A case of breast acinar cell carcinoma combined with metaplastic carcinoma

A case of breast acinar cell carcinoma combined with metaplastic carcinoma | 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 Short Report A case of breast acinar cell carcinoma combined with metaplastic carcinoma Sichun Liu, Huaiyuan Hu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8858807/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background Breast acinar cell carcinoma (AcCC) is a rare subtype of triple-negative breast cancer. Its histological origin remains controversial, and it exhibits poor sensitivity to conventional chemotherapy. High-grade transformation and co-existence with matrix-producing metaplastic carcinoma are uncommon, and their clinical and molecular genetic features are poorly understood. Case Presentation A 42-year-old woman incidentally discovered a breast mass for 10 days. Ultrasound revealed multifocal tumors in the upper inner quadrant of the left breast, classified as BI-RADS 4b, leading to a clinical diagnosis of breast cancer. Microscopically, the tumor comprised two distinct components. Component one exhibited tubular or solid nested patterns with eosinophilic secretions in lumina; some cells were amphophilic, and focal areas showed marked high-grade transformation with significant nuclear atypia. Component two featured tumor cell cords and nests distributed within a chondromyxoid stromal matrix. Immunophenotypically, tumor cells in both components diffusely and strongly expressed S-100, GATA3, AE1/AE3, and EMA. Component one expressed Lysozyme (LYS) and α1-antichymotrypsin (AACT). Both components were negative for ER, PR, HER2, CK5/6, CD117, P63, and Collagen IV. The Ki-67 proliferation index was approximately 10% in the low-grade areas of component one, reached about 30% in its high-grade areas, and was approximately 70% in component two. Molecular genetics: Next-generation sequencing detected a somatic frameshift mutation in the TP53 gene with a variant allele frequency of 36.51%, as well as germline non-pathogenic variants in APC, ATM, BRCA1, BRCA2 , and others. Conclusion This report describes a breast tumor exhibiting concurrent features of AcCC and matrix-producing metaplastic carcinoma, summarizing its immunophenotypic characteristics and molecular genetic alterations. This information may provide diagnostic insights for future encounters with similar cases. AcCC Breast cancer Metaplastic carcinoma Immunohistochemistry NGS Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Breast acinar cell carcinoma (AcCC) is a rare malignant epithelial tumor entity. Its histomorphology and immunophenotype largely align with those of salivary gland AcCC, yet they possess distinct molecular genetic alterations [ 1 ]. The diagnostic basis lies in the presence of eosinophilic and/or basophilic granular cytoplasm and a serous acinar differentiation direction. Although typically categorized as a triple-negative breast cancer (TNBC) subtype, it demonstrates a relatively favorable prognosis. Thus, its histological origin remains unclear. Some scholars propose that breast AcCC should be regarded as a carcinoma arising in microglandular adenosis (MGA) with acinar cell differentiation, rather than a distinct entity [ 2 ]. This report presents a comprehensive comparative analysis of the morphology and immunophenotype of a case of breast AcCC with high-grade transformation co-existing with metaplastic carcinoma (matrix-producing type, constituting approximately 40% of the tumor). It also explores its molecular biological characteristics, aiming to establish a foundation for research on similar future cases. Case Presentation A 42-year-old woman with no family history of breast cancer incidentally discovered a left breast mass for 10 days. Mammography revealed an irregular, dense mass in the upper inner quadrant of the left breast, the largest measuring approximately 6.0 cm × 3.7 cm (Fig. 1 A). Ultrasound showed an irregular hypoechoic lesion at the 12 o'clock position of the left breast measuring 1.54 cm × 1.0 cm, classified as BI-RADS 4b. Enhanced MRI revealed an irregular, patchy area of abnormal signal (Fig. 1 B), with heterogeneous internal signal and surrounding thickened, tortuous vessels (Fig. 1 C). DWI showed a high signal and ADC low signal. The clinical diagnosis was breast cancer. Clinicopathological Features The tumor cells displayed two distinct morphological patterns with an inconspicuous transition between them (Fig. 2 A). Component one consisted of epithelial cells arranged in small glandular structures (Fig. 2 B), solid sheets, or microcystic patterns, with focal infiltration into adipose tissue (Fig. 2 C). The tumor cells had low-grade nuclei and amphophilic, finely granular cytoplasm. Eosinophilic secretions were present within some lumina, and some cells exhibited abundant eosinophilic cytoplasm (Fig. 2 D). Focal areas showed marked high-grade transformation, resembling ductal carcinoma in situ (Fig. 2 E). In these areas, tumor cells were arranged in solid nests with significant nuclear atypia, prominent nucleoli, and frequent mitotic figures (Fig. 2 F). The stroma in some areas contained admixed lymphocytes (Fig. 2 G). Component two showed a nodular growth pattern, with tumor cells arranged in sheets, nests, trabecular structures, or as single cells infiltrating the stroma against a background of chondromyxoid matrix (Fig. 2 H). The nuclei were highly atypical with abundant mitotic figures (Fig. 2 I). Immunophenotype and Molecular Characteristics All tumor cells diffusely and strongly expressed S-100 (Fig. 3 A, B), GATA3, AE1/AE3, and EMA (Fig. 3 C). Notably, tumor cells in component one expressed LYS (Fig. 3 D) and AACT. Both components were negative for ER (Fig. 3 E), PR, HER2, CK5/6, CD117, P63, and Collagen IV (Fig. 3 F). The Ki-67 proliferation index was approximately 10% in the low-grade areas of component one (Fig. 3 G), about 30% in its high-grade areas (Fig. 3 H), and approximately 70% in component two (Fig. 3 I). Next-generation sequencing of different tumor areas detected a somatic frameshift mutation in the TP53 gene (Fig. 4 ) with a variant allele frequency of 36.51%, as well as germline non-pathogenic variants in APC, ATM, BRCA1, BRCA2 , and others (Table 1 ). Table 1 Germline gene variants detected by next-generation sequencing. Gene RefSeq Exon cHGVS pHGVS Variant Type Frequency (%) APC NM_000038 exon 16 c.5465 T > A p.Val1822Asp Missense 100% ATM NM_000051 exon 40 c.5948 A > G p.Asn1983Ser Missense 100% BARD1 NM_000465 exon 4 c. 1134 G > C p.Arg378Ser Missense 99.92% BARD1 NM_000465 exon 6 c. 1519 G > A p.Val507Met Missense 99.9% BRCA1 NM_007294 exon 10 c.3548 A > G p.Lys1183Arg Missense 74. 