Tomotherapy for sinonasal teratocarcinosarcoma with SMARCA4 deletion and CTNNB1 mutation: A case report and literature review

Abstract

Sinonasal teratocarcinosarcoma (SNTCS) is a rare and aggressive malignant tumor that is difficult to diagnose and lacks a standard therapeutic strategies. Here, we report a case of SNTCS harboring a SMARCA4 deletion and a CTNNB1 mutation. Following incomplete surgical resection, the patient received synchronous postoperative chemotherapy with tomotherapy (TOMO) radiation and achieved a complete response lasting for > 47 months with tolerated side effects. This case suggests that SMARCA4 deletion and CTNNB1 mutation may be key molecular events in the development of SNTCS, potentially providing valuable clues for its diagnosis. Moreover, to the best of our knowledge, this is the first case demonstrating that TOMO technology can be a beneficial option for SNTCS radiotherapy.

This study is the first to report an SNTCS patient with SMARCA4 deletion and CTNNB1 mutation who achieved 47 months of complete remission after TOMO radiotherapy in combination with chemotherapy, highlighting the breakthrough efficacy of TOMO in the treatment of SNTCS.

1. INTRODUCTION

Sinonasal teratocarcinosarcoma (SNTCS) is a rare, highly aggressive malignant neoplasm of unknown pathogenesis. It occurs most commonly in adult males and is characterized by a hidden origin, strong invasiveness, early metastasis, poor prognosis, and a lack of imaging specificity. ¹ Owing to its highly complex and heterogeneous pathological manifestations, SNTCS is often difficult to diagnose. ¹ , ² , ³ Recent studies have identified relatively specific molecular markers, such as SMARCA4, that may provide valuable diagnostic clues. ⁴ , ⁵ Although there is no standard treatment, surgical resection with adjuvant chemoradiotherapy has been reported to improve patient survival. ¹ , ³ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ Radiotherapy techniques, such as tomotherapy (TOMO), have improved the precision of radiotherapy while reducing radiotherapy‐related side effects; however, to the best of our knowledge, no study has described the use of TOMO technology in SNTCS. Herein, we report a case of SNTCS with a SMARCA4 deletion and CTNNB1 mutation that achieved remarkable benefits after treatment with surgery, chemotherapy, and TOMO radiotherapy. Relevant literature was reviewed to provide further insights into the diagnosis, treatment, and prognosis of this disease.

2. CASE PRESENTATION

The treatment histories and clinical courses of the patient is summarized in Figure 1. In July 2021, a 22‐year‐old man was admitted to a local hospital with recurrent right‐sided nasal bleeding that persisted for more than a month. Computed tomography (CT) revealed a polypoid mass in the right nasal cavity. To remove the lump, the patient underwent rhinoscopic excision of the right nasal neoplasm. During surgery, a dark purple hematoma‐like lesion originating from the right olfactory region and middle turbinate was observed in the right middle nasal meatus. The patient was referred to our hospital for further evaluation and treatment. Magnetic resonance imaging (MRI) revealed uneven enhancement patches in the right nasal cavity and paranasal sinuses, indicating incomplete tumor removal. No significant abnormalities were observed on abdominal ultrasonography, chest CT, or bone scans. Postoperative histological examination revealed three distinct components within the tumor tissues: an epithelial component consisting of squamous epithelium and adenotubular‐like structures, a mesenchymal component consisting of spindle cells with some mesenchymal mucinous degeneration, and deeply stained small round or short spindle‐shaped cells arranged in a nested or daisy‐like mass (Figure 2). Immunohistochemical assays revealed extensive cytokeratin (CK), epithelial membrane antigen (EMA), and P63 protein expression, and partial positive staining for CK7 and CK19. Spindle cells widely express vimentin and individually express desmin and smooth muscle actin. The deeply stained small round/short spindle cells expressed CgA, SYN, and INSM1 and partially expressed EMA, S‐100, and SALL4. None of the tumor cells expressed SMARCA4 (Figure 3). These results support the pathological diagnosis of SNTCS with SMARCA4 deletion. We also performed programmed death ligand‐1 (PD‐L1) analysis and genetic testing. PD‐L1 expression was negative, whereas a secondary variant gene, CTNNB1, was detected with missense substitution mutations at serine residues 37 or 45. The patient had no specific medical history or comorbidities and was diagnosed with teratocarcinosarcoma of the right nasal cavity and sinus (T4N0M0)(American Joint Committee on Cancer [AJCC] 8th edition).

FIGURE 1.

