Neoadjuvant radiation influences the pseudocapsule in soft tissue sarcoma: A histopathologic and radiographic evaluation
Introduction
Soft tissue sarcomas (STS) are a heterogenous group of mesenchymal-derived tumors comprised of various histologic subtypes. Patient survival can vary broadly depending on tumor stage at presentation with 5-year survival rates of 81% for localized disease and 15% for distant metastatic disease, respectively [1]. However, these rates also vary depending on specific tumor histology as well as tumor grade. Radiation therapy (RT) is often used in the treatment of STS, particularly high-grade tumors. RT has been shown to reduce local recurrence rates and in some STS can induce volume reduction and a regression from adjacent neurovascular structures which may aid in surgical resection [2,3]. The timing of RT, whether performed in neoadjuvant or adjuvant fashion, is oftentimes institutionally dependent, though neoadjuvant radiation offers the benefit of overall lower dose of radiation [4].
Enneking et al. initially defined the surgical margins for resection of STS in 1980 and described the pseudocapsule [5]. The pseudocapsule immediately circumscribes the tumor and is surrounded by a reactive zone that serves as the interface between the pseudocapsule and healthy tissue; however, tumor cells have previously been described to extend beyond the pseudocapsule into the reactive zone [[5], [6], [7]]. Therefore, when using the pseudocapsule as a reference for resection, surgeons should take wider margins to prevent tumor recurrence, as the contaminated tissue bed may increase the risk for local recurrence [8,9].
Decades after its original description, the pseudocapsule remains poorly understood. It was described in a murine model in 1989 and two later studies investigated the pseudocapsule in humans and its response to neoadjuvant treatment [6,7,10]. Other studies have used magnetic resonance imaging (MRI) to evaluate the tissue surrounding STS, investigating tissue edema and potential correlation to existence of tumor cells at the tumor periphery; however, neither study specifically measured the pseudocapsule [11,12].
In the current study, we sought to characterize the STS pseudocapsule and describe its response to neoadjuvant RT. We evaluated the tumor peripheries of high-grade undifferentiated pleomorphic sarcoma (UPS) treated with and without neoadjuvant RT to (1) describe the histopathologic composition and radiographic appearance of the pseudocapsule and (2) assess the effect of neoadjuvant RT on the width and composition of the pseudocapsule.
Section snippets
Patient selection
Following Institutional Review Board approval, our institutional sarcoma database was queried for cases of soft tissue sarcoma (STS) treated between 2011 and 2020. Inclusion criteria were Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade II or grade III STS that underwent surgical treatment within our tertiary academic medical center. Cases of recurrent tumors as well as those that underwent tumor bed re-excisions were excluded. Additionally, cases without MRI images and
Histopathologic and radiographic characteristics
Gross histopathologic evaluation of all resected samples yielded a yellow-brown fibrous pseudocapsule of varying width. Microscopically, the pseudocapsule consisted of a circumferential zone of reactive fibroblastic stroma orthogonal to the radius of the tumor (Fig. 1). The outer border can be clearly distinguished from tumor fibrosis by the circumferential orientation of the fibroblasts and collagen. A reactive zone was observed at the interface of the pseudocapsule and healthy tissue, which
Discussion
Soft tissue sarcomas (STS) are surrounded by a pseudocapsule; however, the clinical significance of the pseudocapsule is poorly understood. This study sought to describe the pseudocapsule from histopathological and radiographic perspectives as well as describe its response to neoadjuvant radiation. Originally described in 1980 by Enneking et al. the pseudocapsule has remained clinically relevant mostly for its use as a landmark for surgical resection and few studies have described the
Ethics approval
Rush University Medical Center obtained individual Institutional Review Board approval prior to beginning any research efforts.
Availability of data
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Conflicts of interest
The authors declare that they have no competing interests.
Funding
None.
Prior presentations
None.
Author contributions
NJW (data collection, analysis, interpretation, drafting, editing, revisions); SCT (analysis, interpretation, drafting, editing, revisions); LL (analysis, interpretation, drafting, editing, revisions); CG (data collection, drafting, editing, revisions); IM (data collection, oversight, editing, revisions); GMW (data collection, oversight, editing, revisions); MLR (data collection, oversight, editing, revisions); DW (oversight, editing, revisions); SG (oversight, editing, revisions); ATB
Declaration of competing interest
ATB: (BMJ Case Reports: Editorial or governing board; Clinical Orthopaedics and Related Research: Editorial or governing board; exparel/pacira: Stock or stock Options; Journal of Oncology Practice: Editorial or governing board; Journal of Surgical Oncology: ad hoc reviewer; Lancet - Oncology: Editorial or governing board; Musculoskeletal Tumor Society: Board or committee member; Onkos Surgical: Paid consultant; Pediatric Blood and Cancer: Editorial or governing board; Rare Tumors: Editorial or
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