Focal Nodular Hyperplasia-Like Lesions With Glypican-3 Positivity in Infancy.

PURPOSE AND CONTEXT: Glypican-3 is often used to discriminate between neoplastic and nonneoplastic liver. In focal lesions, positivity may be considered suggestive of a malignancy such as hepatoblastoma. However, glypican-3 is also normally expressed in the immature liver. We present a series of 5 cases of focal nodular hyperplasia (FNH)-like lesions arising in very young patients with glypican-3 expression and highlight the challenges these lesions present in the differential diagnosis of hepatoblastoma. METHODS: Cases were obtained from the files of 3 tertiary pediatric hospitals. Clinical data were obtained from the electronic medical record and histopathologic material including immunohistochemical stains were reviewed. KEY RESULTS: Patients were aged 2 weeks to 6 months with peak AFP levels ranging from 88.6 to 204,696 ng/mL. Microscopically, all were variably demarcated hepatocellular lesions with cords of hepatocytes, marked sinusoidal dilatation, and occasional fibrous bands and areas reminiscent of central scar with bile ducts. No significant cytologic atypia or increased mitotic activity were present. All showed glypican-3 expression and were negative for nuclear beta-catenin with intact reticulin framework. CONCLUSIONS: Our study highlights the pitfalls of evaluating focal liver lesions in infants when high AFP levels and glypican-3 expression may reflect immaturity rather than neoplasia.

KRIT1-positive hyperkeratotic cutaneous capillary venous malformation.

Cerebral cavernous malformations (CCM) may present in sporadic or familial forms, with different cutaneous manifestations including deep blue nodules, capillary malformations, and hyperkeratotic cutaneous capillary venous malformations (HCCVM). We report the case of an infant with a KRIT1-positive HCCVM associated with familial CCM. Moreover, histopathology showed positive immunohistochemical stain with GLUT1, further expanding the differential diagnosis of GLUT1-positive vascular anomalies.

Aneursymal Bone Cyst: An Uncommon Paraspinal Tumor in Children.

Paraspinal tumors with benign histology in the absence of trauma rarely arise in children. Treatment of such benign tumors, in contrast to malignancies, generally consists of surgical resection of the lesion with confirmation of histology via pathologic evaluation. We present a pediatric case of an atraumatic paraspinal mass with a histologic diagnosis of aneurysmal bone cyst, and USP6 gene rearrangement supporting the histologic diagnosis. The patient underwent gross total resection of the paraspinal lesion with no additional intervention. We highlight the differential diagnosis of paraspinal tumors in children and key features that led to the diagnosis in this patient.

A Case of an Infantile Lingual Leiomyomatous Hamartoma.

Lingual leiomyomatous hamartomas are rare lesions of the tongue with largely unknown mechanisms of formation. These lesions are often asymptomatic, though they may present with symptoms, particularly relating to swallow function. Workup should include imaging of the head and neck, and diagnosis should be made histologically. Treatment is surgical excision. This case is a report of a 4-week-old female who presented for evaluation of an asymptomatic 1 × 1 cm dorsal midline tongue mass discovered at birth. The patient was monitored until the age of 9 months, at which time the mass was surgically excised. The patient had an uncomplicated postoperative course. Pathological analysis yielded a diagnosis of leiomyomatous hamartoma.

Prostatic polyp presenting in a young boy with urinary symptoms.

Congenital urethral polyps are a rare anomaly of the urethra seen primarily in male children that present most commonly with features of voiding dysfunction or urinary obstruction. We report a case of a young boy with a posterior urethral polyp presenting with urinary retention, hematuria, and constipation. We also report a new treatment approach to this rare and challenging clinical finding.

Chemoresistant hepatoblastoma in a patient with mosaic trisomy 18 treated with orthotopic liver transplantation.

