Solid-variant aneurysmal bone cysts in the craniofacial skeleton: the role of genomic analysis.

BACKGROUND: Solid variant aneurysmal bone cysts (SVABCs) are a rare but well-described subtype of ABCs. While classic ABCs are readily identified radiographically, SVABCs lack these characteristic radiographic features and thus have a wide differential diagnosis on presentation (including Ewing sarcoma, Langerhans cell histiocytosis, osteosarcoma, metastasis, and giant cell tumor). Genomic/molecular analyses are often necessary for the diagnosis of SVABCs, with USP6 rearrangements being a characteristic finding. We present two cases in which genomic analysis was critical in the diagnosis of SVABCs and revealed unique gene fusions that may provide insight into SVABC pathogenesis. CASE DESCRIPTIONS: Two 13-year old male children presented to our institution with new mass lesions involving the craniofacial skeleton. Magnetic resonance imaging (MRI) in both cases revealed predominantly solid, avidly enhancing masses, one of the squamous portion of the temporal bone, and the other arising from the sphenopalatine foramen with extension into the ipsilateral maxillary and ethmoid sinuses. Histopathology displayed predominantly solid morphology, and next generation sequencing (NGS) revealed a FAT1-USP6 gene fusion in the temporal lesion, and a MIR22HG-USP6 gene fusion in the maxillofacial lesion, the latter of which was not identified on fluorescence in situ hybridization (FISH). These findings were most consistent with a diagnosis of SVABC in each case. CONCLUSIONS: These two cases highlight novel gene fusions in atypically located SVABCs and emphasize the ability of NGS to more accurately and consistently identify USP6 gene fusions, particularly in SVABCs that may otherwise be indistinguishable from alternative pathologies.

Benign Phyllodes Tumor in Children: A Study of 8 Cases and Review of the Literature.

Phyllodes tumor (PT) occurs predominantly in middle-aged women, and although its occurrence in young women, adolescents, and even children is documented, presentation in the pediatric population has been the least well studied because of its rarity. Incompletely defined in children with PT are recurrence rates and optimal surgical management. We retrospectively studied the pathology database of Hartford Hospital from 2010 to 2017 to find all cases of PT in patients 18 years of age or younger. A series of 8 children/adolescents with breast masses diagnosed as benign PT were identified. Patients were 14 to 16 years of age (mean 15.2 y) and tumor size ranged from 2.2 to 7.2 cm (mean 4.4 cm). Both breasts were equally affected. All patients were treated with excision, tantamount to simple enucleation in most cases, and positive or "tumor-abutting" margins were universal. Mean follow-up after surgery was 27.5 months, during which time a single recurrence (at 9 mo) became manifest, which was re-excised and again showed benign PT. There were no pathologic features (including marginal status) that could have predicted the sole recurrence. Despite positive margins, the local recurrence rate for pediatric benign PT appears acceptably low (1 in 8 cases) such that reflex re-excision is probably unnecessary.

Rare congenital meningothelial hamartoma of the scalp with progressive growth.

Scalp lesions are common pediatric findings that present for neurosurgical evaluation and management. The majority will be benign. Meningothelial hamartomas represent a rare subset of congenital cutaneous lesions with the potential for intracranial extension and microscopic infiltration of the surrounding tissues. The authors report in this paper a case of meningothelial hamartoma of the scalp that demonstrated serial growth and invasion of the scalp. The degree of microscopic involvement and growth necessitated close follow-up and repeat excision.

Congenital Salivary Gland Anlage Tumor: An Unusual Anterior Skull Base Mass in the Neonatal Period.

Congenital salivary gland anlage tumor (SGAT) is a benign nasopharyngeal mass that presents with respiratory distress in infancy. Prior case reports have characterized SGAT as a lesion of the nasopharynx without intracranial extension. We report a unique case of SGAT extending through the anterior skull base and discuss the differential diagnosis and management of this unusual entity.

Congenital Disseminated Malignant Rhabdoid Tumor Mimicking a Vascular Lesion.

