Apocrine Carcinoma of the Breast: A Case Report and Review of the Literature

Apocrine Carcinoma of the Breast: A Case Report and Review of the Literature | 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 Apocrine Carcinoma of the Breast: A Case Report and Review of the Literature Saow Renn Ding, Kelley Tu, Armand Asarian, Philip Xiao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7456105/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: Apocrine carcinoma of the breast is a rare and distinct subtype of invasive ductal carcinoma characterized histologically by large tumor cells with abundant eosinophilic granular cytoplasm and prominent nucleoli. Accurate diagnosis and immunohistochemical profiling are essential for distinguishing this entity from other breast cancer subtypes. Emerging evidence suggests a potential therapeutic role for androgen receptor (AR)-targeted treatments in managing this disease. Case Presentation: The patient was a 55-year-old woman with no significant past medical history who presented for a routine physical examination. A screening mammogram revealed a 1.2 × 0.8 × 0.6 cm superficial mass in the upper outer quadrant of the right breast, along with scattered coarse microcalcifications. A core needle biopsy was performed, and histopathological analysis confirmed the diagnosis of apocrine carcinoma of the breast, a rare subtype of invasive ductal carcinoma. Immunohistochemistry (IHC) demonstrated strong androgen receptor (AR) positivity and negativity for estrogen receptor (ER), progesterone receptor (PR), and HER2. The patient subsequently underwent surgical excision of the tumor. Postoperative recovery was uneventful, and the patient is currently under close clinical follow-up with consideration for AR-targeted therapy in the context of receptor status. Conclusions: Through a review of the current literature, we highlight the key histopathological, molecular, and clinical features of apocrine breast carcinoma. This case study underscores the importance of accurate diagnosis and comprehensive immunohistochemical analysis in guiding effective treatment strategies. The consistent expression of AR in these tumors supports further exploration of AR-targeted therapies as a promising treatment avenue. Apocrine Breast Carcinoma Androgen Receptors Figures Figure 1 Figure 2 Background Apocrine carcinoma of the breast is a rare and distinct histological subtype of invasive ductal carcinoma that accounts for less than 1% of all breast cancers. It is characterized by large tumor cells with abundant eosinophilic, granular cytoplasm; large round to oval nuclei, and prominent nucleoli. A hallmark of apocrine differentiation is the occurence of decapitation secretion, although this feature may not always be prominent. Histologically, apocrine carcinomas may exhibit solid, tubular, or papillary growth patterns and are often accompanied by a desmoplastic stromal response. High mitotic activity, nuclear atypia, areas of necrosis, and calcification can also be observed. Immunohistochemically, these tumors typically demonstrate strong diffuse androgen receptor (AR) positivity, as well as expression of gross cystic disease fluid protein-15 (GCDFP-15), supporting apocrine differentiation. These patients are usually negative for estrogen receptor (ER) and progesterone receptor (PR), while HER2 expression is variable and may influence treatment strategies. The diagnosis can be challenging due to morphological overlap with other rare neoplasms, such as oncocytic carcinomas (1), more common subtypes, such as invasive ductal carcinoma not otherwise specified (IDC-NOS) and invasive lobular carcinoma (ILC). Accurate diagnosis is essential for guiding treatment, particularly given the emerging role of AR-targeted therapies in AR-positive, triple-negative breast cancers. Here, we present a case of apocrine carcinoma of the breast confirmed by histopathology and immunohistochemical profiling to contribute to the limited literature and highlight the diagnostic and therapeutic considerations associated with this rare entity. Case Presentation A 55-year-old female patient presented to her primary care physician for a routine physical examination with no reported breast symptoms. As part of standard screening, a mammogram of the right breast was performed, revealing a superficial mass measuring 1.2 × 0.8 × 0.6 cm located in the upper outer quadrant. Additionally, scattered clustered coarse microcalcifications were noted throughout the right breast parenchyma, raising suspicion for a neoplastic process. The patient was referred for a core needle biopsy of the lesion for histopathological evaluation. The tissue specimens obtained consisted of multiple cores of