An Uncommon Guest to the Axillary Lymph Node – A Case Report of Nodal Metastasis of Synovial Sarcoma

An Uncommon Guest to the Axillary Lymph Node – A Case Report of Nodal Metastasis of Synovial Sarcoma | 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 An Uncommon Guest to the Axillary Lymph Node – A Case Report of Nodal Metastasis of Synovial Sarcoma Azhagunila Adinarayanane, Banushree Chandrasekhar Srinivasamurthy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8806660/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Introduction Synovial sarcoma is a rare and aggressive soft tissue sarcoma having poor prognosis with high tendency to recur and metastasize distantly. Localised disease shows a better prognosis than metastasis. The most common sites of metastasis are lungs, bone and liver. Lymph node is a less common site of metastasis. Case Presentation A 57-year-old male presented with an axillary region swelling with no other symptoms. Two yellowish to grey white to grey brown masses from the abdomen were excised and sent to histopathology. The cut surface of the larger mass showed three lymph nodes that were grey white and firm. The cut surface of the smaller mass showed two lymph nodes that are grey white and firm. Microscopy revealed complete effacement of architecture by pleomorphic spindle cells arranged in fascicles. These cells exhibited a high nuclear-cytoplasmic ratio, vesicular nuclei with prominent nucleoli, and brisk atypical mitoses (6–7/hpf). Tumor necrosis was present, and a subset of cells displayed epithelioid differentiation, arranged in nests. No extranodal extension was identified. Immunohistochemistry revealed positive TLE1, Synaptophysin, PanCK and Vimentin and a partial INI loss. S100, SMA and CD34 were negative. CT revealed multiple lesions at bilateral lungs, kidney, liver and lymphadenopathy in mediastinum and inguinal regions. This case was diagnosed as Synovial Sarcoma and was started on Doxorubicin. Conclusion Synovial sarcoma is an aggressive tumor that may show lymph node metastasis. Axillary lymph node swelling though rare maybe a presenting complaint of synovial sarcomas. It also expresses various markers including TLE1. Synaptophysin which is also a neuroendocrine marker may appear positive. This should be kept in mind as it is imperative to be considerate of the heterogeneity of marker expressions of synovial sarcomas and be vigilant while diagnosing these tumors. Synovial sarcoma Synaptophysin Axillary lymphadenopathy Metastasis Biphasic Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Synovial sarcoma is a rare and aggressive form of soft tissue sarcoma, accounting for 5% to 10% of all soft tissue sarcomas.[ 1 ] It is associated with a poor prognosis owing to its tendency to recur locally and metastasize to distant sites. [ 2 ] The median age at diagnosis is 35 years, with the most common location being the extremities, which is associated with a better prognosis than non-extremity locations. Localized disease typically has a more favorable outcome than that of metastatic disease. The lungs, bones, and liver are the most common sites for metastasis. Although less frequent, lymph node involvement is found in 15–20% of cases at diagnosis. For patients with lymph node metastasis, the 5-year overall survival rate ranges from 12.8% to 34%. [ 3 ] This case shows extremely rare manifestations of nodal metastases and synaptophysin positivity in synovial sarcoma. Case Report A 57-year-old male presented with a four-month history of swelling in the right axillary region. He reported no fever or other swellings elsewhere in the body. His medical history included hypertension, which was under treatment, but no diabetes, bronchial asthma, or tuberculosis. He had no prior similar complaints but noted an unintentional weight loss of 10 kg over the past month. No significant family history was elicited. On examination, an 8x7 cm swelling was observed in the right axillary region, accompanied by warmth and tenderness. A Computed Tomography (CT) scan taken revealed right axillary lymphadenopathy measuring 3.6x3.2cm which was suggestive of metastasis. Additionally, multiple parenchymal and subpleural heterogeneously enhancing nodules were present in both lungs. A focal hypodense lesion was noted on the upper pole of the left kidney. Fine Needle Aspiration Cytology (FNAC) was attempted but yielded inadequate results. Subsequently, an excision biopsy of the right axilla was performed. Intraoperatively, a highly vascular axillary mass with multiple matted lymph nodes was