A 45 year female with a breast lump

Adenomyoepithelioma

Histopathology:

• Demarcated but irregular tumor border and some nodularity
• Tumor composed of small round and tubular glands with prominent proliferation of myoepithelial cells. Myoepithelial cells show clear cytoplasm.
• Some compressed tubules and ducts are seen in the collagenized and hyalinized stroma along with changes of infarction and hemorrhage
• Calponin highlights the prominent myoepithelial cell around unstained luminal cells. Lobulated growth pattern is appreciated.
• Nuclear positivity for P63 also highlights the myoepithelial cells.
• Cytologic atypia and mitotic activity are not seen.

Points of pathoclinics:

1. Adenomyoepithelioma is a benign well delineated/circumscribe single small (1 cm to 8 cm size), multi-nodular/lobulated, greyish-white firm mass/masses of rubbery consistency. Minor degree of irregular and infiltrating margins can be seen. Cystic changes and necrosis may be seen.
2. Adenomyoepithelioma usually composed of many small round ovoid and tubular glands, lined by bland luminal and myoepithelial cells, later should be prominent and striking in appearance. Myoepithelial cells can be spindled, plasmacytoid or polygonal/myoid in appearance.
3. Myoepithelial cells are clear in appearance and more prominent, surrounding the glands and tubules
4. Variable degree of squamous, apocrine, mucinous or sebaceous metaplasia is common in luminal cells.
5. Solid areas within a cystic space admixed with fibrosis, hemorrhage, infarction and hyaline degeneration can be seen. In above case, luminal and myoepithelial cells are extend beyond the fibrous sclerotic and hyalinized tissue with attenuated myoepithelial cells. This pattern can mimic an low grade invasive carcinoma. Evaluation with myoepithelial markers would be helpful.
6. Usually matrix formation is absent or minimal. Focal or rare presence of chondroid metaplasia resembles to salivary gland pleomorphic adenoma, considered as a variants of adenomyoepithelioma.
7. Adenomyoepithelioma is commonly associated with sclerosing or papillary lesions or nodular adenosis (adenosis tumor) or low-Grade adenosquamous Carcinoma
8. Adenomyoepithelioma (lobular variant) can show striking degree of lobules/nodularity with predominant eosinophilic or clear myoepithelial cells
9. Adenomyoepithelioma (spindle cell variant) is rich in spindled myoepithelial cells, may resemble a smooth muscle neoplasm with entrapped ducts
10. Discrete separate nodules of adenomyoepithelioma (satellite nodules) can occurs, may led to local recurrence if missed during surgical excision
11. Adenomyoepithelioma can show focal areas of irregular or an infiltrative border in surrounding normal breast tissue. Atypical features like high-grade nuclear atypia, increased mitotic activity (more than three mitosis per 10 HPF), and focally infiltrative margins should be considered strongly for carcinoma in a background of adenomyoepithelioma. Isolated findings have no significance. These cases have a high potential for recurrence. Wide local excision and close clinical follow-up is recommended management.
12. Adenoid cystic carcinoma can show areas of tubular component of adenomyoepithelioma and adjacent cribriform pattern. In contrast to adenomyoepitheliomas, adenoid cystic carcinoma has have an infiltrative growth pattern. Giving more stress on myoepithelial cells, help to differentiate both entity.
13. Sclerosing adenosis also circumscribed lobulocentric lesion but glands and tubules are distorted by collagen and sclerotic stroma. Myoepithelial markers are usually focally present and not extensive as seen in adenomyoepithelioma. In present case, areas of sclerosis along with proliferation of small tubular compressed ducts mimicking sclerosing adenosis. But, rest of the areas and high number of myoepithelial cells, highlighted by calponin and P63 favors adenomyoepithelioma.
14. Microglandular adenosis is a close mimicker of adenomyoepithelioma due to significant number of small round ducts and tubules containing secretion, embedded in normal breast parenchyma including adipose tissue, without any desmoplastic stromal response. Though benign but lacks myoepithelial cells.
15. Some features like circumscribed mass and lobules of marked proliferation of closely lacked regular round ducts and tubules with open lumina and very little stroma may resembles to tubular adenoma, but tubular adenoma usually lined by single layer of myoepithelial cells while adenomyoepithelioma (tubular variant) show prominent myoepithelial cells proliferation.
16. Low grade invasive ductal carcinoma shows stromal infiltration by irregular haphazardly placed angulated glands and tubules without lobulocentric architecture and without myoepithelial cells. Use two myoepithelial markers to evaluate myoepithelial cells, especially when using muscle markers, which can stain myofibroblasts and mimicking myoepithelial cells.
17. Two most common mutations in adenomyoepitheliomas are PIK3CA and AKT1, which are mutually exclusive.
18. Most estrogen receptor (ER)-positive adenomyoepithelioma have mutations in PI3K pathway genes, whereas ER-negative adenomyoepithelioma usually have concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Later possibly associated with clinically aggressive behavior. PIK3CA, AKT1 and HRAS may serve as potential actionable therapeutic targets in clinically aggressive adenomyoepitheliomas.
19. Malignant transformation may be associated with c-MYC overexpression.

Reference:

Lubin D, Toorens E, Zhang PJ, Jaffer S, Baraban E, Bleiweiss IJ, Nayak A. Adenomyoepitheliomas of the Breast Frequently Harbor Recurrent Hotspot Mutations in PIK3-AKT Pathway-related Genes and a Subset Show Genetic Similarity to Salivary Gland Epithelial-Myoepithelial Carcinoma. Am J Surg Pathol. 2019 Jul;43(7):1005-1013. doi: 10.1097/PAS.0000000000001275. PMID: 31094929.