CASE REPORT |
https://doi.org/10.5005/jp-journals-10001-1559 |
Sinonasal Teratocarcinosarcoma, a Rare Neoplasm with Potential Diagnostic Pitfalls: A Report of Three Cases
1Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
2Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
Corresponding Author: Saikat Mitra, Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, Phone: +91 6392210361, e-mail: saikatmitra123@gmail.com
Received: 20 May 2023; Accepted: 17 October 2023; Published on: 16 January 2024
ABSTRACT
Background: Sinonasal teratocarcinosarcoma (SNTCS) is a very rare aggressive neoplasm of the sinonasal tract and affects older individuals. The tumor accounts for <1% of all sinonasal neoplasm and shows a striking male predominance. The admixture of epithelial, mesenchymal, and primitive neuroepithelial elements is essential for the diagnosis of this tumor. However, the morphological differential diagnosis of SNTCS is wide and can lead to potential diagnostic error if any one of the three elements predominates in a biopsy.
Case description: We report three cases of SNTCS from a single center. All three patients were middle-aged adults, including one male and two female patients. The age range was between 42 and 46 years. All of the three patients presented with nasal obstruction, pain, and nasal bleeding. The imaging study revealed a direct intracranial extension of the tumor in one of the patients. Two patients underwent frontal craniotomy, and the third patient underwent transnasal decompression of the tumor. On light microscopic examination, all three cases revealed similar morphology. The tumor tissue was composed of three distinct components, including malignant epithelial, mesenchymal, and primitive neuroepithelial elements. Immunohistochemistry (IHC) showed strong pan-cytokeratin (AE1/AE3) positivity in the epithelial component. The mesenchymal component showed varied differentiation, including osseous and rhabdomyoblastic differentiation. The primitive neuroepithelial element showed positivity for cluster of differentiation 99 (CD99) and synaptophysin IHC.
Conclusion: Sinonasal teratocarcinosarcoma (SNTCS) is often underdiagnosed because of the rarity of this tumor and its histomorphological overlap with a wide range of sinonasal malignancies. A careful morphological assessment of the biopsy sample and a battery of ancillary investigations, including IHC, confirm the diagnosis.
How to cite this article: Mitra S, Bevinahally N N. Sinonasal Teratocarcinosarcoma, a Rare Neoplasm with Potential Diagnostic Pitfalls: A Report of Three Cases. Int J Head Neck Surg 2023;14(4):71–76.
Source of support: Nil
Conflict of interest: None
Patient consent statement: A written informed consent was obtained from the patient for publication of this article.
Keywords: Case report, Histopathology, Nasal cavity, Sinonasal malignancies, SMARCA4, Teratocarcinosarcoma
INTRODUCTION
Sinonasal teratocarcinosarcoma (SNTCS) is a rare malignant neoplasm of the nasal cavity and paranasal sinuses. The term “teratocarcinosarcoma” was coined by Heffner and Hyams in 1984.1 The mean age of presentation is 54.5 years, with a strong male predilection. The most common clinical presentations include nasal obstruction and epistaxis. This tumor has a high predilection for the nasal cavity, maxillary, and ethmoid sinuses.2 Nearly 20% of cases demonstrate dural and intracranial extension. On histology, the tumor is composed of carcinomatous elements like squamous cell carcinoma or adenocarcinoma. The sarcomatous component mainly consists of the fibroblastic or myofibroblastic components; however, osteoblastic, adipocytic, cartilaginous, and rhabdomyoblastic differentiation can also be detected on microscopic examination. Additionally, an immature neuroepithelial component in solid sheets or nests is noted. Germ cell-type components are characteristically absent. Significant morphological heterogeneity in the tumor tissue can make the diagnosis challenging, particularly while examining small biopsy samples. Surgical removal of the tumor, followed by chemoradiotherapy, is the mainstay of treatment.2 SNTCS has an aggressive clinical course and is prone to recurrence.3
In this article, we report the clinical, radiological, histological, and immunohistochemical (IHC) features of three cases of SNTCS with intracranial extension diagnosed at our center.
CASE DESCRIPTION
Case 1
A 45-year-old female patient presented with complaints of left facial pain and decreased touch sensation for one year, followed by drooping of the left eyelid and diplopia for 3 months. The patient had no prior comorbidities. On examination, her left pupil was nonreactive to light. She had ptosis with left complete ophthalmoplegia.
