Expanding the spectrum of dicer1-associated sarcomas.

DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have been identified in DICER1-associated tumors. With the exception of genitourinary embryonal rhabdomyosarcoma and anaplastic sarcoma of the kidney, sarcomas are rarely reported in DICER1 syndrome. Herein, we report the clinical, histopathologic, and molecular findings of a germline DICER1-associated ovarian sarcoma in a 5-year-old female, a somatic DICER1-associated metastatic peritoneal sarcoma in a 16-year-old female, and a somatic DICER1-associated primary intracranial sarcoma in a 4-year-old male. A comprehensive review of the literature, including 83 DICER1-associated sarcomas, illustrates an unequivocal histologic pattern mimicking pleuropulmonary blastoma, regardless of the site of origin. The features include undifferentiated small round blue cells, poorly differentiated spindle cells, and large bizarre pleomorphic cells (anaplasia), often with rhabdomyoblastic and/or chondroid differentiation, and rare bone/osteoid formation. This unique heterogeneous histologic pattern should raise suspicion for pathogenic DICER1 mutation(s) warranting a detailed review of the family history and DICER1 mutation analysis. In addition to expanding the phenotypic spectrum of DICER1-associated conditions, identification of pathogenic DICER1 variants facilitates optimized genetic counseling, caregiver education and judicious imaging-based surveillance.

A prospective, observational cohort study comparing cancer clinical trial availability and enrollment between early adolescents/young adults and children.

BACKGROUND: Poor enrollment of adolescents and young adults (AYAs) (ages 15-39 years) onto cancer clinical trials (CCTs) may contribute to inferior survival gains compared with children. In this study, the authors assessed whether differences in CCT availability would explain lower CCT enrollment for early AYAs (eAYAs) (ages 15-21 years). METHODS: This prospective, observational cohort study was conducted at a single academic children's hospital. For consecutive patients who were newly diagnosed with cancer over a 13-month period, it was determined whether an appropriate CCT existed nationally or was available locally and whether enrollment on that CCT occurred. The proportions of eAYAs versus children in each category were compared using the chi-square test. The impact of age and other factors on enrollment status was assessed using logistic regression analysis. RESULTS: Among 216 patients, 58 were eAYAs, and 158 were children. There was no difference in the proportion of eAYAs versus children who had an existing CCT (28 of 58 eAYAs [48.3%] vs 85 of 158 children [53.8%]; P = .47) or an available CCT (23 of 58 eAYAs [39.7%] vs 75 of 158 children [47.5%]; P = .31). However, significantly fewer eAYAs were enrolled when a CCT was available (7 of 23 eAYAs [30.4%] vs 50 of 75 children [67.7%]; P = .002). In multivariable analysis, eAYAs were significantly less likely than children to be enrolled in an available CCT (adjusted odds ratio, 0.22; 95% confidence interval, 0.08-0.62). CONCLUSIONS: Equal proportions of children and eAYAs had CCTs available, but significantly fewer eAYAs were enrolled. These findings suggest that, for eAYAs, factors other than CCT availability are important enrollment barriers and should be addressed. Cancer 2018;124:983-90. © 2017 American Cancer Society.

A prospective comparison of cancer clinical trial availability and enrollment among adolescents/young adults treated at an adult cancer hospital or affiliated children's hospital.

