Anatomic Subtype Differences in Extramammary Paget Disease: A Meta-Analysis.

Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management. Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented. Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022. Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded. Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022. Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases). Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.

Yield of Postmortem Skeletal Surveys in Infants Presenting to Emergency Care With Sudden and Unexpected Death.

OBJECTIVES: Child abuse should be considered in cases of sudden unexpected infant death (SUID). Postmortem skeletal surveys (PM-SS) are recommended to evaluate for abusive fractures in SUID. Little is known about the yield of PM-SS among infants presenting to emergency care with SUID. Our objectives were to (1) describe the presentation and care of infants with SUID at a tertiary children's hospital emergency department and (2) report PM-SS use and findings. METHODS: We performed a retrospective study of infants younger than 12 months with SUID presenting to an urban emergency department from 2007 to 2019. We describe their presentation and care, including PM-SS performance and findings, referrals to the medical examiner, and reports to child protective services (CPS). We assessed for associations between race, payer, and presentation with reports to CPS. RESULTS: Of 73 infants with SUID, concern for unsafe sleep was documented in 45 (61.6%) and 71 (97.3%) underwent cardiopulmonary resuscitation by a medical professional. All 73 (100%) underwent PM-SS and were referred to the medical examiner. Twelve definite fractures (11 rib, 1 classic metaphyseal lesion) and 8 possible fractures (7 rib, 1 classic metaphyseal lesion) were identified among 6 (8.2%) infants. Forty-three (58.9%) were reported to CPS. There were no associations between race, payer, age, or history of unsafe sleep and CPS reports. CONCLUSIONS: One in 12 cases of SUID had a possible and/or definite fracture identified on plain radiography. Multicenter studies are needed to compare yield across different postmortem imaging modalities and populations.

Imaging of pediatric abdominal soft tissue tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

This paper provides imaging recommendations for pediatric abdominal tumors that arise outside of the solid viscera. These tumors are rare in children and have been categorized in two groups: abdominal wall and peritoneal tumors (desmoid tumor and desmoplastic small round cell tumor) and tumors that arise from the gastrointestinal tract (gastrointestinal stromal tumor and gastrointestinal neuroendocrine tumor). Authors offer consensus recommendations for imaging assessment of these tumors at diagnosis, during follow-up, and when off-therapy.

KIR/KIR-ligand genotypes and clinical outcomes following chemoimmunotherapy in patients with relapsed or refractory neuroblastoma: a report from the Children's Oncology Group.

BACKGROUND: In the Children's Oncology Group ANBL1221 phase 2 trial for patients with first relapse/first declaration of refractory high-risk neuroblastoma, irinotecan and temozolomide (I/T) combined with either temsirolimus (TEMS) or immunotherapy (the anti-GD2 antibody dinutuximab (DIN) and granulocyte macrophage colony stimulating factory (GM-CSF)) was administered. The response rate among patients treated with I/T/DIN/GM-CSF in the initial cohort (n=17) was 53%; additional patients were enrolled to permit further evaluation of this chemoimmunotherapy regimen. Potential associations between immune-related biomarkers and clinical outcomes including response and survival were evaluated. METHODS: Patients were evaluated for specific immunogenotypes that influence natural killer (NK) cell activity, including killer immunoglobulin-like receptors (KIRs) and their ligands, Fc gamma receptors, and NCR3. Total white cells and leucocyte subsets were assessed via complete blood counts, and flow cytometry of peripheral blood mononuclear cells was performed to assess the potential association between immune cell subpopulations and surface marker expression and clinical outcomes. Appropriate statistical tests of association were performed. The Bonferroni correction for multiple comparisons was performed where indicated. RESULTS: Of the immunogenotypes assessed, the presence or absence of certain KIR and their ligands was associated with clinical outcomes in patients treated with chemoimmunotherapy rather than I/T/TEMS. While median values of CD161, CD56, and KIR differed in responders and non-responders, statistical significance was not maintained in logistic regression models. White cell and neutrophil counts were associated with differences in survival outcomes, however, increases in risk of event in patients assigned to chemoimmunotherapy were not clinically significant. CONCLUSIONS: These findings are consistent with those of prior studies showing that KIR/KIR-ligand genotypes are associated with clinical outcomes following anti-GD2 immunotherapy in children with neuroblastoma. The current study confirms the importance of KIR/KIR-ligand genotype in the context of I/T/DIN/GM-CSF chemoimmunotherapy administered to patients with relapsed or refractory disease in a clinical trial. These results are important because this regimen is now widely used for treatment of patients at time of first relapse/first declaration of refractory disease. Efforts to assess the role of NK cells and genes that influence their function in response to immunotherapy are ongoing. TRIAL REGISTRATION NUMBER: NCT01767194.