On magnetic resonance imaging (MRI) with contrast substance injection, a lesion with increased contrast uptake was identified involving the left cavernous sinus and Meckel’s cave (Fig. 1A). This lesion involved the foramen ovale and foramen rotundum.
Figs 1A to C: (A) Axial T1 weighted contrast-enhanced MRI shows a lesion involving the left cavernous sinus and Meckel’s cave; (B) Coronal T1 weighted MRI shows a lobulated lesion involving the right nasal cavity with intracranial extension into the frontal lobe; (C) Axial T1 weighted MRI with contrast shows a well-defined extraaxial T1 hyperintense homogeneous contrast-enhancing lesion in the nasal cavity and anterior cranial fossa
This patient underwent a left temporal craniotomy with tumor removal. Postoperative courses were unremarkable.
Case 2
A 46-year-old male patient presented with a history of bleeding from the right nostril for 3 months, along with headache, giddiness, and decreased olfaction in the right nostril for 20 days. There was no history of pain, trauma, or purulent discharge from the nose.
On local examination, a reddish-gray, ill-defined lesion was seen in the right nasal cavity with displacement of the septum toward the left. The patient has proptosis of the right eye. Right sixth cranial nerve palsy was noted.
On MRI, an ill-defined lobulated lesion involving the right nasal cavity, ethmoid, and sphenoid sinus was noted. The lesion measured 4.2 × 3.7 × 5 cm in size. The tumor showed intracranial extension into the frontal lobe (Fig. 1B).
The patient underwent bifrontal craniotomy and excision of the intracranial component of the tumor and intradural anterior cranial fossa base repair and exteriorization of the frontal lesion. The patient also underwent endoscopic transnasal decompression of the sinonasal component of the tumor. The tumor was firm in consistency, grayish-white in color, and highly vascular.
The postoperative course was unremarkable.
Case 3
A 42-year-old female patient presented with complaints of epistaxis and nasal blockade for 2 months, associated with holo-cranial headache and two episodes of seizures. On examination, there was a loss of bilateral olfactory nerve function; the rest of the cranial nerves were normal.
On MRI with contrast injection, a 5 × 6 × 4 cm well-defined extra-axial T1 hyperintense homogeneous contrast-enhancing lesion was detected in the anterior cranial fossa (Fig. 1C).
The patient underwent endoscopic biopsy twice before surgical excision. The first biopsy diagnosis was of a poorly differentiated squamous cell carcinoma. The second biopsy diagnosis provided was olfactory neuroblastoma.
The patient underwent bicoronal flap bifrontal craniotomy with near-total decompression of the lesion. The microscopy diagnosis performed for the preoperative squash smear was that of a spindle cell lesion.
Pathological Analysis
In all three cases, the samples were sent as multiple fragmented bits of tumor tissue, ranging in volume from 10 to 15 mL. The entire tissue was processed in all three cases, and five to seven blocks were prepared for each case. Histological examination in all three tumors revealed similar morphology. Tissue fragments were partly lined by respiratory lining epithelium, with areas of surface ulceration. All three tumors were cellular and were composed of three distinct components. The malignant epithelial component was formed of glands, acini, nests, and trabeculae. The tumor cells had a high nucleus-to-cytoplasm ratio, bizarre vesicular nuclei with conspicuous nucleoli, and scant to moderate cytoplasm. The overall percentage of epithelial elements ranged from 20 to 25% of the entire tumor in all three cases (Figs 2A and B). In case 1, few foci of malignant epithelial cells showed squamoid differentiation. The mesenchymal component was predominant in all three tumors, representing almost 65–70% of the entire tumor volume. The mesenchymal component was cellular in all three tumors and was composed of spindle cells in fascicles. Focal myxoid changes were noted in all tumors. Moderate nuclear pleomorphism brisk mitoses were noted in all three tumors (Fig. 2C). In case 3, foci of rhabdomyoblastic differentiation and neoplastic osteoid deposition were also noted (Figs 2D and E). The neuroectodermal component was composed of sheets of undifferentiated round blue cells lying on a scant neuropil matrix. These cells had a high nucleocytoplasmic ratio, hyperchromatic nuclei, and scant cytoplasm (Fig. 2F). This component represented 5–10% of the entire tumor volume. Apoptotic and mitotic activity was brisk in these areas. Tumor necrosis was observed in all three tumors and involved ~5% of the entire tumor volume.
