Potential prognostic determinants for FET::CREB fusion-positive intracranial mesenchymal tumor.

Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and a slight female predominance (female/male ratio = 1.55). Among the confirmed fusions, 25 (33.8%) featured an EWSR1::ATF1 fusion, 24 (32.4%) EWSR1::CREB1, 23 (31.1%) EWSR1::CREM, one (1.4%) FUS::CREM, and one (1.4%) EWSR1::CREB3L3. Among 66 patients with follow-up information available (median: 17 months; range: 1-158 months), 26 (39.4%) experienced progression/recurrences (median 10.5 months; range 0-120 months). Ultimately, three patients died of disease, all of whom underwent a subtotal resection for an EWSR1::ATF1 fusion-positive tumor. Outcome analysis revealed subtotal resection as an independent factor associated with a significantly shorter progression free survival (PFS; median: 12 months) compared with gross total resection (median: 60 months; p < 0.001). A younger age (< 14 years) was associated with a shorter PFS (median: 9 months) compared with an older age (median: 49 months; p < 0.05). Infratentorial location was associated with a shorter overall survival compared with supratentorial (p < 0.05). In addition, the EWSR1::ATF1 fusion appeared to be associated with a shorter overall survival compared with the other fusions (p < 0.05). In conclusion, IMT is a locally aggressive tumor with a high recurrence rate. Potential risk factors include subtotal resection, younger age, infratentorial location, and possibly EWSR1::ATF1 fusion. Larger case series are needed to better define prognostic determinants in these tumors.

The long noncoding RNA lnc-HLX-2-7 is oncogenic in Group 3 medulloblastomas.

BACKGROUND: Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the noncoding RNA genome, in particular long noncoding RNAs (lncRNAs), contributes to MB subgrouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential molecular marker and therapeutic target in Group 3 MBs. METHODS: Publicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify lncRNAs that differentiate between MB subgroups. After characterizing a subset of differentially expressed lncRNAs in vitro and in vivo, lnc-HLX-2-7 was deleted by CRISPR/Cas9 in the MB cell line. Intracranial injected tumors were further characterized by bulk and single-cell RNA-seq. RESULTS: Lnc-HLX-2-7 is highly upregulated in Group 3 MB cell lines, patient-derived xenografts, and primary MBs compared with other MB subgroups as assessed by quantitative real-time, RNA-seq, and RNA fluorescence in situ hybridization. Depletion of lnc-HLX-2-7 significantly reduced cell proliferation and 3D colony formation and induced apoptosis. Lnc-HLX-2-7-deleted cells injected into mouse cerebellums produced smaller tumors than those derived from parental cells. Pathway analysis revealed that lnc-HLX-2-7 modulated oxidative phosphorylation, mitochondrial dysfunction, and sirtuin signaling pathways. The MYC oncogene regulated lnc-HLX-2-7, and the small-molecule bromodomain and extraterminal domain family‒bromodomain 4 inhibitor Jun Qi 1 (JQ1) reduced lnc-HLX-2-7 expression. CONCLUSIONS: Lnc-HLX-2-7 is oncogenic in MB and represents a promising novel molecular marker and a potential therapeutic target in Group 3 MBs.

Chondroblastoma of bone in the extremities: a multicenter retrospective study.