19% BRCA1 NM_007294 exon 10 c.2612 C > T p.Pro871Leu Missense 73.88% BRCA1 NM_007294 exon 10 c.3113 A > G p.Glu1038Gly Missense 68.63% BRCA2 NM_000059 exon 14 c.7397 T > C p.Val2466Ala Missense 100% CHEK1 NM_001114121 exon 13 c. 1411 A > G p.Ile471Val Missense 100% EPCAM NM_002354 exon 3 c.344 T > C p.Met115Thr Missense 67.96% MSH6 NM_000179 exon 1 c. 116 G > A p.Gly39Glu Missense 67.81% PALB2 NM_024675 exon 4 c. 1676 A > G p.Gln559Arg Missense 49.03% PMS2 NM_000535 exon 11 c. 1621 A > G p.Lys541Glu Missense 99.83% PMS2 NM_000535 exon 11 c. 1408 C > T p.Pro470Ser Missense 47.94% PMS2 NM_000535 exon 2 c.59 G > A p.Arg20Gln Missense 46. 19% POLD1 NM_002691 exon 4 c.356 G > A p.Arg119His Missense 99.79% TP53 NM_000546 exon 4 c.215 C > G p.Pro72Arg Missense 27.38% TSC1 NM_000368 exon 19 c.2485 A > C p.Ser829Arg Missense 70.09% Treatment and Prognosis The patient underwent modified radical mastectomy with sentinel lymph node biopsy, followed by adjuvant EC-T chemotherapy. After 13 months of follow-up, the patient remains in good condition with no evidence of recurrence or metastasis. Long-term follow-up is ongoing. Discussion Breast acinar cell carcinoma (AcCC) was first reported by Roncaroli et al. [ 3 ] in 1996, initially termed "acinic cell-like carcinoma of the breast." The 5th edition of the WHO Classification of Breast Tumours lists it among rare salivary gland-type tumors. With increasing recognition, more cases have been reported; as of late November 2024, over 70 cases have been documented in the literature worldwide [ 4 ]. Although its histological patterns overlap with those of salivary gland AcCC, studies indicate they have different genetic alterations. Hence, scholars like Rosen et al. [ 5 ] propose that so-called breast AcCC is essentially "invasive carcinoma arising in microglandular adenosis with acinar cell differentiation," and the spectrum from typical MGA to atypical MGA and associated carcinomas can show different types of differentiation, seemingly supporting Rosen's view. However, in the present case, thorough sampling and immunohistochemical analysis did not reveal MGA or atypical MGA components. Although breast AcCC was previously thought to share the relatively indolent behavior and good prognosis of salivary AcCC, cases with recurrence, metastasis, or death have also been reported [ 6 – 8 ], especially when high-grade morphology or co-existence with other breast carcinoma types is present. Clinical Presentation and Histological Features: A comprehensive clinicopathological analysis of 72 reported cases of breast AcCC reveals no specific trends regarding patient age (range 23–80 years, average 47 years), tumor location, or imaging features. Clinically, patients most often present with a breast mass. Notably, one case of breast AcCC in a 23-year-old male has been reported [ 9 ]. Histologically, breast AcCC typically exhibits acinar cell differentiation similar to salivary glands, characterized by granular cytoplasm and PAS-positive, diastase-resistant granules. At low magnification, it consists of irregular acinar structures lined by one to several layers of epithelial cells. Tumor cells in the classical AcCC component are round or cuboidal with eosinophilic granular cytoplasm and indistinct borders. Myoepithelial cells and a basal membrane are absent around the glands, and eosinophilic secretions are often observed within lumina. When high-grade transformation occurs, acini merge into small solid or cribriform nests, and nuclei become pleomorphic, vesicular with prominent nucleoli, accompanied by significant pathological mitotic figures and a high Ki-67 proliferation index. Besides high-grade transformation, breast AcCC can also co-exist with other types of breast carcinoma, usually invasive carcinoma of no special type. Winkler et al. [ 10 ] and Piscuoglio et al. [ 11 ] reported two cases co-existing with metaplastic carcinoma, similar to the present case. Piscuoglio et al. suggested the term "mixed breast AcCC" when the other carcinoma type constitutes 50%–90% of the tumor. Immunophenotype and Molecular Characteristics: The immunohistochemical profile of breast AcCC sometimes overlaps with TNBC. Most cases are negative for ER, PR, and HER2 and lack myoepithelial markers (CK5/6, p63 and Calponin) and basement membrane markers (Collagen IV and Laminin). The diagnostic utility lies in the frequent strong positivity of AcCC for S-100 and one or more serous differentiation markers such as Lysozyme (LYS), α1-antichymotrypsin (AACT), and α1-antitrypsin (ACT), which are typically absent in TNBC. Table 2 summarizes the immunophenotypic characteristics of breast AcCC from previous reports. Some studies also suggest diagnostic value for CK5/6 and CD117 in breast AcCC [ 12 , 13 ], although, unfortunately, our case did not show immunoreactivity for these markers. Breast AcCC often shares similar molecular genetic alterations with high-grade TNBC, such as mutations in TP53, PIK3CA, MTOR, etc., with TP53 being the most frequently mutated gene. In our case, NGS detected only a TP53 mutation without other genetic alterations. Piscuoglio et al. [ 11 ] performed Sanger sequencing on 10 breast and 20 salivary AcCCs, revealing TP53 (8/10, 80%) and PIK3CA (1/10, 10%) mutations in breast AcCC, while salivary AcCC harbored none of these mutations (0/20, 0%), indicating distinct genetic pathways. Furthermore, Elena et al. [ 14 ] performed genetic testing on four cases of mixed high-grade AcCC (three with invasive ductal carcinoma of no special type, one with metaplastic carcinoma) and found identical somatic mutations in the different components of two cases, suggesting a clonal relationship between the acinar and high-grade non-acinar components. This finding provides indirect genetic evidence that, in some instances, breast AcCC may constitute the precursor lesion for the development of aggressive TNBC with higher histological grade or more aggressive subtypes. Table 2 Immunohistochemical marker expression in previous literature. Immunohistochemical Marker Result Number of Cases (%) ER 阴性 90.9(50/55) PR 阴性 88.9(48/54) HER−2 阴性 95.0(38/40) EMA 阳性 100.0(27/27) S−100 阳性 92.7(51/55) Lys 阳性 95.3(41/43) AACT 阳性 96.0(24/25) AMY 阳性 92.3(24/26) GATA−3 阳性 66.7(4/6) Differential Diagnosis: Utilizing the unique histological features of AcCC (e.g., eosinophilic, granular cytoplasm, eosinophilic intraluminal secretions) and its characteristic immunophenotype (positivity for S-100, LYS, AACT, etc.) aids in distinguishing it from other TNBC subtypes. In our view, the most challenging differential diagnosis involves the spectrum of MGA and atypical MGA, due to their similar morphology and immunophenotype. MGA is a rare benign breast lesion defined as a haphazard proliferation of small glands composed of a single epithelial layer without an accompanying myoepithelial cell layer. When glands in MGA merge into solid or cribriform nests, it is termed atypical MGA. There is extensive histological overlap between the tubular or microglandular structures of breast AcCC and MGA. Currently, the most crucial distinguishing feature is the preservation of the basement membrane in MGA, which can be demonstrated using markers like Collagen IV and Laminin. Some scholars have observed a morphological spectrum from typical MGA to atypical MGA to AcCC within the same case [ 15 , 16 ], coupled with shared genetic alterations like TP53 mutations, further supporting Rosen's view of "invasive carcinoma arising in microglandular adenosis with acinar cell differentiation." However, in our case, no MGA or atypical MGA components were found. Another important consideration is distinguishing primary or metastatic salivary gland AcCC. Besides integrating clinical history, the novel marker NR4A3 has been reported to have significant diagnostic value. Richardson et al. [ 17 ] performed NR4A3 immunohistochemistry on 16 breast AcCCs (8 pure, 8 mixed), all of which were negative. Similarly, Florian et al.