August 2025 Case

Patient in late 60’s who presented for evaluation of right breast calcifications detected on screening mammography. A subsequent core needle biopsy of the area showed atypical ductal hyperplasia (ADH), a radial scar, and lobular carcinoma in situ (LCIS). She subsequent underwent a right breast lumpectomy.

Histological examination revealed lobules containing cells arranged in a cribriform pattern with eosinophilic to basophilic, round to oval, collagen-rich spherules (in this case mucinous spherules - may be called mucinous spherperolosis instead). Adjacent regions demonstrated a monomorphic proliferation of mildly atypical cells with round nuclei, indistinct nucleoli, and dyshesive features, along with intracytoplasmic lumina. Other foci were composed of ducts with monomorphic cells displaying ovoid to rounded nuclei in a solid and cribriform pattern, each focus measuring less than 2 mm. A focal area displayed ducts filled with polymorphous cells with peripheral elongated clefts. Additional ducts exhibited an architecturally “flat” pattern without cytologic atypia. The epithelial lining cells were predominantly columnar, with elongated nuclei oriented perpendicular to the basement membrane.

The excision specimen demonstrated multiple benign and atypical proliferative breast lesions, including atypical ductal hyperplasia, atypical lobular hyperplasia/lobular carcinoma in situ, usual ductal hyperplasia, columnar cell change, and collagenous spherulosis.

Collagenous spherulosis (CS) is a rare, benign intraductal proliferative lesion of the breast¹. It arises from the proliferation of basement membrane material, forming luminal hyaline spherules (eosinophilic to basophilic, occasionally mucoid, like this current case), surrounded by myoepithelial cells. These spherules contain a mixture of basement membrane components, banded collagen, and mineral deposits¹.

Imaging features of collagenous spherulosis are variable and often incidental, as most cases are discovered alongside other benign breast lesions. On mammography, CS may appear as microcalcifications or, less commonly, as a mass, and architectural distortion is uncommon.

CS is commonly associated with other benign breast lesions such as sclerosing adenosis, papillomas, and radial scars. Notably, it can also be found in association with lobular carcinoma in situ (LCIS). Histologically, collagenous spherulosis can mimic malignant lesions such as adenoid cystic carcinoma (ACC), signet ring carcinoma, and cribriform pattern ductal carcinoma in situ (DCIS). ACC is a rare, low-grade basal-like carcinoma that shares histomorphologic features with CS. Molecular analysis can aid differentiation in which breast ACC frequently harbors recurrent MYB gene rearrangements, while CS and DCIS do not^3,4.

Given that collagenous spherulosis is benign, no further clinical management is necessary if no other significant pathology is present, and patients may return to routine screening². However, careful histologic evaluation is necessary as CS is often colonized by LCIS.