BACKGROUND: Low cancer clinical trial (CCT) enrollment may contribute to survival disparities affecting adolescents and young adults (AYAs) (ages 15-39 years). The objective of this study was to evaluate whether differences in CCT availability related to treatment site could explain the low CCT enrollment. METHODS: This prospective, observational cohort study was conducted at an academic children's hospital and its affiliated but geographically separated adult cancer hospital within a National Cancer Institute-designated Comprehensive Cancer Center. For consecutive, newly diagnosed AYA patients, it was determined whether an appropriate CCT existed nationally, was available at the treatment site, and was used for enrollment. Proportions of AYAs in these categories were compared between sites using the chi-square test. RESULTS: One hundred fifty-two consecutive AYA patients were included from the children's hospital (n = 68; ages 15-20 years) and the adult cancer hospital (n = 84; ages 18-39 years). Although there was no difference in CCT existence for individual AYA patients by site (children's hospital [36 of 68 patients; 52.9%] vs adult cancer hospital [45 of 84 patients; 53.6%]; P = .938), CCT availability was significantly lower at the adult cancer hospital (14 of 84 patients [16.7%] vs 30 of 68 [44.1%] at the children's hospital; P < .001). The proportion of AYAs enrolled was low at both sites (8 of 68 patients [11.8%] vs 6 of 84 patients [7.1%], respectively; P = .327). Fewer existing CCTs were available at the adult cancer hospital (4 of 27 patients [14.8%] vs 8 of 14 patients [57.1%], respectively), and those were directed toward solid tumors and new agents. CONCLUSIONS: Efforts to improve low CCT enrollment among AYAs should be differentiated by treatment site. In the adult setting, these efforts should be aimed at improving CCT availability by overcoming site-level barriers to opening existing CCTs.

Epithelioid Hemangioma of the Glans Penis in an Adolescent Male: A Case Report.

Epithelioid hemangioma is a rare vascular lesion consisting of capillaries and inflammatory infiltrate containing lymphocytes, and mast cells. The presentation of penile epithelioid hemangioma has been previously described in the adult literature; however, few cases have been reported in the pediatric population. Herein we present a case of penile epithelioid hemangioma in a 15-year-old patient with regrowth following surgical resection, requiring more extensive surgical excision with urethral reconstruction. This rare case highlights the importance of a proper diagnosis and complete microscopic removal.

The Relevance of and Surgical Approach to the Suprahyoid Region in Thyroglossal Duct Surgery.

OBJECTIVES: Persistent or recurrent disease following excision of a thyroglossal duct cyst/sinus (TGDC) is often found in the suprahyoid region. Cadaver dissections were performed to identify and name important surgical landmarks in the suprahyoid area; a histopathologic analysis of surgical specimens was completed to determine the incidence and extent of microscopic disease; and clinical outcomes were compared to determine the efficacy of a specific anatomic dissection. STUDY DESIGN: Retrospective case series. METHODS: Standardized dissections of four adult cadavers were performed. Consecutive surgical specimens were examined for evidence of microscopic TDGC disease in the suprahyoid region, measuring the greatest width and length of disease. A retrospective review of all consecutive TGDC procedures was completed. RESULTS: The important surgical landmarks in the suprahyoid area were identified in all cadavers. Microscopic disease in the suprahyoid area was found in 79% (37 of 47) of surgical specimens. The mean greatest length and width of microscopic disease was 12.4 mm and 1.4 mm, respectively. Following identification of these landmarks, the incidence of recurrent or persistent disease decreased (P = .02) from 5% (8 of 159) to 0% (0 of 112). CONCLUSION: The majority of pediatric patients with a TGDC will have microscopic disease in the suprahyoid area. The surgical landmark of the fascial plane between the geniohyoid and genioglossus muscles demarcates the anterior and lateral borders of resection in the suprahyoid area. This approach can be used as a reliable and easily reproducible technique in TGDC surgery to increase confidence of achieving complete removal of disease in the suprahyoid area, avoiding persistent or recurrent disease and a revision procedure. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:553-558, 2021.

SWI/SNF complex heterogeneity is related to polyphenotypic differentiation, prognosis, and immune response in rhabdoid tumors.

