This chapter provides a practical guide to cytogenetic analysis of hematologic malignancies in children. It focuses on conventional cytogenetic analysis as well as fluorescent in situ hybridization (FISH), including nomenclature, analytical methodologies, and interpretation of various FISH probes. It also provides information on recurring genetic abnormalities in pediatric hematopoietic neoplasms. The chapter is well illustrated and provides helpful information to pathology trainees and practicing hematopathologists.

Acute leukemia is the most common pediatric malignancy. Both acute lymphoblastic and acute myeloid leukemias are risk-stratified according to the clinical and laboratory features at the time of presentation and response to therapy. This chapter provides up-to-date reviews of the epidemiology, etiology, clinical presentation, risk factors, and risk-stratified treatment options for best response to therapy and overall survival. It reviews recent advances in treatment of childhood acute leukemia such as immunotherapy and chimeric T-cell antigen receptor therapy.

The metastatic potential of pediatric solid tumors to the bone marrow varies. This chapter reviews the indications of bone marrow evaluation in children with solid tumors. The various morphologic and immunohistochemistry patterns of neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and other tumors are presented and well-illustrated. The bone marrow requirements for adequacy and reporting are addressed as well. The chapter also provides helpful information on how to distinguish non-hematopoietic tumor cells from the normal B-cell progenitors, a frequent finding in patients with solid tumors regardless of the metastatic state.

The immune system is not fully developed at birth and continues to evolve in the first several years of life. For that reason, in children, lymphadenopathies are frequent, but most of the time they are transient, self-limiting, and resolve without sequel. This chapter provides a comprehensive review of the reactive lymphadenopathies in children. It starts with key points in the development, structure, and function of lymph nodes and the normal immune reaction. Then, it focuses on the histopathologic features, epidemiology, clinical presentation, and differential diagnosis of the most frequent reactive lymphoid proliferations in children. The emphasis is on those entities that present major diagnostic challenges in distinguishing benign from malignant disorders, as well as those pediatric lymphadenopathies that are seen in conjunction with specific syndromes. Distinctions between pediatric and adult lymphoid proliferations are made. The chapter also provides a diagnostic framework to the pathologist of how to work up a lymph node biopsy of a child. It is well illustrated with numerous figures, tables, and schematics.

Major strides have been made in our understanding of the molecular pathogenesis of the major pediatric acute leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), advances fueled by significant innovation in the technologies available for the high-throughput, large-scale analysis of nucleic acids. These innovations, including polymerase chain reaction and next generation sequencing–based methodologies for the analysis of both DNA and RNA, together with the development of bioinformatic capability to analyze the enormous amount of data generated by these technologies now permit the comprehensive analysis of the genomics and epigenomics of cancer cells in the clinical laboratory at a level of resolution that was inconceivable 20 years ago. Currently available molecular diagnostics permit the precise classification of human malignancies, including ALL and AML, and hold great promise for providing more meaningful prognostication and helping to guide the appropriate use of molecularly targeted therapeutics. This chapter provides an introduction to molecular diagnostics, reviewing those aspects most relevant to evaluation of pediatric acute leukemia and with a focus on currently available technologies, practical aspects of laboratory analysis of clinical samples, and the role of bioinformatics in the analysis of molecular diagnostic data.

The concept of the “histiocyte” (tissue cell) has evolved and is now often used as a collective term for two related groups of immune regulatory cells, the monocyte–macrophage and the dendritic cell–accessory antigen presenting cells. The histiocytic proliferations of childhood encompass reactive as well as benign and malignant clonal accumulations of monocyt–-macrophages and of hematopoietic derived dendritic cells. While distinguishing between their reactive and neoplastic states can be challenging at times, molecular-based testing can help refine the diagnosis of neoplastic accumulations. This comprehensive chapter discusses: 1. the origins and definitions of steady-state native histiocytes; 2. the most common non-neoplastic pathologic accumulations of macrophages and dendritic cells; 3. the updated understanding and nomenclature of macrophage activation and the hemophagocytic syndromes with clinical relevance; and 4. the pathology and differential diagnosis of clonally related histiocytic neoplasms with molecular integration, including Langerhans cell histiocytosis, juvenile xanthogranuloma family lesions with an integrated histopathologic approach, Rosai–Dorfman–Destombes disease, and malignant histiocytic neoplasm, including secondary malignant histiocytosis occurring after leukemia. There is also discussion of new and emerging entities such as ALK-positive histiocytosis and MAPK-related histiocytosis. Lastly, a brief summary on the non-hematopoietic, mesenchymal-derived sarcomas with historical “dendritic” cell nomenclature is discussed.