[ 18 ] conducted immunohistochemical and FISH studies on 64 salivary AcCCs and 99 other salivary gland tumors, finding NR4A3 to be a highly sensitive (98%) and specific (100%) marker for salivary AcCC, especially in cases with high-grade transformation. This further substantiates the different molecular pathways between breast and salivary AcCC. In summary, breast AcCC is a rare salivary gland-type tumor of the breast with a broad morphological spectrum, ranging from well-differentiated tubular or microglandular structures to high-grade and poorly differentiated components. When high-grade transformation occurs or it co-exists with other breast carcinoma types, its metastatic potential appears to increase [ 12 ]. Compared to conventional TNBC, breast AcCC possesses unique biological characteristics and a potentially lower aggressive potential; some patients follow an indolent clinical course and may not require further treatment after surgical excision. However, its histological origin requires accumulation of more cases and further research. This report aims to provide a morphological and molecular basis for understanding the possible mechanisms underlying high-grade lesions and mixed carcinomas in breast AcCC, while offering diagnostic insights for future similar cases to avoid misdiagnosis and improve patient quality of life. Declarations Acknowledgements Not applicable. Authors' contributions SC Liu Responsible for data collection and paper writing. HY Hu responsible for reviewing papers. All authors reviewed the manuscript. Competing interests The authors declare no competing interests. Data availability All data supporting this study are publicly available Clinical trial number Not applicable Funding Not applicable. Ethics approval and Accordance Statement The study protocol was reviewed and approved by the Hefei Anweikang Medical Laboratory Pathology Center, confirming its compliance with the relevant guidelines of the International Committee of Medical Journal Editors (ICMJE). The above content can be reflected in the patient's admission authorization form, and no further ethical approvals are required. All personal data have been processed in an anonymous form to protect patient privacy. Consent to participate Written informed consent was obtained from the patients to participate in this work and to use their case details for teaching and publication. Consent to publish Consent for publication was obtained for the patient’s data included in the study. Accordance Statement All methods in this study were carried out in accordance with relevant guidelines and regulations References Ge Y, Wei X, Liu JN, Sun PL, Gao H. New insights into acinic cell carcinoma of the breast: clinicopathology, origin of histology, molecular features, prognosis, and treatment. Front Oncol. 2024 Sep 2;14:1438179. Qin F, Li J, Zheng Y, Jiang C, Jia Y, Sun H, Xue H, et.al. Breast Carcinomas Resembling Acinic Cell Carcinoma: Comprehensive Analysis of 14 Cases and Review of the Literature. Am J Surg Pathol. 2025 May 1;49(5):448-457. Roncaroli F, Lamovec J, Zidar A, Eusebi V. Acinic cell-like carcinoma of the breast. Virchows Arch. 1996 Sep;429(1):69-74. Lu Y, Kong X, Wang X, Zhang W, Li Y, Dong H, Wang Z, et.al. Deciphering primary acinic cell carcinoma of the Breast: Insights from a comprehensive case series and Systematic review. Cancer Treat Rev. 2024 Dec;131:102830. Rosen PP. So-called acinic cell carcinoma of the breast arises from microgladular adenosis and is not a distinct entity. Mod Pathol. 2017 Oct;30(10):1504. Yang X, Liu F, Li C, Li Z, Wang P, Zhang M, Liu Y, et.al. Clinicopathological, immunohistochemical and molecular features of acinic cell carcinoma of the breast. Oncol Lett. 2024 Jan 18;27(3):107. Sarsiat L, Watkinson G, Turnbull A, Diana A, Oikonomidou O. Primary acinic cell carcinoma Oncol. 2022 Feb;16(2):43. Atta IS Sr. Acinic Cell Carcinoma of the Breast: A Case Report and Review of Literature. Cureus. 2024 Jan 1;16(1):e51427. Shimao K, Haga S, Shimizu T, Imamura H, Watanabe O, Kinoshita J, Nagumo H, et.al. Acinic Cell Adenocarcinoma Arising in the Breast of a Young Male: A Clinicopathological, Immunohistochemical and Ultrastructural Study. Breast Cancer. 1998 Jun 30;5(1):77-81. Winkler N, Morrell G, Factor RE. Invasive carcinoma with acinic cell-like features of the breast. Breast J. 2013 May-Jun;19(3):334-5. 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A case of extensively spreading acinic cell carcinoma of the breast with microglandular features. Pathol Int. 2023 Jan;73(1):45-51. Falleti J, Coletti G, Rispoli E, Scarabeo F, Cervasio M, Tornillo L, Pettinato G, et.al. Acinic cell carcinoma of the breast arising in microglandular adenosis. Case Rep Pathol. 2013;2013:736048. Richardson ET, Selenica P, Pareja F, Cin PD, Hanlon E, Weigelt B, Reis-Filho JS, et.al. NR4A3 Expression Is Consistently Absent in Acinic Cell Carcinomas of the Breast: A Potential Nosologic Shift. Mod Pathol. 2023 Jun;36(6):100144. Haller F, Moskalev EA, Kuck S, Bieg M, Winkelmann C, Müller SK, Ihrler S, et.al. Nuclear NR4A2 (Nurr1) Immunostaining is a Novel Marker for Acinic Cell Carcinoma of the Salivary Glands Lacking the Classic NR4A3 (NOR-1) Upregulation. Am J Surg Pathol. 2020 Sep;44(9):1290-1292. Additional Declarations No competing interests reported. 