The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers.

PURPOSE OF REVIEW: We aim to review the most recent findings in the use of NK cells in childhood cancers. RECENT FINDINGS: Natural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine storm. Cytotoxicity to solid tumors (rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma) is seen with graft versus tumor effect in transplant and in combination with antibodies. Challenges lie in the microenvironment which is suppressive for NK cells. NK cell immunotherapy in childhood cancers is promising and recent works aim to overcome challenges.

Sino-orbital desmoid tumor in a pediatric patient - Case report with review of literature.

We report a case of a 2-year-old female who presented with bilateral progressive proptosis, visual loss, nasal obstruction, and breathing difficulty. Magnetic resonance imaging revealed a large sino-orbital mass that was extending to the orbital apex and skull base. An initial diagnosis of rhabdomyosarcoma was made elsewhere on the basis of the presence of round and spindle cell tumor. Subsequent biopsy with immunohistochemical staining was positive for nuclear staining with ß-catenin, shifting the diagnosis to a myofibroblastic tumor, favoring desmoid-type fibromatosis. With image guidance, near complete excision of tumor was performed by a multidisciplinary team, while respecting danger zones such as the skull base and the optic nerve. Following a recurrence over 2 months, additional excision was performed with a 6-month treatment of methotrexate and vinblastine. Desmoid tumor is a rare form of soft tissue tumor uncommonly seen in the orbital area. Although benign, it is known to be recurrent and infiltrative. Few data are known and further information will aid in the management of these tumors.

AB013. Infantile brainstem high grade glioma: a case report.

BACKGROUND: Congenital infantile brainstem high-grade gliomas (HGGs) are extremely rare. Given the limited literature characterizing this disease, management of these tumors remains challenging. Brainstem HGGs are generally associated with extremely poor prognosis. Limited reports of spontaneous regression of radiologically diagnosed infantile brainstem tumors exist in published literature. We aim to report a unique case of spontaneous regression of a rare infantile HGG brainstem glioma and to review the current literature. CASE DESCRIPTION: In this case report, we document the first histologically proven congenital brainstem HGG with molecular characteristics that did not fall under any previously well-defined pediatric brain tumor classifications. The patient is a full-term female delivered uneventfully via normal vaginal delivery with unremarkable antenatal and fetal abnormality scans. Neuroimaging revealed a relatively focal dorsally located pontomedullary tumor. She subsequently underwent suboccipital craniotomy and biopsy of the lesion. Formal histopathology revealed features consistent with HGG. Methylation profiling classified the neoplasm closest to either "glioblastoma, IDH wildtype, subclass midline" or "pediatric type diffuse HGG". The patient's post-operative recovery was uneventful. The initial plan was to consider safe surgical debulking when the child reaches 6 months of age. However, subsequent neuroimaging revealed spontaneous tumor regression after biopsy, up to 2 years of age. A review of the literature was also performed to identify previously reported infantile brainstem HGGs and the management for such tumors. CONCLUSIONS: Our case highlights the value of performing histopathological confirmation to guide management and the possible existence of a subcategory of a congenital brainstem HGG with better prognosis.

Intracerebral Flexner-Wintersteiner Rosette-Rich Tumor With Somatic RB1 Mutation: A CNS Embryonal Tumor With Retinoblastic Differentiation.

Diagnosis and classification of poorly differentiated tumors with primitive features of the central nervous system heavily relies on molecular and genetic findings of the tumors. Although RB1 gene mutation underlies the development of retinoblastoma and many other systemic cancers, RB1 gene mutation in a brain tumor is mainly limited to infiltrating gliomas. We describe what we believe to be a hitherto unreported case of sellar/suprasellar embryonal tumor with distinctive Flexner-Wintersteiner rosette formation, and somatic RB1 gene mutation in a 5-month-old infant. There were no molecular features associated with the embryonal tumor with multi-layered rosettes, and there were no histological or genetic features of a germ cell tumor. A follow up of 14 months duration showed good clinical response to VETOPEC regimen and no development of retinal disease. Our case shows an interesting association between RB1 mutation and Flexner-Wintersteiner rosettes in an embryonal tumor of the central nervous system and underscores the utility of large scale next generation sequencing in helping to identify the genetic aberrations that may help in clinical pathologic correlations of unusual or out-of-place histologic findings.