Sinonasal Teratocarcinosarcoma Research Articles

Nasosinusal Teratocarcinosarcoma: Case Report and Literature Review

Sinonasal cancers are the most common malignant tumors of the anterior skull base. Teratocarcinosarcomas are extremely unusual malignat tumors involving nasosinusal area, they are characterized by their poor prognosis and high likelihood of recurrence and potentiel intracranial extension. Because of its histological heterogeneity, the diagnosis is very difficult and therefore requires a sufficient sample to avoid erroneous diagnoses. The most commonly used treatment option is radical surgery resection followed by radiotherapy +/- chemotherapy. We report herein the case of 44-year-old woman, presented with sinonasal teratocarcinosarcoma revealed by nasal obstruction and intermittent epistaxis. The diagnosis was confirmed by a histopathological study of surgical specimen. Pre-treatment workup was negative for metastasis disease. She has received adjuvant radiotherapy and chemotherapy after radical endoscopic sinonasal surgery. A follow-up examination at 2 years showed no evidence of recurrence.

Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS).

Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma. Here, we describe 3 cases of carcinoma mimicking IFS from a single institution. Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality. We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

Neoadjuvant Chemotherapy in Locally Advanced Sinonasal Teratocarcinosarcoma a Rare Malignancy: An Audit From an Academic Tertiary Care Centre in India

AimsSinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. MethodsThis was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. ResultsThe data of 27 patients were evaluated from the year 2015–2022. The median age was 42 years (IQR:30–56) and 85.2% (n = 23) were males. The ECOG-PS was 0–1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2–3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0–25.6) and 23months (95%CI:5.94–40.06) respectively. ConclusionNACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.

Sinonasal Teratocarcinosarcoma, a Rare Neoplasm with Potential Diagnostic Pitfalls: A Report of Three Cases

Sinonasal Teratocarcinosarcoma, a Rare Neoplasm with Potential Diagnostic Pitfalls: A Report of Three Cases

Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in SMARCA4 may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including SMARCA4, ARID2, TET2, CDKN2A, WNT7A, NOTCH3 and STAG2, all present both in the primary tumor and in the cell line. Focusing on mutated SMARCA4 as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients.

Teratocarcinosarcoma: A rare malignant tumor of sinonasal tract

Sinonasal teratocarcinosarcoma is an extremely rare malignant tumor arising in the sinonasal tract, having combined histological features of teratoma and carcinosarcoma. Here, we are presenting a case of sinonasal teratocarcinosarcoma in a 44 year‑old male patient. 44 year old male presented to us with complains of nasal obstruction and intermittent epistaxis since 1 month. On examination polypoidal mass was noted in left nasal cavity which bleeds on touch. On MRI, well defined heterogeneously enhancing lesion completely filling the left nasal cavity was noted. Histopathological examination of resected specimen revealed, malignant epithelial components being adenocarcinoma and squamous cell carcinoma, mesenchymal component composed of spindle cells, along with primitive mesenchymal and blastemal components. Immunohistochemistry showed epithelial and stromal markers positive for Cytokeratin and Vimentin respectively. Sinonasal teratocarcinosarcoma (TCS) is a rare and aggressive malignant neoplasm characterized by the combination of malignant teratoma and carcinosarcoma. Most common presentation being nasal obstruction and epistaxis with male preponderance. The tumor shows heterogeneous morphology with varying proportions of benign and malignant epithelial, mesenchymal, and blastemal components. Less than 100 cases have been reported in literature. Teratocarcinosarcoma is a rare aggressive sinonasal tumor. Total excision of the tumor and aggressive sampling for histopathological examination is necessary to avoid misdiagnosis of olfactory neuroblastoma and carcinosarcoma.

