CASE REPORT

© 2001 Blackwell Science Inc., 1075-122X/01/$15.00/0The Breast Journal, Volume 7, Number 4, 2001 263–265

Pseudoangiomatous Stromal Hyperplasia: Presentation as a

Mass in the Female Nipple

Dan Iancu, MD and Lucien E. Nochomovitz, MD

Department of Pathology, Winthrop-University Hospital,Mineola, New York

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Abstract:

Pseudoangiomatous stromal hyperplasia (PASH)is a benign, localized fibroblastic and myofibroblastic over-growth that occurs almost exclusively in premenopausal womenas a painless, palpable intramammary mass. The lesion has apale, fibrous, and homogeneous cut surface, is typically well cir-cumscribed, and may have a diameter of 2.0–15 cm. Its ramify-ing slits lined by flattened myofibroblastic cells are apt to bemistaken for vascular spaces, leading to an erroneous diagno-

sis of angiosarcoma. The etiology of the condition is unknown,but a relationship to myofibroblastoma has been postulated.Hormonal factors, too, are thought to play a developmentalrole. The potential for PASH to create a palpable breast masshas been only quite recently advanced in the medical litera-ture, and it has evidently not been reported in the nipple.

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Key Words:

areola, breast, fibroma, nipple, PASH,pseudoangiomatous stromal hyperplasia

CASE REPORT

A 37-year-old nonpregnant woman (G2P2) presentedwith a painless nodule in the nipple-areola complex.There was no history of a prior breast disorder, but a700 g mesenteric desmoid had been removed in 1992.

The nipple skin showed no encrustation or ulceration,and there was no discharge. An excisional biopsy wasperformed in 1999 at Winthrop-University Hospital.

MATERIALS AND METHODS

The excised biopsy specimen was fixed in 10% buff-ered formalin. The margins were inked and the lesionwas serially cut into 5 mm slices that were submitted forprocessing into paraffin blocks for histologic examina-tion. Sections 4

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m thick were stained with hematoxylinand eosin. Immunohistochemical stains were performedon 5

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m, formalin-fixed, paraffin-embedded tissue sec-tions and on appropriate controls using the followingmonoclonal antisera: CK23 cocktail (Biomeda, FosterCity, CA), vimentin (Biogenex, San Remo, CA), desmin(1:25, Dako, Carpinteria, CA), S-100 protein (Dako),smooth muscle actin (Biogenex), CD34 (Biogenex), es-trogen receptor (1:50, Immunotech, Marseille, France),and progesterone receptor (Biogenex). Polyclonal anti-sera were deployed for factor VIII-related antigen (Dako)and S-100 protein (Dako).

RESULTS

Gross Findings

The specimen comprised a grossly normal skin ellipsecontiguous with a subcutaneous 1.3 cm nodule with apale, firm homogeneous cut surface.

Address correspondence and reprint requests to: L. E. Nochomovitz,MD, Department of Pathology, Winthrop-University Hospital, 222 StationPlaza North, Suite 618, Mineola, NY 11501.

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Histologic Findings

A circumscribed dermal nodule lay immediately deepto the basal layer of the epidermis. Low-power examina-tion showed a stromal proliferation of collagen bundlesarranged in a more or less circular pattern, vaguely rem-iniscent of a keloid, but without dense hyalinization(Fig. 1). The stroma was permeated by narrow anasto-mosing slits lined by elongated cells with mainly flat-tened, tapering nuclei, but some lining cells had plumper,more vesicular nuclei and inconspicuous nucleoli (Fig.2). There were no confluent cellular aggregates. The le-sion had no ducts and did not resemble a fibroadenoma.Thin-walled, evenly spaced blood vessels were presentthroughout. The epidermis was normal.

Immunohistochemical Findings

The cells lining the stromal clefts showed strong ex-pression of CD34, vimentin, and progesterone receptor.There was weak expression of S-100 protein. A cytokera-tin cocktail (CD23), smooth muscle actin, desmin, factorVIII-related antigen, and estrogen receptor were negative.

DISCUSSION

PASH, a benign fibroblastic and myofibroblastic in-tramammary lesion, is a comparatively recent diagnosticentity (1,2). The main histologic finding is a dense col-lagenous stroma permeated by anastomosing slitlikespaces that are either lined by bland spindled myofibro-blasts or have no lining at all. Rosen’s (1) account statesthat mitoses are absent, but that nuclear hyperchroma-sia may be present. He illustrates examples in which my-

ofibroblasts aggregate into fascicles, suggesting that PASHand myofibroblastoma have a common histogenesis. Sup-porting that interpretation are foci of PASH in two of ninecases of myofibroblastoma reported by Hamele-Bena etal. (3). CD34, a myofibroblastic marker, is also expressedby the cells lining the spaces of PASH. Almost exclusiveto premenopausal women, PASH is thought to be hor-monally induced and can produce diffuse breast enlarge-ment during pregnancy (1,4,5). Although often forming aclinically palpable lump, the condition may be an inciden-tal microscopic finding associated with benign or malig-nant breast conditions. Its ramifying spaces must not beinterpreted as vascular, that is, leading to a mistaken diag-nosis of angiosarcoma (6,7). In addition to CD34, the lin-ing cells are immunohistochemically strongly reactive forvimentin, and may express progesterone receptor (1,8). Es-trogen receptor expression is absent or weak (8,9); cyto-keratin and factor VIII-related antigen are absent (1).

Palpable nipple-areola masses are usually caused byan epithelial growth, such as a lactiferous ductal papil-loma, florid papillomatosis (sclerosing and nonscleros-ing), subareolar sclerosing ductal hyperplasia, syringo-matous adenoma, invasive carcinoma, or Paget’s disease.Rare examples of nipple-areola fibromas, several of whichwere pedunculated, are on record, but the articles provideeither no photomicrographs or images without stromaldetails (10–14). Smooth muscle neoplasms, neural le-sions, hemangiomas, and lipomas may also occur inthis region (13,15–18). The lesion presented in this re-port is histologically identical to PASH that occurs inthe mammary stroma. Whether this nipple-related mass

Figure 1. Circumscribed relatively acellular nodule occupyingdermis of nipple (magnification �40).

Figure 2. Dense stroma intersected by vacant cells (magnification�200).

Nipple-Areola Complex with PASH

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developed from subjacent breast tissue or arose fromthe dermis cannot be stated. We do not believe that it isa hypertrophic scar or keloid because it lacks a denselyhyalinized, eosinophilic keloidal texture and there is noindication of previous injury to the area. The shape of

the mass, the absence of alternating cellular and less cellulartracts, and the occurrence of diffuse slits removes fibromato-sis from consideration. Nodular fasciitis, even in its healedphase, would not possess the distinctive architecture ofPASH. The lesion does not resemble a fibrous histiocytomaand lacks the cellularity and infiltrative attributes of der-matofibrosarcoma protuberans. That PASH should form anipple-related mass is not surprising, but ours appears to bethe only example presently on record, broadening the differ-ential diagnosis of mesenchymal lesions involving the nip-ple-areola complex.

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