy, bilateral papillary cysts of the epididymis, and a giant cyst of the left kidney with complex glandular foci. At 22 years a 3-cm meningioma containing adipose tissue was resected, and at 24 years a 3-cm cellular nodule of the rete testis with hyperchromatic foci, probably an adenoma, was removed. The features of Proteus syndrome were those of hyperplasia and neoplasia of mostly mesodermal tissues. Unlike other reported cases, overgrowth of a finger recurred at 25 years.

Maldescent of the thymus: 34 necropsy and 10 surgical cases, including 7 thymuses medial to the mandible.

Among 3236 pediatric necropsies over 23 years, abnormal position of thymic tissue was recorded in 34 cases. Cardiac anomalies, predominantly those seen in DiGeorge syndrome, were present in 24; 3 had noncardiac anomalies only, 4 had other diseases, and 3 were sudden infant deaths. Mediastinal thymic tissue was absent in 22 cases, small or unilateral in 7, and normal in 5. The maldescended thymic tissue was unilateral in 18, bilateral in 11, and multiple on one or both sides in 5. It was situated near the thyroid gland in 19, lower in the neck in 6, and higher in 9, including 7 medial to the submandibular salivary gland and 1 at the base of the skull. The maldescended tissue approached the size of a normal lobe of thymus in eight and was 2.4 to 0.1 cm in the remainder. Over the same period, in only two cases was no thymic tissue found. Among 68,000 surgical specimens over 40 years, there were 10 cases of ectopic thymus in the neck, including 1 cutaneous and 4 cystic. This frequency of thymic tissue in the neck may explain why lymphoid tissues are sometimes relatively normal in cases of absent mediastinal thymus and behooves a search in the submandibular salivary gland region and higher before diagnosing thymic agenesis.

Male pseudohermaphroditism in XY children with female phenotype.

Twenty-two children with female external genitalia, testes, and 46,XY karyotype, most presenting with inguinal lumps or hernias, underwent bilateral gonadal excision (21 patients) or biopsy. On clinical and biochemical grounds, 13 were classed as androgen resistance (AR), 6 as testosterone biosynthetic defect, 2 as XY gonadal dysgenesis, and 1 as 5 alpha-reductase deficiency. The main pathological difference between the groups was that in AR the gonocytes were present in normal numbers, whereas in testosterone biosynthetic defect, gonocytes, though present in infancy, were rare or absent by 12 years. In all groups, Leydig cells, normally not recognizable between 1 year and puberty, were often present and could not always be attributed to a gonadotropin stimulation test. In four cases the tubules were more heterogeneous than those seen in control testes, but tubular atrophy and increased stroma were indistinguishable from those in age-matched cryptorchid controls. Small Sertoli cell nodules were found in three children, but no carcinoma in situ was identified. The epididymis, said to be absent in adult cases of AR, was consistently present but often cystic or atrophic. Oviduct-like structures were found in three cases of AR, and smooth muscle resembling round ligament in four. Because of the difficulty in distinguishing the types of male pseudohermaphroditism microscopically, we recommend that XY female children should undergo thorough endocrinologic investigation before orchidectomy.

A comprehensive microcomputer network program for histopathology.

For a small hospital with a limited budget, a stand-alone histopathology microcomputer network may be more valuable to the pathologist than one running off the hospital's main computer. In return for sacrificing the limited benefit of screen reading of pathology reports in the wards, one receives the great advantage of more rapid retrieval of disease data. Commercial relational database programs for microcomputers can now achieve nearly all the power of a minicomputer program, with more versatility. Using an application developed on such software, we now have 30,000 pathology reports entered, from which we can retrieve a list of pathology numbers, with patients' names, age, sex, disease, and site, for any diagnosis in 3-5 seconds. The application includes full biopsy reports for doctors and wards, autopsy final diagnoses, computer-assisted Snomed coding, outside consultations, literature abstracts, daybook printing, workload statistics and billing codes and charges, and a cytology module has been added for another hospital. Moreover, the interested pathologist can easily make his own alterations to menus, entry screens, fields, and screen listing or printout formats.

Sequestrated meningoceles of scalp: extracranial meningeal heterotopia.

