A Rare Case of Metastatic Carcinosarcoma Presenting as a Simple Upper Lip Mass

A Rare Case of Metastatic Carcinosarcoma Presenting as a Simple Upper Lip Mass | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Case of Metastatic Carcinosarcoma Presenting as a Simple Upper Lip Mass Ha Eun Park, Chongsoo Park This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7350412/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Carcinosarcoma is a rare, aggressive malignancy exhibiting both epithelial and mesenchymal components. It typically arises in the uterus, lung, or gastrointestinal tract, and oral cavity involvement is extremely uncommon. Here, we report a rare case where a metastatic carcinosarcoma initially presented as a benign-appearing upper lip lesion. Case presentation: A 47-year-old male presented with a painless upper lip mass persisting for two months. The lesion appeared benign but was excised and revealed malignant features on frozen section. Systemic imaging identified multiple hypermetabolic lesions in the lung, colon, liver, pancreas, adrenal glands, and lymph nodes. Histopathology of the lip, colon, and lung lesions showed a high-grade biphasic tumor. Immunohistochemistry confirmed co-expression of cytokeratin and vimentin, consistent with carcinosarcomatous differentiation and epithelial-mesenchymal transition. No primary tumor was identified, and the case was diagnosed as metastatic carcinosarcoma of unknown origin. The patient began palliative chemotherapy. Conclusions: This case emphasizes the importance of early biopsy and thorough systemic evaluation of persistent oral lesions. Carcinosarcoma, though rare, should be considered in the differential diagnosis of aggressive tumors in atypical locations. Carcinosarcoma Lip Mass EMT Metastatic Sarcoma High-grade Tumor Cancer of Unknown Primary (CUP) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Carcinosarcomas are a rare, high-grade subtype of epithelial carcinoma characterized by the presence of both epithelial and mesenchymal components [ 1 – 4 ]. Carcinosarcoma had previously been considered a mixed epithelial-mesenchymal tumor but is now considered a subtype of epithelial carcinoma consisting of high-grade carcinomatous and sarcomatous components [ 5 ]. These tumors often exhibit aggressive biological behavior, with a propensity for rapid growth and widespread metastasis. Histologically features of epithelial-mesenchymal transition (EMT) are revealed, through co-expression of epithelial markers (e.g. cytokeratin) and mesenchymal markers (e.g. vimentin) on immunohistochemical (IHC) staining [ 6 ]. These tumors tend to behave aggressively, with a high propensity for local invasion and distant metastasis [ 7 ]. Although carcinosarcomas are more frequently found in the uterus, lungs, or gastrointestinal tract, the occurrence in the oral cavity—especially in the lip—is exceedingly rare [ 8 – 11 ]. In these atypical sites, it may present with deceptively benign features, such as a painless and slow-growing mass, leading to potential delays in diagnosis and management [ 12 , 13 ]. Because of the rarity and deceptively benign appearance, such tumors may be misdiagnosed or overlooked. Clinicians should maintain a degree of suspicion for malignancy when evaluating persistent, atypical, or rapidly enlarging lip lesions—even though the majority of such lesions may be benign, as mucoceles, fibromas, and hemangiomas are [ 14 ]. We present a rare case of a patient with an initially suspected benign, non-healing upper lip mass, which was ultimately diagnosed as a metastatic high-grade carcinosarcoma involving multiple organs. This case highlights the importance of prompt biopsy, detailed histopathologic assessment, and comprehensive systemic evaluation in the management of atypical oral lesions. Case Report A 47-year-old male with no significant past medical history presented to our clinic with a two-month history of a painless, non-healing mass on the left upper lip (Fig. 1 ). The lesion was firm, mobile, and measured approximately 15mm in diameter. There were no associated ulceration, bleeding, or constitutional symptoms. The mass was clinically presumed to be benign, possibly a mucous cyst or fibroma. The patient underwent excisional biopsy under local anesthesia. Intraoperative frozen section analysis unexpectedly revealed features suggestive of malignancy (Fig. 2 ). Same-day discharge was initially planned as per the routine excisional procedure at the day surgery center. However, due to the unexpected finding of a lesion highly suspicious of malignancy, discharge was postponed. The patient was admitted for further evaluation, and a multidisciplinary approach was undertaken to assess for possible metastatic disease. A comprehensive systemic evaluation was initiated. Contrast-enhanced CT and MRI scans, followed by positron emission tomography–computed tomography (PET-CT), revealed multiple hypermetabolic lesions in the lungs, liver, colon, pancreas, adrenal glands, and multiple lymph nodes (Fig. 3 ). Colonoscopy was performed to evaluate suspected colonic involvement. Endoscopically, the lesions in the cecum and descending colon appeared suspicious of lymphoma, melanoma, or other poorly differentiated neoplasms. (Fig. 4 ). Core needle biopsies from the pulmonary and colonic lesions also revealed histologic features identical to those of the lip mass. Permanent hematoxylin and eosin staining (H&E) sections demonstrated a high-grade spindle cell neoplasm characterized by marked nuclear atypia and brisk mitotic activity (Fig. 5 ). IHC staining demonstrated co-expression of cytokeratin and vimentin (Fig. 6 ), indicating a biphasic epithelial–mesenchymal phenotype consistent with carcinosarcomatous differentiation. Although this immunophenotypic overlap is uncommon, it has been reported in certain sarcomas and poorly differentiated carcinomas. Based on the histological and IHC features, the tumor was diagnosed as a metastatic high-grade carcinosarcoma with poorly