BACKGROUND: Chondroblastoma is a rare benign cartilage tumor that commonly occurs in children and adolescents. This study was designed to review the epidemiologic characteristics and outcomes of surgical management in a large series of patients with extremity chondroblastoma. METHODS: We performed a multicenter retrospective analysis of 199 patients with extremity chondroblastoma. Clinical data, radiographic images, histological findings, treatment, and outcome were analyzed. RESULTS: There were 145 male patients and fifty-four female patients with a mean age of 18.0 years. The most commonly involved bone was the proximal part of the tibia (fifty-five patients [27.6%]), followed by the proximal part of the femur (fifty-two patients [26.1%]) and the distal part of the femur (thirty-eight patients [19.1%]). Prior to presentation, 73.4% (146 of 199 patients) experienced pain. The mean duration of pain and other symptoms was 8.7 months. The physis was open in 25.7%, it was closing in 22.2%, and it was closed in 52.1% of the patients at the time of presentation. One hundred and twenty-six patients had at least twenty-four months of follow-up; their mean follow-up duration was 62.1 months (range, twenty-four to 190 months). Initial treatment was curettage for 119 patients (94.4%) and en bloc resection for seven patients (5.6%). The local recurrence rate was 5.0% after curettage and 0% after resection. The only significant factor related to recurrence was the location of the lesion in the proximal part of the humerus (p = 0.001). CONCLUSIONS: Chondroblastoma occurs most frequently in the proximal part of the tibia and the proximal part of the femur with significant male predilection. In this series, recurrence was most frequent in the proximal part of the humerus. Our results suggest that curettage and bone-grafting provide favorable local control and satisfactory functional outcome for patients with this disease. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Primary Burkitt's lymphoma of the colon--an uncommon cause of acute constipation and abdominal pain.

Constipation is a common problem in children and adolescents, accounting for over 25% of all visits to pediatric gastroenterologists. Approximately 95% of childhood constipation is functional in nature. Primary gastrointestinal malignancies are rare in childhood and adolescence. When present in the gastrointestinal tract, Burkitt's lymphoma is typically located in the ileocecal region. We present a case of primary Burkitt's lymphoma of the transverse colon in an adolescent presenting with acute exacerbation of constipation, abdominal pain, and later, rectal bleeding and progressive weight loss.

Surgical management of perineal masses in patients with anorectal malformations.

BACKGROUND: The aim of this study was to review the outcome of surgical management of various types of perineal masses encountered in patients with anorectal malformations (ARM). METHODS: Retrospective review from 2 large pediatric anorectal referral centers. RESULTS: Twenty-two patients with a perineal mass were identified in more than 2000 patients treated for an ARM over a 15-year period. The 22 patients (4 men) represented all levels of severity of ARMs. The lesions were of 3 types: lipomas (n = 10), vascular anomalies (n = 4), and hamartomas/choristomas (n = 8). The lipomas were carefully removed from between the muscle fibers during the posterior sagittal anorectoplasty. The vascular anomalies (3 of 4 were hemangiomas) underwent magnetic resonance imaging preoperatively, but none were found to invade deeply and all were excised at the time of the posterior sagittal anorectoplasty. The hamartomas/choristomas all occurred in women, and 50% arose as a pedunculated mass from the vulva. The lesions contained tissues such as glia, osteoid, nephrogenic rests, and endocervical-type mucosa. One was initially misinterpreted as a teratoma, prompting a wider excision. This and all subsequent patients have been correctly diagnosed pathologically as having either hamartomas or choristomas, which were not widely excised. Follow-up ranges from 5 months to 12 years. Six of the 10 lipoma patients are continent. One vascular anomaly was re-excised and there was minor wound separation in another. None of the hamartoma/choristoma lesions recurred. CONCLUSION: The presence of unusual perineal masses can add to the complexity of ARMs; however, most of these lesions can be carefully excised with preservation of the muscle complex and ultimate continence. Hamartomatous lesions can be mistaken for teratomas but do not require aggressive excision with clear margins.

Ewing sarcoma/peripheral primitive neuroectodermal tumor: adult abdominal tumors with an Ewing sarcoma gene rearrangement demonstrated by fluorescence in situ hybridization in paraffin sections.