pink-tan soft tissue measuring up to 1.4 × 0.2 cm in aggregate. Microscopic examination demonstrated sheets of infiltrating large tumor cells arranged in solid nests and clusters. The tumor cells exhibited abundant eosinophilic, finely granular cytoplasm, large centrally located nuclei, and prominent nucleoli—features characteristic of apocrine differentiation (Figure 1). No features suggestive of invasive lobular carcinoma or other specific subtypes were observed. Immunohistochemical analysis was performed to further classify the tumors. The neoplastic cells showed strong and diffuse nuclear positivity for the androgen receptor (AR) (Figure 2). In contrast, the tumor was negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, confirming a triple-negative but AR-positive immunoprofile—an immunophenotype frequently associated with apocrine carcinoma of the breast. Following diagnosis, the patient underwent surgical excision of the tumor. The surgical procedure was uneventful, and the patient recovered without complications. Final pathology confirmed clear surgical margins, and there was no evidence of lymphovascular invasion. Given the tumor's AR-positive status, the patient is currently under close clinical follow-up with consideration for adjuvant AR-targeted therapy, in accordance with emerging treatment approaches for AR-positive triple-negative breast cancer. Ongoing surveillance is planned as part of her long-term management strategy. Discussion Apocrine carcinoma of the breast presents with infiltrating tumor cells displaying apocrine morphology: abundant eosinophilic and granular cytoplasm, well-defined cell borders, enlarged round nuclei, and prominent nucleoli. This apocrine appearance is typically present in more than 90% of tumor cells. These tumors are usually high-grade or poorly differentiated and are frequently associated with ductal carcinoma in situ (DCIS), which exhibits apocrine features. Cytologically, they manifest as sheets, clusters, or single cells with abundant eosinophilic cytoplasm; large nucleoli showing variable pleomorphism; and often prominent multinucleation. Clinically, apocrine carcinomas may present as palpable masses or abnormalities detected via mammography. They are firm with distinct boundaries from surrounding tissue and often appear tan to yellowish due to their lipid content. Histologically, these tumors exhibit solid growth patterns with sheets of tumor cells, tubular formations resembling gland-like structures, or papillary configurations with fibrovascular cores. A desmoplastic stromal reaction characterized by dense fibrous tissue, sometimes accompanied by an inflammatory response with lymphocytes and plasma cells, is common. Molecularly, apocrine carcinoma of the breast is distinct from other types of breast cancer. It is characterized by androgen receptor (AR) positivity and typically lacks estrogen receptor (ER) and progesterone receptor (PR) expression. Some tumors demonstrate HER2 overexpression or amplification. Mutations in the PIK3CA gene that activate the PI3K/AKT pathway have been observed, suggesting the potential of treatment with PI3K pathway inhibitors. (2) Moreover, apocrine carcinomas may harbor TP53 mutations, which contibute to genomic instability, as well as BRCA1 or BRCA2 mutations, linking them to hereditary breast cancer syndromes and influencing treatment decisions such as those related to the use of PARP inhibitors. Changes in DNA methylation and histone modification patterns impact gene expression and tumor progression. (3) The presence of gross cystic disease fluid protein-15 (GCDFP-15) serves as a marker of apocrine differentiation while EGFR protein expression is common. (4) CK5/6 are variably expressed and can aid in the differential diagnosis of apocrine carcinoma from other triple-negative breast cancers. Elevated Ki-67 indices reflects aggressive tumor behavior. Activation of survival pathways, such as the PI3K/AKT and AR signaling pathways, contributes to the growth and maintenance of tumor cells. A hallmark of apocrine differentiation is the occurence of decapitation secretion, where the apical portion of the cell is pinched off into the glandular lumen, although this feature is not always prominent. In some cases, tumor cells may have a histiocytoid appearance with abundant foamy cytoplasm. (5) Apocrine carcinoma of the breast shares histological features with other breast cancers such as invasive ductal carcinoma, complicating differentiation based on morphology alone. While typically expressing AR and GCDFP-15, not all patients are positive for these markers. Moreover, the absence of ER and PR expression distinguishes apocrine carcinoma from other types of cancer, although this