differentiation. Given the extensive metastatic burden and lack of a definitive primary site, the patient was referred to the hemato-oncology department and commenced on palliative chemotherapy. Treatment aimed to alleviate symptoms and slow disease progression. At the time of this report, the patient is undergoing systemic therapy and remains under close oncologic surveillance. Discussion Over the years, carcinosarcoma like malignancies have been referred to by various terms—pseudosarcoma, sarcomatoid carcinoma, and collision tumor—reflecting historical uncertainty regarding its pathogenesis (Table 1) [15, 16]. These tumors were once thought to arise from a dual origin or represent reactive stromal responses. However, recent consensus has clarified their classification. According to the 5th edition of the WHO Classification of Head and Neck Tumors (2022), carcinosarcoma is now defined as a high-grade epithelial malignancy composed of both carcinomatous and sarcomatous components, defined as a true subtype of epithelial carcinoma rather than a biphasic or mixed tumor of dual origin [17]. Carcinosarcomas typically arise in the uterus, lungs, or gastrointestinal tract, but have also been reported in sites such as the larynx, salivary glands, skin, esophagus, pancreas, colon, and ovaries. Involvement of the oral or perioral region—especially the upper lip—is extremely rare. Oral metastases account for only about 1% of all oral malignancies, most commonly affecting the gingiva or mandible [18]. The lip, therefore, is an unusual site for presentation. In this case, the absence of an identifiable primary tumor and the initial metastatic presentation suggest a possible diagnosis of Cancer of Unknown Primary (CUP), which accounts for approximately 2.3–4.2% of all malignancies [19]. Sarcomatoid carcinoma of unknown primary (SCUP) represents a rare histological subtype, accounting for approximately 4% of all CUP cases in a recent report from another institutional cohort—higher than previously reported [16]. This suggests SCUP may be underrecognized and emphasizes its distinct clinical and pathological characteristics within the CUP spectrum. Carcinomas and sarcomas differ fundamentally in their tissue of origin and biological behavior. Carcinomas arise from epithelial tissue and typically spread via the lymphatic system, whereas sarcomas originate from mesenchymal tissue and tend to metastasize in hematogenous form. Histologically, carcinomas form nests, glands, or cords with desmoplastic stroma and express epithelial markers such as cytokeratin (CK) and epithelial membrane antigen (EMA). In contrast, sarcomas are composed of spindle, round, or pleomorphic cells, often with myxoid or collagenous stroma, and are positive for mesenchymal markers such as vimentin, desmin, and smooth muscle actin (SMA). (Table 2) Several theories have been proposed to explain the pathogenesis of carcinosarcoma. The collision theory suggests that the epithelial and mesenchymal components arise as two independent tumors that coexist, often observed in sun-damaged skin. The composition theory considers the mesenchymal component to represent a pseudosarcomatous stromal reaction to an epithelial malignancy. The combination theory proposes that both components originate from a single pluripotent stem cell, resulting in a true biphasic tumor through divergent differentiation. Lastly, the conversion model, now the most widely supported hypothesis, proposes that the epithelial component evolves into a sarcomatous phenotype via EMT [20]. Molecular and genomic data—including monoclonality analysis and detection of identical TP53 (Tumor Protein 53) and KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutations in both carcinomatous and sarcomatous elements—provide substantial support for this model, reinforcing the concept of a metaplastic epithelial origin of carcinosarcoma [21]. Several examples illustrate EMT-associated sarcomatoid transformation. Lung adenocarcinoma can evolve into sarcomatoid carcinoma, especially under therapeutic pressure. Post-radiation sarcomatoid change has been observed in head and neck squamous cell carcinoma, as well as basal cell carcinoma undergoing sarcomatoid transformation after treatment with hedgehog inhibitors such as vismodegib [22]. In this case report, the patient was 47-year-old male with no significant medical history, who sought evaluation for a painless, non-healing mass on the upper lip [23]. Clinically, the lesions resembled benign entities such as mucoceles, fibromas, or hemangiomas—conditions far more prevalent in this anatomic region. This led to an initial low index of suspicion for malignancy, and simple excisional biopsy was planned in an outpatient setting. However, intraoperative frozen section revealed malignant features, necessitating inpatient admission for further evaluation and multidisciplinary management. A retrospective review of the CUP database and tumor registry at MD Anderson Cancer Center identified 48 patients diagnosed with sarcomatoid carcinoma of unknown primary (SCUP) between 2001 and 2017 [16]. SCUP itself is a rare entity, but to our knowledge, a case of carcinosarcoma of CUP initially presenting as a tumor in the lip with subsequent systemic metastasis has not been previously reported in the literature, making this case particularly unusual. As is well recognized, carcinogenesis is typically a gradual process that unfolds over several years or even decades. Although the patient became aware of the upper lip mass only two months prior to presentation, the malignancy was likely already in an advanced state by that time. In this regard, the moment of diagnosis reflects not the onset of disease, but rather the point at which the disease becomes clinically apparent. Whether earlier detection by a few months would have led to a better outcome remains uncertain. However, it is encouraging that the diagnosis was made while the patient maintained a good general condition (ECOG PS–1), which is likely to contribute