Pseudoangiomatous Stromal Hyperplasia Breast
Pseudoangiomatous stromal hyperplasia (PASH) is a rare and benign breast lesion belonging to an informal group of benign stromal lesions, which include
Pseudo-angiomatous stromal hyperplasia can be a difficult differential diagnosis at times, because the radiological appearance of the lesion mimics that of breast fibroadenoma. In addition, sometimes pathologists may confuse the histological-microscopic features of PASH with low-grade angiosarcoma.
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Breast pseudo-angiomatous stromal hyperplasia typically occurs in premenopausal women, but is not altogether uncommon in men, and is frequently found incidentally during biopsy for suspected gynecomastia.
Symptoms of PASH Lesions
The condition may present clinically as a firm but painless breast mass. If pseudo-angiomatous stromal hyperplasia develops during pregnancy, it may cause massive breast enlargement and skin necrosis.
Around 30% of PASH lesions present as a palpable mass, with the other 70% detected radiologically, or as an incidental finding while looking for something else on biopsy.
Patients usually describe a palpable PASH mass as mobile, firm, and painless. The average age of development of pseudo-angiomatous stromal hyperplasia of the breast is about 50, but there is quite a bit of variability. PASH of the breast usually presents in females within the ‘child bearing’ age group, but has been noted in children as young as 12, and in women in their early 70s.
Pseudoangiomatous stromal hyperplasia is a ‘mesenchymal‘ lesion (one that forms from genetically immature muscle and connective tissue cells). Myofibroblasts and also sometimes glandular components form the lesion.
The cause of pseudoangiomatous hyperplasia of the breast is unknown, but it is suspected that the ‘aberrant reactivity’ of myofibroblasts to endogenous or exogenous hormones, and in particular the sex hormones, might be an important contributing factor.
Pseudo-angiomatous breast hyperplasia may occur alone, or along with other proliferative and non-proliferative breast changes. PASH is found as an incidental finding with other benign breast fibrocystic changes at a rate of about 23%. Nowadays, pseudo-angiomatous stromal hyperplasia (PASH) is a well recognized and established category of benign breast lesion, but it was first reported in 1986.
Mammographic features of PASH of the breast
Mammographic images of PASH are often inconclusive. There is usually a clearly circumscribed oval mass, but with indistinct margins and some spiculation.
Sometimes the X-ray only reveals areas of of asymmetric density, but the most common appearance of PASH on mammography is of a solitary, non-calcified mass. Sometimes PASH appears with a local increase in the stroma.
Ultrasound appearance of pseudo-angiomatous stromal hyperplasia may be quite heterogenous
In some cases, PASH lesions also show posterior acoustic shadowing, and the presence of what appear to be vascular channels. Occasionally, sonography reveals spiculated borders. In addition, there may be some presentations of breast PASH with small cystic components.
Some PASH lesions are more heterogeneous in appearance, which may be due to the presence of elements other than than fibrous stroma, such as adipose tissue (fat) or cystic fluids.
Histological aspects of Pseudoangiomatous Stromal Hyperplasia of the Breast
The microscopic appearance of pseudo-angiomatous stromal hyperplasia of the breast is a striking pattern, with complex inter-connected channels lined by ‘spindle‘ shaped cells.
Biopsy specimens of pseudoangiomatous stromal hyperplasia of the breast will often show a diffuse network of spaces in collagenous stroma, along with anastomosing (connecting) ‘slitlike‘ channels which are outlined by these spindle like myofibroblasts.
It is also common to see various ducts and lobules scattered among the lesion. Occasionally there can be unusual variations of the neoplasm which feature ‘giant‘ cells. Sometimes some of the myofibroblasts may have enlarged and mildly hyperchromatic nuclei, but on the whole they appear normal looking.
Histological features which distinguish breast PASH from angiosarcoma
The ‘channels‘ found in a pseudo-angiomatous stromal hyperplasia breast lesion do mimic the appearance of the rich anastomosing vascular channels seen in low-grade angiosarcoma.
But in contrast to a true ‘vascular‘ neoplasm (a growth of ‘blood supply’ related components) the spaces in pseudo-angiomatous stromal hyperplasia are derived from the separation and disruption of collagen fibers around myofibroblasts in the intralobular and interlobular stroma.
Also, with pseudo-angiomatous stromal breast hyperplasia the spaces usually contain mucopolysaccharide. Myofibroblasts will usually only present along one side of a space, not both sides. Whereas with angiosarcoma the vascular lumina are completely surrounded by endothelial cells, and contain red blood cells.
Highly reactive to actin and vimentin
In terms of immunoreactivity, the proteins in psuedo-angiomatous stromal breast hyperplasia often show reactivity to vimentin and actin in the spindle stromal cells, which confirms them to be myofibroblasts.
But they are not reactive to the CD31 or factor VIII, which helps discriminate PASH further from angiosarcoma. Psuedo-angiomatous stromal breast hyperplasia will most often, but not always, show reactivity for CD34, which is usually a fairly reliable marker for myofibroblasts.
There can be some cross-reactivity with CD34 in other lesions, including angiosarcoma, so it is not a reliable differential marker in this case.
Treatment and recurrence rates for pseudoangiomatous breast stromal hyperplasia
Pseudoangiomatous breast stromal hyperplasia is considered to be a lesion of BI-RADS 3, which means ‘probably benign‘.
Treatment for PASH is usually with a wide local excision. However, if there is a diffuse (scattered) presentation of PASH, that can present a management problem which may necessiate a mastectomy.
There are some reports of patients with pseudoangiomatous breast stromal hyperplasia and symptoms of breast enlargement and pain who respond well to tamoxifen. However, considering the potential side effects of long term Tamoxifen use, this is really not recommended.
Pseudoangiomatous breast stromal hyperplasia in generally benign and really not serious enough to merit any kind of chemical therapy. The recurrence rate of excision is low, but not negligible, ranging from 15% to 22%.
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