Primary pulmonary myxoid sarcoma with detected EWSR1 gene translocation: a case report

Introduction

Primary pulmonary myxoid sarcoma (PPMS) represents an exceptionally uncommon, low-grade malignant mesenchymal neoplasm. First identified as an endobronchial myxoid tumor of pulmonary origin, this entity was initially characterized by Nicholson and colleagues in 1999 (1). PPMS gained formal recognition as a distinct diagnostic entity in the 2015 World Health Organization (WHO) tumor classification system. Its classification was further refined in the 2021 WHO Classification of Lung Tumors, where it was designated as a lung-specific mesenchymal neoplasm (2). The presence of EWSR1 rearrangement and EWSR1::CREB1 fusion is hallmark genetic feature of PPMS and serves as critical diagnostic marker (3). Clinically, PPMS often presents with nonspecific symptoms and is occasionally detected incidentally during routine health examinations, making it challenging to differentiate from other pulmonary neoplasms. Herein, we report a case of PPMS treated with surgical resection. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-190/rc).

Case presentation

A 52-year-old Chinese female nonsmoker with no personal history of heart disease, hypertension, diabetes mellitus, or cancer presented to hospital in May 2024 following the incidental detection of a nodule in the middle lobe of the right lung during a routine health examination three months prior. Chest computed tomography (CT) revealed a solid nodule in the medial segment of the right middle lobe, measuring approximately 15 mm × 13 mm (Figure 1A), with well-defined margins and slight pleural indentation. Positron emission tomography-computed tomography (PET-CT) demonstrated mildly increased radiotracer uptake, with a maximum standardized uptake value (SUVmax) of 2.7. Although a comprehensive pathological examination was recommended, the patient declined a biopsy. Tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA 21-1), were assessed and found to be within normal limits.

Figure 1 Patient radiological findings, surgical specimen, frozen section HE staining, and FISH test results. (A) Chest CT showing a solid nodule in the medial segment of the right middle lung lobe (as indicated by the red arrow). (B) Pathology reveals well-defined gray-white tissue (as indicated by the red arrow). (C) Frozen section HE staining revealed short spindle cells and myxoid changes, accompanied by significant infiltration of lymphoid cells and plasma cells in the surrounding tissue (×400). (D) FISH showing EWSR1 gene translocation detected (as indicated by the red arrow). CT, computed tomography; FISH, fluorescence in situ hybridization; HE, hematoxylin and eosin.

In May 2024, the patient underwent uniportal video-assisted thoracoscopic surgery (UVATS) for right middle lobectomy under general anesthesia. Intraoperative findings revealed a spherical nodule approximately 15 mm in diameter located in the medial segment of the right middle lobe, adjacent to the hilum, with dense adhesion to the middle lobe vein. The cut surface of the nodule appeared white and well-demarcated (Figure 1B). Frozen section analysis identified short spindle cells and myxoid changes, accompanied by significant infiltration of lymphoid cells and plasma cells in the surrounding tissue (Figure 1C). Based on the frozen section results, the lesion was considered likely benign, and lymph node (LN) dissection was not performed. The patient recovered uneventfully and was discharged postoperatively. At the 6-month follow-up, no abnormalities were observed.

Pathological diagnosis: histopathological examination revealed a tumor with a myxoid background and short spindle cells, surrounded by significant lymphocyte and plasma cell infiltration. The case was referred to West China Hospital of Sichuan University for specialized pathological consultation, which confirmed the diagnosis of mesenchymal tumor: PPMS with EWSR1::CREB1 fusion. Immunohistochemical staining results were as follows: WT-1 (+), CR (−), D2-40 (−), BAP1 (no loss), CD34 (−), ERG (−), CK5/6 (−), P63 (−), Calponin (−), CK7 (−), TTF-1 (−), Desmin (−), S100 (−), SOX-10 (−), ALK-V (−), CD117 (−), SMA (−), PAX-8 (−), and Ki-67 index: 5%. Fluorescence in situ hybridization (FISH) analysis confirmed the presence of EWSR1 gene translocation (Figure 1D).

