Congenital mesoblastic nephroma 50 years after its recognition: A narrative review.

Congenital mesoblastic nephroma (CMN) is a rare pediatric renal tumor with low malignant potential that most commonly occurs early in infancy. Treatment strategies are based on the few published CMN series, while a significant number of CMN patients have been described in case reports. The aim of this narrative review was to create an up-to-date overview of the literature. Complete surgical removal is curative in most cases. The risk of treatment-related mortality (both surgery- and chemotherapy-related) is relatively high in the first weeks of life, indicating that these young patients deserve special attention with respect to timing and type of treatment.

Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. PATIENTS AND METHODS: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. RESULTS: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%). CONCLUSIONS: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.

[Primitive neuroectodermal tumor of the kidney in children; its differential diagnosis with Wilms tumor].

There may be a number of tumors made up by small round blue cells in the kidneys of children. One of them is primitive neuroectodermal tumor (PNET). The differences in therapeutic approaches determine the need to establish an accurate diagnosis. The differential diagnosis of PNET and the blastemal component of Wilms tumor can be difficult due to the similar histological pattern. There is a need for a close analysis of morphological manifestations, by keeping in mind the age of patients, and supplementary studies. A strong CD99 membrane expression and nuclear FLI1 expression in tumor cells are the signs of PNET. Reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization can determine PNET-specific translocations [t(11;22)(q24;q12), by involving the EWS gene.

Outcome of localised blastemal-type Wilms tumour patients treated according to intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal Tumour Study Group (SIOP-RTSG).

Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.

Fibrochondrogenesis in a 17-week fetus: a case expanding the phenotype.

Fibrochondrogenesis is a very rare form of lethal short-limb dwarfism, with 8 cases described since it was first reported in 1978. It is becoming clear that this condition has certain radiological and histological characteristics that distinguish it from other skeletal dysplasias. We herein present a further case of fibrochondrogenesis diagnosed in a fetus of 17 weeks, which is the youngest patient reported so far. In addition, the fetus showed severe micrognathia and a bifid tongue. These are not previously described manifestations, which extend the phenotype of this rare condition.

Bilateral femoral agenesis in femoral facial syndrome in a 19-week-old fetus.

Although the cause in most cases is unknown, there is a strong association of the femoral facial syndrome (FFS) with maternal diabetes mellitus. We describe an unusual presentation of FFS in the first pregnancy of a diabetic mother terminated at 19 weeks gestation because of bilateral femoral agenesis diagnosed on ultrasound scan. Autopsy confirmed the absence of the femora and acetabula and the presence of the facial traits of FFS in a female fetus.

Improving the quality of perinatal and infant necropsy examinations: a follow up study.

AIM: To compare the quality of perinatal and infant necropsy examinations in 1996 with those performed in 1993. METHODS: Cohort analysis, with data from the All Wales Perinatal Survey, of 1027 deaths (540 in 1993; 487 in 1996) of babies between 20 weeks' gestation and one year of age. The quality of the necropsy was assessed by scoring aspects identified as being part of the investigation. RESULTS: Necropsy was performed in 335 cases (62%) in 1993 and in 320 cases (66%) in 1996. The proportion done in a regional centre increased significantly from 39% (131/335) in 1993 to 76% (243/320) in 1996 (p < 0.0001). The quality of necropsy was above the minimum standard in 54% of cases in 1993 (171/314) compared with 93% in 1996 (289/312) (p < 0.0001). Improvement occurred in all categories. For stillbirths, 35% (46/133) were above the minimum standard in 1993 compared with 90% (104/116) in 1996 (p < 0.0001); for cases not classified as sudden unexpected death in infancy (SUDI), the improvement was from 62% in 1993 (40/65) to 97% in 1996 (73/75) (p < 0.0001); and for SUDI cases, the improvement was from 32% in 1993 (10/31) to 91% in 1996 (21/23) (p < 0.0001). The quality of both non-regional and regional necropsies improved. For non-regional cases, the score was above the minimum standard in 28% (51/183) in 1993 compared with 69% (52/75) in 1996 (p < 0.0001); for regional cases it improved from 92% (120/131) in 1993 to 100% (237/237) in 1996 (p < 0.0001). CONCLUSIONS: The quality of perinatal and infant necropsies improved considerably between 1993 and 1996, reflecting better awareness of the importance of good quality examination and an increase in referrals to paediatric centres.

