Adenoid cystic carcinoma of the breast, from diagnosis to management: a case report

Abstract

Background

Adenoid cystic carcinoma of the breast is a rare subtype, constituting less than 3.5% of primary breast carcinomas. Despite being categorized as a type of triple-negative breast cancer, it generally has a favorable prognosis. The primary management approach typically involves breast-conserving surgery. Due to its rarity, diagnosis can be challenging, emphasizing the importance of histopathological confirmation with clinical and imaging correlation. Although this tumor often has a favorable prognosis, additional research is necessary to better understand its clinical, radiological, and pathological features.

Case presentation

We present the case of a 54-year-old Colombian woman of Hispanic ethnicity who had a lesion detected by mammography at the junction of the upper quadrants. Breast ultrasound revealed a Breast Imaging Reporting & Data System category 5 solid nodule, 0.8 × 0.7 cm, with irregular borders in the left breast and no axillary abnormalities. A biopsy confirmed infiltrating carcinoma with tubular and cribriform patterns. Immunohistochemistry was consistent with adenoid cystic carcinoma of the breast (triple-negative). Contrast-enhanced breast magnetic resonance imaging showed a primary tumor measuring 18 × 11 × 15 mm at the upper quadrant interface, along with another suspicious mass measuring 50 × 10 mm in the retroareolar region, as well as multiple adjacent enhancing foci suggestive of multicentric tumor involvement with probable ductal extension. Due to potential multifocality, the patient underwent a nipple-sparing mastectomy and sentinel node dissection. Pathology revealed a unifocal retroareolar adenoid cystic carcinoma measuring 2.5 mm, situated less than 1 mm from the deep surgical margin and with a positive anterior margin. There was no evidence of lymphovascular or perineural invasion. The final diagnosis was triple-negative adenoid cystic carcinoma, classic subtype. A multidisciplinary board recommended radiotherapy and imaging follow-up. Postoperative outcomes remained satisfactory during follow-up with the breast surgeon.

Conclusion

This case report aims to raise awareness within the medical community regarding this rare cancer, highlighting the importance of accurate clinicopathological recognition and diagnosis. Multidisciplinary management remains crucial as the cornerstone of care, especially for offering therapies tailored to each patient’s specific needs.

Background

Adenoid cystic carcinoma (ACC) of the breast is a rare cancer subtype, constituting 0.1–3.5% of primary breast carcinomas [1]. Due to its rarity, accurate diagnosis requires a strict clinical and imaging correlation, with histopathological confirmation serving as the cornerstone [2]. Most cases arise as unifocal lesions in women aged 50–60 years, though occasional cases have been documented in men. Histologically, ACC has epithelial and myoepithelial components, showing varied architecture with solid, cribriform, and tubular–trabecular patterns [3].

Most breast ACC cases have a favorable prognosis, even within the triple-negative subgroup [4]. Given its generally favorable clinical behavior and low rates of metastasis and recurrence, breast-conserving surgery is typically the primary treatment, with limited benefit observed from adjuvant therapy [5]. Correct diagnosis is essential to prevent overtreatment. Here, we discuss a case of a 54-year-old woman with a mass identified on imaging at the junction of the upper left breast quadrants. Histopathologic testing confirmed adenoid cystic carcinoma, and the patient underwent total mastectomy.

Case presentation

A 54-year-old Colombian woman of Hispanic ethnicity, who was asymptomatic and postmenopausal, was referred to our hospital following the mammographic detection of a lesion at the junction of the upper breast quadrants. Her medical history included a great-grandmother and a maternal aunt diagnosed with breast cancer under the age of 40 years. Breast ultrasound showed a solid nodule, 0.8 × 0.7 cm, with irregular borders at the 12 o’clock position, 5 cm from the nipple in the left breast. No axillary abnormalities were detected. The lesion was classified as Breast Imaging Reporting & Data System (BI-RADS) category 5, and biopsy was performed.

