A case of nodular pseudoangiomatous stromal hyperplasia (PASH)

Article · February 2006with137 Reads
DOI: 10.2325/jbcs.13.349 · Source: PubMed
Abstract
Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a common microscopic lesion that is found at breast biopsy, and presents with proliferation of the stromal cells and slit-like pseudovascular spaces with endothelial-like spindle cells. In contrast, nodular PASH is relatively rare. We report here a case of nodular PASH with multiple palpable masses. A 49-year-old woman who had experienced gradual enlargement of her breasts for 13 years noticed an elastic but firm palpable mass in her breast. We were able to detect 7 masses in her right breast and 2 in the left. Ultrasonography and mammography demonstrated nonspecific findings, and FNA and CNB did not establish a diagnosis. An excisional biopsy was performed, and the pathological findings revealed nodular PASH. Eighteen months after the excisional biopsy, the size of the nodules and the whole breast had decreased remarkably. While the possibility of a change in the hormonal background or the influence of drugs was considered, we were not able to reach a single specific conclusion regarding the pathogenesis.
349
Breast Cancer
Vol. 13 No. 4 October 2006
Case Report
Pseudoangiomatous stromal hyperplasia
(PASH), which was first reported in 1986
1)
, is a
type of benign proliferative lesion of the breast
stroma that is characterized by slit-like pseudovas-
cular spaces lined by endothelial-like spindle cells
in keloid fibrosis
1, 2)
. PASH is often accompanied
by other benign and malignant breast lesions
2, 3)
,
although it is relatively rare for PASH to form a
palpable nodule. It is generally considered that
hormones, especially progesterone, can contri-
bute to the formation of PASH. We report here a
case in which breast enlargement and palpable
nodules including PASH shrank naturally, 18 mon-
ths after excisional biopsy.
Case Report
A 36-year-old woman noticed slow, progressive
enlargement of her breasts (the right was larger
than the left) in 1990. After she detected soft nod-
ules in her right breast, she visited a local hospital
in March 2003. She underwent mammography
(MMG), ultrasonography (US), computed tomog-
raphy (CT), fine needle aspiration (FNA) and core
needle biopsy (CNB). FNA was not useful beca-
use of low cellularity, and CNB performed twice
demonstrated fibrotic proliferation, suggestive of
phyllodes tumors. She was subsequently referred
to our hospital. Seven nodules almost completely
occupied the right breast and peau-de-orange
changes of the skin were observed in the lower
inner portion. There were two nodules in the left
breast (Fig 1A, B). The nodules were firm, elastic
and well-defined. The right breast was obviously
larger than the left (Fig 1A). MMG showed no dis-
tinct tumor shadow because the breasts were
large and firm with some nodules and sufficient
pressure could not be applied. US demonstrated
seven tumors in the right and two in the left bre-
ast, which had regular borders for the most part
and showed low but partly heterogeneous echo-
Reprint requests to Kae Okoshi, Department of Surgery, Graduate
School of Medicine, Kyoto University, 54-Shogoin Kawara-cho,
Sakyo-ku, Kyoto 606-8507, Japan.
E-mail: kae_md@kuhp.kyoto-u.ac.jp
Abbreviations:
PASH, Pseudoangiomatous stromal hyperplasia; US, Ultrasono-
graphy; MMG, Mammography; FNA, Fine needle aspiration;
CNB, Core needle biopsy; CT, Computed tomography; MRI,
Magnetic resonance imaging; CD, Cluster of differentiation;
SMA, Smooth muscle actin
Received October 12, 2005; accepted May 8, 2006
Key words: Pseudoangiomatous stromal hyperplasia (PASH), Breast tumor, Myofibroblast
1
Department of Surgery, Graduate School of Medicine, Kyoto University,
2
Department of Surgery,
3
Department of
Pathology, and
4
Department of Radiology, Otsu Red Cross Hospital, Japan.
