Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation.

Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and DICER1-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3-14 years). Primary sites of origin included the fallopian tube (four cases), serosal surface of the colon (one case), and pelvic sidewall (two cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB, and the remaining five had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic DICER1 variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of DICER1 pathogenic variation whose pathologic features are also recapitulated in DICER1-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor DICER1 testing.

Surveillance imaging in pediatric ependymoma.

BACKGROUND: Management of pediatric patients with ependymoma includes posttreatment surveillance imaging to identify asymptomatic recurrences. However, it is unclear whether early detection translates into improved survival. The objective was to determine whether detection of ependymoma relapses on surveillance imaging translates into a survival benefit. PROCEDURE: Patients with ependymoma aged <21 years at diagnosis treated in the Nemours' Children's Health System between January 2003 and October 2016 underwent chart review. Relapsed patients' charts were assessed for details of initial therapy, surveillance imaging regimen, details of relapse including detection and therapy, and outcome. Median follow up of the entire cohort was 6.5 years from diagnosis and 3.5 years from relapse. RESULTS: Ninety of 198 (45%) patients experienced relapse with 61 (68%) detected by surveillance imaging and 29 (32%) detected based on symptoms. Five-year OS in the surveillance group was 67% (confidence interval [CI] 55-82%, SE 0.1) versus 51% (CI 35-73%, SE 0.19) in the symptoms group (P = .073). From relapse, the 3-year OS in the surveillance group was 62% (CI 50-78%, SE 0.11) versus 55% (CI 39-76%, SE 0.17) in the symptoms group (P = .063) and the 3-year SPFS was 45% (CI 33-61%, SE 0.16) in the surveillance group versus 32% (CI 19-55%, SE 0.27) in the symptoms group (P = .028). CONCLUSION: Surveillance imaging may identify recurrences in patients when they are more amenable to salvage therapy, resulting in superior 3-year SPFS, but given limited salvage options for children with recurrent ependymoma, the survival advantage of frequent surveillance imaging in asymptomatic patients remains ambiguous.

A Case of Vitamin K Deficiency Bleeding in a Newborn: Catastrophic Yet Preventable.

A four-week-old full-term male infant presented to the emergency department with blood in the diaper, increasing lethargy, and vomiting and was found to have multiple intracranial hemorrhages on CT. He was delivered at home and did not receive vitamin K. Coagulation studies were abnormal, and des-gamma carboxyprothrombin (DCP) was 481, diagnostic of vitamin K deficiency. He received vitamin K and required multiple antiepileptic medications for seizure control. Vitamin K deficiency bleeding (VKDB) is a preventable disease that can have devastating consequences and could present as early, classical, or late-onset. The typical presentation manifests with cutaneous, gastrointestinal, or intracranial hemorrhage most commonly in fully breastfed infants. Vitamin K prophylaxis has proven to be effective. With increasing out-of-hospital delivery and online misinformation, there is a declining administration of intramuscular vitamin K at birth. It is the responsibility of healthcare providers to properly inform patients and their families of the importance of vitamin K prophylaxis at or before the time of delivery.

Long-term outcomes following proton therapy for non-metastatic central nervous system germinoma in children and adolescents.

BACKGROUND/PURPOSE: Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG. MATERIALS METHODS: We enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 - September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5. RESULTS: Median follow-up was 6.2 years (range, 0.9---15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed. CONCLUSIONS: When utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.

Small Bowel Obstruction and Enterococcus Meningitis: Rare Complications of Ventriculoperitoneal Shunt Placement.

A ventriculoperitoneal (VP) shunt is a commonly used mechanical device indicated for congenital and acquired hydrocephalus in children. Although VP shunt failure is not uncommon, the symptomatology and cause of failure can vary. In this case, we describe intestinal obstruction in a three-year-old Caucasian female with a history of Pilomyxoid Astrocytoma and VP shunt placement for the management of hydrocephalus. Surgical exploration revealed ischemia of the terminal ileum secondary to VP shunt tubing-induced adhesions requiring bowel resection. A secondary VP shunt infection due to Enterococcus faecalis was also noted. Our case highlights a unique presentation of intestinal obstruction and infection that should serve to increase provider suspicion when evaluating patients presenting with abdominal distention and pain with presence of a VP shunt.

Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study.

PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy. METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors. RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007). CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

Molecular Heterogeneity in Pediatric Malignant Rhabdoid Tumors in Patients With Multi-Organ Involvement.

Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with SMARCB1 germline alterations. Here we present data from seven RTs from three pediatric patients who all had multi-organ involvement. The tumors were analyzed using a multimodal molecular approach, which included exome sequencing of tumor and germline comparator and RNA sequencing and DNA array-based methylation profiling of tumors. SMARCB1 germline alterations were identified in all patients and in all tumors. We observed a second hit in SMARCB1 via chr22 loss of heterozygosity. By methylation profiling, all tumors were classified as rhabdoid tumors with a corresponding subclassification within the MYC, TYR, or SHH AT/RT subgroups. Using RNA-seq gene expression clustering, we recapitulated the classification of known AT/RT subgroups. Synchronous brain and kidney tumors from the same patient showed different patterns of either copy number variants, single-nucleotide variants, and/or genome-wide DNA methylation, suggestive of non-clonal origin. Furthermore, we demonstrated that a lung and abdominal metastasis from two patients shared overlapping molecular features with the patient's primary kidney tumor, indicating the likely origin of the metastasis. In addition to the SMARCB1 events, we identified other whole-chromosome events and single-nucleotide variants in tumors, but none were found to be prognostic, diagnostic, or offer therapeutic potential for rhabdoid tumors. While our findings are of biological interest, there may also be clinical value in comprehensive molecular profiling in patients with multiple rhabdoid tumors, particularly given the potential prognostic and therapeutic implications for different rhabdoid tumor subgroups demonstrated in recent clinical trials and other large cohort studies.

Vaping the Venom: Oral Cavity Cancer in a Young Adult With Extensive Electronic Cigarette Use.

Squamous cell carcinoma (SCC) of the oral cavity is one of the most common malignancies of the head and neck. Risk factors for the development of SCC include infection with human papillomavirus (HPV), tobacco use, and alcohol use. HPV-positive SCC of the oral cavity is more commonly seen in young adult patients, whereas HPV-negative disease is more prevalent in older patients with histories of alcohol and tobacco use. We describe the case of a young adult with an extensive history of vaping using nicotine-delivery systems who was diagnosed with HPV-negative SCC that was rapidly progressive and fatal.

Clinically aggressive pediatric spinal ependymoma with novel MYC amplification demonstrates molecular and histopathologic similarity to newly described MYCN-amplified spinal ependymomas.

Primary spinal cord tumors contribute to ≤ 10% of central nervous system tumors in individuals of pediatric or adolescent age. Among intramedullary tumors, spinal ependymomas make up ~ 30% of this rare tumor population. A twelve-year-old male presented with an intradural, extramedullary mass occupying the dorsal spinal canal from C6 through T2. Gross total resection and histopathology revealed a World Health Organization (WHO) grade 2 ependymoma. He recurred eleven months later with extension from C2 through T1-T2. Subtotal resection was achieved followed by focal proton beam irradiation and chemotherapy. Histopathology was consistent with WHO grade 3 ependymoma. Molecular profiling of the primary and recurrent tumors revealed a novel amplification of the MYC (8q24) gene, which was confirmed by fluorescence in situ hybridization studies. Although MYC amplification in spinal ependymoma is exceedingly rare, a newly described classification of spinal ependymoma harboring MYCN (2p24) amplification (SP-MYCN) has been defined by DNA methylation-array based profiling. These individuals typically present with a malignant progression and dismal outcomes, contrary to the universally excellent survival outcomes seen in other spinal ependymomas. DNA methylation array-based classification confidently classified this tumor as SP-MYCN ependymoma. Notably, among the cohort of 52 tumors comprising the SP-MYCN methylation class, none harbor MYC amplification, highlighting the rarity of this genomic amplification in spinal ependymoma. A literature review comparing our individual to reported SP-MYCN tumors (n = 26) revealed similarities in clinical, histopathologic, and molecular features. Thus, we provide evidence from a single case to support the inclusion of MYC amplified spinal ependymoma within the molecular subgroup of SP-MYCN.