Benign Breast Diseases: Classification, Diagnosis, and Management

Proliferative Stromal Lesions

Diabetic Fibrous Mastopathy
Diabetic fibrous mastopathy is an uncommon form of lymphocytic mastitis and stromal fibrosis. It occurs both in premenopausal women and (rarely) in men with long-standing type 1 insulin-dependent diabetes mellitus, who have severe diabetic microvascular complications. Clinically, diabetic fibrous mastopathy is characterized by solitary or multiple ill-defined, painless, immobile, discrete lesions in one or both breasts that raise the suspicion of carcinoma. The mammographic and sonographic findings of these lesions are also highly suspicious for breast cancer, so a biopsy is always essential for definitive diagnosis. The characteristic pathologic findings of this entity are dense keloid-like fibrosis; periductal, lobular, or perivascular lymphocytic infiltration with predominantly B cells; lobular atrophy; and epithelioid fibroblasts embedded in dense fibrous stroma. The pathogenesis of diabetic fibrous mastopathy is unknown. The disease probably represents an immune reaction to the abnormal accumulation of altered extracellular matrix in the breast, which is a manifestation of the effects of hyperglycemia on connective tissue.

Routine annual follow-up of patients with diabetic fibrous mastopathy is recommended. Core needle biopsy may be useful in the diagnosis of recurrent lesions on follow-up.

Pseudoangiomatous Stromal Hyperplasia of the Breast
Pseudoangiomatous stromal hyperplasia (PASH) is a benign myofibroblastic proliferation of nonspecialized mammary stroma. Its clinicopathologic spectrum ranges from incidental, microscopic foci to clinically and mammographically evident breast masses. Originally, hormonal stimulation (particularly with progesterone) was suggested in the etiology of PASH, on the basis of observations that this disease is most frequently seen in premenopausal women or in elderly women taking hormone-replacement therapy, and because similar histologic findings are seen in normal mammary stroma during the luteal phase of the menstrual cycle. However, the lesion has since been found in men and in women not taking hormone therapy, and only a small percentage of PASH cases are positive for estrogen receptors or for progesterone receptors.

Clinically, rare cases of PASH present as a well-circumscribed, dense, rubbery mass mimicking a fibroadenoma or a phyllodes tumor. Both the mammographic and sonographic features in PASH are nonspecific, so biopsy of these lesions is necessary to exclude a malignancy.

On gross examination, PASH is usually a well-demarcated mass with a smooth external surface. The cut surface consists of homogeneous white and rubbery tissue. Histologically, a complex network of anastomosing slit-like spaces within a densely collagenous stroma characterizes PASH. The histologic appearance may cause confusion with mammary angiosarcoma, so immunohistochemical vascular markers are used for distinction. Immunohistochemically, the bland spindle cells that line these spaces are strongly positive for vimentin and CD34 and negative for cytokeratin and factor VIII.

The recommended treatment for PASH is wide local excision. Although PASH can recur, patient prognosis is good.

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