Biopsy results showed infiltrating carcinoma with tubular and cribriform patterns, along with mucinous and eosinophilic luminal secretions. Immunohistochemistry revealed cytokeratin (CK) 7, epithelial membrane antigen (EMA), and CD117 positivity in epithelial cells, and tumor protein (p) 63 and calponin positivity in myoepithelial cells (Fig. 1). The tumor was estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2 negative, with a Ki-67 index of 10% and a programmed death ligand 1 (PD-L1) combined positive score (CPS; Clon 22C3) of 15. Findings and immunophenotype were consistent with adenoid cystic carcinoma of the breast, histologic grade I (Nottingham score). Contrast-enhanced breast magnetic resonance imaging (MRI) revealed multicentric tumor involvement with probable ductal extension (Fig. 2), but no lymphadenopathy.

Fig. 1.

Ultrasound-guided core needle biopsy of a mass in the left breast. A Tumoral epithelial proliferation with a cribriform growth pattern (hematoxylin and eosin 10×). B Dual population of tumor cells forming tubules with mucinous (red asterisk) and eosinophilic secretion (black triangle; hematoxylin and eosin 40×). C Epithelial cells highlighted by cytokeratin 7 immunohistochemical stain (10×). D Myoepithelial cells highlighted by tumor protein 63 immunohistochemical stain (10×)

Fig. 2.

Left breast imaging. Contrast-enhanced nuclear magnetic resonance imaging in axial (A) and sagittal (B) views revealed a primary tumor measuring 18 × 11 × 15 mm located at the interface of the upper quadrants, as well as another suspicious mass measuring 50 × 10 mm in the retroareolar region. Additionally, multiple adjacent enhancing foci were observed, suggestive of multicentric tumor involvement with probable ductal extension. In contrast, the breast ultrasound examination (C, D) showed a single solid nodule with irregular, spiculated borders, a thick echogenic ring, and antiparallel orientation. It measured 7 × 8 mm and was located at the 12 o’clock position, 5 cm from the nipple

Given the potential for multifocal disease, the patient underwent nipple-sparing mastectomy and sentinel node dissection. Mastectomy analysis identified three areas of interest: area #1 (2.5 cm, biopsy site, with clip, 1.4 cm from deep margin), area #2 (0.6 cm, 1.5 cm from anterior margin), and area #3 (2.5 cm, 1 cm from deep margin). Histopathology confirmed adenoid cystic carcinoma, classic subtype, in areas #1 and #2, with intervening tissue, while area #3 showed no tumor presence. This confirmed a unifocal cystic adenoid carcinoma, Grade I, measuring 2.5 cm (Fig. 3). There was no lymphovascular or perineural invasion. Despite the macroscopic distance of the lesion from margins, tumor infiltration was noted through fibrous septa, with a tumor less than 1 mm from the posterior/deep margin and a positive anterior margin. Four sentinel lymph nodes were negative for carcinoma. The final pathological staging was pT2snN0MX (Stage I, AJCC 8th edition), classic subtype triple-negative adenoid cystic carcinoma. Radiotherapy was recommended due to positive margins, along with imaging follow-up. BRCA1–2 germline testing was advised given the triple-negative nature and family history.

Fig. 3.

Carcinoma lesions in total mastectomy. A Macroscopic appearance of a total mastectomy. B Two solid lesions with ill-defined borders and a whitish color, measuring 2.5 cm and 0.6 cm respectively in their largest diameters, were identified in the total mastectomy specimen (blue circles). C The tissue collected for microscopic evaluation includes representation of both nodules and the tissue between the two lesions (1, 2, 3). D Histological findings found in the three areas represented macroscopically in C demonstrate involvement by the same neoplasia throughout

At 1 week post-surgery, follow-up evaluation demonstrated satisfactory results (Fig. 4). However, in the following month, the patient developed complications, including neuropathic pain and seroma formation. The neuropathic pain was refractory to pharmacologic treatment and required neurolysis for relief, while the seroma was managed effectively through multiple (a total of six) ultrasound-guided drainages. At the 6-month multidisciplinary follow-up visit, the patient exhibited a favorable clinical course with improvement of the neuropathic pain and seromas. A chest computed tomography scan at this time showed no signs of recurrence or new complications (Fig. 5).

Fig. 4.

Surgical management outcome. A Appearance of the left breast prior to surgery, showing a cutaneous hematoma associated with the diagnostic biopsy. B Appearance of the left breast after surgical management, which included nipple-sparing total mastectomy, sentinel lymph node biopsy, and reconstruction

Fig. 5.

