Adenoid Cystic Carcinoma Breast: a Rare Entity

Background

Adenoid cystic carcinomas of the breast (bACCs) are rare triple-negative basal-like breast carcinomas. They account for less than 0.1% of all breast cancers [1]. This variant of adenocarcinoma is usually seen in salivary glands but has also been reported in other organs, i.e. breast, skin, lung, cervix, larynx and bartholin gland [2]. Unlike that of salivary gland, bACCs have a good prognosis with rare axillary metastases. They can metastasize to the lungs and local recurrences are less likely in cases with mastectomy [3]. We report a case of bACC diagnosed on histopathology and confirmed by immunohistochemistry.

Case Presentation

A 62-year-old post-menopausal female presented with a lump in the left breast and tenderness for 6 months. She had no prior medical history or family history. Breast examination revealed a lump in central quadrant of the left breast below the nipple-areola complex with retraction. The lump was located subcutaneously with restricted mobility and measured 2 × 2 cm. No axillary nodes were palpable on clinical examination. The contralateral breast was also unremarkable.

On ultrasonography, the left central quadrant breast showed an oval-shaped hypoechoic lesion measuring 12.9 × 8.3 mm. Bilateral mammogram revealed a radio-opaque lesion in the left breast central quadrant along with fibroglandular component, suggestive of fibroadenoma, BIRAD-IV (Fig. 1). Based on the radiological findings and clinical examination, the patient was clinically staged as stage I (T1c, N0, M0). Ultrasonography of the abdomen did not show any significant abnormality.

Fig. 1.

Bilateral mammogram showing a radio-opaque lesion in the left breast central quadrant along with fibroglandular component

Following a non-representative true-cut biopsy, patient underwent incisional biopsy of the left breast lump. Histopathology revealed tissue lined by stratified squamous epithelium with irregular acanthosis. The papillary dermis was unremarkable. The deeper dermis showed an infiltrative tumour arranged in nests, cords, trabeculae and focally glandular pattern. These tumour cells showed mild to moderate nuclear pleomorphism, high nuclear-cytoplasmic ratio, hyperchromatic nuclei, inconspicuous nucleoli and scant cytoplasm. Few mitotic figures were also seen. The tumour cells showed prominent peri-neural infiltration along with infiltration into the subcutaneous adipose tissue included in the biopsy. Stroma showed myxoid change and focal collection of foamy macrophages. The case was reported as adenoid cystic carcinoma of the breast. Following which the patient underwent modified radical mastectomy with axillary clearance in levels 1 and 2.

We received a gross specimen measuring 26 × 15 × 5 cm with overlying elliptical skin measuring 14 × 5cm. Nipple areola area showed puckering of the skin at the superior end. On serial sectioning, an infiltrative grey white, solid-cystic lesion was seen in the retro-areolar region measuring 2.0 × 1.5 × 1.5 cm (Fig. 2a–c). The tumour was 1 cm, 3 cm, 13 cm, 12 cm and 9 cm away from the base, superior margin, medial margin, inferior margin and lateral margins respectively. A total of 20 lymph nodes, of varying sizes ranging from 1.0 to 0.5 cm, were isolated.

Fig. 2.

Gross specimen showing nipple-areola region with an infiltrative grey white, solid cystic lesion in the retro-areolar region measuring 2.0 × 1.5 × 1.5 cm

Histopathology sections examined from the nipple and retro-areolar region showed unremarkable epidermis with underlying dermis showing an infiltrating tumour, separated from the epidermis by a grenz zone. The tumour was arranged predominantly in nests, cord, tubules, ducts, solid and cribriform pattern surrounded by a fibrous and hyalinized stroma. Tumour cells were basaloid in appearance with vague peripheral palisading, had scant cytoplasm, mildly pleomorphic hyperchromatic nuclei and indistinct nucleoli. Focal areas showed tumour cells arranged in cribriform pattern with cystic spaces filled with faint basophilic material. Prominent perineural invasion was seen along with areas depicting comedo-necrosis. The intervening stroma was infiltrated by lymphocytic infiltrate.