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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-8858807","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":600044900,"identity":"b2b3c8b6-1511-4aa8-ac02-745d85e9b26d","order_by":0,"name":"Sichun Liu","email":"","orcid":"","institution":"Hefei Anweikang Medical Laboratory Pathology Center","correspondingAuthor":false,"prefix":"","firstName":"Sichun","middleName":"","lastName":"Liu","suffix":""},{"id":600044901,"identity":"63ab8fc5-b682-40ed-b12d-8133a650402b","order_by":1,"name":"Huaiyuan Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYBACfvaGhAMJFTZyQAaRWiR7Djw88OFMmjGQQaQWgxuJjw/ObDucuOFGArEuu5GccJiH7TBjw83HG28w1NhEE9TB2PMMqIUnnZlxdlqxBcOxtNwGQlqY2XOAWiSs2Zilc8wkGBsOE9bCxpD/4TCPATMPm+QZIrXwcCQkHJyR4CzBI8FDpBYJngMJBz4cSDOQ4AH6JYEYv9gfb0j+kPjPpn7/8cMbb3yosSGsBRkYSCSQohyihVQdo2AUjIJRMDIAAHm8RR7NVlO/AAAAAElFTkSuQmCC","orcid":"","institution":"Hefei Anweikang Medical Laboratory Pathology Center","correspondingAuthor":true,"prefix":"","firstName":"Huaiyuan","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2026-02-12 07:23:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8858807/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8858807/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104404641,"identity":"fd6c15ee-67de-432e-918b-fa4c284d6d12","added_by":"auto","created_at":"2026-03-11 12:20:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":297353,"visible":true,"origin":"","legend":"\u003cp\u003eClinical imaging findings. Mammography shows an irregular, dense mass in the upper inner quadrant of the left breast (\u003cstrong\u003eA\u003c/strong\u003e). Enhanced MRI reveals an irregular, patchy area of abnormal signal (\u003cstrong\u003eB\u003c/strong\u003e) with surrounding thickened, tortuous vessels (\u003cstrong\u003eC\u003c/strong\u003e).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8858807/v1/97d9ccb62ec0129c650cd551.png"},{"id":104175732,"identity":"bdff7699-5ca1-457e-b235-f87fecacf2c4","added_by":"auto","created_at":"2026-03-08 16:32:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1773761,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological examination. The tumor exhibits two distinct histomorphologies with a clear boundary (\u003cstrong\u003eA\u003c/strong\u003e, H\u0026amp;E, 20x). Tumor cells form small tubular structures with low-grade nuclei and eosinophilic secretions within lumina (\u003cstrong\u003eB\u003c/strong\u003e, H\u0026amp;E, 100x). Tumor cells with abundant cytoplasm infiltrate adipose tissue (\u003cstrong\u003eC\u003c/strong\u003e, H\u0026amp;E, 40x). Tumor cells exhibit prominent eosinophilic cytoplasm (\u003cstrong\u003eD\u003c/strong\u003e, H\u0026amp;E, 100x). High-grade area resembling ductal carcinoma in situ (\u003cstrong\u003eE\u003c/strong\u003e, H\u0026amp;E, 100x). High-grade area with solidly arranged, markedly atypical cells and frequent mitoses (\u003cstrong\u003eF\u003c/strong\u003e, H\u0026amp;E, 200x). Area with abundant mature small lymphocytes in the tumor stroma (\u003cstrong\u003eG\u003c/strong\u003e, H\u0026amp;E, 100x). Metaplastic carcinoma area with chondromyxoid stromal background (\u003cstrong\u003eH\u003c/strong\u003e, H\u0026amp;E, 100x). Metaplastic carcinoma area with marked cellular atypia (\u003cstrong\u003eI\u003c/strong\u003e, H\u0026amp;E, 100x).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8858807/v1/8b4f6f1ee4f8e54b3942cf65.png"},{"id":104175731,"identity":"7b256800-b1bc-4289-8ade-18153ff9969e","added_by":"auto","created_at":"2026-03-08 16:32:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1849972,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical findings. Tumor cells in different areas express S-100: component one (\u003cstrong\u003eA\u003c/strong\u003e, BOND Polymer DS9800, 100x) and component two (\u003cstrong\u003eB\u003c/strong\u003e, BOND Polymer DS9800, 40x). Tumor cells in different areas express EMA (\u003cstrong\u003eC\u003c/strong\u003e, BOND Polymer DS9800, 20x). Tumor cells in component one express Lysozyme (LYS) (\u003cstrong\u003eD\u003c/strong\u003e, BOND Polymer DS9800, 100x). Tumor cells are negative for ER (\u003cstrong\u003eE\u003c/strong\u003e, BOND Polymer DS9800, 100x) and Collagen IV (\u003cstrong\u003eF\u003c/strong\u003e, BOND Polymer DS9800, 100x). The Ki-67 index is approximately 10% in the low-grade area of component one (\u003cstrong\u003eG\u003c/strong\u003e, BOND Polymer DS9800, 100x), about 30% in its high-grade area (\u003cstrong\u003eH\u003c/strong\u003e, BOND Polymer DS9800, 100x), and approximately 70% in component two (\u003cstrong\u003eI\u003c/strong\u003e, BOND Polymer DS9800, 100x).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8858807/v1/b707d8b7ca9727e8d55e50c8.png"},{"id":104175729,"identity":"768af7e4-9c7e-4988-a0ec-5d780b92e3b0","added_by":"auto","created_at":"2026-03-08 16:32:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":105083,"visible":true,"origin":"","legend":"\u003cp\u003eNext-generation sequencing detected only a \u003cem\u003eTP53\u003c/em\u003e frameshift mutation across different tumor areas.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8858807/v1/66023afd27c9f35478204a05.png"},{"id":104408978,"identity":"bbab6442-f24c-4866-9455-f411d3025723","added_by":"auto","created_at":"2026-03-11 12:43:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4827260,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8858807/v1/c25eb922-88d3-4f77-8bcd-4bed4e5f55cf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of breast acinar cell carcinoma combined with metaplastic carcinoma","fulltext":[{"header":"Background","content":"\u003cp\u003eBreast acinar cell carcinoma (AcCC) is a rare malignant epithelial tumor entity. Its histomorphology and immunophenotype largely align with those of salivary gland AcCC, yet they possess distinct molecular genetic alterations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The diagnostic basis lies in the presence of eosinophilic and/or basophilic granular cytoplasm and a serous acinar differentiation direction. Although typically categorized as a triple-negative breast cancer (TNBC) subtype, it demonstrates a relatively favorable prognosis. Thus, its histological origin remains unclear. Some scholars propose that breast AcCC should be regarded as a carcinoma arising in microglandular adenosis (MGA) with acinar cell differentiation, rather than a distinct entity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This report presents a comprehensive comparative analysis of the morphology and immunophenotype of a case of breast AcCC with high-grade transformation co-existing with metaplastic carcinoma (matrix-producing type, constituting approximately 40% of the tumor). It also explores its molecular biological characteristics, aiming to establish a foundation for research on similar future cases.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 42-year-old woman with no family history of breast cancer incidentally discovered a left breast mass for 10 days. Mammography revealed an irregular, dense mass in the upper inner quadrant of the left breast, the largest measuring approximately 6.0 cm \u0026times; 3.7 cm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Ultrasound showed an irregular hypoechoic lesion at the 12 o'clock position of the left breast measuring 1.54 cm \u0026times; 1.0 cm, classified as BI-RADS 4b. Enhanced MRI revealed an irregular, patchy area of abnormal signal (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), with heterogeneous internal signal and surrounding thickened, tortuous vessels (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). DWI showed a high signal and ADC low signal. The clinical diagnosis was breast cancer.