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Background: Adenoid cystic carcinoma (ACC) is primarily a disease of the salivary glands and is exceptionally rare in the male breast, representing less than 0.1% of all male breast cancers. Due to its rarity, there is no established consensus or recognised guidelines for management. This review aims to synthesise existing literature to improve clinical awareness and knowledge of male breast ACC (MB-ACC).
Methods: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Google Scholar for cases of MB-ACC published between 1969 and 2025. Inclusion criteria focused on peer-reviewed case reports providing clinical, histopathological, and immunohistochemical data. Approximately 20 cases were identified and analysed.
Results: MB-ACC often presents as a slow-growing, subareolar mass, with a median age of onset (41.5 years) younger than typical male breast cancer. Diagnosis is confirmed via histopathology showing cribriform, tubular, or solid patterns with a double-layered cell structure. Most tumours are triple-negative (ER-/PR-/HER2-), though they paradoxically exhibit an indolent clinical course and favourable long-term prognosis compared with other triple-negative cancers. Management is primarily surgical, with modified radical mastectomy being the most frequently reported procedure.
Conclusion: Although MB-ACC shares histological features with aggressive basal-like carcinomas, it carries a favourable prognosis. Early diagnosis through awareness is essential to avoid advanced presentation. Given the potential for late recurrence, long-term follow-up is recommended.
Keywords: Adenoid Cystic Carcinoma, Immunohistochemistry, Male Breast Neoplasms, Modified Radical Mastectomy, Rare Diseases, Triple Negative Breast Neoplasms
Male breast cancer (MBC) accounts for less than 1% of all breast cancer diagnoses worldwide, making it a rare disease in comparison with female breast cancer [1, 2]. According to histopathology, invasive ductal carcinoma of no special type (NST) accounts for most of MBC (75%–90%), with tumours frequently being luminal A or B molecular subtypes [3]. Papillary carcinoma and, rarely, invasive lobular carcinoma are other, less prevalent variants. Male breast adenoid cystic carcinoma (MB-ACC) is an exceptionally rare type of MBC [4]. It is a distinct cancer with clinicopathological characteristics that set it apart from other types of MBC, but due to its extreme rarity, the literature is meagre. Adenoid cystic carcinoma (ACC) was first described by Robin and Laboulbene in 1853 as “ tumeur heteradenique”, and Geschikter in 1945 was the first to use the term “ACC” in breast oncology [4]. Ferlito [5] was the first to report MB-ACC in 1969, and about 20 cases have been reported in peer-reviewed literature since then. Due to the scarcity of literature, the diagnostic and therapeutic recommendations for MB-ACC have yet to be determined; currently, both diagnostic and therapeutic modalities rely on guidelines developed for female patients [4]. The purpose of this narrative review is to highlight the pathophysiology, clinical characteristics, and existing treatment options to increase healthcare providers’ awareness and add to the existing body of information.
To identify all documented cases of primary male breast adenoid cystic carcinoma (MB-ACC), a systematic literature search was conducted between August and December 2025. The search encompassed the PubMed/MEDLINE, Scopus, and Google Scholar databases, covering the period from 1969 (the date of the first reported case) through December 2025. The search strategy utilized a combination of Medical Subject Headings (MeSH) and free-text keywords, including: “male breast cancer,” “adenoid cystic carcinoma,” “MB-ACC,” and “primary breast adenoid cystic carcinoma.” Study Selection and Systematic Filtering Following the initial identification of records, titles and abstracts were screened for relevance. Fulltext articles were then retrieved and evaluated against strict inclusion and exclusion criteria to ensure diagnostic and clinical accuracy. Studies were included if they were peer-reviewed case reports, case series, or observational studies involving male patients with a confirmed diagnosis of primary adenoid cystic carcinoma (ACC) of the breast, and if they provided sufficiently granular clinical, histopathological, or immunohistochemical (IHC) data. Studies were excluded where anatomical specificity was lacking, such as cases in which ACC originated from extra-mammary sites (for example, salivary glands, lung, or skin) with secondary metastasis to the breast. We also excluded abstracts, letters, and conference proceedings that did not provide definitive pathological confirmation—such as clear descriptions of cribriform, tubular, or solid growth patterns—or relevant IHC markers (for example, CD117/c-KIT and p63). Studies focused exclusively on female cohorts, or those in which male-specific data could not be separated, were likewise excluded. To avoid double-counting rare cases, potentially overlapping reports from the same institution or author were cross-referenced using patient age and clinical history, and only the most comprehensive or most up-to-date report was retained. Data Extraction and Synthesis Data were systematically extracted regarding patient demographics, clinical presentation (e.g., mass location, duration of symptoms), imaging characteristics, surgical interventions, adjuvant treatments (radiotherapy/chemotherapy), and long-term oncological outcomes. Given the rarity of MB-ACC, the data were qualitatively synthesized to provide a comprehensive overview of the current diagnostic and therapeutic landscape.