A congenital disseminated malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive pediatric cancer marked by the presence of malignant rhabdoid cells in various organs, including the brain, kidneys, and soft tissues, at birth. It is often detected prenatally or shortly post-birth. The malignancy's aggressiveness results in a bleak prognosis, offering limited treatment options and low survival rates. Early diagnosis and comprehensive medical intervention are crucial, but managing this condition is complicated by its rarity. We herein presented a case of a 37 and 1/7 week gestation male infant with a rapidly growing arm soft tissue mass within two weeks, diagnosed as an MRT. Post-delivery examinations revealed multiple lesions in the lungs, kidney, liver, and adrenal glands. Notably, chemotherapy yielded a significant improvement in the arm lesion, contrasting with other lesions showing a limited response. This observation suggests potential tumor heterogeneity, emphasizing the necessity of diverse therapeutic regimens. Our case underscores the complexities of congenital disseminated MRT, prompting a reevaluation of treatment strategies for enhanced efficacy in managing this challenging pediatric cancer.

Characterizing clinical features and location-specific gene expression profiles associated with pain burden in children with functional dyspepsia.

BACKGROUND: In children with functional dyspepsia (FD), genes involved in pain modulation may be differentially expressed contributing to chronic pain. METHODS: Children with suspected FD (cases) and known eosinophilic esophagitis (controls) undergoing esophagogastroduodenoscopy completed the Rome IV Diagnostic, Pain Burden and Frequency Severity-Duration questionnaires. Two antral and two duodenal biopsies were collected and relative fold differences in gene expression for 84 pain-associated genes compared to pain-free controls were calculated. RESULTS: Sixty-six subjects with FD (postprandial distress syndrome = 34, epigastric pain syndrome = 7, both = 25; 65% female; mean age 13.7 years) and 13 pain-free controls (8% female; mean age 12.7) were studied. There were no significant differences in antral and duodenal eosinophilic counts or distribution between the pain and pain-free groups. Pain severity and burden did not differ significantly between FD subgroups and neither measure significantly correlated with eosinophil counts in the antrum or duodenum. Analysis of 47 antral and 39 duodenal biospecimens revealed 5 candidate genes significantly associated with pain burden: antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A (p < 0.01). Subsequent stringent statistical analysis comparing those with significant pain versus no pain revealed antral PTGES3 and duodenal SCN3A were the highest priority candidate genes (p < 0.001). CONCLUSIONS: Pain burden in pediatric FD may be linked to antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A differential expression. These genes are known to be involved in pain conduction, modulation, and neurotransmission, suggesting potential therapeutic targets for managing pain in FD.

Effect of gluten-free diet on growth and glycemic control in children with type 1 diabetes and asymptomatic celiac disease.

We aimed to evaluate the effects of a gluten-free diet on growth and glycemic control in children with type 1 diabetes mellitus (DM) and asymptomatic, biopsy-proven celiac disease (CD). Each case of CD was compared to two children with DM and no CD. We studied weight, height, and hemoglobin A1c (HgbAlc) up to 12 months pre- and post- CD diagnosis in 29 cases and 58 controls. The change in body mass index (deltaBMI Z-score) over 2 years was significantly higher in CD cases vs. controls (mean +/- SD 0.33 +/- 0.74 vs. +/- 0.08 +/- 0.46; p = 0.023). However, BMI Z-score did not change in CD patients diagnosed with DM for > 1 year. Mean HgbA1c was similar between groups throughout the study. In conclusion, children with asymptomatic CD and DM do not have significant changes in BMI, height Z-score or metabolic control 1 year post-diagnosis.

Pediatric Patient With Concurrent Eosinophilic Esophagitis, Erosive Reflux Esophagitis, and Barrett's Esophagus.

Eosinophilic esophagitis and Barrett's esophagus are believed to be separate disease processes, with erosive esophagitis leading to Barrett's esophagus. We report a rare case of concurrent diagnoses in a pediatric patient and examine the relevant genetic profiles in the esophagus.