similarity with triple-negative breast cancer (TNBC) lacking ER, PR, and HER2 expression can lead to diagnostic complexity. Differential diagnosis between apocrine carcinoma and other breast tumors with similar morphologies is crucial for accurate classification and treatment (6). Invasive breast carcinoma with focal apocrine differentiation, is a type of invasive ductal carcinoma of no special type (NST) that shows some areas resembling apocrine sweat gland cells, with up to 60% of such carcinomas exhibiting these features. However, to be classified specifically as having apocrine differentiation, more than 90% of the tumors must exhibit this morphology. Invasive breast carcinoma, (NST) with an oncocytic carcinoma pattern, displays tumor cells with abundant eosinophilic and granular cytoplasm, well-defined borders, round centrally located nuclei and prominent nucleoli. These tumors are often estrogen receptor (ER)-positive and may show specific chromosomal gains at 11q13.1-q13.2 and 19p13. Granular cell tumors are rare and consist of large, round to polygonal cells with eosinophilic and granular cytoplasm and small central hyperchromatic nuclei; they typically test positive for S100 and CD68 markers but not for keratins. Apocrine ductal carcinoma in situ (DCIS) is a form of DCIS with apocrine cytology characterized by the presence of a myoepithelial cell layer around the ducts. Apocrine adenosis or atypical apocrine adenosis involves a lobulocentric proliferation of cells with apocrine features, often distorted by stromal fibrosis or sclerosis, also characterized by the presence of a myoepithelial cell layer. Surgery remains the primary treatment for early-stage apocrine carcinoma of the breast, and the choice between lumpectomy and mastectomy is based on the by tumor size, location, and patient preference. Successful tumor removal is correlated with improved outcomes depending on the disease stage. Following lumpectomy, radiation therapy is typically recommended to reduce the risk of local recurrence. Postmastectomy may also be considered for patients with high-risk features such as large tumor size or lymph node involvement, improving overall survival, particularly in early-stage disease. Chemotherapy plays a crucial role, particularly in treating higher-grade or advanced-stage apocrine carcinomas, utilizing standard regimens such as anthracyclines, taxanes, and platinum-based agents to reduce recurrence risk and increase survival, especially in node-positive or high-risk patients. (7) AR-targeted therapies, such as bicalutamide or enzalutamide, are promising options due to the high AR expression in apocrine carcinoma of the breast and are especially beneficial in AR-positive, ER-negative tumors. Hormonal therapies such as tamoxifen are generally ineffective due to the usual ER and PR negativity in these cancers. (8) Clinical guidelines should stress routine AR testing and the inclusion of GCDFP-15 in diagnostic panels to confirm apocrine differentiation. A multidisciplinary approach involving regular tumor board meetings is essential for tailored treatment planning and comprehensive management of apocrine carcinoma of the breast. Conclusion In conclusion, diagnosing apocrine carcinoma of the breast remains challenging due to its histological similarities with other breast cancers. Immunohistochemical markers like AR and GCDFP-15 are crucial for accurate identification. Prognosis and treatment decisions are significantly influenced by hormone receptor status (AR positivity, ER/PR negativity) and HER2 status. Current treatment strategies include surgery, radiation, chemotherapy, and targeted therapies, particularly AR inhibitors and HER2-targeted agents, which have shown promise in improving outcomes for specific molecular subtypes. Comprehensive immunohistochemical profiling and multidisciplinary team involvement are essential for managing this unique breast cancer subtype effectively. Ongoing research focuses on novel therapies such as AR inhibitors and immunotherapies, aiming to further optimize treatment approaches. Future studies should prioritize clinical trials to explore new therapeutic targets and refine treatment protocols, ultimately aiming to enhance patient outcomes in apocrine carcinoma of the breast. Declarations Written informed consent for participation and publication was obtained from the patient. Ethics declaration: Not applicable Consent for publication: Not applicable Availability of data and Materials Availability: Not applicable Competing interests: Not applicable Funding: No funding Author contributions: S.D, P.X and K.T. wrote the main manuscript text. P.X. prepared Figures 1-2. All the authors reviewed the manuscript. Acknowledgment: Not applicable References 1. Semir Vranic 1 , Zoran Gatalica(2021) An Update on the Molecular and Clinical Characteristics of Apocrine Carcinoma of the Breasthttps://doi.org/10.1016/j.clbc.2021.12.009 2. Semir Vranic, Fernando Schmitt, Anna Sapino, Jose Luis Costa, Sandeep Reddy, Michael Castro and Zoran Gatalica (2013) Apocrine carcinoma of the breast: a comprehensive review https://doi.org/10.14670/hh-28.1393 3. Jing Wang 1 , Yan Peng 2 , Hongxia Sun 3 , Phyu P Aung 1 , Erika Resetkova 1 , Clinton Yam 4 , Aysegul A Sahin 1 , Lei Huo 1 , Qingqing Ding 1 (2024) TRPS1 and GATA3 Expression in Invasive Breast Carcinoma With Apocrine Differentiation https://doi.org/10.5858/arpa.2022-0289-OA 4. Sawsan Ismail, 1,2 Haidara Kherbek, 3 Jana Skef, 3 Nadim Zahlouk, 4 Rafik Abdulal, 5 and Zuheir Alshehabi(2021) Triple-negative apocrine carcinoma as a rare cause of a breast lump in a Syrian female: a case report and review of the literature https://doi.org/10.1186%2Fs12905-021-01539-3 5. S Shimizu 1 , H Kitamura, T Ito, T Nakamura, J Fujisawa, H Matsukawa (1998) Histiocytoid breast carcinoma: histological, immunohistochemical, ultrastructural, cytological and clinicopathological studies https://doi.org/10.1111/j.1440-1827.1998.tb03948.x 6. Lawrence Hsu Lin 1 , Ivy Tran 1 , Yiying Yang 1 , Guomiao Shen 1 , Pabel Miah 2 , Paolo Cotzia 1 , Daniel Roses 2 , Freya Schnabel 2 , Farbod Darvishian 1 , Matija Snuderl 3 (2023) DNA Methylation Identifies Epigenetic Subtypes of Triple-Negative Breast Cancers With Distinct Clinicopathologic and Molecular Featureshttps://doi.org/10.1016/j.modpat.2023.100306 7. Semir Vranic, 1,2,* Rebecca Feldman, 3 and Zoran Gatalica 4 (2017) Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers https://doi.org/10.17305%2Fbjbms.2016.1811 8. Semir Vranic4 Faruk Skenderi1 · Mohamad Alhoda Mohamad Alahmad2 · Emin Tahirovic3 · Yaman M. Alahmad4,5 · Zoran Gatalica6 (2022) HER2‑positive apocrine carcinoma of the breast: a population‑based analysis of treatment and outcome https://doi.org/10.1007/s10549-022-06578-4 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7456105","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":505739825,"identity":"4a26a39f-1599-498d-a2bf-a60f946266cb","order_by":0,"name":"Saow Renn Ding","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYJAC5r//bOT42RuATAMLIvXwsKUZS/YcAGmRIFrL4cQNMxJATCK0mLf3HnsgwcOcuEHy+dUNPwokGPjbuxPwapE5cy7dwECCzXi7dE7ZzR6gwyTOnN2AV4uERI6ZRIIBj+zO2TlpN3iAWgwkcglokX9jJnEgQYJxw80zaTf/EKVFgsdMsuGAgeKGG+zHbhNnC0+OmTRjQwIwkHPYbssYSPAQ9gv7GZCW/8CoPP7s5ps/wDht78WvBQnwGIBJYpWDAPsDUlSPglEwCkbBCAIAV3pCnD/oOrMAAAAASUVORK5CYII=","orcid":"","institution":"St. George’s University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Saow","middleName":"Renn","lastName":"Ding","suffix":""},{"id":505739828,"identity":"92ed9699-c010-4c5a-820f-3212ac79549f","order_by":1,"name":"Kelley Tu","email":"","orcid":"","institution":"Brown University","correspondingAuthor":false,"prefix":"","firstName":"Kelley","middleName":"","lastName":"Tu","suffix":""},{"id":505739836,"identity":"7f4bec9c-ecc7-4b27-ba56-0743ae4494ee","order_by":2,"name":"Armand Asarian","email":"","orcid":"","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"prefix":"","firstName":"Armand","middleName":"","lastName":"Asarian","suffix":""},{"id":505739839,"identity":"dc72b93f-e10e-4a90-90a4-24dad8f91c7e","order_by":3,"name":"Philip Xiao","email":"","orcid":"","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"prefix":"","firstName":"Philip","middleName":"","lastName":"Xiao","suffix":""}],"badges":[],"createdAt":"2025-08-25 17:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7456105/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7456105/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90318609,"identity":"cb0ee642-634b-4913-a76a-73f1dd044147","added_by":"auto","created_at":"2025-09-01 10:35:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":953559,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopic examination revealing sheets of infiltrating large tumor cells with abundant eosinophilic granular cytoplasm and prominent nucleoli (H\u0026amp;E 40x).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7456105/v1/24f4d3c636d26913ebd18e61.jpg"},{"id":90317446,"identity":"f6538244-fa47-4514-bd99-db6d835a1742","added_by":"auto","created_at":"2025-09-01 10:27:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":655232,"visible":true,"origin":"","legend":"\u003cp\u003eTumor cells exhibit strong diffuse positivity for the androgen receptor (AR) (IHC 40x)\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7456105/v1/bcbcf3732517ccce42b0897f.jpg"},{"id":90320143,"identity":"6f8dde60-9011-4eb9-9997-a189aaf3f04f","added_by":"auto","created_at":"2025-09-01 10:43:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1857124,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7456105/v1/1214f30b-ceab-4958-bd2a-ea178a1f0f74.