to more favorable treatment outcomes, especially when compared with cases discovered only after catastrophic events such as intestinal perforation [24]. Patients with malignancy generally desire prompt diagnosis and initiation of treatment. Delays in establishing a diagnosis—particularly those that postpone the onset of definitive therapy—can result in considerable psychological distress [25]. This case underscores the clinical imperative of pursuing early diagnostic workup when the disease course deviates from typical patterns, even in lesions that may initially appear benign. Early recognition and timely intervention not only have the potential to improve oncologic outcomes but may also alleviate the psychological burden associated with diagnostic uncertainty and treatment delays. Conclusion This case exemplifies the diagnostic pitfalls of metastatic sarcomas with atypical lip presentations. It underscores the importance of maintaining vigilance when evaluating persistent oral lesions, employing comprehensive diagnostic modalities including IHC, and adopting a multidisciplinary approach for management. Early detection and accurate diagnosis are paramount in facilitating timely and appropriate therapeutic interventions, which are crucial for improving patient outcomes in such aggressive malignancies.​ Abbreviations CUP : Cancer of Unknown Primary EMT : Epithelial-mesenchymal transition IHC : Immunohistochemical SCUP : Sarcomatoid carcinoma of unknown primary CK : Cytokeratin EMA : Epithelial membrane antigen SMA : Smooth muscle actin TP53 : Tumor protein 53 KRAS : Kirsten rat sarcoma viral oncogene homolog ECOG PS : Eastern cooperative oncology group performance status H&E : Hematoxylin and Eosin staining Declarations None Acknowledgements None Authors’ contributions All authors have read and approved the final version of the manuscript. CP designed and supervised this study. CP and HEP contributed to draft the manuscript, major revision of the manuscript and took the whole responsibility of literature search. CP performed the surgery. CP contributed to the data acquisition. CP and HEP contributed by correction of this paper. Availability of data and material All datasets that the conclusion is based upon is referred in the manuscript text. The datasets analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the Ethics Committee (IRB no. BPIRB 2025-03-037) in the Inje University Busan Paik hospital. Informed consent was obtained from subject and all methods were performed in accordance with the relevant guidelines and regulations in accordance with the WMA Declaration of Helsinki. Clinical trial number: not applicable Consent for publication Written informed consent for publication was obtained from participant. Competing interests The authors declare that they have no competing interests Funding This work was supported by clinical research grant from Pusan National University Hospital in 2025 References Gnepp, D.R., et al., Chapter 6 - Salivary and Lacrimal Glands , in Diagnostic Surgical Pathology of the Head and Neck (Second Edition) , D.R. Gnepp, Editor. 2009, W.B. Saunders: Philadelphia. p. 413-562. Hormuzdi, D., et al., Carcinosarcoma: A rare case report of a recurrent mass in the neck region. J Oral Maxillofac Pathol, 2020. 24 (2): p. 327-331. Le, T., et al., Upper lip metastasis of sarcomatoid carcinoma of the lung – an unusual site of disease: a case report. Journal of Medical Case Reports, 2017. 11 (1): p. 18. Wang, J.R., et al., 45 - Malignant Tumors , in Surgery of the Salivary Glands , R.L. Witt, Editor. 2021, Elsevier. p. 286-301. Turashvili, G. and R. Lastra, What’s new in gynecologic pathology 2021: ovary and fallopian tube. J Pathol Transl Med, 2021. 55 (5): p. 366-367. 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Fizazi, Carcinoma of unknown primary (CUP). Crit Rev Oncol Hematol, 2009. 69 (3): p. 271-8. Ho, G.Y., et al., Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin. Cancer Res, 2022. 82 (23): p. 4457-4473. Pang, A., et al., Carcinosarcomas and Related Cancers: Tumors Caught in the Act of Epithelial-Mesenchymal Transition. J Clin Oncol, 2018. 36 (2): p. 210-216. Silverman, D., et al., Transformation of facial basal cell carcinoma to squamous cell carcinoma following vismodegib. Otolaryngology Case Reports, 2021. 20 : p. 100284. Katib, Y. and M. Essatari, Case report: A rare case of oral sebaceous carcinoma in the upper lip. Pathol Oncol Res, 2024. 30 : p. 1611968. Shim, H.J., et al., Carcinosarcoma on ascending colon found by bowel perforation: a case report. 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Synonyms and variant terminologies used to describe carcinosarcoma in the literature Carcinosarcoma Bizarre squamous cell carcinoma Carcino(pseudo)sarcoma Carcinoma with pseudosarcoma High-grade epithelioid neoplasm High-grade or poorly differentiated carcinoma Malignant neoplasm favor sarcoma Malignant spindle cell and epithelioid neoplasm Metaplastic carcinoma Pleomorphic carcinoma Pleomorphic sarcomatoid malignant neoplasm Polypoid squamous cell carcinoma Poorly differentiated carcinoma with sarcomatoid features Pseudocarcinoma Pseudocarcinosarcoma Pseudosarcoma Pseudosarcomatous carcinoma Sarcomatoid carcinoma Sarcomatoid malignant neoplasm Sarcomatoid malignant neoplasm favor anaplastic carcinoma Spindle cell (sarcomatoid) carcinoma Spindle cell carcinoma Spindle cell variant of squamous carcinoma Squamous cell carcinoma with pseudosarcoma Squamous cell carcinoma with sarcoma-like stroma Table 2. Comparative histopathological and clinical features of carcinoma and sarcoma Feature Carcinoma Sarcoma Tissue Origin Epithelial tissue Mesenchymal tissue Common Sites Skin, lung, breast, GI tract Bone, fat, muscle, blood vessels Metastasis Route Lymphatic spread Hematogenous spread Frequency Common Rare Examples Adenocarcinoma, SCC Osteosarcoma, Leiomyosarcoma Histology Markers Cytokeratin, EMA Vimentin, Desmin, SMA Histologic Features Forms nests, glands, cords; desmoplastic stroma Composed