Successful use of transarterial radioembolization with yttrium-90 (TARE-Y90) in two children with hepatoblastoma.

Primary malignant liver tumors are rare but all require surgical resection as part of therapy with curative intent. A minority of patients have resectable tumors at diagnosis. Chemotherapy has a therapeutic role in hepatoblastoma but only one-third of patients have resectable disease at diagnosis. Two children with hepatoblastoma and suboptimal responses to initial chemotherapy received therapy with transarterial radioembolization utilizing yttrium-90 (TARE-Y90) and had significant response leading to resection and remission. The role of TARE-Y90 needs to be studied further to define its use in primary pediatric liver neoplasms.

Post-transplant lymphoproliferative disease of the larynx.

Laryngeal post-transplant lymphoproliferative disease (PTLD) is rare. Here, we describe two pediatric cases. The first, a 15-month-old who underwent liver transplantation at 5 weeks, presented with airway distress. Airway evaluation identified epiglottic and arytenoid infiltrate, and biopsy was consistent with polymorphic PTLD. The second, a 23-month-old who underwent liver transplantation at 13 months, presented with progressive stridor. Airway evaluation revealed sub-mucosal infiltrate of the epiglottis, arytenoids, post-cricoid region, and uvula. Biopsy was consistent with monomorphic PTLD. Airway findings and symptoms resolved for both after immunosuppression reduction. PTLD diagnosis requires a high index of suspicion in post-transplant patients with airway obstruction.

Association between Testicular Microlithiasis and Testicular Neoplasia: Large Multicenter Study in a Pediatric Population.

Purpose To retrospectively define the strength of association between testicular microlithiasis and testicular neoplasia in a large geographically diverse pediatric population. Materials and Methods Retrospective review of scrotal ultrasonographic (US) examination reports and pathology specimens obtained between January 2000 and May 2014 at six academic pediatric hospitals in North America was performed. Reported cases were reviewed to confirm microlithiasis. Radiology and pathology data bases were searched for pathology-proven testicular tumors (benign or malignant germ cell or stromal tumors). Association strength (risk) was expressed in terms of odds ratios (ORs) with and without adjustment for fixed study site effects based on logistic regression. Results A total of 37 863 individuals underwent scrotal US during the study period. Mean age was 11.1 years ± 4.7 [standard deviation] in boys with microlithiasis and 9.1 years ± 5.9 in boys without microlithiasis (P < .001). Microlithiasis was confirmed in 2.90% of patients (1097 of 37 863; range, 1.61%-5.25% across sites). It was unilateral in 21.97% (241 of 1097) of patients and bilateral in 78.0% (856 of 1097). Tumor was identified in 4.64% (51 of 1097) of boys with microlithiasis and 0.33% (122 of 36 766) of boys without (unadjusted OR, 14.65; 95% confidence interval [CI]: 10.29, 20.84; adjusted OR, 14.19). Malignant germ cell tumors were identified in 2.8% (31 of 1097) of boys with microlithiasis and 0.12% (45 of 36 766) of boys without microlithiasis (unadjusted OR, 17.26; 95% CI: 11.8, 25.25; adjusted OR, 22.37). Sex cord-stromal tumors were identified in 0.46% (five of 1097) of boys with microlithiasis and 0.079% (29 of 36 766) of boys without (unadjusted OR, 5.8; 95% CI: 2.1, 16; adjusted OR, 6.39). Conclusion There is a strong association between testicular microlithiasis and primary testicular neoplasia in this pediatric population. © RSNA, 2017.

Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report.

Behcet disease is a potentially life-threatening multisystemic vasculitis with thrombotic tendency. Mucocutaneous ulcers, arthritis, and uveitis are the most recognizable features, but may be absent at the time of medical evaluation. We report a case in which a 8-year old patient presented with spontaneous bilateral lower extremity deep venous thromboses, and screening for rheumatologic symptoms led to diagnosing Behcet. This case demonstrates that deep venous thromboses can be the initial event bringing a patient with Behcet to medical attention, highlighting the importance of screening for underlying rheumatologic diseases in pediatric patients who present with unprovoked thrombosis.

Malignant rhabdoid tumor of the bladder and ganglioglioma in a 14 year-old male with a germline 22q11.2 deletion.

