Langerhans cell histiocytosis: retrospective analysis of 217 cases in a single center.

Langerhans cell histiocytosis (LCH) is a disorder with unclear etiology and pathogenesis, which is characterized by abnormal clonal proliferation and accumulation of langerhans cells at various tissue and organs. A total of 217 patients with LCH were evaluated retrospectively for clinicopathological features, laboratory findings, treatment modalities, long-term outcome, and factors affecting the outcome. Median age at the time of diagnosis was 3.5 years and male/female ratio was 1.8. The most common complaint at presentation was a bone lesion-related symptom. Fifty percent of the patients younger than 2 years had organ dysfunction (OD). Treatment consisted of surgery, chemotherapy, and radiotherapy alone or in combination. Vinblastine with or without prednisolone was the most common used chemotherapy regimen. Overall (OS) and event-free survival (EFS) rates were 84% and 51.5%, respectively, at an 8-year median follow-up time. Overall survival was significantly lower in patients younger than 2 years of age and patients with OD. The age at diagnosis, pulmonary, liver, or hematological involvement, and elevated acute-phase reactants were found to have a statistically significant effect on the OS or EFS rates.

Immunohistochemical detection of Helicobacter pylori infection in gastric biopsies of urea breath test-positive and -negative pediatric patients.

Helicobacter pylori (H. pylori) is a common cause of gastritis in both children and adults, and its incidence increases every year. The aims of this study were to evaluate the histopathologic features of H. pylori gastritis and to compare immunohistochemical with histochemical [hematoxylin-eosin (HE) and Giemsa] staining of gastric biopsy specimens for the detection of H. pylori infection from urea breath test (UBT) (-) and UBT (+) children. Seventy-eight gastric biopsies from pediatric patients who were administered UBT were included in this study. Gastric biopsy specimens were evaluated histopathologically and graded according to the Sydney system. HE, Giemsa and immunohistochemical staining was performed for the identification of H. pylori. The frequency of H. pylori gastritis was higher in the antrum than corpus. All biopsies with H. pylori colonization showed chronic inflammation with activity. By using immunohistochemical method, coccoid forms of H. pylori and spiral bacteria with low density were observed easily. With histochemical staining, 1/10 (10%) UBT (-) biopsies were H. pylori (+), while with immunohistochemical staining, 3 of the biopsies from UBT (-) patients were found to be H. pylori (+). Biopsies from 65 of 78 (83.3%) UBT (+) patients were H. pylori (+) with histochemical staining, but only 53 of these biopsies were found to be H. pylori (+) immunohistochemically. We conclude that immunohistochemical staining is more specific than histochemical staining and UBT for the detection of H. pylori infection.

Successful treatment of retroperitoneal giant cell-type malignant fibrous histiocytoma in a 5-year-old boy.

Malignant fibrous histiocytoma, usually seen in patients older than 10 years, is an aggressive soft-tissue sarcoma occurring mostly in the extremities and the trunk, but it is extremely rare in children. We report the clinical, radiological and pathologic features of a five-year-old boy who was diagnosed as a retroperitoneally originated malignant fibrous histiocytoma. The patient with unresectable mass was successfully treated with multidisciplinary approach, with chemotherapy, surgery and radiotherapy, by using combined chemotherapy consisting of vincristine, cisplatinum, adriamycin, cyclophosphamide, actinomycin D and dacarbazine.

Late recurrence in children with Wilms' tumor.

We aimed in this study to evaluate the clinical and radiological features of the late recurrence of Wilms' tumor in children. Among 553 children diagnosed with Wilms' tumor between 1972 and 2004, four cases were determined to be late recurrences. Clinical, histopathological parameters, treatment details, and outcomes of the patients were evaluated retrospectively. The ages of the patients at the time of diagnosis were 2, 5, 5, and 9 years and the male/female ratio was 1/3. Two patients had stage II disease and two had stage IV characteristics. Histopathological examination showed favorable histology in all of the patients. Initial treatment was surgery and chemotherapy, which included vincristine and actinomycin-D. Abdominal radiotherapy was performed in two patients. Recurrence times were 36, 41, 51, and 96 months. Local recurrence and lung metastasis were detected in two patients, local recurrence in one, and lung nodules in the fourth patient. At the time of relapse, the chemotherapy protocols were as follows: vincristine, actinomycin-D, adriamycin, and cyclophosphamide in two patients; vincristine, actinomycin-D, and epirubicin in one patient; and vincristine, actinomycin-D, and adriamycin in the last patient. In the cases with late local recurrence, one patient had a local spillage and one patient had regional lymph node involvement. Although the other patient had local spillage, regional lymph node involvement, and renal artery invasion, isolated lung recurrence was observed. Only one patient had progressive disease and is still under treatment, whereas the other patients died with disease. Major recurrence sites were both local and the lungs. All of the patients had regional features including spillage, regional lymph node involvement, and vascular or capsular involvement. Late recurrence in patients with Wilms' tumor is a poor prognostic factor and should be treated with an intensified regimen.

