Pediatric Pathology Research Articles

Spitz tumours and mimickers.

Since their initial description in 1948, Spitz tumours have always been a challenge in the field of dermatopathology and paediatric pathology. Advances in molecular pathology have confirmed they are associated with specific anomalies, mainly gene fusions. They display a wide range of clinical presentations and histological subtypes. Most cases are Spitz nevi and very few lesions match the criteria to be diagnosed as atypical Spitz tumours. Even fewer are labelled as Spitz melanomas. Follow-up studies of genetically characterized cases have repeatedly confirmed that, even if the regional lymph node is involved, the overall outcome remains favourable. The aims of this review are to cover the variety of morphological presentations of Spitz tumours and illustrate the most rare subtypes. When possible, we have pointed out the potential trends between some unusual morphological features and the frequently associated genetic drivers. Spitz tumours have many differential diagnoses, the main being superficial spreading melanoma, with overlapping morphological features in early lesions. Essential clues to discriminate Spitz from mimickers have been listed and illustrated.

Hypoprolactinemia, a neglected endocrine disorder.

This special issue of Reviews in Endocrine and Metabolic Disorders is dedicated to hypoprolactinemia. Prolactin is known for its actions on the mammary gland including development, preparation for postpartum lactation, as well as synthesis and maintenance of milk secretion. However, prolactin has many other physiological effects on reproduction, embryonic and fetal development, homeostasis, neuroprotection, behavior, and immunoregulation. In clinical practice, physiopathology and clinical consequences of increased prolactin secretion are generally well understood, and medical treatment to decrease prolactin levels is available and effective in most cases. Unlike prolactin excess, hypoprolactinemia has been a neglected endocrine disorder and nospecific replacement therapy is commercially available. Prolactin is the only anterior pituitary hormone not addressed by clinical hypopituitarism guidelines. In recent years, human studies have revealed that hypoprolactinemia is associated with metabolic, sexual and neuropsychologic alterations. Therefore, this special issue of Reviews in Endocrine and Metabolic Disorders is aimed to enhance our incomplete understanding of hypoprolactinemia. A total of 17 articles were authored by respected scientists and clinicians from a variety of disciplines including adult and pediatric endocrinology, pathology, gynecology, reproductive medicine, oncology, and neurosurgery.

Gastrointestinal stromal tumours (GIST) in children: An update of this orphan disease

Gastrointestinal stromal tumours (GIST) are tumours of the digestive tract that mainly develop in adults. Recommendations for the management of GIST in pediatrics are limited. We performed an updated review of the literature serving as a basis for the development of diagnostic and therapeutic recommendations for GIST in children and young adults (YA). GIST in pediatric population can have a sporadic presentation but occur more often in a syndromic and/or familial context. Currently more than 170 cases of sporadic GIST or in association with Carney-Stratakis syndrome or Carney's triad family cases of familial GIST have been described in children and YA. These syndromes are frequently associated with germline or somatic alterations in a sub-unit of Succinate Dehydrogenase (SDH). In contrast, the frequency of somatic KIT and PDGFRα oncogene mutations (±15%) is significantly lower as compared to adults with GIST. The recommendations for the management of children with GIST are generally comparable to those used for adult patients, although certain biological differences influence the therapeutic attitude. International collaborations have been deployed in order to increase the clinical and biological knowledge of this orphan pathology in pediatrics.

Benign and malignant breast lesions in children and adolescents - diagnostic and therapeutic approach.

Benign and malignant breast lesions in children and adolescents are rare compared to adults. Most tumors are benign. Malignant breast lesions are extremely rare. Fibroadenomas are the most common, accounting for 95% of all lesions. Diagnosis is based on history and physical examination of the breast and armpit. Imaging studies include ultrasound, mammography, and magnetic resonance imaging. Ultrasound is the most commonly used imaging test. Other tests are used in cases of diagnostic doubt. Core needle biopsy should be considered for appropriate diagnostic management. Excisional biopsy should be considered for complex clinical conditions and imaging studies. Except in doubtful situations in children and adolescent girls, a conservative approach and observation of the lesions along with periodic ultrasound examination initially every 6-12 months is advisable. Management of malignant breast lesions in children typically involves a multidisciplinary team consisting of pediatric oncologists, surgeons, radiation oncologists, pathologists, and other specialists and depends on the clinical condition of the patient. An important aspect is the experience of the clinician and radiologist in the treatment of breast lesions, as well as increasing patient and family awareness of possible breast lesions and self-examination. This review aims to provide a scoping overview of the available literature on benign and malignant lesions of the breast in pediatric and adolescent populations to assist physicians and surgeons in making decisions regarding the appropriate diagnosis and management of pediatric breast disease.