An audit of neoadjuvant chemotherapy in sinonasal teratocarcinosarcoma from an academic tertiary care centre in India.

e18109 Background: Sinonasal teratocarcinosarcoma (SNTCS) are rare types of sinonasal malignancies, incidence is approximately 3% of all head and neck cancers and less than 1% of all tumors. There is very limited literature available on SNTCS and most of the literature available is in the form of case reports and small case series. The management of these tumors is complicated because of the location and paucity of data available in such scenarios where resection becomes difficult in extensive disease and the role of neoadjuvant chemotherapy (NACT) becomes significant. This audit was performed to study the tolerance and outcomes with NACT followed by surgery(Sx) in these treatment protocols. Methods: A retrospective analysis of a prospectively maintained database approved by the IEC of TMH. The baseline characteristics, extent of tumor, type of NACT, adverse events was curated from the EMR and patients' hospital files. Patients with clinically or radiologically extensive/inoperable disease at presentation were planned for NACT for a duration of 6-8 weeks. Post NACT these patients underwent axial imaging for response assessment.(RECIST v1.1). The adverse events due to NACT were noted as per CTCAE v5.0. Results: There were 27 patients of SNTCS. The median age of the whole cohort was 42 years (IQR 30-56) and 85.2% (n=23) were male. The ECOG PS was 0-1 in 24 (88.8%) patients and only 3 (11.1%) patients had ECOG PS 2. 17 patients (63%) had a history of addiction. 7 patients had clinical palpable regional nodes (25.9%) and 1 patient (3.7%) had lung metastasis at presentation. All 27 patients received NACT in view of extensive disease .15 patients (55.6%) had intracranial extension of disease with intradural extension. Only 10 patients (37%) had intraparenchymal disease. 22 patients (81.5%) had Kadish stage C-D disease and the remaining 5 patients (18.5%) had Kadish stage B at baseline. 20 patients (74.1%) received Cisplatin & Etoposide as NACT and remaining 7 received other chemotherapy. Median number of chemotherapy cycles was 2 (Q1 is 2 - Q3 is 3). 1 patient (3.7%) did not complete the planned NACT due to toxicity. The incidence of grade 3-5 toxicity in accordance with CTCAE version 5.0 was 37.03%. There was 1 death (3.7%) due to chemotherapy toxicity. Details of response to NACT are given in the table. 18 patients (77.8%) underwent Sx, 5 patients (18.5%) received CTRT and 2 patients (7.4%) received definitive RT and 2 patients (7.4%) did not receive any local therapy .Post Sx in local node was found in 3 patients (11.11%).The 2 years progression free survival was 53.2%(95%CI 31.3 - 70.9) and 2 years overall survival was 60.9%(95%CI 37.6 - 77.8). Conclusions: NACT improves survival in locally advanced SNTC with significant response rates. [Table: see text]

26P Characterization of a unique immortal tumor cell line as preclinical model for sinonasal teratocarcinosarcoma

26P Characterization of a unique immortal tumor cell line as preclinical model for sinonasal teratocarcinosarcoma

Sinonasal teratocarcinosarcoma in an adolescent male: A case report of an unusual neoplasm.

Sinonasal teratocarcinosarcoma (SNTCS) is an extremely rare and aggressive malignant tumor arising in the sinonasal tract, having a combined clinicopathological feature of teratoma and carcinosarcoma. It shows a male predominance and affects adults with an age range of 18-79 years and a mean age of 60 years. Here, we report a case of SNTCS in a 14-year-old male patient who presented with swelling over the upper right alveolus and pain in the right jaw for 2 months. The tumor was completely removed by right total maxillectomy with orbital mess reconstruction, and postoperative radiotherapy with chemotherapy was given. The follow-up of the patient for 2 years has shown evidence of recurrence and is now on palliative care.

Sinonasal Teratocarcinosarcoma Involving Orbital and Intracranial Extension: A Rare Case Report.