A case of homozygous familial hypercholesterolemia with focal segmental glomerulosclerosis.

Familial hypercholesterolemia (FH) is a common autosomal dominant inherited disorder characterized by increased levels of circulating plasma low-density lipoprotein cholesterol (LDL-C), tendon xanthomas, and premature atherosclerotic cardiovascular disease. Homozygous FH occurs in only one in a million people. Focal segmental glomerulosclerosis (FSGS) is clinically characterized by proteinuria, which is marked in the majority of cases and accompanied by nephrotic syndrome, high incidence of hypertension, and progression to renal failure. To our knowledge, we herein report for the first time a case of homozygous FH associated with FSGS. A seven-and-a-half-year-old boy was referred to our hospital due to cutaneous xanthomata and growth retardation. He had multiple nodular yellowish cutaneous xanthomatous lesions each 1 cm in size over his knees and sacral region. Laboratory data included cholesterol level of 1,050 mg/dl, low density lipoprotein cholesterol (LDL-C) 951 mg/dl, high-density lipoprotein cholesterol (HDL-C) 29 mg/dl, triglycerides 168 mg/dl, total protein 6.3 g/dl, and albumin 3.2 g/dl. Urinary protein excretion was 78 mg/m(2) per hour. A percutaneous renal biopsy was performed, and histological findings showed FSGS. Treatment with cholestyramine and atorvastatin was unsuccessful in terms of lowering lipids, and he was placed on weekly sessions of plasmapheresis. Total cholesterol was reduced from 1,050 mg/dl to 223 mg/dl, LDL-C from 951 mg/dl to 171 mg/dl, and urinary protein excretion from 78 mg/m(2) per hour to 42 mg/m(2) per hour after eight sessions of plasmapheresis. It is our belief that plasmapheresis is a treatment of choice in patients with FSGS associated with FH.

Extranodal type T/NK-cell lymphoma with an atypical clinical presentation.

Peripheral-type natural killer (NK)- or T-cell lymphomas are rare disorders characterized with clonal proliferation of mature lymphocytes. They have been linked to chronic and active Epstein-Barr virus infection (CAEBV), which itself is not defined as a malignant hematological disorder. The authors present a patient with T/NK-cell lymphoma involving skin, kidneys, spleen, pancreas, and meninges. She was remarkable for having the mosaic feature of more than one type of extranodal T/NK-cell lymphoma. She also had mixed findings of CAEBV that might have been attributed both to hypersensitivity to mosquito bites and to hemophagocytic lymphohistiocytosis.

Histological response to injected dextranomer-based implant in a rat model.

To investigate the short and long term histopathological alterations caused by submucosal injection of dextranomers in sodium hyaluronan (DiHA) based on an experimental rat model. Sixty Sprague-Dawley rats were assigned into two groups as group I and II, each containing 30 rats. Totally 0.1 ml of saline solution and 0.1 ml of DiHA were injected into the submucosa of bladder of first (control) and second groups, respectively. Both group I and II were further subdivided into three other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrificial period. Group IA and IIA, IB and IIB, IC and IIC rats (ten rats for each group) were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary growth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at 10x magnification. The results were assessed using t-tests for paired and independent samples, with P<0.05 considered to indicate significant differences; all values were presented as the mean (SD). Migration to the brain was not detected in any group. Significant histopathological changes in the DiHA injected groups were granuloma formation in 43.3%, foreign body type giant cells in 76.6%, inflammatory infiltration in 100%, and fibroblasts surrounding microspheres in 100% of the rat bladder. The interaction between granuloma formation and long-term tissue effects in children is still obscure. We emphasize that further prospective human (and/or animal) studies are required to clarify the long-term effects of granuloma formation with regard to clinical applications.