Incorporating client perspectives: moving towards digital outcome measurement in pediatric speech-language pathology

ABSTRACT Caregivers’ needs and preferences regarding outcome measurement in pediatric speech-language pathology are not well-understood, but are critical to the development and implementation of meaningful clinical tools. This project engaged caregivers of preschoolers with speech, language and communication needs to understand their views on the potential for, and their preferences surrounding a digital version of one participation-focused outcome measure called the Focus on the Outcomes of Communication Under Six (FOCUS-34). Fifteen caregivers of preschoolers who were receiving services in a large health system participated in one of four 30–60-minute virtual focus groups or one of three individual interviews. Caregivers shared their perceptions of whether and how a digital FOCUS-34 may improve their service experience, and their preferred features and formats to make it useful. An inductive content analysis was used to identify relevant categories that described caregivers’ perspectives. Data were sorted into two categories: (1) caregivers believe a digital solution would improve their service experience, and (2) caregivers want a user-friendly digital FOCUS-34 to measure and give feedback on intervention outcomes. Multiple sub-categories were also identified, which further described caregivers’ views on how a digital measure would improve the feasibility of outcome measurement, family engagement in services, and transparent communication with providers. Sub-categories also outlined caregivers’ preferences for the features and functions of a digital measure and their suggested considerations for developers of the digital tool. Results provide new insight into caregivers’ perspectives on digital outcome measurement and will inform efforts to improve the utility of the FOCUS-34 for families.

Current situation of neuropathology in Central America.

The present situation of neuropathology practice in the Central American region has not been addressed in the past. These are low middle-income countries, and therefore, many do not have a basic immunohistochemistry panel. Cytogenetics and molecular studies are not available in most of Central America. Pediatric brain tumors are diagnosed either by anatomical pathologists or by pediatric pathologists. Access to a weakly Latin American Tumor Board is available to consult cases, but most countries do not participate in these expert meetings. The most recent World Health Organization brain tumor book has a very broad molecular classification of pediatric brain tumors. All these factors make it very difficult to properly diagnose pediatric brain tumors in the region, and this impacts the treatment and overall survival of children with brain tumors.

A Case Report of Congenital Wilms’ Tumor and a Comprehensive Literature Review highlighting the spectrum between Wilms’ Tumor and Nephroblastomata’s

Abstract Introduction/Objective Wilms’ Tumour (WT) represents the most frequently encountered malignant renal neoplasm within pediatric pathology. To delineate the histopathological features of WT with perilobar nephrogenic rests (PLNR) and intralobar nephrogenic rests (ILNR) from nephroblastomatosis, we report a case with literature review to evaluate the clinical implications of WT with or without nephrogenic rests (NR), and nephroblastomatosis. Methods/Case Report Our patient is a 2-week-old neonate with VACTERL, germline mosaic triple X, and stage 1 WT with PLNR and substantial ILNR. The management approach involved radical nephrectomy exclusively. Obtaining a unifying clinical syndrome as well as deciding between WT or nephroblastomatosis was challenging in this case. The molecular testing with VACTERL panel was indeterminate and WT panel revealed DIS3L2 mutation that is indeterminate but likely pathogenic. She has been stable for 12 months and placed on 4-monthly left kidney ultrasound surveillance. Results (if a Case Study enter NA) Our literature review showed that the most common histologic subtype in WT patients without NR (n=59) and with NR (n=33) were classic triphasic (28.8%) and stromal-predominant (39.3%), respectively. WT patients with or without NR, underwent radical nephrectomy followed by adjuvant chemotherapy. Loss of heterozygosity (LOH) in TRIM28 was 4-fold higher in cases with NR. Mortality and relapse rates (12.5%) were higher in non-NR cohort. Conversely, nephroblastomatosis patients (n=14) underwent neoadjuvant chemotherapy, ipsilateral radical nephrectomy, and contralateral nephron-sparing surgery. Nephroblastomatosis patients had higher mortality (22.2%) and relapse rate (30%), with no identifiable mutations on molecular testing. Conclusion WT patients with NR have an earlier diagnosis and lower mortality and relapse rates compared to those without NR. The higher frequency of LOH in TRIM28 in WT patients with NR warrants future exploration to assess its implication in progression free survival. Nephroblastomatosis exhibits higher mortality and relapse rates, emphasizing the importance of reporting nephroblastomatosis in co-existing WT cases.

