Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign condition in the breast characterized by an overgrowth of connective tissue. It is a proliferative lesion of the breast stroma, classified as a mesenchymal tumor by the World Health Organization. Despite being harmless, PASH frequently challenges pathologists because its microscopic appearance mimics a far more serious condition. This visual ambiguity often leads to initial misdiagnosis, creating anxiety and complicating clinical management.
Understanding Pseudoangiomatous Stromal Hyperplasia
PASH is a proliferation of myofibroblasts, cells that share characteristics of both smooth muscle cells and fibroblasts. The condition typically affects premenopausal women, but it is also found in postmenopausal women receiving hormone replacement therapy and, rarely, in men with gynecomastia. This pattern suggests that PASH growth is sensitive to hormonal stimulation, particularly progesterone, as the involved myofibroblasts often stain positive for progesterone receptors.
Under a microscope, PASH is defined by dense collagenous tissue containing numerous slit-like, complex, and interconnected spaces. These spaces are lined by slender, spindle-shaped myofibroblasts and appear remarkably similar to the endothelial channels of true blood vessels. This striking resemblance to a vascular lesion gives PASH its name, “pseudoangiomatous,” meaning “false vessel-like.”
The clinical presentation of PASH varies widely. It is often found incidentally during a biopsy performed for another reason, accounting for its presence in up to 23% of breast biopsies. PASH can also manifest as a distinct, firm, mobile, and painless lump, known as nodular or tumorous PASH. When presenting as a mass, the size can range significantly, sometimes causing visible breast enlargement.
The Conditions PASH Can Be Confused With
The most serious diagnostic confusion arises from the microscopic similarity between PASH and low-grade angiosarcoma, a rare and aggressive cancer originating from blood vessel lining cells. Both lesions feature a network of anastomosing, slit-like channels within the breast tissue. Distinguishing between them is crucial, as PASH is benign and requires minimal intervention, while angiosarcoma is malignant and requires aggressive treatment like mastectomy and chemotherapy.
The primary visual difference relies on subtle pathological details that can be missed on small tissue samples. In PASH, the lining cells are myofibroblasts, and the spaces they create are clefts devoid of red blood cells. In contrast, low-grade angiosarcoma involves true, invasive vascular channels lined by atypical endothelial cells, showing evidence of cellular malignancy, such as nuclear irregularity and increased cell division (mitoses).
PASH can also be confused with other, more common fibroepithelial lesions of the breast, such as fibroadenoma and phyllodes tumors. On imaging, a palpable PASH mass typically presents as a well-circumscribed, hypoechoic mass on ultrasound, an appearance nearly indistinguishable from a fibroadenoma in a younger patient. This imaging overlap necessitates tissue sampling to confirm the mass’s exact nature.
Histologically, PASH is frequently found adjacent to or intermixed with fibroadenoma tissue, which complicates the initial core biopsy diagnosis. Phyllodes tumors, which range from benign to malignant, also share a similar overall architecture of proliferating stromal cells and can be mistaken for PASH, especially if the sample is small. Clinicians must consider these possibilities when reviewing a biopsy result, particularly if the initial pathology report does not fully correlate with the imaging findings.
Achieving a Definitive Diagnosis
The initial challenge in diagnosis often stems from the limitations of the core needle biopsy (CNB), the standard first step in breast tissue sampling. A CNB removes only a small fraction of the lesion, which can lead to an inconclusive finding or capture only surrounding tissue, resulting in a misdiagnosis like stromal fibrosis or fibrocystic changes. Studies show that a significant percentage of PASH cases diagnosed by subsequent surgical excision were initially misidentified by CNB.
When the initial biopsy is inconclusive, or if the lesion is large, growing, or overlaps with angiosarcoma features, a more substantial tissue sample is required. This involves a vacuum-assisted biopsy, which removes a larger volume of tissue, or a surgical excisional biopsy, which removes the entire mass. Obtaining sufficient, high-quality tissue is necessary for the pathologist to observe the full architecture of the lesion and definitively rule out malignancy.
Immunohistochemistry (IHC) staining is the primary tool for resolving diagnostic ambiguity, using antibodies to identify specific proteins within the tissue cells. PASH cells consistently stain positive for the myofibroblast marker CD34 and are negative for endothelial markers like CD31 and Factor VIII. This specific staining pattern distinguishes PASH from a true vascular tumor.
In contrast, angiosarcoma cells test positive for the endothelial markers CD31 and Factor VIII, confirming their vascular origin. The specialist pathologist uses this difference in protein expression to confirm the benign nature of PASH and prevent unnecessary aggressive treatments. Due to the rarity and subtlety of PASH features, an expert pathological review is often sought to ensure the correct interpretation of the findings.