The exact aetiology of male breast adenoid cystic carcinoma (MB-ACC) remains largely elusive. In general, male breast cancer risk factors such a BRCA2 mutations, Klinefelter syndrome, and hyperestrogenism are well-recognized [6]. However, these factors have not been consistently linked to the ACC subtype in men, which often lacks the strong hormonal association seen in ductal MBC. Unlike the more common hormone-receptor-positive MBCs, MB-ACC typically presents a triple-negative phenotype. At the molecular level, the MYB-NFIB gene fusion, resulting from the t(6;9)(q22-23;p23-24) translocation, is considered a hallmark of salivary gland ACC and has been confirmed in cases of female breast ACC [7, 8]. The genomic data for male patients is still very limited; however, this genetic rearrangement is hypothesised to be a key driver of MB-ACC. It contributes to the distinct “triple-negative paradox,” where aggressive markers are present alongside an indolent clinical course [9]. In the end, a significant information gap in the literature is the absence of extensive genetic research in MB-ACC. To ascertain whether the aetiological causes of MB-ACC are similar to those of its salivary gland counterparts or if distinct male-specific variables exist, more research employing next-generation sequencing (NGS) is required.
The incidence of MB-ACC is very low, with fewer than 20 cases reported since its first description by Ferlito in 1969 [5]. Of these, about half of the cases were reported in the past decade, which may indicate a trend toward increased incidence [4]. The susceptibility of various racial subpopulations to MB-ACC is definitely not known, although 75% of the cases reported in the past three decades were reported in Asia [4]. Regarding the female variant of breast ACC, a population-based cohort study conducted in the USA by Ghabach et al. [9] indicated that black females have a lower rate of incidence than their white counterparts. The age of onset for MB-ACC is lower (median 41.5 years) than that seen in other male breast cancer patients, and many cases have been reported in patients in their teens and twenties. This contrasts with female breast ACC patients, where the median age of onset is 58-66 years old [4].
The most consistent presentation of MB-ACC is a slow-growing, hard, palpable subareolar lump that may be accompanied by pain and/or tenderness [10-12]. The tumour mass is solitary in most cases, and the mean tumour size in the reported cases ranges between 1.2 and 5 cm (the median is 2.6 cm). There is no significant difference in incidence between the left and right breasts [4]. Less common symptoms include skin ulceration, discharge, nipple retraction, and distant metastasis. Delays in seeking medical treatment may result from the lump's extremely slow growth [11]. Li et al. [4] reported a case of MB-ACC in a 24-year-old male who presented with a 1 cm left subareolar lump that had been growing slowly for 5 years. Similarly, Wan et al. [12] described a 38-year-old male who experienced nipple retraction with minimal pain and redness in 2013, but chose not to seek medical help. The condition worsened over time until he presented to the hospital in 2015. Clinical Contraindications and Divergence While the literature generally characterises MB- ACC as an “indolent” disease, individual case reports present sharp contradictions regarding its biological behaviour. Most patients demonstrate an indolent course and can remain asymptomatic for years [4,12].
