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Right Breast Mass With Atypical Features.

The patient was a 33-year-old woman with a 10-year history of controlled type 2 diabetes mellitus. She presented with a slow-growing mass in her right breast, which was detected during self-examination 6 months before presentation. Mammography and ultrasonography (Figure 1) revealed a 2.2-cm solid mass in the right upper quadrant. A core biopsy showed fibroadipose tissue with stromal calcification and no evidence of malignancy. The mass was then excised at the patient's request.

[Figure 1 ILLUSTRATION OMITTED]

Gross examination of the specimen revealed a well-circumscribed, firm nodule measuring 2.4 x 2.0 x 1.5 cm. The cut surface was firm, tan-gray, and had a whorled appearance. Microscopically, the tumor consisted of an expanded fibrous stroma with variable cellularity and compression of the evenly distributed glandular structures into slitlike spaces by the stromal connective tissue (Figure 2). Also present within the stroma were numerous atypical giant cells, many of which had a bizarre appearance (Figure 3). The giant cells were scattered randomly throughout the fibrous stroma, measured 50 to 75 [micro]m, and some were multinucleated. The nuclei were multilobed and hyperchromatic. No mitotic figures were identified. Nucleoli were barely discernible.

[Figures 2-3 ILLUSTRATION OMITTED]

Immunoperoxidase stains using antibodies against cytokeratin, desmin, smooth muscle actin, estrogen receptor, progesterone receptor, and CD68 were negative in the stromal giant cells; however, these cells stained strongly positive with vimentin immunostain (Figure 4). Staining for [Alpha]-smooth muscle actin was focally positive in both the giant cells and the myofibroblastic stromal cells.

[Figure 4 ILLUSTRATION OMITTED]

What is your diagnosis?

Pathologic Diagnosis: Fibroadenoma With Atypical Stromal Giant Cells

This case demonstrates the presence of numerous multinucleated stromal giant cells (MSGCs) that were confined to the stroma of an otherwise typical mammary fibroadenoma.

Multinucleated stromal giant cells similar to these occurring in breast have been described in other sites, including the vagina,[1] uterine cervix,[2] nasal polyps,[3] urinary bladder epithelium,[4] and in lesions of the oral cavity.[5] A number of benign neoplasms also have been described to harbor theses bizarre giant cells. These include pleomorphic lipoma, pleomorphic leiomyoma,[6] ancient schwannoma,[7] pleomorphic fibroma,[8] and variants of dermatofibroma with atypical cells, known as dermatofibroma with monster cells.[9] All these reports caution against the over-interpretation of these bizarre cells as evidence of malignancy.

Immunohistochemical studies of the MSGCs in fibroadenoma show consistent positivity for vimentin and focal positive staining reaction with histiocytic markers ([[Alpha].sub.1]-antitrypsin, [[Alpha].sub.1]-antichymotrypsin, HAM-56, CD34, and CD68). As demonstrated in this case and also in agreement with previous reports, they consistently stain negatively with immunostains for estrogen and progesterone receptors, cytokeratins (AE 1/3 and CAM 5.2), S100 protein, and desmin.

The histogenesis of MSGCs remains very unclear and controversial. The immunohistochemical profile suggests that these cells could be derived from a primitive mesenchymal cell (consistent vimentin positivity) or a myofibroblastic origin (positive staining with vimentin and [Alpha]-smooth muscle actin with negative staining with desmin). However, in the past, numerous other cells have been proposed as the origin of MSGCs. Nielson and Ladefoged[10] favored a myoepithelial origin, hypothesizing that the myoepithelial cells enlarge and merge together to form a syncytium. However, later studies did not support this hypothesis. Berean et al[11] proposed a fibroblastic origin for MSGCs, based on electron microscopic findings of anastomosing rough endoplasmic reticulum in the cells and mature collagen in the surrounding stroma, as well as the absence of filaments, micropinocytic inclusions, and basal lamina. These authors reported that the MSGCs did not stain for vimentin and actin antibodies. Powell et al[12] favored a fibrohistiocytic origin of MSGCs, arguing that the stromal cells formed a morphologic continuum from small spindle cells, to enlarged mononuclear cells with nuclear lobation, to fully formed MSGCs and consistent vimentin positivity and histiocytic markers. Powell et al also proposed a role of endogenous or exogenous hormones in the development of MSGCs, but the constant absence of expression of estrogen and progesterone receptors does not support that notion.

The presence of these pleomorphic, bizarre, multinucleated large cells in small specimens, such as fine-needle aspiration or core biopsy specimens, may be misinterpreted as a sarcomatous malignant process. Awareness of the existence of these benign but bizarre-looking pleomorphic giant cells may help prevent such diagnostic pitfalls.

References

[1.] Elliot GB, Elliot JD. Superficial stromal reactions of lower genital tract. Arch Pathol. 1973;95:100-101.

[2.] Clement PB. Multinucleated stromal giant cells of the uterine cervix. Arch Pathol Lab Med. 1985;109:200-202.

[3.] Compango J, Hyams VJ, Lepose MI. Nasal polyposis with stromal atypia. Arch Pathol lab Med. 1976;100:224-226.

[4.] Young RH. Fibroepithelial polyp of the bladder with atypical stromal cells. Arch Pathol Lab Med. 1986;100:241-242.

[5.] Houston GD. The giant cell fibroma: a review of 464 cases. Oral Med Oral Pathol. 1982;53:582-587.

[6.] Schmookler BM, Enzinger FM. Pleomorphic lipoma: a benign tumor simulating liposarcoma: a clinicopathologic analysis of 48 cases. Cancer. 1981;47: 126-133.

[7.] Dahl I. Ancient neurilemmoma (schwannoma) Acta. Pathol Microbiol Scand [A]. 1977;85:812-818.

[8.] Kamino H, Lee JY, Berke A. Pleomorphic fibroma of the skin: a benign neoplasm with cytologic atypia. A clinicopathologic study of eight cases. Am J Surg Pathol. 1989;13:107.

[9.] Tamada S, Ackerman AB. Dermatofibroma with monster cells. Am J Dermatopathol. 1987;95:380-387.

[10.] Nielson BB, Ladefoged C. Fibroadenoma of female breast with multinucleated giant cells. Pathol Res Pract. 1985;180:721-724.

[11.] Berean K, Tron VA, Churg A, Clement PB. Mammary fibroadenoma with multinucleated stromal giant cells. Am J Surg Pathol. 1986;10:823-827.

[12.] Powell CM, Cranor ML, Rosen PP. Multinucleated stromal giant cells in mammary fibroepithelial neoplasm. Arch Pathol Lab Med. 1994;118:912-916.

Accepted for publication December 2, 1999.

From the Department of Pathology, University of Texas Medical Branch, Galveston, Tex.

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Author:Sovani, Vinayak K.; Adegboyega, Patrick A.
Publication:Archives of Pathology & Laboratory Medicine
Geographic Code:1USA
Date:Nov 1, 2000
Words:980
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