Hiding in Plain Sight: Radiologic and Pathologic Findings Can Identify Beckwith-Wiedemann Syndrome in Patients With Wilms Tumor.

Most pediatric specialists, including hematologists/oncologists, surgeons, radiologists, and pathologists, are familiar with the diagnosis and management of Wilms tumor (WT). However, it may be challenging to identify the underlying conditions causing cancer predisposition, which can change the management for the patient and potentially their entire family. In this paper, we present 3 cases of clinically suspected WT associated with Beckwith-Wiedemann syndrome (BWS). We review the radiologic and histologic findings to diagnose BWS. We also discuss the implications of a BWS diagnosis on the clinical management of WT and follow-up guidelines for BWS patients.

The implementation of molecular tumor profiling in the practice of pediatric cancer pathology: The pathologists' experience.

The increased accessibility and utilization of molecular testing including next-generation sequencing (NGS) has impacted the practice of pediatric pathology, with diagnostic, prognostic, and therapeutic implications for our patients. This survey is the first to describe the utilization of molecular testing in the routine practice of pediatric pathology for the care of children with known or suspected solid tumors. The Society for Pediatric Pathology Practice Committee distributed a survey to our membership asking 25 questions about training, practice setting, molecular ordering practices, and barriers to testing. Seventy-five pathologists responded to the survey. The survey provides valuable insight into the current use of molecular testing for the care of children with known or suspected solid tumors. Most respondents reported that they are increasingly using a variety of molecular techniques, with increased use over time, and that NGS is useful. These results highlight a variety of barriers to molecular testing, including cost, insurance coverage, turnaround time, limitations of available assays (including limited coverage of pediatric-specific alterations), and difficulty in determining the most appropriate test to order. These data may be useful in supporting pediatric pathologists in their practice.

Paediatric staphyloma classification: new perspectives via ultrawide field three-dimensional swept-source optical coherence tomographic angiography

AimTo employ ultrawide field three-dimensional swept-source optical coherence tomographic angiography (UWF 3D SS-OCTA) modality, integrating novel strategies, posterior eye curvature maps and posterior eye height maps, in characterising the features...

Approaches to the Diagnosis and Management of Paediatric Ovarian Tumours and Oncological Outcomes in a Single-centre Study. Evidence in Support Of IPSO Reccomendations

BackgroundApproaches to paediatric ovarian tumours vary. Cross-sectional imaging is reliable but not always performed. Laparoscopic tumourectomy, although popular, is not recommended by International Paediatric Surgical Oncology Society (IPSO); tumour spillage remains the main concern. We aimed to investigate the reliability of preoperative evaluation and identify perioperative factors associated with adverse outcomes. MethodsSingle-centre retrospective study (2015–2022) of clinical presentation, preoperative investigation, operative approaches and oncological outcomes in all females <18 years treated for ovarian tumours. Logistic regression was used to identify predictors of malignancy and of second disease events. Data are presented as median (IQR) or rates. ResultsSixty girls aged 12.5 (10–15) years with follow-up of 51 (30.5–76.3) months were included. Incidence of malignant and low malignant potential tumours was 19/60 (32%). Tumour size and consistency proved predictive of malignancy. Clinical assessement, tumour markers and cross-sectional imaging combined showed 75% sensitivity, 100% specificity and 7% misclassified malignancy rate. Second disease events (11/60, 18%) were associated with misclassified malignancy (2/11 vs. 1/49, p = 0.04) and positive margins (4/11 vs. 5/49, p = 0.02). Ovarian-sparing surgery did not influence second events (5/11 vs. 28/49, p = 0.48). There was no significant association between second events and laparoscopic tumourectomy (3/11 vs. 20/49, p = 0.40); spillage rate was however more frequent with laparoscopy (5/11 vs. 2/32, p = 0.008). ConclusionMisclassified malignancy, noted in 7% of patients undergoing optimal work-up, adversely impacted outcomes, highlighting the importance of oncological principles in both oophorectomy and ovarian-sparing surgery. Malignancy incidence and misclassification can be underestimated when tumours with malignant behaviour potential, such as immature teratomas and borderline tumours, are grouped as benign. There was no direct association between operative approaches and second events. Laparoscopy, however, failed to maintain oncological principles more frequently than open surgery and hence risks upstaging of paediatric ovarian pathology. Level of evidenceIII.