Sinonasal teratocarcinosarcoma (SNTCS) is one of the rarest and most highly invasive malignant neoplasms often found in the nasal cavity and paranasal sinuses. SNTCS is often misdiagnosed because of its morphological heterogeneity. Due to its rarity, clinical characteristics and optimal therapy have not been well-established. Here, we present a case of SNTCS with orbital and intracranial extensions. A 48-year-old male patient presented with left-side nasal obstruction for 3years. He appeared with visual and neurological symptoms 2months ago. On radiographic examination, a mass was observed in the left paranasal sinuses with orbital and intracranial extension involvement. The mass was surgically resected. In the future, knowledge of this entity may assist in the accurate diagnosis and proper management of SNTCS.

Comprehensive Molecular Profiling of Sinonasal Teratocarcinosarcoma Highlights Recurrent SMARCA4 Inactivation and CTNNB1 Mutations.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor defined by intermixed neuroepithelial, mesenchymal, and epithelial elements. While its etiology was historically ambiguous, we recently reported frequent SMARCA4 loss by immunohistochemistry, suggesting that TCS might be related to SMARCA4-deficient sinonasal carcinomas. However, other molecular alterations including CTNNB1 mutation have been reported in TCS, and its full genetic underpinnings are unclear. Here, we performed the first comprehensive molecular analysis of sinonasal TCS to better understand its pathogenesis and classification. We collected 30 TCS including 22 cases from our initial study. Immunohistochemical loss of SMARCA4 was seen in 22 cases (73%), with total loss in 18 cases (60%). β-catenin showed nuclear localization in 14 cases (64%) of the subset tested. We selected 17 TCS for next-generation sequencing with enrichment for partial or intact SMARCA4 immunoexpression. We identified inactivating SMARCA4 mutations in 11 cases (65%) and activating CTNNB1 mutations in 6 cases (35%), including 5 cases with both. Of 5 cases that lacked SMARCA4 or CTNNB1 mutation, 2 harbored other SWI/SNF complex and Wnt pathway alterations, including 1 with SMARCB1 inactivation and 1 with concomitant APC and ARID1A mutations, and 3 had other findings, including DICER1 hotspot mutation. These findings confirm that SMARCA4 inactivation is the dominant genetic event in sinonasal TCS with frequent simultaneous CTNNB1 mutations. They further underscore a possible relationship between TCS and sinonasal carcinomas with neuroendocrine/neuroectodermal differentiation. However, while SMARCA4 and β-catenin immunohistochemistry may help confirm a challenging diagnosis, TCS should not be regarded as a molecularly defined entity.

Neoadjuvent chemotherapy in rare sinonasal teratocarcinosarcoma: Long-term result from tertiary center.

e18005 Background: Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly aggressive disease entity having poor outcomes with available treatment modalities. Surgery followed by radiation or radical chemoradiation are considered standard therapy. However, in very locally advanced diseases surgery or radiation is not feasible and such patients are subjected to palliative therapy and have dismal outcomes. Methods: We identified 21 patients with very locally advanced SNTCS in our prospectively maintained head and neck cancer database over the last 8 years. All patients were seen in a multidisciplinary clinic prior to the start of therapy and were deemed unfit for local therapy. They were planned for 2 – 3 cycles of Neoadjuvant chemotherapy (NACT). They were then assessed in the multidisciplinary clinic for local therapy. Depending upon the response and performance status further therapy was planned. SPSS version 20 was used for the analysis. Descriptive statistics were performed and the Kaplan Meier method was used to evaluate overall survival(OS) and progression-free survival(PFS). Results: Median age was 50 years (range 27-80 Years) with male to female ratio being 6:1. ECOG PS was 0 in 3(14%), PS 1 in 14(67%) and PS 2 in 2 (9%) patients. 14 (67%) patients had Kadish C and the rest (33%) had Kadish D stage at presentation. Cisplatin & Etoposide was the chemotherapy of choice for the majority of patients (14/21 patients, 67%) with Docetaxel – Cisplatin (5/21 patients,19%), and Ifosfamide – Adriamycin (2/21 patients, 9%) being the other regimens. After NACT 14/21(66%) patients underwent surgery,1/21(4%) underwent radical Chemoradiation,1/21(4%) for palliative radiation therapy and rest for best supportive care. R0 resection was achieved in 11 out of 14 (78.6%) patients. The median PFS of the study was 17.5 months (95% CI 8.2 – 26.7) and the median OS was 19 months (95% CI = 0 -47). Those who underwent surgery after NACT have achieved a median OS of 37.3 months(95% CI 0-77.7) in comparison to 6.3 months (95% CI 0.3 -12.2) for those without surgery (p value 0.02). Conclusions: NACT in very locally advanced SNTCS achieves resectability in ⅔ patients who were unresectable upfront and would have received palliative therapy. This is important as patients who undergo surgery have prolonged overall survival.