Unlike other organ systems, the hematopoiesis is unique, and its anatomic location shifts during the embryogenesis and fetal development from yolk sac to fetal liver, and to bone marrow. At birth and thereafter, it is restricted to the bone marrow, which continues to evolve to accommodate the changing oxygenation needs of the growing child. The composition of the bone marrow in young children reflects such physiologic transformation and differs compared to adults, particularly early in life. Knowledge of such differences is imperative, so changes due to normal development are not misinterpreted as pathologic processes.

This is a case of pediatric respiratory distress in which airway foreign body should be very high on the differential. The physician can wait for ENT assistance as the child is not immediately crashing, but needs to prepare for emergent airway management.

This chapter discusses the immunophenotypic features of adult and pediatric follicular lymphoma (FL), including those with atypical immunophenotypes such as CD5+ or CD10−. The differential diagnosis includes CD10+ non-neoplastic but monotypic B-cell processes and CD10+ B-cell lymphomas/leukemias other than FL.

This is a case of HUS in a child following an episode of diarrhea. It highlights the recognition, management, and likely good outcome of HUS in children.

Our chapter explores the ethical and systemic challenges faced by healthcare staff when caring for an adolescent patient boarding in the emergency room (ER). We use the case of Samantha, an indigenous adolescent, brought to the ER after trying to elope from her youth treatment center. Samantha’s prolonged stay in the ER highlights significant gaps in healthcare; society’s struggle to address the needs of vulnerable populations; and the healthcare staff’s efforts to fulfill the duties of beneficence, nonmaleficence, and justice. Samantha’s case underscores the need for improved clinical and institutional processes and support systems. We advocate for better access to ethics support, enhanced community resources, and a more inclusive approach to care that considers the unique needs of marginalized individuals. Our case also reflects on the emotional and moral toll experienced by healthcare providers, exacerbated by systemic injustice and an unclear pathway to access our ethics committee at the time. We hope this case provides insights for healthcare systems to develop comprehensive strategies to support adolescents boarding in the ER ensuring their dignity.

This chapter contains order sets for pediatric patients for vital signs, activity, diet, nursing interventions, respiratory interventions, laboratory tests, radiology studies, interventional radiology procedures, cardiac studies, neurology studies, and various pediatric consultants

Although the principles of pediatric observation medicine are the same as for adults; e.g. more efficient, safer, cost-effective care with decreased length of stay and equivalent or better patient outcomes; there are differences between pediatric and adult observation unit (OU) patients. The diagnoses are somewhat different with asthma, dehydration, gastroenteritis among the top pediatric diagnoses. Pediatric patients tend to need less cardiac monitoring, fewer medications and fewer laboratory and radiologic studies than adults and have a shorter length of stay. Respiratory illnesses, infections and dehydration/gastroenteritis are the predominant pediatric presenting complaints versus cardiac complaints for adults.

This chapter includes sample medication content that can be used to design order sets for a variety of pediatric clinical conditions that are commonly managed in a pediatric emergency medicine observation unit setting and are intended to be used as examples for clinicians practicing in this setting. The medication content includes typical dosing regimens for selected pediatric medications as well as listings of commonly-encountered formulations. Clinical highlights relating to adverse effects and place in therapy are also included in selected instances.

Pediatric medicine is inherently seasonal, with influenza, respiratory syncytial virus, and other viruses peaking in the winter; this may result in an observation unit (OU) that is full at certain times of the year, while near-empty at others. In order to offset this problem, many pediatric OUs have become hybridized. A hybrid unit is one that serves other functions in addition to the primary role of caring for the typical observation patients. Set standards (including admission criteria, documentation, discharge criteria, length of stay, chain of command and proper staffing) and compliance with these standards is necessary for a pediatric OU to function optimally.