Case presentation. TOMO, tomotherapy; EP, etoposide and cisplatin; CT, computed tomography; MRI, magnetic resonance imaging; PR, partial remission; CR, complete remission; T1, T1‐weighted imaging; T2, T2‐weighted imaging. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

FIGURE 2.

Representative histological slides of hematoxylin‐eosin staining. (A) Keratinized squamous epithelium in the tumor. (B) The epithelial component of the tumor is a glandular tube structure. (C) The mesenchymal component of the tumor is composed of spindle‐shaped cells. (D) Primitive neuroepithelial component.

FIGURE 3.

Immunohistochemistry findings. (A) Tumor epithelial components express a broad spectrum of cytokeratins. (B) Tumor squamous epithelial components expressing P63. (C) Primitive neuroepithelial components expressing SYN. (D) Tumor cells lose the expression of SMARCA4.

On evaluation, the patient had a Karnofsky Performance Status score of 80. After multidisciplinary consultation, six cycles of etoposide (day 1‐5, 100 mg/ day) and cisplatin (day 1‐3, 45 mg/ day) were administered, and the patient also received synchronous tomotherapy (TOMO) radiotherapy to the residual tumor at a total dose of 72.6 Gy (33 fractions of 2.2 Gy) from August to October 2021. The prescription doses for the other targets were as follows: clinical target volume (CTV), including gross tumor volume (GTV) + (5–10 mm) margin plus areas at risk for microscopic involvement, including the entire nasal cavity, paranasal sinus, ethmoid sinus, sphenoid sinus, and part of the frontal lobe. In areas where the CTV was adjacent to critical normal structures (i.e., eyeball or optic nerve), the margin could be reduced to 0‐1 mm, with a prescribed dose of 60 Gy (33 fractions of 1.8 Gy); CTV ln included bilateral levels I‐III at a total dose of 50.4 Gy (28 fractions of 1.8 Gy) (Figure 4). Dmaxs delivered to key organs at risk (OARs) were as follows: the left lens, 6.11 Gy; the right lens, 6.59 Gy; the left eyeball, 51.31 Gy; the right eyeball, 51.75 Gy; the left optic nerve, 51.34 Gy; the right optic nerve, 52.02 Gy; the chiasm, 50.96 Gy; the brainstem, 51.68 Gy; the temporal lobe, 56.59 Gy. Treatment‐related toxicities were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. During chemoradiotherapy, the patient experienced grade 3 myelosuppression, grade 2 oral mucositis, and grade 1 radiation‐induced skin injury. All adverse effects improved after treatment, and the patient achieved a complete response after chemoradiotherapy. No tumor recurrence or metastasis was recorded during follow‐up over 47 months. To date, the patient has shown good cosmetic and functional results with only grade 1 xerostomia.

FIGURE 4.

Delineation method and irradiation dose. (A‐C) Representative slices of the target delineation. GTV (red), CTV (yellow), CTV ln (pink). (D) Isodose curves of 72.6, 66.0, 60.0, and 50.0 Gy are shaded red, sky blue, green, and orange, respectively.

3. DISCUSSION

SNTCS is a highly aggressive malignant tumor with features of teratomas, carcinomas, and sarcomas. ³ It was first introduced by Heffner and Hyams in 1984 and was officially named by the World Health Organization in 2005. ¹¹ SNTCS most commonly involves the nasal cavity and paranasal sinuses, especially the ethmoid and maxillary sinuses; however, a few cases have been reported in the nasopharynx, oral cavity, or orbit. ¹ The most common clinical manifestations of SNTCS are nasal obstruction (76% of cases), recurrent epistaxis (53.5%), and frontal headaches (20%). ¹ , ¹²

Pathological examination and immunohistochemistry are the basis for confirming the diagnosis of SNTCS. Histologically, SNTCS presents as a complex mixture of benign, atypical, or malignant epithelial and mesenchymal components (including malignant teratomas, carcinomas, and sarcomas), as well as immature neuronal or blastemal‐appearing components without specific germ cell tumor components. ² , ³ Tumors such as sarcomatoid carcinomas and immature teratomas also have similar tissue compositions, and inadequate sampling during biopsy can lead to misdiagnosis. A fetal‐like squamous epithelial structure is an important feature that can be observed in approximately 75% of cases ¹¹ and may aid in the identification. A recent report (the largest and most complete to date) identified 73% SMARCA4 loss using immunohistochemistry and 35% activating CTNNB1 mutations using next‐generation sequencing, suggesting that SMARCA4 inactivation may be the predominant genetic event in this tumor type, with frequent simultaneous CTNNB1 mutations. ⁴ In agreement with this report, both SMARCA4 deletion and CTNNB1 mutations were detected in the present case. Although the complete genetic basis of SNTCS remains unclear, immunohistochemical staining for SMARCA4 and CTNNB1 (β‐catenin) may help confirm this challenging diagnosis. Additionally, CTNNB1 mutations may lead to aberrant activation of the transcription factor β‐catenin, facilitating tumorigenesis and therapeutic response. ¹³ , ¹⁴ At present, numerous clinical trials are underway targeting β‐catenin, making it a promising therapeutic target for disease management. ¹⁵ , ¹⁶ , ¹⁷