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eClinicopathological Features\u003c/h2\u003e \u003cp\u003eThe tumor cells displayed two distinct morphological patterns with an inconspicuous transition between them (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Component one consisted of epithelial cells arranged in small glandular structures (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB), solid sheets, or microcystic patterns, with focal infiltration into adipose tissue (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). The tumor cells had low-grade nuclei and amphophilic, finely granular cytoplasm. Eosinophilic secretions were present within some lumina, and some cells exhibited abundant eosinophilic cytoplasm (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Focal areas showed marked high-grade transformation, resembling ductal carcinoma in situ (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE). In these areas, tumor cells were arranged in solid nests with significant nuclear atypia, prominent nucleoli, and frequent mitotic figures (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF). The stroma in some areas contained admixed lymphocytes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eG). Component two showed a nodular growth pattern, with tumor cells arranged in sheets, nests, trabecular structures, or as single cells infiltrating the stroma against a background of chondromyxoid matrix (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eH). The nuclei were highly atypical with abundant mitotic figures (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eI).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eImmunophenotype and Molecular Characteristics\u003c/h3\u003e\n\u003cp\u003eAll tumor cells diffusely and strongly expressed S-100 (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, B), GATA3, AE1/AE3, and EMA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Notably, tumor cells in component one expressed LYS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD) and AACT. Both components were negative for ER (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE), PR, HER2, CK5/6, CD117, P63, and Collagen IV (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF). The Ki-67 proliferation index was approximately 10% in the low-grade areas of component one (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eG), about 30% in its high-grade areas (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eH), and approximately 70% in component two (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eI). Next-generation sequencing of different tumor areas detected a somatic frameshift mutation in the \u003cem\u003eTP53\u003c/em\u003e gene (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) with a variant allele frequency of 36.51%, as well as germline non-pathogenic variants in \u003cem\u003eAPC, ATM, BRCA1, BRCA2\u003c/em\u003e, and others (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGermline gene variants detected by next-generation sequencing.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" 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align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000059\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec.7397 T\u0026thinsp;\u0026gt;\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Val2466Ala\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCHEK1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_001114121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec. 1411 A\u0026thinsp;\u0026gt;\u0026thinsp;G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Ile471Val\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEPCAM\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_002354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec.344 T\u0026thinsp;\u0026gt;\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Met115Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e67.96%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMSH6\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec. 116 G\u0026thinsp;\u0026gt;\u0026thinsp;A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Gly39Glu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e67.81%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePALB2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_024675\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec. 1676 A\u0026thinsp;\u0026gt;\u0026thinsp;G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Gln559Arg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49.03%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePMS2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000535\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec. 1621 A\u0026thinsp;\u0026gt;\u0026thinsp;G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Lys541Glu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e99.83%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePMS2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000535\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec. 1408 C\u0026thinsp;\u0026gt;\u0026thinsp;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Pro470Ser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e47.94%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePMS2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000535\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec.59 G\u0026thinsp;\u0026gt;\u0026thinsp;A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Arg20Gln\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e46. 19%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePOLD1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_002691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec.356 G\u0026thinsp;\u0026gt;\u0026thinsp;A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Arg119His\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e99.79%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTP53\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec.215 C\u0026thinsp;\u0026gt;\u0026thinsp;G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Pro72Arg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27.38%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTSC1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNM_000368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexon 19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec.2485 A\u0026thinsp;\u0026gt;\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Ser829Arg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70.09%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eTreatment and Prognosis\u003c/h3\u003e\n\u003cp\u003eThe patient underwent modified radical mastectomy with sentinel lymph node biopsy, followed by adjuvant EC-T chemotherapy. After 13 months of follow-up, the patient remains in good condition with no evidence of recurrence or metastasis. Long-term follow-up is ongoing.