Kae Okoshi
1
, Hiroki Ogawa
2
, Hirofumi Suwa
2
, Tatsuyoshi Saiga
3
, and Hisato Kobayashi
4
Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a common microscopic lesion that is
found at breast biopsy, and presents with proliferation of the stromal cells and slit-like pseudovascular
spaces with endothelial-like spindle cells. In contrast, nodular PASH is relatively rare. We report here a
case of nodular PASH with multiple palpable masses.
A 49-year-old woman who had experienced gradual enlargement of her breasts for 13 years noticed an
elastic but firm palpable mass in her breast. We were able to detect 7 masses in her right breast and 2 in
the left. Ultrasonography and mammography demonstrated nonspecific findings, and FNA and CNB did
not establish a diagnosis. An excisional biopsy was performed, and the pathological findings revealed nodu-
lar PASH. Eighteen months after the excisional biopsy, the size of the nodules and the whole breast had
decreased remarkably. While the possibility of a change in the hormonal background or the influence of
drugs was considered, we were not able to reach a single specific conclusion regarding the pathogenesis.
Breast Cancer 13:349-353, 2006.
A Case of Nodular Pseudoangiomatous Stromal Hyperplasia (PASH)
genicity. In October 2003 an excisional biopsy was
performed on a mass in the upper inner quadrant
of her right breast to confirm the histological diag-
nosis (Fig 1B). The specimen was a well-circumsc-
ribed yellow-gray tumor, 3.8×3.0×1.9 cm in size.
She underwent MRI examination to investigate
the residual masses. The MRI showed several
high-intensity lesions on fat-suppressed T2-weigh-
ted images, and these lesions exhibited some sep-
tae with surrounding low-intensity signals (Fig 2).
Furthermore, the time-intensity curves showed
gradual increase, which suggested that the tum-
ors were benign.
In April 2005, the size of both breasts and the
remaining tumors had decreased remarkably, and
the two nodules in the left breast were no longer
palpable.
Pathological Findings
Initially, fibrocystic disease of the mammary
glands with stromal hyperplasia was diagnosed.
The epithelial proliferation included cystic dilata-
tion of the ducts with apocrine metaplasia, blunt
duct adenosis, and duct papillomatosis (Fig 3A).
The diagnosis was determined by noting the pro-
liferative epithelial changes. After some discus-
sion, PASH was subsequently diagnosed. The vas-
cular endothelial-like spindle cells formed a ves-
sel-like slit in the stroma (Fig 3B) and immunohis-
tochemical staining for CD34, CD31, D2-40, smoo-
th muscle actin (SMA) and Factor supported
this diagnosis. The spindle cells were positive for
CD34 and, in part, SMA (Fig 3C, D) and negative
for CD31, D2-40 and Factor . The slits were the-
refore neither true lymph nor blood vessels and
were covered with myofibroblasts. The nuclei of
the ductal epithelial cells were immunopositive for
both estrogen and progesterone receptor, where-
as the stromal cells were negative.
Discussion
Pseudoangiomatous stromal hyperplasia
(PASH), which was first reported by Vuitch et al.
1)
in 1986, is a benign proliferative lesion of the bre-
ast stroma. Although the vascular endothelial-like
spindle cells form vessel-like slits in the stroma,
they are not true vessels covered with endothelia,
but rather vacant spaces bordered with myofibro-
blasts. PASH can be accompanied by other types
Okoshi K, et al Nodular PASH of the Breast
350
Fig 1A: There were seven masses in the right breast and
two in the left, which occupied almost the entire breast. The
right breast was obviously larger than the left and accompa-
nied by peau-de-orange change of the skin (arrowheads). B:
The gray circles in the schema demonstrated the distribution
of the palpable nodules. Excisional biopsy was performed on a
mass in the upper inner quadrant of the right breast (arrow).
Fig 2MRI showed several high-intensity lesions on fat-sup-
pressed T2-weighted imaging. These lesions exhibited some
septae with surrounding low-intensity signals (arrowheads).
of breast tumors. Ibrahim et al.
2)
reported that
PASH could be detected microscopically (at least
one lesion) in 23% of 200 cases of benign and mali-
gnant breast tumors. Morita et al.
