Bilateral Presentation of Fibroadenoma With Digital Fibroma-Like Inclusions in the Male Breast
By Shin, Sandra J Rosen, Paul Peter
* Fibroepithelial lesions are uncommon in the male breast. Most published reports describe phyllodes tumors. Fibroadenomas are very common in female breasts, but are exceedingly rare in the male breast. Gynecomastia and/or lobular differentiation have been known to coexist in both types of fibroepithelial lesions in men. We report an exceptional case of recurrent, bilateral fibroadenomas in a man under treatment for prostatic carcinoma. Intracytoplasmic inclusion bodies in stromal cells identical to those seen in infantile digital fibromatosis were identified in one fibroadenoma. To the best of our knowledge, this is the first reported case of bilaterally occurring fibroadenomas in the male breast, one of which also contained digital fibroma- like inclusions, a second unreported phenomenon. (Arch Pathol Lab Med. 2007;131:1126-1129)
Fibroepithelial lesions are uncommon in the male breast. Gynecomastia and/or lobular differentiation have been known to coexist with male fibroadenomas and phyllodes tumors. We report an exceptional case of recurrent fibroadenomas occurring bilaterally at one point in time in a man undergoing treatment with Lupron for prostatic carcinoma. In addition, intracytoplasmic inclusion bodies in stromal cells identical to those seen in infantile digital fibromatosis were identified in one fibroadenoma.
REPORT OF A CASE
A 66-year-old man was diagnosed with prostatic cancer in November 1992. He subsequently underwent a prostatectomy that was followed by radiation therapy. The precise grade of the tumor and stage of disease are not known. The patient began Lupron therapy in 1993, a regimen he continues to the present day. Seven years after starting Lupron therapy, he presented with a left breast mass that was confirmed by mammography in August 2000. A fine-needle aspiration and subsequent surgical biopsy revealed a fibroadenoma. In 2004, bilateral breast masses were removed by surgical excision; both masses were fibroadenomas. In 2006, the patient underwent bilateral breast biopsies that revealed a fibroadenoma and gynecomastia in the left and right breast, respectively. Currently, there is no evidence of prostatic or breast disease. His current medications are Norvasc, metaprolol (Lopressor), Aldactazide, and Lupron.
PATHOLOGIC FINDINGS
Hematoxylin-eosin-stained slides of bilateral breast biopsies from 2004 and 2006 were available for review. The 2004 specimens revealed grossly identifiable masses measuring 4.5 and 3.5 cm, respectively. Microscopically, the left breast mass consisted of a fibroadenoma with a circumscribed, knobby contour (Figure 1). The epithelial component showed florid duct hyperplasia (Figure 1, inset) and focal secretory lobular hyperplasia. The stromal component was mildly cellular but devoid of mitoses. The overall appearance was reminiscent of a juvenile fibroadenoma. Scattered eosinophilic, acellular bodies were identified within the stroma (Figure 2). Immunohistochemical stains showed these bodies to be strongly positive for smooth muscle actin (Figure 2, inset) and musclespecific actin. Trichrome stain showed the bodies to stain red. The morphologic appearance in conjunction with the immunohistochemical results were consistent with digital fibroma- like inclusions. The surrounding mammary tissue was scant and showed no gynecomastia or lobular differentiation. The right breast mass consisted of a complex fibroadenoma with florid and focally atypical duct hyperplasia and adenosis (Figure 3).
A left excisional biopsy was performed in 2006 for a clinically apparent mass that was described by the surgeon as being the size of a grapefruit. On gross examination, a well-circumscribed, tan mass measuring 3.0 cm in greatest dimension was identified. Histologically, the mass was a complex fibroadenoma with cellular stroma and florid, focally atypical duct hyperplasia. Like the prior fibroadenoma in the left breast, it had features of juvenile fibroadenoma with well-defined tumor borders (Figure 4). The surrounding mammary parenchyma showed fibrous gynecomastia with minimal duct hyperplasia. The right excisional biopsy specimen consisted of fibroadipose mammary tissue with cystic areas. Microscopically, gynecomastia with focal lobular differentiation was seen (Figure 5).
COMMENT
The fibroepithelial lesions described in this report were classified as fibroadenomas because of the roughly equal proportions of the epithelial (glandular) and stromal components seen in pericanalicular examples. Although mildly cellular in the fibroadenomas found in the left breast, the stroma was characteristically homogeneous, contrary to what is seen in phyllodes tumors. Other hallmark features of benign phyllodes tumors such as stromal mitoses and so-called popcorn stromal nuclei were also absent.1 The sharply defined borders of these lesions were also supportive of the diagnosis of fibroadenoma. Fibroepithelial lesions uncommonly arise in male patients, and most represent phyllodes tumors. Although very common in female patients, fibroadenomas are exceedingly rare in the male breast. In fact, some question their existence. For instance, Holleb et al2 stated that no true fibroadenoma is formed in men; others have stated that the lesions reported to be fibroadenomas by some authors are poorly documented or appear to be nodular foci of gynecomastia.3 Nonetheless, fibroadenomas in the male breast have been documented sporadically in the medical literature as single case reports and in a rare series of 4 patients.4-12 Less convincing reports include a 15-year- old adolescent who presented with a fibroepithelial lesion and concurrent gynecomastia, in which the reported presence of ”occasional mitotic figures” in the stroma raises suspicion that this represents a phyllodes tumor and not a fibroadenoma.8 In our patient, the phenomenon of ”recurrent” fibroadenomas in the left breast would suggest that this tumor alternatively represents a locally recurring benign phyllodes. However, as detailed earlier, there were no histologic findings to suggest this diagnosis. Additionally, scar tissue or changes suggestive of prior biopsy were not appreciated in adjacent mammary parenchyma in the left excisional specimen of 2006.