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

PPMS is a rare, low-grade lung sarcoma, with limited reports available in the literature. Miao et al. documented 39 cases (3), noting the absence of unique clinical manifestations and the typically normal results of routine blood tests and tumor markers. Histologically, PPMS is characterized by spindle or epithelial-like cells arranged in a reticular or lace-like pattern within a rich myxoid stroma, often accompanied by chondrocyte-like or vacuolated cell morphologies (4). The molecular hallmark of PPMS is the EWSR1 gene translocation, particularly the EWSR1::CREB1 fusion transcript formed through the t(2;22)(q33;q12) chromosomal translocation, which serves as a critical diagnostic marker (5). Although the multifunctionality of the EWSR1 gene allows for recombination with various partner genes, leading to diverse tumor phenotypes, the EWSR1::CREB1 fusion exhibits high specificity in PPMS, aiding in its differentiation from other EWSR1-related tumors.

Differential diagnosis should prioritize angiomatoid fibrous histiocytoma (AFH) and extraskeletal myxoid chondrosarcoma (EMC). PPMS and AFH share similar histological features, clinical presentations, immunophenotypes, and molecular alterations, making differentiation challenging. However, immunophenotypic differences can serve as distinguishing factors, with AFH typically demonstrating positivity for CD68, CD163, desmin, epithelial membrane antigen (EMA), and ALK (6). The relationship between EWSR1-positive PPMS and AFH remains unresolved—whether they constitute distinct phenotypic variants of a shared pathological entity or arise independently from primitive mesenchymal precursors under the influence of analogous EWSR1 fusion oncogenes. This critical distinction requires further elucidation through dedicated research. While EMC and PPMS exhibit morphological similarities, EMC is generally more aggressive. A key distinguishing factor is their genetic differences; EMC typically lacks the EWSR1::CREB1 fusion and more commonly displays NR4A3-related translocations (7).

Complete surgical resection remains the primary treatment modality for PPMS; however, some cases may experience local recurrence or lung metastases. Thway et al. reported a case of postoperative mortality due to brain metastasis (8), highlighting the potential for aggressive behavior in certain instances. A critical challenge for surgeons is determining the extent of surgical resection when frozen section analysis does not provide a definitive diagnosis. Another unresolved question is whether systematic LN dissection should be routinely performed during PPMS surgery. In the present case, LN dissection was not conducted due to the absence of malignancy suggested by the frozen section, and the diagnosis was only confirmed postoperatively with assistance from West China Hospital of Sichuan University. This decision was made after thorough intraoperative consultation between the surgical and pathology teams, weighing the potential benefits against the additional surgical risk. Nevertheless, we acknowledge that in retrospect, given the final malignant diagnosis (albeit low-grade), a more aggressive approach with LN sampling could have been considered. Given the limited number of cases, a standardized tumour, node, and metastasis (TNM) staging system for PPMS has yet to be established, and surgical protocols remain undefined.

The prognosis of PPMS is generally better than that of other high-grade sarcomas, but further case accumulation is necessary to clarify its biological behavior. Future research should focus on elucidating the molecular pathogenesis of PPMS and exploring potential targeted therapies to improve patient management (9).

Conclusions

PPMS harboring the EWSR1::CREB1 fusion gene is an exceptionally uncommon, indolent mesenchymal malignancy that predominantly arises within the bronchial tree and pulmonary parenchyma. Due to the lack of specific molecular markers, diagnosis relies on genetic testing, with EWSR1 rearrangement and the EWSR1::CREB1 fusion serving as critical diagnostic markers. Surgical resection remains the primary treatment modality, and most patients recover well, although some cases may experience local recurrence or lung metastasis. Standardized surgical protocols require further data and long-term follow-up for validation. The efficacy of adjuvant therapies, including radiotherapy, chemotherapy, and targeted immunotherapy, warrants further investigation to optimize patient outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-190/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-190/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-190/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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