identified. Laboratory tests, including serum calcium, phosphorus, uric acid, magnesium, and random blood sugar, were within normal limits. Serological tests for HIV, HBV, and HCV were non-reactive. The biopsy specimens consisted of two yellowish-to-grey-brown soft tissue masses, measuring 2.5x2x0.7 cm and 2x1.7x0.4 cm, respectively. The outer surfaces of the masses appeared yellowish and grey-white to grey-brown. The cut surface of the larger mass revealed three lymph nodes (measuring 0.8x0.7x0.7 cm, 0.5x0.5x0.7 cm, and 0.3x0.3x0.7 cm), which were grey-white and firm, surrounded by adipose tissue. The smaller mass contained two lymph nodes (each measuring 0.8x0.4x0.4 cm), also grey-white and firm, with surrounding adipose tissue. ( Fig. 1 ) Microscopic examination of all five lymph nodes showed complete architectural effacement by pleomorphic spindle cells arranged in fascicles. These cells exhibited a high nuclear-cytoplasmic ratio, vesicular nuclei with prominent nucleoli, and brisk atypical mitoses (6–7/hpf). Lymphoid follicles were preserved in some areas, and tumor cells were observed in the subcapsular sinuses. Tumor necrosis was present, and a subset of cells displayed epithelioid differentiation, arranged in nests. No extranodal extension was identified. ( Fig. 2 ). Immunohistochemical analysis revealed the following: TLE1 showed diffuse strong nuclear positivity in tumor cells ( Fig. 3 ) , CD15 was negative in tumor cells but positive in immunoblasts, synaptophysin exhibited strong diffuse cytoplasmic positivity ( Fig. 4 ) , pan-CK showed patchy cytoplasmic positivity, and vimentin demonstrated strong diffuse cytoplasmic positivity in tumor cells. INI1 showed a partial loss ( Fig. 5 ) , while S100, SMA, and CD34 were negative in tumor cells, with positive internal controls. Based on the histopathological and immunohistochemical findings, a diagnosis of Metastatic Synovial Sarcoma in the Right Axillary Lymph Nodes was established. The patient was subsequently referred to a higher center for further evaluation and management, wherein multiple parenchymal and subpleural heterogeneously enhancing nodules were noted in bilateral lungs, the largest measuring 9x5mm in CECT. Multiple enlarged mediastinal lymph nodes were also found, the largest measuring 15x10mm in para-aortic station. Multiple hypodense lesions were found on the right and left lobe of liver, the largest measuring 2.1x2.2cm in the segment V of the liver. A hypodense non-enhancing cystic lesion was also noted in the upper pole of left kidney measuring 12x14mm. Bilateral inguinal lymphadenopathy was also found. Hence the patient was found to be having Metastatic Synovial Sarcoma. Primary could not be identified. The patient is currently under treatment and Doxorubicin is being given for the past six months. Discussion The initial documentation of synovial sarcoma dates back to 1954, as reported by Jenström. These rare and aggressive soft tissue tumors can develop in any anatomical region and are classified into two subtypes: monophasic, consisting spindle or ovoid cells, and biphasic, containing both epithelial structures forming glandular patterns and also spindle cells. [ 4 ] The hallmark genetic alteration associated with synovial sarcoma is chromosomal translocation t(X;18)(p11.2;q11.2), leading to the formation of fusion oncogenes, including SSX1, SSX2, and SSX4. [ 5 ] Extremities are the most common sites where synovial sarcomas occur. Among the extremities, the lower extremity is the most prevalent site. However, they can also arise in other areas such as the head and neck, thorax, and abdomen. The symptoms associated with synovial sarcomas can show wide variation depending upon their location.[ 6 ] Molecular studies have indicated frequent copy number gains in the p53 gene, as well as alterations in the AKT/PTEN signaling pathway. In addition, activation of the AKT/mTOR and WNT pathways was observed. Mutations in the PTEN, CTNNB1, and APC genes, as well as upregulation of mediators associated with the WNT, NOTCH, Hedgehog, FGF, and BMP pathways, have also been reported.