Figs 2A to F: (A) Malignant epithelial component (black arrow) admixed with the cellular mesenchymal component (red asterisk) [hematoxylin and eosin (H&E), 40×]; (B) Malignant epithelial component showed tumor cells forming glands, trabeculae, and acini (H&E, 200×); (C) The malignant mesenchymal component showed a moderately pleomorphic spindled tumor cells arranged in fascicles (H&E, 200×); (D) Rhabdomyoblastic differentiation in mesenchymal component (H&E, 200×); (E) Focal osteoblastic differentiation in mesenchymal component (black asterisk) (H&E, 200×); (F) Primitive neuroectodermal component showed undifferentiated round blue cells (H&E, 200×)
On IHC evaluation, the malignant epithelial component was stained strongly and diffusely with cytokeratin and epithelial membrane antigen (EMA) (Fig. 3A). Mesenchymal elements showed positivity for vimentin IHC in all cases (Fig. 3B). IHC for desmin showed focal cytoplasmic staining in case 3 (Fig. 3C). The primitive neuronal component showed strong membranous staining for cluster of differentiation 99 (CD99) IHC in all cases (Fig. 3D). Synaptophysin staining was variable in the underlying neuropil background. Ki67 labeling index was high in all cases, ranging between 40 and 50% in primitive neuronal components. Markers for germ cell tumors, that is, placental alkaline phosphatase, α-fetoprotein, β-human chorionic gonadotropin, and CD30, were not expressed in the tumor cells. Further, IHC for β-catenin was performed, which did not show nuclear positivity in any of the cases.
Figs 3A to D: (A) Immunohistochemistry (IHC) for pan-cytokeratin highlighted the malignant epithelial component; (B) Malignant mesenchymal component highlighted by vimentin IHC; (C) Rhabdomyoblastic component highlighted by desmin IHC; (D) Neuroectodermal component highlighted by CD99 IHC
The pathological and IHC features of all three cases are summarized in Table 1.
| Epithelial | Mesenchymal | Neuroectodermal | |
|---|---|---|---|
| Case 1 | Malignant glandular component with foci of squamoid differentiation | Undifferentiated pleomorphic sarcoma component | Undifferentiated blue round cell with scant neuropil matrix |
| Case 2 | Malignant glandular component | Undifferentiated pleomorphic sarcoma component | Undifferentiated blue round cell with scant neuropil matrix |
| Case 3 | Malignant glandular component | Undifferentiated pleomorphic sarcoma component with foci of rhabdomyoblastic differentiation and osteoid matrix production | Undifferentiated blue round cell with scant neuropil matrix |
| IHC | Pan-cytokeratin+, EMA+ | Vimentin+, desmin+ (case 3) | CD99—diffuse membranous staining, synaptophysin—focally positive |
The immediate postoperative follow-ups were uneventful for all three patients. However, long-term follow-ups were not available in any cases.
DISCUSSION
Sinonasal teratocarcinosarcoma (SNTCS) is a rare and aggressive malignant neoplasm that is characterized by a constellation of malignant epithelial, mesenchymal, and neuroepithelial elements.1,4 Although first described in 1984, this tumor found its place in the World Health Organization classification of the 2005 version of Pathology and Genetics of Head and Neck Tumors.5 This is a rare tumor, and approximately 127 cases have been published in English literature so far.6 The rarity of this tumor makes it difficult to ascertain the demographic, clinical, and pathological features. Misra et al.2 reviewed 86 cases of reported SNTCS. This tumor is frequently detected in elderly individuals. However, isolated cases have been reported in adolescents and even newborns.7,9 In our series, all three patients were middle-aged adults. A strong male predilection (M:F—7:1–8:1) has been noted in the majority of studies.10 SNTCS arises from the nasal cavity and commonly shows sinus infiltration. Intracranial extension, cribriform plate, or anterior cranial fossa involvement is present in about 20.9% of cases.2 In our series, all three patients had evidence of intracranial extension.