Characterizing the inflammatory response in esophageal mucosal biopsies in children with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an emerging allergic, IgE- and non-IgE (Th2 cell)-mediated disease. There are major gaps in the understanding of the basic mechanisms that drive the persistence of EoE. We investigated whether esophageal biopsies from children with EoE demonstrate an inflammatory response that is distinct from normal controls. We prospectively enrolled 84 patients, of whom 77 were included in our analysis, aged 4-17 years (12.8±3.8 years; 81% males). Five esophageal biopsies were collected from each patient at the time of endoscopy. Intramucosal lymphocytes were isolated, phenotyped and stimulated with phorbol 12-myristate 13-acetate/ionomycin to measure their potential to produce cytokines via flow cytometry. We also performed cytokine arrays on 72-h biopsy culture supernatants. CD8(+) T cells, compared with CD4(+) T cells, synthesized more TNF-α and interferon (IFN)-γ after mitogen stimulation in the EoE-New/Active vs EoE-Remission group (P=0.0098; P=0.02) and controls (P=0.0008; P=0.03). Culture supernatants taken from explant esophageal tissue contained 13 analytes that distinguished EoE-New/Active from EoE-Remission and Controls. Principal component analysis and cluster analysis based on these analytes distinctly separated EoE-New/Active from EoE-Remission and Controls. In summary, we have identified a previously unappreciated role for CD8(+) T lymphocytes with potential to produce TNF-α and IFN-γ in EoE. Our results suggest that CD8(+) T cells have a role in the persistence or progression of EoE. We have also identified a panel of analytes produced by intact esophageal biopsies that differentiates EoE-New/Active from EoE-Remission and controls. Our results suggest that esophageal epithelial cells may have specific immune effector functions in EoE that control the type and amplitude of inflammation.

Ovarian steroid cell tumor, not otherwise specified, associated with congenital adrenal hyperplasia: rare tumors of an endocrine disease.

Ovarian steroid cell tumors, not otherwise specified (OSCTs), are extremely rare and present a diagnostic challenge when evaluating an ovarian mass. We present a case of such a tumor in a patient with known Congenital Adrenal Hyperplasia (CAH), secondary to 21-hydroxylase deficiency, who was noncompliant with her medications. The workup, diagnosis, and treatment of this rare condition are described.

Primary renal synovial sarcoma in a 13-year-old boy.

Primary renal synovial sarcoma is a rare entity with fewer than 40 cases reported in the literature. Its clinical presentation and radiographic features, namely, its often complex cystic appearance, make it difficult to differentiate from other benign or malignant renal lesions. Although there are certain consistent morphological and immunohistochemical features, diagnosis ultimately depends on molecular studies. Prognosis is poor, and there currently exists no defined treatment protocol. Herein, we describe the youngest reported case of primary renal synovial sarcoma in the literature.

Congenital subcostal hernia with unusual contents.

Congenital hernias arising in the subcostal region are rare. We describe a case of a former preterm infant, born with congenitally fused right 11th and 12th ribs and a protuberant mass in the right subcostal region. This mass was associated with a small fascial defect and herniation of abdominal contents. At operation, the mass was determined to be a hernia with an incarcerated ovarian remnant and fallopian tube.

Proliferative and neoplastic disorders in children with acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is a multisystem disease and, besides infections, various proliferative and neoplastic disorders are seen in cytology, biopsy, and autopsy specimens from infected children. These lesions can be classified into four types: systemic lymphoproliferation, smooth muscle tumors, Kaposi sarcoma (KS), and human papilloma (HPV)-related genital lesions. In addition, isolated cases of multiple miscellaneous tumors have been reported. Proliferative and neoplastic disorders are categorized as lesions of undetermined pathogenesis; however, there are certain factors that are suggested to be related to their pathogenesis. The symptoms related to them may be atypical or difficult to appreciate, and proliferative and neoplastic disorders may clinically mimic an opportunistic infection. The type and site of proliferative and neoplastic disorder also tends to be atypical as compared with those seen in non HIV-infected children. This is a brief but detailed review of these disorders in children with AIDS.

Soft tissue perineuriomas in children: report of three cases and review of the literature [corrected].

Perineuriomas (PN) are uncommon, slowly growing, usually benign tumors composed of well-differentiated perineural cells. Two variants are recognized: intraneural perineuriomas and soft tissue perineurioma, which includes a sclerosing subset of tumors. They are usually reported in the adult population. We present three cases of soft tissue perineuriomas in children. One was located in the deep soft tissue of the retroperitoneum in a 14-year-old girl, the second one in the left thumb of a 14-year-old boy, and the third one in the index finger of a 16-year-old boy. This report, which describes the clinicopathologic, immunohistochemical, and ultrastructural features of these tumors, should alert pathologists to the occurrence of perineuriomas in children. A review of the English language literature on perineuriomas in children is also included.