of spindle, round, pleomorphic cells; stroma may be myxoid or collagenous Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Oct, 2025 Reviews received at journal 07 Oct, 2025 Reviewers agreed at journal 26 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviews received at journal 24 Sep, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers invited by journal 20 Sep, 2025 Editor invited by journal 12 Sep, 2025 Editor assigned by journal 03 Sep, 2025 Submission checks completed at journal 15 Aug, 2025 First submitted to journal 15 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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08:10:17","extension":"xml","order_by":37,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":64714,"visible":true,"origin":"","legend":"","description":"","filename":"673e464a752144cbab4ee48926998ea91structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/df58f63e45cd47a195f348e1.xml"},{"id":92574072,"identity":"648de18c-e979-4761-9f30-88e93c0d1ce9","added_by":"auto","created_at":"2025-10-01 08:10:16","extension":"html","order_by":38,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73027,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/35f94c93845d1fda4e07f2ba.html"},{"id":92574038,"identity":"ce8014d0-f7c5-481a-8e83-98fcbc2722c2","added_by":"auto","created_at":"2025-10-01 08:10:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":546680,"visible":true,"origin":"","legend":"\u003cp\u003eInitial clinical presentation of the patient’s left upper lip lesion. A 47-year-old male presented with a two-month history of progressive swelling and mild pain involving the upper lip. The lesion appeared as a firm, submucosal nodule without ulceration. Needle aspiration was attempted but yielded no material.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/319d2f7f2cf41bdf5204d3d6.png"},{"id":92575050,"identity":"bf3057cb-e58c-4ed8-b75d-44f5458f71d8","added_by":"auto","created_at":"2025-10-01 08:18:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1024750,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative findings following excisional biopsy of the upper lip mass (1.1 × 0.9 cm). The mass appeared firmly adherent to the surrounding tissues. Grossly, the cut surface revealed atypical, incohesive epithelioid cells suggestive of malignancy prior to frozen section analysis.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/12e07fa758ee718413157762.png"},{"id":92574044,"identity":"f512c111-38c2-4199-ae06-a3d95b8ee3de","added_by":"auto","created_at":"2025-10-01 08:10:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":616897,"visible":true,"origin":"","legend":"\u003cp\u003eCross-sectional imaging demonstrating widespread metastatic disease.\u003c/p\u003e\n\u003cp\u003e(A) Chest CT showing multiple pulmonary nodules.\u003c/p\u003e\n\u003cp\u003e(B) Abdominal CT revealing metastatic lesions in the colon, liver, pancreas, and adrenal glands.\u003c/p\u003e\n\u003cp\u003e(C) PET-CT scan confirming systemic metastases across multiple organs.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/a3d95f01a6d5b72d75347d20.png"},{"id":92575051,"identity":"12f5dd75-af45-4269-bd2a-70ca659af124","added_by":"auto","created_at":"2025-10-01 08:18:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":382792,"visible":true,"origin":"","legend":"\u003cp\u003eColonoscopy findings of metastatic carcinosarcoma involving the colon.\u003c/p\u003e\n\u003cp\u003e(A) Colonoscopy revealed a large, fungating, ulcero-infiltrative mass with yellowish exudate in the cecum.\u003c/p\u003e\n\u003cp\u003e(B) Another ulcero-infiltrative mass with hemorrhagic and necrotic surface was noted in the descending colon.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/0e5853feb354e2a6dee27f3c.png"},{"id":92574047,"identity":"77ec90f3-7994-49db-b327-ec98ce044be2","added_by":"auto","created_at":"2025-10-01 08:10:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1594736,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological features of the primary and metastatic lesions. (H\u0026amp;E ×200)\u003c/p\u003e\n\u003cp\u003e(A) The lip mass shows a biphasic, poorly differentiated carcinoma with both epithelial and mesenchymal components, consistent with carcinosarcoma.\u003c/p\u003e\n\u003cp\u003e(B, C) Histologic sections from the colon and lung reveal metastatic tumors exhibiting similar biphasic morphology, suggesting a common origin.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/5f003a261449cdb8a0281229.png"},{"id":92575052,"identity":"4866a644-8a60-4dc1-b1d1-0970f123c843","added_by":"auto","created_at":"2025-10-01 08:18:16","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":2083977,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical (IHC ×200) staining demonstrating shared features across metastatic sites. Representative IHC images showing consistent expression patterns of epithelial and mesenchymal markers in the high-grade carcinosarcoma, supporting a common origin.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/1d5f59eb88d8d06c65247a0b.png"},{"id":92578138,"identity":"ea34fc92-fdbc-4615-9121-757dbb9dda64","added_by":"auto","created_at":"2025-10-01 08:42:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7551990,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7350412/v1/f766ec02-10f3-4525-b14a-870f2c01e85a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case of Metastatic Carcinosarcoma Presenting as a Simple Upper Lip Mass","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCarcinosarcomas are a rare, high-grade subtype of epithelial carcinoma characterized by the presence of both epithelial and mesenchymal components [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Carcinosarcoma had previously been considered a mixed epithelial-mesenchymal tumor but is now considered a subtype of epithelial carcinoma consisting of high-grade carcinomatous and sarcomatous components [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These tumors often exhibit aggressive