Malignant rhabdoid tumors (MRTs) are rare pediatric malignancies characterized by clinically aggressive lesions that typically show loss of SMARCB1 expression. We herein describe a case of a malignant rhabdoid tumor of the bladder in a 14-year-old male with an autism spectrum disorder and a de novo 3 Mb germline deletion in chromosome band 22q11.2 that included the SMARCB1 gene. The malignancy developed in the setting of chronic hematuria (>2 years) following the occurrence of two other lesions: a central nervous system ganglioglioma and an intraoral dermoid cyst. MRTs of the bladder are exceedingly rare, and this patient is the oldest child reported with this tumor to date. This case adds to the growing body of literature regarding the recently described, phenotypically diverse, distal 22q11.2 syndrome. Furthermore, this is the first reported case in which an MRT of the bladder appears to have developed from a pre-existing bladder lesion. Finally, this case further supports a rhabdoid tumorigenesis model in which heterozygous loss of SMARCB1 predisposes to initial tumor formation with intact SMARCB1 expression, with subsequent inactivation of the other SMARCB1 allele, which results in transformation into more malignant lesions.

Lipofibromatosis: an institutional and literature review of an uncommon entity.

We report six new cases of lipofibromatosis, an uncommon pediatric soft tissue neoplasm. This is the only series of patients to be described since the initial case series of 45 patients that characterized this entity in 2000. The purpose of this study was to characterize the presentation of lipofibromatosis to further define the clinical phenotype of this rare entity. Six patients were diagnosed with lipofibromatosis at our institution from 2000 to 2012. Patient age, sex, and ethnicity were recorded, along with tumor site and size, management, and recurrence data. Half of our patients were younger than 2 years old at presentation and the other half were school age. Boys and girls were affected with equal frequency. In five of six patients, lipofibromatosis presented in its "classic" form as a mass on the distal extremities. These tumors typically measured 1 to 2 cm in diameter, in contrast to case reports in the medical literature highlighting the occurrence of lipofibromatosis of greater size and at varied anatomic sites. The tumors in our series were managed using excision, with recurrence noted in 33%. Lipofibromatosis is an uncommon tumor typically found on the distal extremities of infants, although it can appear in various sizes and locations. It should be considered in the differential diagnosis of pediatric soft tissue neoplasms.

Intra-articular nodular fasciitis of the knee in a pediatric patient.

The differential diagnosis for an intra-articular lesion in the knee of a pediatric patient is broad. Diagnostic considerations include pigmented villonodular synovitis (PVNS)-the most common intra-articular tumor-and a variety of both benign and malignant tumors, including lipomas, hemangiopericytomas, nodular fasciitis, parosteal osteosarcomas, and fibromyxoid sarcomas. If there is concern over possible malignant lesions, a tumor surgeon should be consulted. Precise pathologic diagnosis is ideal for identifying these enigmatic lesions and for determining the appropriate treatment plan. This article presents the case of a 13-year-old boy who presented with 1-month duration of knee pain and no history of trauma to the extremity. Physical examination revealed pain along the medial and lateral joint lines, pain with range of motion, and limited range of motion of the affected knee. Magnetic resonance imaging revealed a 3×1×3-cm lesion in the posterolateral corner that was believed to be localized PVNS. Arthroscopically, there was no evidence of PVNS, but a posterolateral soft tissue mass was found and removed, which was pathologically diagnosed as a rare, benign, intra-articular nodular fasciitis. When working with intra-articular masses, it is important to assess the likelihood of malignancy and to both consult a tumor surgeon and use the appropriate surgical tumor principles when malignancy is a concern. Additionally, the pathology team should be consulted prior to surgery and be on standby during arthroscopic evaluation of the knee to help with precise diagnosis of the intra-articular mass. Discussing the case with the pathologist with imaging studies present is helpful and often aids in the diagnosis of the lesion.

DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma.

The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and 'hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma.

Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. Current management strategies for EoE are nonspecific, and thus there is a need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis has been unclear. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE, but was dependent on TSLP and basophils, as targeting TSLP or basophils during the sensitization phase limited disease. Notably, therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. In human subjects with EoE, we observed elevated TSLP expression and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses in patients with EoE. Together, these data suggest that the TSLP-basophil axis contributes to the pathogenesis of EoE and could be therapeutically targeted to treat this disease.

