Printer Friendly

A 41-year-old woman with bilateral nodular breasts. (Pathologic Quiz Case).

A 41-year-old woman with no family history of breast cancer, but with a long history of bilateral nodular breasts, complained of increasing breast size. Three previous breast biopsies (the right breast in 1973 and 1983 and the left in 1992) were all reported as benign fibrocystic changes. Physical examination showed pendulous but symmetrical breasts with no noted skin changes. Palpation revealed multiple, discrete, large, firm, and mobile breast masses bilaterally. No axillary adenopathy was detected. Mammography revealed multiple homogeneously dense well-circumscribed masses present in both breasts (Figure 1), which were compatible with giant fibroadenomata or multiple phyllodes tumors. Ultrasonography showed multiple well-demarcated masses with focal cystic change. Ultrasound-guided 14-gauge needle core biopsy of the fight and left breast was performed, and microscopic examination of the biopsied tissue revealed dense stromal fibrosis and a few epithelial ducts. The fibrotic areas showed thick bundles of dense collagen admixed with a complex arrangement of cleftlike spaces resembling lymphovascular structures lined by flattened spindle cells, but without red blood cells in the spaces. No atypical epithelial hyperplasia or carcinoma was identified. A diagnosis was suggested. Two weeks later, resection of the bilateral masses along with reduction mammoplasty of both breasts was performed. On the right side, 13 white-pink well-circumscribed nodules with a total weight of 748 g (range: 4 to 382 g) were resected. The nodules had a smooth external surface and ranged in size from 3 to 17 cm in greatest dimension (Figure 2). On the left side, 10 white-pink well circumscribed nodules with a total weight of 214 g (range: 2 to 84 g) were resected. Morphologically, the nodules were similar to those seen in the right breast and ranged in size from 1.5 to 11 cm in greatest dimension. The cut surfaces of the nodules showed a generally homogeneous white fibrous parenchyma with occasional cystic spaces. No hemorrhage or necrosis was noted grossly. Microscopically, the breast nodules showed histopathologic changes similar to those seen in the needle core biopsies, showing large areas of dense stromal fibrosis containing numerous cleftlike spaces, often in a complex arrangement (Figure 3). In some areas, the cleftlike spaces and flattened spindle cells were concentrically arranged around breast lobules. The cleftlike spaces did not contain red blood cells. The adjacent breast parenchyma showed focal fibrocystic changes (sclerosing adenosis, simple dilated cysts, apocrine metaplasia, and dense fibrosis). Multifocal microcalcifications were present. Neither atypical duct hyperplasia nor carcinoma was identified in any of the masses or breast tissue.


What is your diagnosis?

Pathologic Diagnosis: Pseudoangiomatous Hyperplasia of Mammary Stroma

Pseudoangiomatous hyperplasia of mammary stroma (PHMS) is a grossly well-circumscribed mammary stromal proliferation consisting of complex interanastomosing channels lined by slender spindle cells, first described by Vuitch et al. (1) Clinically, patients are premenopausal or perimenopausal women (age range: 19 to 52 years), (1-3) although 4 cases in postmenopausal women (4) and one case occurring in a 39-year-old immunosuppressed man with axillary gynecomastia have been reported. (5) Additionally, rapidly growing PHMS has been noted in a clinical setting of human immunodeficiency virus infection. (6) Stromal changes with PHMS have been noted in association with gynecomastia, (7,8) and such changes are a relatively common finding in women with fibrocystic changes and fibroadenomas. (2,3,9) The lesions are typically discrete and painless, with a firm, rubbery consistency. Recommended treatment consists of excision biopsy. Local recurrences have been reported. (1,2,4)

Grossly, the lesions are well demarcated, with a smooth external surface that can resemble a capsule. (1) The size of the lesions ranges from 2 to 15 cm in greatest dimension. The cut surface of the lesions shows a white, gray, or tan fibrous homogeneous parenchyma without hemorrhage or necrosis. Microscopically, these lesions are characterized by a proliferation of stromal elements with intermixed breast ducts. (1,3) The ducts can show hyperplastic and fibrocystic changes. The dense, fibrous, keloidlike stroma has an anastomosing pattern of slitlike empty spaces lined by a single layer of flattened spindle cells, which resemble endothelial cells. (1,9) Immunohistochemical studies show the expression of vimentin and CD34 in the spindle cells of PHMS, but not factor VIII, CD31, or keratin. (2,8) In some cases of PHMS, patchy, intense labeling of stromal cells with antibodies to progesterone receptor has been reported? with more intense staining in the extralobular component compared to the intralobular stromal cells. Stromal cells in controls were negative.

