|VOL 63, NO 1/JANUARY 2007 Contemporary Surgery ©2007 Quadrant HealthCom Inc.
What is this breast mass a mammogram detected?James Harris, MD
Department of Surgery, Dwight D. Eisenhower Army Medical Center, Fort Gordon, GA
Was this 8-cm right-breast tumor an angiosarcoma, a phyllodes tumor, or something else?
A 47-year-old premenopausal woman was referred for surgical evaluation after mammography (FIGURE 1) and a follow-up US identified an 8-cm right-breast mass.
The patient had not found the mass on self-exam, and she denied skin changes, nipple discharge, or other masses. She had not had a mammogram, used oral contraceptives, or smoked in the past ten years. She had no family history of breast cancer.
Core-needle biopsy showed benign breast parenchyma with focal sclerosing adenosis and stromal fibrosis.
On physical exam, we found an 8-cm lobulated, well-circumscribed infra-areolar mass in the patient’s right breast. No skin changes, nipple discharge, or retraction were evident. She had no left-breast masses or axillary lymphadenopathy.
Core-needle biopsy showed a benign breast parenchyma with focal sclerosing adenosis and stromal fibrosis. Based on these findings, we developed a differential diagnosis of fibroadenoma or phyllodes tumor.
FIGURE 1 Finding the breast mass
Mammogram showed a lower-inner quadrant, mildly lobulated, smoothly marginated, 8-cm mass. No suspicious microcalcifications or architectural distortion were evident.
FIGURE 2 Specimen provided more information
The cut surface of the mass was gray-white with a rubbery, nodular consistency and completely surrounded by a thin layer of fibrous connective tissue and some fibroadiopse soft tissue. Cut surfaces were free of necrosis or hemorrhage.
PASH can be mistaken for low-grade angiosarcoma at low magnification.
Given the patient’s history and the size of the mass, we recommended an excisional biopsy.
The biopsy specimen consisted of a 9-cm well-circumscribed mass of gray-white rubbery tissue with partial lobulation (FIGURE 2). Histologic examination revealed abundant fibrous stroma containing clefts lined by spindle cells (FIGURE 3). The mass was completely surrounded by a thin layer of fibrous connective tissue and some fibroadiopse soft tissue. Cut surfaces were free of necrosis or hemorrhage. Histology did not identify a true capsule.
The lining cells of stromal clefts were strongly immunoreactive with vimentin and CD34 (FIGURE 4), focally reactive with smooth muscle Actin, and not reactive for progesterone, estrogren, desmin, and factor VIII. We diagnosed pseudoangiomatous stromal hyperplasia (PASH).
At 6-month follow-up, the patient showed no evidence of recurrence.
What is PASH?
First reported in 1986, PASH is a rare, proliferative, benign disorder of breast stromal tissue. Fewer than 120 cases of palpable PASH have been reported.1-5
While it can be a dominant mass, PASH more frequently presents as an incidental pathologic finding with other lesions. The combined incidence is controversial. One study of 1661 breast biopsies identified PASH in 0.4% of subjects.6 A second reported a focus of PASH in 23% of 200 consecutive breast biopsies.7
Patients with PASH range from ages 12 to 67,8,9 are both male and female, and may be immunosuppressed. Usually, PASH is found in native breast tissue (breast or axillary) of premenopausal females, although one case reported PASH in the anogenital region of 3 females.2
Patients generally present with a 1–18-cm palpable mass that is well-circumscribed, non-encapsulated, rubbery, and lobulated.10 PASH cannot be distinguished from fibroadenoma on physical exam.
Microscopic PASH has been seen in normal tissue, gynecomastia, and lobular hyperplasia, and with other changes such as fibrocystic disease, invasive ductal carcinoma, fibroadenoma, and benign phyllodes tumor.11,12
Causes of PASH
The etiology of PASH remains unproven. Authors have theorized it is hormonally related for three reasons:
Its appearance is similar to the normal changes in mammary stroma during the luteal phase.
Its occurrence in premenopausal women and postmenopausal women taking estrogen replacement.
Its association with gynecomastia1,10,11
PASH is considered a neoplastic process due to its ability to recur. However, PASH is not premalignant. In situ or invasive carcinoma within a PASH mass has not been reported.
On mammography, PASH appears as a round or ovoid circumscribed, or semi-circumscribed, mass. Ultrasound demonstrates a hypoechoic, solid mass.
The cytologic appearance of PASH is nonspecific, similar to fibroadenoma. So fine-needle aspiration is seldom helpful in obtaining a diagnosis, whereas core biopsy may provide a diagnosis.
PASH is considered a neoplastic process due to its ability to recur, but it is not premalignant.
At low magnification, the lesion can easily be mistaken for a low-grade angiosarcoma due to the complex pattern of interconnecting spaces partially lined by spindle cells. Unlike angiosarcoma, however, the spaces in PASH do not contain erythrocytes. No cytologic atypia or mitotic activity exists.
The spaces in PASH probably arise from disruption and separation of stromal collagen fibers. One can further differentiate it from angiosarcoma based on the negative reaction to endothelial markers such as CD31 and factor VIII-related antigen. The spindle stromal cells are typically reactive to CD34 and vimentin antibodies.
Use CD34 staining
CD34 staining is seen in the perilobular stroma in the normal breast, in phyllodes tumor, and fibroadenoma. Phyllodes tumor has less CD34 staining than PASH, and malignant phyllodes disease has less than the benign variant. Authors have described CD34-positive fibroblast-like cells in the mesenchyme of tissues including the skin, gastrointestinal tract, cervix, and testes.
Like PASH, a variety of other CD34-positive lesions, such as dermatofibrosarcoma protuberans of the skin and intestinal fibroid polyps, arise at sites populated with normal CD34-positive fibroblast-like cells. As in stromal tumors of the breast, CD34 staining decreases with differentiation.13
Once you diagnose PASH, treat it as a benign lesion of the breast. Large and enlarging lesions generally prompt surgical excision with 1–2-cm margins.
FIGURE 3 Pathology suggests PASH
Microscopic examination revealed abundant fibrous stroma containing clefts lined by spindle cells giving them a classic pseudoangiomatous appearance (H & E stain).
FIGURE 4 CD34 reaction confirms disease
The cells lining stromal clefts were strongly positive for CD34 and vimentin, and negative for factor VIII, confirming PASH
The surgical management of PASH ranges from simple excision to mastectomy with appropriate long-term follow-up to evaluate for tumor recurrence.
There is less CD34 staining in a phyllodes tumor than PASH.
Recurrence can be problematic. Multiple, bilateral and/or recurrent lesions have required mastectomy in isolated cases. Surgical excision is curative for most lesions.
In the largest reported case series, 5 of 40 patients developed ipsilateral recurrent PASH following excision with a mean follow-up of 4½ years.14 In a second study, 2 of 9 patients developed recurrent PASH following excisional biopsy with a follow-up extending to 30 months.1
Treatment with tamoxifen was reported in one patient with recurrent biopsy-proven PASH with resolution of the lesion.15
MALPRACTICE MINUTE (P 7)
The court ruled for the defense
DILEMMA (P 26)
CASE QUIZ (P 35)
The authors have no competing interests to declare.
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