Renal cell carcinoma in children: experience of a single center.

OBJECTIVE: To evaluate the clinical features and outcome of children with renal cell carcinoma (RCC). PATIENTS AND METHODS: Eleven patients with RCC who were diagnosed between 1972 and 2004 were retrospectively analyzed. Clinical features, histopathology, treatment regimens and outcomes of the patients were evaluated. RESULTS: The male/female ratio was 3:8, with a median age of 10 years. The stage distribution was as follows: 3 patients in stage I, 1 patient in stage II, 3 patients in stage IIIb, and 4 patients in stage IV. Five of 7 patients with stage II-IV received an actinomycin D-based regimen, one received a cisplatin-based regimen, and the other was given 5-fluorouracil (5-FU). In the last patient, interferon-alpha was given in combination with 5-FU; 1 of the patients on the actinomycin D regimen received interferon-alpha as well. All of the stage I patients are alive without disease. Three patients with stage IIIb, stage IV and stage II disease are alive without disease 8, 14 and 26 years after their diagnosis, respectively. The other stage IV and stage IIIb patients died of the disease. CONCLUSION: Nephroureterectomy is the main treatment modality, and it is sufficient for stage I patients. For patients with stage II-IV RCC, interferon-alpha and/or actinomycin D-based chemotherapy is the treatment of choice.

Simple cyst of the testis: a rare and benign cause of testicular swelling in infancy.

We report a five-month-old boy who was referred to the hospital with a presumptive diagnosis of hydrocele of the cord. Ultrasonography revealed a cystic mass within the left testis. A complete removal of the cystic mass was done. Histopathological diagnosis was simple cyst of the testis. This rare lesion should be considered in the differential diagnosis of cystic testicular lesions in infancy. The treatment of choice is simple enucleation of the cyst with sparing of the testis and related structures.

Improved survival of children with wilms tumor.

To analyze changes in the overall survival (OS) rate of children with Wilms tumor treated in a single institute over nearly 30 years. This study included 327 children with a newly diagnosed Wilms tumor. Their median age was 3 years, and the male:female ratio was 1.1. Survival rates were analyzed according to the stage of disease, histopathology, and different treatment regimens used between 1972 and 1999. At diagnosis, 51.1% of patients had advanced stage disease. Ten patients had anaplasia, and; 97% (317 patients) of the tumors had favorable histopathology. The 10-year OS rate was 60.6% for the entire group, but varied according to the years in which the patients were treated, the chemotherapy regimen, and stage of disease. Patients treated during the periods of 1972 to 1979, 1980 to 1989, and 1990 to 1999 had 10-year OS rates of 48.5%, 64.3%, and 72.8%, respectively. The 10-year OS rate in children treated with actinomycin only was 36.7% compared with 48% for children treated with the actinomycin-D+vincristine regimen with a 3-month interval, 67% for the actinomycin-D+vincristine regimen with a 1.5-month interval, 54.5% for the poor-risk regimen (actinomycin-D, vincristine, cyclophosphamide, and adriamycin), and 53.4% for the SIOP-9 protocol. Children with stage I to IV disease had 10-year OS rates of 75%, 77.1%, 54.4%, and 30.4%, respectively. The 10-year OS rates for children with stage III and IV disease increased from 46.4% and 13.4% for patients treated between 1972 to 1979 period to 75% and 54.5% for children treated during 1990 to 1999. The 10-year OS rate for children with Wilms tumor improved as treatment strategies evolved, illustrating that pediatric oncology in Turkey is developing parallel to the Western world.

Histone mRNA in situ hybridization and Ki 67 immunohistochemistry in pediatric adrenocortical tumors.