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBreast acinar cell carcinoma (AcCC) was first reported by Roncaroli et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] in 1996, initially termed \"acinic cell-like carcinoma of the breast.\" The 5th edition of the WHO Classification of Breast Tumours lists it among rare salivary gland-type tumors. With increasing recognition, more cases have been reported; as of late November 2024, over 70 cases have been documented in the literature worldwide [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although its histological patterns overlap with those of salivary gland AcCC, studies indicate they have different genetic alterations. Hence, scholars like Rosen et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] propose that so-called breast AcCC is essentially \"invasive carcinoma arising in microglandular adenosis with acinar cell differentiation,\" and the spectrum from typical MGA to atypical MGA and associated carcinomas can show different types of differentiation, seemingly supporting Rosen's view. However, in the present case, thorough sampling and immunohistochemical analysis did not reveal MGA or atypical MGA components. Although breast AcCC was previously thought to share the relatively indolent behavior and good prognosis of salivary AcCC, cases with recurrence, metastasis, or death have also been reported [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], especially when high-grade morphology or co-existence with other breast carcinoma types is present.\u003c/p\u003e \u003cp\u003eClinical Presentation and Histological Features: A comprehensive clinicopathological analysis of 72 reported cases of breast AcCC reveals no specific trends regarding patient age (range 23\u0026ndash;80 years, average 47 years), tumor location, or imaging features. Clinically, patients most often present with a breast mass. Notably, one case of breast AcCC in a 23-year-old male has been reported [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Histologically, breast AcCC typically exhibits acinar cell differentiation similar to salivary glands, characterized by granular cytoplasm and PAS-positive, diastase-resistant granules. At low magnification, it consists of irregular acinar structures lined by one to several layers of epithelial cells. Tumor cells in the classical AcCC component are round or cuboidal with eosinophilic granular cytoplasm and indistinct borders. Myoepithelial cells and a basal membrane are absent around the glands, and eosinophilic secretions are often observed within lumina. When high-grade transformation occurs, acini merge into small solid or cribriform nests, and nuclei become pleomorphic, vesicular with prominent nucleoli, accompanied by significant pathological mitotic figures and a high Ki-67 proliferation index. Besides high-grade transformation, breast AcCC can also co-exist with other types of breast carcinoma, usually invasive carcinoma of no special type. Winkler et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and Piscuoglio et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] reported two cases co-existing with metaplastic carcinoma, similar to the present case. Piscuoglio et al. suggested the term \"mixed breast AcCC\" when the other carcinoma type constitutes 50%\u0026ndash;90% of the tumor.\u003c/p\u003e \u003cp\u003eImmunophenotype and Molecular Characteristics: The immunohistochemical profile of breast AcCC sometimes overlaps with TNBC. Most cases are negative for ER, PR, and HER2 and lack myoepithelial markers (CK5/6, p63 and Calponin) and basement membrane markers (Collagen IV and Laminin). The diagnostic utility lies in the frequent strong positivity of AcCC for S-100 and one or more serous differentiation markers such as Lysozyme (LYS), α1-antichymotrypsin (AACT), and α1-antitrypsin (ACT), which are typically absent in TNBC. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the immunophenotypic characteristics of breast AcCC from previous reports. Some studies also suggest diagnostic value for CK5/6 and CD117 in breast AcCC [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], although, unfortunately, our case did not show immunoreactivity for these markers. Breast AcCC often shares similar molecular genetic alterations with high-grade TNBC, such as mutations in TP53, PIK3CA, MTOR, etc., with TP53 being the most frequently mutated gene. In our case, NGS detected only a TP53 mutation without other genetic alterations. Piscuoglio et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] performed Sanger sequencing on 10 breast and 20 salivary AcCCs, revealing \u003cem\u003eTP53\u003c/em\u003e (8/10, 80%) and \u003cem\u003ePIK3CA\u003c/em\u003e (1/10, 10%) mutations in breast AcCC, while salivary AcCC harbored none of these mutations (0/20, 0%), indicating distinct genetic pathways. Furthermore, Elena et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] performed genetic testing on four cases of mixed high-grade AcCC (three with invasive ductal carcinoma of no special type, one with metaplastic carcinoma) and found identical somatic mutations in the different components of two cases, suggesting a clonal relationship between the acinar and high-grade non-acinar components. This finding provides indirect genetic evidence that, in some instances, breast AcCC may constitute the precursor lesion for the development of aggressive TNBC with higher histological grade or more aggressive subtypes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImmunohistochemical marker expression in previous literature.