We present a 9-month-old male with mosaic trisomy 18 with a right hepatic lobe mass. The tumor was completely resected and identified as pure fetal histology hepatoblastoma but contained increased mitotic activity. Adjuvant chemotherapy consisted of cisplatin, vincristine, and 5-fluorouracil. After the first and fourth cycles of chemotherapy, recurrent tumor developed. The patient underwent rescue orthotopic liver transplantation, and is currently alive without evidence of hepatoblastoma 28 months after transplantation. This report demonstrates the use of orthotopic liver transplantation in a child with mosaic trisomy 18 and hepatoblastoma.

Disseminated Rhizomucor pusillus causing early multiorgan failure during hematopoietic stem cell transplantation for severe aplastic anemia.

Matched sibling donor hematopoietic stem cell transplantation is the standard of care for severe aplastic anemia, with an overall survival of 80% to 90%. Only 60% to 70% of patients respond to treatment with immunosuppressive therapy. The main life threatening complications are infections, graft failure, and graft versus host disease. A 10-year-old patient with severe aplastic anemia underwent matched sibling donor hematopoietic stem cell transplantation, but developed sudden onset of fatal multiorgan failure on day +12. The cause of death was found only after autopsy.

Magnetic Resonance Elastography of the Liver in Children and Adolescents: Assessment of Regional Variations in Stiffness.

RATIONALE AND OBJECTIVES: We describe our experience in measuring parenchyma stiffness across the liver Couinaud segments in lieu of the conventional practice of using a single slice-wise "global" region-of-interest. We hypothesize that the heterogeneous nature of fibrosis can lead to regional stiffness within the organ, and that it can be reflected by Couinaud segment-based magnetic resonance elastography measurements. MATERIALS AND METHODS: This retrospective study involved from 173 patients (116 males, 57 females, 1.0-22.5 years, 14.7 ± 3.5 years) who underwent exams between June 2017 and September 2018. Liver stiffness across the eight Couinaud segments was measured in addition to a single-slice global measurement by two analysts. Inter- and intrarater analysis was performed in a subset of 20 cases. Individual segment stiffness values, the average across the segments, and the coefficients of variation (CoV) were compared to global single-slice-derived values using linear and Lin's concordance correlation coefficients. Linear correlations between stiffness values versus age, gender, and body-mass-index (BMI) were also evaluated. RESULTS: We observed CoVs ranging from 3.1%-79.2%, 17.2 ± 7.2%. The CoV was not correlated with age or BMI (r2 < 0.01, p = 0.99 for both). The CoV did not differ between males (17.1 ± 5.6%) and females (17.3 ± 9.8%) (p = 0.88). There were no correlations between global stiffness versus age (r2 = 0.02, p = 0.84) or BMI (r2 = 0.03, p = 0.68). A range of 0.58-0.86 was observed for Lin's concordance correlation coefficient between segmental stiffness, the average stiffness across segments, and global stiffness. Segments II and VII had the highest frequency of being the stiffest Couinaud segment. The average stiffness across the segments correlated strongly with the single-slice global measurement (r2 = 0.88, p< 0.01). CONCLUSION: There exists potential variations in parenchyma stiffness across the liver Couinaud segments, which may reflect the heterogeneous nature of fibrosis. This variation can potentially provide additional diagnostic and clinical information.

Primary testicular presentation of ALK-1-negative anaplastic large cell lymphoma in a pediatric patient.

Anaplastic large cell lymphoma is a heterogeneous group of malignant non-Hodgkin lymphomas that occurs in up to 15% of all pediatric non-Hodgkin lymphomas. It is characterized by B-symptoms and involvement of extranodal sites such as skin, bone, and soft tissue. This brief report describes first reported case of pediatric primary testicular anaplastic large cell lymphoma in a 14-year-old boy. The presentation included acute testicular pain, fever, and vomiting. After chemotherapy and unilateral radical orchiectomy, patient continues in complete remission.

Ultrasound Elastography as a Non-Invasive Method to Monitor Liver Disease in Children with Short Bowel Syndrome: Updated Results.

