A Case of Pleomorphic Adenoma and Ductal Carcinoma In Situ in the Same Mammary Gland

Abstract

INTRODUCTION: Pleomorphic adenoma is a benign tumor that frequently occurs in the salivary glands; however, it occurs in the breast rarely. There have been few reports of breast cancer complicated by pleomorphic adenoma of the mammary gland.

CASE PRESENTATION: A 70-year-old woman was found to have a mass lesion in her left breast during a medical examination. A needle biopsy was performed, and a diagnosis of pleomorphic adenoma was made. We performed a partial mastectomy with a margin of several millimeters from the tumor. Pathological examination revealed a diagnosis of pleomorphic adenoma with ductal carcinoma in situ. The resection margin was sufficient, and the patient was followed up.

CONCLUSIONS: Pleomorphic adenoma arising in the mammary gland is difficult to differentiate from adenomyoepithelioma, mucocele-like tumor, and metaplastic carcinoma. Since the tumor can become malignant, resection with a narrow margin is recommended, along with special efforts not to damage the capsule at diagnosis.

Abbreviations

BI-RADS

breast imaging reporting and data system

DCIS

ductal carcinoma in situ

ER

estrogen receptor

HER2

human epidermal growth factor receptor-2

PgR

progesterone receptor

INTRODUCTION

Pleomorphic adenoma is a benign tumor that predominantly affects the salivary glands while rarely occurring in the breast. There have been few reports of breast cancer in the setting of pleomorphic adenoma of the mammary gland. We report a case of pleomorphic adenoma of the mammary gland with ductal carcinoma in situ (DCIS).

CASE PRESENTATION

The patient was a 70-year-old woman with no chief complaint. Her medical history included dyslipidemia, and her family history was unremarkable. She was diagnosed with pleomorphic adenoma of the mammary gland by needle biopsy performed by a local doctor. She was referred to our department for further examination and treatment. Mammography revealed an asymmetric shadow in the left U (Fig. 1). Breast imaging reporting and data system (BI-RADS) classification is category 3.

Fig. 1 Mammography revealed focal asymmetric density in the left breast.

Ultrasonography revealed a 6 mm-long, smooth, well-defined mass in the left C area. There was no evidence of hypervascularization or increased blood flow (Fig. 2). BI-RADS classification is category 3. A needle biopsy showed a broad cartilaginous matrix and epithelial components with slightly acidophilic cytoplasm, accompanied by glandular duct formation. Based on these findings, a diagnosis of pleomorphic adenoma was made. The patient was treated with tumor resection to differentiate between metaplastic carcinoma and mucinous carcinoma. Partial mastectomy was performed under local anesthesia with a margin of several millimeters from the tumor. Postoperative pathological examination revealed tubular to cord-like epithelial components against a background of chondromyxoid stroma with cartilage formation and no intraductal papilloma component. The diagnosis of pleomorphic adenoma with DCIS was made based on the presence of intraductal proliferative lesions, some of which were composed of highly atypical cells with atypical mitosis (Fig. 3). The size of pleomorphic adenoma is 7 × 6 × 5 mm, and the closest margin is 2 mm. The size of DCIS is 6 × 3 × 2 mm, intermediate-grade DCIS, and the closest margin is 2 mm.

Fig. 2 Ultrasound revealed a 6 mm, smooth, well-defined mass in the left C area.

Fig. 3 (A) Histological imaging. Hematoxylin–eosin stain (×20 at original magnification). This specimen shows a mixture of pleomorphic adenoma and DCIS. (B) Histological imaging. Hematoxylin–eosin stain (×100 at original magnification). In the background of myxochondromatous mesenchymal-like elements, loosely arranged spindle cells and ducts lined by cuboidal cells were observed. (C) Histological imaging. Hematoxylin–eosin stain (×100 at original magnification). Intraductal epithelial proliferation with a solid-to-cribriform pattern. Nuclear atypia was evident, and atypical mitosis was observed.

DCIS, ductal carcinoma in situ

Immunostaining revealed estrogen receptor (ER) (−), progesterone receptor (PgR) (−), human epidermal growth factor receptor-2 (HER2) (0–1+), and Ki-67 (<3%) expression in the pleomorphic adenoma region, and ER (−), PgR (−), HER2 (2+), Ki-67 (15%), and AR (+) in the DCIS region (Fig. 4). Since the activities of Ki-67 are quite different, we considered the two to be distinct lesions. We decided that additional resection and irradiation were unnecessary because the DCIS was small, and the margins were negative. We followed up with the patient. One year after surgery, no recurrence was observed.

Fig. 4 (A) Immunohistochemistry Ki-67 antibody in pleomorphic adenoma (×100 at original magnification). (B) Immunohistochemistry Ki-67 antibody in DCIS (×100 at original magnification).