biological behavior, with a propensity for rapid growth and widespread metastasis. Histologically features of epithelial-mesenchymal transition (EMT) are revealed, through co-expression of epithelial markers (e.g. cytokeratin) and mesenchymal markers (e.g. vimentin) on immunohistochemical (IHC) staining [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These tumors tend to behave aggressively, with a high propensity for local invasion and distant metastasis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough carcinosarcomas are more frequently found in the uterus, lungs, or gastrointestinal tract, the occurrence in the oral cavity\u0026mdash;especially in the lip\u0026mdash;is exceedingly rare [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In these atypical sites, it may present with deceptively benign features, such as a painless and slow-growing mass, leading to potential delays in diagnosis and management [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBecause of the rarity and deceptively benign appearance, such tumors may be misdiagnosed or overlooked. Clinicians should maintain a degree of suspicion for malignancy when evaluating persistent, atypical, or rapidly enlarging lip lesions\u0026mdash;even though the majority of such lesions may be benign, as mucoceles, fibromas, and hemangiomas are [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWe present a rare case of a patient with an initially suspected benign, non-healing upper lip mass, which was ultimately diagnosed as a metastatic high-grade carcinosarcoma involving multiple organs. This case highlights the importance of prompt biopsy, detailed histopathologic assessment, and comprehensive systemic evaluation in the management of atypical oral lesions.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 47-year-old male with no significant past medical history presented to our clinic with a two-month history of a painless, non-healing mass on the left upper lip (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The lesion was firm, mobile, and measured approximately 15mm in diameter. There were no associated ulceration, bleeding, or constitutional symptoms. The mass was clinically presumed to be benign, possibly a mucous cyst or fibroma.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe patient underwent excisional biopsy under local anesthesia. Intraoperative frozen section analysis unexpectedly revealed features suggestive of malignancy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Same-day discharge was initially planned as per the routine excisional procedure at the day surgery center. However, due to the unexpected finding of a lesion highly suspicious of malignancy, discharge was postponed. The patient was admitted for further evaluation, and a multidisciplinary approach was undertaken to assess for possible metastatic disease.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA comprehensive systemic evaluation was initiated. Contrast-enhanced CT and MRI scans, followed by positron emission tomography\u0026ndash;computed tomography (PET-CT), revealed multiple hypermetabolic lesions in the lungs, liver, colon, pancreas, adrenal glands, and multiple lymph nodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Colonoscopy was performed to evaluate suspected colonic involvement. Endoscopically, the lesions in the cecum and descending colon appeared suspicious of lymphoma, melanoma, or other poorly differentiated neoplasms. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Core needle biopsies from the pulmonary and colonic lesions also revealed histologic features identical to those of the lip mass.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePermanent hematoxylin and eosin staining (H\u0026amp;E) sections demonstrated a high-grade spindle cell neoplasm characterized by marked nuclear atypia and brisk mitotic activity (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). IHC staining demonstrated co-expression of cytokeratin and vimentin (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e), indicating a biphasic epithelial\u0026ndash;mesenchymal phenotype consistent with carcinosarcomatous differentiation. Although this immunophenotypic overlap is uncommon, it has been reported in certain sarcomas and poorly differentiated carcinomas. Based on the histological and IHC features, the tumor was diagnosed as a metastatic high-grade carcinosarcoma with poorly differentiation.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eGiven the extensive metastatic burden and lack of a definitive primary site, the patient was referred to the hemato-oncology department and commenced on palliative chemotherapy. Treatment aimed to alleviate symptoms and slow disease progression. At the time of this report, the patient is undergoing systemic therapy and remains under close oncologic surveillance.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOver the years, carcinosarcoma like malignancies have been referred to by various terms\u0026mdash;pseudosarcoma, sarcomatoid carcinoma, and collision tumor\u0026mdash;reflecting historical uncertainty regarding its pathogenesis (Table 1) [15, 16]. These tumors were once thought to arise from a dual origin or represent reactive stromal responses. However, recent consensus has clarified their classification. According to the 5th edition of the WHO Classification of Head and Neck Tumors (2022), carcinosarcoma is now defined as a high-grade epithelial malignancy composed of both carcinomatous and sarcomatous components, defined as a true subtype of epithelial carcinoma rather than a biphasic or mixed tumor of dual origin [17].