The histogenesis of SNTCS is controversial. SNTCS is thought to originate from totipotent stem cells in the olfactory/sinonasal membrane, while the prevailing thought is that these primitive cells are capable of differentiation into divergent types of somatic cells1,4,11,12 Shimazaki et al. proposed a neuroectodermal origin of this tumor with divergent differentiation.13 Thomas et al. proposed the possibility of the origin of this tumor from pluripotent embryonic stem cells from the basal layer of sinonasal epithelium.14 This hypothesis was based on the identification of α-fetoprotein positive yolk-sac element in one case of SNTCS as well as the presence of an extra copy of chromosome 12 in a distinct population of tumor cells.14,15 However, no other studies documented the presence of malignant germ cell components viz germinoma, yolk sac tumor, embryonal carcinoma, or choriocarcinoma component in any of the cases. In a recent study by Birkeland et al., targeted exome sequencing identified activating p.S45F mutation of a β-catenin gene in one case of SNTCS. This mutation induces intranuclear localization of β-catenin, which was confirmed by nuclear positivity by IHC. We performed beta-catenin immunostain in our series, however, none of our cases showed nuclear β-catenin positivity.16 Inactivation of SMARCA4 in chromosome 19p13.2 has been identified in several sinonasal tumors previously diagnosed as small-cell or large-cell neuroendocrine tumors. Rooper et al. studied 22 cases of SNTCS and demonstrated loss of SMARCA4 by IHC in 68% of cases.17SMARCA4 mutations could not be tested in our series.
Sinonasal teratocarcinosarcoma (SNTCS) is composed of an admixture of epithelial, mesenchymal, and neuroepithelial components. The carcinoma component can have squamous as well as glandular differentiation. Similar findings were observed in our series, where the predominant epithelial component was adenocarcinoma, while one case showed a nonkeratinizing squamous cell carcinoma component. Solid nests of immature cells with round nuclei on a neuropil background form the primitive neuroepithelial component in this tumor. Rhabdomyosarcomatous differentiation was noted in the case series by Heffner and Hyams1 as well as by several other authors.18-21 Case 3 in our series exhibited focal rhabdomyosarcomatous areas, which were highlighted on desmin IHC. Neoplastic osteoid production was noted in our case, which was also described previously.1,21
Sinonasal teratocarcinosarcoma (SNTCS), being a rare tumor and having an extremely heterogeneous morphology, are prone to be misdiagnosed.22,23 There are no specific clinical and radiological features of this tumor, and histology remains the gold standard in diagnosis. However, paranasal sinus tumors are often difficult to excise, and hence, the histological diagnosis is mostly based on endoscopic biopsy. The sampling bias can cause difficulty in diagnosis. As SNTCS is composed of a mixture of epithelial, mesenchymal, and primitive neuroectodermal components, the predominance of a particular element in a given sample can change the histological diagnosis. The epithelial component can mimic squamous cell carcinoma or adenocarcinoma of paranasal tract, which are well-known tumors in this location. The mesenchymal component of SNTCS can be confused with a wide range of sarcomas. In this series, one of the cases showed both neoplastic osteoid formation as well as rhabdomyoblastic differentiation; hence, a possible differential of osteosarcoma and rhabdomyosarcoma could also be considered. The primitive neuroendocrine component can show morphologic overlap with Sinonasal undifferentiated carcinoma, NUT-midline carcinoma, poorly differentiated squamous cell carcinoma, neuroendocrine carcinoma, olfactory neuroblastoma, alveolar rhabdomyosarcoma or Ewing’s sarcoma. Amelanotic malignant melanoma can have a wide range of morphology and becomes a close differential diagnosis, especially in elderly individuals. In this series, case 3 underwent endoscopic biopsy twice before surgery, and a diagnosis of poorly differentiated squamous cell carcinoma and olfactory neuroblastoma was made, which could be attributed to the sampling bias in this case. A panel of IHC including an epithelial marker (cytokeratin), mesenchymal marker (vimentin), and neuroendocrine marker (synaptophysin, chromogranin or neuron-specific enolase) along with melanoma markers (HMB-45, melan-A, etc.) would help the pathologist to narrow down the differential diagnosis. Focal and weak synaptophysin positivity has been documented both in sinonasal undifferentiated carcinoma as well as SNTCS. Moreover, positivity for other specific neuroendocrine markers like insulinoma-associated protein 1 has been documented in SNTCS.21 Positivity for NKX2.2 has been seen in SNTCS as well; hence, differentiating from olfactory neuroblastoma becomes challenging. Loss of SMARCA4 (BRG-1) and nuclear positivity for β-catenin and Sal-like protein 4 can act as a promising ancillary IHC marker in SNTCS; however, the data is limited.16,17,24 Hence, morphological identification of all three components in the tumor remains the best way to make a correct diagnosis.