DCIS, ductal carcinoma in situ

DISCUSSION

Pleomorphic adenomas are benign tumors that predominantly occur in the salivary glands and account for 55%–70% of all salivary gland tumors.¹⁾ Although the mammary glands are histologically similar to the salivary glands, primary pleomorphic adenomas of the mammary gland are extremely rare. Pleomorphic adenomas are thought to arise from intraductal papilloma.²⁾ On mammography, they are often depicted as masses with clear borders and uniform density, but they may present with findings suspicious of malignancy, such as microcalcifications or masses with indistinct borders. Ultrasonography has revealed a well-defined, smooth, or lobulated, internally homogeneous mass with often enhanced posterior echogenicity.³⁾ Pathologically, there is a mixture of epithelial and mesenchymal components within the tumor and a variety of histologic features, including adenoductal, myoepithelial, myxoid-like, and cartilaginous components.¹⁾ Therefore, it is not uncommon for a needle biopsy to be diagnosed as a malignant lesion and a postoperative surgical specimen to be diagnosed as a benign tumor, resulting in overdiagnosis. Primary pleomorphic adenomas of the mammary gland tend to be located around the nipple,⁴⁾ and cases of recurrence⁵⁾ and lymph node metastasis⁶⁾ have been reported.

Ahmad et al. reviewed 77 patients with pleomorphic adenoma; some patients had mastectomies, and most underwent lumpectomy.⁷⁾ It is important to avoid rupture of the capsule to prevent recurrence.⁸⁾ If the capsule is damaged, local recurrence may occur due to the seeding of tumor cells. Follow-up is recommended for at least 5 years.⁵⁾

Salivary gland tumors and mammary gland tumors are morphologically similar, and salivary gland-like tumors of the breast have been reported.^9–11) There have been reports of cases in which pleomorphic adenomas and invasive ductal carcinoma of the breast were found in different breasts,¹²⁾ reports investigating biomarkers in 8 patients with simultaneous or heterochronic salivary gland pleomorphic adenoma and invasive breast cancer,¹³⁾ and cohort studies showing that salivary gland cancer and pleomorphic adenomas slightly increased the risk of developing breast cancer.¹⁴⁾

Reports of breast cancer in the setting of pleomorphic adenoma of the mammary gland are extremely rare. Therefore, there are no classification criteria. On the other hand, carcinomas derived from pleomorphic adenomas of the salivary glands are classified as intraepithelial carcinoma, minimally invasive carcinoma, or extensively invasive carcinoma. Malignant transformation of salivary gland pleomorphic adenomas is more likely to occur in pleomorphic adenomas that have been neglected for a long time or have recurred repeatedly.¹⁵⁾ The malignant transformation of pleomorphic adenomas of the salivary glands has been suggested to be associated with molecular alterations such as the overexpression of HER2 protein and androgen receptor expression.^16,17) Scarini et al. reported that genetically, PLAG1 and HMG2 gene expression is the most common genetic event in pleomorphic adenomas and carcinomas of salivary gland origin.¹⁸⁾ Ma et al. reported the involvement of the TRPS1-PLAG1 fusion gene in the malignant transformation of mammary pleomorphic adenomas.¹⁹⁾ This represents a small number of related reports, and further genetic studies are needed. Hayes et al. reported 3 cases of carcinoma from pleomorphic adenoma of the mammary gland, two of which had grade-3 invasive ductal carcinoma and areas of high-grade metaplastic carcinoma with chondroid matrix. One of which had pure high-grade matrix-producing metaplastic carcinoma. Also, a few ducts adjacent to the tumor contained high-grade solid in situ carcinoma. In their article, the distinction between carcinoma ex-pleomorphic adenoma and carcinoma of matrix-producing type was discussed. It was difficult to confirm that they were carcinoma ex-pleomorphic adenoma because there was no long history of a pre-existing stable nodule showing sudden onset of growth, and two of the three had no HER-2 neu amplification. However, the exquisite organization of myoepithelial cells at the periphery of ductal structures in the benign pleomorphic adenoma component was observed; Hayes et al. believe that they were carcinoma ex-pleomorphic adenoma.²⁰⁾

In this case, we observed intermediate-grade DCIS in close pleomorphic adenoma. There was no intraductal papilloma component. It was difficult to distinguish between carcinoma derived from a pleomorphic adenoma and carcinoma adjacent to it, but the possibility that DCIS may have developed from pleomorphic adenoma is suggested by the fact that pleomorphic adenoma may increase the risk of developing breast cancer and that pleomorphic adenoma-derived carcinoma has been reported. As in the aforementioned article, there was no evidence of invasive carcinoma; it may be a preliminary stage from pleomorphic adenoma to invasive carcinoma. The resection margin was adequate; the patient did not receive chemotherapy or radiation therapy and was recurrence-free for 1 year.

CONCLUSIONS

We encountered a rare case of pleomorphic adenoma of the mammary gland with ductal carcinoma in situ.