Adjacent breast parenchyma showed focal apocrine change and few dilated cysts filled with keratinous material. The deep resected margin was free of tumour. The architectural grade was grade II and nuclear grade was grade I based on the 3-tier system (Figs. 3a, b, c, d and 4a, b). Twenty lymph nodes dissected out from axillary tail and level II showed features of reactive lymphoid hyperplasia. No tumour deposits were seen in the lymph nodes. Immunohistochemistry was done for CD-117, CK-7, Estrogen receptor, Progesterone receptor, Vimentin and Her2/neu. CD-117 and CK-7 were strongly positive, vimentin was focally positive while Estrogen receptor, Progesterone receptor and Her were negative, hence confirming the histopathological diagnosis (Fig. 4c, d). The final stage of the patient was reported as left breast cancer (bACC) pT1N0M0 stage I triple-negative subtype.

Fig. 3.

a–d Microscopy from the nipple and retro-areolar region showing unremarkable epidermis with a grenz zone from the tumour. The infiltrative tumour cells are arranged in predominantly solid, nests, cord, tubules, ducts and cribriform patterns surrounded by fibrous and hyalinized stroma. Extensive perineural component is also seen (H&E, × 4, × 10, × 40)

Fig. 4.

a, b The infiltrative tumour cells with perineural pattern. The tumour cells are basaloid appearance with peripheral vague palisading. c, d Immunohistochemistry for CD 117 showing strong positivity (H&E, × 40; IHC, × 40)

The post-operative recovery of the patient was unremarkable. No systemic adjuvant therapy was performed due to low risk of recurrence, absence of lymph node metastasis and favorable prognosis of bACCs. No local recurrence or adverse outcome was reported after completion of 1 year of surgery.

Discussion

Adenoid cystic carcinomas of the breast, a rare basal-like breast carcinoma, account for less than 0.1% of all breast malignancies [1]. It was first described by Geschickter and Copeland in 1945, earlier the term “Cylindroma”, coined by Billroth in 1856, was used for such lesions [4]. However, the term “Cylindroma” is now exclusively used in the context of benign appendageal tumours of the skin [5]. Few authors have cleverly termed this tumour as the “Dr Jekyll and Mr Hyde of exocrine gland carcinomas” due to its aggressive course and predilection to metastasis when located in the salivary gland and rather an indolent course with rare lymph nodal involvement of metastasis [6].

ACCs are infrequently detected outside of salivary glands in locations, i.e. Bartholin’s gland uterine cervix, Bartholin’s glands, lacrimal glands, auditory canal, cutaneous region, upper respiratory tract, lung, kidney, oesophagus, prostate and breast [6, 7]. The most common presenting symptom includes a palpable breast mass although pain is not a typical feature of bACCs. There is no preferential laterality or quadrant localization of the tumour; rather, these tumours are usually located in the peri-areolar region. These lesions normally measure 2–3 cm and are unifocal in nature; however, multifocal tumours and tumours measuring more than 15 cm have also been reported.

These lesions are slow-growing, over the course of months to years without any evidence of extra-mammary spread. Majority of the patients present with localized breast disease (~ 92%) [1, 6, 8]. There are few cases of incidental detection on routine screening mammograms of asymptomatic patients. The radiologic appearance is generally nonspecific and there is paucity of literature regarding the specific mammographic and ultrasonographic features of bACCs [9]. The tumour has a heterogenous morphology with solid, tubular and cribriform patterns. The diagnostic criteria for bACCs are presence of a biphasic population of tumour cells consisting of epithelial cells (basaloid and ductal) and myoepithelial cells, arranged in specific pattern. bACCs can be divided into 3 grades based on the percentage of solid growth pattern [10, 11] (Table 1).

Table 1.

3-tier grading system of adenoid cystic carcinoma

Grade	Architectural	Nuclear
I	No solid areas	Mild atypia, slight pleomorphism, 0–1 mitosis/10 hpf
II	< 30% solid areas	Moderate atypia, 2–4 mitosis/10 hpf
III	At least 30% solid areas	Higher degree of atypia, prominent nucleoli, 5–10 mitosis/10 hpf

Available clinical data suggests a favorable outcome in bACCs. Thus, belying the conventional thought process that hormone receptor-negative tumours are associated with poor outcomes. The overall solid component in tumour correlates with prognosis. The cribriform like spaces may have basement membrane-like material (myxoid or mucinous) possibly originating from the myoepithelial-like cells lining [5].

