Breast fibroadenoma with pseudoangiomatous (PASH-like) stroma

Abstract

Pseudoangiomatous stromal hyperplasia (PASH) is a breast stromal change, histologically characterized by anastomosing, slit-like spaces lined by slender myofibroblasts and surrounded by dense collagenous stroma. Mass forming cases clinically and radiologically simulate fibroadenoma. A middle aged women presented with unpalpable breast nodule discovered on ultrasound examination. The ultrasound characteristics were typical for fibroadenoma, while fine-needle aspiration cytology was inconclusive. The histological examination of the lumpectomy specimen showed fibroadenoma with peculiar stromal alteration consistent with pseudoangiomatous stromal hyperplasia. The presented case of fibroadenoma with pseudoangiomatous hyperplasia within its stroma demonstrates the relationship between these two entities not only clinically and radiologically, but also histologically.

Introduction

Pseudoangiomatous stromal hyperplasia (PASH) is an alteration of breast stroma which is histologically characterized by a proliferation of myofibroblasts within sclerotic matrix. These myofibroblasts line anastomosing, slit-like stromal spaces in a manner resembling angiomatous blood vessels. In the PASH cases presenting with a nodule or mass the main radiological and clinical diagnosis is fibroadenoma (FA) [3,5,8,10]. Although PASH can rarely form palpable mass by itself, it is usually encountered in mammary hamarthomas in which this type of stromal alteration is common finding [4]. Herein, we have described a case of FA with PASH-like stroma demonstrating that these two common breast lesions are related not only clinically and radiologically, but also histologically.

Case report

A 44-year-old woman presented with unpalpable nodule of the left breast, detected by ultrasound examination as solid, oval, homogenous hypoechogenic zone of 1 cm in diameter, without acoustic enhancement. The physical examination of breast and axillary tissue was without abnormalities, while mammography showed dense and fatty breast tissue without visible nodule. The presented imaging finding was suggestive of a benign tumor such as FA. Fine-needle aspiration cytology showed acellular specimen. The lumpectomy was performed.

On gross examination the tumor was a well-defined, elastic, gray-white nodule with smooth surface, measuring 0.8 cm in the greatest diameter. The tissue was fixed in neutral buffered formalin and embedded in paraffin for routine histological examination.

Histologically, the nodule was composed of proliferating myofibroblastic stroma encircling and partially compressing the proliferating epithelial structures (Fig. 1). The epithelial structures were composed of dilated and compressed ducts lined by epithelial and myoepithelial layer of cells, with focal short, finger like stromal intraluminal protrusions (Figs 1 and 2). The stromal cells lined anastomosing slit-like spaces which were surrounded by dense collagenous background (Fig. 2). The histological diagnosis was consistent with fibroadenoma with pseudoangiomatous (PASH-like) stroma.

Discussion

PASH of the breast, first described by Vuitch et al. in 1986, is histologically characterized by myofibroblastic proliferation with anastomosing, angulated slit-like spaces [10]. These spaces are lined by attenuated spindle to ovoid myofibroblasts which resemble endothelial cells. It is not clear whether this condition is an artefact secondary to the retraction of the stroma after tissue processing, or the spaces are genuine due to the loss of cohesiveness between the myofibroblasts [4,10]. The fact that PASH is usually found in premenopausal and perimenopausal women, as well as in gynecomastoid man, and associated with gynecomastia-like changes in female breast suggests its etiological relationship with hormonal factors. An association with the use of exogenous sex hormones, such as contraceptive or hormone replacement therapy, has also been described [1–3].

Usually, PASH is an incidental histological finding in breast tissue removed for other reasons. Rarely, PASH can be presented as a palpable, mass forming lesion [3,8]. Mass forming PASH lesions are probably not influenced by hormonal control mechanisms, and initial physiologic stromal lobular changes are replaced with autonomous myofibroblastic proliferation [3,10]. Mass forming PASH clinically and radiologically resembles FA and phyllodes tumor, while histologically it can be confused with low-grade angiosarcoma. Histological examination is sufficient for the diagnosis of fibroepithelial tumors, while in the case of low grade angiosarcoma true vascular spaces are lined by cells showing cytological atypia and mitotic activity. In doubtful cases immunohistochemistry is recommended because the endothelial cells in angiosarcoma express CD31, CD34, and F VIII, while the myofibroblasts in PASH react positively only to CD34 immunomarker.

The PASH-like stromal changes in FA are rarely described in the literature. Kuijper et al., while describing the histopathologic changes in 396 cases of FA, found focal pseudoangiomatous changes in 3.8% of cases [7]. The additional published case of FA with PASH stroma was described by Kazakov et al., but this case occurred in anogenital mammary-like glands [6]. In their series of 26 cases of tumor forming PASH, Ferreira et al. found out that some cases were associated with some benign breast lesions. These benign lesions included, among others, fibroadenomatoid changes [3]. We believe that described fibroadenomatoid changes were only focal as a result of the involvement of intralobular stroma by PASH. In our case the stroma around the epithelial elements was more cellular, with fewer pseudovascular spaces. Because Fisher et al. have found PASH in 25 of 35 cases of breast hamartoma (71,4%), we included this nodular benign lesion in differential diagnosis in the evaluation of our case [4]. Finding of compressed ducts in the manner of intracanalicular FA, and periductal stromal accentuation with small stromal projections in some dilated ducts suggested fibroepithelial lesion. The adipose tissue, characteristic histological finding in breast hamartomas, was not presented here [4].

The stromal changes in FA include increased stromal cellularity in juvenile FA, myoid and osteochondroid metaplasia, finding of stromal giant cells and myxoid change [9]. Among these stromal alterations, FA with myxoid change has the greatest clinical significance. Myxomatous FAs may show rapid growth presenting with larger size, associated with posterior echo enhancement and internal hyperechogeneicity, which can require the needle biopsy in order to differentiate between FA and carcinoma [11].

In this paper, we have described the finding of FA with PASH-like stroma. The clinical imaging findings of mass forming PASH are non-specific, usually mimicking FA. Here, the reported finding of fibroadenoma with PASH-like stroma relates these two entities not only clinically and radiologically, but also histologically.