4)
described that
PASH was associated with mastopathy (14.1%),
fibroadenoma (0.9%), and carcinoma (6.7%). On
the other hand, nodular PASH is relatively rare.
The histopathological differentiation between
PASH and a low-grade angiosarcoma is important.
In the case of PASH, there are no blood cells in
the slit-like spaces, and the lesions do not exhibit
any atypia or mitotic activity
1)
.
Since the spindle cells that cover the vascular-
like-slit were immunopositive for CD34
3, 5)
and
vimentin
2, 3, 6)
but immunonegative for Factor
2, 3)
,
they were also useful markers for making the his-
tological diagnosis. Furthermore, PASH exhibits
variable immunoreactivity for SMA
5)
. In this study,
the spindle cells covering the vascular-like slits
were positive for CD34 and, in part, SMA. The
immunostaining pattern suggested that the spin-
dle cells consisted of a spectrum of cells, ranging
from relatively juvenile mesenchymal cells to
myofibroblasts. The term pseudo-angiomatous str-
omal hyperplasia expresses only the stromal form
of this lesion. It is often accompanied by hyperpla-
sia of the ducts and lobular epithelium, as well as
apocrine metaplasia and cyst formation
2, 5, 7)
. Some
cases might not be diagnosed as PASH because
the ductal proliferative changes are apparently
more remarkable than those of the stroma. It is
necessary to differentiate PASH from other types
of benign breast tumors such as hamartomas,
fibroadenomas and phyllodes tumors
8-11)
.
PASH occurs in premenopausal, perimenopos-
al or postmenopausal women who have taken hor-
mone replacement therapy
5, 8)
, and in 23.8% of men
who have gynecomastia
3)
. Furthermore, proges-
terone receptor immunoreactivity is often posit-
ive
5, 6, 8)
. Hence many authors have described PASH
351
Breast Cancer Vol. 13 No. 4 October 2006
Fig 3A: Microscopy demonstrated that the lesion consisted of stromal hyperplasia, with epithelial proliferation,
papillomatous proliferation, and cystic dilatation of the ducts with apocrine metaplasia (arrowheads). B: The vascular
endothelial-like spindle cells (arrows) formed a vessel-like slit (arrowheads) in the stroma. C: Immunopositivity for
CD34 was evident all over the spindle cells covering the vessel-like slits. D: Immunopositivity for
α-SMA was evident
in the smooth muscle of the true blood vessels (arrowheads) and partly in the spindle cells lining the pseudovascular
slits (arrows).
as being hormone-dependent; in other words,
PASH is hyperplasia of the stromal cells induced
by an excessive response to progesterone
8)
. In
this case the patient was perimenopausal when
she came to our hospital, however, on immunos-
taining neither estrogen nor progesterone recep-
tor was apparent in stromal cells. Thus, there was
only indirect evidence of a hormonal etiology in
this case.
Since she had been treated with loxoprofen
sodium, bucillamine and famotigine for articular
rheumatism, the possibility that the lesion was
drug-induced was raised. There has been one
case report of remarkable breast enlargement
while taking bucillamine
12)
. Famotigine sometimes
causes gynecomastia in men, and, rarely, lactation
and swelling of the breasts in women. In this case,
because the breasts had started to enlarge before
she was treated with the drugs in 2002, and the
lesions were asymmetric, the drugs might not
have been the main cause of the nodules but may
have exerted some influence on the growth of the
nodules. The patient stopped taking these drugs
in December 2003.
It is very difficult to diagnose of PASH by
imaging alone, with MMG, US and MRI
7, 9-11)
. On
MMG, PASH exhibits no calcification, but usually
a totally or partially regular border, and some-
times an irregular one
7, 9-11)
. PASH is often detected
in progressive asymmetrical breast tissues by
MMG
13)
. On US, it exhibits variable findings, from
homogeneous, low to iso- and high-echoic solid
lesions to masses including a cystic structure.
