Wilms' Tumour – Histology and Differential Diagnosis

Wilms’ tumour (WT) is the most common paediatric renal tumour, which can present as a single nodule, as multifocal unilateral lesions or as bilateral tumours. Typically, WT comprises three histological components namely blastemal, epithelial and stromal. The proportion and the degree of maturation of these components vary significantly, making the histological appearance of each tumour unique. Classical triphasic WT rarely presents diagnostic difficulty for pathologists, but when only one component is present, especially in a small biopsy specimen, the differential diagnosis may include renal cell carcinoma, metanephric adenoma and hyperplastic nephrogenic rest for epithelial elements and clear cell sarcoma of the kidney, mesoblastic nephroma and synovial sarcoma for stromal elements. Pure blastemal-type WT may be difficult to distinguish from other embryonal ‘small round blue cell tumours’, including neuroblastoma, primitive neuroectodermal tumour/Ewing sarcoma, desmoplastic small round cell tumour and lymphoma. All the three components, though usually blastema, can become anaplastic, leading to the diagnosis of either focal or diffuse anaplasia. WT with diffuse anaplasia and WT with blastemal predominance (after preoperative chemotherapy) are regarded as high-risk tumours and require more aggressive treatment. Careful assessment of the tumour and the normal kidney is critical for accurate subtyping and staging of WT, which is the basis for post-operative treatment. In addition, the identification and correct interpretation of nephrogenic rests may affect prognosis and management. Histological distinction between WT and nephrogenic rest is not always possible based on morphology alone, and implementation of new molecular genetic tools may aid in this regard. Other molecular genetic signatures of WT, such as P53 mutation and MYCN dysregulation, may provide future additional prognostic and therapeutic information

Prognostic significance of histopathological response to preoperative chemotherapy in unilateral Wilms' tumor: An analysis of 899 patients treated on the SIOP WT 2001 protocol in the UK-CCLG and GPOH studies

In the SIOP Wilms' tumor (WT) studies, preoperative chemotherapy is used as primary treatment, and tumors are classified thereafter by pathologists. Completely necrotic WTs (CN-WTs) are classified as low-risk tumors. The aim of the study was to evaluate whether a subset of regressive type WTs (RT-WTs) (67%-99% chemotherapy-induced changes [CIC]) showing an exceptionally good response to preoperative chemotherapy had comparably excellent survivals as CN-WTs, and to establish a cut-off point of CIC that could define this subset. The study included 2117 patients with unilateral, nonanaplastic WTs from the UK-CCLG and GPOH-WT studies (2001-2020) treated according to the SIOP-WT-2001 protocol. There were 126 patients with CN-WTs and 773 with RT-WTs, stages I-IV. RT-WTs were subdivided into subtotally necrotic WTs (>95% CIC) (STN-WT96-99) (124 patients) and the remaining of RT-WT (RR-WT67-95) (649 patients). The 5-year event-free survival (EFS) and overall survival (OS) for CN-WTs were 95.3% (±2.1% SE) and 97.3% (±1.5% SE), and for RT-WTs 85.7% (±1.14% SE, P < .01) and 95.2% (±0.01% SE, P = .59), respectively. CN-WT and STN-WT96-99 groups showed significantly better EFS than RR-WT67-95 (P = .003 and P = .02, respectively), which remained significantly superior when adjusted for age, local stage and metastasis at diagnosis, in multivariate analysis, whereas OS were superimposable (97.3 ± 1.5% SE for CN-WT; 97.8 ± 1.5% SE for STN-WT96-99; 94.7 ± 1.0% SE for RR-WT67-95). Patients with STN-WT96-99 share the same excellent EFS and OS as patients with CN-WTs, and although this was achieved by more treatment for patients with STN-WT96-99 than for patients with CN-WT, reduction in postoperative treatment of these patients may be justified