Imaging follow-up of the patient. A Left breast ultrasound examination revealed a fluid collection with an estimated volume of 35 cc, appearing as a well-defined, hypoechoic area consistent with seroma. The drainage catheter is visible in this view. The surrounding breast tissue appears heterogeneous due to post-surgical changes. B, C Chest computed tomography scan demonstrates post-surgical changes from the left mastectomy with breast reconstruction, with significant residual fibrotic changes and no fluid collections. There is no evidence of secondary neoplastic involvement in the thorax. Appearance of the left breast prior to surgery, showing a cutaneous hematoma associated with the diagnostic biopsy. B Appearance of the left breast after surgical management, which included nipple-sparing total mastectomy, sentinel lymph node biopsy, and reconstruction

Discussion and conclusion

Adenoid cystic carcinoma (ACC) is a rare breast tumor with diverse clinical and imaging presentations; therefore, its diagnosis relies primarily on microscopic examination [6]. Morphologically, it resembles salivary gland tumors, exhibiting patterns such as tubular–trabecular, cribriform, and solid-basaloid structures [7]. Immunohistochemistry typically confirms two cell types: epithelial and myoepithelial. Epithelial cells stain positive for CK7, CK8, and EMA, while myoepithelial cells are positive for CK14, CK5/6, and p63, among others [8, 9].

From a molecular perspective, most ACCs studied thus far harbor the MYB-NFIB fusion gene, a feature also observed in salivary gland ACC. Tumors lacking this fusion gene may exhibit MYBL1 rearrangements or MYB amplification. Additionally, commonly mutated genes include MYB, BRAF, FBXW7, SMARCA5, SF3B1, and FGFR2 [10]. High-grade transformed histologic subtypes often harbor mutations in EP300, NOTCH1, ERBB2, and FGFR1, along with the MYB-NFIB fusion gene. Notably, these tumors lack mutations typically associated with triple-negative breast cancer, such as TP53 mutations [5].

ACC of the breast is generally negative for estrogen and progesterone receptors, as well as HER2 amplification/expression, classifying it as a triple-negative tumor [4, 9]. However, epidemiological studies categorize it as a triple-negative breast tumor with low malignant potential [11].

Efforts to identify prognostic factors have focused on histological findings, including cell proliferation indices and histological grading [12]. The histological grading system for breast ACC evaluates the proportion of solid growth: Grade I tumors lack a solid component, Grade II tumors have less than 30% solid component, and Grade III tumors have 30% or more solid component. However, histological grade and proliferation indices, such as Ki-67, do not consistently correlate with clinical outcomes [13]. Currently, histological subtype remains one of the most reliable prognostic indicators, with three subtypes identified: classic, solid-basaloid, and ACC with high-grade transformation [11].

The classic subtype, predominant in most cases, typically has a favorable prognosis with rare regional and distant metastases, leading to better survival rates than invasive breast carcinoma [14]. It features cribriform areas surrounded by tubular architecture, comprising epithelial and myoepithelial cells with glandular spaces producing mucins. Classic ACC generally lacks significant nuclear atypia or necrosis and demonstrates low mitotic activity. Immunohistochemical staining reveals epithelial cells positive for CK7, CK8, and EMA, and myoepithelial cells positive for CK5/6 and p63. CD117 expression is strong in the luminal component. Differential diagnosis relies on immunostaining and histological features (Table 1). For instance, the tubular component of classic ACC differs from microglandular adenosis and tubular carcinoma in cell composition and mucin production, while distinguishing the cribriform component from collagenous spherulosis and cribriform carcinoma is essential [8].

Table 1.