Perinatal and infant postmortem examinations: how well are we doing?

AIM: To investigate the quality of perinatal and infant necropsies and assess the relation between the quality and value of this investigation in different outcome groups. METHODS: Cohort analysis of 540 deaths during 1993 of babies between 20 weeks' gestation and one year of age born to women usually resident in Wales. Cases were identified from the All Wales Perinatal Survey. Each case was assessed to establish whether the necropsy yielded clinically relevant information. The quality of necropsy was assessed by scoring aspects identified as being part of the necropsy. RESULTS: Necropsy was performed in 335 (62%) cases, and the report was available for assessment in 314 cases. The quality of necropsy was below the minimum standard in 46% (143/314) of cases. The highest quality necropsies were carried out on fetal deaths at 20 to 23 weeks' gestation (12% (10/85) below standard), compared with 65% (87/133) below standard on stillbirths and 68% (21/31) on sudden unexpected infant death. Overall, 42% (131/314) of necropsies were performed in a regional paediatric pathology centre including 88% (76/88) of fetal deaths, 23% (31/133) of stillbirths and 30% (29/96) of infant deaths. The quality score for the necropsy performed in a regional centre failed to achieve the minimum acceptable score in 8% (11/131) of cases compared with 72% (132/182) for those done elsewhere. The cause of death was detected by necropsy in 17% (52/314) of cases. The quality of necropsy was significantly higher when the cause of death was revealed than when nothing new was found. CONCLUSIONS: The overall quality of the perinatal and infant necropsy is poor. This is regrettable as valuable information can be revealed frequently by a good quality necropsy. Adherence to Guidelines for Postmortem Reports recently published by the Royal College of Pathologists should improve the situation.

Non-Hodgkin's lymphoma of the uterus and CNS.

We report a case of a non-Hodgkin's lymphoma of the uterus and central nervous system in an 8-year-old female. The neurologic signs included blurred vision, neck stiffness, and walking difficulties but no abdominal problems. She deteriorated further, and repeated lumbar punctures revealed the presence of malignant cells in the cerebrospinal fluid. A repeated ultrasound scan of the abdomen demonstrated a markedly enlarged uterus. Biopsy revealed B-cell non-Hodgkin's lymphoma. Treatment according to the Berlin-Frankfurt-Münster protocol was initiated, but she developed hyperventilation syndrome and required mechanical ventilation. Her condition improved after 1 week but then deteriorated again, and despite additional chemotherapy she developed myelosuppression and septicemia with multiresistant Klebsiella pneumoniae and eventually died 13 months after her first admission to the hospital. No clinical or laboratory signs of relapse were evident at the time of death.

The immunocytochemical demonstration of a relative lack of nerve fibres in the atrioventricular node and bundle of His in the sudden infant death syndrome (SIDS).

Whilst examining the variation with age of the nerve fibre content of the cardiac conduction system (CCS), using an immunocytochemical approach, it became evident that in two sudden infant death syndrome (SIDS) cases there was a selective lack of S100 positive nerve fibres in the atrioventricular (AV) node and His bundle. In the present study therefore, the examination of CCS with S100 was extended to a further five SIDS cases and three cases of sudden explained death. Also, in addition to S100--which selectively marks Schwann cells associated with both myelinated and non-myelinated nerves--PGP 9.5 (protein gene product) was used to reveal the presence of nerve axonal elements associated with the CCS. The results showed a uniform presence of S100 and PGP 9.5 positive nerve fibres in the sinoatrial (SA) node, the AV node and His bundle tissue of all three control cases. In contrast, five out of seven SIDS cases showed a uniform lack of staining with these markers in the AV node and His bundle tissue, whilst in the two remaining cases it was present in greatly diminished amounts. Staining in the SA node, although present in all seven cases, was reduced when compared with the control cases. This is the first time the CCS of SIDS cases has been studied with immunocytochemical markers of nerve elements. The overall results taken in conjunction with the epidemiology of SIDS suggest that the lack of AV node and His bundle innervation most probably reflects a delay in the development or maturation of the nerve elements of the CCS, similar to that noted for other parts of the central and peripheral nervous systems in SIDS.

Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths.

OBJECTIVES: To evaluate the contribution that perinatal and infant necropsy makes to clinical practice and to see how this might be influenced by the quality of the investigation. DESIGN: Cohort analysis, with data from the all Wales perinatal survey, of perinatal and infant deaths during 1993 of babies born to mothers usually resident in Wales. The clinicopathological classification of death based on clinical details was compared with the classification after necropsy. Similarly, cases in which necropsy yielded new information were identified. The quality of the necropsy was assessed by scoring six aspects of the examination. SUBJECTS: 400 consecutive deaths at 20 weeks of gestation to 1 year of age. MAIN OUTCOME MEASURES: Necropsy rate, effect of necropsy on clinicopathological classification, new information disclosed by necropsy, quality of necropsies, and the link between new information and quality of the necropsy. RESULTS: Necropsy was performed in 232 cases (58%). The clinicopathological classification was altered by necropsy in 29 cases (13%). New information was obtained in 60 cases (26%), and in 42 (18%) it disclosed the cause of death. The quality of necropsy was substantially higher when the main cause of death was detected than when nothing new was found. CONCLUSION: Necropsy is underused. Clinicians should be more positive about necropsies and realise how much clinically relevant information can be obtained from a good quality examination.

Clear cell sarcomas of the kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP Renal Tumour Study Group.

PURPOSE: Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood renal tumour. Only a few homogeneously treated CCSK cohorts have been reported. This study aims to describe clinical characteristics and survival of CCSK patients treated according to recent International Society of Pediatric Oncology (SIOP) protocols. PATIENTS AND METHODS: We analysed the prospectively collected data of patients with a histologically verified CCSK, entered onto SIOP 93-01/2001 trials. RESULTS: A total of 191 CCSK patients (64% male) were analysed, with a median age at diagnosis of 2.6 years. Stage distribution for stages I, II, III and IV was 42%, 23%, 28% and 7%, respectively. Pre-operative chemotherapy was administered to 169/191 patients. All patients underwent total nephrectomy and 189/191 patients received post-operative chemotherapy. Radiotherapy was applied in 2/80 stage I, 33/44 stage II, 44/54 stage III and 6/13 stage IV patients. Five year event-free survival (EFS) and overall survival (OS) were 79% (95% confidence interval (CI): 73-85%) and 86% (95% CI: 80-92%) respectively. Stage IV disease and young age were significant adverse prognostic factors for event-free survival. Factors such as gender, tumour volume and type of initial treatment were not found to be prognostic for EFS and OS. CONCLUSION: In this largest SIOP cohort described so far, overall outcome of CCSK is reasonable, although treatment of young and advanced-stage disease patients is challenging. As further intensification of treatment is hampered by direct and late toxicity, future directions should include the development of targeted therapy based on specific molecular aberrations of CCSK.

Clear cell sarcoma of the kidney: a review.

Clear cell sarcoma of the kidney (CCSK) is a rare renal tumour that is observed most often in children under 3years of age. Only a few large series of CCSK have been reported and patients with CCSK are often included among patients with other types of childhood renal tumours. The purpose of this paper is to review the published series and case reports of CCSK and to create an up-to-date overview of clinical and histological features, genetics, treatment, and outcome.

The pathology of Wilms' tumour (nephroblastoma): the International Society of Paediatric Oncology approach.