Sinonazální teratokarcinosarkom

Sinonasal teratocarcinosarcoma is a rare and locally aggressive malignant tumour of the nose and paranasal sinuses, which has histological features of teratoma and carcinosarcoma. It is more common in men without age predilection. It often relapses locally. Due to the rarity, the exact therapeutic procedure is not defined. In our case, we provide a case report of a 56-year-old man patient with sinonasal teratocarcinosarcoma affecting the left nasal cavity. The symptomatology, dia­gnostic and therapeutic procedure of this rare tumour are discussed. Key words sinonasal teratocarcinosarcoma – proton therapy – tumours of the nose and paranasal sinuses

Proceedings of the North American Society of Head and Neck Pathology, Los Angeles, CA, March 20, 2022: SWI/SNF-deficient Sinonasal Neoplasms: An Overview

The pathology of poorly differentiated sinonasal malignancies has been the subject of extensive studies during the last decade, which resulted into significant developments in the definitions and histo-/pathogenetic classification of several entities included in the historical spectrum of “sinonasal undifferentiated carcinomas (SNUC)” and poorly differentiated unclassified carcinomas. In particular, genetic defects leading to inactivation of different protein subunits in the SWI/SNF chromatin remodeling complex have continuously emerged as the major (frequently the only) genetic player driving different types of sinonasal carcinomas. The latter display distinctive demographic, phenotypic and genotypic characteristics. To date, four different SWI/SNF-driven sinonasal tumor types have been recognized: SMARCB1(INI1)-deficient carcinoma (showing frequently non-descript basaloid, and less frequently eosinophilic, oncocytoid or rhabdoid undifferentiated morphology), SMARCB1-deficient adenocarcinomas (showing variable gland formation or yolk sac-like morphology), SMARCA4-deficient carcinoma (lacking any differentiation markers and variably overlapping with large cell neuroendocrine carcinoma and SNUC), and lastly, SMARCA4-deficient sinonasal teratocarcinosarcoma. These different tumor types display highly variable immunophenotypes with SMARCB1-deficient carcinomas showing variable squamous immunophenotype, while their SMARCA4-related counterparts lack such features altogether. While sharing same genetic defect, convincing evidence is still lacking that SMARCA4-deficient carcinoma and SMARCA4-deficient teratocracinosarcoma might belong to the spectrum of same entity. Available molecular studies revealed no additional drivers in these entities, confirming the central role of SWI/SNF deficiency as the sole driver genetic event in these aggressive malignancies. Notably, all studied cases lacked oncogenic IDH2 mutations characteristic of genuine SNUC. Identification and precise classification of these entities and separating them from SNUC, NUT carcinoma and other poorly differentiated neoplasms of epithelial melanocytic, hematolymphoid or mesenchymal origin is mandatory for appropriate prognostication and tailored therapies. Moreover, drugs targeting the SWI/SNF vulnerabilities are emerging in clinical trials.