\u003c/p\u003e\n\u003cp\u003eCarcinosarcomas typically arise in the uterus, lungs, or gastrointestinal tract, but have also been reported in sites such as the larynx, salivary glands, skin, esophagus, pancreas, colon, and ovaries. Involvement of the oral or perioral region\u0026mdash;especially the upper lip\u0026mdash;is extremely rare. Oral metastases account for only about 1% of all oral malignancies, most commonly affecting the gingiva or mandible [18]. The lip, therefore, is an unusual site for presentation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this case, the absence of an identifiable primary tumor and the initial metastatic presentation suggest a possible diagnosis of Cancer of Unknown Primary (CUP), which accounts for approximately 2.3\u0026ndash;4.2% of all malignancies [19]. Sarcomatoid carcinoma of unknown primary (SCUP) represents a rare histological subtype, accounting for approximately 4% of all CUP cases in a recent report from another institutional cohort\u0026mdash;higher than previously reported [16]. This suggests SCUP may be underrecognized and emphasizes its distinct clinical and pathological characteristics within the CUP spectrum.\u003c/p\u003e\n\u003cp\u003eCarcinomas and sarcomas differ fundamentally in their tissue of origin and biological behavior. Carcinomas arise from epithelial tissue and typically spread via the lymphatic system, whereas sarcomas originate from mesenchymal tissue and tend to metastasize in hematogenous form. Histologically, carcinomas form nests, glands, or cords with desmoplastic stroma and express epithelial markers such as cytokeratin (CK) and epithelial membrane antigen (EMA). In contrast, sarcomas are composed of spindle, round, or pleomorphic cells, often with myxoid or collagenous stroma, and are positive for mesenchymal markers such as vimentin, desmin, and smooth muscle actin (SMA). (Table 2)\u003c/p\u003e\n\u003cp\u003eSeveral theories have been proposed to explain the pathogenesis of carcinosarcoma. The collision theory suggests that the epithelial and mesenchymal components arise as two independent tumors that coexist, often observed in sun-damaged skin. The composition theory considers the mesenchymal component to represent a pseudosarcomatous stromal reaction to an epithelial malignancy. The combination theory proposes that both components originate from a single pluripotent stem cell, resulting in a true biphasic tumor through divergent differentiation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLastly, the conversion model, now the most widely supported hypothesis, proposes that the epithelial component evolves into a sarcomatous phenotype via EMT [20]. Molecular and genomic data\u0026mdash;including monoclonality analysis and detection of identical TP53 (Tumor Protein 53) and KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutations in both carcinomatous and sarcomatous elements\u0026mdash;provide substantial support for this model, reinforcing the concept of a metaplastic epithelial origin of carcinosarcoma [21].\u003c/p\u003e\n\u003cp\u003eSeveral examples illustrate EMT-associated sarcomatoid transformation. Lung adenocarcinoma can evolve into sarcomatoid carcinoma, especially under therapeutic pressure. Post-radiation sarcomatoid change has been observed in head and neck squamous cell carcinoma, as well as basal cell carcinoma undergoing sarcomatoid transformation after treatment with hedgehog inhibitors such as vismodegib [22].\u003c/p\u003e\n\u003cp\u003eIn this case report, the patient was 47-year-old male with no significant medical history, who sought evaluation for a painless, non-healing mass on the upper lip [23]. Clinically, the lesions resembled benign entities such as mucoceles, fibromas, or hemangiomas\u0026mdash;conditions far more prevalent in this anatomic region. This led to an initial low index of suspicion for malignancy, and simple excisional biopsy was planned in an outpatient setting. However, intraoperative frozen section revealed malignant features, necessitating inpatient admission for further evaluation and multidisciplinary management.\u003c/p\u003e\n\u003cp\u003eA retrospective review of the CUP database and tumor registry at MD Anderson Cancer Center identified 48 patients diagnosed with sarcomatoid carcinoma of unknown primary (SCUP) between 2001 and 2017 [16]. SCUP itself is a rare entity, but to our knowledge, a case of carcinosarcoma of CUP initially presenting as a tumor in the lip with subsequent systemic metastasis has not been previously reported in the literature, making this case particularly unusual.\u003c/p\u003e\n\u003cp\u003eAs is well recognized, carcinogenesis is typically a gradual process that unfolds over several years or even decades. Although the patient became aware of the upper lip mass only two months prior to presentation, the malignancy was likely already in an advanced state by that time. In this regard, the moment of diagnosis reflects not the onset of disease, but rather the point at which the disease becomes clinically apparent. Whether earlier detection by a few months would have led to a better outcome remains uncertain. However, it is encouraging that the diagnosis was made while the patient maintained a good general condition (ECOG PS\u0026ndash;1), which is likely to contribute to more favorable treatment outcomes, especially when compared with cases discovered only after catastrophic events such as intestinal perforation [24].\u003c/p\u003e\n\u003cp\u003ePatients with malignancy generally desire prompt diagnosis and initiation of treatment. Delays in establishing a diagnosis\u0026mdash;particularly those that postpone the onset of definitive therapy\u0026mdash;can result in considerable psychological distress [25]. This case underscores the clinical imperative of pursuing early diagnostic workup when the disease course deviates from typical patterns, even in lesions that may initially appear benign. Early recognition and timely intervention not only have the potential to improve oncologic outcomes but may also alleviate the psychological burden associated with diagnostic uncertainty and treatment delays.