PURPOSE: The purpose of the study was to determine the accuracy of acoustic radiation force impulse (ARFI) ultrasound elastography in assessing the degree of liver disease in children with short bowel syndrome (SBS). METHODS: A prospective observational cohort study of patients with SBS who underwent a liver biopsy and ARFI elastography was performed. Mean shear wave speed (SWS) and stage of fibrosis was evaluated using t-tests. Receiver operating characteristic curves (ROC) were generated and the area under the curves (AUC) estimated in order to assess the accuracy of SWS measurements to discriminate between stages of fibrosis. RESULTS: Thirty-seven paired elastography and biopsy samples from 31 patients were included. The median age was 0.6 years, and 61% were male. There was a significant positive correlation between stage of fibrosis and mean SWS (ß=0.16 m/s increase per stage, p=<0.001). ROC analysis revealed that mean SWS had good accuracy for discriminating between mild liver fibrosis (F0-F1) and moderate to severe fibrosis (F2-F4) (AUC=0.80, 95% CI 0.65-0.95). In addition, ROC analysis demonstrated that mean SWS can also accurately discriminate between mild to moderate fibrosis (F0-F2) and more severe fibrosis (F3-F4) (AUC=0.84, 95% CI 0.71-0.96). CONCLUSION: ARFI elastography is an accurate, non-invasive method to monitor liver disease in children with SBS. TYPE OF STUDY: Retrospective Cohort Study LEVEL OF EVIDENCE: II.

A pilot study of ultrasound elastography as a non-invasive method to monitor liver disease in children with short bowel syndrome.

BACKGROUND: Our objective was to evaluate the accuracy of acoustic radiation force impulse (ARFI) elastography in determining extent of liver fibrosis in pediatric patients with short bowel syndrome (SBS). METHODS: This prospective cohort study included pediatric patients with SBS who underwent ultrasound with ARFI measurements of shear wave speed (SWS) and liver biopsy within 30days of each other between 12/2014-9/2015. The mean and median SWS were compared to the stage of fibrosis. Receiver operating characteristic curves (ROC) were also generated to assess the classification accuracy of SWS measurements for mild (F0-F1) versus moderate/severe fibrosis (F2-F4). RESULTS: Twelve patients were included with median age 1.4years and median weight 11.3kg. The median direct bilirubin level was 0.3mg/dL at the time of biopsy. On liver biopsy, 6 patients had mild fibrosis (F1), 3 had septal fibrosis (F3), and 3 had cirrhosis (F4). The area under the ROC curve for elastography to differentiate moderate/severe liver fibrosis from mild disease was 0.83 (95CI 0.58-1.00) and 0.86 (95CI 0.63-1.00) for the median SWS and mean SWS, respectively. CONCLUSIONS: These early results suggest that ARFI ultrasound elastography may be a reliable non-invasive method to monitor liver fibrosis in pediatric patients with SBS. TYPE OF STUDY: Prospective observational cohort. LEVEL OF EVIDENCE: 3.

A Strategy for Helicobacter Immunohistochemistry Utilization in Pediatric Practice: Insights From Morphologic and Cost-Benefit Analyses.

OBJECTIVES: Recent studies in adults have examined the utility of immunohistochemistry (IHC) in detecting Helicobacter in gastric biopsy specimens and reached differing conclusions. Dedicated cost-benefit analysis of Helicobacter IHC in pediatric gastric biopsy specimens has not been performed. METHODS: From 1,955 pediatric gastric biopsies in a 1-year period, we identified 63 Helicobacter -positive and 120 Helicobacter -negative biopsy specimens. All cases were scored according to the Updated Sydney System for the severity of inflammation. RESULTS: We observed that pediatric Helicobacter infection was significantly associated with germinal center formation, active inflammation, oxyntic mucosa with moderate to severe chronic inflammation, and antral mucosa with any chronic inflammation, exclusive of mild and superficial chronic inflammation. At least one associated pattern was seen in each Helicobacter -positive biopsy specimen. In comparison with adults, pediatric Helicobacter -positive biopsy specimens are more likely to lack acute inflammation and more likely to show moderate to marked chronic inflammation. CONCLUSIONS: We recommend performing Helicobacter IHC on pediatric gastric biopsy specimens with any of the above inflammatory patterns. This approach can sensitively identify pediatric patients with Helicobacter gastritis, limit IHC staining to approximately 30% of all gastric biopsy specimens, and reduce costs by up to $55,306.90 per 1,000 biopsy specimens.