[ 7 ] Jacobs AJ et al. study (2018) noted that only 4.2% of synovial sarcoma cases present with lymph node metastasis, highlighting the rarity of the current case, which involves axillary lymph node spread. [ 8 , 9 ] Immunohistochemically, these tumors show variable profiles, typically expressing markers such as Vimentin, Keratin, EMA, and TLE1, along with others like SMA, beta-catenin, and CD99. It is common for the Ki67 proliferation index to be as high as 50%. Additionally, variants with granular cell features may display reactivity to Synaptophysin and Inhibin. The presence of synaptophysin positivity in synovial sarcomas may suggest the possibility of some degree of neuroendocrine differentiation. Furthermore, partial loss of INI1 expression, as described by Kohashi et al. (2010), is observed in monomorphic, biphasic, poorly differentiated subtypes, and those exhibiting rhabdoid features. [ 10 ] Metastatic disease, especially extrapulmonary spread, is associated with a poor prognosis and is commonly treated with chemotherapeutic agents such as Ifosfamide and Doxorubicin. [ 11 ] Numerous genetic mutations characterize both primary and secondary synovial sarcomas. In primary synovial sarcomas, mutations have been identified in ARID1B, CSMD1, CSNK2A1, and DOT1L. On the other hand, metastatic synovial sarcomas exhibit mutations in ADAM17, ARID1B, CSMD1, ATM, CRLF2, JAK1, and KDM5C. [ 12 ] Lung metastasis is common, followed by bone metastasis. Renal metastasis is comparatively rarer. This case has both liver and kidney lesions and axillary metastases are an even rarer phenomenon. Synovial sarcoma appears as heterogeneously enhancing lesion in the lung in CECT, as in our case. Thoracic CTs allow us to evaluate the tumor site, its endothoracic and exothoracic extension. It also helps in staging of the tumor. [ 13 ] The present case highlights a rare instance of synovial sarcoma metastasising to the axillary lymph nodes. This case is significant because of the positivity for synaptophysin, which underscores the diagnostic complexity and diverse immunohistochemical behavior of the tumor. Conclusion Synovial sarcoma is a rare but highly aggressive cancer known for its ability to spread to distant sites. While metastasis most commonly affects the lungs, bones, and liver, lymph node involvement can also occur, although it is rare. This aspect deserves clinical attention during diagnostic evaluations. Interestingly, synovial sarcoma can sometimes show synaptophysin positivity - a marker usually associated with neuroendocrine tumors - adding complexity to its diagnosis. This tumor is recognized for its diverse immunohistochemical profile, expressing various markers such as vimentin, keratin, EMA, and TLE1, among others. The unexpected presence of synaptophysin highlights the diagnostic challenges due to the tumor's phenotypic diversity. Clinicians and pathologists must remain vigilant, as this heterogeneity requires comprehensive immunohistochemical panels to differentiate synovial sarcoma from other conditions that may appear similar, such as neuroendocrine tumors, melanoma, or other types of sarcomas. Understanding the variable expression of markers, including the rare occurrence of synaptophysin reactivity, is crucial to avoid misdiagnosis and guide appropriate treatment strategies, particularly in atypical cases involving lymph node metastasis. Declarations Ethics committee approval and consent to participate - Not applicable for case report Clinical Trial Number - Not applicable Name of ethics committee that waived need for approval – Institute Ethics Committee, IGMC&RI. Consent for publication - Obtained from the patient for the publication of this case report Availability of data and materials - Not applicable Competing interests - The authors declare that they have no competing interests Funding - Nil Acknowledgements - Not applicable Code availability - All authors are making sure that all data and materials as well as software application or custom code support their published claims and comply with field standards. Authors contributions Dr. AS performed the surgery Dr. BCS reported the case and edited the manuscript Dr. AA grossed the specimen and prepared the manuscript References Blay JY, von Mehren M, Jones RL, et al. Synovial sarcoma: characteristics, challenges, and evolving therapeutic strategies. ESMO Open. 2023;8(5):101618. Krieg AH, Hefti F, Speth BM, Jundt G, Guillou L, Exner U et al. Synovial sarcomas usually metastasize after > 5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors. AnnOn.2011;22(2):458 – 67. de Necochea-Campion R, Zuckerman LM, Mirshahidi HR, Khosrowpour S, Chen CS, Mirshahidi S. Metastatic biomarkers in synovial sarcoma. Biomark Res. 2017;5:4. Fisher C. Synovial sarcoma. Ann Diagn Pathol. 1998;2(6):401–21. Thway K, Fisher C. Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol. 2014;18(6):369–80. Bakri A, Shinagare AB, Krajewski KM, Howard SA, Jagannathan JP, Hornick JL, et al. Synovial Sarcoma: Imaging Features of Common and Uncommon Primary Sites, Metastatic Patterns, and Treatment Response. Am J Roentgenol. 