Male Breast Lesions Male Breast Lesions
Contents
13.1 Gynecomastia . . . 366
13.1.1 Definition . . . 366
13.1.2 Macroscopy . . . 366
13.1.3 Microscopic Features . . . 366
13.1.4 Additional Comments . . . 366
13.1.5 Further Reading . . . 366
13.2 Papilloma . . . 367
13.3 Primary Male Breast Carcinoma . . . 367
13.4 Further Reading . . . 367
13
13.1 Gynecomastia
13.1.1 Definition
A non-neoplastic, potentially reversible enlargement of the male breast with proliferation of ductal epithelial and mesenchymal components. The lesion usually presents as a bilateral, diffuse enlargement of the breasts.
13.1.2 Macroscopy
When diffuse, gynecomastia appears ill defined. In the discrete form, the hyperplastic tissue is well circumscribed. Rubbery or firm consistency and a greyish-white cut surface are typical.
13.1.3 Microscopic Features (Figs. 89 and 90a)
●
Proliferation of ductal epithelial cells and mesenchymal com- ponents resembling fibroadenomatous hyperplasia or “peri- canalicular” type of fibroadenoma of the female breast.
●
The florid phase is characterized by prominent ductal hyper- plasia, usually with a tufting pattern. Periductal stroma is of- ten cellular; it can also be edematous.
●
The fibrous or inactive phase occurs in late stages, showing mild epithelial proliferation. But the stroma is more collage- nous, with less edema and vascularity.
●
The intermediate phase has both florid and fibrous changes.
●
The proliferating epithelial cells in the florid phase may show enlarged hyperchromatic nuclei with an increased nuclear- cytoplasmic ratio. Numerous mitotic figures may be present.
Caution
●
The cytologic features and growth pattern of intraepithelial proliferation may appear atypical, particularly in the florid phase. The micropapillary-like proliferation (tufting pattern) can be pronounced in such cases and should not be mistaken for DIN (DCIS).
●
The cell population of intraepithelial proliferation in the florid phase is always heterogeneous, composed of epithelial and modified myoepithelial cells. If one is in doubt, immunostains for CK5/6 or CK34BE12 can be very helpful; these are always positive in ductal hyperplasia.
●
On rare occasions, DIN (DCIS) may occur in the background of gynecomastia. The neoplastic cells of DIN lack a modified myoepithelial cell component and, therefore, are negative for CK5/6 in the vast majority of DIN (DCIS) cases associated with gynecomastia.
●
Some cases of gynecomastia may be associated with promi- nent pseudoangiomatous stromal hyperplasia (PASH). This should not be mistaken for vascular neoplasia (angiosarco- ma).
●
In gynecomastia induced by antiandrogen therapy, there may be strong focal prostate-specific antigen (PSA) immunoreac- tivity in normal or hyperplastic ductal epithelium.This finding should not be mistaken for metastasis from a prostatic ade- nocarcinoma.
13.1.4 Additional Comments
Gynecomastia is generally a transient disease in the adolescent male. In patients older than 25 years, symptomatic gynecomastia is often a manifestation of underlying disease (hepatic disease, renal disease, hyperthyroidism, etc.), or it reflects a hormonal imbalance (such as gonadal dysfunction, Klinefelter’s syndrome, and hyperprolactinemia) or the use of a variety of drugs (includ- ing spironolactone, digitalis, and cimetidine) [1, 3, 7, 9, 10].
Gynecomastia is a significant problem in men undergoing hor- monal therapy for prostate cancer. It requires prompt recogni- tion, evaluation, and management [3, 10]. Rarely, unilateral gynecomastia can occur.
13.1.5 Further Reading
1. Al-qattan M, Hassanian J, Mahmoud S, et al. On the neglected entity of unilateral gynecomastia. Ann Plast Surg 2005;55:255–257.
2. Bannayan GA, Hajdu SI: Gynecomastia: clinicopathologic study of 351 cases. Am J Clin Pathol 1972;57:431–437.
3. Di Lorenzo G, Autorino R, Perdona S, De Placido S. Management of gynecomastia in patients with prostate cancer: a systematic review.
Lancet Oncol 2005;6:972–979.
4. Nicolis GL, Modlinger RS, Gabrilone JL. A study of the histopathol- ogy of human gynecomastia. J Clin Endocrinol 1971;32:173–178.
5. Pinedo F, Vargas J, DeAugustin P, et al. Epithelial atypia in gyneco- mastia induced by chemotherapeutic drugs. A possible pitfall in fine needle aspiration biopsy. Acta Cytol 1991;35:229–233.
6. Schwartz CH, Wilens SL. The formation of acinar tissue in gyneco- mastia. Am J Pathol 1963;43:797–807.
7. Sirtori C, Veronesi U. Gynecomastia. A review of 218 cases. Cancer 1957;10:645–654.
8. Stepanas AV, Samaan NA, Schultz PN, et al. Endocrine studies in tes- ticular tumor patients with and without gynecomastia: a report of 45 cases. Cancer 1978;41:112–118.
9. Wilson JD. Gynecomastia. A continuing diagnostic dilemma. N Engl J Med 1991;324:334–335.
10. Wise GL, Roorda AK, Kalter R. Male breast disease. J Am Coll Surg
2005;200:255–269.