Sequestrated meningocele of the scalp has seldom been reported and is difficult to diagnose. Clinically it resembles dermoid cyst, hemangioma, or alopecia; radiographs and computed tomographic scans reveal no cranial bone defect, and surgery discloses no communication with the cranial cavity. Histologically, the lesion is characterized by a loose arrangement of connective tissue in dermis and subcutis, associated with flattened cells around collagen fibers (meningothelial cells). Most examples are very vascular, sometimes mimicking angioma, and about one third contain small necrotic foci. The meningothelial nature of the lesion is shown by its architectural similarity to communicating meningocele, and its identical immunoperoxidase reactions with vimentin and epithelial membrane antigen. In the 12 cases reported herein, most lesions were small (1 to 1.5 cm), and all but one were noted at birth but usually not resected until the patient had reached age 1 to 4, and one not until the patient was 31 years of age. Five lesions were not midline. We have been unable on histologic grounds to determine whether meningoceles are communicating or sequestrated. Compared with 20 communicating meningoceles, the sequestrated lesions were usually smaller, found in slightly older patients, and much less likely to be associated with hydrocephalus. The local excision of scalp lesions in children should include a search for a small intracranial connection.

Nasal cerebral heterotopia: the so-called nasal glioma or sequestered encephalocele and its variants.

Twenty two nasal cerebral heterotopias were compared with 11 nasal encephaloceles. No histological feature was found that would allow a communication with the brain to be confidently identified or excluded. Even laminated cerebral cortex with neurones and ependymal canals, suggestive of encephalocele, were found in heterotopias. Distinction required radiological and surgical evidence. However, CT scan could be misleading, in one infant suggesting a cribriform plate defect when none was found at craniotomy. Three children had multiple extracranial glial lesions, two with both heterotopia and encephalocele in the same patient. In a few older children it was extremely difficult to identify brain tissue because of marked replacement by fibrous tissue (up to 95%), leading to one misdiagnosis as fibroma, and considerable fibrosis occurred also in five of six recurrences and in a longstanding small encephalocele. In two heterotopias, cellularity in places approached that of low-grade neoplastic glioma. One nasopharyngeal heterotopia contained multiple mesenchymal tissues suggestive of teratoma. Two midline nasopharyngeal encephaloceles showed adjacent epithelium, possibly vestiges of Rathke's pouch.

Balanitis xerotica obliterans in children.

Balanitis xerotica obliterans was studied in 48 fully developed and 6 early cases in children aged 2-15 years. It occurred in 9% of 100 consecutive circumcisions for all, including religious, reasons and in 19% of 232 other circumcisions for disease of the prepuce and penis. Seven cases developed after surgery for hypospadias. The boys nearly always presented with inability to retract the prepuce; half also had discomfort after micturition, and a quarter had obstructive signs, usually minor. At surgery, half had involvement of glans or meatus, previously considered rare in childhood, 3 requiring meatotomy. The condition, once seen, was easily recognized clinically as well as microscopically. The early cases, characterized by focal narrow hyaline edematous zones in severe diffuse chronic balanitis, suggest that the condition may be an inflammation in which the usual increased permeability of small vessels in inflammatory reaction is accentuated in a loose vascular region.

Rapid frozen section in pediatric pathology.

Frozen section examination in pediatrics differs from that in adult practice in two ways. First, there is a high proportion of undifferentiated small-cell cancers in which it it difficult to make a definitive diagnosis without additional information. Second, there are special categories of congenital disorders where one is seeking not neoplasia but the presence, absence, or size of normal structures. In 520 pediatric frozen sections, there was a comparatively high incidence of deferred (5.6%) or inaccurate diagnoses (3.5%). However, as there were 99 small-cell cancers, it is perhaps surprising that the number was not greater. In the nervous system (208 cases), it was sometimes difficult to distinguish between malignant ependymoma and medulloblastoma. In other neoplasms, e.g., soft tissues and bone, the most important requirement was adequate clinical and radiological information. In Hirschsprung's disease (132 cases), ganglion cell detection was 100% accurate. In measuring the diameter of bile ducts in the porta hepatis during surgery for biliary atresia (18 cases), it was sometimes difficult to recognize ducts that had lost their epithelial lining.

Generalized arterial calcification of infancy: three case reports, including spontaneous regression with long-term survival.

Generalized arterial calcification in infancy is a rare disorder in which death usually occurs in infancy, the diagnosis generally being made at autopsy. Three patients are reported. The diagnosis was made during life in two, enabling new information to be collected. Cardiac catheterization in one provided evidence suggesting stiffness of pulmonary and systemic arterial walls. Another is a long-term survivor with spontaneous regression of calcification. The third case, diagnosed at necropsy, was associated with endocardial fibroelastosis.

Sacrococcygeal developmental abnormalities and tumors in children.

