Primary Breast Leiomyosarcoma Presenting as Recurrent Spindle Cell Lesions: Diagnostic Pitfalls, Immunohistochemical Insights, and Multidisciplinary Management of a Rare Tumor

Primary Breast Leiomyosarcoma Presenting as Recurrent Spindle Cell Lesions: Diagnostic Pitfalls, Immunohistochemical Insights, and Multidisciplinary Management of a Rare Tumor | 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 Primary Breast Leiomyosarcoma Presenting as Recurrent Spindle Cell Lesions: Diagnostic Pitfalls, Immunohistochemical Insights, and Multidisciplinary Management of a Rare Tumor Ashwini Pitambra, Ashutosh Rath, Immanuel Pradeep, Krishna Ramavath, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7569958/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Primary leiomyosarcoma of the breast is extremely rare, accounting for less than 1% of breast tumors. Diagnosis is often difficult because it can mimic other spindle cell lesions, and standard treatment guidelines are lacking. Reporting such cases helps improve the understanding and management of these uncommon tumors. Case Presentation: A 44-year-old woman presented with a rapidly growing, firm lump in her left breast. She had previous surgeries elsewhere with diagnoses of leiomyoma and desmoid-type fibromatosis. Imaging showed a large lobulated mass (14.8 cm) without lymph node involvement or distant metastasis. Core needle biopsy revealed a spindle cell tumor with moderate atypia and mitotic activity, but it was not definitive. Excisional histopathology demonstrated intersecting fascicles of pleomorphic spindle cells, necrosis, and dermal invasion. Immunohistochemistry confirmed smooth muscle origin (SMA and desmin positive), excluding epithelial, neural, and vascular tumors. The tumor was graded as Grade 2. The patient underwent a modified radical mastectomy followed by adjuvant radiotherapy and planned chemotherapy. Conclusion Primary breast leiomyosarcoma is rare and can present with diagnostic challenges. Core biopsy and cytology alone may be misleading. Immunohistochemistry was essential to reach the correct diagnosis and to differentiate from other spindle cell tumors. Management requires a multidisciplinary approach, including surgery with clear margins and tailored adjuvant therapy. This case adds to the limited literature and offers lessons on diagnosis, management, and follow-up of rare spindle cell breast tumors. Primary breast leiomyosarcoma spindle cell tumor immunohistochemistry diagnosis rare breast tumor multidisciplinary management Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Primary leiomyosarcoma of the breast is a rare malignant neoplasm, representing less than 1% of breast tumors and posing significant diagnostic and therapeutic challenges due to limited data and the absence of standardized guidelines (Alimi et al. 2025 ). The tumor arises from smooth muscle or mesenchymal stem cells, differentiating into smooth muscle tissue (Samenova et al. 2023 ). Clinically, patients often present with a rapidly growing, painless breast mass, and the diagnosis is frequently made incidentally during excisional histopathology (Ahuja et al. 2022 ). Immunohistochemical profiling is essential in differentiating leiomyosarcoma from other spindle-cell lesions (Ni and Tse 2023 ). Given the unpredictable biological behavior and lack of consensus protocols, treatment is based on extrapolation from soft tissue sarcoma guidelines (Ilyas et al. 2019 ). Prognosis may be relatively favorable compared to other subtypes, yet metastasis remains a risk (Singh et al. 2017 ). Case presentation A 44-year-old woman presented with an enlarging, firm lump in the upper outer quadrant of her left breast, measuring 15 × 15 cm, with overlying erythema and a previous surgical scar (Fig. 1 ). She had a history of recurrent breast lesions, including prior diagnoses of leiomyoma and desmoid-type fibromatosis, both diagnosed at an outside facility and managed with lumpectomies. Recent fine-needle aspiration cytology (FNAC), performed elsewhere, suggested proliferative breast disease with atypia, prompting further evaluation. Ultrasound suggested a BI-RADS 4B lesion, and PET-CT imaging showed a 14.8 cm heterogeneously enhancing tumor with lobulated margins and central necrosis. The tumor was closely abutting the skin but did not invade the pectoral muscle or adjacent fat planes. Axillary lymph nodes showed no abnormal FDG (fluorodeoxyglucose) uptake and had a preserved fatty hilum, suggesting the absence of metastatic involvement. A core biopsy confirmed a spindle cell tumor composed of elongated cells arranged in fascicles, showing moderate pleomorphism and 8–10 mitotic figures per 10 high-power fields (HPF). The differential diagnoses included borderline or malignant phyllodes tumor, metaplastic carcinoma, and other mesenchymal tumors, necessitating definitive surgical intervention. Immunohistochemistry (IHC) could not be performed to further characterize the tumor on the biopsy. The patient underwent a left modified radical mastectomy, with the resected specimen measuring 24 × 20 × 11 cm. The tumor, measuring 14 × 10 × 7 cm, occupied a substantial portion of the breast and was associated with overlying skin ulceration (Fig. 2 ). Microscopic evaluation confirmed a spindle cell tumor with infiltrative margins, pleomorphic hyperchromatic nuclei, high mitotic activity (11 per 10 HPF; 6/mm²), and necrosis (Fig. 3 a-d). The tumor invaded the dermis but showed no vascular or lymphatic invasion, and all nine dissected lymph nodes were uninvolved. Immunohistochemistry showed positivity for SMA (smooth muscle actin) and desmin, confirming a smooth muscle origin, while pancytokeratin, p63, BCL2, S100, and CD34 were negative, ruling out epithelial and other soft tissue tumors (Fig. 4 a, b). The Ki-67 index was 15% (Fig. 4 c). Based