Differential diagnosis of classic subtype adenoid cystic carcinoma [23]

Cribiform component of the classical subtype
	Adenoid cystic carcinoma	In situ/infiltrating cribriform carcinoma	Collagenous spherulosis
Breast mass	Yes	Yes	No
Epithelial component	Present	Present	Present
Myoepithelial component	Present	Present/absent	Absent
Spaces with mucin and basement membrane material	Present	Present	Present
Hormone receptors (estrogen and progesterone receptors)	Negative	Positive	Positive
CD117 immunostaining	Positive	Negative	Negative
Tubular component of the classical subtype
	Adenoid cystic carcinoma	Tubular carcinoma	Microglandular adenosis
Epithelial component	Present	Present	Present
Myoepithelial component	Present	Absent	Absent
Spaces with mucin and basement membrane material	Present	Absent	Absent (without eosinophilic material)
Hormone receptors (estrogen and progesterone receptors)	Negative	Positive	Negative

The solid-basaloid subtype presents solid nests of basaloid cells with marked nuclear atypia, high mitotic activity, and necrosis. Perineural invasion is common. Differential diagnosis includes other basaloid carcinomas and small-cell neuroendocrine carcinoma, with typical ACC areas aiding the diagnosis [15]. This subtype demonstrates more aggressive behavior, with axillary node metastases, perineural invasion, and a higher likelihood of local recurrences and distant metastases, particularly to the lungs, bones, and skin [16].

ACC with high-grade transformation represents a rare but aggressive subset associated with poor outcomes. These cases may involve multiple areas of differentiation, including small-cell carcinoma, invasive ductal carcinoma, and malignant adenomyoepithelioma. Molecular studies suggest a clonal relationship between ACC and high-grade components, indicating an aggressive potential. However, treatment strategies remain challenging due to the rarity and heterogeneity of these cases [17].

Breast ACC predominantly affects elderly women, often presenting as a palpable mass. Radiologically, the lesion is usually unifocal, with the retroareolar region being the most common site [2]. In our patient, the diagnosis was made without a palpable mass, underscoring the importance of surveillance in women over 50 years of age. The tumor’s location at the upper quadrant junction was an uncommon clinical presentation in our case.

Radiologically, breast ACC lacks distinctive features [18]. Mammography may show an irregular or well-defined round mass resembling benign lesions, complicating classification. Ultrasonography typically reveals an irregular hypoechoic mass with angular, indistinct, or microlobulated margins and mild peripheral blood flow. Contrast-enhanced magnetic resonance imaging offers high sensitivity for tumor size assessment and surgical planning [19]. In our case, MRI revealed adjacent breast tissue involvement. Although the tumor initially appeared multifocal radiologically, a histopathology test confirmed its unifocal nature.

Surgical management, such as lumpectomy with radiotherapy or mastectomy, often achieves effective control of breast ACC [20]. Axillary lymph node dissection is usually unnecessary due to the low incidence of nodal metastasis, except when nodal involvement is suspected [21]. Adjuvant systemic therapies remain controversial, with limited benefits observed. Chemotherapy is rarely indicated but may be considered for high-grade lesions larger than 3 cm or with nodal involvement. Given the risk of late local relapse, long-term clinical and radiological follow-up is essential [4].

In conclusion, breast ACC is a rare, infiltrating triple-negative carcinoma classified as a low-grade malignant tumor. It typically carries an excellent prognosis, with low rates of distant metastasis, lymph node involvement, and recurrence, often allowing for curative surgical resection. The tumor’s rarity poses diagnostic challenges owing to its diverse imaging and clinical presentations, highlighting the importance of histological confirmation. While understanding of this tumor continues to expand, multidisciplinary management remains pivotal in providing tailored therapies for affected patients.

Abbreviations

ACC

Adenoid cystic carcinoma

BI-RADS

Breast Imaging Reporting & Data System

CK

Cytokeratin

EMA

Epithelial membrane antigen

ER

Estrogen receptor

PR

Progesterone receptor

HER-2

Human epidermal growth factor receptor 2

PD-L1

Programmed death ligand 1

CPS

Combined positive score

AJCC

American Joint Committee on Cancer

Author contributions

DMMU analyzed and interpreted patient data concerning the clinicopathological aspects of the disease. BW participated in the clinical evaluation and follow-up. FT performed the surgery. PARU and DC conducted the histological examination of the biopsy and mastectomy, establishing the diagnosis. GIP was involved in the radiological diagnosis. All authors made significant contributions to writing the manuscript and have read and approved of the final version.

Funding

Not applicable.

Availability of data and materials

Not applicable.

Declarations

Ethics approval and consent to participate

This study was approved by the ethics committee Comité Corporativo de Ética en Investigación at Fundación Santa Fe de Bogotá Hospital under approval number 16623-2024.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.