2012;199(2):W208–15. Landuzzi L, Manara MC, Pazzaglia L, Lollini PL, Scotlandi K. Innovative Breakthroughs for the Treatment of Advanced and Metastatic Synovial Sarcoma. Cancers. 2023;15(15):3887. Jacobs AJ, Morris CD, Levin AS. Synovial Sarcoma Is Not Associated With a Higher Risk of Lymph Node Metastasis Compared With Other Soft Tissue Sarcomas. Clin Orthop Relat Res. 2018;476(3):589–98. Ordóñez NG, Mahfouz SM, Mackay B. Synovial sarcoma: an immunohistochemical and ultrastructural study. Hum Pathol. 1990;21(7):733–49. Kohashi K, Oda Y, Yamamoto H, Tamiya S, Matono H, Iwamoto Y, Taguchi T, Tsuneyoshi M. Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Mod Pathol. 2010;23(7):981–90. Babu KG, Patidar R, Kuntegowdanahalli CL, Dasappa L, Jacob LA, Babu S, et al. Metastatic synovial sarcoma: Experience from a tertiary care center from India. Indian J Med Paediatr Oncol. 2019;40:S95–8. Xing Z, Wei L, Jiang X, Conroy J, Glenn S, Bshara W, Yu T, Pao A, Tanaka S, Kawai A, Choi C, Wang J, Liu S, Morrison C, Yu YE. Analysis of mutations in primary and metastatic synovial sarcoma. Oncotarget. 2018;9(96):36878–88. Laasri K, Zhim M, Halfi IM, Imrani K, Billah NM. Nassar I.Metastatic pulmonary synovial sarcoma: A double coincidence: Case report. Radiol Case Rep. 2023;18(3):878–81. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 19 Mar, 2026 Reviews received at journal 09 Mar, 2026 Reviews received at journal 03 Mar, 2026 Reviewers agreed at journal 02 Mar, 2026 Reviews received at journal 27 Feb, 2026 Reviewers agreed at journal 27 Feb, 2026 Reviewers agreed at journal 25 Feb, 2026 Reviewers invited by journal 25 Feb, 2026 Editor assigned by journal 25 Feb, 2026 Submission checks completed at journal 24 Feb, 2026 First submitted to journal 06 Feb, 2026 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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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8806660","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":597177809,"identity":"919c4ce1-1f7e-407f-ae67-e8200d72d743","order_by":0,"name":"Azhagunila Adinarayanane","email":"","orcid":"","institution":"Indira Gandhi Medical College and Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Azhagunila","middleName":"","lastName":"Adinarayanane","suffix":""},{"id":597177810,"identity":"943872c5-0a46-464c-83ed-254d2b36b5f6","order_by":1,"name":"Banushree Chandrasekhar 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12:15:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":75284,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMicroscopic image of the lymph node, 400x\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8806660/v1/3f6688ed70d64123ea83fd41.jpg"},{"id":104007420,"identity":"c572777a-3096-4f14-89e1-872aeb694700","added_by":"auto","created_at":"2026-03-05 15:17:42","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74968,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTLE1 positivity, 400x\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8806660/v1/e9747ac26b03c1517a5eadb8.jpg"},{"id":104007417,"identity":"6b25a504-b027-4303-9fee-aa4b0724fe67","added_by":"auto","created_at":"2026-03-05 15:17:42","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":93160,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynaptophysin positivity, 400x\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8806660/v1/3787aa390d7abbd220a84723.jpg"},{"id":104402755,"identity":"54e71440-af0a-4924-a319-045ea2b31b00","added_by":"auto","created_at":"2026-03-11 12:16:18","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":55882,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePartial loss of INI, 400x\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8806660/v1/abbcd457b9f8e5a7b26967af.jpg"},{"id":104410768,"identity":"5eb0c911-b5de-4cd7-ac15-692e508214d3","added_by":"auto","created_at":"2026-03-11 12:53:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":683481,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8806660/v1/87ed59e1-547e-4732-90ab-bafa12cec3c1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"An Uncommon Guest to the Axillary Lymph Node – A Case Report of Nodal Metastasis of Synovial Sarcoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSynovial sarcoma is a rare and aggressive form of soft tissue sarcoma, accounting for 5% to 10% of all soft tissue sarcomas.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] It is associated with a poor prognosis owing to its tendency to recur locally and metastasize to distant sites. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] The median age at diagnosis is 35 years, with the most common location being the extremities, which is associated with a better prognosis than non-extremity locations. Localized disease typically has a more favorable outcome than that of metastatic disease. The lungs, bones, and liver are the most common sites for metastasis. Although less frequent, lymph node involvement is found in 15\u0026ndash;20% of cases at diagnosis. For patients with lymph node metastasis, the 5-year overall survival rate ranges from 12.8% to 34%. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] This case shows extremely rare manifestations of nodal metastases and synaptophysin positivity in synovial sarcoma.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 57-year-old male presented with a four-month history of swelling in the right axillary region. He reported no fever or other swellings elsewhere in the body. His medical history included hypertension, which was under treatment, but no diabetes, bronchial asthma, or tuberculosis. He had no prior similar complaints but noted an unintentional weight loss of 10 kg over the past month. No significant family history was elicited. On examination, an 8x7 cm swelling was observed in the right axillary region, accompanied by warmth and tenderness. A Computed Tomography (CT) scan taken revealed right axillary lymphadenopathy measuring 3.6x3.2cm which was suggestive of metastasis. Additionally, multiple parenchymal and subpleural heterogeneously enhancing nodules were present in both lungs. A focal hypodense lesion was noted on the upper pole of the left kidney. Fine Needle Aspiration Cytology (FNAC) was attempted but yielded inadequate results. Subsequently, an excision biopsy of the right axilla was performed. Intraoperatively, a highly vascular axillary mass with multiple matted lymph nodes was identified. Laboratory tests, including serum calcium, phosphorus, uric acid, magnesium, and random blood sugar, were within normal limits. Serological tests for HIV, HBV, and HCV were non-reactive.\u003c/p\u003e \u003cp\u003eThe biopsy specimens consisted of two yellowish-to-grey-brown soft tissue masses, measuring 2.5x2x0.7 cm and 2x1.7x0.4 cm, respectively. The outer surfaces of the masses appeared yellowish and grey-white to grey-brown. The cut surface of the larger mass revealed three lymph nodes (measuring 0.8x0.7x0.7 cm, 0.5x0.5x0.7 cm, and 0.3x0.3x0.7 cm), which were grey-white and firm, surrounded by adipose tissue. The smaller mass contained two lymph nodes (each measuring 0.8x0.4x0.4 cm), also grey-white and firm, with surrounding adipose tissue.\u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMicroscopic examination of all five lymph nodes showed complete architectural effacement by pleomorphic spindle cells arranged in fascicles. These cells exhibited a high nuclear-cytoplasmic ratio, vesicular nuclei with prominent nucleoli, and brisk atypical mitoses (6\u0026ndash;7/hpf). Lymphoid follicles were preserved in some areas, and tumor cells were observed in the subcapsular sinuses. Tumor necrosis was present, and a subset of cells displayed epithelioid differentiation, arranged in nests. No extranodal extension was identified. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eImmunohistochemical analysis revealed the following: TLE1 showed diffuse strong nuclear positivity in tumor cells \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e, CD15 was negative in tumor cells but positive in immunoblasts, synaptophysin exhibited strong diffuse cytoplasmic positivity \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e, pan-CK showed patchy cytoplasmic positivity, and vimentin demonstrated strong diffuse cytoplasmic positivity in tumor cells. INI1 showed a partial loss \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e, while S100, SMA, and CD34 were negative in tumor cells, with positive internal controls.\u003c/p\u003e \u003cp\u003eBased on the histopathological and immunohistochemical findings, a diagnosis of Metastatic Synovial Sarcoma in the Right Axillary Lymph Nodes was established.