A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone.

The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE.

A prospective study of pediatric and adolescent renal cell carcinoma: A report from the Children's Oncology Group AREN0321 study.

Background: To the authors' knowledge, AREN0321 is the first prospective clinical study of pediatric and adolescent renal cell carcinoma (RCC). Goals of the study included establishing epidemiological, treatment, and outcome data and confirming that patients with completely resected pediatric RCC, including lymph node-positive disease (N1), have a favorable prognosis without adjuvant therapy.

Methods: From 2006 to 2012, patients aged <30 years with centrally reviewed pathology of RCC were enrolled prospectively.

ADVL1522: A phase 2 study of lorvotuzumab mertansine (IMGN901) in children with relapsed or refractory wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor, or synovial sarcoma-A Children's Oncology Group study.

Background: Lorvotuzumab mertansine (IMGN901) is an antibody-drug conjugate linking an antimitotic agent (DM1) to an anti-CD56 antibody (lorvotuzumab). Preclinical efficacy has been noted in Wilms tumor, rhabdomyosarcoma, and neuroblastoma. Synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), and pleuropulmonary blastoma also express CD56.

The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing.

Background: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG).

Imaging of renal medullary carcinoma in children and young adults: a report from the Children's Oncology Group.

Background: Renal medullary carcinoma is a rare renal malignancy of childhood. There are no large series describing the imaging appearance of renal medullary carcinoma in children.

Objective: To characterize the clinical and imaging features of pediatric renal medullary carcinoma at initial presentation.

Congenital capillary proliferation of the kidney: a distinctive renal vascular lesion of childhood.

Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1).

Diagnostic Utility of Pax8, Pax2, and NGFR Immunohistochemical Expression in Pediatric Renal Tumors.

Pediatric renal tumors (PRT) with small round blue or spindle cell morphology can be diagnostically challenging and only a limited number of immunohistochemical markers have been documented to help in the diagnosis: paired box (Pax) 2 and nerve growth factor receptor (NGFR) positivity have been demonstrated in Wilms tumor (WT) and clear cell sarcoma of the kidney (CCSK), respectively. However, the immunohistochemical expression of these markers in other PRT remains unknown. This study investigated Pax8, Pax2, and NGFR immunophenotype in a large series of PRT.

BRAF exon 15 mutations in pediatric renal stromal tumors: prevalence in metanephric stromal tumors.

Metanephric stromal tumors (MSTs) are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors, along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in MSTs and in other pediatric renal stromal tumors.

ALK-rearranged renal cell carcinomas in children.

Knowledge of the clinicopathological and molecular spectrum of pediatric renal cell carcinomas (RCC) remains limited, and approximately 16%-24% of these neoplasms cannot be classified into specific subtypes. In this review of 168 pediatric RCC prospectively registered on Children's Oncology Group AREN03B2 protocol, six RCC (3.5%) that demonstrated a unique epithelioid morphology and a peculiar immunophenotypic profile that includes expression of ALK, TFE3, and retention of INI1 was identified.

Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations.

Cystic nephromas (CNs) are uncommon benign renal neoplasms that present with a bimodal age distribution, affecting either infants/young children or adult females. Although differences between these age groups have been suggested, large studies of pediatric CN have not been conducted. As a result, the nomenclature and diagnostic criteria for these lesions remain controversial.

Expanding the Spectrum of Renal Tumors in Children: Primary Renal Myoepithelial Carcinomas With a Novel EWSR1-KLF15 Fusion.

We report the first 2 examples of primary renal myoepithelial carcinoma (MEC), both occurring in children. Both tumors had the unique morphologic features, immunophenotype, and EWSR1 gene rearrangements supporting the diagnosis. In keeping with the previous observations of an aggressive behavior in pediatric MEC, both cases presented with advanced local stage and distant metastases at the time of diagnosis.

Juvenile xanthogranuloma: an unusual cause of intratesticular mass in childhood.

Juvenile xanthogranuloma (JXG) is a common histiocytic disorder of infancy and early childhood, most frequently presenting with cutaneous lesions. Whereas involvement of several visceral sites is well documented, only 4 cases of primary testicular JXG have been reported. Although this benign disorder typically presents with a favorable clinical outcome, the unusual presentation as an intratesticular lesion can lead to diagnostic challenges.

DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma.

The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor.

Chronic cyclic bladder over distention up-regulates hypoxia dependent pathways.

Purpose: Bladder over distention secondary to anatomical or functional obstruction can eventually lead to pathological changes, including decreased elasticity and contractile dysfunction. We hypothesized that chronic bladder distention in a murine model would activate hypoxia dependent signaling pathways despite intermittent relief of distention.

Materials And Methods: Female C57Bl/6 mice were oophorectomized at age 5 to 6 weeks and underwent urethral catheterization and 90-minute bladder distention.

Crucial roles of the protein kinases MK2 and MK3 in a mouse model of glomerulonephritis.

Elevated mitogen-activated protein kinase p38 (p38 MAPK) signaling has been implicated in various experimental and human glomerulopathies, and its inhibition has proven beneficial in animal models of these diseases. p38 MAPK signaling is partially mediated through MK2 and MK3, two phylogenetically related protein kinases that are its direct substrates. The current study was designed to determine the specific roles of MK2 and MK3 in a mouse model of acute proliferative glomerulonephritis, using mice with disrupted MK2 and/or MK3 genes.

GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker.

Objective: To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry.

Introduction: Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types.

Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings.

Uniparental disomy (UPD) is defined by the inheritance of both copies of a chromosome pair from one single parent. Although 23 cases of paternal UPD6 have been reported earlier, the occurrence of trisomy 6 rescue with paternal UPD6 has not been previously reported. The phenotype of paternal UPD6 results from biallelic expression of the maternally imprinted, paternally expressed ZAC and HYMAI genes, and includes transient neonatal diabetes mellitus (TNDM), intra-uterine growth restriction (IUGR), macroglossia, and minor anomalies.

Evaluation of human polyomavirus BK as a potential cause of villitis of unknown etiology and spontaneous abortion.

Polyomavirus BK (BKV) is a widely latent pathogen in man. Although viral reactivation during pregnancy has been demonstrated, and polyomaviruses have been linked to chromosomal abnormalities, a pathogenic role for BKV in fetoplacental disease has not been explored. We performed in situ hybridization studies with BKV probes on cases of villitis of unknown etiology (102), diffuse villitis (25), and spontaneous abortion (22).

Sox9 expression is not limited to chondroid neoplasms: variable occurrence in other soft tissue and bone tumors with frequent expression by synovial sarcomas.

The transcription factor Sox9 is known to play a crucial role in normal chondrogenesis, and antibodies against Sox9 have been proposed as a diagnostic tool for neoplasms with chondroid differentiation. However, the pattern of Sox9 immunohistochemical expression by other bone and soft tissue neoplasms, as well as its diagnostic specificity, remain unexplored. The authors have performed immunohistochemistry with antibodies against Sox9 in 106 chondroid and nonchondroid bone and soft tissue neoplasms.

Cystic dysplasia of the epididymis: a disorder of mesonephric differentiation associated with renal maldevelopment.

The occurrence of congenital epididymal malformations with a cystic component has not been fully characterized. Most epididymal cysts occur later in life and are likely acquired. In addition, congenital malformations of the male excretory system are extremely uncommon in fetuses and neonates, and epididymal dysplastic changes have not been reported in these cases.

MT1G hypermethylation: a potential prognostic marker for hepatoblastoma.

Hepatoblastoma comprises only 1% of all cancers in childhood. Because of its low frequency, a small number of prognostic factors are described in hepatoblastoma and most of them are related to resectability. Microarray studies showed a large number of underexpressed genes in hepatoblastoma.

Gaucher or pseudo-Gaucher? The challenge of several diseases colliding in a pediatric patient.

We present here an unusual case in which 3 distinct, apparently unrelated clinical entities were diagnosed in a pediatric patient. A 6-year-old female, previously diagnosed with neurofibromatosis type 1, presented with a mediastinal T-cell lymphoblastic lymphoma; the metabolic and molecular confirmation of Gaucher disease were obtained after typical Gaucher cells were found in the patient's bone marrow after a staging biopsy. The morphological and ultrastructural findings leading to the incidental diagnosis of this rare metabolic disorder are illustrated.