Congenital mydriasis associated with megacystis microcolon intestinal hypoperistalsis syndrome.

We report a case of congenital mydriasis in a neonate with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS). Pilocarpine testing and gastrointestinal pathology in our patient suggest that the mydriasis is due to an underlying smooth muscle myopathy of the iris sphincter muscle. These findings may have important implications regarding the pathogenesis of MMIHS.

Low back pain in a child associated with acute onset cauda equina syndrome: a rare presentation of an aggressive vertebral hemangioma: a case report.

BACKGROUND: Back pain prevalence in the pediatric age group is less compared with adults. There is a wide range of possible etiologies, and tumors such as primary spinal hemangiomas are uncommon. Most are incidental findings and asymptomatic; however, painful lesions can be presented in up to 0.9% to 1.2% of cases. These lesions can produce neurologic involvement either spinal cord compression or cauda equina syndrome as in our case. The aim of this study is to describe a case of low back pain in a child due to a vertebral hemangioma complicated with acute cauda equina syndrome, and performed a literature review that will help us to recognize this aggressive variance making an early treatment feasible. METHODS: A 13-year-old female, follow-up in an outer health care center due to a L1 vertebral hemangioma, characterized by 3 years of low back pain without neurologic symptoms presented to our emergency department with an acute cauda equina syndrome. RESULTS: An outside magnetic resonance imaging showed complete obliteration of the spinal canal at the level of the conus medullaris related to retropulsion of bone at L1. She underwent 2-stage surgical treatment: complete posterior L1 laminectomy and partial T12-L2 laminectomies, with partial L1 vertebrectomy and posterior fusion with instrumention from T11 to L3. Three weeks later, embolization before anterior fusion with inner body cage was performed. Forty months after surgery, she is doing well with no neurologic deficits. CONCLUSIONS: Even though hemangiomas are not a common cause of back pain, they should be taken into account. It is important to recognize the aggressive variance so an early treatment could be performed. There is no enough clinical data to establish guidelines of management in children, therefore, the treatment should be individualized.

Imaging of pediatric ovarian neoplasms.

We review the clinical and imaging characteristics of the most common ovarian neoplasms in children and adolescents. Because of the widespread use of diagnostic imaging, incidental ovarian neoplasms might be encountered during the evaluation of abdominal pain, trauma or other indications and might pose a diagnostic dilemma. Conducting adequate imaging studies under these conditions is important, as management strategies differ according to the size and appearance of the lesion as well as the age of the patient. US dominates in gynecological imaging because of its excellent visualization, absence of ionizing radiation and sedation risks and comparatively low cost. For further examination of indeterminate lesions found using US, MRI is being used more progressively in this field, particularly for the evaluation of complex pelvic masses with the aim of distinguishing benign and malignant conditions and conditions requiring surgical intervention. CT is reserved primarily for tumor staging and follow-up and for emergency situations.

Leclercia adecarboxylata cellulitis in a child with acute lymphoblastic leukemia.

Leclercia adecarboxylata is a rare, gram-negative rod that has been infrequently reported in the literature. The organism has been documented to cause solitary infections in immunocompromised hosts and polymicrobial wound infections in the immunocompetent. We present a case of an 8-year-old boy with significant past medical history of acute lymphoblastic leukemia who developed cellulitis due to local infection by L. adecarboxylata. This case is presented to raise awareness of this rare organism's ability to cause common cutaneous disease, especially in the immunocompromised.

Idiopathic orbital inflammation leading to unilateral blindness over a 2-day presentation in a child.

An 8-year-old boy developed vision loss to no light perception on the left side over a 2-day period. He initially presented with unilateral eyelid swelling, which progressed to bilateral edema and an eventual left-sided orbital apex syndrome. Orbital imaging revealed enlarged extraocular muscles, and biopsy confirmed idiopathic orbital inflammation. Despite subsequent orbital decompression, high-dose steroids, and additional steroid-sparing therapy, he did not regain vision after 9 months of follow up.

Lnk constrains myeloproliferative diseases in mice.

