Pseudoangiomatous stromal hyperplasia of the breast.
Abstract: * Pseudoangiomatous stromal hyperplasia is a relatively common lesion of the breast. In general, it is less commonly found as a clinically palpable mass and is more commonly found as incidental microscopic foci. It is a benign proliferative, probably neoplastic, hormonally driven process of the mammary stromal myofibroblasts. The clinical, radiologic, and cytologic findings can resemble those of fibroadenoma. Histologically, it can be confused with low-grade angiosarcoma. The exact etiology of pseudoangiomatous stromal hyperplasia is still controversial, but a neoplastic process of the stromal myofibroblasts, with a hormonal stimulus in its development and progression, is the favored theory. Most lesions can be cured by complete surgical excision, and patients undergoing the excision have a good prognosis.

(Arch Pathol Lab Med. 2009;133:1335-1338)
Article Type: Disease/Disorder overview
Subject: Hyperplasia (Development and progression)
Hyperplasia (Care and treatment)
Breast tumors (Development and progression)
Breast tumors (Care and treatment)
Author: AbdullGaffar, Badr
Pub Date: 08/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: August, 2009 Source Volume: 133 Source Issue: 8
Topic: Canadian Subject Form: Breast tumours; Breast tumours
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 230247126
Full Text: Pseudoangiomatous stromal hyperplasia (PASH) of the breast was first described in the English literature by Vuitch et al in 1986. (1) So far, approximately 100 cases have been reported, presenting as a clinically palpable mass in the breast. (2,3) Pseudoangiomatous stromal hyperplasia is relatively infrequent when presenting as a solitary, clinically evident mass; however, it is more frequently found as incidental microscopic foci in the female breast and in gynecomastia of the male breast. (4,5) Clinically, PASH should be recognized as a potential mimicker of fibroadenoma. Histologically, it can be misdiagnosed as a low-grade angiosarcoma. (2,3,6,7)


Pseudoangiomatous stromal hyperplasia can present as an incidental microscopic focus; as a solitary, clinically palpable mass; as multifocal nodules; or as a diffuse massive process with asymmetry of the breasts. (2-4) In most cases, PASH is unilateral, but bilateral lesions can occur. (2,4) It can be multifocal in 60% of the cases. (4) Most patients are premenopausal women and elderly women with estrogen replacement therapy; however, the age range is wide and can extend from teenaged girls to postmenopausal women without hormone replacement therapy. (2-4) It can even occur in men, especially in association with gynecomastia, in the range of 20% to 47% of the cases. (5,8-10) Pseudoangiomatous stromal hyperplasia was reported to involve the breasts of patients with immunosuppression-including patients with human immunodeficiency virus-and in association with neurofibromatosis type 1. (8,9,11,12) Few cases have been reported to occur as extramammary lesions, for example, as anogenital area and axilla. (13,14) Lesions that grow rapidly within a short period can occur in few cases. (2,3,11,15)

The radiologic findings of PASH are nonspecific and can resemble those of fibroadenoma. (2,6,16) Mammography shows a well-circumscribed, dense, homogenous, and usually noncalcified mass. Sonographic findings are predominantly of a hypoechoic, solid mass with or without cystic spaces. The current imaging studies are not specific enough to make a definite diagnosis of PASH, and therefore, histologic examination is required. (2,6,16)


Grossly, PASH can resemble fibroadenoma. It typically presents as a well-defined and discrete, single, firm to rubbery mass. The cut surface is of homogenous, white, fibrous tissue, with or without slitlike cystic spaces. Areas of necrosis or hemorrhage are usually absent. The size can vary from microscopic foci to clinically palpable masses, which can range from 1 to 18 cm. (1-4,12,17)


Pseudoangiomatous stromal hyperplasia is usually a round to oval mass that is well-demarcated from the surrounding breast tissue and adipose tissue (Figure, A). The mass is characterized by interlobular stromal expansion with irregular spacing of the mammary lobules (Figure, B). Pseudoangiomatous stromal hyperplasia has a characteristic growth pattern of interanastomosing, angulated, slitlike, empty channels separated by dense, keloidlike, wavy, acellular collagenous stroma. The spaces are falsely lined by attenuated spindle to ovoid myofibroblasts, which can be plump but not atypical. Multinucleated giant cells can be seen, especially in association with gynecomastia and neurofibromatosis type 1. (8,9) The nature of the pseudovascular spaces is controversial. Some believe that these spaces are, in fact, artifacts secondary to retraction of the stroma after tissue processing. (1) They are typically devoid of erythrocytes, in contrast with the true endotheliumlined blood vessels (Figure, C). Others believe that they are genuine spaces because of the myofibroblasts' loss of cohesiveness when present in frozen sections. (18-20) These spaces may serve as a potential pathway for the spread of breast carcinoma. (18) No foci of necrosis or hemorrhage should be detected.


