First, Understand the Breast Stroma The breast is not just made of glands and ducts. It also contains connective tissue call
Stromal Tumors of the Breast --- First, Understand the Breast Stroma The breast is not just made of glands and ducts. It also contains connective tissue called stroma — the supporting framework that holds everything together. There are two types of stroma in the breast, and each gives rise to different tumors: Intralobular stroma — the delicate connective tissue found inside each lobule, right next to the glands. This is sensitive to hormones and gives rise to breast-specific tumors — fibroadenoma and phyllodes tumor. Interlobular stroma — the denser connective tissue found between lobules. This gives rise to the same tumors you would find in connective tissue anywhere else in the body — lipomas, angiosarcomas, fibromatosis. --- Biphasic Tumors — What Does That Mean? Fibroadenoma and phyllodes tumor are called biphasic because they contain two components: A stromal component — the neoplastic part that is actually driving the tumor An epithelial component — the glands and ducts that get dragged along; they are not neoplastic but are stimulated to proliferate by growth factors released by the stromal cells Think of it like this: the stroma is the engine, and the epithelium is the passenger. Both tumors are driven by mutations in a gene called MED12 — a gene that controls how DNA is read and transcribed. Interestingly, uterine fibroids (leiomyomas) also carry MED12 mutations — both the breast and uterus are organs sensitive to female sex hormones. --- Fibroadenoma What is it? The most common benign tumor of the female breast. It arises from intralobular stroma. Two thirds carry MED12 mutations. Who gets it and when? Most common in women in their 20s and 30s Often multiple and bilateral Hormonally responsive — grows during pregnancy, shrinks after menopause In older women, found as a mammographic density or calcifications rather than a palpable lump What does it look like? Well-circumscribed, rubbery, grayish-white nodule Bulges above surrounding tissue when cut Contains slit-like spaces lined by epithelium Stroma is delicate, often myxoid — meaning it has a loose, jelly-like quality similar to normal intralobular stroma Two patterns of epithelium within it: Pericanalicular — stroma surrounds the glands/ducts Intracanalicular — stroma compresses and distorts the glands into slit-like spaces In older women — stroma becomes densely hyalinized (thickened and glassy) and epithelium atrophies Clinical points Rapid growth during pregnancy can mimic cancer — important not to panic Women on cyclosporin A after kidney transplant develop multiple bilateral fibroadenomas that resolve when the drug is stopped Slightly increased cancer risk if complex features are present — cysts larger than 0.3 cm, sclerosing adenosis, epithelial calcifications, or papillary apocrine change The increased risk is likely due to other concurrent lesions in the surrounding breast tissue rather than the fibroadenoma itself --- Phyllodes Tumor What is it? A tumor also arising from intralobular stroma, much less common than fibroadenoma. The old name was cystosarcoma phyllodes — but this is misleading because most are benign and most are not cystic. The preferred name is simply phyllodes tumor. Like fibroadenoma, most carry MED12 mutations. The difference is that malignant phyllodes tumors acquire additional mutations — particularly in TERT , the gene that encodes telomerase, which allows cancer cells to keep dividing indefinitely. Who gets it and when? Peaks in the sixth decade — about 10 to 20 years later than fibroadenoma Presents as a palpable mass; occasionally found on mammogram What does it look like? Varies from a few centimeters to massive tumors replacing the entire breast Larger tumors have bulbous leaf-like protrusions — phyllodes comes from the Greek word for leaf-like These protrusions are nodules of proliferating stroma covered by epithelium, sometimes projecting into cystic spaces Distinguished from fibroadenoma by: higher cellularity, more mitoses, nuclear pleomorphism, stromal overgrowth, and infiltrative borders Low grade — looks like fibroadenoma but more cellular and mitotically active High grade — looks like a sarcoma Clinical behavior Most are low grade — occasionally recur locally but do not metastasize Borderline and high grade — recur locally unless widely excised or mastectomy done Regardless of grade, lymph node spread is rare — axillary lymph node dissection is contraindicated High grade tumors spread via blood (hematogenous) to distant organs in about one third of cases Only the stromal component metastasizes — the epithelial component stays behind --- Tumors of Interlobular Stroma These tumors have no epithelial component — purely stromal. They are uncommon. Myofibroblastoma Made of myofibroblasts — cells that are a cross between fibroblasts and smooth muscle cells The only breast tumor equally common in males and females Lipoma Made of fat cells Palpable soft mass; seen on mammogram as a fat-containing lesion Compl