\u003c/p\u003e \u003cp\u003eThe patient was subsequently referred to a higher center for further evaluation and management, wherein multiple parenchymal and subpleural heterogeneously enhancing nodules were noted in bilateral lungs, the largest measuring 9x5mm in CECT. Multiple enlarged mediastinal lymph nodes were also found, the largest measuring 15x10mm in para-aortic station. Multiple hypodense lesions were found on the right and left lobe of liver, the largest measuring 2.1x2.2cm in the segment V of the liver. A hypodense non-enhancing cystic lesion was also noted in the upper pole of left kidney measuring 12x14mm. Bilateral inguinal lymphadenopathy was also found. Hence the patient was found to be having Metastatic Synovial Sarcoma. Primary could not be identified. The patient is currently under treatment and Doxorubicin is being given for the past six months.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe initial documentation of synovial sarcoma dates back to 1954, as reported by Jenstr\u0026ouml;m. These rare and aggressive soft tissue tumors can develop in any anatomical region and are classified into two subtypes: monophasic, consisting spindle or ovoid cells, and biphasic, containing both epithelial structures forming glandular patterns and also spindle cells. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] The hallmark genetic alteration associated with synovial sarcoma is chromosomal translocation t(X;18)(p11.2;q11.2), leading to the formation of fusion oncogenes, including SSX1, SSX2, and SSX4. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Extremities are the most common sites where synovial sarcomas occur. Among the extremities, the lower extremity is the most prevalent site. However, they can also arise in other areas such as the head and neck, thorax, and abdomen. The symptoms associated with synovial sarcomas can show wide variation depending upon their location.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMolecular studies have indicated frequent copy number gains in the p53 gene, as well as alterations in the AKT/PTEN signaling pathway. In addition, activation of the AKT/mTOR and WNT pathways was observed. Mutations in the PTEN, CTNNB1, and APC genes, as well as upregulation of mediators associated with the WNT, NOTCH, Hedgehog, FGF, and BMP pathways, have also been reported.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eJacobs AJ et al. study (2018) noted that only 4.2% of synovial sarcoma cases present with lymph node metastasis, highlighting the rarity of the current case, which involves axillary lymph node spread. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Immunohistochemically, these tumors show variable profiles, typically expressing markers such as Vimentin, Keratin, EMA, and TLE1, along with others like SMA, beta-catenin, and CD99. It is common for the Ki67 proliferation index to be as high as 50%. Additionally, variants with granular cell features may display reactivity to Synaptophysin and Inhibin. The presence of synaptophysin positivity in synovial sarcomas may suggest the possibility of some degree of neuroendocrine differentiation. Furthermore, partial loss of INI1 expression, as described by Kohashi et al. (2010), is observed in monomorphic, biphasic, poorly differentiated subtypes, and those exhibiting rhabdoid features. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMetastatic disease, especially extrapulmonary spread, is associated with a poor prognosis and is commonly treated with chemotherapeutic agents such as Ifosfamide and Doxorubicin. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eNumerous genetic mutations characterize both primary and secondary synovial sarcomas. In primary synovial sarcomas, mutations have been identified in ARID1B, CSMD1, CSNK2A1, and DOT1L. On the other hand, metastatic synovial sarcomas exhibit mutations in ADAM17, ARID1B, CSMD1, ATM, CRLF2, JAK1, and KDM5C. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eLung metastasis is common, followed by bone metastasis. Renal metastasis is comparatively rarer. This case has both liver and kidney lesions and axillary metastases are an even rarer phenomenon. Synovial sarcoma appears as heterogeneously enhancing lesion in the lung in CECT, as in our case. Thoracic CTs allow us to evaluate the tumor site, its endothoracic and exothoracic extension. It also helps in staging of the tumor. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe present case highlights a rare instance of synovial sarcoma metastasising to the axillary lymph nodes. This case is significant because of the positivity for synaptophysin, which underscores the diagnostic complexity and diverse immunohistochemical behavior of the tumor.