The successful treatment of recurrent nephrotic syndrome with the MOPP regimen in a patient with a remote history of Hodgkin's disease.

The association of Hodgkin's disease and minimal-change nephrotic syndrome is well established. We describe a gentleman who developed Hodgkin's disease that was treated successfully. Two years later, he developed minimal-change nephrotic syndrome that responded to steroids. Over the next 9 years, the patient experienced two episodes of nephrotic syndrome due to focal segmental glomerulonephritis that were successfully treated with the mustard/vincristine/prednisone/procarbazine (MOPP) regimen. There was no evidence of recurrence of Hodgkin's lymphoma during any episode of nephrotic syndrome.

Pancreatoblastoma and solid and cystic papillary tumor: two tumors related to pancreatic ontogeny.

Two tumors of the pancreas are related to pancreatic ontogeny. The pancreatoblastoma is a tumor of children, more commonly boys than girls and progresses with a slow, sluggishly malignant course. Surgery successfully controls the disease in about half the cases. Morphologic and immunohistochemical studies reveal undifferentiated areas, ductular areas, acinar areas, and occasionally neuroendocrine differentiation. Very characteristic is the presence of nodules of squamous epithelium. These features reflect the potencies of the pancreatic anlage somewhat earlier than the fourteenth week of development. The solid and cystic papillary epithelial tumor of the pancreas is a tumor of adolescent and young adult females, often non-Caucasian. Surgical excision is often successful, but deaths from local persistence and metastases have been described. These tumors have features of ductulo-acinar neoplasms of uncommitted pancreatic primordia exceptionally with neuroendocrine differentiation.

Ewing sarcoma of bone in infants and toddlers. A clinicopathologic report from the Intergroup Ewing's Study.

BACKGROUND: Nineteen patients with Ewing sarcoma of bone, each younger than 3 years of age at the time of initial presentation, are reported. These children represent an unusually young age group for documented Ewing sarcoma and represent 2.6% of all patients registered in the Intergroup Ewing's Sarcoma Study (IESS). METHODS: The diagnosis was made on combined histologic, clinical, and radiographic grounds and was supported by immunohistochemistry in nine patients and electron microscopic study in eight patients. Immunohistochemical studies showed no staining against neuro-specific enolase, chromogranin, or S-100 in any patients, and in only one in nine patients were results of such studies focally positive against Leu-7. RESULTS: The most marked clinical variation between this group of infants and the general IESS patient population was a striking predominance of female patients in the younger age group (P < 0.001). There was a trend toward more rib, pelvis, and proximal long bone tumors in the infants and toddlers. The overall survival rate of the infants was 56%, almost identical to the survival rates of the older children. All of the infants who died of disease did so within 4 years. Extended follow-up as long as 9.9 years has found no late deaths attributable to tumor. The most significant late complications of therapy included cardiotoxicity with cerebral embolization from the heart and a short lower limb secondary to radiation therapy. CONCLUSIONS: Ewing sarcoma must be considered in the differential diagnosis of small cell, round cell, and blue cell tumors in bone, even in infants and toddlers.

renal tumors and tumor-like lesions in pediatric patients.

Renal enlargement presenting as an abdominal mass(es) is attended by a lengthly differential diagnosis of non-neoplastic and neoplastic lesions with a range in serious connotations and consequences. Simple compensatory hypertrophy and unilateral multicystic dysplasia are relatively innocuous and easily recognized with appropriate imaging studies; they are also related in the sense that the normal contralateral kidney hypertrophies in the absence of a non-functioning dysplastic kidney. Bilateral nephromegaly in a neonate is generally a sign of autosomal recessive polycystic kidney disease or multicystic dysplasia secondary to distal obstructive uropathy. Primary neoplasms of kidney in the pediatric population in the past were traditionally classified as Wilms' tumors, but that erroneous practice has been eliminated with the recognition of several distinctive neoplasms in addition to classic Wilms' tumor. Separating a typical Wilms' tumor from mesoblastic nephroma, clear cell sarcoma of the kidney and the malignant rhabdoid tumor, for treatment and prognostic purposes, has become the accepted norm in the past 12-13 years. Another important advance at the cellular level is the recognition of a deletion in the short arm of chromosome 11 in the cultured cells of Wilms' tumor and in the germ cell line in certain clinical settings of Wilms' tumors. A dramatic expansion in the understanding and management of childhood renal neoplasms has occurred through the multimodality approach of laboratory investigation and applied clinical research.

Multilocular renal cyst. Immunohistochemical and lectin-binding study.