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunohistochemical Marker\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResult\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of Cases (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阴性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90.9(50/55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阴性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e88.9(48/54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER\u0026minus;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阴性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e95.0(38/40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阳性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100.0(27/27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS\u0026minus;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阳性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92.7(51/55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLys\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阳性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e95.3(41/43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAACT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阳性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96.0(24/25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阳性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92.3(24/26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGATA\u0026minus;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e阳性\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66.7(4/6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDifferential Diagnosis: Utilizing the unique histological features of AcCC (e.g., eosinophilic, granular cytoplasm, eosinophilic intraluminal secretions) and its characteristic immunophenotype (positivity for S-100, LYS, AACT, etc.) aids in distinguishing it from other TNBC subtypes. In our view, the most challenging differential diagnosis involves the spectrum of MGA and atypical MGA, due to their similar morphology and immunophenotype. MGA is a rare benign breast lesion defined as a haphazard proliferation of small glands composed of a single epithelial layer without an accompanying myoepithelial cell layer. When glands in MGA merge into solid or cribriform nests, it is termed atypical MGA. There is extensive histological overlap between the tubular or microglandular structures of breast AcCC and MGA. Currently, the most crucial distinguishing feature is the preservation of the basement membrane in MGA, which can be demonstrated using markers like Collagen IV and Laminin. Some scholars have observed a morphological spectrum from typical MGA to atypical MGA to AcCC within the same case [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], coupled with shared genetic alterations like TP53 mutations, further supporting Rosen's view of \"invasive carcinoma arising in microglandular adenosis with acinar cell differentiation.\" However, in our case, no MGA or atypical MGA components were found. Another important consideration is distinguishing primary or metastatic salivary gland AcCC. Besides integrating clinical history, the novel marker NR4A3 has been reported to have significant diagnostic value. Richardson et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] performed NR4A3 immunohistochemistry on 16 breast AcCCs (8 pure, 8 mixed), all of which were negative. Similarly, Florian et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] conducted immunohistochemical and FISH studies on 64 salivary AcCCs and 99 other salivary gland tumors, finding NR4A3 to be a highly sensitive (98%) and specific (100%) marker for salivary AcCC, especially in cases with high-grade transformation. This further substantiates the different molecular pathways between breast and salivary AcCC.\u003c/p\u003e \u003cp\u003eIn summary, breast AcCC is a rare salivary gland-type tumor of the breast with a broad morphological spectrum, ranging from well-differentiated tubular or microglandular structures to high-grade and poorly differentiated components. When high-grade transformation occurs or it co-exists with other breast carcinoma types, its metastatic potential appears to increase [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Compared to conventional TNBC, breast AcCC possesses unique biological characteristics and a potentially lower aggressive potential; some patients follow an indolent clinical course and may not require further treatment after surgical excision. However, its histological origin requires accumulation of more cases and further research. This report aims to provide a morphological and molecular basis for understanding the possible mechanisms underlying high-grade lesions and mixed carcinomas in breast AcCC, while offering diagnostic insights for future similar cases to avoid misdiagnosis and improve patient quality of life.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSC Liu Responsible for data collection and paper writing. HY Hu responsible for reviewing papers. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting this study are publicly available\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and Accordance Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was reviewed and approved by the Hefei Anweikang Medical Laboratory Pathology Center, confirming its compliance with the relevant guidelines of the International\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCommittee of Medical Journal Editors (ICMJE). The above content can be reflected in the patient's admission authorization form, and no further ethical approvals are required. All personal data have been processed in an anonymous form to protect patient privacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patients to participate in this work and to use their case details for teaching and publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained for the patient’s data included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAccordance Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods in this study were carried out in accordance with relevant guidelines and regulations\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGe Y, Wei X, Liu JN, Sun PL, Gao H. New insights into acinic cell carcinoma of the breast: clinicopathology, origin of histology, molecular features, prognosis, and treatment. Front Oncol. 2024 Sep 2;14:1438179. \u003c/li\u003e\n\u003cli\u003eQin F, Li J, Zheng Y, Jiang C, Jia Y, Sun H, Xue H, et.al. Breast Carcinomas Resembling Acinic Cell Carcinoma: Comprehensive Analysis of 14 Cases and Review of the Literature. Am J Surg Pathol. 2025 May 1;49(5):448-457. \u003c/li\u003e\n\u003cli\u003eRoncaroli F, Lamovec J, Zidar A, Eusebi V. Acinic cell-like carcinoma of the breast. Virchows Arch. 1996 Sep;429(1):69-74. \u003c/li\u003e\n\u003cli\u003eLu Y, Kong X, Wang X, Zhang W, Li Y, Dong H, Wang Z, et.al. Deciphering primary acinic cell carcinoma of the Breast: Insights from a comprehensive case series and Systematic review. Cancer Treat Rev. 2024 Dec;131:102830. \u003c/li\u003e\n\u003cli\u003eRosen PP. So-called acinic cell carcinoma of the breast arises from microgladular adenosis and is not a distinct entity. Mod Pathol. 2017 Oct;30(10):1504. \u003c/li\u003e\n\u003cli\u003eYang X, Liu F, Li C, Li Z, Wang P, Zhang M, Liu Y, et.al. Clinicopathological, immunohistochemical and molecular features of acinic cell carcinoma of the breast. Oncol Lett. 2024 Jan 18;27(3):107. \u003c/li\u003e\n\u003cli\u003eSarsiat L, Watkinson G, Turnbull A, Diana A, Oikonomidou O. Primary acinic cell carcinoma Oncol. 