Immunohistochemically, bACCs have a basal-like subtype of breast carcinoma, even supported by microarray-based studies [10]. Triple-negative/basal-like carcinoma breast is characterized by negative ER and PR and no expression for HER-2-neu. The possible cause of ER-negativity is not known but could be due to poor differentiation, preserved polarity and differentiation of epithelial-myoepithelial cells. As already known, triple-negative breast cancer (TNBC) has high proliferative activity; however, low proliferation rate (Ki-67) with an indolent course has been reported in bACCs, probable cause being specific molecular characteristics [9, 12].

bACCs need to be differentiated from both benign and malignant entities, i.e. collagenous spherulosis and invasive cribriform carcinoma. Collagenous spherulosis has a cribriform architecture with central eosinophilic material consisting of acellular spherules, creating an adenoid cystic-like pattern [13, 14]. However, the lumens are irregular with myoepithelial cells around the spherules not being readily identified on H&E stained sections but prominent on IHC stains for myoepithelial cells. Cribriform carcinoma and bACCs share a few common features, i.e. low nuclear grade and a cribriform pattern. However, former is positive for ER/PR and has negative PAS/Alcian blue staining with desmoplastic stromal reaction. The spectrum of metaplastic lesions of the breast may include the differentials of collagenous spherulosis, ACC and low-grade adeno-squamous carcinoma [5, 12].

Management of bACCs is similar to that of ACC salivary gland, i.e. wide excision surgical margins/breast conservative surgery followed by postoperative radiotherapy or mastectomy [15]. ACCs of salivary glands are locally aggressive and show local recurrence. There is no common consensus on the best treatment modality for bACCs due to rarity of the tumour. Evidence regarding the use of chemotherapy or axillary lymph node dissection is also limited. The most common site for metastasis is the lung [9]. Leeming et al. had evaluated 24 cases and had 37.5% cases with local recurrence after undergoing local excision because there is no clear data regarding the relationship between margin status and recurrence. The 10-year survival rate is in a range of 85–100% for bACCs [1, 16–18] (Table 2).

Table 2.

Summary of few major studies on ACC of breast

Reference	No. of pts	Breast-conserving surgery (%)	Follow up duration (months)	Lymph node involvement (%)	Distant metastasis	ER/PR/Her-2-neu status (positivity %)	5/10-year survival (%)
Kulkarni et al. [16]	933	69.8	65.7 (median)	5.1	-	15/13/-	88/-
Coates et al. [17]	376	60.3	62 (mean)	6.1	1.1%	12/10/-	94/86
Ghabach et al. [5]	338	-	-	1.7	< 15	10/8/-	98/95
Thompson et al. [8]	244	-	-	4.9	2.9%	-/-/-	96/95
Khanfir et al. [7]	61	67	79 (median)	0	6.5%	3/5/-	94/86

To conclude, bACCs are rare basal-like triple-negative tumours with a good prognosis. These tumours also have unique histological features with distinct IHC expression and molecular phenotype. With a rare chance of distant metastasis and late recurrence, regular follow-up is required. This case report will help us in understanding the role of correct histological classification of special types of breast tumours, prognostic and treatment guide for surgical pathologists, breast surgeons and oncologists, leading to personalized therapy for this rare tumour subtype.

Abbreviations

bACC

breast adenoid cystic carcinoma

BIRADs

Breast Imaging Reporting and Data System

CD

cluster of differentiation

CK

Cytokeratin

ER

Estrogen receptor

Her

Human epidermal receptor

IHC

immunohistochemistry

PAS

periodic acid Schiff’s

PR

Progesterone receptor

TNBC

triple-negative breast cancer

Authors’ Contributions

TS and DJ carried out data acquisition, data analysis and manuscript preparation will stand as guarantor also. SP, AT, AM and PS carried out concepts, design, literature search and participated in clinical study. NK carried out concepts, design and literature search. All the authors have read and approved the final manuscript.

Data Availability

All the data regarding the findings are available within the manuscript.

Compliance with Ethical Standards

Ethics Approval and Consent to Participate

Not applicable

Consent to Publish

Written consent for publication for this case study and any additional related information was taken from the patient involved in the study.

Competing Interests

The authors declare that they have no competing interests.