Maude Abbott: "A Feminine Misfit in an Exclusive Male Environment" and Her Strategies for Success.

Maude Abbott was a pioneering female Canadian physician who became a world authority on medical museums and congenital heart disease. Abbott spent almost all her career in highly sexist, discriminatory work environments. This paper reviews Abbott's life and accomplishments, but, more importantly, analyzes her pathway to success in the masculine world of early 20th-century academic pathology. Abbott, though well-trained as a pathologist, never provided clinical service, but instead worked as museum curator at McGill University. She established the International Association of Medical Museums (predecessor to the International Academy of Pathology), edited its journal, and essentially ran the organization. Abbott, surrounded by influential males, dealt differently with each. In general, she recognized that male doctors believed women lacked the gravitas to lead major initiatives but that she could circumnavigate this supposed impediment by co-leading projects with male counterparts, preferably ones too busy to get in her way. She repeatedly used this approach, and by doing most of the work but sharing credit, succeeded in gaining reputation, accomplishment, and advancement. Abbott's pioneering work on congenital heart disease established her as one of the founders of pediatric pathology, and, overall, her career promoted the entry of women physicians into the pathology profession.

Hair Today, OR Tomorrow: A Multicenter Case Series of Gastric Bezoars in Children Diagnosed With Point-of-Care Ultrasound.

Point-of-care ultrasound (POCUS) can expedite the diagnosis of pediatric abdominal pathologies including appendicitis and intussusception. In this patient series, we present cases from multiple pediatric emergency departments that demonstrate the use of POCUS in the diagnosis of trichobezoars in children. POCUS findings include the presence of an intragastric hyperechoic mass or a hyperechoic arch and associated posterior acoustic shadowing. These findings in the appropriate clinical context should prompt further diagnostic imaging and/or surgical consultation for removal.

Exploring the Impact and Prospects of Social Media in Advancing Pediatric Pathology.

Social media has been recently highlighted as a unique and modern virtual force that allows for worldwide connection, collaboration, communication, and engagement between pathologists, trainees, and medical students. Much literature has been focused on the role of social media in recruitment and medical education practices of different pathology subspecialties, such as dermatopathology and hematopathology. However, current literature on pathology social media's status and potential future roles in promoting pediatric pathology is sparse. Herein, this review intends to narrow this knowledge gap by reviewing how social media has been utilized in different pediatric subspecialties, the current use of social media in pathology, and how the future of pediatric pathology social media use may look moving forward regarding education, research, and recruitment. Specific tips and related online resources are provided.

Report of the German Society of Pathology Working Group on Pediatric and Fetal Pathology

Report of the German Society of Pathology Working Group on Pediatric and Fetal Pathology

Neurologist and Neurosurgeon: A ‘Sine Qua Non’ in Paediatric Intracranial Pathology Management

Neurologist and Neurosurgeon: A ‘Sine Qua Non’ in Paediatric Intracranial Pathology Management

Conflict between parents, physicians, and healthcare professionals in medical decision-making: How to address it-A systematic review from the ESPGHAN Ethics Committee.

Medical decisions about pediatric gastroenterology pathologies often involve collaboration between the medical team and the family. On occasions, conflict may arise between the individuals involved in decision making (team-family conflict) causing delays in managing a child's health condition. Little is known on the strategies that can be implemented to address such conflicts. Using the systematic review model by McCullough et al., an electronic literature search was conducted using PUBMED databases and SCOPUS. Studies published between 2001 and 2022 were analyzed to identify high-risk families, the barriers and facilitators involved in the team-family conflict and the circumstances in which healthcare professionals can be ethically justified to override parents' medical decisions and to trigger the state intervention. The present review provides recommendations on the more suitable ways to manage team-family conflict and gives a practical approach using a case vignette.