The cytologic findings of PASH are nonspecific and can resemble those of fibroadenoma, but the smears are usually less cellular, probably because of the stromal hyalinization. When the smears are more cellular, a differential diagnosis of phyllodes tumor-especially in a rapidly growing mass and in older women-can not be ruled out. (3,7,15)


Clinically, radiologically, and cytologically, PASH can resemble fibroadenoma in younger-aged women. (2,4,6,16) Rapidly growing lesions can raise a suspicion for malignancy. (2,3) In older-aged women, it can be confused with phyllodes tumor. (3) Pseudoangiomatous stromal hyperplasia has a characteristic histologic morphology that helps in excluding the above differential diagnoses.

Histologically, PASH can be confused with low-grade angiosarcoma. In contrast with PASH, angiosarcoma has endothelium-lined vascular channels with red blood cells. (1,3) Atypical endothelial cells and mitotic figures are usually features of angiosarcoma but not of PASH.

Immunohistochemistry and Electron Microscopy

The stromal myofibroblastic cells of PASH are constantly positive for vimentin, CD34 (Figure, D), progesterone receptors (Figure, E), smooth muscle actin, desmin, and BCL-2. (18,21,22) They are focally and weakly positive for estrogen receptors (ER). (21,22) They are consistently negative for CD31, Factor VIII, and Ulex europeus. (21,22) They are also negative for cytokeratin and S100 (21,22) and are negative for p63 (B.A., unpublished data, February 2008). In difficult cases, the above immunohistochemistry findings help to rule out low-grade angiosarcoma.

The spindle stromal cells of PASH show nondescript ultrastructural features. They consistently lack Weibel-Palade bodies, pinocytic vesicles, and a completely surrounded basement membrane, that is, they have no endothelial features. (1,4,18)

Etiology and Pathogenesis

The exact cause and pathogenesis of PASH is still controversial. Early reports point out that PASH is a form of stromal hyperplasia with an exaggerated intralobular stromal response to progesterone in estrogen-primed tissue, that is, a hormone-dependent process. (10,21,22) This is supported by PASH being found most often in premenopausal women, in older-aged women on hormone replacement therapy, and during pregnancy. (2,4,10,21,22) The response to tamoxifen in some cases and the strongly positive progesterone-receptor results also reinforce this theory. (2,23) Observation against this notion is that PASH has been reported in postmenopausal women without estrogen replacement therapy, and in a rapidly growing number of male patients, where progesterone receptors and estrogen receptor results were negative. (10) Few authors believe that PASH could be a form of breast hamartoma. (19)

Another hypothesis suggests a neoplastic myofibroblastic lesion of the breast. (4,21,22) This is supported by findings that PASH can recur, can be multifocal, can be found as incidental microscopic foci in association with other breast tumors, and can occur in extramammary tissue. (13,22)

Few authors suggest that the cells of PASH are "attenuated lymphatic endothelial cells," that is, that PASH is but a modified form of lymphangioma! (18)


The treatment options for PASH are either surgical or nonsurgical. The surgical treatment is a complete excision of the mass with good safety margins and regular clinical follow up, similar to fibroadenoma. This is best suited for solitary well-demarcated lesions. (2) When PASH is diffuse, mastectomy with reconstruction surgery is an alternative approach. The medical treatment involves the use of hormonal manipulation using tamoxifen. (23)

The recurrence rate can range from 15% to 22%. (1,2,22) No documented malignant transformation has been reported, even though a few authors believe that, rarely, myofibroblastoma or even sarcoma may arise from PASH. (13,17) In general, PASH has a benign clinical course, and patients with PASH have a good long-term prognosis. (2,4,22)


Pseudoangiomatous stromal hyperplasia is a relatively common benign stromal lesion of the breast and patients have a good prognosis. However, its origin and the exact nature of its pseudovascular spaces are still controversial. Hormonal stimulation may play a central role in its development. It has overlapping clinical, radiologic, and cytologic features with fibroadenoma. Under histologic examination, it can be confused with a vascular tumor, especially low-grade angiosarcoma, which can be excluded by immunohistochemistry studies.


(1.) Vuitch MF, Rosen PP, Erlandson RA. Pseudoangiomatous hyperplasia of mammary stroma. Hum Pathol. 1986;17(2):185-191.

(2.) Sng KK, Tan SM, Mancer JFK, et al. The contrasting presentation and management of pseudoangiomatous stromal hyperplasia of the breast. Singapore Med J. 2008;49(3):e82-e85.

(3.) Castro CY, Whitman GJ, Sahin AA. Pseudoangiomatous stromal hyperplasia of the breast. Am J Clin Oncol. 2002;25(2):213-216.

(4.) Ibrahim RE, Sciotto CG, Weidner N. Pseudoangiomatous hyperplasia of mammary stroma: some observations regarding its clinicopathological spectrum. Cancer. 1989;63(6):1154-1160.