However, Yoo et al. reported a strikingly aggressive outlier: a 41-year-old patient who presented with advanced distant metastases to the lungs, bone marrow, and axial skeleton [13]. Although axillary lymphadenopathy is generally rare in male breast ACC (MB-ACC), contradictory findings have been described. For example, Li et al. reported postoperative PET/CT evidence of metabolically active lymph nodes in the neck and bilateral axillae [4]. Clinically, most cases present as a simple breast mass; nevertheless, unusual presentations have been reported, particularly among elderly patients. These include aggressive ulcero-proliferative lesions and persistent mucinous discharge, which can mimic more typical invasive breast carcinomas [14].
Mammography: MB-ACC may appear as a lobulated or circumscribed mass in the subareolar area, sometimes with unclear margins or spiculations, thereby resembling other benign or malignant tumours [10]. Ultrasonography: Ultrasonography (USG) is typically used to evaluate the mass, but findings are often non-specific, including clear or indistinct boundaries, irregular shapes, and hypoechoic and heterogeneous masses [4,10]. In the case reported by Tang et al. [10], USG revealed an irregular, mixed echoic, partially compressible mass (21 mm × 20 mm × 9 mm) in the subareolar region of the right breast. Ultrasonography in a case presented by Pang et al. [15] revealed an irregular hypoechoic lesion (12.8 mm × 9.9 mm × 6.7 mm) with an unclear boundary and minimal vascularity. The lesion had an attachment to the nipple and did not display any posterior acoustic shadowing or echogenic halo. In the case presented by Li et al. [4], serial ultrasonography revealed a well-defined oval hypoechoic mass in the retroareolar region of the left breast that progressively enlarged over the course of 2 years (Figure 1).
Computed tomography (CT) scan: By displaying the size, location, and possible dissemination to bone or lymph nodes, a CT scan can aid in the diagnosis of MB-ACC. Features such as osteolytic (bone-destroying) lesions, an uncommon but typical pattern of bone metastases for this cancer type, can be seen on the scan [10]. Magnetic resonance imaging (MRI): MRI findings for MB-ACC are not specific enough for a definitive diagnosis but can provide valuable information that can aid in management, including a characteristic enhancement pattern with gadolinium, T2 signal, and potential internal structures. Pang et al. [15], in 2019, were the first to use this modality to evaluate MB-ACC when they demonstrated its appearance as a solitary oval subareolar nodule with a spiculated margin and invasion of the nipple. The lesion displayed low signal intensity on T1WI and high signal intensity on T2WI. The time-signal intensity curve demonstrated plateau enhancement kinetics, and tumour enhancement was rapid and homogeneous on dynamic contrast-enhanced scanning MRI. Positron emission tomography (PET): The local extent of MB-ACC and its distant spread can be found using PET. Li et al. [4] re-evaluated their operated case when a biopsy revealed the diagnosis of MB-ACC and, as depicted in Figure 2, the 18 F-FDG PET-CT (Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) revealed a disordered subcutaneous structure in the left breast region accompanied by increased metabolism, indicating postoperative changes. No significant metabolic abnormalities were observed anywhere else, except in a few small lymph nodes in the neck and both the axillae.
Figure 2. Whole-body evaluation by 18 F-FDG PET/CT. The 18 F-FDG PET/CT MIP (a) shows uptake (SUVmax 2.5) in the left breast lesion (b and d, red arrows), with a disordered tissue structure (c, red arrow). Small lymph nodes were found in the bilateral neck and bilateral axillary regions (e-g, red arrows, SUVmax 1.65). 18 F-FDG PET/CT: 18 F- fluorodeoxyglucose positron emission tomography/computed tomography; MIP: maximum intensity projection; SUVmax: maximum standardized uptake value. Image source: Li et al. (4) doi: 10.14740/jmc3790; reused under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License.
Histopathological examinations are essential to confirm the diagnosis of MB-ACC (Figure 3).