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Apocrine Carcinoma of the Breast: A Case Report and Review of the Literature","fulltext":[{"header":"Background","content":"\u003cp\u003eApocrine carcinoma of the breast is a rare and distinct histological subtype of invasive ductal carcinoma that accounts for less than 1% of all breast cancers. It is characterized by large tumor cells with abundant eosinophilic, granular cytoplasm; large round to oval nuclei, and prominent nucleoli. A hallmark of apocrine differentiation is the occurence of decapitation secretion, although this feature may not always be prominent.\u003c/p\u003e\n\u003cp\u003eHistologically, apocrine carcinomas may exhibit solid, tubular, or papillary growth patterns and are often accompanied by a desmoplastic stromal response. High mitotic activity, nuclear atypia, areas of necrosis, and calcification can also be observed. Immunohistochemically, these tumors typically demonstrate strong diffuse androgen receptor (AR) positivity, as well as expression of gross cystic disease fluid protein-15 (GCDFP-15), supporting apocrine differentiation. These patients are usually negative for estrogen receptor (ER) and progesterone receptor (PR), while HER2 expression is variable and may influence treatment strategies.\u003c/p\u003e\n\u003cp\u003eThe diagnosis can be challenging due to morphological overlap with other rare neoplasms, such as oncocytic carcinomas (1), more common subtypes, such as invasive ductal carcinoma not otherwise specified (IDC-NOS) and invasive lobular carcinoma (ILC). Accurate diagnosis is essential for guiding treatment, particularly given the emerging role of AR-targeted therapies in AR-positive, triple-negative breast cancers.\u003c/p\u003e\n\u003cp\u003eHere, we present a case of apocrine carcinoma of the breast confirmed by histopathology and immunohistochemical profiling to contribute to the limited literature and highlight the diagnostic and therapeutic considerations associated with this rare entity.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 55-year-old female patient presented to her primary care physician for a routine physical examination with no reported breast symptoms. As part of standard screening, a mammogram of the right breast was performed, revealing a superficial mass measuring 1.2 × 0.8 × 0.6 cm located in the upper outer quadrant. Additionally, scattered clustered coarse microcalcifications were noted throughout the right breast parenchyma, raising suspicion for a neoplastic process. The patient was referred for a core needle biopsy of the lesion for histopathological evaluation.\u003c/p\u003e\n\u003cp\u003eThe tissue specimens obtained consisted of multiple cores of pink-tan soft tissue measuring up to 1.4 × 0.2 cm in aggregate. Microscopic examination demonstrated sheets of infiltrating large tumor cells arranged in solid nests and clusters. The tumor cells exhibited abundant eosinophilic, finely granular cytoplasm, large centrally located nuclei, and prominent nucleoli—features characteristic of apocrine differentiation (Figure 1). No features suggestive of invasive lobular carcinoma or other specific subtypes were observed.\u003c/p\u003e\n\u003cp\u003eImmunohistochemical analysis was performed to further classify the tumors. The neoplastic cells showed strong and diffuse nuclear positivity for the androgen receptor (AR) (Figure 2). In contrast, the tumor was negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, confirming a triple-negative but AR-positive immunoprofile—an immunophenotype frequently associated with apocrine carcinoma of the breast.\u003c/p\u003e\n\u003cp\u003eFollowing diagnosis, the patient underwent surgical excision of the tumor. The surgical procedure was uneventful, and the patient recovered without complications. Final pathology confirmed clear surgical margins, and there was no evidence of lymphovascular invasion. Given the tumor's AR-positive status, the patient is currently under close clinical follow-up with consideration for adjuvant AR-targeted therapy, in accordance with emerging treatment approaches for AR-positive triple-negative breast cancer. Ongoing surveillance is planned as part of her long-term management strategy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eApocrine carcinoma of the breast presents with infiltrating tumor cells displaying apocrine morphology: abundant eosinophilic and granular cytoplasm, well-defined cell borders, enlarged round nuclei, and prominent nucleoli. This apocrine appearance is typically present in more than 90% of tumor cells. These tumors are usually high-grade or poorly differentiated and are frequently associated with ductal carcinoma in situ (DCIS), which exhibits apocrine features. Cytologically, they manifest as sheets, clusters, or single cells with abundant eosinophilic cytoplasm; large nucleoli showing variable pleomorphism; and often prominent multinucleation.