The College of American Pathologists guidelines for whole slide imaging validation are feasible for pediatric pathology: a pediatric pathology practice experience.

Whole slide imaging (WSI) is rapidly transforming educational and diagnostic pathology services. Recently, the College of American Pathologists Pathology and Laboratory Quality Center (CAP-PLQC) published recommended guidelines for validating diagnostic WSI. We prospectively evaluated the guidelines to determine their utility in validating pediatric surgical pathology and cytopathology specimens. Our validation included varied pediatric specimen types, including complex or less common diagnoses, in accordance with the guidelines. We completed WSI review of 60 surgical pathology cases and attempted WSI review of 21 cytopathology cases. For surgical pathology cases, WSI diagnoses were highly concordant with glass slide diagnoses; a discordant diagnosis was observed in 1 of 60 cases (98.3% concordance). We found that nucleated red blood cells and eosinophilic granular bodies represented specific challenges to WSI review of pediatric specimens. Cytology specimens were more frequently discordant or failed for technical reasons, with overall concordance of 66.7%. Review of pediatric cytopathology specimens will likely require image capture in multiple focal planes. This study is the first to specifically evaluate WSI review for pediatric specimens and demonstrates that specimens representing the spectrum of pediatric surgical pathology practice can be reviewed using WSI. Our application of the proposed CAP-PLQC guidelines to pediatric surgical pathology specimens is, to our knowledge, the first prospective implementation of the CAP-PLQC guidelines.

Infantile osteopetrosis and juvenile xanthogranuloma presenting together in a newborn: a case report and literature review.

Osteopetrosis (OP) is a clinically and genetically heterogeneous disorder characterized by increased bone density. Associations between OP and other clinical entities are rare but include muscular degeneration, Dandy-Walker syndrome, craniosynostosis, and poikiloderma. Infantile OP has also been diagnosed in a group of infants with neuronal storage disease. An association between OP and juvenile xanthogranuloma (JXG) has never been previously reported. Herein we present a case of an intermediate form of OP in a newborn who presented with hepatosplenomegaly and pancytopenia. Histologic evaluation of a bone marrow biopsy demonstrated abnormally thickened bony trabeculae. A liver biopsy demonstrated prominent expansion of portal areas by a histiocytic infiltrate expressing CD45, CD14, CD68, CD163, factor XIIIa, and fascin, while the biopsy was negative for S100 and CD1a. These findings were those associated with JXG. Genetic testing demonstrated a mutation involving the Pleckstrin homology domain-containing family M member 1 ( PLEKHM1 ) gene. A different mutation in this gene has been previously reported in one other patient with OP. Our case is the 2nd reported case with PLEKHM1 mutation in a patient with a mild form of OP. It also demonstrates the 1st reported occurrence of OP concomitantly with JXG.

Autoimmune lymphoproliferative syndrome (ALPS): a case with congenital onset.

We describe a case of autoimmune lymphoproliferative syndrome (ALPS), which is very unusual with regard to a clinical onset soon after birth, and a clinical picture dominated by splenomegaly, jaundice, and consumptive peripheral blood cytopenias, with minimal lymphadenopathy. Our documented close follow up demonstrated initial involvement of the spleen, followed by involvement of the bone marrow and the peripheral blood. The patient underwent bone marrow transplant and is alive and well 20 months after diagnosis.