Hematopoietic stem and progenitor cell (HSPC) expansion is regulated by intrinsic signaling pathways activated by cytokines. The intracellular kinase JAK2 plays an essential role in cytokine signaling, and activating mutations in JAK2 are found in a number of hematologic malignancies. We previously demonstrated that lymphocyte adaptor protein (Lnk, also known as Sh2b3) binds JAK2 and attenuates its activity, thereby limiting HSPC expansion. Here we show that loss of Lnk accelerates and exacerbates oncogenic JAK2-induced myeloproliferative diseases (MPDs) in mice. Specifically, Lnk deficiency enhanced cytokine-independent JAK/STAT signaling and augmented the ability of oncogenic JAK2 to expand myeloid progenitors in vitro and in vivo. An activated form of JAK2, unable to bind Lnk, caused greater myeloid expansion than activated JAK2 alone and accelerated myelofibrosis, indicating that Lnk directly inhibits oncogenic JAK2 in constraining MPD development. In addition, Lnk deficiency cooperated with the BCR/ABL oncogene, the product of which does not directly interact with or depend on JAK2 or Lnk, in chronic myeloid leukemia (CML) development, suggesting that Lnk also acts through endogenous pathways to constrain HSPCs. Consistent with this idea, aged Lnk-/- mice spontaneously developed a CML-like MPD. Taken together, our data establish Lnk as a bona fide suppressor of MPD in mice and raise the possibility that Lnk dysfunction contributes to the development of hematologic malignancies in humans.

Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease.

Ubiquitin ligases play an important role in the regulation of the immune system. Absence of Itch E3 ubiquitin ligase in mice has been shown to cause severe autoimmune disease. Using autozygosity mapping in a large Amish kindred, we identified a linkage region on chromosome 20 and selected candidate genes for screening. We describe, in ten patients, identification of a mutation resulting in truncation of ITCH. These patients represent the first reported human phenotype associated with ITCH deficiency. These patients not only have multisystem autoimmune disease but also display morphologic and developmental abnormalities. This disorder underscores the importance of ITCH ubiquitin ligase in many cellular processes.

Mesenteric lipoblastoma presenting as a segmental volvulus.

Mesenteric lipoblastoma is a rare tumor and, its presentation as a bowel obstruction with possible midgut volvulus has only been reported once before. A 7-year-old girl presented with nausea and vomiting but a benign abdominal examination. Upper gastrointestinal contrast study demonstrated possible malrotation with midgut volvulus. During emergency laparotomy, segmental small bowel volvulus secondary to a large mesenteric lipoblastoma was found. The lipoblastoma was resected with a segment of small bowel. Resection margins were negative for tumor, and the patient is doing well with no evidence of recurrence.

Analysis of loss of heterozygosity in single-system and multisystem Langerhans' cell histiocytosis.

The contribution of molecular mutations to the progression of Langerhans' cell histiocytosis (LCH) is not well understood. This study analyzes fractional allelic loss (FAL) across a series of tumor suppressor genes (TSGs) comparing LCH of various clinical stages and LCH involving organs of various degrees of prognostic risk. Polymerase chain reaction (PCR) amplification, using fluorescent-labeled primers targeting 6 TSGs, was performed on extracted DNA. The PCR products were analyzed using a capillary electrophoresis genetic analyzer. Ratios of the peak heights in informative cases were compared between unaffected and lesional tissue to identify loss of heterozygosity (LOH). Fisher's exact testing was used to analyze the results. Fourteen children with single-system involvement (SS-LCH) and 10 with multisystem involvement (MS-LCH) were included. High-risk or special-site organ involvement was seen in 13 children and low-risk organ involvement in 10. The mean FAL in MS-LCH (62.7%) was statistically significantly higher than in SS-LCH (40.3%). The FAL in children with risk or special-site LCH (53.2%) was also significantly higher than in children with low-risk LCH (39.6%). Markers on 5q had significantly higher FAL in MS-LCH (76.3%) and children with risk or special-site organ involvement (72.7%) compared with SS-LCH (46.2%) and children with low-risk organ involvement (37.5%). These data suggest that more extensive and higher-risk forms of LCH have evidence of more mutational events at TSGs. Further investigation of the potential use of LOH at 5q23 will be necessary to establish utility for this assay to predict disease progression and poor outcome.