Answer: B - Fibroepithelial lesion, Cellular FA vs Phyllodes Tumor

Option B is the best answer choice. This is a biphasic lesion with patchy increase in stromal cellularity and mild cytologic atypia. Although there are foci with myxoid stromal change, the biphasic nature of the lesion precludes a diagnosis of myxoma (hence choice D is incorrect). Distinguishing between a cellular fibroadenoma and a phyllodes tumor can be problematic on biopsies. It is prudent to render a diagnosis of fibroepithelial lesion, to indicate a differential of cellular fibroadenoma (FA) versus phyllodes tumor (PT), and to recommend surgical excision for further evaluation of the entire lesion (hence choices a and c are not the best answers).

Both FA and phyllodes tumor are biphasic lesions. Usual FA has either an intracanalicular or a pericanalicular growth pattern (containing compressed glandular lumens in the former and open glandular lumens in the latter pattern). Stromal component in usual FA is often uniformly cellular, lacks atypia and has no or rare if any mitosis. Juvenile FA is characterized by increased stromal cellularity and typically greater epithelial atypia than seen in usual FA. Juvenile FA often has a pericanalicular growth pattern with fascicular stromal arrangements, epithelial hyperplasia and gynecomastoid-like micropapillary projections. JFA can be large or show a rapid growth rate leading to marked distortion of the breast. Complex FA is composed of cystic structures (typically more than 0.3 cm) with sclerosing adenosis, epithelial calcifications and/or papillary apocrine metaplasia.

In comparison with usual FA, phyllodes tumors are less common, tend to occur in older patients, and are often larger (average size 4-5 cm). Unlike fibroadenoma, benign PT can recur and both its stromal and epithelial components can progress to malignancy. Radiologic studies (US and mammography) cannot reliably distinguish FA from PT.

On gross examination, PT has a whorled appearance and can be multinodular. Histologically, there is a leaf-like, prominent intracanalicular pattern with increased stromal cellularity. Benign PT are characterized by moderate stromal cellularity with condensation commonly around ducts/ clefts, mild pleomorphism and a few mitosis (< 5/10 HPF or < 2.5/mm²). The tumor border is often well- defined. Malignant PT have moderate to marked stromal pleomorphism with increased cellularity and prominent mitotic activity (≥ 10/10 HPF or ≥ 5/mm²), stromal overgrowth (at least one 4x magnification microscopic field with only stroma and no glandular elements), and often an invasive tumor frond. Heterologous elements can be noted in both benign and malignant PT but more commonly in the latter. Of note, presence of any malignant heterologous element upgrades a PT to the malignant category.

In summary, in core biopsies, distinguishing cellular FA from PT can be challenging. Histologic features predictive of phyllodes tumor include stromal overgrowth, scattered mitoses, fat infiltration with stromal fragmentation, subepithelial stromal condensation and stromal nuclear pleomorphism. A spectrum of dysplastic or in situ and infiltrative epithelial or stromal malignancies can occur in PT. Therefore, adequate and extensive sampling of the excised tissue is recommended for accurate categorization.

References:

Huang IC, Li PC, Ding DC. Recurrent juvenile fibroadenoma of the breast in an adolescent: A case report. Medicine (Baltimore). 2018;97(20):e10765.

Islam S, Saroop S, Bheem V, Naraynsingh V. Largest giant juvenile fibroadenoma of the breast. BMJ Case Rep. 2019;12(1):e227277. Published 2019 Jan 28. 

Papas, Yasmine et al. “Malignant phyllodes tumors of the breast: A comprehensive literature review.” The breast journal vol. 26,2 (2020): 240-244.

Panda KM, Naik R. A Clinicopathological Study of Benign Phyllodes Tumour of Breast with Emphasis on Unusual Features. J Clin Diagn Res. 2016;10(7):EC14-EC17.

Zhang, Yanhong, and Celina G Kleer. “Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates.” Archives of pathology & laboratory medicine vol. 140,7 (2016): 665-71.