on histopathological and immunohistochemical findings, the tumor was diagnosed as primary leiomyosarcoma of the breast, grade 2, according to the French Federation of Cancer Centres Sarcoma Group grading system. Given the high-grade nature, large tumor size (> 10 cm, pT3), and moderate proliferative activity, a multimodal treatment approach was planned. Adjuvant radiation therapy (60 Gy in 30 fractions) was administered to the chest wall, given the close surgical margins (0.3 cm), and to reduce the risk of local recurrence. The patient has been planned to undergo six cycles of AIM chemotherapy (doxorubicin + ifosfamide + mesna) after radiation therapy, out of which 1st cycle has been completed. Patient has tolerated radiotherapy well and chemotherapy well so far. Supportive care measures include mesna for uroprotection during ifosfamide therapy and G-CSF (Pegfilgrastim/ Filgrastim) support to prevent neutropenia. Discussion Primary sarcomas are rare tumors that may originate in any organ; however, their development in the breast is exceptionally uncommon, comprising nearly 1% of breast malignancies and fewer than 5% of all soft tissue sarcomas (Alimi et al. 2025 ). The clinical presentation is often non-specific, with most patients presenting with an enlarging, painless breast mass, as seen in our case. Tumour sizes have been reported to range from 0.3 to 16 cm, with an average size of 4.7 cm (Masadah et al. 2023 ). While predominantly affecting women, a few rare cases have been reported in men as well (Cheikh et al. 2021). The tumour origin is believed to be from smooth muscle cells of the lactiferous ducts, blood vessels, or erector pili muscles in the periareolar region (Sethi et al. 2024 ). Secondary cases may arise after prior radiation therapy or in the setting of chronic lymphedema (Hayashi et al. 2015). Imaging modalities such as mammography and ultrasound generally lack specificity and often result in misclassification as fibroadenoma or phyllodes tumour, further complicating diagnosis (Rafey et al. 2025 ). The initial cytological evaluation in our case was performed using fine-needle aspiration cytology (FNAC), which revealed spindle-shaped cells arranged in fascicles with blunt-ended nuclei. However, FNAC often presents significant diagnostic limitations in such cases due to cytomorphologic overlap with other spindle cell lesions of the breast (Jun Wei et al. 2003). Under the Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology, spindle cell tumours may be classified as "Suspicious for Malignancy" or "Malignant", depending on the degree of cellular atypia, presence of mitosis, and necrosis (Yu et al. 2023). The absence of epithelial elements in the smears and the presence of pleomorphic spindled cells in clusters may lean toward a "Malignant" category. According to the WHO Reporting System for Soft Tissue Cytopathology, such a lesion may be placed under "Soft tissue neoplasm of uncertain malignant potential (STNUMP)" if only mildly pleomorphic spindle cells are observed. However, if significant nuclear atypia is present, the tumour would fall under "Suspicious for Malignancy." If mitotic figures and/or necrosis are evident, though often difficult to appreciate cytologically, it would be classified as "Malignant"(Bui 2025). Several spindle cell lesions must be considered in the cytological differential diagnosis. Metaplastic carcinoma may mimic sarcomas cytologically, demonstrating pleomorphic spindle cells with vacuolated cytoplasm and occasional epithelial clusters. Malignant phyllodes tumour, a relatively more common entity in this context, should be carefully ruled out. It typically exhibits atypical spindled nuclei within stromal fragments and numerous naked nuclei in a background of hypercellularity. In contrast, leiomyosarcoma (LMS) is more likely to show cohesive clusters and fascicles of pleomorphic spindled cells. Undifferentiated pleomorphic sarcoma shows marked pleomorphism and bizarre multinucleated giant cells (Rakha et al. 2022 ). In contrast, benign spindle cell lesions like fibromatosis show bland, uniform spindle cells lacking significant pleomorphism or mitotic activity, making their identification crucial to avoid overtreatment. Thus, FNAC alone is often inadequate for a definitive diagnosis, necessitating histologic confirmation via core needle or excisional biopsy, along with immunohistochemistry (Gupta et al. 2000 ). A core needle biopsy was subsequently performed in this case. Although it offers architectural clues superior to FNAC, diagnostic limitations persist—especially due to the absence of ductal epithelial elements in primary sarcomas like leiomyosarcoma. This can lead to diagnostic uncertainty and difficulty in distinguishing sarcomas from metaplastic carcinoma, which often contains an epithelial component. Consequently, correlation with definitive excisional histopathology and immunohistochemistry (IHC) is essential (Sandhya et al. 2010). On histopathologic examination of the surgical specimen, classic features of leiomyosarcoma were noted—intersecting fascicles of spindle cells with eosinophilic cytoplasm, elongated, blunt-ended nuclei, moderate to severe nuclear atypia, and brisk mitotic activity. These features are consistent with prior literature descriptions of breast leiomyosarcoma (Tharwani et al. 2024 ). Importantly, no lymph node involvement was seen, aligning with the general observation that nodal metastasis is uncommon in breast leiomyosarcoma (Masadah et al. 2023 ). Given the overlapping histologic appearances, several benign and malignant spindle cell tumours of the breast must be ruled out. Fibromatosis typically exhibits uniform, bland spindle cells with positivity for β-catenin and SMA, but is negative for desmin and S100 (Ni and Tse 2023 ). Nodular fasciitis presents with plump spindle