Rare non-Wilms' tumors in children

We report our institutional experience of the management of 2 cases of rare non-Wilms' tumors; a rhabdoid tumor in a 17-month old boy and a clear cell sarcoma in a 5-year old girl. The two patients were treated with ifosfamide/carboplatin/etoposide (ICE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and cyclophosphamide/etoposide (CE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and radiotherapy, respectively. Both patients showed full response with no significant adverse events. At 2-year follow up, they are disease and relapse free. Although contemporary treatment regimens are very promising, multicenter collaborative studies are needed in order to define a standard treatment for non-Wilms' tumors

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

Adult urinary bladder tumors with rabdomyosarcomatous differentiation: Clinical, pathological and immunohistochemical studies

Adult rhabdomyosarcoma (RMS) in the urinary bladder is rare, and is the subject of case reports and small series. It consists of sheets of small round blue cells with high nuclear cytoplasmic ratio, brisk mitosis and apoptosis. In this study, we reported one case of pure rhabdomyosarcoma and two cases of urothelial carcinomas with extensive rhabdomyosarcomatous differentiation. In addition, their immunohistochemical profile was compared to that of small cell carcinoma of the bladder. Our study showed that sufficient sampling was critical for the diagnosis of urothelial carcinoma with extensive rhabdomyosarcomatous differentiation. As adult RMS in the bladder and urothelial carcinoma with rhabdomyosarcomatous differentiation shared morphological features with small cell carcinoma of the bladder, appropriate immunohistochemical stains were necessary in the differential diagnosis. We showed both rhabdomyosarcoma and rhabdomyosarcomatous areas of the urothelial carcinoma were positive for myogenin, negative for cytokeratin and chromogranin stains. In contrast, small cell carcinoma was positive for cytokeratin, and 7 out of 9 cases were also positive for chromogranin. Both rhabdomyosarcoma and small cell carcinoma could be positive for synaptophysin, a potential pitfall to avoid. In addition, all of the tumors with rhabdomyosarcomatous differentiation were negative for FKHR rearrangement

Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and/or nephroblastomatosis: The 30-year SIOP-RTSG experience

BACKGROUND: WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence. METHODS: Clinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) registries and the SIOP-RTSG network (1989-2019). Events were defined as relapse, metachronous tumors, or death. RESULTS: Forty-three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6-44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5-year event-free survival rate was 84.3% (95% confidence interval, 72.4%-98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%-100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1). CONCLUSIONS: Patients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised. LAY SUMMARY: WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor. In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) and the SIOP-RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur. Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93‐01, 2001 and UK‐IMPORT database: A report of the SIOP‐Renal Tumor Study Group

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing

High Cyclin E Staining Index in Blastemal, Stromal or Epithelial Cells Is Correlated with Tumor Aggressiveness in Patients with Nephroblastoma

PURPOSE: Identifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as a regulator of progression through the cell cycle and Ki-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies. METHODOLOGY/PRINCIPAL FINDINGS: A staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotherapy nephroblastoma including 42 nephroblastoma without metastasis and 12 with metastases. Median cyclin E and Ki-67 SI were 46% and 33% in blastemal cells, 30% and 10% in stromal cells, 37% and 29.5% in epithelial cells. The highest values were found for anaplastic nephroblastoma. A correlation between cyclin E and Ki-67 SI was found for the blastemal component and for the epithelial component. Univariate analysis showed prognostic significance for metastases with cyclin E SI in stromal cells, epithelial cells and blastemal cells (p = 0.03, p = 0.01 and p = 0.002, respectively) as well as with Ki-67 SI in blastema (p<10(-4)). The most striking data were that both cyclin E SI and blastemal Ki-67 SI discriminated between patients with metastases and patients without metastasis among intermediate-risk nephroblastoma. CONCLUSIONS: Our findings show that a high cyclin E SI in all components of nephroblastoma is correlated with tumor aggressiveness and metastases, and that assessment of its expression may have prognostic value in the categorization of nephroblastoma

Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma

Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed.info:eu-repo/semantics/publishedVersio