A 41-year-old woman with bilateral nodular breasts. (Pathologic Quiz Case).
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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: firstname.lastname@example.org).