BACKGROUND: Rhabdoid tumors (RTs) arise within (atypical teratoid/rhabdoid tumor [AT/RT]) or outside the brain (extra [e]CNS-RT) and are driven mainly by inactivation of the SWItch/sucrose nonfermentable (SWI/SNF) complex subunit SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1). A pathognomonic hallmark of RTs is heterogeneous multilineage differentiation, including anomalous neuronal differentiation in some eCNS-RTs. Because remodeling of the SWI/SNF complex regulates differentiation, we hypothesized that SWI/SNF Brahma-associated factors (BAF) and polybromo-associated BAF (PBAF) complex heterogeneity are related to both multilineage differentiation and clinical outcome. METHODS: We performed an integrated analysis of SWI/SNF complex alterations in the developing kidney and cerebellum (most common regions of RT origin) in comparison to eCNS-RT (n = 14) and AT/RT (n = 25) tumors. RT samples were interrogated using immunohistochemistry, DNA methylation, and gene expression analyses. RESULTS: The SWI/SNF BAF paralogs actin-like protein (ACTL)6A and ACTL6B were expressed in a mutually exclusive manner in the developing cerebellum and kidney. In contrast, a subset of eCNS-RTs lost mutual exclusivity and coexpressed both subunits. These tumors showed aberrant DNA methylation of genes that regulate neuronal and renal development and demonstrated immunohistochemical evidence of neuronal differentiation. In addition, low expression of the PBAF subunit polybromo-1 (PBRM1) identified a group of AT/RTs in younger children with better overall prognosis. PBRM1-low AT/RT and eCNS-RTs showed altered DNA methylation and gene expression in immune-related genes. PBRM1 knockdown resulted in lowering immunosuppressive cytokines, and PBRM1 levels in tumor samples showed an inverse relationship with cluster of differentiation (CD)8 cytotoxic T-cell infiltration. CONCLUSIONS: Heterogeneity in SWI/SNF BAF (ACTL6A/ACTL6B) and PBAF (PBRM1) subunits is related to histogenesis, contributes to the immune microenvironment and prognosis in RTs, and may inform opportunities to develop immunotherapies.

An Unusual Cardiac Cause of Unilateral Neonatal Wheezing.

A neonate presented three days after birth with left-sided unilateral inspiratory wheezing, intermittent respiratory distress, and desaturations. She was found to have a large ductus arteriosus aneurysm that caused compression of her left mainstem bronchus and left pulmonary artery. This lesion was not identified prior to birth on routine prenatal screening, which included fetal ultrasonography. Diagnosis was made on day of life (DOL) 5 by a computed tomography with angiography scan. On DOL 7, she underwent cardiac surgery which included resection of the ductal aneurysm, patch reconstruction of the transverse aortic arch and descending aorta, patent ductus arteriosus excision, and atrial secundum septal defect repair. There were no postoperative complications, and she has been asymptomatic since.

Molecular, Histologic, and Radiologic Findings of High-Grade Invasive Adenocarcinoma Arising in Oncocytic Subtype of Intraductal Papillary Mucinous Neoplasm: A Case Report and Review of Literature.

Background: We present a case of adenocarcinoma arising in the oncocytic subtype of intraductal papillary mucinous neoplasm (O-IPMN), with emphasis on the molecular findings in the adenocarcinoma component. Tissue microdissection and next-generation sequencing were performed using a 26 gene panel (AKT1, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SMAD4, SRC, STK11, TP53) of cancer-related genes. Case Presentation: A 69-year-old Caucasian female presented with chest pain and was found to have findings consistent with acute pancreatitis. During her work-up, computed tomography scan revealed a large cystic and solid mass in the tail of the pancreas. She recovered from her acute pancreatitis and was discharged home. She later returned for resection of her mass. Results: Evaluation of three microdissected regions of tumor demonstrated no identifiable nonsynonymous alterations in any of the three regions, within the targeted genes. Conclusion: This case demonstrates that the O-IPMN is a molecularly distinct subtype, and we conclude that adenocarcinoma arising in these neoplasms shows molecularly distinct tumorigenesis from traditional pancreatic ductal adenocarcinoma. These differences may help explain the improved survival with invasive adenocarcinoma arising from these lesions compared with traditional ductal adenocarcinoma.