Sinonasal teratocarcinosarcoma, A rare neoplasm; Case report and literature review

Abstract Introduction/Objective Sinonasal teratocarcinosarcoma (SNTCS) is an unusual neoplasm with high malignant potential. Histologically it consists of epithelial and mesenchymal constituents, with a combination of teratoma and carcinosarcoma. It primarily occurs in the nasal cavity and paranasal sinuses. This aggressive neoplasm has a high recurrence rate with a five-year survival of 30-50 percent. To this date, less than a hundred cases have been mentioned in the literature. Early diagnosis and management of the tumor can enhance the prognosis. Methods/Case Report We present to you a case of a 63-year-old woman presenting with epistaxis, nasal congestion, and blockage. The tumor was completely removed surgically and postoperative radiation therapy was given. Grossly the tumor was gray-white, with a solid texture. Postsurgical microscopic examination of the sections from different areas showed variegated appearance having a mix of teratoid; carcinomatous; sarcomatous and primitive neuroectodermal elements. Immunohistochemical staining revealed tumor cells expressing desmin, EMA, and cytokeratin. The follow-up examination was done after a year and showed no sign of recurrence. Results (if a Case Study enter NA) N/A Conclusion Because of the scarcity and mixed cell lines of this tumor pathological diagnosis of the neoplasm is hard. Since this neoplasm is highly malignant and locally aggressive proper identification and removal are necessary for improving morbidity as well as mortality.

Sinonasal teratocarcinosarcoma: a case report

<p class="abstract">Sinonasal teratocarcinosarcoma (TCS) is a very rare malignant neoplasm of sinonasal tract with intermixed teratomatous, carcinomatous and sarcomatous elements. While the diagnosis is largely based on tissue analysis and immunohistochemistry, the mode of management demands further study. Surgical resection with or without chemotherapy and radiation therapy is currently the most accepted treatment regimen. Locally aggressive, while also associated with metastatic lesions, SNTCS is not easily resectable owing to its location and possible intracranial extension. Due to its aggressive nature over one-third of TCS tend to recur leading to treatment failure with a mean survival time of 1.9 years. Possible differentials include squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma, malignant mixed tumor of salivary gland type, undifferentiated carcinoma, malignant craniopharyngioma, mucoepidermoid carcinoma, transitional carcinoma of Schneiderian type and adenosquamous carcinoma. In this report, we present a case of TCS in a 55 years old male patient who presented to us with complaints of hyposmia, blurring of vision, diplopia and epiphora.</p>

SALL-4 and Beta-Catenin Expression in Sinonasal Teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (SNTCS) is a rare, aggressive malignancy that displays a heterogeneous combination of malignant blastema-like, epithelial and mesenchymal components. Its exact histogenesis is unknown with hypotheses ranging from true germ cell derivation to origin from pluripotent stem cells. However, despite this tumor's multiphenotypic histology, which includes frequent glandular, squamous, and neuroectodermal differentiation similar to adnexal germ cell tumors, SNTCS appears to have some differences from adnexal teratomas. For example, unlike adnexal teratomas, SNTCS has never been described as a component in a mixed germ cell tumor. Accurate recognition of SNTCS is difficult due to its rarity and histologic overlap with other sinonasal tumors. It is even more problematic on biopsy, since not all elements may be present in small samples. SNTCS can also share similar staining patterns with other neoplasms in the differential diagnosis. A recent study found nuclear β-catenin expression in a single TCS, but this has yet to be confirmed in additional cases. SALL-4, a marker of germ cell tumors, has not been examined. We performed β-catenin and SALL-4 immunohistochemistry on whole sections of 7 SNTCS and 19 other sinonasal neoplasms to assess whether β-catenin and SALL-4 are of utility in establishing a diagnosis of SNTCS. Intensity of expression and percentage of staining was noted for each tumor. For SNTCS, distribution of staining within each histologic component (immature neuroectodermal, epithelial, and mesenchymal) was also documented. Nuclear β-catenin expression was not identified in any SNTCS, with all cases demonstrating membranous expression (6 cases) or cytoplasmic and membranous expression (1 case). SALL-4 immunohistochemistry, however, was relatively sensitive (85.7%) and specific (89.5%) for SNTCS. SALL-4 expression was also identified in one poorly differentiated neuroendocrine carcinoma and one case of sinonasal undifferentiated carcinoma. SALL-4 appears to have utility in distinguishing SNTCS from other high grade sinonasal tumors.

