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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 nodular

marked with, or resembling, nodules.


nodular dermatofibrosis
see dermatofibrosis.

nodular episcleritis
see nodular fasciitis (below).

nodular fasciitis
a firm painless nodular swelling, 0.
 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 fibrocystic /fi·bro·cys·tic/ (-sis´tik) characterized by an overgrowth of fibrous tissue and development of cystic spaces, especially in a gland.

fi·bro·cys·tic
adj.
 changes. Physical examination showed pendulous pendulous /pen·du·lous/ (-lus) hanging loosely; dependent.

pendulous

hanging loosely; dependent.


pendulous crop
see pendulous crop.
 but symmetrical breasts with no noted skin changes. Palpation palpation /pal·pa·tion/ (pal-pa´shun) the act of feeling with the hand; the application of the fingers with light pressure to the surface of the body for the purpose of determining the condition of the parts beneath in physical diagnosis.  revealed multiple, discrete, large, firm, and mobile breast masses bilaterally. No axillary ax·il·lar·y
n.
Relating to the axilla.


Axillary
Located in or near the armpit.

Mentioned in: Mastectomy


axillary

of or pertaining to the armpit.
 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 Stromal
A type of tissue that is associated with the support of an organ.

Mentioned in: Wilms' Tumor
 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 Red blood cells
Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.

Mentioned in: Bone Marrow Transplantation

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 Nodules
A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.

Mentioned in: Leprosy
 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 circumscribed /cir·cum·scribed/ (serk´um-skribd) bounded or limited; confined to a limited space.

cir·cum·scribed
adj.
Bounded by a line; limited or confined.
 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 Parenchyma

A ground tissue of plants chiefly concerned with the manufacture and storage of food. The primary functions of plants, such as photosynthesis, assimilation, respiration, storage, secretion, and excretion—those associated with living
 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 Lobules
A small lobe or subdivision of a lobe (often on a gland) that may be seen on the surface of the gland by bumps or bulges.

Mentioned in: Fibrocystic Condition of the Breast
. 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 multifocal /mul·ti·fo·cal/ (mul?te-fo´k'l) arising from or pertaining to many foci.

mul·ti·fo·cal
adj.
Relating to or arising from many foci.
 microcalcifications were present. Neither atypical duct hyperplasia nor carcinoma was identified in any of the masses or breast tissue.

[FIGURE 1-3 OMITTED]

What is your diagnosis?

Pathologic Diagnosis: Pseudoangiomatous Hyperplasia of Mammary Stroma stroma /stro·ma/ (stro´mah) pl. stro´mata   [Gr.] the matrix or supporting tissue of an organ.stro´malstromat´ic

stro·ma
n. pl. stro·ma·ta
1.
 

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 perimenopausal adjective Referring to a period of a ♀'s life–age 45 to 55-ish–in which menstrual periods become irregular; perimenopause is immediately before, during and after menopause. See Menopause.  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 gynecomastia

Breast enlargement in a male. It usually involves only the nipple and nearby tissue of one breast. More rarely, the whole breast grows to a size normal in a female. True gynecomastia is related to an increase in estrogens.
 have been reported. (5) Additionally, rapidly growing PHMS has been noted in a clinical setting of human immunodeficiency virus human immunodeficiency virus
n.
HIV.


Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans.
 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 keratin (kĕr`ətĭn), any one of a class of fibrous protein molecules that serve as structural units for various living tissues. The keratins are the major protein components of hair, wool, nails, horn, hoofs, and the quills of feathers. . (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 neoplastic /neo·plas·tic/ (ne?o-plas´tik)
1. pertaining to a neoplasm.

2. pertaining to neoplasia.


neoplastic

pertaining to neoplasia or a neoplasm.
 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 angiosarcoma /an·gio·sar·co·ma/ (an?je-o-sahr-ko´mah) a malignant neoplasm arising from vascular endothelial cells; the term may be used generally or may denote a subtype, such as hemangiosarcoma. . Features that favor a diagnosis of angiosarcoma include a grossly hemorrhagic soft lesion with poorly defined areas of thickening or induration induration /in·du·ra·tion/ (in?du-ra´shun)
1. sclerosis or hardening.

2. hardness.

3. an abnormally hard spot or place.
, interanastomosing vascular channels with invasion of the structure into the breast parenchyma, papillary papillary /pap·il·lary/ (pap´i-lar?e) pertaining to or resembling a papilla, or nipple.
papillary,
adj similar to a small, nipple-shaped elevation or projection.
 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.

References

(1.) Vuitch NIF NIF

See: Note issuance facility
, 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 The U.S. News & World Report ranked USC 27th among all universities in the United States in its 2008 ranking of "America's Best Colleges", also designating it as one of the "most selective universities" for admitting 8,634 of the almost 34,000 who applied for freshman admission , 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: cote-r@norsur.hsc.usc.edu).
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Author:Wang, Lina; Ohara, John A.; Cote, Richard J.
Publication:Archives of Pathology & Laboratory Medicine
Date:Feb 1, 2002
Words:1439
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