\u003c/p\u003e\n\u003cp\u003eClinically, apocrine carcinomas may present as palpable masses or abnormalities detected via mammography. They are firm with distinct boundaries from surrounding tissue and often appear tan to yellowish due to their lipid content. Histologically, these tumors exhibit solid growth patterns with sheets of tumor cells, tubular formations resembling gland-like structures, or papillary configurations with fibrovascular cores. A desmoplastic stromal reaction characterized by dense fibrous tissue, sometimes accompanied by an inflammatory response with lymphocytes and plasma cells, is common.\u003c/p\u003e\n\u003cp\u003eMolecularly, apocrine carcinoma of the breast is distinct from other types of breast cancer. It is characterized by androgen receptor (AR) positivity and typically lacks estrogen receptor (ER) and progesterone receptor (PR) expression. Some tumors demonstrate HER2 overexpression or amplification. Mutations in the PIK3CA gene that activate the PI3K/AKT pathway have been observed, suggesting the potential of treatment with PI3K pathway inhibitors. (2)\u003c/p\u003e\n\u003cp\u003eMoreover, apocrine carcinomas may harbor TP53 mutations, which contibute to genomic instability, as well as BRCA1 or BRCA2 mutations, linking them to hereditary breast cancer syndromes and influencing treatment decisions such as those related to the use of PARP inhibitors. Changes in DNA methylation and histone modification patterns impact gene expression and tumor progression. (3) The presence of gross cystic disease fluid protein-15 (GCDFP-15) serves as a marker of apocrine differentiation while EGFR protein expression is common. (4)\u003c/p\u003e\n\u003cp\u003eCK5/6 are variably expressed and can aid in the differential diagnosis of apocrine carcinoma from other triple-negative breast cancers. Elevated Ki-67 indices reflects aggressive tumor behavior. Activation of survival pathways, such as the PI3K/AKT and AR signaling pathways, contributes to the growth and maintenance of tumor cells.\u003c/p\u003e\n\u003cp\u003eA hallmark of apocrine differentiation is the occurence of decapitation secretion, where the apical portion of the cell is pinched off into the glandular lumen, although this feature is not always prominent. In some cases, tumor cells may have a histiocytoid appearance with abundant foamy cytoplasm. (5)\u003c/p\u003e\n\u003cp\u003eApocrine carcinoma of the breast shares histological features with other breast cancers such as invasive ductal carcinoma, complicating differentiation based on morphology alone. While typically expressing AR and GCDFP-15, not all patients are positive for these markers. Moreover, the absence of ER and PR expression distinguishes apocrine carcinoma from other types of cancer, although this similarity with triple-negative breast cancer (TNBC) lacking ER, PR, and HER2 expression can lead to diagnostic complexity.\u003c/p\u003e\n\u003cp\u003eDifferential diagnosis between apocrine carcinoma and other breast tumors with similar morphologies is crucial for accurate classification and treatment (6). Invasive breast carcinoma with focal apocrine differentiation, is a type of invasive ductal carcinoma of no special type (NST) that shows some areas resembling apocrine sweat gland cells, with up to 60% of such carcinomas exhibiting these features. However, to be classified specifically as having apocrine differentiation, more than 90% of the tumors must exhibit this morphology. Invasive breast carcinoma, (NST) with an oncocytic carcinoma pattern, displays tumor cells with abundant eosinophilic and granular cytoplasm, well-defined borders, round centrally located nuclei and prominent nucleoli. These tumors are often estrogen receptor (ER)-positive and may show specific chromosomal gains at 11q13.1-q13.2 and 19p13. Granular cell tumors are rare and consist of large, round to polygonal cells with eosinophilic and granular cytoplasm and small central hyperchromatic nuclei; they typically test positive for S100 and CD68 markers but not for keratins. Apocrine ductal carcinoma in situ (DCIS) is a form of DCIS with apocrine cytology characterized by the presence of a myoepithelial cell layer around the ducts. Apocrine adenosis or atypical apocrine adenosis involves a lobulocentric proliferation of cells with apocrine features, often distorted by stromal fibrosis or sclerosis, also characterized by the presence of a myoepithelial cell layer.