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSynovial sarcoma is a rare but highly aggressive cancer known for its ability to spread to distant sites. While metastasis most commonly affects the lungs, bones, and liver, lymph node involvement can also occur, although it is rare. This aspect deserves clinical attention during diagnostic evaluations. Interestingly, synovial sarcoma can sometimes show synaptophysin positivity - a marker usually associated with neuroendocrine tumors - adding complexity to its diagnosis. This tumor is recognized for its diverse immunohistochemical profile, expressing various markers such as vimentin, keratin, EMA, and TLE1, among others. The unexpected presence of synaptophysin highlights the diagnostic challenges due to the tumor's phenotypic diversity. Clinicians and pathologists must remain vigilant, as this heterogeneity requires comprehensive immunohistochemical panels to differentiate synovial sarcoma from other conditions that may appear similar, such as neuroendocrine tumors, melanoma, or other types of sarcomas. Understanding the variable expression of markers, including the rare occurrence of synaptophysin reactivity, is crucial to avoid misdiagnosis and guide appropriate treatment strategies, particularly in atypical cases involving lymph node metastasis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cli\u003eEthics committee approval and consent to participate - Not applicable for case report\u003c/li\u003e\n \u003cli\u003eClinical Trial Number - Not applicable\u003c/li\u003e\n \u003cli\u003eName of ethics committee that waived need for approval – Institute Ethics Committee, IGMC\u0026amp;RI.\u003c/li\u003e\n \u003cli\u003eConsent for publication - Obtained from the patient for the publication of this case report\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials - Not applicable\u003c/li\u003e\n \u003cli\u003eCompeting interests - The authors declare that they have no competing interests\u003c/li\u003e\n \u003cli\u003eFunding - Nil\u003c/li\u003e\n \u003cli\u003eAcknowledgements - Not applicable\u003c/li\u003e\n \u003cli\u003eCode availability - All authors are making sure that all data and materials as well as software application or custom code support their published claims and comply with field standards.\u003c/li\u003e\n \u003cli\u003eAuthors contributions\u003c/li\u003e\n \u003cli\u003eDr. AS performed the surgery\u003c/li\u003e\n \u003cli\u003eDr. BCS reported the case and edited the manuscript\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDr. AA grossed the specimen and prepared the manuscript\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBlay JY, von Mehren M, Jones RL, et al. Synovial sarcoma: characteristics, challenges, and evolving therapeutic strategies. ESMO Open. 2023;8(5):101618.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrieg AH, Hefti F, Speth BM, Jundt G, Guillou L, Exner U et al. Synovial sarcomas usually metastasize after \u0026gt;\u0026thinsp;5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors. AnnOn.2011;22(2):458\u0026thinsp;\u0026ndash;\u0026thinsp;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Necochea-Campion R, Zuckerman LM, Mirshahidi HR, Khosrowpour S, Chen CS, Mirshahidi S. Metastatic biomarkers in synovial sarcoma. Biomark Res. 2017;5:4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFisher C. Synovial sarcoma. Ann Diagn Pathol. 1998;2(6):401\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThway K, Fisher C. Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol. 2014;18(6):369\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBakri A, Shinagare AB, Krajewski KM, Howard SA, Jagannathan JP, Hornick JL, et al. Synovial Sarcoma: Imaging Features of Common and Uncommon Primary Sites, Metastatic Patterns, and Treatment Response. Am J Roentgenol. 2012;199(2):W208\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLanduzzi L, Manara MC, Pazzaglia L, Lollini PL, Scotlandi K. Innovative Breakthroughs for the Treatment of Advanced and Metastatic Synovial Sarcoma. Cancers. 2023;15(15):3887.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJacobs AJ, Morris CD, Levin AS. Synovial Sarcoma Is Not Associated With a Higher Risk of Lymph Node Metastasis Compared With Other Soft Tissue Sarcomas. Clin Orthop Relat Res. 2018;476(3):589\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrd\u0026oacute;\u0026ntilde;ez NG, Mahfouz SM, Mackay B. Synovial sarcoma: an immunohistochemical and ultrastructural study. Hum Pathol. 1990;21(7):733\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKohashi K, Oda Y, Yamamoto H, Tamiya S, Matono H, Iwamoto Y, Taguchi T, Tsuneyoshi M. Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Mod Pathol. 