2022 Feb;16(2):43. \u003c/li\u003e\n\u003cli\u003eAtta IS Sr. Acinic Cell Carcinoma of the Breast: A Case Report and Review of Literature. Cureus. 2024 Jan 1;16(1):e51427. \u003c/li\u003e\n\u003cli\u003eShimao K, Haga S, Shimizu T, Imamura H, Watanabe O, Kinoshita J, Nagumo H, et.al. Acinic Cell Adenocarcinoma Arising in the Breast of a Young Male: A Clinicopathological, Immunohistochemical and Ultrastructural Study. Breast Cancer. 1998 Jun 30;5(1):77-81. \u003c/li\u003e\n\u003cli\u003eWinkler N, Morrell G, Factor RE. Invasive carcinoma with acinic cell-like features of the breast. Breast J. 2013 May-Jun;19(3):334-5. \u003c/li\u003e\n\u003cli\u003ePiscuoglio S, Hodi Z, Katabi N, Guerini-Rocco E, Macedo GS, Ng CK, Edelweiss M, et.al. Are acinic cell carcinomas of the breast and salivary glands distinct diseases? Histopathology. 2015 Oct;67(4):529-37. \u003c/li\u003e\n\u003cli\u003eGuerini-Rocco E, Hodi Z, Piscuoglio S, Ng CK, Rakha EA, Schultheis AM, Marchi\u0026ograve; C, et.al. The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis-generating study. J Pathol. 2015 Oct;237(2):166-78. \u003c/li\u003e\n\u003cli\u003eConlon N, Sadri N, Corben AD, Tan LK. Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype. Hum Pathol. 2016 May;51:16-24. \u003c/li\u003e\n\u003cli\u003eGuerini-Rocco E, Hodi Z, Piscuoglio S, Ng CK, Rakha EA, Schultheis AM, Marchi\u0026ograve; C, et.al. The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis-generating study. J Pathol. 2015 Oct;237(2):166-78. \u003c/li\u003e\n\u003cli\u003eSugino T, Kakuda Y, Yasui H, Oishi T, Norose T, Kawata T, Tadokoro Y, et.al. A case of extensively spreading acinic cell carcinoma of the breast with microglandular features. Pathol Int. 2023 Jan;73(1):45-51. \u003c/li\u003e\n\u003cli\u003eFalleti J, Coletti G, Rispoli E, Scarabeo F, Cervasio M, Tornillo L, Pettinato G, et.al. Acinic cell carcinoma of the breast arising in microglandular adenosis. Case Rep Pathol. 2013;2013:736048. \u003c/li\u003e\n\u003cli\u003eRichardson ET, Selenica P, Pareja F, Cin PD, Hanlon E, Weigelt B, Reis-Filho JS, et.al. NR4A3 Expression Is Consistently Absent in Acinic Cell Carcinomas of the Breast: A Potential Nosologic Shift. Mod Pathol. 2023 Jun;36(6):100144. \u003c/li\u003e\n\u003cli\u003eHaller F, Moskalev EA, Kuck S, Bieg M, Winkelmann C, M\u0026uuml;ller SK, Ihrler S, et.al. Nuclear NR4A2 (Nurr1) Immunostaining is a Novel Marker for Acinic Cell Carcinoma of the Salivary Glands Lacking the Classic NR4A3 (NOR-1) Upregulation. Am J Surg Pathol. 2020 Sep;44(9):1290-1292. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"AcCC, Breast cancer, Metaplastic carcinoma, Immunohistochemistry, NGS","lastPublishedDoi":"10.21203/rs.3.rs-8858807/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8858807/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBreast acinar cell carcinoma (AcCC) is a rare subtype of triple-negative breast cancer. Its histological origin remains controversial, and it exhibits poor sensitivity to conventional chemotherapy. High-grade transformation and co-existence with matrix-producing metaplastic carcinoma are uncommon, and their clinical and molecular genetic features are poorly understood.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eA 42-year-old woman incidentally discovered a breast mass for 10 days. Ultrasound revealed multifocal tumors in the upper inner quadrant of the left breast, classified as BI-RADS 4b, leading to a clinical diagnosis of breast cancer. Microscopically, the tumor comprised two distinct components. Component one exhibited tubular or solid nested patterns with eosinophilic secretions in lumina; some cells were amphophilic, and focal areas showed marked high-grade transformation with significant nuclear atypia. Component two featured tumor cell cords and nests distributed within a chondromyxoid stromal matrix. Immunophenotypically, tumor cells in both components diffusely and strongly expressed S-100, GATA3, AE1/AE3, and EMA. Component one expressed Lysozyme (LYS) and α1-antichymotrypsin (AACT). Both components were negative for ER, PR, HER2, CK5/6, CD117, P63, and Collagen IV. The Ki-67 proliferation index was approximately 10% in the low-grade areas of component one, reached about 30% in its high-grade areas, and was approximately 70% in component two. Molecular genetics: Next-generation sequencing detected a somatic frameshift mutation in the \u003cem\u003eTP53\u003c/em\u003e gene with a variant allele frequency of 36.51%, as well as germline non-pathogenic variants in \u003cem\u003eAPC, ATM, BRCA1, BRCA2\u003c/em\u003e, and others.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis report describes a breast tumor exhibiting concurrent features of AcCC and matrix-producing metaplastic carcinoma, summarizing its immunophenotypic characteristics and molecular genetic alterations. This information may provide diagnostic insights for future encounters with similar cases.\u003c/p\u003e","manuscriptTitle":"A case of breast acinar cell carcinoma combined with metaplastic carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 16:32:20","doi":"10.21203/rs.3.rs-8858807/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-06T23:52:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-06T16:17:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246023034976938496384336558465150056131","date":"2026-03-04T14:12:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7111138307321383454654016251612083034","date":"2026-03-03T08:06:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-03T02:41:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-02T03:52:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"242180067270424318930041136084482325790","date":"2026-03-01T14:59:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"278386384129812846311975767045125049456","date":"2026-02-28T23:58:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70564903345327725984394041004312419889","date":"2026-02-28T01:28:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18169049217962828735408886710663518039","date":"2026-02-27T14:55:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-27T11:39:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-24T06:27:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-24T04:09:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-23T13:21:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-02-23T13:16:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a4d0a1f-76d1-463e-a01e-ef71629a1542","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T23:38:47+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 16:32:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8858807","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8858807","identity":"rs-8858807","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}