Practical Approach to Congenital Anomalies of the Kidneys: Focus on Anomalies With Insufficient or Abnormal Nephron Development: Renal Dysplasia, Renal Hypoplasia, and Renal Tubular Dysgenesis.

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for up to 30% of antenatal congenital anomalies and is the main cause of kidney failure in children worldwide. This review focuses on practical approaches to CAKUT, particularly those with insufficient or abnormal nephron development, such as renal dysplasia, renal hypoplasia, and renal tubular dysgenesis. The review provides insights into the histological features, pathogenesis, mechanisms, etiologies, antenatal and postnatal presentation, management, and prognosis of these anomalies. Differential diagnoses are discussed as several syndromes may include CAKUT as a phenotypic component and renal dysplasia may occur in some ciliopathies, tumor predisposition syndromes, and inborn errors of metabolism. Diagnosis and genetic counseling for CAKUT are challenging, due to the extensive variability in presentation, genetic and phenotypic heterogeneity, and difficulties to assess postnatal lung and renal function on prenatal imaging. The review highlights the importance of perinatal autopsy and pathological findings in surgical specimens to establish the diagnosis and prognosis of CAKUT. The indications and the type of genetic testing are discussed. The aim is to provide essential insights into the practical approaches, diagnostic processes, and genetic considerations offering valuable guidance for pediatric and perinatal pathologists.

Valgus-Related Elbow Pathology is not Associated with Decreased Baumann’s Angle: A Case-Control Study

BackgroundPrevious studies have demonstrated that varus alignment of the elbow has been associated with lateral condylar fractures. However, for other pediatric and adolescent elbow pathologies, the influence of upper extremity alignment has not been investigated. This study aimed to compare elbow alignment (quantified using Baumann’s angle) among patients with medial epicondyle humeral fractures and capitellum osteochondritis dissecans (OCD) and age- and sex-matched control patients. MethodsPediatric and adolescent patients (ages 5-18, inclusive) treated at a tertiary care hospital for medial epicondyle fractures (MEFx) and capitellum OCD lesions from January 2016 and October 2023 were retrospectively reviewed. Patients aged 5-18 with anteroposterior (AP) elbow radiographs demonstrating no elbow pathology were included as controls. Patients were matched 1:1:1 based on sex and chronologic age within 2 years and placed into cohorts by injury. Baumann’s angle was compared across groups using one-way ANOVA after data normality was established via Shapiro Wilk tests. Linear regression was used to assess whether fracture displacement in millimeters (in the medial epicondyle fracture group) or OCD lesion size (in the capitellum OCD group) correlated with Baumann’s angle. Two-tailed significance threshold was set as p≤0.05. Results72 matched patients were included (24 MEFx, 24 OCD, 24 controls). Mean age of the overall sample was 13.8±1.9 years, with 79% male. Mean Baumann’s angle was 75.7±5.9 degrees in MEFx, 71.7±7.9 degrees in OCD, and 74.1±5.2 degrees in controls (p=0.181). There was no association between fracture displacement and Baumann’s angle in the MEFx group (p=0.75), and there was no association between OCD lesion size and Baumann’s angle in the OCD group (p=0.31). ConclusionsThere was no difference in Baumann’s angle among pediatric and adolescent patients with MEFx, capitellum OCD lesions, and age and sex-matched controls. These findings suggest that static distal humerus alignment does not increase the risk for these injuries. Future studies should seek to evaluate dynamic alignment and its influence on these pathologies. Level of EvidenceIII

Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy.

Dr. Sidney Farber (Farber) was a distinguished pediatric pathologist and widely recognized pioneer of modern chemotherapy. In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia. The findings laid the basis for developing and using additional chemotherapies, individually or in combination, for treating pediatric and adult cancers. Farber also introduced actinomycin D to treat Wilms tumor in various stages. Underneath his oversight, the 'Jimmy Fund,' one of the earliest dedicated pediatric oncology centers, and the Children's Cancer Research Foundation, which subsequently evolved into the Dana-Farber Cancer Institute, was established. Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted.