Pseudoangiomatous Stromal Hyperplasia: Imaging Findings With Pathologic and Clinical Correlation

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1 Women s Imaging Pictorial Essay Jones et al. Pseudoangiomatous Stromal Hyperplasia Women s Imaging Pictorial Essay WOMEN S IMGING Katie N. Jones 1 Katrina N. Glazebrook 1 arol Reynolds 2 Jones KN, Glazebrook KN, Reynolds Keywords: breast diseases, mammography, MRI, pseudoangiomatous stromal hyperplasia, sonography DOI: /JR Received July 7, 2009; accepted after revision pril 8, Department of Radiology, Mayo linic, 200 First St. SW, Rochester, MN ddress correspondence to K. N. Glazebrook. 2 Division of natomic Pathology, Mayo linic, Rochester, MN. JR 2010; 195: X/10/ merican Roentgen Ray Society Pseudoangiomatous Stromal Hyperplasia: Imaging Findings With Pathologic and linical orrelation OJETIVE. The purpose of this article is to describe the imaging characteristics of pseudoangiomatous stromal hyperplasia, where the primary histologic component was pseudoangiomatous stromal hyperplasia. ONLUSION. The tumoral form of pseudoangiomatous stromal hyperplasia is rare. The most common mammographic and sonographic finding is a circumscribed mass. Its appearance on MRI is nonspecific, but it may present as clumped nonmasslike persistent enhancement on contrast-enhanced imaging. iopsy guided by MRI may be necessary to confirm the diagnosis. P seudoangiomatous stromal hyperplasia (PSH) is a benign disease of the breast characterized by a complex network of slitlike spaces lined by slender spindle cells within a background of stromal hyperplasia [1] (Figs. 1 and 1D). The etiologic factors of PSH are unknown, but most investigators think that it represents a proliferative response of myofibroblasts, probably to hormonal stimuli [1 3]. The purpose of the present study was to describe the imaging appearance of PSH with pathologic and clinical correlation. We performed a retrospective review of our institution s surgical pathology database for the histologic diagnosis of PSH from January 1998 through December ases without available imaging results or in which PSH was an incidental finding were excluded. We identified 57 cases, all in female subjects (mean age, 48 years; range, 9 76 years), for which PSH was the sole or dominant pathologic finding and for which imaging results were available. Diagnosis was obtained for 48 patients from percutaneous biopsies: two en bloc 12-mm radiofrequency biopsies, 12 biopsies with vacuum-assisted devices (9- and 11-gauge), and 34 core needle biopsies (14-gauge needle, 29 biopsies; 16-gauge needle, three biopsies; and 18-gauge needle, two biopsies). Nine cases were identified from excisional biopsies. Pathologic Factors PSH is a common diagnosis histologically, with approximately 23% of breast speci- mens containing microscopic PSH [4]. The tumoral form of PSH is rare. The slitlike channels may be mistaken for a low-grade angiosarcoma. However, angiosarcoma can be differentiated on the basis of malignant cytologic features and positive immunohistochemical staining to endothelial markers, including D31 and factor VIII related antigen. linical Presentation palpable abnormality prompted evaluation for 25 (44%) of the 57 patients; for 30 (53%) patients, an abnormality was detected on screening mammography. For the other two patients, PSH was detected incidentally during evaluation for different abnormalities. mong the patients, 23 (40%) were postmenopausal and 34 (60%) were premenopausal. One patient was prepubescent (age, 9 years). t the time of diagnosis, 11 (19%) patients were taking hormone replacement therapy, and three (5%) were taking oral contraceptives. The series by Mercado et al. [5] showed a strong hormonal association in PSH, with 12 of the 14 patients in their series being premenopausal and the other two being postmenopausal and taking hormone replacement therapy. Reports of PSH responding to hormonal therapy, such as tamoxifen citrate, have also appeared in the medical literature [6]. In our series, 44 (77%) patients either were premenopausal or were postmenopausal and taking hormone replacement therapy JR:195, October 2010

2 Pseudoangiomatous Stromal Hyperplasia Follow-Up Follow-up information was available for 48 patients (10 who underwent surgical excision and 38 who underwent percutaneous biopsy) and covered a period ranging from 6 months to 11 years (mean, 4 years). mong the patients with surgical excision, seven had no recurrence; two patients had progressive enlargement of the breasts and proceeded to mastectomy. There was one recurrence of PSH in a premenopausal woman taking oral contraceptives, which required additional surgical excision. Of the 38 patients who had percutaneous biopsies only, 28 lesions were stable at imaging follow-up. Four lesions that were only seen and biopsied on MRI had decreased in size or resolved on follow-up MRI. In six patients, the biopsied lesions had increased in size and required a further biopsy, which confirmed PSH. One of these patients had an additional biopsy for continued growth, which again showed PSH. Subsequent follow-up of these six patients showed stable imaging findings. No lesions were upgraded on additional biopsies, and no malignancies were found on follow-up of the biopsied breast in the study population. Imaging Findings Mammography Mammograms were available for 55 patients. n abnormality was detected in 43 (78%) cases. In 12 (22%) cases, the abnormality was not detected mammographically. Recently, one study reported that 69% of patients who had PSH presented with no mammographic abnormality; however, that series included cases in which PSH was incidentally noted histologically [7]. Other smaller studies have described 100% of PSH lesions detected mammographically [8 10]. The most common appearance of PSH mammographically has been reported as noncalcified, circumscribed, or partially circumscribed masses, rarely with irregular margins [8, 9]. Piccoli et al. [11] evaluated 21 patients with developing asymmetric tissue. Review of 13 biopsies showed PSH in all 13 cases. The mammographic appearance of the asymmetric tissue was similar to that of normal fibroglandular breast tissue. No associated architectural distortion or microcalcifications were seen. The most common presentations in our study were of a mass, which occurred in 25 (44%) cases (Figs. 1, 2, and 2), and focal asymmetry, which occurred in 18 (32%) cases (Figs. 3, 4, and 4). These findings are consistent with those of prior reports [7, 9, 10]. No cases of architectural distortion or calcifications were identified. Sonography In 86% of cases (48/56), a lesion was detected on sonography. Sonography was not performed in one case. Most cases of PSH (66% [37/56]) presented as a circumscribed oval hypoechoic mass, rarely with a cystic component (Fig. 2). lthough these findings are nonspecific, they favor a benign process [10, 12]. less common appearance (20% of cases [11/56]) was a heterogeneous or echogenic area with hypoechoic central areas (Figs. 3D and 4). Piccoli et al. [11] described this finding in association with a developing focal asymmetry seen mammographically. Eight cases (14%) showed irregular or poorly defined borders and were classified as I-RDS 4 sonographically (Fig. 5). Sizes ranged from 3 mm to 7 cm. T PSH may be seen on T as a circumscribed mass (Fig. 5). Three unenhanced T scans of the chest identified incidental circumscribed masses in the breast that, on subsequent biopsy, proved to be PSH. MRI MRI was performed for nine patients: three for screening of patients with prior breast malignancy, two for staging of breast cancer before definitive surgery, two for asymmetric breast enlargement, and two for areas of clinical concern and negative results on imaging. MRI showed an abnormality in the region of subsequent biopsy-proven PSH in eight of these cases. In seven cases, MRI showed an appearance of a persistent or a plateau area of focal or segmental clumped enhancement (Figs. 3, 6, and 7). One case showed an irregular mass (Fig. 8). Three patients had lesions found on sonography and had percutaneous biopsies performed sonographically. Four patients had MRI-guided biopsies because there were no correlative findings on mammography or sonography. Repeat MRI at 6 months or 1 year showed decreased enhancement or resolution of enhancement in the area of PSH. One patient with persistent breast enlargement and MRI results negative for focal abnormality had surgical excision, which showed PSH. She proceeded to bilateral mastectomies because of persistent breast enlargement; PSH extensively involved both breasts. Prior case reports have shown persistent (type 1) enhancement in PSH [5, 10, 13, 14], but clumped focal nonmasslike enhancement or irregular mass with plateau and washout enhancement kinetics has not been reported previously. Ductal carcinoma in situ or invasive carcinoma could not be excluded in these patients, and this lack of exclusion prompted biopsy. The pathologic diagnosis of PSH was believed to be concordant with the imaging findings. No evidence of tumor was found in follow-up of these cases. predominant histologic diagnosis of PSH (rather than focal microscopic PSH) is concordant in our experience, and close interval follow-up with careful clinical and imaging correlation is acceptable, rather than necessitating surgical excision. Nuclear Medicine Studies Molecular breast imaging was performed for four patients with imaging available for evaluation. The imaging showed negative results in two patients and positive results in two patients. In one patient, the area of increased tracer uptake (Fig. 6) corresponded to the area of progressive clumped focal enhancement on MRI. The patient elected to have a prophylactic mastectomy, and pathologic evaluation showed a 3.6-cm ill-defined nodular area of PSH. PSH may also have a false-positive result on PET studies. The PET scan showed a focal area of increased activity in the right upper outer breast, corresponding to a focal asymmetry seen mammographically (Fig. 3). The activity was similar to that seen in the patient s extensive lobular carcinoma of the left breast. MRI showed an area of clumped progressive focal enhancement. Sonographically guided biopsy showed PSH. In conclusion, mammary PSH is usually detected as an incidental microscopic finding and rarely presents in tumoral form. The current study is limited because of the retrospective nature of the study and the small sample size, because only lesions for which PSH was the predominant finding on biopsy were included. Most often, PSH is stable over time, but it may increase rapidly in size or may recur. Mammographically, it may present as a circumscribed mass or as a developing focal asymmetry. Sonographically, it most often presents as a circumscribed mass with or without cystic areas. It may appear similar to echogenic fibroglandular tissue, containing linear hypoechoic structures similar to ducts within the area of hyperechogenicity. MRI may show clumped nonmasslike areas of JR:195, October

3 Jones et al. persistent or plateau enhancement. This appearance may be similar to ductal carcinoma in situ on MRI and may require MRI-guided biopsy to confirm the benign nature of this enhancement pattern, particularly in highrisk patients. References 1. Vuitch MF, Rosen PP, Erlandson R. Pseudoangiomatous hyperplasia of mammary stroma. Hum Pathol 1986; 17: nderson, Ricci Jr, Pedersen, artun 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. m J Surg Pathol 1991; 15: Powell M, ranor ML, Rosen PP. Pseudoangiomatous stromal hyperplasia (PSH): a mammary stromal tumor with myofibroblastic differentiation. m J Surg Pathol 1995; 19: Ibrahim RE, Sciotto G, Weidner N. Pseudoangiomatous hyperplasia of mammary stroma: some observations regarding its clinicopathologic spectrum. ancer 1989; 63: Mercado L, Naidrich S, Hamele-ena D, Fineberg S, uchbinder SS. Pseudoangiomatous stromal hyperplasia of the breast: sonographic features with histopathologic correlation. reast J 2004; 10: Pruthi S, Reynolds, Johnson RE, Gisvold JJ. Tamoxifen in the management of pseudoangiomatous stromal hyperplasia. reast J 2001; 7: Hargaden G, Yeh ED, Georgian-Smith D, et al. nalysis of the mammographic and sonographic features of pseudoangiomatous stromal hyperplasia. JR 2008; 191: ohen M, Morris E, Rosen PP, Dershaw DD, Liberman L, bramson F. Pseudoangiomatous stromal hyperplasia: mammographic, sonographic, and clinical patterns. Radiology 1996; 198: Polger MR, Denison M, Lester S, Meyer JE. Pseudoangiomatous stromal hyperplasia: mammographic and sonographic appearances. JR 1996; 166: Salvador R, Lirola JL, Dominguez R, Lopez M, Risueno N. Pseudo-angiomatous stromal hyperplasia presenting as a breast mass: imaging findings in three patients. reast 2004; 13: Piccoli W, Feig S, Palazzo JP. Developing asymmetric breast tissue. Radiology 1999; 211: Stavros T. Ultrasound of solid breast nodules: distinguishing benign from malignant. In: Stavros T, Rapp L, Parker SH, eds. reast ultrasound. Philadelphia, P: Lippincott Williams & Wilkins, 2004: luemke D, Gatsonis, hen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JM 2004; 292: Teh HS, hiang SH, Leung JW, Tan SM, Mancer JF. Rapidly enlarging tumoral pseudoangiomatous stromal hyperplasia in a 15-year-old patient: distinguishing sonographic and magnetic resonance imaging findings and correlation with histologic findings. J Ultrasound Med 2007; 26: Fig year-old woman with pseudoangiomatous stromal hyperplasia., ilateral mediolateral oblique mammogram views show large mass in right breast, which had increased in size since previous mammogram. Results of excisional biopsy showed pseudoangiomatous stromal hyperplasia., Gross specimen shows pseudoangiomatous stromal hyperplasia that formed well-circumscribed cm mass. (Fig. 1 continues on next page) 1038 JR:195, October 2010

4 Pseudoangiomatous Stromal Hyperplasia Fig. 1 (continued) 49-year-old woman with pseudoangiomatous stromal hyperplasia. and D, Photomicrographs of histopathologic specimen show stromal hyperplasia with slitlike channels (arrows) lined by attenuated spindle cells interspersed between normal breast glandular tissue. (H and E, original magnification 10 in [] and 40 [D]). Fig year-old woman with pseudoangiomatous stromal hyperplasia., Screening mammogram (mediolateral oblique view) from January 2002 shows circumscribed dense mass with partially obscured margins in right outer breast., Right craniocaudal mammogram from July 2002 shows that circumscribed mass has increased in size since January 2002, and it has now become palpable. iopsy results showed pseudoangiomatous stromal hyperplasia., Sonogram of palpable abnormality shows well-circumscribed oval homogeneous mass consistent with fibroadenoma. D JR:195, October

5 Jones et al. Fig year-old woman with extensive lobular carcinoma of left breast., Image shows exaggerated craniocaudal view of right breast with palpable marker overlying area of focal asymmetry in right outer breast (arrow)., PET scan shows focal increased activity in right upper outer breast (straight arrow) corresponding to area of asymmetric density seen mammographically and of similar intensity to left breast cancer (curved arrow)., Sagittal 3D gadolinium-enhanced fast spoiled gradient-echo MR image, obtained immediately after gadolinium administration, of contralateral right breast shows clumped nonmasslike enhancement in asymmetric tissue in right upper outer breast (arrow). rea shows persistent kinetics. D, Sonogram of right upper outer breast shows area of echogenic parenchyma with linear serpiginous hypoechoic areas (arrows). Sonographically guided biopsy showed pseudoangiomatous stromal hyperplasia. D 1040 JR:195, October 2010

6 Pseudoangiomatous Stromal Hyperplasia Fig year-old woman with pseudoangiomatous stromal hyperplasia., Screening mammogram (mediolateral oblique view) shows developing asymmetric density in right breast (arrow), which has increased since screening mammogram 2 years previously., Sonogram of right breast shows area of echogenicity with linear, hypoechoic structures (arrow) suggestive of ducts within it., Small amount of iodinated contrast agent was injected under sonographic guidance into area of echogenicity (arrow) seen sonographically. Repeat right breast mediolateral oblique view shows that sonographic abnormality corresponded to mammographic asymmetric density. Fig year-old woman with pseudoangiomatous stromal hyperplasia., Incidental circumscribed mass in lateral right breast (arrow) detected on unenhanced chest T scan., Sonographic scan of mass detected on T shows mass containing cystic areas (straight arrows) and microlobulated border (curved arrow) in right breast. Percutaneous biopsy showed pseudoangiomatous stromal hyperplasia. JR:195, October

7 Jones et al. Fig year-old woman with prior left mastectomy for rhabdomyosarcoma., Sagittal 3D gadolinium-enhanced fast spoiled gradient-echo MR image, obtained immediately after gadolinium administration, of right breast shows area of nonmasslike clumped enhancement in upper right breast (arrows). Finding shows persistent enhancement. MRI-guided biopsy shows pseudoangiomatous stromal hyperplasia., Right mediolateral oblique view from molecular breast imaging study shows area of abnormal sestamibi uptake in right superior breast (arrow), corresponding to area of clumped enhancement on MRI. linical follow-up for 3 years was negative for malignancy; however, patient elected to have prophylactic mastectomy. Pathologic evaluation showed pseudoangiomatous stromal hyperplasia forming ill-defined 3.6-cm mass in right upper outer breast. Fig year-old woman with biopsy-proven ductal carcinoma in situ of right breast. Sagittal 3D gadolinium-enhanced fast spoiled gradient-echo MR image, obtained immediately after gadolinium administration, of left breast shows clumped segmental enhancement (arrows). Ductal carcinoma in situ could not be excluded. MRI-guided biopsy showed pseudoangiomatous stromal hyperplasia. Fig year-old woman with prior left mastectomy for ductal carcinoma in situ at age 32 years. Screening 3D subtraction sagittal gadolinium-enhanced fast spoiled gradient-echo MR image, obtained immediately after gadolinium administration, of right breast shows irregular mass in medial right breast with persistent and plateau kinetics (arrow). MRI-guided percutaneous biopsy showed pseudoangiomatous stromal hyperplasia. Follow-up MRI at 6 months showed decrease in size of mass. Patient elected to have prophylactic mastectomy 1 year later. Focal pseudoangiomatous stromal hyperplasia was identified. No malignancy was found at biopsy site. Follow-up MRI at 6 months (not shown) showed decrease in size of mass JR:195, October 2010