\u003c/p\u003e\n\u003cp\u003eSurgery remains the primary treatment for early-stage apocrine carcinoma of the breast, and the choice between lumpectomy and mastectomy is based on the by tumor size, location, and patient preference. Successful tumor removal is correlated with improved outcomes depending on the disease stage. \u0026nbsp; Following lumpectomy, radiation therapy is typically recommended to reduce the risk of local recurrence. Postmastectomy may also be considered for patients with high-risk features such as large tumor size or lymph node involvement, improving overall survival, particularly in early-stage disease.\u003c/p\u003e\n\u003cp\u003eChemotherapy plays a crucial role, particularly in treating higher-grade or advanced-stage apocrine carcinomas, utilizing standard regimens such as anthracyclines, taxanes, and platinum-based agents to reduce recurrence risk and increase survival, especially in node-positive or high-risk patients. (7)\u003c/p\u003e\n\u003cp\u003eAR-targeted therapies, such as bicalutamide or enzalutamide, are promising options due to the high AR expression in apocrine carcinoma of the breast and are especially beneficial in AR-positive, ER-negative tumors. Hormonal therapies such as tamoxifen are generally ineffective due to the usual ER and PR negativity in these cancers. (8)\u003c/p\u003e\n\u003cp\u003eClinical guidelines should stress routine AR testing and the inclusion of GCDFP-15 in diagnostic panels to confirm apocrine differentiation. A multidisciplinary approach involving regular tumor board meetings is essential for tailored treatment planning and comprehensive management of apocrine carcinoma of the breast.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, diagnosing apocrine carcinoma of the breast remains challenging due to its histological similarities with other breast cancers. Immunohistochemical markers like AR and GCDFP-15 are crucial for accurate identification. Prognosis and treatment decisions are significantly influenced by hormone receptor status (AR positivity, ER/PR negativity) and HER2 status.\u003c/p\u003e\u003cp\u003eCurrent treatment strategies include surgery, radiation, chemotherapy, and targeted therapies, particularly AR inhibitors and HER2-targeted agents, which have shown promise in improving outcomes for specific molecular subtypes. Comprehensive immunohistochemical profiling and multidisciplinary team involvement are essential for managing this unique breast cancer subtype effectively.\u003c/p\u003e\u003cp\u003eOngoing research focuses on novel therapies such as AR inhibitors and immunotherapies, aiming to further optimize treatment approaches. Future studies should prioritize clinical trials to explore new therapeutic targets and refine treatment protocols, ultimately aiming to enhance patient outcomes in apocrine carcinoma of the breast.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eWritten informed consent for participation and publication was obtained from the patient.\u003c/p\u003e\n\u003cp\u003eEthics declaration: Not applicable\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and Materials Availability: Not applicable\u003c/p\u003e\n\u003cp\u003eCompeting interests: Not applicable\u003c/p\u003e\n\u003cp\u003eFunding: No funding\u003c/p\u003e\n\u003cp\u003eAuthor contributions: S.D, P.X and K.T. wrote \u0026nbsp;the main manuscript text. P.X. prepared Figures 1-2. All the authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgment: Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1. Semir Vranic\u003csup\u003e1\u003c/sup\u003e, Zoran Gatalica(2021) An Update on the Molecular and Clinical Characteristics of Apocrine Carcinoma of the Breasthttps://doi.org/10.1016/j.clbc.2021.12.009\u003c/p\u003e\n\u003cp\u003e2. Semir Vranic, Fernando Schmitt, Anna Sapino, Jose Luis Costa, Sandeep Reddy, Michael Castro and Zoran Gatalica (2013) Apocrine carcinoma of the breast: a comprehensive review https://doi.org/10.14670/hh-28.1393\u003c/p\u003e\n\u003cp\u003e3. Jing Wang\u003csup\u003e1\u003c/sup\u003e, Yan Peng\u003csup\u003e2\u003c/sup\u003e, Hongxia Sun\u003csup\u003e3\u003c/sup\u003e, Phyu P Aung\u003csup\u003e1\u003c/sup\u003e, Erika Resetkova\u003csup\u003e1\u003c/sup\u003e, Clinton Yam\u003csup\u003e4\u003c/sup\u003e, Aysegul A Sahin\u003csup\u003e1\u003c/sup\u003e, Lei Huo\u003csup\u003e1\u003c/sup\u003e, Qingqing Ding\u003csup\u003e1\u003c/sup\u003e(2024) TRPS1 and GATA3 Expression in Invasive Breast Carcinoma With Apocrine Differentiation https://doi.org/10.5858/arpa.2022-0289-OA\u003c/p\u003e\n\u003cp\u003e4. Sawsan Ismail,\u003csup\u003e1,2\u003c/sup\u003e Haidara Kherbek,\u003csup\u003e3\u003c/sup\u003e Jana Skef,\u003csup\u003e3\u003c/sup\u003e Nadim Zahlouk,\u003csup\u003e4\u003c/sup\u003e Rafik Abdulal,\u003csup\u003e5\u003c/sup\u003e and Zuheir Alshehabi(2021) Triple-negative apocrine carcinoma as a rare cause of a breast lump in a Syrian female: a case report and review of the literature https://doi.org/10.1186%2Fs12905-021-01539-3\u003c/p\u003e\n\u003cp\u003e5. S Shimizu\u003csup\u003e1\u003c/sup\u003e, H Kitamura, T Ito, T Nakamura, J Fujisawa, H Matsukawa (1998) Histiocytoid breast carcinoma: histological, immunohistochemical, ultrastructural, cytological and clinicopathological studies https://doi.org/10.1111/j.1440-1827.1998.tb03948.x\u003c/p\u003e\n\u003cp\u003e6. Lawrence Hsu Lin\u003csup\u003e1\u003c/sup\u003e, Ivy Tran\u003csup\u003e1\u003c/sup\u003e, Yiying Yang\u003csup\u003e1\u003c/sup\u003e, Guomiao Shen\u003csup\u003e1\u003c/sup\u003e, Pabel Miah\u003csup\u003e2\u003c/sup\u003e, Paolo Cotzia\u003csup\u003e1\u003c/sup\u003e, Daniel Roses\u003csup\u003e2\u003c/sup\u003e, Freya Schnabel\u003csup\u003e2\u003c/sup\u003e, Farbod Darvishian\u003csup\u003e1\u003c/sup\u003e, Matija Snuderl\u003csup\u003e3\u003c/sup\u003e(2023) DNA Methylation Identifies Epigenetic Subtypes of Triple-Negative Breast Cancers With Distinct Clinicopathologic and Molecular Featureshttps://doi.org/10.1016/j.modpat.2023.100306\u003c/p\u003e\n\u003cp\u003e7. Semir Vranic,\u003csup\u003e1,2,*\u003c/sup\u003e Rebecca Feldman,\u003csup\u003e3\u003c/sup\u003e and Zoran Gatalica\u003csup\u003e4\u003c/sup\u003e(2017) Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers https://doi.org/10.17305%2Fbjbms.2016.1811\u003c/p\u003e\n\u003cp\u003e8. Semir Vranic4 Faruk Skenderi1 \u0026middot; Mohamad Alhoda Mohamad Alahmad2 \u0026middot; Emin Tahirovic3 \u0026middot; Yaman M. Alahmad4,5 \u0026middot; Zoran Gatalica6 (2022) HER2‑positive apocrine carcinoma of the breast: a population‑based analysis of treatment and outcome https://doi.org/10.1007/s10549-022-06578-4\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Apocrine, Breast, Carcinoma, Androgen, Receptors","lastPublishedDoi":"10.21203/rs.3.rs-7456105/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7456105/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Apocrine carcinoma of the breast is a rare and distinct subtype of invasive ductal carcinoma characterized histologically by large tumor cells with abundant eosinophilic granular cytoplasm and prominent nucleoli. Accurate diagnosis and immunohistochemical profiling are essential for distinguishing this entity from other breast cancer subtypes. Emerging evidence suggests a potential therapeutic role for androgen receptor (AR)-targeted treatments in managing this disease.\u003c/p\u003e\n\u003cp\u003eCase Presentation: The patient was a 55-year-old woman with no significant past medical history who presented for a routine physical examination. A screening mammogram revealed a 1.2 × 0.8 × 0.6 cm superficial mass in the upper outer quadrant of the right breast, along with scattered coarse microcalcifications. A core needle biopsy was performed, and histopathological analysis confirmed the diagnosis of apocrine carcinoma of the breast, a rare subtype of invasive ductal carcinoma. Immunohistochemistry (IHC) demonstrated strong androgen receptor (AR) positivity and negativity for estrogen receptor (ER), progesterone receptor (PR), and HER2. The patient subsequently underwent surgical excision of the tumor. Postoperative recovery was uneventful, and the patient is currently under close clinical follow-up with consideration for AR-targeted therapy in the context of receptor status.\u003c/p\u003e\n\u003cp\u003eConclusions: Through a review of the current literature, we highlight the key histopathological, molecular, and clinical features of apocrine breast carcinoma. This case study underscores the importance of accurate diagnosis and comprehensive immunohistochemical analysis in guiding effective treatment strategies. The consistent expression of AR in these tumors supports further exploration of AR-targeted therapies as a promising treatment avenue.\u003c/p\u003e","manuscriptTitle":"Apocrine Carcinoma of the Breast: A Case Report and Review of the Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 10:26:57","doi":"10.21203/rs.3.rs-7456105/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":"5ebdca3d-9076-46a4-9bbf-63b80bf63913","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T10:26:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 10:26:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7456105","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7456105","identity":"rs-7456105","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}