The pathogenesis of these lesions is unknown. Powell et al (4) demonstrated the expression of vimentin, desmin, smooth muscle actin, and CD34 in the stromal cells of PHMS, consistent with a fibroblast/myofibroblastic cell origin. It is uncertain if these lesions represent a neoplastic process, especially in the tumorous form as suggested by Powell et al, (4) or an exaggerated, altered physiologic process (eg, a hyper-response to progesterone in estrogenprimed tissue) as proposed by Vuitch et al (1) and Anderson et al. (2) Zanella et al (3) indicated that PHMS represents a proliferation of local myofibroblasts, likely related to a hormonal stimulus and that the lesion may represent a local, nonspecific change rather than a true clinicopathologic entity. The clinicopathologic importance of these lesions is that they present as firm masses and microscopically must be distinguished from a low-grade angiosarcoma. Features that favor a diagnosis of angiosarcoma include a grossly hemorrhagic soft lesion with poorly defined areas of thickening or induration, interanastomosing vascular channels with invasion of the structure into the breast parenchyma, papillary endothelial growth, and hyperchromatic endothelial cells. (10)

In the present case, the patient is clinically similar to previously described cases of PHMS in that she is pre-menopausal (age 41) and had lesions that were grossly and histologically similar to previously described cases of PHMS. Immunohistochemical studies showed that the spindle cells lining the cleftlike spaces were strongly positive for progesterone receptor expression, rivaling that of the neighboring breast ductal epithelium. The spindle cells were also strongly positive for vimentin, but negative for factor VIII and CD31, which further confirmed that the pseudoangiomatous spaces were not real vascular spaces. The unusual features of this case include bilateral breast involvement by multiple lesions, as well as the size of the largest lesion (17 cm). Another unusual feature of this case was the role that core needle biopsy had in initially suggesting the diagnosis of PHMS and guiding the surgical management of this patient. In the present case, the results of the core needle biopsy provided an opportunity to discuss management of the patient prior to therapy. Given the progesterone receptor positivity of PHMS, hormonal manipulation prior to surgical excision was considered. However, surgical management was chosen, consisting of resection of the masses along with bilateral breast reduction and reconstruction. Short-term follow-up at 7 months showed no evidence of recurrence.


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

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

(3.) Zanella M, Falconieri G, Lamovec J, Bittesini L. Pseudoangiomatous hyperplasia of the mammary stroma. Pathol Res Pract. 1998;194:535-540.

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

(5.) Seidman JD, Borkowski A, Aisner SC, Sun C-CJ. Rapid growth of pseudoangiomatous hyperplasia of mammary stroma in axillary gynecomastia in an immunosuppressed patient. Arch Pathol tab Med. 1993;117:736-738.

(6.) de Saint Aubain Somerhausen N, Larsimont D, Cluydts N, Heymans O, Verhest A. Pseudoangiomatous hyperplasia of mammary stroma in an HW patient. Gen Diagn Pathol. 1997; 143:215-214.

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

(8.) Milanezi ME Saggioro FP, Zanati SG, Bazan R, Schmitt FC. Pseudoangiomatous hyperplasia of mammary stroma associate with gynaecomastia. J Clin Pathol. 1998;51:204-206.

(9.) Ibrahim PE, Sciotto CG, Weidner N. Pseudoangiomatous hyperplasia of mammary stroma: some observations regarding its clinic pathologic spectrum. Cancer. 1989;63:1154-1160.

(10.) Donnell RM, Rosen PP, Lieberman PH, et al. Angiosarcoma and other vascular tumors of the breast: pathologic analysis as a guide to prognosis. Am J Surg Pathol. 1981;5:629-642.

Accepted for publication June 4, 2001.

From the Department of Pathology, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, Calif.

Reprints: Richard J. Cote, MD, Department of Pathology, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Los Angeles, CA 90033 (e-mail:
COPYRIGHT 2002 College of American Pathologists
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Wang, Lina; Ohara, John A.; Cote, Richard J.
Publication:Archives of Pathology & Laboratory Medicine
Date:Feb 1, 2002
Previous Article:Universal leukocyte reduction: state of the art and the nature of decision making. (State of the Art in Clinical and Anatomic Pathology).
Next Article:Incidental hepatic nodule on abdominal laparotomy. (Pathologic Quiz Case).

Related Articles
Primary Bilateral Mucosa-Associated Lymphoid Tissue Lymphoma of the Breast With Atypical Ductal Hyperplasia and Localized Amyloidosis A Case Report...
Recurrent Dysplasia in an Elderly Patient 20 Years After Treatment for Achalasia.
Coding for the female patient in 2002. (Featured Cme topic: Female Patient).
Postmortem diagnosis of "occult" Klinefelter syndrome in a patient with chronic renal disease and liver cirrhosis. (Case Reports).
Bilateral multinodular oncocytomas of the parotid arising in a background of bilateral oncocytic nodular hyperplasia.
Breast Reduction Surgery May Help Cancer Detection.

Terms of use | Copyright © 2016 Farlex, Inc. | Feedback | For webmasters