SWI/SNF-deficient head and neck neoplasms: An overview.

With wide-spread use of next generation sequencing tools in surgical pathology, a variety of neoplasms have been increasingly recognized to be associated with specific recurrent defining genetic abnormalities. This has led to recognition of new genetically defined entities and refinements of preexisting heterogeneous neoplastic categories. Among these, neoplasms associated with inactivating mutations involving different subunits of the SWI/SNF chromatin remodeling complex have received special attention. In the head and neck area, SMARCB1 (INI1) and SMARCA4 (BRG1) are the main two SWI/SNF components responsible for several recently described highly aggressive undifferentiated malignancies with predilection for the soft tissue of the neck (SMARCB1-deficient malignant rhabdoid tumors in children and rare epithelioid sarcoma cases in adults) and the sinonasal tract (SMARCB1-deficient sinonasal carcinoma including a small subset of adenocarcinomas, SMARCA4-deficient sinonasal undifferentiated carcinoma and SMARCA4-deficient sinonasal teratocarcinosarcoma). Molecular studies confirmed paucity of additional genetic abnormalities in these diseases underlining the central role of SWI/SNF deficiency as the primary and frequently sole genetic driver of these lethal diseases. Initiation of clinical trials using drugs that target the SWI/SNF collapse encourages recognition and correct classification of these morphologically frequently overlapping malignancies and underpins the role of SWI/SNF immunohistochemistry as emerging powerful adjunct tool in surgical pathology of the head and neck.

Recurrent Loss of SMARCA4 in Sinonasal Teratocarcinosarcoma.

Molecular analysis has reshaped the landscape of high grade sinonasal tumors by defining novel entities and identifying recurrent mutations in established tumor types. However, sinonasal teratocarcinosarcoma (TCS), a rare and aggressive tumor with intermixed teratomatous, carcinomatous, and sarcomatous elements, remains poorly understood. The multiphenotypic differentiation of TCS has engendered persistent controversy about its histogenesis and leads to diagnostic overlap with several other malignancies. In this study, we evaluated the molecular underpinnings of TCS to clarify its pathogenesis and diagnosis. We performed SMARCA4 immunohistochemistry (IHC) on 22 TCS and 153 other sinonasal tumors. We identified loss of SMARCA4 expression in 18 TCS (82%), including 15 (68%) with complete loss and 3 (14%) with partial loss. Although we also identified partial SMARCA4 loss in 1 of 8 SMARCB1-deficient sinonasal carcinomas (13%), SMARCA4 was intact in all other sinonasal carcinomas and neuroendocrine tumors. We then selected 3 TCS with complete SMARCA4 loss by IHC for a targeted next-generation sequencing panel that included 1425 cancer-related genes. We confirmed biallelic somatic inactivation of SMARCA4 without other known oncogenic mutations in these 3 cases. Overall, these findings suggest that SMARCA4 inactivation may be the dominant genetic event in TCS, expanding understanding of this gene's role in sinonasal tumorigenesis. They also raise the possibility that TCS is on a diagnostic spectrum with the newly described SMARCA4-deficient sinonasal carcinoma, blurring the lines between established and emerging sinonasal entities. In addition, SMARCA4 IHC may provide a useful adjunct for confirming a diagnosis of TCS in limited material.

A clinical study of sinonasal teratocarcinosarcoma: Report of four cases

A clinical study of sinonasal teratocarcinosarcoma: Report of four cases