In the International Society of Paediatric Oncology renal tumour trials, preoperative chemotherapy has been successfully applied with resulting reduction of tumour rupture and increased favourable stage distribution of nephroblastoma. Postoperative treatment includes chemotherapy and sometimes radiotherapy in a risk-adapted approach based on histological sub-classification and stage of the tumour. However, preoperative chemotherapy alters the tumour's histological features and distribution of subtypes, and makes staging more difficult. The paper highlights the most common practical diagnostic difficulties that a pathologist is faced with in dealing with pretreated nephroblastomas. It emphasises the importance of a systematic, step-by-step analysis based on adequately sampled material, in order to accurately sub-classify a nephroblastoma as a low, intermediate or high risk tumour and assign its genuine stage. Finally, it outlines the standard operating procedure for submission of renal tumours for rapid central pathology review which allows the treating oncologists to apply the optimal treatment protocol.

Congenital cystic mesoblastic nephroma: a rare cystic renal tumour of childhood. Case report.

A 3-month-old baby boy presented with a right-sided abdominal mass that was shown on radiographic and ultrasonographic examination to be cystic and within the kidney. Histological examination of the right nephrectomy specimen showed it to be a congenital cystic mesoblastic nephroma. The patient made an uneventful recovery and there were no signs of recurrence eight years later. Though this tumour is extremely rare it should be considered as a differential diagnosis in infancy as its prognosis and treatment are different from those of other tumours.

Teratoid Wilms' tumor: report of a unilateral case.

A unilateral teratoid Wilms' tumor was removed 2.5 weeks after the institution of chemotherapy. Teratoid Wilms' tumor is an extremely rare renal tumor, and only four cases, all bilateral, have been reported. Because of the finding of deep cortical intralobar nephroblastomatosis, strongly associated with bilateral Wilms' tumors, the patient has been closely followed since surgery without evidence of tumor in the remaining kidney at 2 years.

Diversion colitis in children: an iatrogenic appendix vermiformis?

AIMS: Diversion colitis (DC) is a localized, relatively benign, iatrogenic condition which occurs in almost 100% of diverted colonic segments in patients who undergo ileostomy/colostomy for various reasons. The aim of this study was to establish histological features of DC in children. METHODS AND RESULTS: Twenty-three cases of DC following colostomy for Hirschsprung's disease in young children were analysed. The distinguishing features included prominent follicular lymphoid hyperplasia (100%), chronic mucosal inflammation (100%), accompanied by a variable degree of acute inflammation (78%) and Paneth cell metaplasia (26%). Less frequent histological findings were as follows: mild goblet cell depletion (22%), foci of cryptitis (13%), crypt abscesses (13%) and mild architectural distortion (22%). A previously unrecognized feature was the presence of mucosal aggregates of eosinophils, found in 43% of cases. A striking similarity between the normal appearance of the vermiform appendix and pathological features in DC was noted and the possible relationship between the two is discussed. CONCLUSIONS: Histological features of DC in children are very similar to those described in adults. They should help to distinguish it from ulcerative colitis and Hirschsprung's-associated enterocolitis in order to prevent inappropriate therapy and follow-up. There are many similarities between DC and the normal appendix vermiformis.

New case of Beemer-Langer syndrome.

We present the case of a male infant born at 37 weeks gestation with multiple congenital anomalies, including hydrops fetalis, facial and visceral abnormalities, short ribs, and short limbs without polydactyly. We believe that this represents a further case of the Beemer-Langer syndrome, a relatively recently described form of lethal osteochondrodysplasia with an autosomal recessive mode of inheritance. This case also showed some less frequently described anomalies, including arachnoid cysts of the brain and short intestines.

Inflammatory pseudotumor of the lung in children.

Two children with inflammatory pseudotumor (IPT) of the lung are reported. Symptomless "cystic" lesions were present on routine chest x ray. Morphological study of these peculiar lesions included light microscopic, immunohistochemical, and ultrastructural analysis. Histologic appearance of the lesion varied from the features of granulation tissue on the periphery to bundles of spindle-shaped cells in the central area. Immunohistochemical findings had no diagnostic value but were helpful in excluding other tumors. Ultrastructural analysis confirmed the mixed cellular composition and benign nature of the lesion. Etiopathogenesis of this process is unknown. IPT can be differentiated from similar lesions and must not be mistaken for malignant tumor. Proper treatment by complete surgical removal of the lesion usually cures the patient.