(5.) Badve S, Sloane JP. Pseudoangiomatous hyperplasia of male breast. Histopathology. 1995;26(5):463-466.

(6.) Cohen MA, Morris EA, Rosen PP, Dershaw DD, Liberman L, Abramson AF. Pseudoangiomatous stromal hyperplasia: mammographic, sonographic and clinical patterns. Radiology. 1996;198(1):117-120.

(7.) McCluggage WG, Allen M, Anderson NH. Fine needle aspiration cytology of mammary pseudoangiomatous stromal hyperplasia: a case report. Acta Cytol. 1999;43(6):1147-1149.

(8.) Damiani S, Eusebi V. Gynecomastia in type-1 neurofibromatosis with features of pseudoangiomatous stromal hyperplasia with giant cells: report of two cases. Virchows Arch. 2001;438(5):513-516.

(9.) Zamecnik M, Michal M, Gogora M, Mukensnabl P, Dobias V, Vano M. Gynecomastia with pseudoangiomatous stromal hyperplasia and multinucleated giant cells: association with neurofibromatosis type-1. Virchows Arch. 2002; 441(1):85-87.

(10.) Milanezi MFG, Saggioro FP, Zanati SG, Bazan R, Schmitt FC. Pseudoangiomatous hyperplasia of mammary stroma associated with gynecomastia. J Clin Pathol. 1998;51(3):204-206.

(11.) Seidman JD, Borkowskin A, Aisner SC, Sjn C-CJ. Rapid growth of pseudoangiomatous hyperplasia of mammary stroma in axillary gynecomastia in an immunosuppressed patient. Arch Pathol Lab Med. 1993;117(7):736-738.

(12.) de Saint Aubain, Somerhausen N, Larsimont D, Heymans O, Verhest A. Pseudoangiomatous hyperplasia of mammary stroma in an HIV patient. Gen Diagn Pathol. 1997;143(4):251-254.

(13.) Kazakov DV, Bisceglia M, Mukensnab P, Michal M. Pseudoangiomatous stromal hyperplasia in lesions involving anogenital mammary-like glands. Am J Surg Pathol. 2005;29(9):1243-1246.

(14.) Lee JS, Oh HS, Min KW. Mammary pseudoangiomatous stromal hyperplasia presenting as an axillary mass. Breast. 2005;14:61-64.

(15.) Viacandi B, Jimenez-Heffernan JA, Lopez-Ferrer P, Ortega L, Viguer JM. Nodular pseudoangiomatous stromal hyperplasia of the breast: cytologic features. Acta Cytol. 1998;42(2):335-341.

(16.) Polger MR, Denison CM, Lester S, Meyer JE. Pseudoangiomatous stromal hyperplasia: mammographic and sonographic appearances. Am J Roentgenol. 1996;166(2):349-352.

(17.) Iancu D, Nochomovitz E. Pseudoangiomatous stromal hyperplasia: presentation as a mass in the female breast. Breast J. 2001;7(4):263-265.

(18.) Damiani S, Eusebi V, Peterse JL. Malignant neoplasms infiltrating pseudoangiomatous stromal hyperplasia of the breast: an unrecognized pathway of tumour spread. Histopathology. 2002;41(3):208-215.

(19.) Fisher CJ, Hanby AM, Robinson L, Millis RR. Mammary hamartoma: a review of 35 cases. Histopathology. 1992;20(2):99-106.

(20.) Hartveit F. Attenuated cells in breast stroma: the missing lymphatic system of the breast. Histopathology. 190;16(6):533-543.

(21.) Anderson C, Ricci A Jr, Pedersen CA, Cartun RW. Immunocytochemical analysis of estrogen and progesterone receptors in benign stromal lesions of the breast: evidence of hormonal etiology in pseudoangiomatous hyperplasia of mammary stroma. Am J Surg Pathol. 1991;15(2):145-149.

(22.) Powell CM, Cranor ML, Rosen PP. Pseudoangiomatous stromal hyperplasia (PASH): a mammary stromal tumor with myofibroblastic differentiation. Am J Surg Pathol. 1995;19(3):270-277.

(23.) Pruthi S, Reynolds C, Johnson RE, Gisvold JJ. Tamoxifen in the management of pseudoangiomatous stromal hyperplasia. Breast J. 2001;7(6):434-439.

Badr Abdull Gaffar, MD

Accepted for publication September 12, 2008.

From the Department of Histopathology, Dubai Hospital, Dubai, United Arab Emirates.

The author has no relevant financial interest in the products or companies described in this article.

Reprints: Badr AbdullGaffar, MD, Histopathology Department, Dubai Hospital, PO Box 7272, Dubai, United Arab Emirates (e-mail:
Gale Copyright: Copyright 2009 Gale, Cengage Learning. All rights reserved.