2010;23(7):981\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBabu KG, Patidar R, Kuntegowdanahalli CL, Dasappa L, Jacob LA, Babu S, et al. Metastatic synovial sarcoma: Experience from a tertiary care center from India. Indian J Med Paediatr Oncol. 2019;40:S95\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXing Z, Wei L, Jiang X, Conroy J, Glenn S, Bshara W, Yu T, Pao A, Tanaka S, Kawai A, Choi C, Wang J, Liu S, Morrison C, Yu YE. Analysis of mutations in primary and metastatic synovial sarcoma. Oncotarget. 2018;9(96):36878\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaasri K, Zhim M, Halfi IM, Imrani K, Billah NM. Nassar I.Metastatic pulmonary synovial sarcoma: A double coincidence: Case report. Radiol Case Rep. 2023;18(3):878\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003c/ol\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":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Synovial sarcoma, Synaptophysin, Axillary lymphadenopathy, Metastasis, Biphasic","lastPublishedDoi":"10.21203/rs.3.rs-8806660/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8806660/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eSynovial sarcoma is a rare and aggressive soft tissue sarcoma having poor prognosis with high tendency to recur and metastasize distantly. Localised disease shows a better prognosis than metastasis. The most common sites of metastasis are lungs, bone and liver. Lymph node is a less common site of metastasis.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eA 57-year-old male presented with an axillary region swelling with no other symptoms. Two yellowish to grey white to grey brown masses from the abdomen were excised and sent to histopathology. The cut surface of the larger mass showed three lymph nodes that were grey white and firm. The cut surface of the smaller mass showed two lymph nodes that are grey white and firm. Microscopy revealed complete effacement of architecture by pleomorphic spindle cells arranged in fascicles. These cells exhibited a high nuclear-cytoplasmic ratio, vesicular nuclei with prominent nucleoli, and brisk atypical mitoses (6\u0026ndash;7/hpf). Tumor necrosis was present, and a subset of cells displayed epithelioid differentiation, arranged in nests. No extranodal extension was identified. Immunohistochemistry revealed positive TLE1, Synaptophysin, PanCK and Vimentin and a partial INI loss. S100, SMA and CD34 were negative. CT revealed multiple lesions at bilateral lungs, kidney, liver and lymphadenopathy in mediastinum and inguinal regions. This case was diagnosed as Synovial Sarcoma and was started on Doxorubicin.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSynovial sarcoma is an aggressive tumor that may show lymph node metastasis. Axillary lymph node swelling though rare maybe a presenting complaint of synovial sarcomas. It also expresses various markers including TLE1. Synaptophysin which is also a neuroendocrine marker may appear positive. This should be kept in mind as it is imperative to be considerate of the heterogeneity of marker expressions of synovial sarcomas and be vigilant while diagnosing these tumors.\u003c/p\u003e","manuscriptTitle":"An Uncommon Guest to the Axillary Lymph Node – A Case Report of Nodal Metastasis of Synovial Sarcoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-05 15:17:31","doi":"10.21203/rs.3.rs-8806660/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-19T12:22:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-09T09:58:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-03T23:46:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265227282485675731831247265080380585040","date":"2026-03-02T09:29:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-27T10:28:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338330050026888704119197951662593856857","date":"2026-02-27T10:18:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13801602243399001719029509975028382960","date":"2026-02-25T22:13:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-25T08:58:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T07:28:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-25T03:09:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2026-02-06T10:50:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"dcf5acc7-2aa7-4555-8803-aa26c5fe257a","owner":[],"postedDate":"March 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-08T18:09:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-05 15:17:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8806660","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8806660","identity":"rs-8806660","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}