The differential diagnosis of small round cell tumors is exhaustive and requires ancillary studies. Relatively recently, fluorescence in situ hybridization (FISH) using probes for specific gene rearrangements has gained wide acceptance. This technique is particularly useful in the differential diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) and desmoplastic small round-cell tumor (DSRCT). In ES/PNET, the EWS gene is juxtaposed to the FLI-1 gene in 85% of cases and to the ERG gene in another 7% of cases; the EWS gene is juxtaposed to the WTI gene in DSRCT. Documentation of the EWS gene rearrangements in EWS/PNET has previously been demonstrated in frozen tissue. We report 2 unusual cases of EWS/PNET diagnosed in abdominal tumors in adults. Although the immunohistochemical results supported a diagnosis of ES/PNET, 1 case morphologically resembled DSRCT. The diagnosis in these 2 cases was confirmed by the FISH demonstration of EWS/FLI-1 gene fusion in paraffin-embedded tissue. Thus, the usefulness of FISH demonstration of an EWS gene rearrangement with these specific probes in such unusual cases is supported and is demonstrated in paraffin-embedded tissue.

Extralobar pulmonary sequestration presenting with torsion.

The current report describes the case of a 13-year-old girl with an extralobar pulmonary sequestration who presented with chest and back pains without evidence of infection. Her symptoms were discovered to be secondary to torsion and infarction of the pulmonary sequestration. Although pulmonary sequestration is not an uncommon differential diagnosis for chest masses, it is rare for it to present in this manner.

The gastric cardia: to be or not to be?

The origin and biologic significance of cardiac gastric mucosa are controversial. Traditionally, it has been considered native mucosa and part of normal foregut development. It has been recently suggested that cardiac mucosa is present only as a metaplastic response to gastroesophageal reflux disease and therefore always abnormal. We evaluated the esophagogastric junction in 100 pediatric autopsy samples to determine the existence, characteristics, and length of pure cardiac mucosa at different ages. No patient had a history of gastroesophageal reflux disease. Cardiac mucosa immediately distal and contiguous to the esophageal squamous mucosa was identified in all 100 samples, varying in length from 0.1 to 3 mm; the mean length was 1 mm. There was an inverse correlation between patient age and length of cardiac mucosa; gender had no influence on measured length. Three patients had mild to moderate histologic esophagitis; two had gastritis. No metaplastic features or Helicobacter pylori were identified. These findings support the concept that there is a normal, variably narrow developmental zone at the esophagogastric junction covered by cardiac mucosa and is present at birth. When cardiac type mucosa is found in biopsy material, it does not necessarily represent evidence of a mucosal metaplastic response to gastroesophageal reflux disease.

Successful multimodality therapy of recurrent multifocal juvenile granulosa cell tumor of the ovary.

Juvenile granulosa cell tumor (JGCT) of the ovary, a rare pediatric cancer, carries a very poor prognosis in advanced and recurrent cases. A 10-year-old girl with stage IA JGCT, initially treated with resection only, presented with extensive unresectable multifocal pelvic recurrence. She underwent surgery, chemotherapy (cisplatin/paclitaxel alternating with cisplatin/cyclophosphamide/etoposide/bleomycin), myeloablative chemotherapy (carboplatin/etoposide/melphalan) with autologous bone marrow transplant, and pelvic radiation. She tolerated therapy well and is in complete remission 69 months after her recurrence.

Maternal pulmonary adenocarcinoma metastatic to the fetus: first recorded case report and literature review.

We report the first maternal pulmonary adenocarcinoma metastatic to the fetus as well as an updated literature review. Review of the literature revealed that there have been only 67 cases of maternal malignancy metastatic to the products of conception. These were mostly malignant melanoma and hematopoietic tumors. A 46-year old multiparous woman with metastatic pulmonary adenocarcinoma, diagnosed at 23 weeks gestation, delivered a male infant who appeared normal at birth. The mother died 2 days after delivery. The child developed multiple scalp tumors a 2 weeks of age. The tumors recurred rapidly after initial resection. Wide local excision of the involved scalp and skin graft coverage was performed at 14 weeks of age. Histopathology of these tumors was identical to that of the maternal tumor. The maternal origin of these tumors was confirmed by fluorescence in situ hybridization (FISH). The child is now 5 years old and free of disease.