Rearrangements in the nuclear protein in testis (NUT) gene cause carcinomas that represent a rare but aggressive tumor type that often present at advanced stages in midline structures. Survival rarely exceeds 12 months from the time of diagnosis. There have been no reports of a primary cardiac presentation, and few studies have reported on the numerous treatment strategies. Given their aggressive and invasive nature, NUT midline carcinomas present a therapeutic dilemma. Treatment may include surgical resection, chemotherapy, or radiotherapy, but no consistently successful treatment has been established. Surgical resection is indicated to reduce symptomatic mass effect whenever present. Novel therapies with bromodomain extra-terminal inhibitors may be associated with potential survival benefit. Here, we describe an unusual presentation of this tumor. Literature review with management considerations is underlying.
Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation states: t(2;13) (q35;q14) producing PAX3-FOXO1, t(1;13) (p36;q14) producing PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with greater disease severity and mortality than t(1;13) positive or translocation negative patients. Consistent with this fact, previous work concluded that a molecular analysis of RMS translocation status is essential for the accurate determination of prognosis and diagnosis. However, despite this knowledge, most diagnoses rely on histology and in some cases utilize fluorescence in situ hybridization (FISH) probes unable to differentiate between translocation products. Along these same lines, diagnostic RT-PCR analysis, which can differentiate translocation status, is unable to determine intratumoral translocation heterogeneity, making it difficult to determine if heterogeneity exists and whether correlations exist between this heterogeneity and patient outcomes. Using newly developed FISH probes, we demonstrate that intratumoral heterogeneity exists in ARMS tumors with respect to the presence or absence of the translocation product. We found between 3 and 98% of cells within individual tumor samples contained a translocation event with a significant inverse correlation (R 2 = 0.66, p = 0.001) between the extent of intratumoral translocation heterogeneity and failurefree survival of patients. Taken together, these results provide additional support for the inclusion of the molecular analysis of these tumors and expand on this idea to support determining the extent of intratumoral translocation heterogeneity in the diagnosis of ARMS to improve diagnostic and prognostic indicators for patients with these tumors.
Congenital disorders of glycosylation are a group of inherited disorders affecting the addition of a carbohydrate moiety to a protein. A defect in this pathway can cause adverse effects in most organ systems, often presenting early in life. The most common of these disorders is CDG type 1a / PMM2-CDG). In this disorder the loss of the enzyme phosphomannomutase-2 prevents the conversion of mannose-6-phosphate to mannose-1-phosphate. This has previously been associated with deficiencies of protein C, protein S, antithrombin III, factor IX and factor XI and a subsequent imbalance of coagulation pathways leading to thrombotic events. We present the case of a 14-year-old male with known history of CDG1a and previous bleeding complications following left orchiopexy at age 3, at that time coagulation screening showed a normal PT/PTT and surgery was deemed safe. The patient now presented to our pediatric hematology/oncology clinic for further evaluation of coagulation abnormalities prior to pediatric surgery performing right orchiopexy. Laboratory values at this time showed coagulation deficiencies, of ATIII, Factor XI, Protein C and Protein S, PT/ PTT , F VIII, FIX and vWF where normal. Prior to surgery, patient was given fresh frozen plasma and ATIII concentrate the patient underwent a successful Stage One Fowler-Stephen Procedure with adequate hemostasis. Several months later the patient developed leg swelling and was diagnosed right femoral DVT. This resolved with ATIII substitution and anticoagulation with LMW heparin. The patient's immediate family was tested for bleeding/clotting disorders and results were found to be normal. This report not only supports the association of bleeding but also thrombosis with CDG1a. We propose that in patients with known CDG routine PT/PTT will not uncover a hemostatic abnormality but further screening isolated factor deficiency need to be performed and prophylactic factor substitution be performed prior to any surgical interventions. Also an awareness of the highly procoagulant state in these patients that predispose to DVT and central nervous system vascular thrombosis need to be present. Disclosures No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.