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case exemplifies the diagnostic pitfalls of metastatic sarcomas with atypical lip presentations. It underscores the importance of maintaining vigilance when evaluating persistent oral lesions, employing comprehensive diagnostic modalities including IHC, and adopting a multidisciplinary approach for management. Early detection and accurate diagnosis are paramount in facilitating timely and appropriate therapeutic interventions, which are crucial for improving patient outcomes in such aggressive malignancies.​\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCUP : Cancer of Unknown Primary\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEMT : Epithelial-mesenchymal transition\u003c/p\u003e\n\u003cp\u003eIHC : Immunohistochemical\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSCUP : Sarcomatoid carcinoma of unknown primary\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCK : Cytokeratin\u003c/p\u003e\n\u003cp\u003eEMA : Epithelial membrane antigen\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSMA : Smooth muscle actin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTP53 : Tumor protein 53\u003c/p\u003e\n\u003cp\u003eKRAS : Kirsten rat sarcoma viral oncogene homolog\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eECOG PS\u0026nbsp;:\u0026nbsp;Eastern cooperative oncology group performance status\u003c/p\u003e\n\u003cp\u003eH\u0026amp;E : Hematoxylin and Eosin staining\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eNone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final version of the manuscript. CP designed and supervised this study. CP and HEP contributed to draft the manuscript, major revision of the manuscript and took the whole responsibility of literature search. CP performed the surgery. CP contributed to the data acquisition. CP and HEP contributed by correction of this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll datasets that the conclusion is based upon is referred in the manuscript text. The datasets analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee (IRB no. BPIRB 2025-03-037) in the Inje University Busan Paik hospital. Informed consent was obtained from subject and all methods were performed in accordance with the relevant guidelines and regulations in accordance with the WMA Declaration of Helsinki. \u003cstrong\u003eClinical trial number: not applicable\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from participant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by clinical research grant from Pusan National University Hospital in 2025\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGnepp, D.R., et al., \u003cem\u003eChapter 6 - Salivary and Lacrimal Glands\u003c/em\u003e, in \u003cem\u003eDiagnostic Surgical Pathology of the Head and Neck (Second Edition)\u003c/em\u003e, D.R. 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WHO Classification of Tumours Series, ed. I.A. Cree, et al. Vol. 9. 2022, Lyon: International Agency for Research on Cancer.\u003c/li\u003e\n\u003cli\u003eBeena, V., et al., \u003cem\u003eMultiple metastatic tumors in the oral cavity.\u003c/em\u003e J Oral Maxillofac Pathol, 2011. \u003cstrong\u003e15\u003c/strong\u003e(2): p. 214-8.\u003c/li\u003e\n\u003cli\u003ePavlidis, N. and K. Fizazi, \u003cem\u003eCarcinoma of unknown primary (CUP).\u003c/em\u003e Crit Rev Oncol Hematol, 2009. \u003cstrong\u003e69\u003c/strong\u003e(3): p. 271-8.\u003c/li\u003e\n\u003cli\u003eHo, G.Y., et al., \u003cem\u003eEpithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin.\u003c/em\u003e Cancer Res, 2022. \u003cstrong\u003e82\u003c/strong\u003e(23): p. 4457-4473.\u003c/li\u003e\n\u003cli\u003ePang, A., et al., \u003cem\u003eCarcinosarcomas and Related Cancers: Tumors Caught in the Act of Epithelial-Mesenchymal Transition.\u003c/em\u003e J Clin Oncol, 2018. \u003cstrong\u003e36\u003c/strong\u003e(2): p. 210-216.\u003c/li\u003e\n\u003cli\u003eSilverman, D., et al., \u003cem\u003eTransformation of facial basal cell carcinoma to squamous cell carcinoma following vismodegib.\u003c/em\u003e Otolaryngology Case Reports, 2021. \u003cstrong\u003e20\u003c/strong\u003e: p. 100284.\u003c/li\u003e\n\u003cli\u003eKatib, Y. and M. Essatari, \u003cem\u003eCase report: A rare case of oral sebaceous carcinoma in the upper lip.\u003c/em\u003e Pathol Oncol Res, 2024. \u003cstrong\u003e30\u003c/strong\u003e: p. 1611968.\u003c/li\u003e\n\u003cli\u003eShim, H.J., et al., \u003cem\u003eCarcinosarcoma on ascending colon found by bowel perforation: a case report.\u003c/em\u003e J Korean Soc Coloproctol, 2010. \u003cstrong\u003e26\u003c/strong\u003e(5): p. 368-72.\u003c/li\u003e\n\u003cli\u003eye, Y., et al., \u003cem\u003ePsychological distress of cancer patients caused by treatment delay during the COVID-19 pandemic in China: A cross-sectional study.\u003c/em\u003e Psycho-Oncology, 2022. \u003cstrong\u003e31\u003c/strong\u003e(9): p. 1607-1615.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Synonyms and variant terminologies used to describe carcinosarcoma in the literature\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95.3541%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCarcinosarcoma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eBizarre squamous cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eCarcino(pseudo)sarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eCarcinoma with pseudosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eHigh-grade epithelioid neoplasm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eHigh-grade or poorly differentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eMalignant neoplasm favor sarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eMalignant spindle cell and epithelioid neoplasm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eMetaplastic carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePleomorphic carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePleomorphic sarcomatoid malignant neoplasm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePolypoid squamous cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePoorly differentiated carcinoma with sarcomatoid