Another striking feature in our case was the presence of digital fibroma-like inclusions in one fibroadenoma. These intracytoplasmic inclusions, which are a characteristic feature of digital fibrous proliferations of infancy, have also been described in other locations as well as in adulthood. They appear as round, hyaline bodies and are composed of tightly packed actin filaments. They are exclusively located in the cytoplasm of actin-rich cells, including myofibroblasts and smooth muscle cells.13 The commonly held belief is that these inclusions are the product of disturbed metabolism of proliferating myofibroblasts, suggesting a defective regulation of cellular filaments of actin.13,14 Bittesini and colleagues15 were the first to describe these bodies in a mammary fibroepithelial tumor of a 34-year-old woman. Since then, several additional cases occurring in fibroepithelial tumors, 2 of which were in benign phyllodes tumors, were described in female patients. 13,16-18 Two cases identified in mammary fibromatosis were also described.14 To the best of our knowledge, this report describes the first male patient with digital fi- broma-like inclusions in a mammary fibroepithelial tumor (fibroadenoma).
Our patient had bilateral presentation of fibroadenomas, occurring synchronously at one point in time. Multiple fi- broadenomas occur in about 15% of female patients, with equal proportions detected synchronously and metachronously in the same or opposite breast.1 In contrast, multiple or bilateral fibroadenomas have not been described in the male breast until now.
It has been speculated that hormonal imbalances, some due to medication use, cause proliferative changes in the male breast, such as gynecomastia, lobular differentiation, and fibroepithelial lesions. Although coexisting gynecomastia appears to be a consistent finding in male patients with fibroadenomas, the presence of lobular differentiation with or without associated gynecomastia is less common. Lobular differentiation was found in 2 reports of male to female transsexuals who were undergoing demasculinization and feminization via hormonal (ethinyloestradiol and ciproterone acetate) and surgical treatment. 6,19 It is known that the slight increase of plasma estrogen to androgen ratio observed in idiopathic prepubertal or senile gynecomastia usually will not induce acinar and lobular formation in the male breast,4,5 but full acini and lobular formation will occur in transsexuals in whom progestagenic antiandrogens are combined with feminizing estrogen therapy.6,7 Ciproterone acetate is such a progestagenic with a strong androgen receptor-blocking effect. 6,7
Lobular differentiation was also found in 4 men with fibroadenomas in the series reported by Ansah-Boateng and Tavassoli10; all patients also had concurrent gynecomastia. One patient was taking estrogen and another was taking methyldopa chlordiazepoxide. Two patients were not taking any medications at the time of diagnosis. Nielsen11 reported a case of bilateral fibroadenomatoid hyperplasia in a 69-year-old man who was taking digoxin, furosemide, and spironolactone. Both breasts had become diffusely enlarged with multiple fibroadenomatoid nodules during the last 4 years prior to presentation, when spironolactone was added; hence, it was surmised that this was the causative agent. Lastly, a 19-year-old woman with complete androgen insensitivity syndrome who was taking exogenous estrogen was reported to develop a juvenile fibroadenoma.12 The presence/absence of lobular differentiation was not mentioned. Since gynecomastia is often coexistent in reported cases of fibroadenomas, it is diffi- cult to discern whether exogenous drugs/medications leading to hormonal imbalances are causative of one or both lesions. To the best of our knowledge, there are no reports of fibroadenomas in male patients who did not have concurrent gynecomastia. The use of causative medications was not addressed in one case of a fibroadenoma in a 40-year-old man.20 It is likely that in our patient, the long-standing use of Lupron, a luteinizing hormone-releasing hormone agonist that is used to decrease testosterone levels for the treatment of advanced prostate cancer, contributed to the development of gynecomastia, lobular differentiation, and/or fibroadenomas. Breast enlargement is a known side effect of this medication. In summary, this is an exceptional case of bilateral fi- broadenomas that developed in a man undergoing treatment for prostatic carcinoma with Lupron. One fibroadenoma contained digital fibroma-like inclusion bodies in the stromal cells. To the best of our knowledge, this is the first reported case of bilaterally occurring fibroadenomas in the male breast, one of which also contained digital fibroma-like inclusions, a second unreported phenomenon.
The authors thank Daniel Rubin, MD, and Steven Kanter, MD, for contributing pathologic and clinical information.
References
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Sandra J. Shin, MD; Paul Peter Rosen, MD
Accepted for publication January 9, 2007.
From the New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY.
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: Sandra J. Shin, MD, Department of Pathology and Laboratory Medicine-Starr 1009, New York Presbyterian Hospital- Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021 (e-mail: sjshin@med.cornell.edu).
Copyright College of American Pathologists Jul 2007
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