Multilocular renal cyst is an uncommon lesion of uncertain pathogenesis seen in children and adults. We report the immunohistochemical and lectin-binding profiles of three MRC occurring in adults. All cases had strong and uniform cytoplasmic staining of lining epithelial cells for keratin and binding sites for arachis hypogaea lectin, similar to that seen for the distal convoluted tubules or collecting ducts in normal kidney. However, we found variable expression of other distal nephron markers, including epithelial membrane antigen and Ber-EP4. Furthermore, lining cells in some lesions coexpressed proximal nephron markers such as alpha-1-antitrypsin and lysozyme, as well as binding sites for lotus tetragonolobus lectin. Immunostaining for type IV (basement membrane) collagen demonstrated a continuous subepithelial basement membrane zone and basal laminae surrounding desmin-positive stromal cells. Areas of active collagen synthesis and stromal procollagen deposition were visualized within the interlocular septae using a monoclonal antibody to type I procollagen. Significant proliferative activity was not detected in the lining epithelium or stroma using the anti-proliferating cell nuclear antigen. In conclusion, MRC show aberrant tubular epithelial glycoprotein and glycoconjugate expression, low proliferative activity, and associated activation of interlocular stromal cells.

Early occurrence of end-stage renal disease in a patient with infantile nephropathic cystinosis.

We report the case of a patient with infantile nephropathic cystinosis who required renal transplantation at age 30 months. Exhaustive evaluation did not identify a cause of progressive renal failure other than cystinosis. The patient's genetic lesion was allelic with those of other patients with cystinosis; fusion of this patient's fibroblasts with fibroblasts from another patient with infantile nephropathic cystinosis did not demonstrate complementation of the biochemical defect.

Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study.

A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable).

HLA extended haplotypes in steroid-sensitive nephrotic syndrome of childhood.

Idiopathic nephrotic syndrome has been postulated to have an immunopathogenic basis. To determine whether steroid-sensitive nephrotic syndrome is associated with greater than expected frequencies of specific extended haplotypes of the major histocompatibility complex, we studied genetic markers (Class I, II, III HLA alleles and glyoxalase I) in 173 subjects in 42 families of patients with nephrotic syndrome of childhood. The single allele, DQW2, was found in 72% of steroid sensitive patients compared with only 35% of the controls (P = 0.003). In half of 32 steroid sensitive, but not 10 steroid resistant, patients, one or both of two specific extended haplotypes (alleles that segregate together) were identified. The first, [HLA-A1, B8, DR3, DRW52, SCO1], occurred in 11 of 64 haplotypes, or 17%, compared to 5% of controls (P = 0.017). The other, [HLA-B44, DR7, DRW53, FC31], occurred in 10 of 64 haplotypes, 16% compared to 3.8% of controls (P = 0.014). Five patients had both haplotypes. Patients with these specific extended haplotypes had a greater frequency of relapses than did those with other haplotypes. These data provide additional support for the hypothesis that steroid-sensitive nephrotic syndrome has an immunogenetic basis.

The effect of Gd-dimeglumine on subcutaneous tissues: a study with rats.

Gadopentetate dimeglumine and a saline solution of similar osmolality of 2100 mOs/kg H2O were placed in the paws and in the thigh muscles and subcutaneous tissue of Sprague-Dawley rats weighing 225-250 g. The paws were serially photographed for 4 weeks and the thighs were examined histologically for up to 4 weeks. Gross and histologic reactions to gadopentetate dimeglumine were greater than those to the saline solution, and included tissue sloughs. When risk factors for extravascular extravasation are present, such as infusion sites in the dorsum of the hand or foot, or around the ankle, or when soft tissues are obscured by bandages, caution should be exercised when injecting gadopentetate dimeglumine.

Renal cysts in pediatric patients. A classification and overview.

Renal cysts are relatively common. They may be single, multiple, or innumerable, cortical or medullary. Most renal cysts are spherical, thin-walled, epithelial-lined structures that contain fluid with features of a plasma ultrafiltrate. A clinically useful classification must include characteristics such as age of onset, family history and association with extrarenal lesions, as well as morphologic parameters. Renal dysplasia is disturbed renal histogenesis, either syndromic or non-syndromic, which usually gives rise to morphologically characteristic renal cysts. Two important and distinctive familial forms of renal polycystic disease occur. Autosomal dominant polycystic disease characteristically becomes manifest in adulthood but is becoming increasingly diagnosed in young individuals. Autosomal recessive infantile polycystic disease has complex relationships with "congenital hepatic fibrosis". Other cystic renal lesions are less common in young patients, but their occurrence in association with other abnormalities provokes speculation regarding pathogenesis.

Comparison of soft tissue effects of conventional ionic, low osmolar ionic and nonionic iodine containing contrast material in experimental animals.

