Renal Tumors of Childhood: Radiologic-Pathologic Correlation Part 2. The 2nd Decade: From the Radiologic Pathology Archives.

Malignant renal tumors account for 7% of childhood cancers, and Wilms tumors are by far the most common-but not in older children and adolescents. Among individuals in the latter half of their 2nd decade of life, renal cell carcinoma (RCC) is more common than Wilms tumor. The histopathologic spectrum of RCCs in children differs from that in adults. The most common subtype of RCC in children and adolescents is Xp11.2 translocation RCC, which is distinguished by hyperattenuation at nonenhanced computed tomography, a defined capsule, and associated retroperitoneal lymphadenopathy. Papillary RCC is the second most common histologic subtype. It enhances less intensely compared with the adjacent renal parenchyma and has a propensity for calcification. Clear cell RCC is seen in patients with von Hippel-Lindau disease and is distinguished by its relatively hypervascular nature. Medullary carcinoma affects adolescents with the sickle cell trait and is characterized by an infiltrative growth pattern and extensive metastasis at presentation. Angiomyolipoma is seen in children with tuberous sclerosis complex and is often multifocal and hypervascular, with macroscopic fat. Metanephric tumors are central, circumscribed, and typically calcified. Lymphoma usually manifests as multifocal masses, but it may involve a solitary mass or infiltrative pattern. Extensive adenopathy and involvement of the gastrointestinal tract or other organs also may be seen. Primitive neuroectodermal tumor is an aggressive neoplasm that is typically quite large at diagnosis. Knowledge of the clinical, biologic, and histopathologic features of renal tumors in older children and adolescents and their effects on the imaging appearance can help the radiologist offer a useful preoperative differential diagnosis.

Renal Tumors of Childhood: Radiologic-Pathologic Correlation Part 1. The 1st Decade: From the Radiologic Pathology Archives.

Wilms tumor is the second most common pediatric solid tumor and by far the most common renal tumor of infants and young children. As most tumors are large at presentation and are treated with nephrectomy, the role of imaging is primarily in preoperative planning and evaluation for metastatic disease. However, with treatment protocols increasingly involving use of preoperative (neoadjuvant) chemotherapy (the standard in Europe) and consideration of nephron-sparing surgery, the role of imaging is evolving to include providing initial disease staging information and a presumptive diagnosis to guide therapy. Differential diagnostic considerations include lesions that are clinically benign and others that require more intensive therapy than is used to treat Wilms tumor. In part 1 of this article, the unique histologic spectrum of renal neoplasms of infants and young children is reviewed with emphasis on radiologic-pathologic correlation. Part 2 will focus on renal tumors of older children and adolescents.

From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologic-pathologic correlation.

Genetic defects of cilia cause a wide range of diseases, collectively known as ciliopathies. Primary, or nonmotile, cilia function as sensory organelles involved in the regulation of cell growth, differentiation, and homeostasis. Cilia are present in nearly every cell in the body and mutations of genes encoding ciliary proteins affect multiple organs, including the kidneys, liver, pancreas, retina, central nervous system (CNS), and skeletal system. Genetic mutations causing ciliary dysfunction result in a large number of heterogeneous phenotypes that can manifest with a variety of overlapping abnormalities in multiple organ systems. Renal manifestations of ciliopathies are the most common abnormalities and include collecting duct dilatation and cyst formation in autosomal recessive polycystic kidney disease (ARPKD), cyst formation anywhere in the nephron in autosomal dominant polycystic kidney disease (ADPKD), and tubulointerstitial fibrosis in nephronophthisis, as well as in several CNS and skeletal malformation syndromes. Hepatic disease is another common manifestation of ciliopathies, ranging from duct dilatation and cyst formation in ARPKD and ADPKD to periportal fibrosis in ARPKD and several malformation syndromes. The unifying molecular pathogenesis of this emerging class of disorders explains the overlap of abnormalities in disparate organ systems and links diseases of widely varied clinical features. It is important for radiologists to be able to recognize the multisystem manifestations of these syndromes, as imaging plays an important role in diagnosis and follow-up of affected patients.

From the radiologic pathology archives: precocious puberty: radiologic-pathologic correlation.