cells in a myxoid stroma, showing SMA positivity but negative β-catenin and S100 expression. Myofibroblastoma appears well-circumscribed and is immunoreactive for desmin, CD34, and Estrogen Receptor (ER) / Progesterone Receptor (PR) (Hou and Li 2021 ). Among malignant differentials, metaplastic carcinoma is particularly challenging as it may show a monophasic spindle cell pattern that histologically mimics sarcomas. It is usually positive for cytokeratin and p63 and lacks S100 expression. Malignant phyllodes tumours demonstrate stromal overgrowth with CD34 and SMA positivity but are cytokeratin negative. MPNST (Malignant Peripheral Nerve Sheath Tumour) shows wavy spindle cells with frequent mitoses and is positive for S100 and SOX10 (Rakha et al. 2022 ). Additionally, NTRK fusion-positive sarcomas exhibit minimal pleomorphism, fascicular architecture, and require molecular confirmation due to potential therapeutic implications (Schwartz et al. 2025 ). In the present case, IHC played a decisive role in confirming the diagnosis. The tumour showed diffuse immunoreactivity for smooth muscle actin (SMA), desmin, and caldesmon, confirming smooth muscle lineage (Samenova et al. 2023 ). Negative staining for pan-cytokeratin effectively ruled out metaplastic carcinoma, while lack of CD34, S100, SOX10, and β-catenin expression helped exclude phyllodes tumour, MPNST, and fibromatosis, respectively (Rakha et al. 2022 ). Surgical excision with clear margins remains the mainstay of treatment. A simple mastectomy was performed in our case, which is the most frequently adopted approach. Wide local excision may be feasible for smaller tumours. Achieving negative surgical margins is critical, as it significantly reduces local recurrence rates (Alimi et al. 2025 ). The roles of chemotherapy and radiotherapy are not well established due to limited evidence. However, anthracycline-based chemotherapy is often employed in high-risk or metastatic cases, while radiation therapy may be considered in cases with positive margins or larger tumour (Samenova et al. 2023 ). The prognosis for breast leiomyosarcoma is generally favourable compared to other soft tissue sarcomas. However, hematogenous metastasis occurs in approximately 25% of cases, most commonly affecting the lungs, liver, and bones. Metastases can develop years after the initial treatment, emphasising the need for long-term surveillance (Masadah et al. 2023 ). Given its rarity, current treatment protocols are largely extrapolated from soft tissue sarcoma guidelines, underscoring the need for more comprehensive studies and case accumulation to guide standardized management (Alimi et al. 2025 ). Conclusions This case highlights that primary leiomyosarcoma of the breast is a rare malignancy with significant challenges in diagnosis and treatment. Accurate diagnosis requires a detailed pathological evaluation, as conventional imaging and cytology may be inconclusive. Histopathology and immunohistochemistry play a crucial role in distinguishing this tumour from other spindle cell lesions. The case emphasizes the importance of clinical awareness and multidisciplinary collaboration in managing rare breast tumours. Since there are no standardized treatment guidelines, management is often adapted from soft tissue sarcoma protocols. While surgical removal with clear margins remains the primary treatment, the role of chemotherapy and radiation therapy is still uncertain and requires further study. Given the risk of recurrence and metastasis, long-term follow-up is essential for optimal patient care. Abbreviations AIM – Doxorubicin + Ifosfamide + Mesna (chemotherapy regimen) BI-RADS – Breast Imaging Reporting and Data System CD – Cluster of Differentiation ER – Estrogen Receptor FDG – Fluorodeoxyglucose FNAC – Fine-Needle Aspiration Cytology G-CSF – Granulocyte Colony-Stimulating Factor Gy – Gray (unit of radiation dose) HPF – High-Power Field IHC – Immunohistochemistry LMS – Leiomyosarcoma MRM – Modified Radical Mastectomy MPNST – Malignant Peripheral Nerve Sheath Tumor NTRK – Neurotrophic Tyrosine Receptor Kinase PET-CT – Positron Emission Tomography–Computed Tomography PR – Progesterone Receptor SMA – Smooth Muscle Actin SOX10 – SRY-related HMG-box gene 10 STNUMP – Soft Tissue Neoplasm of Uncertain Malignant Potential WHO – World Health Organization Declarations Ethics approval and consent to participate Informed consent for publication (including images) was obtained from the patient. Consent for publication Informed consent was obtained from the patient to publish this case report and accompanying images. Availability of data and materials No datasets were generated or analyzed during the current study. Competing interests The authors declare that they have no competing interests. Funding No external funding was received for this study. Authors' contributions AP and AR contributed to manuscript preparation and histopathological diagnosis. IP assisted in histopathological diagnosis. KR and AM were involved in surgical management and provided clinical images. CR contributed radiation oncology expertise. All authors participated in manuscript drafting and revision, and all have read and approved the final manuscript. Acknowledgements The authors acknowledge the Departments of Surgery and Radiation Oncology for their contributions to clinical images and treatment. References Ahuja M, Mallya V, Mandal S, Tomar R, Aggarwal R, Khurana N, et al. 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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-7569958","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":524333456,"identity":"4ec7d71e-d004-4733-9f3e-f8240893f43d","order_by":0,"name":"Ashwini Pitambra","email":"","orcid":"","institution":"All India Institute of Medical Sciences Bibinagar","correspondingAuthor":false,"prefix":"","firstName":"Ashwini","middleName":"","lastName":"Pitambra","suffix":""},{"id":524333458,"identity":"2c58e8c5-6040-4ddc-bde0-4978848bedb0","order_by":1,"name":"Ashutosh 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12:11:23","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":56156,"visible":true,"origin":"","legend":"","description":"","filename":"e367dc96dc0442f6a16cad1a378f926e1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/ba033cc24cafeca21b0041c4.xml"},{"id":92860702,"identity":"142127e0-aadd-4545-a0d8-104c170fb290","added_by":"auto","created_at":"2025-10-06 12:11:23","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65113,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/be11665efadbb42c45f0c302.html"},{"id":92860691,"identity":"0de8a6ec-63c0-4f5e-a817-db81c4ad542d","added_by":"auto","created_at":"2025-10-06 12:11:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20879797,"visible":true,"origin":"","legend":"\u003cp\u003eClinical image showing a 15 × 13 cm left breast mass in the upper outer quadrant with overlying erythema and a pre-existing surgical scar.\u003c/p\u003e","description":"","filename":"Fig1tiff.png","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/1a931d9b09eb0fc0d3610d43.png"},{"id":92860698,"identity":"7418b709-092a-47fb-a9f7-2e9386c9baba","added_by":"auto","created_at":"2025-10-06 12:11:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21543979,"visible":true,"origin":"","legend":"\u003cp\u003eGross cut surface showing a firm, grey-white tumor with a whorled appearance.\u003c/p\u003e","description":"","filename":"Fig2tiff.png","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/14607b1e7532e03231ec4abe.png"},{"id":92860695,"identity":"a9c22ee8-5e44-47db-9ba2-353b304e2384","added_by":"auto","created_at":"2025-10-06 12:11:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":20392888,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological features of primary breast leiomyosarcoma. \u003cstrong\u003ea\u003c/strong\u003eInterlacing fascicles of spindle cells (hematoxylin and eosin [H\u0026amp;E], ×40). \u003cstrong\u003eb\u003c/strong\u003e Pleomorphic spindle cells with hyperchromatic nuclei and nuclear atypia (H\u0026amp;E, ×400). \u003cstrong\u003ec\u003c/strong\u003e Atypical mitotic figure (arrow) (H\u0026amp;E, ×400). \u003cstrong\u003ed\u003c/strong\u003e Area of tumor necrosis with adjacent viable pleomorphic spindle cells (H\u0026amp;E, ×400).\u003c/p\u003e","description":"","filename":"Fig3tiff.png","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/63358460b3e09861226bc3d5.png"},{"id":92860712,"identity":"98fffdfd-73a6-4584-aa35-64310f6c78bd","added_by":"auto","created_at":"2025-10-06 12:11:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":19183369,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical staining of the tumor. \u003cstrong\u003ea\u003c/strong\u003e Desmin-positive tumor cells (×400). \u003cstrong\u003eb\u003c/strong\u003e Smooth muscle actin (SMA)-positive tumor cells (×400). \u003cstrong\u003ec\u003c/strong\u003eKi-67 labeling index of 15% in tumor cells (×400).\u003c/p\u003e","description":"","filename":"Fig4tiff.png","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/0ca2aaea849fff73de7a28b4.png"},{"id":94505828,"identity":"33820c9c-c5f8-4417-b5a1-2e44f0f2aafa","added_by":"auto","created_at":"2025-10-28 16:23:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":75930273,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7569958/v1/ad37a7e9-cabd-4665-87ba-df16201b2728.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Primary Breast Leiomyosarcoma Presenting as Recurrent Spindle Cell Lesions: Diagnostic Pitfalls, Immunohistochemical Insights, and Multidisciplinary Management of a Rare Tumor","fulltext":[{"header":"Background","content":"\u003cp\u003ePrimary leiomyosarcoma of the breast is a rare malignant neoplasm, representing less than 1% of breast tumors and posing significant diagnostic and therapeutic challenges due to limited data and the absence of standardized guidelines (Alimi et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The tumor arises from smooth muscle or mesenchymal stem cells, differentiating into smooth muscle tissue (Samenova et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Clinically, patients often present with a rapidly growing, painless breast mass, and the diagnosis is frequently made incidentally during excisional histopathology (Ahuja et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eImmunohistochemical profiling is essential in differentiating leiomyosarcoma from other spindle-cell lesions (Ni and Tse \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Given the unpredictable biological behavior and lack of consensus protocols, treatment is based on extrapolation from soft tissue sarcoma guidelines (Ilyas et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Prognosis may be relatively favorable compared to other subtypes, yet metastasis remains a risk (Singh et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 44-year-old woman presented with an enlarging, firm lump in the upper outer quadrant of her left breast, measuring 15 \u0026times; 15 cm, with overlying erythema and a previous surgical scar (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). She had a history of recurrent breast lesions, including prior diagnoses of leiomyoma and desmoid-type fibromatosis, both diagnosed at an outside facility and managed with lumpectomies. Recent fine-needle aspiration cytology (FNAC), performed elsewhere, suggested proliferative breast disease with atypia, prompting further evaluation.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eUltrasound suggested a BI-RADS 4B lesion, and PET-CT imaging showed a 14.8 cm heterogeneously enhancing tumor with lobulated margins and central necrosis. The tumor was closely abutting the skin but did not invade the pectoral muscle or adjacent fat planes. Axillary lymph nodes showed no abnormal FDG (fluorodeoxyglucose) uptake and had a preserved fatty hilum, suggesting the absence of metastatic involvement.\u003c/p\u003e\u003cp\u003eA core biopsy confirmed a spindle cell tumor composed of elongated cells arranged in fascicles, showing moderate pleomorphism and 8\u0026ndash;10 mitotic figures per 10 high-power fields (HPF). The differential diagnoses included borderline or malignant phyllodes tumor, metaplastic carcinoma, and other mesenchymal tumors, necessitating definitive surgical intervention. Immunohistochemistry (IHC) could not be performed to further characterize the tumor on the biopsy.\u003c/p\u003e\u003cp\u003eThe patient underwent a left modified radical mastectomy, with the resected specimen measuring 24 \u0026times; 20 \u0026times; 11 cm. The tumor, measuring 14 \u0026times; 10 \u0026times; 7 cm, occupied a substantial portion of the breast and was associated with overlying skin ulceration (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Microscopic evaluation confirmed a spindle cell tumor with infiltrative margins, pleomorphic hyperchromatic nuclei, high mitotic activity (11 per 10 HPF; 6/mm\u0026sup2;), and necrosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-d). The tumor invaded the dermis but showed no vascular or lymphatic invasion, and all nine dissected lymph nodes were uninvolved.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eImmunohistochemistry showed positivity for SMA (smooth muscle actin) and desmin, confirming a smooth muscle origin, while pancytokeratin, p63, BCL2, S100, and CD34 were negative, ruling out epithelial and other soft tissue tumors (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea, b). The Ki-67 index was 15% (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec). Based on histopathological and immunohistochemical findings, the tumor was diagnosed as primary leiomyosarcoma of the breast, grade 2, according to the French Federation of Cancer Centres Sarcoma Group grading system.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eGiven the high-grade nature, large tumor size (\u0026gt;\u0026thinsp;10 cm, pT3), and moderate proliferative activity, a multimodal treatment approach was planned. Adjuvant radiation therapy (60 Gy in 30 fractions) was administered to the chest wall, given the close surgical margins (0.3 cm), and to reduce the risk of local recurrence. The patient has been planned to undergo six cycles of AIM chemotherapy (doxorubicin\u0026thinsp;+\u0026thinsp;ifosfamide\u0026thinsp;+\u0026thinsp;mesna) after radiation therapy, out of which 1st cycle has been completed. Patient has tolerated radiotherapy well and chemotherapy well so far. Supportive care measures include mesna for uroprotection during ifosfamide therapy and G-CSF (Pegfilgrastim/ Filgrastim) support to prevent neutropenia.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary sarcomas are rare tumors that may originate in any organ; however, their development in the breast is exceptionally uncommon, comprising nearly 1% of breast malignancies and fewer than 5% of all soft tissue sarcomas (Alimi et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The clinical presentation is often non-specific, with most patients presenting with an enlarging, painless breast mass, as seen in our case. Tumour sizes have been reported to range from 0.3 to 16 cm, with an average size of 4.7 cm (Masadah et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). While predominantly affecting women, a few rare cases have been reported in men as well (Cheikh et al. 2021).\u003c/p\u003e\u003cp\u003eThe tumour origin is believed to be from smooth muscle cells of the lactiferous ducts, blood vessels, or erector pili muscles in the periareolar region (Sethi et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Secondary cases may arise after prior radiation therapy or in the setting of chronic lymphedema (Hayashi et al. 2015). Imaging modalities such as mammography and ultrasound generally lack specificity and often result in misclassification as fibroadenoma or phyllodes tumour, further complicating diagnosis (Rafey et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe initial cytological evaluation in our case was performed using fine-needle aspiration cytology (FNAC), which revealed spindle-shaped cells arranged in fascicles with blunt-ended nuclei. However, FNAC often presents significant diagnostic limitations in such cases due to cytomorphologic overlap with other spindle cell lesions of the breast (Jun Wei et al. 2003).\u003c/p\u003e\u003cp\u003eUnder the Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology, spindle cell tumours may be classified as \"Suspicious for Malignancy\" or \"Malignant\", depending on the degree of cellular atypia, presence of mitosis, and necrosis (Yu et al. 2023). The absence of epithelial elements in the smears and the presence of pleomorphic spindled cells in clusters may lean toward a \"Malignant\" category.\u003c/p\u003e\u003cp\u003eAccording to the WHO Reporting System for Soft Tissue Cytopathology, such a lesion may be placed under \"Soft tissue neoplasm of uncertain malignant potential (STNUMP)\" if only mildly pleomorphic spindle cells are observed. However, if significant nuclear atypia is present, the tumour would fall under \"Suspicious for Malignancy.\" If mitotic figures and/or necrosis are evident, though often difficult to appreciate cytologically, it would be classified as \"Malignant\"(Bui 2025).\u003c/p\u003e\u003cp\u003eSeveral spindle cell lesions must be considered in the cytological differential diagnosis. Metaplastic carcinoma may mimic sarcomas cytologically, demonstrating pleomorphic spindle cells with vacuolated cytoplasm and occasional epithelial clusters. Malignant phyllodes tumour, a relatively more common entity in this context, should be carefully ruled out. It typically exhibits atypical spindled nuclei within stromal fragments and numerous naked nuclei in a background of hypercellularity. In contrast, leiomyosarcoma (LMS) is more likely to show cohesive clusters and fascicles of pleomorphic spindled cells. Undifferentiated pleomorphic sarcoma shows marked pleomorphism and bizarre multinucleated giant cells (Rakha et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn contrast, benign spindle cell lesions like fibromatosis show bland, uniform spindle cells lacking significant pleomorphism or mitotic activity, making their identification crucial to avoid overtreatment. Thus, FNAC alone is often inadequate for a definitive diagnosis, necessitating histologic confirmation via core needle or excisional biopsy, along with immunohistochemistry (Gupta et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2000\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA core needle biopsy was subsequently performed in this case. Although it offers architectural clues superior to FNAC, diagnostic limitations persist\u0026mdash;especially due to the absence of ductal epithelial elements in primary sarcomas like leiomyosarcoma. This can lead to diagnostic uncertainty and difficulty in distinguishing sarcomas from metaplastic carcinoma, which often contains an epithelial component. Consequently, correlation with definitive excisional histopathology and immunohistochemistry (IHC) is essential (Sandhya et al. 2010).\u003c/p\u003e\u003cp\u003eOn histopathologic examination of the surgical specimen, classic features of leiomyosarcoma were noted\u0026mdash;intersecting fascicles of spindle cells with eosinophilic cytoplasm, elongated, blunt-ended nuclei, moderate to severe nuclear atypia, and brisk mitotic activity. These features are consistent with prior literature descriptions of breast leiomyosarcoma (Tharwani et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Importantly, no lymph node involvement was seen, aligning with the general observation that nodal metastasis is uncommon in breast leiomyosarcoma (Masadah et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eGiven the overlapping histologic appearances, several benign and malignant spindle cell tumours of the breast must be ruled out. Fibromatosis typically exhibits uniform, bland spindle cells with positivity for β-catenin and SMA, but is negative for desmin and S100 (Ni and Tse \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Nodular fasciitis presents with plump spindle cells in a myxoid stroma, showing SMA positivity but negative β-catenin and S100 expression. Myofibroblastoma appears well-circumscribed and is immunoreactive for desmin, CD34, and Estrogen Receptor (ER) / Progesterone Receptor (PR) (Hou and Li \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAmong malignant differentials, metaplastic carcinoma is particularly challenging as it may show a monophasic spindle cell pattern that histologically mimics sarcomas. It is usually positive for cytokeratin and p63 and lacks S100 expression. Malignant phyllodes tumours demonstrate stromal overgrowth with CD34 and SMA positivity but are cytokeratin negative. MPNST (Malignant Peripheral Nerve Sheath Tumour) shows wavy spindle cells with frequent mitoses and is positive for S100 and SOX10 (Rakha et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Additionally, NTRK fusion-positive sarcomas exhibit minimal pleomorphism, fascicular architecture, and require molecular confirmation due to potential therapeutic implications (Schwartz et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the present case, IHC played a decisive role in confirming the diagnosis. The tumour showed diffuse immunoreactivity for smooth muscle actin (SMA), desmin, and caldesmon, confirming smooth muscle lineage (Samenova et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Negative staining for pan-cytokeratin effectively ruled out metaplastic carcinoma, while lack of CD34, S100, SOX10, and β-catenin expression helped exclude phyllodes tumour, MPNST, and fibromatosis, respectively (Rakha et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSurgical excision with clear margins remains the mainstay of treatment. A simple mastectomy was performed in our case, which is the most frequently adopted approach. Wide local excision may be feasible for smaller tumours. Achieving negative surgical margins is critical, as it significantly reduces local recurrence rates (Alimi et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The roles of chemotherapy and radiotherapy are not well established due to limited evidence. However, anthracycline-based chemotherapy is often employed in high-risk or metastatic cases, while radiation therapy may be considered in cases with positive margins or larger tumour (Samenova et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe prognosis for breast leiomyosarcoma is generally favourable compared to other soft tissue sarcomas. However, hematogenous metastasis occurs in approximately 25% of cases, most commonly affecting the lungs, liver, and bones. Metastases can develop years after the initial treatment, emphasising the need for long-term surveillance (Masadah et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Given its rarity, current treatment protocols are largely extrapolated from soft tissue sarcoma guidelines, underscoring the need for more comprehensive studies and case accumulation to guide standardized management (Alimi et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case highlights that primary leiomyosarcoma of the breast is a rare malignancy with significant challenges in diagnosis and treatment. Accurate diagnosis requires a detailed pathological evaluation, as conventional imaging and cytology may be inconclusive. Histopathology and immunohistochemistry play a crucial role in distinguishing this tumour from other spindle cell lesions.\u003c/p\u003e\u003cp\u003eThe case emphasizes the importance of clinical awareness and multidisciplinary collaboration in managing rare breast tumours. Since there are no standardized treatment guidelines, management is often adapted from soft tissue sarcoma protocols. While surgical removal with clear margins remains the primary treatment, the role of chemotherapy and radiation therapy is still uncertain and requires further study. Given the risk of recurrence and metastasis, long-term follow-up is essential for optimal patient care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eAIM\u003c/strong\u003e \u0026ndash; Doxorubicin + Ifosfamide + Mesna (chemotherapy regimen)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBI-RADS\u003c/strong\u003e \u0026ndash; Breast Imaging Reporting and Data System\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCD\u003c/strong\u003e \u0026ndash; Cluster of Differentiation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eER\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; Estrogen Receptor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFDG\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; Fluorodeoxyglucose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFNAC\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; Fine-Needle Aspiration Cytology\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eG-CSF\u003c/strong\u003e \u0026ndash; Granulocyte Colony-Stimulating Factor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGy\u003c/strong\u003e \u0026ndash; Gray (unit of radiation dose)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPF\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; High-Power Field\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIHC\u003c/strong\u003e \u0026ndash; Immunohistochemistry\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLMS\u003c/strong\u003e \u0026ndash; Leiomyosarcoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRM\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; Modified Radical Mastectomy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMPNST\u003c/strong\u003e \u0026ndash; Malignant Peripheral Nerve Sheath Tumor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNTRK\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; Neurotrophic Tyrosine Receptor Kinase\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePET-CT\u003c/strong\u003e \u0026ndash; Positron Emission Tomography\u0026ndash;Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePR\u003c/strong\u003e \u0026ndash; Progesterone Receptor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSMA\u003c/strong\u003e \u0026ndash; Smooth Muscle Actin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSOX10\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; SRY-related HMG-box gene 10\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTNUMP\u003c/strong\u003e \u0026ndash; Soft Tissue Neoplasm of Uncertain Malignant Potential\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWHO\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026ndash; World Health Organization\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent for publication (including images) was obtained from the patient.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the patient to publish this case report and accompanying images.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analyzed during the current study.\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\u003eNo external funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAP and AR contributed to manuscript preparation and histopathological diagnosis. IP assisted in histopathological diagnosis. KR and AM were involved in surgical management and provided clinical images. CR contributed radiation oncology expertise. All authors participated in manuscript drafting and revision, and all have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the Departments of Surgery and Radiation Oncology for their contributions to clinical images and treatment.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAhuja M, Mallya V, Mandal S, Tomar R, Aggarwal R, Khurana N, et al. Primary breast sarcoma: A case series. Indian Journal of Pathology and Microbiology. 2022 Jan;65(1):152\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eAlimi A, Abbassi H, Abid S, Dinari A, Khlifi A, Hidar S, et al. Leiomyosarcoma of the Breast: Case Report and Review of the Literature. ejbh [Internet]. 2025 May 29 [cited 2025 July 25]; Available from: https://www.eurjbreasthealth.com/articles/leiomyosarcoma-of-the-breast-case-report-and-review-of-the-literature/doi/ejbh.galenos.2025.2024-10-8\u003c/li\u003e\n\u003cli\u003eBui MM. World Health Organization Reporting System for Soft Tissue Cytopathology: A Concise Review with a Practical Diagnostic Approach. J Clin Transl Pathol. 2025 June 24;000(000):000\u0026ndash;000. \u003c/li\u003e\n\u003cli\u003eCheikh TE, Hamza K, Hicham B, Fatiha EM, Hajar EO, Mustapha B, et al. Leiomyosarcoma of the male breast: Case report. Annals of Medicine \u0026amp; Surgery [Internet]. 2021 July [cited 2025 June 17];67. Available from: https://journals.lww.com/10.1016/j.amsu.2021.102495\u003c/li\u003e\n\u003cli\u003eGupta RK, Kenwright D, Naran S, Lallu S, Fauck R. Fine Needle Aspiration Cytodiagnosis of Leiomyosarcoma of the Breast. Acta Cytologica. 2000;44(6):1101\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eHayashi S, Kitada M, Matsuda Y, Ishibashi K, Takahashi N. Leiomyosarcoma arising in irradiated region after breast-conserving surgery: a case report. surg case rep [Internet]. 2015 Dec [cited 2025 July 26];1(1). Available from: http://www.surgicalcasereports.com/content/1/1/76\u003c/li\u003e\n\u003cli\u003eHou Y, Li Z. Spindle cell lesions of the breast. Human Pathology Reports. 2021 Nov;26:300565. \u003c/li\u003e\n\u003cli\u003eIlyas MIM, Nazir S, Xiao PQ. Breast Leiomyosarcoma: A Systematic Review and Recommendations for Management. International Surgery. 2019 May 1;104(5\u0026ndash;6):196\u0026ndash;202. \u003c/li\u003e\n\u003cli\u003eJun Wei X, Hiotis K, Garcia R, Hummel Levine P. Leiomyosarcoma of the breast: A difficult diagnosis on fine‐needle aspiration biopsy. Diagnostic Cytopathology. 2003 Sept;29(3):172\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eMasadah R, Anwar F, Nelwan BJ, Faruk M. Primary leiomyosarcoma of the breast: A case report and literature review. International Journal of Surgery Case Reports. 2023 May;106:108290. \u003c/li\u003e\n\u003cli\u003eNi Y, Tse GM. Spindle Cell Lesions of the Breast: A Diagnostic Algorithm. Archives of Pathology \u0026amp; Laboratory Medicine. 2023 Jan 1;147(1):30\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eRafey M, Khan M, Siddiqui B, Hassan M, Faridi S. A rare case report of primary breast leiomyosarcoma presenting clinicoradiologically as phyllodes tumour. IJPO. 2025 Mar 28;12(1):86\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eRakha EA, Brogi E, Castellano I, Quinn C. Spindle cell lesions of the breast: a diagnostic approach. Virchows Arch. 2022 Jan;480(1):127\u0026ndash;45. \u003c/li\u003e\n\u003cli\u003eSamenova D, Midlenko A, Khamzina Y, Kaldybayev M, Khamzina S. Primary Leiomyosarcoma of the Breast: A Successful Surgical Treatment in a 45-Year-Old Woman. Am J Case Rep. 2023 Aug 21;24:e939437. \u003c/li\u003e\n\u003cli\u003eSandhya B, Babu V, Parthasarathy G, Kate V, Ananthakrishnan N, Krishnan R. Primary leiomyosarcoma of the breast: A case report and review of literature. Indian J Surg. 2010 July;72(S1):286\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eSchwartz CJ, Ye J, Devine WP, Chen Y. NTRK ‐fusion spindle cell tumour in the breast: expanding the differential of challenging spindle cell lesions on core biopsy. Histopathology. 2025 May;86(6):1018\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eSethi E, Misra S, Ahuja A. Primary leiomyosarcoma with osteosarcomatous differentiation of the breast. Autops Case Rep. 2024;14:e2024476. \u003c/li\u003e\n\u003cli\u003eSingh G, Sharma D, Goyal S. Primary Leiomyosarcoma of Breast Presenting with Metastasis: An Atypical Presentation with Dismal Prognosis. Indian J Med Paediatr Oncol. 2017;38(4):535\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eTharwani ZH, Habib Z, Ahmed Y, Ishrat S, Nashwan AJ. A Rare Case of High-Grade Spindle Cell Sarcoma of the Breast: A Case Report. Case Rep Oncol. 2024;17(1):217\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eYu W, Gan Q, Gong Y. The Yokohama System for Reporting Breast Cytopathology. J Clin Transl Pathol. 2023 June 20;000(000):000\u0026ndash;000. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Primary breast leiomyosarcoma, spindle cell tumor, immunohistochemistry, diagnosis, rare breast tumor, multidisciplinary management","lastPublishedDoi":"10.21203/rs.3.rs-7569958/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7569958/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePrimary leiomyosarcoma of the breast is extremely rare, accounting for less than 1% of breast tumors. Diagnosis is often difficult because it can mimic other spindle cell lesions, and standard treatment guidelines are lacking. Reporting such cases helps improve the understanding and management of these uncommon tumors.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e\u003cp\u003eA 44-year-old woman presented with a rapidly growing, firm lump in her left breast. She had previous surgeries elsewhere with diagnoses of leiomyoma and desmoid-type fibromatosis. Imaging showed a large lobulated mass (14.8 cm) without lymph node involvement or distant metastasis. Core needle biopsy revealed a spindle cell tumor with moderate atypia and mitotic activity, but it was not definitive. Excisional histopathology demonstrated intersecting fascicles of pleomorphic spindle cells, necrosis, and dermal invasion. Immunohistochemistry confirmed smooth muscle origin (SMA and desmin positive), excluding epithelial, neural, and vascular tumors. The tumor was graded as Grade 2. The patient underwent a modified radical mastectomy followed by adjuvant radiotherapy and planned chemotherapy.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003ePrimary breast leiomyosarcoma is rare and can present with diagnostic challenges. Core biopsy and cytology alone may be misleading. Immunohistochemistry was essential to reach the correct diagnosis and to differentiate from other spindle cell tumors. Management requires a multidisciplinary approach, including surgery with clear margins and tailored adjuvant therapy. This case adds to the limited literature and offers lessons on diagnosis, management, and follow-up of rare spindle cell breast tumors.\u003c/p\u003e","manuscriptTitle":"Primary Breast Leiomyosarcoma Presenting as Recurrent Spindle Cell Lesions: Diagnostic Pitfalls, Immunohistochemical Insights, and Multidisciplinary Management of a Rare Tumor","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-06 12:11:17","doi":"10.21203/rs.3.rs-7569958/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"567ff522-017b-429e-b0be-0f03cfac8583","owner":[],"postedDate":"October 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T13:56:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-06 12:11:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7569958","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7569958","identity":"rs-7569958","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}