Lesions from the SC region of children examined histologically at the RAHC were: 1. Malformations almost always associated with spina bifida aperta or occulta: 183 myelomeningocele (MM), 32 meningocele (M), 35 lipoMM and lipoma, 19 dermoid cyst, six occult meningocele, two Pacinian hamartoma, one short filum, four hindgut cysts or sinuses, two tailgut cysts, and two epithelial heterotopia. 2. Neoplasms, usually without spina bifida: 56 teratomas (11 malignant), five ependymomas (two purely subcutaneous), and 14 miscellaneous primary malignancies, (most neuroblastoma and rhabdomyosarcoma). Distinction between MM with glial tissue and M without glial tissue is important as M had a much better prognosis, less than a third developing hydrocephalus, and 77% walking unaided. Of those with glial tissue, the eight without Arnold-Chiari malformation were myelocystocele associated with cloacal exstrophy (six), caudal regression syndrome (one), and microcephaly (one). Postsacral glial tissue without paraplegia may occur with a subcutaneous vestige of filum terminale, or with herniation of the nonfunctioning half of a diplomyelia. Of postsacral "lipomas" and dermoids, 70% had an intraspinal connection through an occult spina bifida. This posterior vertebral defect is easily overlooked as the arches normally may not ossify until after 6 years. Therefore, the pathologist receiving a postsacral specimen may wish to alert the clinician to the high incidence of late effects from an occult intraspinal component or tethering of the spinal cord. Transsacral hindgut herniations and cysts probably result from ectoendodermal adhesions. Presacral multicystic malformations with mixed squamous and mucus cell lining are probably tailgut remnants or anorectal duplications, and may be mistaken for dermoid or teratoma. In SC teratoma in infants, contrary to some reports on ovarian teratoma in adults, immature tissues do not indicate a worse prognosis. Malignancy is virtually confined to teratomas including a carcinomatous or "yolk sac" component. It is more common in predominantly presacral examples and rare before the age of 4 months. SC ependymoma differs from ependymoma elsewhere in that it may be primary outside the craniospinal cavity (presacral or postsacral), may have a myxopapillary pattern special to the region, and although low-grade and slow growing, is more likely to metastasize beyond the central nervous system. Postsacral examples arise from vestiges of the filum terminale which are normal in the subcutis there. Combinations of all these lesions occur with vertebral defects and with each other.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis and behavior of juvenile rhabdomyosarcoma.

The main problems in the diagnosis of rhabdomyosarcoma are 1) distinction of undifferentiated examples from other small cell malignancies, especially soft-tissue Ewing's tumor and lymphoma; 2) distinction of spindling examples from fibrosarcoma, leiomyosarcoma, malignant fibrous histiocytoma, polyhistioma, and other sarcomas; 3) recognition of minimal criteria on small samples such as needle biopsy specimens or frozen sections; and 4) recognition of rhabdomyosarcoma in uncommon sites such as bone (mandible), perineum, retroperitoneum, and chest. In 95 pediatric cases diagnosed and treated at Royal Alexandria Hospital for Children--45 after the introduction of combined therapy--minimal diagnostic criteria were assessed. Cross-striations were found in only one third of cases; longitudinal myofibrils were more common and more helpful. There was much overlap between histologic types, and the microscopic patterns had little bearing on prognoses in preadolescent children. Fourteen cases could not be further differentiated ("embryonal sarcoma, probably rhabdomyosarcoma")--nine small-cell tumors; four tumors from genitourinary tract or head for which very small biopsy specimens were available, and one spindling retroperitoneal neoplasm. In all, slight evidence suggested embryonal rhabdomyosarcoma; this evidence included oat-shaped nuclei and, in a few cells, deeply eosinophilic cytoplasm, small elongated processes, or myxoid or alveolar foci--features that exclude lymphoma and Ewing's tumor. In six cases that were originally classified as poorly differentiated or undifferentiated, later material confirmed the presence of rhabdomyosarcoma by showing a predominantly well-differentiated (pleomorphic) or alveolar pattern after therapy. In 14 remaining undifferentiated cases, immunoperoxidase staining with antihuman-myoglobin serum was positive in five. With combined therapy there was 100 per cent survival among patients with paratesticular, limb, and stage I and stage II tumors; considerably improved survival among patients with head and neck, pelvic, and stage III tumors; and 100 per cent mortality among patients with intra-abdominal and stage IV tumors.

Endoscopy and biopsy in gastroesophageal reflux in infants and children.