Precocious puberty represents a unique diagnostic problem in which imaging plays an important role. Development of secondary sex characteristics may result from inappropriate activation of the hypothalamic-pituitary axis with release of gonadotropin, or from gonadotropin-independent secretion of sex steroids by the adrenal glands or gonads. A variety of lesions can manifest with precocious puberty, including various central nervous system (CNS) lesions, adrenal lesions, and sex cord-stromal tumors of the testis or ovary. CNS lesions causing precocious puberty are much more common in boys than in girls and are well evaluated with brain magnetic resonance imaging. Neoplastic (hypothalamic-chiasmatic astrocytoma, suprasellar germinoma) and nonneoplastic (hypothalamic hamartoma, hydrocephalus, trauma, empty sella, infection, congenital midline anomalies) conditions may affect the function of the hypothalamic-pituitary axis. The adrenal cortex may produce sex hormones. Some adrenal cortical neoplasms (ACNs) in patients under 5 years of age are related to a mutation of the tumor suppressor gene p53 and represent a disease that is distinct from ACNs in older children and adults. Adrenal cortical hyperplasia secondary to an enzymatic defect in steroid biosynthesis causes virilization and salt wasting, which usually manifest in the neonatal period; however, milder forms of the disease may manifest in childhood. Female precocious puberty may be caused by an autonomously functioning ovarian cyst or a juvenile granulosa cell tumor of the ovary. Male precocious puberty may be caused by a sex steroid-producing Leydig or Sertoli cell tumor of the testis. Ultrasonography is the primary modality for evaluating the sex organs and may also be used to evaluate for adrenal abnormalities.

From the archives of the AFIP: Pediatric liver masses: radiologic-pathologic correlation. Part 2. Malignant tumors.

Malignant primary hepatic tumors in children include lesions unique to the pediatric age group and others that are more common in adults. Important considerations when evaluating a child with a liver tumor are the age of the patient, laboratory findings, and specific imaging features. The most common primary malignant hepatic tumor in the pediatric population, hepatoblastoma occurs almost exclusively in patients younger than 5 years with no history of liver disease. Hepatoblastoma is associated with elevated serum α-fetoprotein (AFP) level and appears predominantly solid. Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in older children, often with a history of liver disease. HCC is associated with elevated serum AFP level and also appears as a solid mass. Fibrolamellar carcinoma occurs in adolescents without elevated AFP level and contains a T2-hypointense fibrous scar that usually does not enhance. Undifferentiated (embryonal) sarcoma occurs in young children, contains cystic and mucoid components, and mimics a cyst at magnetic resonance imaging and computed tomography but appears solid at ultrasonography. Epithelioid hemangioendothelioma is a multifocal vascular tumor in older children with a distinctive imaging appearance of confluent peripheral nodules with adjacent capsular retraction. Angiosarcoma rarely occurs in young children and frequently shows evidence of hemorrhage. Embryonal rhabdomyosarcoma of the biliary tree is unique to children, usually under 5 years of age, and frequently demonstrates an intraductal growth pattern. Knowledge of the pathologic features of these tumors and their imaging appearances can help radiologists offer an appropriate differential diagnosis and management plan.

Educational Case: Hydatidiform Molar Pregnancy.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Basal Cell Carcinoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Osteoid Osteoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Ewing Sarcoma of Bone.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040. 1.

Educational Case: Neisseria Meningitis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040.1.

From the archives of the AFIP: Pediatric liver masses: radiologic-pathologic correlation part 1. Benign tumors.

Benign hepatic tumors in children include lesions that are unique to the pediatric age group and others that are more common in adults. Infantile hemangioendothelioma, or infantile hepatic hemangioma, is a benign vascular tumor that may cause serious clinical complications. It is composed of vascular channels lined by endothelial cells. At imaging, large feeding arteries and draining veins and early, intense, peripheral nodular enhancement with centripetal filling on delayed images are characteristic features. Mesenchymal hamartoma of the liver occurs in young children and is characterized pathologically by mesenchymal proliferation with fluid-containing cysts of varying size and number. The mesenchymal component or cystic component may predominate; this predominance determines the imaging appearance of the tumor. Benign epithelial tumors that are common in adults may infrequently occur in childhood. These include focal nodular hyperplasia (FNH), hepatocellular adenoma, and nodular regenerative hyperplasia. All are composed of hyperplastic hepatocytes similar to surrounding liver parenchyma and may be difficult to discern at imaging. Preferential hepatic arterial phase enhancement helps distinguish FNH and hepatic adenoma from uninvolved liver. Hepatic adenoma often has intracellular fat and a propensity for intratumoral hemorrhage, neither of which are seen in FNH. Unlike adenoma, FNH often contains enough Kupffer cells to show uptake at sulfur colloid scintigraphy. Nodular regenerative hyperplasia is often associated with portal hypertension, which may be evident at imaging. Knowledge of how the pathologic features of these tumors affect their imaging appearances helps radiologists offer an appropriate differential diagnosis and management plan.