Ideal treatment strategies are difficult to identify because these cases are rare. Radical surgical resection followed by radiation therapy appears to be the mode of treatment. In a systematic review by Chapurin et al.,6 surgery was found to be the primary mode of treatment in 90% of patients. 55% of patients received surgery and radiotherapy, while 20% of patients received additional adjuvant chemotherapy. Multimodal therapy has a significant survival advantage. Despite the common treatment strategies currently used, recurrence occurs in 26.1% of cases, metastasis in 10.9% of cases, and both metastasis and recurrence in 8.7% of cases.2 Cervical lymph node, spinal axis, and respiratory tract metastasis have been described.25,26 The 2-year survival rate for SNTCS is approximately 55%. SMARCA4 deficient tumors of the lung have responded to checkpoint inhibitors.27 Threonine tyrosine kinase inhibitors are undergoing clinical trials for catenin β1 mutated tumors.28 Recent identification of SMARCA4-loss and β-catenin gene mutation can open further avenues for targeted therapies in this aggressive tumor, which needs to be validated in large-scale studies.
CONCLUSION
To summarize, SNTCS is a rare and malignant neoplasm, which should be kept in differential diagnosis while dealing with a sinonasal tumor, especially in adults. A thorough sampling and careful microscopic evaluation are key to avoiding misdiagnosis. The pathobiology of SNTCS is still evolving, and further large-scale studies would help us know better about proper management.
ORCID
Saikat Mitra https://orcid.org/0000-0002-0208-3108
Nandeesh Bevinahally N https://orcid.org/0000-0002-3401-449X
REFERENCES
1. Heffner DK, Hyams VJ. Teratocarcinosarcoma (malignant teratoma?) of the nasal cavity and paranasal sinuses. A clinicopathologic study of 20 cases. Cancer 1984;53(10):2140–2154. DOI: 10.1002/1097-0142(19840515)53:10<2140::aid-cncr2820531025>3.0.co;2-y
2. Misra P, Husain Q, Svider PF et al. Management of sinonasal teratocarcinosarcoma: a systematic review. Am J Otolaryngol 2014;35(1):5–11. DOI: 10.1016/j.amjoto.2013.04.010
3. Contrera KJ, Woody NM, Rahman M, et al. Clinical management of emerging sinonasal malignancies. Head Neck 2020;42(2):2202–2212. DOI: 10.1002/hed.26150
4. Smith SL, Hessel AC, Luna MA, et al. Sinonasal teratocarcinosarcoma of the head and neck: a report of 10 patients treated at a single institution and comparison with reported series. Arch Otolaryngol Head Neck Surg 2008;134(6):592–595. DOI: 10.1001/archotol.134.6.592
5. Thompson L. World Health Organization classification of tumors: pathology and genetics of head and neck tumors. Ear Nose Throat J 2006;85(2):74. PMID: 16579185.
6. Chapurin N, Totten DJ, Morse JC, et al. Treatment of sinonasal teratocarcinosarcoma: a systematic review and survival analysis. Am J Rhinol Allergy 2021;35(1):132–141. DOI: 10.1177/1945892420959585
7. Agrawal N, Chintagumpala M, Hicks J, et al. Sinonasal teratocarcinosarcoma in an adolescent male. J Pediatr Hematol Oncol 2012;34(7):e304–e307. DOI: 10.1097/MPH.0b013e318266baa8
8. Budrukkar A, Agarwal JP, Kane S, et al. Management and clinical outcome of sinonasal teratocarcinosarcoma: single-institution experience. J Laryngol Otol 2010;124(7):739–743. DOI: 10.1017/S0022215109992866
9. Rotenberg B, El-Hakim H, Lodha A, et al. Nasopharyngeal teratocarcinosarcoma. Int J Pediatr Otorhinolaryngol 2002;62(2):159–164. DOI: 10.1016/s0165-5876(01)00575-4
10. Wei S, Carroll W, Lazenby A, et al. Sinonasal teratocarcinosarcoma; report of a case with review of literature and treatment outcomes. Ann Diagn Pathol 2008;12(6):415–425. DOI: 10.1016/j.anndiagpath.2007.05.003