The clinical features of abnormal gastroesophageal reflux in infants and children extend beyond repeated vomiting and include dysphagia, pain, bleeding, failure to thrive, esophageal stricture, and recurrent respiratory symptoms including aspiration pneumonitis and cyanotic attacks. The unreliability of the traditional barium swallow examination as a diagnostic test is well known. This study reports the results of endoscopic assessment and esophageal biopsy in 100 infants and children and relates them to the clinical findings and the changes in the contrast esophagogram. The results show that further valuable diagnostic information can be gained from endoscopic examination of the esophageal mucosa, especially when there is esophagitis with ulceration, bleeding, or stricture. Endoscopic biopsies are useful to confirm the presence of esophagitis but biopsies alone do not give absolute diagnostic information.

Sacrococcygeal paciniomas.

Two well differentiated pure Paciniomas, bearing no resemblance to neurofibromas, were resected from infants with spinal deformities. Each was in the form of a thick cord running from a sacral dimple through a low occult spina bifida to the spinal dura. The lesions are considered to be a malformation or hamartomatous overgrowth. Control sacrococcygeal regions from necropsies on 15 infants were examined histologically, and Pacinian corpuscles were found in 7, usually near the tip of the coccyx, and never numerous.

Ependymal rests and subcutaneous sacrococcygeal ependymoma.

A 2 cm subcutaneous ependymoma was resected from the natal cleft of a 4-yr-old girl. The coccyx was not removed and there has been no recurrence in 14 years. A study of the post-coccygeal region in 15 control infants revealed subcutaneous islands of ependyma, unconnected with the cauda equina, in 4/4 infants with post-anal dimples and in 6/11 infants with no external post-coccygeal anomaly.

Congenital cystic malformation of the lung. A form of congenital bronchiolar ("adenomatoid") malformation.

Of 41 cases of cystic lungs in children, 21 were found by microscopy to be due to congenital cystic malformation. In most of the remainder, chronic inflammation and fibrosis precluded differentiation from postinflammatory pneumatocele. A few were intermediate between cystic malformation and congenital lobar emphysema. The cystic malformations were 17 surgical and four necropsy specimens, and two thirds of the patients were under 1 year old. The condition was unilobar, and the cysts were thin-walled, up to 8 cm in diameter, multiple or multilocular, and microscopically resembled proliferated, dilated bronchioles communicating with alveoli. There was a wide range of size, shape, and number of cysts, and no sharp demarcation from adenomatoid malformation in stillborn infants. Thus, bronchiolar malformations fall into two overlapping clinicopathologic groups: (1) adenomatoid malformation in edematous stillborn and premature infants with perdominantly solid lobes showing more epithelial proliferation and immature terminal airways and (2) cystic malformation in term infants and children with predominantly cystic lobes and interspresed mature alveoli.

Teratomas in childhood.

Of 109 teratomas in children 86 were benign and 23 malignant. Sacro-coccygeal and pelvic teratomas predominated 52 cases, and these fell into three groups, post-sacral, dumb bell and pre-sacral. The 34 purely posterior tumours were always congenital and benign whilst the incidence of malignancy in dum bell and pre-sacral teratomas increased as the tumour became more internal. Other sites affected in order of frequency were: the gonads, head and neck, retroperitoneal anterior mediastinum and the central nervous system. Malignant teratomas were carcinomas usually containing glandular, capillary and clear cell areas, and metastases were similar. Immature tissues in benign teratomas were usually neural or connective tissue. They did not give rise to neuroblastomas or sarcomas and did not indicate a worse prognosis. Only two originally benign teratomas later developed malignancy.

Epignathus, double pituitary and agenesis of corpus callosum.

Two infants from unrelated families died on the 1st day of life with epignathus, duplication of the entire pituitary, infundibulum and sella, and widening or separation of midline structures of the head including absent corpus callosum. We suggest that some infants surviving surgery for large epignathi may have relatively symptomless absent corpus callosum or double pituitary.

Necropsy findings in childhood leukaemia, emphasizing neutropenic enterocolitis and cerebral calcification.

In 50 necropsies on leukaemic children, the major cause of death was infection. In patients dying during therapy for induction or reinduction of remission, the most frequent infection was a distinctive neutropenic enterocolitis or typhlitis. This was seen in 46% of the whole series and was a major factor in the death in 38%. Other infections were predominantly bacterial pneumonia in patients in relapse, and viral disease, e.g. measles pneumonia, in those in remission. One patient treated for meningeal leukaemia showed an unusual linear calcification of the cortical grey matter.