Imaging of pediatric renal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper focused on Wilms tumor and nephrogenic rests.

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus-based imaging guidelines for the initial evaluation of a child with suspected WT and follow-up during and after therapy co-developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.

Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up.

What is diversity?

This article introduces the topic of diversity in this minisymposium by defining the terminology as well as providing descriptions of the positive impact of diversity. We aimed not only to examine the proven effects of diversity, but also to understand the barriers present so we can effectively mitigate these at the individual, institutional and systemic levels.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

An Atypical Case of Meckel's Diverticulum Assessed by SPECT/CT Imaging.

ABSTRACT: A 17-year-old adolescent boy presented with multiple episodes of hematochezia. After a negative 99mTcO4 scan, upper endoscopy, colonoscopy, and CT angiography, the patient underwent a second 99mTcO4 scan with ranitidine. The anterior images demonstrated a faint, delayed focus of uptake in the midabdomen without correlate on lateral projections. SPECT/CT was performed for localization with the focus of activity seen in an anterior loop of distal small bowel adjacent to the umbilicus. The patient subsequently underwent diagnostic laparoscopy and resection of the diverticulum with postoperative resolution of the symptoms.

Value of chest CT over skeletal surveys in detection of rib fractures in pediatric patients.

Recent literature has raised concerns about the sensitivity and accuracy of radiographs at diagnosing rib fractures. Studies have shown that chest computed tomography (CT) has far greater sensitivity at detecting rib fractures than radiographs. The purpose of this study was to evaluate the sensitivity of skeletal survey (SS) radiographs at diagnosis of rib fractures compared to CT in the pediatric population. This retrospective review included 57 patients who had undergone both a SS and a CT chest or CT chest/abdomen/pelvis within 30 days of each other for the indication of either non-accidental (NAT) or accidental trauma between 2009 and 2017. Images and reports were analyzed by a pediatric radiology fellow for presence/absence of fracture, evidence of healing and location of rib fracture, including rib level, location within the rib (anterior, lateral, and posterior), and side (right versus left). 225 rib fractures were identified in 25 patients on CT. 38 of those fractures were missed on the preceding SS, yielding a miss rate of 17%. Acute fractures were more likely to be missed than chronic or healing fractures (p ≤ 0.01). Location within the rib did not impact rib detection on radiographs. Left-sided rib fractures were not more common in NAT patients, compared to accidental trauma. SS miss approximately 17% of all rib fractures and CT is more sensitive modality in the detection of rib fractures, particularly acute rib fractures, regardless of location. Low-dose Chest CT could be a helpful modality in the work-up of NAT trauma.

Pilot study for comparative assessment of dual-energy computed tomography and single-photon emission computed tomography V/Q scanning for lung perfusion evaluation in infants.

OBJECTIVE: To evaluate clinical applications of dual-energy computed tomography (DECT) in pediatric-specific lung diseases and compare ventilation and perfusion findings with those from single-photon emission computed tomography (SPECT-CT) V/Q. METHODS: All patients at our institution who underwent exams using both techniques within a 3-month period were included in this study. Two readers independently described findings for DECT, and two other readers independently analyzed the SPECT-CT V/Q scan data. All findings were compared between readers and disagreements were reassessed and resolved by consensus. Inter-modality agreements are described throughout this study. RESULTS: Eight patients were included for evaluation. The median age for DECT scanning was 3.5 months (IQR = 2). Five of these patients were scanned for both DECT and SPECT-CT V/Q studies the same day, and three had a time gap of 7, 65, and 94 days between studies. The most common indications were chronic lung disease (5/8; 63%) and pulmonary hypertension (6/8; 75%). DECT and SPECT-CT V/Q identified perfusion abnormalities in concordant lobes in most patients (7/8; 88%). In one case, atelectasis limited DECT perfusion assessment. Three patients ultimately underwent lobectomy with corresponding perfusion abnormalities identified by all reviewers on both DECT and SPECT-CT V/Q in all resected lobes. CONCLUSION: DECT is a feasible technique that could be considered as an alternative for SPECT-CT V/Q for lung perfusion evaluation in infants.