Currently, there is no standard treatment regimen for SNTCS. Surgery is the mainstay of treatment for primary tumors, and postoperative synchronous chemoradiotherapy is reportedly associated with better outcomes. ¹⁸ Because SNTCS frequently recurs locally, complete surgical excision is difficult but essential to reduce local recurrence. ⁸ For patients with lesions close to critical structures, such as the brainstem, temporal lobe, and optic nerve, TOMO radiotherapy demonstrates significant dosimetric advantages, particularly in terms of target‐area dose coverage homogeneity and OAR protection. TOMO employs spiral tomography irradiation technology, which enables a highly shaped and uniform dose distribution within an irregular target area, thereby avoiding the problem of field connections caused by traditional techniques. Additionally, TOMO's dynamic multileaf collimator technology and helical scanning modes enable more precise sculpting of the dose distribution and reduce the volume of high‐dose irradiation to structures such as the brainstem, optic nerves, and optic chiasm, thus reducing the probability of side effects. ¹⁹ , ²⁰ , ²¹ , ²² Based on these advantages, we innovatively adopted TOMO technology for radiotherapy. It has been reported that in patients with SNTCS, the radiation target, including the selective cervical lymphatic drainage area, had a better locoregional control ratio than the target with only involved‐field radiotherapy (IFRT). ²³ Therefore, after an MDT meeting, the patient finally received TOMO extended‐range radiotherapy, which included the cervical lymphatic drainage area, and is currently recurrence‐free 47 months post‐diagnosis. To date, this is the first patient with SNTCS who received TOMO treatment and achieved an encouraging therapeutic effect with tolerable side effects (grade 1 xerostomia as a late complication).

The prognosis for SNTCS is poor, with a two‐year disease‐free survival rate of 28% and an overall survival rate of 46%‐55%, respectively, while the mortality rate is approximately 60% within three years. ¹ , ⁶ , ¹⁸ Recurrence or metastasis rates are also high, occurring in 57.1% of patients treated with surgery alone and 45.7% of patients treated with surgery and radiation. ¹ After incomplete surgery with postoperative chemotherapy and TOMO radiation, the patient had an OS of over 47 months (follow‐up is ongoing), exceeding the median survival period of 1.7 years reported in the literature. ¹¹ Although such beneficial effects may be sporadic, our results indicate that surgical resection, postoperative synchronous chemotherapy, and TOMO‐based radiotherapy are potential treatment options for patients with SNTCS.

In conclusion, SNTCS are difficult to diagnose and treat because of their rarity and complexity. Our case adds to the growing evidence that SMARCA4 deletions and CTNNB1 mutations are key molecular events in the development of SNTCS, which may provide valuable clues for diagnosing this rare disease. Additionally, to the best of our knowledge, we present the first case suggesting that TOMO technology may be valuable for SNTCS radiotherapy because of its beneficial results and relatively few side effects. Further well‐designed clinical trials are required to validate these findings. We hope that our report will provide clues for improving diagnosis and establishing standardized treatment plans for this disease in the future.

AUTHOR CONTRIBUTIONS

Concept and design: Siyu Xie, Lei Yang and Chenyu Ren. Statistical analysis: Fanglei Duan, Peng Xu, and Shun Lu. Data acquisition, analysis, and interpretation: Siyu Xie, Yang Liu, Yue Zhao, and Shun Lu. Drafting the manuscript: Siyu Xie drafted the manuscript with the support from Jie Zhou. Critical revision of the manuscript for intellectual content: All the authors.

CONFLICT OF INTEREST STATEMENT

All authors declare no conflict of interest.

CONSENT FOR PUBLICATION

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This study was approved by the Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital (SCCHEC‐02‐2025‐163).

Xie S, Ren C, Yang L, et al. Tomotherapy for sinonasal teratocarcinosarcoma with SMARCA4 deletion and CTNNB1 mutation: A case report and literature review. Prec Radiat Oncol. 2025;9:314–318. 10.1002/pro6.70038

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author.