Educational Case: Acute Appendicitis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Gender Parity in Gainful Employment and Other Gender Trends in the Job Market for Recent Pathology Graduates.

CONTEXT.­: Gender-based barriers to equal salary, career advancement, and leadership still exist in medicine. Herein we provide the first report of data comparing the experiences of men and women seeking their first nonfellowship position in pathology. OBJECTIVE.­: To identify gender trends regarding pathologists taking their first job after training and the relationship to various demographic factors, job search satisfaction, and outcome. DESIGN.­: Aggregate data from the College of American Pathologists Graduate Medical Education Committee Job Market surveys (2015-2018) were analyzed across multiple domains including residency focus, number and subspecialty of fellowships completed, and extent to which expectations were met in regard to work duties, geographic preference, benefits, and salary. These data were examined in the context of assessing gender-based differences. RESULTS.­: Comparable results were identified in all measured outcomes according to gender. There were no differences between gender and medical school type, relocation, residency training focus, number of fellowships completed, overall satisfaction with position accepted, salary, or extent to which the position met expectations. Similarly, there were also no discrepancies between gender and the geographic region in which positions were accepted, practice setting, practice subspecialty, partnership track, length of job search, or difficulty finding a position. CONCLUSIONS.­: Analysis from 4 years of job market survey data shows equivalent results between men and women looking for their first nonfellowship position in pathology. There were no significant differences with regard to difficulty finding a position, overall satisfaction with the position accepted, salary, benefits, or access to partnership track.

Entry of Graduates of US Pathology Residency Programs Into the Workforce: Cohort Data Between 2008 and 2016 Remain Positive and Stable.

The pathologist workforce in the United States is a topic of interest to the health-care community as a whole and to institutions responsible for the training of new pathologists in particular. Although a pathologist shortage has been projected, there has been a pervasive belief by medical students and their advisors that there are "no jobs in pathology." In 2013 and again in 2017, the Program Directors Section of the Association of Pathology Chairs conducted surveys asking pathology residency directors to report the employment status of each of their residents graduating in the previous 5 years. The 2013 Program Directors Section survey indicated that 92% of those graduating in 2010 had obtained employment within 3 years, and 94% of residents graduating in 2008 obtained employment within 5 years. The 2017 survey indicated that 96% of those graduating in 2014 had obtained employment in 3 years, and 97% of residents graduating in 2012 obtained positions within 5 years. These findings are consistent with residents doing 1 or 2 years of fellowship before obtaining employment. Stratification of the data by regions of the country or by the size of the residency programs does not show large differences. The data also indicate a high percentage of employment for graduates of pathology residency programs and a stable job market over the years covered by the surveys.

Educational Case: Barrett Esophagus.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Educational Case: Pediatric Osteosarcoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Educational Case: Wilms Tumor (Nephroblastoma).

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Hemolysin of uropathogenic Escherichia coli evokes extensive shedding of the uroepithelium and hemorrhage in bladder tissue within the first 24 hours after intraurethral inoculation of mice.

Many uropathogenic Escherichia coli (UPEC) strains produce both hemolysin (Hly) and cytotoxic necrotizing factor type 1 (CNF1), and the loci for these toxins are often linked. The conclusion that Hly and CNF1 contribute to urovirulence is supported by the results of epidemiological studies associating the severity of urinary tract infections (UTIs) with toxin production by UPEC isolates. Additionally, we previously reported that mouse bladders and rat prostates infected with UPEC strain CP9 exhibit a more profound inflammatory response than the organs from animals challenged with CP9cnf(1) and that CNF1 decreases the antimicrobial activities of polymorphonuclear leukocytes. More recently, we created an Hly mutant, CP9Delta hlyA(1)::cat, and showed that it was less hemolytic and destructive for cultured bladder cells than CP9 was. Here we evaluated the relative effects of mutations in hlyA(1) or cnf(1) alone or together on the pathogenicity of CP9 in a mouse model of ascending UTI. To do this, we constructed an hlyA(1)-complemented clone of CP9Delta hlyA(1)::cat and an hlyA(1) cnf(1) CP9 double mutant. We found that Hly had no influence on bacterial colonization of the bladder or kidneys in single or mixed infections with the wild type and CP9Delta hlyA(1)::cat but that it did provoke sloughing of the uroepithelium and bladder hemorrhage within the first 24 h after challenge. Finally, we confirmed that CNF1 expression induces bladder inflammation and, in particular, as shown in this study, submucosal edema. From these data, we speculate that Hly and CNF1 may be largely responsible for the signs and symptoms of cystitis in humans infected with toxigenic UPEC.