features\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePseudocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePseudocarcinosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePseudosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003ePseudosarcomatous carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSarcomatoid carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSarcomatoid malignant neoplasm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSarcomatoid malignant neoplasm favor anaplastic carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSpindle cell (sarcomatoid) carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSpindle cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSpindle cell variant of squamous carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSquamous cell carcinoma with pseudosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 99.9395%;\"\u003e\n \u003cp\u003eSquamous cell carcinoma with sarcoma-like stroma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. Comparative histopathological and clinical features of carcinoma and sarcoma\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFeature\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCarcinoma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSarcoma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTissue Origin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eEpithelial tissue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eMesenchymal tissue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommon Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eSkin, lung, breast, GI tract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eBone, fat, muscle, blood vessels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetastasis Route\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eLymphatic spread\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eHematogenous spread\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eCommon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eRare\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExamples\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eAdenocarcinoma, SCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eOsteosarcoma, Leiomyosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistology Markers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eCytokeratin, EMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eVimentin, Desmin, SMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistologic Features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eForms nests, glands, cords; desmoplastic stroma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 233px;\"\u003e\n \u003cp\u003eComposed of spindle, round, pleomorphic cells; stroma may be myxoid or collagenous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Carcinosarcoma, Lip Mass, EMT, Metastatic Sarcoma, High-grade Tumor, Cancer of Unknown Primary (CUP)","lastPublishedDoi":"10.21203/rs.3.rs-7350412/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7350412/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003cbr\u003e\nCarcinosarcoma is a rare, aggressive malignancy exhibiting both epithelial and mesenchymal components. It typically arises in the uterus, lung, or gastrointestinal tract, and oral cavity involvement is extremely uncommon. Here, we report a rare case where a metastatic carcinosarcoma initially presented as a benign-appearing upper lip lesion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e\u003cbr\u003e\nA 47-year-old male presented with a painless upper lip mass persisting for two months. The lesion appeared benign but was excised and revealed malignant features on frozen section. Systemic imaging identified multiple hypermetabolic lesions in the lung, colon, liver, pancreas, adrenal glands, and lymph nodes. Histopathology of the lip, colon, and lung lesions showed a high-grade biphasic tumor. Immunohistochemistry confirmed co-expression of cytokeratin and vimentin, consistent with carcinosarcomatous differentiation and epithelial-mesenchymal transition. No primary tumor was identified, and the case was diagnosed as metastatic carcinosarcoma of unknown origin. The patient began palliative chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003cbr\u003e\nThis case emphasizes the importance of early biopsy and thorough systemic evaluation of persistent oral lesions. Carcinosarcoma, though rare, should be considered in the differential diagnosis of aggressive tumors in atypical locations.\u003c/p\u003e","manuscriptTitle":"A Rare Case of Metastatic Carcinosarcoma Presenting as a Simple Upper Lip Mass","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-01 08:10:11","doi":"10.21203/rs.3.rs-7350412/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-21T10:24:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-07T05:33:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300288460059497019787971688839710008738","date":"2025-09-26T16:21:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"653971719557470281271852140525392038","date":"2025-09-25T15:32:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-24T20:41:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140995297573678731362905524345924784725","date":"2025-09-22T16:43:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-20T15:26:30+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-12T15:51:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-03T12:16:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-15T05:02:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-08-15T04:59:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"877c2037-4d96-4bd1-9a9c-2e1a055add14","owner":[],"postedDate":"October 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-29T10:53:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-01 08:10:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7350412","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7350412","identity":"rs-7350412","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}