The SWI/SNF complex act as a complex to regulate chromatin remodeling, thereby regulating gene expression and cell proliferation. The complex consists of several core subunits (encoding SMARCB1) and 2 catalytic subunits: SMARCA2 (encoding BRM protein) and SMARCA4 (encoding BRG1 protein).
SMARCB1 is encoded on chromosome 22q11.2 and plays a tumor-suppressor role by regulating cell proliferation and gene transcription. It can be expressed in all normal cells. Abnormal inactivation of SMARCB1 is not unique to certain tumors. Which include atypical teratoid/ rhabdoid tumors in children, rhabdoid tumors in the kidney and soft tissue, and so on. All of them are characterized by high degree of malignancy, invasive features, and poor prognosis. It is unclear whether the deletion of this gene may be due to mutation or inheritance.
The most common site of SDSC is the ethmoid sinus, easy to invade the orbit and basis cranii. It has also been reported that some SDSCs grow up expansively and compress the surrounding bone wall to thin. In this case, the tumor occurred in the anterior ethmoid sinus and the lamina papyracea was destroyed, suggesting that the tumor is most likely to invade the orbit. A better understanding of disease characteristics can help clinicians to detect and diagnose tumors early.
The most common symptoms of SDSC are unilateral nasal congestion, epistaxis, and headache. If the tumor compresses the orbit, it will cause diplopia, difficulty in eye movement, and even acute blindness. Horacio reported that the tumor can metastasize within the dural, resulting in the symptoms of cranial nerve compression and even paralysis. .As shown in this case, the imaging presentation is not all typical for patients, especially in the early stages of the tumour, so it should be taken seriously to pay attention to clinical symptoms, rather than relying solely on imaging findings.
Another prominent feature of SDSC is that tumor tissues have obvious characteristics of high invasiveness, such as high mitotic rate, invasion of bone, lymph and vessels. In some cases, there are all necrotic tissues, and tumor cells may not be found at all in the first pathological examination. Therefore, when a high-grade malignant tumor is clinically suspected, attention should be paid to multiple examinations during the pathological examination. In the present case, the imaging manifestations of lamina papyracea were destroyed, and the exact pathological tissue could not be obtained by nasal endoscopy. Timely nasal endoscopic surgery is essential for a definite diagnosis and subsequent treatment.
The most important pathological feature of SDSC is, of course, the complete loss of SMARCB-1 staining, but SMARCB-1 is expressed in all normal tissues, including inflammatory tissues. In terms of morphology, SDSCs are poorly differentiated or undifferentiated, lacking a propensity to differentiate into any particular cell (such as squamous cells, glandular cells, or other cells). However, some tumor cells exhibit p63,p16 immune response, which may lead to misdiagnosis of nonkeratinizing/ basaloid squamous cell carcinoma and HPV-related squamous cell carcinoma. Most tumor cells of SDSC have rhabdoid features, and some tumors contain basal-like cells, which are often misdiagnosed as other types of malignant tumors. Hence, attention should be paid to the identification.
The therapeutic methods of SDSC are mostly based on other sinus malignancies at present. The preferred treatment method is still surgery, followed by postoperative radiotherapy, chemotherapy and other further treatments. However, due to the few cases reported, the prognosis of different treatment methods has not been compared, but all patients have a poor prognosis with an average survival time of about 2 years. Therefore, some start further exploration of other therapeutic approaches that utilize the deletion of SMARCB-1 for targeted therapy.
The current study shows that the SWI/SNF complex binds to the EZH2 promoter to inhibit EZH2 gene expression. Loss of INI-1 disrupts SWI/SNF complex function, leading to an increase in EZH2 activity. This pathway can be effectively targeted by Tazemetostat, a potent small molecule for competitively inhibiting EZH2, which has become a promising target for INI-1-deficient malignant tumors. Tazemetostat has been approved by the FDA in 2020 for metastatic or advanced epithelioid sarcomas, which is not suitable for surgical resection, and more clinical studies are still in progress.Breakthroughs have also been made in commonly used chemotherapy, platinum-based chemotherapeutics haxe success in cases of SMARCA4- deficient lung cancer , a histological entity similar to SDSC.
Current treatment modalities are still exploratory, and more research is needed to determine optimal treatment modalities and management.
This case is accompanied by a deficiency of factor XI (FXI).FXI deficiency is an autosomal recessive bleeding disorder, known as hemophilia C. FXI deficiency can be inherited or caused by mutations in the gene that synthesizes the FXI protein. Whether FXI deficiency is related to SMARCB-1 deficiency also provides a possible direction for further research.