Quantifying lung and diaphragm morphology using radiographs in normative pediatric subjects, and predicting CT-derived lung volume.

OBJECTIVE: To quantify the effect of age on two-dimensional (2D) radiographic lung and diaphragm morphology and determine if 2D radiographic lung measurements can be used to estimate computer tomography (CT)-derived lung volume in normative pediatric subjects. MATERIALS AND METHODS: Digitally reconstructed radiographs (DRRs) were created using retrospective chest CT scans from 77 pediatric male and female subjects aged birth to 19 years. 2D lung and diaphragm measurements were made on the DRRs using custom MATLAB code, and Spearman correlations and exponential regression equations were used to relate 2D measurements with age. In addition, 3D lung volumes were segmented using CT scans, and power regression equations were fitted to predict each lung's CT-derived volume from 2D lung measurements. The coefficient of determination (R2 ) and standard error of the estimate (SEE) were used to assess the precision of the predictive equations with p < .05 indicating statistical significance. RESULTS: All 2D radiographic lung and diaphragm measurements showed statistically significant positive correlations with age (p < .01), including lung major axis (Spearman rho ≥ 0.90). Precise estimations of CT-derived lung volumes can be made using 2D lung measurements (R2 ≥ 0.95), including lung major axis (R2 ≥ 0.97). INTERPRETATIONS: The reported pediatric age-specific reference data on 2D lung and diaphragm morphology and growth rates could be clinically used to identify lung and diaphragm pathologies during chest X-ray evaluations. The simple, precise, and clinically adaptable radiographic method for estimating CT-derived lung volumes may be used when pulmonary function tests are not readily available or difficult to perform.

Debunking Fringe Beliefs in Child Abuse Imaging: AJR Expert Panel Narrative Review.

Child abuse is a global public health concern. Injuries from physical abuse may be clinically occult and not appreciable on physical examination. Imaging is therefore critical in identifying and documenting such injuries. The radiologic approach for a child who has potentially been abused has received considerable attention and recommendations according to decades of experience and rigorous scientific study. Nonetheless, fringe beliefs describing alternative explanations for child abuse-related injuries have emerged and received mainstream attention. Subsequently, imaging findings identified in abused children have been attributed to poorly supported underlying medical conditions, clouding the evidence basis for radiologic findings indicative of nonaccidental trauma. Fringe beliefs that attribute findings seen in child abuse to alternate pathologies such as genetic disorders, birth trauma, metabolic imbalances, vitamin D deficiency, and short-distance falls typically have limited evidence basis and lack professional society support. Careful review of the scientific evidence and professional society consensus statements is important in differentiating findings attributable to child abuse from fringe beliefs used to discount the possibility that a child's constellation of injuries is consistent with abuse. This review refutes fringe beliefs used to provide alternative explanations in cases of suspected child abuse and reinforces the key literature and scientific consensus regarding child abuse imaging.

Evaluation of the abdomen in the setting of suspected child abuse.

Abusive intra-abdominal injuries are less common than other types of injuries, such as fractures and bruises, identified in victims of child physical abuse, but they can be deadly. No single abdominal injury is pathognomonic for abuse, but some types and constellations of intra-abdominal injuries are seen more frequently in abused children. Identification of intra-abdominal injuries can be important clinically or forensically. Injuries that do not significantly change clinical management can still elevate a clinician's level of concern for abuse and thereby influence subsequent decisions affecting child protection efforts. Abusive intra-abdominal injuries can be clinically occult, necessitating screening laboratory evaluations to inform decisions regarding imaging. Once detected, consideration of developmental abilities of the child, type and constellation of injuries, and the forces involved in any provided mechanism of trauma are necessary to inform assessments of plausibility of injury mechanisms and level of concern for abuse. Here we describe the clinical, laboratory and imaging evaluation of the abdomen in the setting of suspected child abuse.