Adrenocortical tumors in the pediatric population are rare. Classification of these tumors as adenomas or carcinomas using histological criteria is often difficult. Immunohistochemical expressions of proliferative markers are currently under investigation for utilization in the differential diagnosis and prediction of clinical outcomes. The value of histone proteins as prognostic markers in adrenocortical tumors has not yet been elucidated. We evaluated the histological features, immunohistochemical staining of Ki 67, and in situ hybridization for histone mRNA in 30 pediatric adrenocortical tumors. We investigated the relationship between these parameters and the prognosis. Using the classification proposed by Weiss, 19 tumors were classified as carcinomas and 11 as adenomas. Ki 67 and histone mRNA labeling indices (LIs, the percentage of Ki 67-positive and histone mRNA-positive tumor cells, respectively) were significantly higher in carcinomas than in adenomas (Ki 67 LI was 14.62+/-5.79 in adenomas and 20.35+/-6.23 in carcinomas, p=0.02. Histone mRNA LI was 1.73+/-1.71 in adenomas and 6.62+/-2.28 in carcinomas, p=0.00). The proliferative activity assessed by histone mRNA was lower than that assessed by Ki 67 in both diagnostic groups. The cut off point for the diagnosis of malignancy was found to be 14.55 for Ki 67 LI and 5.75 for histone mRNA LI. A correlation was found between a histone mRNA LI>or=5 and poor prognosis (recurrence, metastasis, or death). We concluded that the proliferative activity of the tumor assessed by Ki 67 and histone mRNA may assist in differentiating adrenocortical adenomas and carcinomas. In addition, our results suggest that the most reliable parameter to predict prognosis in pediatric adrenocortical tumors is the histone mRNA LI.

Paratesticular metastasis from Wilms tumor associated with a hydrocele.

Metastatic sites other than the lungs, lymph nodes, and liver are unusual for Wilms tumor (WT). Intra-scrotal metastasis is very rare. We report a 3-year-old boy with stage IIA WT, who experienced paratesticular metastasis 2 months after surgery for an abdominal recurrence. He had right scrotal hydrocele at initial diagnosis. The patient underwent right radical orchiectomy, and pathological examination revealed paratesticular WT metastasis. Intra-abdominal and peritoneal disseminated metastases followed. We considered that tumor cells spread through the patent processus vaginalis and grew at paratesticular space in hydrocele. One month after the end of 12 months of salvage chemotherapy and abdominal radiotherapy, the patient has no evidence of disease.

Focal segmental glomerulosclerosis associated with mitochondrial cytopathy: report of two cases with special emphasis on podocytes.

We report two children with focal segmental glomerulosclerosis (FSGS) associated with mitochondrial cytopathy (MC). Case 1 was diagnosed as MC with the findings of ptosis, ophthalmoplegia, failure to thrive, high serum lactate and pyruvate levels, ragged red fibers in muscle biopsy and the common 4.9 kb deletion in mtDNA when she was four years old. She subsequently developed FSGS four years later. Case 2 was a four month-old girl presenting with feeding difficulty from birth, with vomiting, seizures and nystagmoid eye movements, nephrotic proteinuria and hematuria. Renal biopsy revealed FSGS. Ultrastructural study demonstrated markedly pleomorphic mitochondria in podocytes with a severe effacement of foot processes. The analyses of muscle biopsy and skin fibroblasts for respiratory chain enzymes were found to be normal, while mitochondrial DNA analysis revealed the population of a single deleted mtDNA in the heteroplasmic state. The present cases illustrate FSGS as a rare renal complication of mitochondrial disease and provide further evidence of podocytes possessing abnormal mitochondria which may cause glomerular epithelial cell damage leading to glomerulosclerosis.

The triad of nesidioblastosis, congenital neuroblastoma and glomerulocystic disease of the newborn: a case report.

Neuroblastoma is the most common malignant tumor of the newborn, comprising 20% of all malignancies encountered during the neonatal period. We herein report a newborn who was born after 29 weeks' gestation and died unexpectedly at the 12th hour of life with no response to vigorous cardiopulmonary resuscitation. Autopsy findings revealed a right pararenal mass; microscopic examination showed neuroblastoma. Although the pancreas was grossly normal, its microscopic sections revealed a reduced number of islets of Langerhans and dispersion of the islet cells throughout the exocrine cells of the pancreas, and immunocytochemistry for the pancreatic hormones confirmed the dispersion of the islet cells. Final pathologic interpretation thus concluded the presence of nesidioblastosis. Furthermore, microscopic examination of the kidney showed glomerulocystic disease. Although the association of congenital neuroblastoma and nesidioblastosis has recently been defined as a new complex, neurocristopathy, the triad of congenital neuroblastoma, nesidioblastosis and glomerulocystic disease of the newborn has not been reported previously. To our knowledge, our case is the first reported newborn presenting with this triad. In conclusion, the association of nesidioblastosis and/or renal glomerulocystic disease should be kept in mind when encountering a case of congenital neuroblastoma. However, whether the presence of glomerulocystic disease in association with those other neurocristopathic pathologies is a coincidental finding or shares a common pathophysiological mechanism remains to be determined.

Cirrhosis in children with celiac disease.

BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. RESULTS: Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.

Is Dandy-Walker malformation associated with "distal 13q deletion syndrome"? Findings in a fetus supporting previous observations.

We report on a fetus with a large deletion of the distal part of the long arm of chromosome 13, (del(13)(q14 --> qter)) congenital anomalies of the urinary system, lungs and extremities, and Dandy-Walker malformation (DWM). Although DWM has been associated with many chromosomal abnormalities and genetic syndromes, its relation to the distal 13q has been demonstrated recently. In 2002, McCormack et al., described two patients with deletions of the long arm of chromosome 13 who had multiple congenital abnormalities along with holoprosencephaly (HPE) and DWM. The phenotypic features and autopsy findings of a fetus with "distal 13q deletion syndrome" at 22 weeks gestation are discussed and comparison with the previous two cases is made. The findings support the previous hypothesis suggesting that haploinsufficiency at a locus within 13q22-33 due to microdeletions may be responsible for isolated DWM in some of the patients. Detailed examination of 13q (13q22-33) by means of conventional and molecular cytogenetic methods is necessary in cases with DWM.

Apoptosis and proliferation in childhood acute proliferative glomerulonephritis.

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p <0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03+/-2% versus 0.32+/-0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4+/-1.9 versus 1.52+/-0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89+/-0.8 versus 0.73+/-0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.

Cavoatrial tumor extension in children with wilms tumor: a retrospective review of 17 children in a single center.

The aim of this study was to evaluate the clinical characteristics and treatment results of 17 children with cavoatrial tumor extension of Wilms tumor. Of the 360 Wilms tumors diagnosed between 1980 and 2000, 17 patients with intracaval thrombus were identified from the medical records at the pediatric oncology department of Hacettepe University. The following data were collected and reviewed: age, sex, presenting symptoms, tumor site, presence of anaplasia, stage, associated congenital anomalies, localization of tumor thrombus, radiologic findings, type and duration of preoperative chemotherapy, response to preoperative chemotherapy, recurrences, and survival. The frequency of cavoatrial extension in this group was 4.7% (15 in the inferior vena cava and 2 in the right atrium). Fourteen patients received preoperative chemotherapy consisting of two-drug regimen (vincristine and actinomycin D) ranging from 1 to 12 weeks (median 4 weeks). Since intravascular invasion is often asymptomatic, a careful radiologic examination to detect tumor thrombus before surgery is essential. There is no need for aggressive surgery in the presence of tumor thrombus. It may be resolved by preoperative chemotherapy. Surgical removal of the thrombus should be considered in the presence of life-threatening tumor thrombosis at diagnosis and in patients who had residual thrombus after chemotherapy.

Prognostic significance of metastatic site at diagnosis in Wilms' tumor: results from a single center.

The purpose of this study was to identify the prognostic significance of pulmonary and liver involvements present at diagnosis in children with Wilms' tumor. From 1971 to 2002, 57 patients with stage IV Wilms' tumor were diagnosed, treated, and followed in the authors' institution. Metastases were detected by chest radiography, abdominal ultrasonography, and/or thoracoabdominal computed tomography. Nephrectomy with tumor resection was performed and appropriate chemotherapy was given to all the patients. The Kaplan-Meier survival method was used to calculate survival. The log-rank test was used to compare the groups with respect to survival. The age range was 1.25 to 15 years (median 4 years). Thirty-seven patients had only lung metastases, 12 had only liver metastases, 6 had both lung and liver metastases, 1 had adrenal gland metastases, and 1 had other site metastases. The overall survival rate in the whole group was 37.1%. The overall survival rates for lung and liver metastases were 50.2% and 16.6%, respectively. The overall survival rates were significantly different between the two groups (P = 0.005). Only one patient survived in the group with liver involvement. Liver involvement at diagnosis indicates a worse prognosis than lung involvement. Wilms' tumor patients with liver metastases should be treated with more intensive regimens than those with lung metastases.