Conventional, low osmolar, and non-ionic iodine containing contrast media and saline controls were placed in the paws, muscles, and subcutaneous tissues of Sprague-Dawley rat thighs. The paw injections were observed and photographed, while the thighs were examined histologically. Results showed that although the low osmolar and non-ionic agents did produce inflammatory reactions and focal necrosis in the soft tissues, they were much better tolerated than were the conventional ionic agents. A non-ionic or low osmolar ionic contrast agent should be strongly considered when a possibility for extravasation exists.

Sonographically detectable cysts in polycystic kidney disease in newborn and young infants.

Autosomal dominant (adult type) and autosomal recessive (infantile type) polycystic kidney disease are 2 distinct forms of hereditary cystic renal disease with differing pathologic and clinical features. Glomerulocystic kidney disease is probably a separate entity, whose pathologic features may closely resemble those of autosomal dominant polycystic kidney disease, especially in small infants. An example of each of these conditions in a small infant is presented, all of which had sonographically detectable cysts. Pathologic correlation was available in each case. While there are typical sonographic features of autosomal dominant and autosomal recessive polycystic kidney disease in newborn and young infants, there is no specific appearance of either condition, and glomerulocystic kidney disease can apparently resemble either one. Other investigations, particularly family studies and pathologic verification, are important in order to establish the correct diagnosis.

Primary Ewing's sarcoma involving the bones of the head and neck.

Ewing's sarcoma is a rare tumor of the bone. In the Intergroup Ewing's Sarcoma Study (IESS) approximately 4% of the primary bone tumors arose in the bones of the head and neck. The mean age of patients was 10.9 years; boys slightly dominated the group. Signs and symptoms were local in distribution, with a mass or swelling most frequent. As in other sites, we categorized the dominant histologic pattern as diffuse or filigree, the latter carrying a more unfavorable prognosis. The radiographic appearance may be atypical as compared to Ewing's sarcoma at other sites. Prognosis of head and neck Ewing's is significantly better than Ewing's sarcoma overall. The gnathic bones were commonly affected, yet there was no associated mortality. No patient with primary disease in the bones of the head and neck who survived for 5 years on any of the IESS protocols has subsequently died.

Thromboxane synthesis and blood pressure in spontaneously hypertensive rats.

The present study examines effects of administration of OKY 046, an inhibitor of thromboxane synthesis, for 100 days on systemic blood pressure and renal function in spontaneously hypertensive rats and in normotensive control rats. Untreated spontaneously hypertensive rats had higher values for thromboxane excretion in the urine and higher values for blood pressure than did normotensive control rats. Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats. Administration of OKY 046 decreased thromboxane excretion in the urine of normotensive control rats but had no effect on blood pressure or protein excretion. Renal function, as assessed by the clearances of inulin and p-aminohippuric acid, was greater in spontaneously hypertensive rats treated with OKY 046 than in those receiving vehicle alone. In normotensive control rats, OKY 046 administration did not affect renal function. These results suggest that increased renal synthesis of thromboxane may play a role in the pathogenesis of the elevated blood pressure of spontaneously hypertensive rats.

Use of beta 2 microglobulin to diagnose tubulo-interstitial renal lesions in children.

Fractional excretion (FE) of beta 2 microglobulin (beta 2M) was studied in children with glomerular (N = 114), tubular (N = 50) or other (N = 18) renal diseases. FE-beta 2M (normal less than 0.36%) was significantly (P less than 0.001) lower in glomerular diseases (mean 0.104%) than in tubular lesions (mean 4.27%). Unexpectedly, several patients with glomerular disease were found to have increased values for FE-beta 2M. To determine whether this was due to a tubular component in a primary glomerular disease process, FE-beta 2M was measured in 30 children with various glomerulopathies who underwent renal biopsy. Thirteen of these patients had tubulo-interstitial lesions in addition to their glomerular disease. FE-beta 2M in these patients averaged 3.76% (range 0.14 to 44.6%); only two results were normal. Mean FE-beta 2M in the 17 patients without biopsy evidence of tubulo-interstitial disease was 0.063% (range 0.02 to 0.34%); all values were in the normal range. The types of glomerular diseases in the two groups of patients were similar. Patients with a glomerular lesion complicated by tubulo-interstitial lesions had a poorer prognosis than did those with a pure glomerular disease. The high incidence of tubulo-interstitial lesions in patients with glomerular diseases was unexpected. Our data demonstrates that FE-beta 2M represents a reliable non-invasive method to diagnose such involvement. Measurements of beta 2M also provide a convenient method to follow the course and response to treatment of renal tubular injury.

The renal lesions of tuberous sclerosis.

Renal involvement in the tuberous sclerosis complex includes angiomyolipomas, cysts, and carcinomas. Angiomyolipomas, despite a sometimes frightening histopathologic appearance, are benign. Cystic disease, apparently resulting from tubular epithelial hyperplasia, causes hypertension and renal insufficiency, progressing to end-stage renal disease. The same epithelial hyperplasia predisposes to renal carcinoma.