Context.— Biphenotypic sinonasal sarcoma (BSNS) is a rare, slow-growing soft tissue sarcoma of the sinonasal tract, typically presenting with nonspecific obstructive nasal symptoms. Although recurrences are common, no metastases have been reported, and only 1 patient has died of disease thus far. It characteristically demonstrates rearrangements of PAX3 with multiple fusion partners, the most common of which is MAML3. Objectives.— To highlight the most important diagnostic features, including morphologic, immunohistochemical, and molecular findings, and to provide comparisons to other entities in the differential diagnosis. We also aim to provide a summary of the clinical features and outcomes in cases reported to date. Data Sources.— Recently published literature encompassing BSNS and its synonym, low-grade sinonasal sarcoma with neural and myogenic differentiation. Conclusions.— BSNS is a sinonasal tumor that is important to recognize because its biologic behavior differs from most of the entities in the differential diagnosis. The diagnosis can typically be rendered through a combination of morphology, immunohistochemical stains, and ancillary testing for characteristic PAX3 rearrangements.
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by germline mutations in the FH gene, and is associated with increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma (HLRCC-associated RCC). Absent immunohistochemical expression of fumarate hydratase (FH) has previously been used to diagnose HLRCC-associated RCC, but immunohistochemical staining of leiomyomas is not standard practice. We performed immunohistochemistry (IHC) on whole sections from consecutive cutaneous leiomyomas from our archives to evaluate for both FH and succinate dehydrogenase B expression, in addition to clinicopathologic data collection and review of all hematoxylin and eosin-stained slides for blinded morphologic evaluation of features reported to be seen in HLRCC-associated uterine leiomyomas. Ninety-six cutaneous leiomyomas from 87 patients were identified; 12 of these specimens were from 7 patients with documented HLRCC. FH expression by IHC was absent in 9 specimens and retained in 85 specimens; 2 cases were equivocal with minimal FH expression. Seven of the 9 absent expression specimens were from patients with HLRCC, as were both of the equivocal specimens. The overall sensitivity and specificity of absent FH expression in leiomyomas for detection of patients with HLRCC were 70.0% and 97.6%, respectively. Inclusion of cases classified as equivocal increased sensitivity to 75.0%. Succinate dehydrogenase B expression was retained in 95 specimens and equivocal in 1 specimen. None of the evaluated morphologic features showed any association with leiomyomas in HLRCC. Loss of FH immunohistochemical expression in cutaneous leiomyomas is a sensitive and specific marker for detection of HLRCC, thus suggesting a role for prospective FH IHC in patients with these tumors to screen for HLRCC.
The molecular events driving low-grade endometrioid endometrial carcinoma (LGEC) development-like in many cancers-are incompletely understood. Hence, here we performed multiregion, comprehensive somatic molecular profiling of routinely processed formalin-fixed, paraffin-embedded (FFPE) material from 13 cases of LGEC totaling 64 minute, spatially defined cell populations ranging from presumed precursor lesions through invasive LGEC. Shared driving PTEN, PIK3R1, or PIK3CA mutations support clonal origin of the samples in each case, except for two cases with two clonally distinct neoplastic populations, consistent with unexpected multiclonality in LGEC development. Although substantial heterogeneity in driving somatic alterations was present across populations in nearly all cases, these alterations were usually clonal in a given population, supporting continued selection and clonal sweeping of driving alterations in populations with both precursor and LGEC histology. Importantly, CTNNB1 mutational status, which has been proposed as both prognos-tic and predictive in LGEC, was frequently heterogeneous and subclonal, occurring both exclusively in precursor or cancer populations in different cases. Whole-transcriptome profiling of coisolated RNA from 12 lesions (from 5 cases) was robust and confirmed histologic and molecular heterogeneity, including activated Wnt signaling in CTNNB1-mutant versus wild-type populations. Taken together, we demonstrate clinically relevant multiclonality and intratumoral heterogeneity during LGEC development with important implications for diagnosis, prognosis, and therapeutic prediction. More broadly, our methodology is broadly scalable to enable highthroughput genomic and transcriptomic characterization of precursor and invasive cancer populations from routine FFPE specimens.Implications: Multiregion profiling of LGEC populations using a highly scalable approach demonstrates clinically relevant multiclonality and intratumoral heterogeneity.
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.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.