11. Pai SA, Naresh KN, Masih K, et al. Teratocarcinosarcoma of the paranasal sinuses: a clinicopathologic and immunohistochemical study. Hum Pathol 1998;29(7):718–722. DOI: 10.1016/s0046-8177(98)90281-7
12. Ling FT, Gerin-Lajoie J, Wang D. Sinonasal teratocarcinosarcoma. J Otolaryngol 2004;33(3):203–206. DOI: 10.2310/7070.2004.03012
13. Shimazaki H, Aida S, Tamai S, et al. Sinonasal teratocarcinosarcoma: ultrastructural and immunohistochemical evidence of neuroectodermal origin. Ultrastruct Pathol 2000;24(2):115–122. DOI: 10.1080/01913120050118602
14. Thomas J, Adegboyega P, Iloabachie K, et al. Sinonasal teratocarcinosarcoma with yolk sac elements: a neoplasm of somatic or germ cell origin? Ann Diagn Pathol. 2011 Apr; 15(2):135–139. DOI: 10.1016/j.anndiagpath.2010.01.004
15. Vranic S, Caughron SK, Djuricic S, et al. Hamartomas, teratomas and teratocarcinosarcomas of the head and neck: report of 3 new cases with clinico-pathologic correlation, cytogenetic analysis, and review of the literature. BMC Ear Nose Throat Disord 2008;8:8. DOI: 10.1186/1472-6815-8-8
16. Birkeland AC, Burgin SJ, Yanik M, et al. Pathogenetic analysis of sinonasal teratocarcinosarcomas reveal actionable β-catenin overexpression and a β-catenin mutation. J Neurol Surg B Skull Base 2017;78(4):346–352. DOI: 10.1055/s-0037-1601320
17. Rooper LM, Uddin N, Gagan J, et al. Recurrent Loss of SMARCA4 in Sinonasal Teratocarcinosarcoma. Am J Surg Pathol 2020;44(10):1331–1339. DOI: 10.1097/PAS.0000000000001508
18. Fernandez PL, Cardesa A, Alos L, et al. Sinonasal teratocarcinosarcoma: an unusual neoplasm. Pathol Res Pract 1995;191(2):166–171; discussion 172–173. DOI: 10.1016/S0344-0338(11)80567-4
19. Ogawa T, Ikeda K, Watanabe M, et al. A case report of sinonasal teratocarcinosarcoma. Tohoku J Exp Med 2000;190(1):51–59. DOI: 10.1620/tjem.190.51
20. Takasaki K, Sakihama N, Takahashi H. A case with sinonasal teratocarcinosarcoma in the nasal cavity and ethmoid sinus. Eur Arch Otorhinolaryngol 2006;263(6):586–591. DOI: 10.1007/s00405-006-0014-1
21. Fatima SS, Minhas K, Din NU, et al. Sinonasal teratocarcinosarcoma: a clinicopathologic and immunohistochemical study of 6 cases. Ann Diagn Pathol 2013;17(4):313–318. DOI: 10.1016/j.anndiagpath.2013.01.003
22. Leelamma JP, Mohan BP, Srinivasan A. Sinonasal teratocarcinosarcoma- a rare tumour not so rarely misdiagnosed. Iran J Pathol 2018;13(1):85–88. PMID: 29731800.
23. Jin W, Teng Y, Zhao P, et al. Sinonasal teratocarcinosarcoma masquerading as olfactory neuroblastoma. Int J Clin Exp Pathol 2018;11(2):910–915. PMID: 31938183.
24. Compton ML, Lewis JS Jr, Faquin WC, et al. SALL-4 and beta-catenin expression in sinonasal teratocarcinosarcoma. Head Neck Pathol 2022;16(1):229–235. DOI: 10.1007/s12105-021-01343-3
25. Tchoyoson Lim C C, Thiagarajan A, Sim C S, et al. Craniospinal dissemination in teratocarcinosarcoma. J Neurosurg 2008;109(2):321–324. DOI: 10.3171/JNS/2008/109/8/0321
26. Carrizo F, Pineda-Daboin K, Neto A G, et al. Pharyngeal teratocarcinosarcoma: a review of the literature and report of two cases. Ann Diagn Pathol 2006;10(6):339–342. DOI: 10.1016/j.anndiagpath.2006.03.006
27. Naito T, Umemura S, Nakamura H, et al. Successful treatment with nivolumab for SMARCA4-deficient non-small cell lung carcinoma with a high tumor mutation burden: a case report. Thorac Cancer 2019;10(5):1285–1288. DOI: 10.1111/1759-7714.13070
28. Zaman GJR, de Roos JADM, Libouban MAA, et al. TTK inhibitors as a targeted therapy for CTNNB1(β-catenin) mutant cancers. Mol Cancer Ther 2017;16(11):2609–2617. DOI: 10.1158/1535-7163.MCT-17-0342
________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.