ACKNOWLEDGMENTS

We thank Ichiro Maeda (Department of Pathology, Kitasato University School of Medicine). We also thank all the people who contributed to this work.

DECLARATIONS

Funding

The authors received no financial support for the preparation of this case report.

Authors’ contributions

SN and KM conceived and designed the case report and wrote the main body of the manuscript. KT and KH evaluated the biopsy and resected specimens. EK, RM, YS, TW, TM, KH, SS, KS, IH, IY, and TF participated in the patients’ care and critically reviewed the manuscript. All authors have read and approved the final manuscript. All authors agree to be responsible for all aspects of the study.

Availability of data and materials

The datasets of this case report are available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Informed consent was obtained from the patient for the publication of this case report and accompanying images.

Competing interests

The authors have no related conflicts of interest to declare.

REFERENCES

• 1)  Higuchi K. Pleomorphic adenoma. In: The Japanese Salivary Gland Society ed. Atlas of salivary gland tumors. Tokyo: Kanehara; 2005, p.40–50.
• 2)  Leekha N, Muralee M, Mathews A, et al. Pleomorphic adenoma of breast-a case report and review of literature. Indian J Surg Oncol 2014; 5: 152–4.
• 3)  Takahashi R, Nakagawa S, Inoue Y, et al. A case report of pleomorphic adenoma of the breast undistinguishable from mucinous carcinoma. Nihon Rinsho Geka Gakkai Zasshi 2014; 75: 1491–6.
• 4)  Foschini MP, Morandi L, Asioli S, et al. The morphological spectrum of salivary gland type tumours of the breast. Pathology 2017; 49: 215–27.
• 5)  Inoue H, Chishima T, Kimura M, et al. Recurrences of pleomorphic adenoma of the right breast. Nihon Rinsho Geka Gakkai Zasshi 2012; 73: 3052–6.
• 6)  Ando T, Endo K, Hirai T, et al. Pleomorphic adenoma of male mammary gland-a case report. J Breast Cancer 1994; 9: 359–62.
• 7)  Ahmad M, Naumaan A, Munoz Zuluaga C, et al. Pleomorphic adenoma of the breast: a rare benign lesion masquerading as a metaplastic breast carcinoma on core-needle biopsy. Cureus 2023; 15: e38827.
• 8)  John BJ, Griffiths C, Ebbs SR. Pleomorphic adenoma of the breast should be excised with a cuff of normal tissue. Breast J 2007; 13: 418–20.
• 9)  Pia-Foschini M, Reis-Filho JS, Eusebi V, et al. Salivary gland-like tumours of the breast: surgical and molecular pathology. J Clin Pathol 2003; 56: 497–506.
• 10)  Camelo-Piragua SI, Habib C, Kanumuri P, et al. Mucoepidermoid carcinoma of the breast shares cytogenetic abnormality with mucoepidermoid carcinoma of the salivary gland: a case report with molecular analysis and review of the literature. Hum Pathol 2009; 40: 887–92.
• 11)  Marchiò C, Weigelt B, Reis-Filho JS. Adenoid cystic carcinomas of the breast and salivary glands (or ‘The strange case of Dr Jekyll and Mr Hyde’ of exocrine gland carcinomas). J Clin Pathol 2010; 63: 220–8.
• 12)  Di Bonito M, Cantile M, Cerrone M, et al. Synchronous pleomorphic adenoma and invasive ductal carcinoma in distinct breasts. Breast J 2015; 21: 428–30.
• 13)  Longo F, Sabatino R, Aquino G, et al. Pleomorphic adenoma of salivary gland and synchronous/metachronous invasive ductal breast cancer: a casual coincidence or a clinical presentation resulting from common genetic events? Int J Clin Exp Pathol 2018; 11: 1712–4.
• 14)  Valstar MH, Schaapveld M, van den Broek EC, et al. Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands. Cancer Med 2021; 10: 424–34.
• 15)  Morinaga S, Takata T, Nagao T. Evaluation of pathological grade of salivary gland carcinoma, Head and neck tumors I salivary gland tumors: a tumor pathology differential diagnosis atlas. Tokyo: Bunkodo; 2015, p.187–95.
• 16)  Skálová A, Stárek I, Vanecek T, et al. Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry. Histopathology 2003; 42: 348–56.
• 17)  Di Palma S, Skálová A, Vanìèek T, et al. Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/neu and MIB1 immunohistochemistry. Histopathology 2005; 46: 144–52.
• 18)  Scarini JF, de Lima-Souza RA, Lavareze L, et al. Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights. Front Oral Health 2023; 4: 942604.
• 19)  Ma S, Zhao D, Liu Y, et al. Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands. Histopathology 2021; 79: 1030–9.
• 20)  Hayes MM, Lesack D, Girardet C, et al. Carcinoma ex-pleomorphic adenoma of the breast. Report of three cases suggesting a relationship to metaplastic carcinoma of matrix-producing type. Virchows Arch 2005; 446: 142–9.