Nevertheless, PASH typically presents with a reg-
ular border and a hypo-echoic lesion
7, 9, 11)
. There
have been a few case reports of MRI for PASH. In
one case report, PASH exhibited mainly interme-
diate signals with some low-intensity regions using
gadolinium-enhanced T1-weighted imaging, and
some lesions included high- and low-intensity are-
as covered with a low-intensity capsule
11)
. In anoth-
er case report, the findings from the time-intensity
curve demonstrated almost the same pattern as a
fibroadenoma
9)
, although the MRI was more use-
ful for examining the size, border and nature of
the tumor than the other imaging methods
11)
.
Since the FNA findings for PASH are not spe-
cific
6)
, it is insufficient for diagnosis, as in this
case. Even when CNB is performed, it is neces-
sary to keep the possibility of PASH in mind
11)
.
Although there has been a case report of
PASH that was treated by tamoxifen
14)
, some auth-
ors have recommended local widespread excisi-
on
1, 5)
. Nevertheless, PASH sometimes recurs after
excision
1, 5)
. Powel et al. reported a case in which
bilateral mastectomy was performed for multiple
recurrences
5)
. However, there have been no cases
in which PASH became malignant. Moreover,
some authors have reported that when the find-
ings of imaging, US or MRI, and CNB are consis-
tent with PASH and were able to exclude malig-
nancy, resection is not necessary with close imag-
ing follow-up
7, 9)
.
In this case, we found a total of 9 masses in
both breasts, one of which was diagnosed as
PASH. Since PASH often occurs in multiples, the
other 8 lesions could have been also PASH or oth-
er types of tumor. In order to definitively diagnose
all the tumors, we considered it necessary to res-
ect them all, because CNB was not sufficient for
definitive diagnosis. Since 7 nodules were distrib-
uted all over the right breast and occupied many
parts of the breast, we would have needed to per-
form right mastectomy to remove all the masses.
However, the findings from all the imaging proce-
dures indicated benign lesions, and the patient
preferred to continue with conservative manage-
ment. Thus we did not choose to perform such an
aggressive surgical procedure on her breasts and
decided to closely follow the lesions periodically.
Even though the remaining tumors shrank natu-
rally 18 months later, it may have been appropri-
ate to perform CNB on all residual nodules to con-
firm the diagnosis.
Acknowledgements
We thank Dr. Paul Peter Rosen (New York-Presbyter-
ian Hospital Weill Cornell Medical Center), Dr. Goi
Sakamoto (The Cancer Institute of Japanese Foundation
for Cancer Research), Dr. Shu Ichihara and Dr. Suzuko
Moritani (National Hospital Organization Nagoya Medical
Center), and Dr. Yasuaki Nakashima (Kyoto University
Hospital) for their significant advice.
A summary of this report was presented at the 13th
annual meeting of the Japanese Breast Cancer Society in
Kurashiki in 2005.
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Breast Cancer Vol. 13 No. 4 October 2006
    • Pseudoangiomatous stromal hyperplasia (PASH) is an unusual benign breast condition that was first described in 1986 [1]. The reported age range of patients is 14-67 years, although the vast majority of PASH patients present in their late thirties and forties [2]. It is histologically defined as a complex network of slit-like spaces lined by endothelial-like spindle cells against a background of stromal hyperplasia [3].
    [Show abstract] [Hide abstract] ABSTRACT: Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion, characterized by a dense proliferation of stromal mesenchymal cells of myofibroblastic origin forming empty, slit-like channels. We report PASH in a 12-year-old girl with a huge rapidly enlarged right breast. Biopsy of the mass showed histopathologic features characteristic of PASH. Immunohistochemical studies revealed diffuse positive membranous immunoreactivity to CD34. Although it is a benign lesion, lumpectomy was performed to minimize the damage from developing breast tissue.
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    • To delineate the differentiation of the primary mammary sarcomatous lesion, differentiation specific markers may be helpful, including CD31 for vascular differentiation, S100 for chondroid and lipomatous differentiation, smooth muscle actin for leiomyomatous differentiation and myogenin for rhabdomyomatous differentiation. CD34 can also be used to identify vascular lesion, DFSP and PASH[57].
    [Show abstract] [Hide abstract] ABSTRACT: Spindle cell lesions of the breast represent an interesting diagnostic problem, as the differential diagnoses are wide. Diagnosing this is particularly problematic but important when encountered in a needle core biopsy, as treatments of different entities are different. In the histologic assessment of spindle cell lesions, the simplified approach is to evaluate the spindle cells and the accompanying epithelial cells. In the biphasic lesions with predominance of spindle cells with benign epithelial component, fibroepithelial lesions including fibroadenomas and phyllodes tumors are the most common, followed by pseudoangiomatous stromal hyperplasia, hamartoma and adenomyoepithelioma. For biphasic lesions with predominance of spindle cells with malignant epithelial component, the biphasic metaplastic carcinoma is likely. For monophasic lesions with pure pleomorphic spindle cell only, the monophasic metaplastic carcinoma is more common than the rare primary sarcomas like malignant fibrous histiocytoma, angiosarcoma, and other high grade sarcomas. In monophasic lesions with pure bland spindle cells only, the possible lesions include fibromatosis, fibromatosis like metaplastic carcinoma and other unusual conditions like dermatofibrosarcoma protuberance. By careful searching for the accompanying epithelial element, and with the aid of appropriate clinical input and judicious use of immunohistochemistry, many of these lesions can be confidently diagnosed in the needle core biopsy, thus facilitating appropriate treatments.
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  • [Show abstract] [Hide abstract] ABSTRACT: 乳腺の偽血管腫様過形成が腫瘤を形成する場合はpseudoangiomatous stromal hyperplasia (PASH) と呼ばれ, 稀とされている. 今回われわれはPASHの1例を経験したので報告する. 症例は28歳, 女性. 右乳房腫瘤を主訴に当科を受診した. 右乳房A領域に大きさ30×25mm, 境界明瞭で弾性硬, 可動性良好の腫瘤を触知した. 超音波検査, 穿刺吸引細胞診では線維腺腫が疑われたが, 比較的腫瘍が大きいため腫瘤摘出術が行われた. 病理組織学的所見では紡錘形細胞を伴ったスリット状, 血管様の間隙が不規則にみられた. 免疫組織学的染色ではVimentin, α-SMA, Desmin, CD34が陽性でありPASHと診断された. PASHは術前診断が困難な場合が多く, 時に低悪性度の血管肉腫と鑑別を要することもあり注意が必要である.
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  • [Show abstract] [Hide abstract] ABSTRACT: To present a case of pseudoangiomatous stromal hyperplasia (PASH) and its findings under 1. mammography - MG, 2. ultrasonography - USG and 3. magnetic resonance imaging - MRI. A woman 39 years of age with a history of mass in her right breast of 3 months duration was subjected to a routine examination of the mass using MG & USG. According to the modality findings a core cut biopsy was done following which the samples were send for histological analysis. Later, MRI was done as advocated by the surgeon to get a better picture of the extent of the lesion prior to surgery. Bilateral mammogram views revealed in the patient's right breast a huge well-bordered tumour of lobulated contour without halo sign. Sonography revealed a big well-demarcated tumour in the central part of the right breast which was cystic and lobulated in shape. Histological analysis of the sample confirmed pseudoangiomatous stromal hyperplasia (PASH). MRI under a breast array coil revealed a mass of 85 x 75 x 35mm in the right breast. Finally, based on the clinical, radiological and histological report the mass was diagnosed as benign and despite the massive size of the mass, tumour excision alone was done and not mastectomy. The right breast after the huge tumour excision was almost normal in size compared to the left. PASH should be included in the differential diagnosis of a circumscribed or partially circumscribed mass, especially in the pre-menopausal female population. These benign masses often grow over time and can recur locally. Radiological diagnosis of PASH is usually done by MG and USG followed by core cut biopsy for histological analysis. However great the mass is, excision only of the tumor mass is recommended and not mastectomy.
    Full-text · Article · Jul 2008
  • [Show abstract] [Hide abstract] ABSTRACT: Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.
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