Morphologically, MB-ACC and salivary gland ACC are similar. Microscopic examination of the excised tissue usually reveals diffuse tumour invasion of the subcutaneous tissue, with cells arranged in three microscopic growth patterns, either alone or in combination—cribriform, tubular, and solid [16]. Occasionally, microcystic patterns may be present. Within each tumour pattern, double-layered structures comprising inner glandular epithelial and outer myoepithelial/basal cells can be found. The glandular epithelial cells exhibit a cuboidal shape, acidophilic cytoplasm, round nucleus, and occasional nucleoli, whereas the myoepithelial/basal cells exhibit a spindle shape, low cytoplasmic volume, intense nuclear staining, and sporadic mitosis [12]. However, unlike salivary gland ACC, MB-ACC uncommonly features nerve infiltration [4]. Ro et al. [17] have proposed a classification of breast ACC (either gender) based on the proportion of solid components within the lesion. Accordingly, there are three grades: grade I with no solid growth, grade II with solid growth less than 30%, and grade III with solid growth more than 30%. They have further observed that grade II and III tumours tend to be larger in size and more prone to relapse.
The immunohistochemical characteristics of MB- ACC resemble those of basal-like carcinoma (Figure 3). The outer myoepithelial cells are usually positive for 34βE12, smooth muscle actin (SMA), calponin, vimentin, S-100, and P63 markers, whereas the inner glandular epithelial cells often express CD117 (C-kit), epithelial membrane antigen (EMA), CK5/6, CK8/18, and CK14, but mostly do not express oestrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER- 2), though some cases with weak ER positivity have been reported [8]. The basement membrane is highlighted by collagen type IV staining.
MYB is a proto-oncogene located in 6q22-23 and has been documented in a variety of malignant lesions. A defining molecular event in ACC is the recurrent reciprocal translocation of t(6;9)(q22- 23;p23-24), which results in the MYB-NFIB gene fusion [7-8,18]. Frequency in MB-ACC: The molecular genetic data of MB-ACC are limited. Among the cases reported in the literature, only three were reported to have undergone MYB gene testing, and MYB- NFIB gene fusion was detected in only one case [12]. Diagnostic significance: The MYB-NFIB fusion has high diagnostic significance. It serves as a specific biomarker that distinguishes ACC from its mimics, such as solid papillary carcinoma or cribriform ductal carcinoma in situ (DCIS). While MYB protein overexpression (detected via IHC) is a sensitive surrogate, the presence of the actual gene fusion via FISH is considered the gold standard for confirming the diagnosis in challenging or high-grade cases [19]. Prognostic significance: To date, the presence of the MYB-NFIB fusion does not have clear prognostic significance in MB-ACC. Studies in both breast and salivary ACC have failed to show a definitive correlation between fusion status and overall survival or recurrence risk [18]. Recommendations for routine testing: Routine molecular testing for the MYB-NFIB fusion is not currently mandatory for all cases, as the diagnosis can often be established through classic histomorphology and a standard IHC panel (p63, CD117, and triple-negative status). However, it can strengthen the diagnosis in cases with an aggressive clinical course, high ‐ grade histological features, or those with a “solid” variant morphology where the differential diagnosis is broader [19]. The clinical and pathological characteristics of the identified cases of MB-ACC are summarized in Table 1.
Male breast adenoid cystic carcinoma (MB-ACC) represents a rare clinical paradox, characterised by a triple-negative phenotype that behaves with a remarkably indolent clinical course. While the long-term prognosis remains favourable compared with other male breast malignancies, management is complicated by a lack of standardised protocols and the absence of large-scale genomic data. Histological grade is the main factor influencing clinical outcomes, and solid growth patterns are important indicators of recurrence. A comprehensive, long-term surveillance program is essential due to the ongoing risk of late recurrence. Furthermore, a holistic approach to care is necessary to address the significant psychosocial impact of mastectomy and the high healthcare resource utilisation required for a definitive diagnosis. Ultimately, the rarity of MB-ACC remains a significant barrier to evidence-based practice. Future efforts must prioritise the establishment of international registries and the exploration of molecular drivers to move toward more personalised and targeted therapeutic strategies for this unique patient population.
MB-ACC: Male breast adenoid cystic carcinoma MBC: Male breast cancer ACC: Adenoid cystic carcinoma SLNE: Sentinel lymph node excision CDC: Cribriform ductal carcinoma ICC: Invasive cribriform carcinoma ER: Estrogen receptors PR: Progesterone receptors HER-2: Human epidermal growth factor receptor-2 USG: Ultrasonography CT: Computed tomography PROMs: Patient-reported outcome measures