13.2 Papilloma
The macroscopic and microscopic features are the same as those of papilloma in females.
Caution
●
Because of the high proportion of papillary lesions among carcinomas of the male breast, all male papillary tumors should be carefully evaluated.
13.3 Primary Male Breast Carcinoma (Fig. 90b)
Papillary carcinomas, often with a prominent intracystic compo- nent, are more common among men than women. Most papil- lary carcinomas in men are noninvasive and intracystic (intra- cystic papillary carcinomas) [14].
Male breast carcinoma represents only 1% of all mammary cancers. In Egypt, the incidence of male breast cancer is 5%
that of the female population; this high percentage is related to hyperestrogenism secondary to bilharzial disease [2, 3, 11, 15].
The varieties of carcinoma that occur in the male breast are morphologically indistinguishable from their female counter- parts. Invasive lobular carcinoma is extremely rare in men, even in those exposed to endogenous or exogenous hormonal stimu- lation.
Men develop breast carcinoma at an older age than women.
Skin ulceration is more common in men, and male breast carci- nomas have a slightly worse prognosis than carcinomas in women [1].
Occasionally, the distinction between a primary carcinoma of the breast and metastatic prostatic carcinoma may be difficult, particularly when ductal intraepithelial neoplasia (DIN; ductal carcinoma in situ [DCIS]) is lacking. The immunohistochemical demonstration of both PSA and prostatic acid phosphatase (PAP) is almost diagnostic of metastatic prostatic carcinoma. It is, however, important to note that in gynecomastia induced by antiandrogen therapy, immunoreaction for PSA in normal or hyperplastic duct epithelium can be positive, whereas PAP im- munoreactivity is negative [12, 16, 27].
13.4 Further Reading
1. Adami HO, Holmberg L, Malker B, et al. Long-term survival in 406 males with breast cancer. Br J Cancer 1985;52:99–103.
2. Anderson WF, Devesa SS. In situ male breast carcinoma in the Sur- veillance, Epidemiology, and End Results database of the National Cancer Institute. Cancer 2005;104:1733–1741.
3. Borgen P, Senie RT, McKinnon WMP, Rosen PP. Carcinoma of the male breast. Analysis of prognosis compared with matched female patients. Ann Surg Oncol 1997;4:385–388.
4. Bruce DM, Heys SD, Payne S, et al. Male breast cancer: clinicopatho- logical features, immunohistochemical characteristics and progno- sis. Eur J Surg Oncol 1996;22:42–46.
5. Campagnaro EL, Woodside KJ, Xiao SY, et al. Cystosarcoma phyl- lodes (phyllodes tumor) of the male breast. Surgery 2003;133:
689–691.
6. Camus MG, Joshi MG, Macharem G, et al. Ductal carcinoma in situ of the male breast. Cancer 1994;74:1289–1293.
7. Ciatto S, Iossa A, Bonardi R, et al. Male breast carcinoma: review of a multicenter series of 150 cases. Tumori 1990;76:555–558.
8. Cunha F, Andre S, Soares J. Morphology of male breast carcinoma in the evaluation of prognosis. Pathol Res Pract 1990;186:745–750.
9. Donegan WL, Redlich PN, Lang J, et al. Carcinoma of the breast in males: a multi-institutional survey. Cancer 1998:83:498–509.
10. Gennari R, Curigliano G, Jereczek-Fossa BA, et al. Male breast can- cer: a special therapeutic problem. Anything new? (review) Int J Oncol 2004;24:663–670.
11. Giordano SH, Cohen DS, Buzdar AU, et al. Breast carcinoma in men:
a population-based study. Cancer 2004;101:51–57.
12. Green LK, Klima M. The use of immunohistochemistry in metastat- ic prostatic adenocarcinoma to the breast. Hum Pathol 1991;22:242–
246.
13. Guinee VF, Olsson H, Moller T, et al. The prognosis of breast cancer in males: a report of 335 cases. Cancer 1993;71:154–161.
14. Hittmair AP, Lininger RA, Tavassoli FA: Spectrum of ductal carcino- ma in situ (DCIS) in the male breast: morphologic study of 94 cases of pure DCIS and 30 cases of DCIS associated with invasive carcino- ma – a preliminary report. Cancer 1998;83:2283–2291.
15. Joshi Mg, Lee AKC, Loda M, et al. Male breast carcinoma: An evalu- ation of prognostic factors contributing to poorer outcome. Cancer 1996;77:490–498.
16. Kidwai N, Gong Y, Sun Y, et al. Expression of androgen receptor and prostate-specific antigen in male breast carcinoma. Breast Cancer Res 2004;6:R18–23.
17. Lobaccarro JM, Lumbroso S, Belon C, et al. Androgen receptor gene mutation in male breast cancer. Hum Mol Genet 1993;2:1799–1802.
18. Maly B, Maly A, Pappo I, et al. Pleomorphic variant of invasive lobu- lar carcinoma of the male breast. Virchows Arch 2005;446:344–345.
19. Michaeles BM, Nunn CR, Roses DF. Lobular carcinoma of the male breast. Surgery 1994;115:402–405.
20. Niveditha SR, Bajaj P, Nangia A. Secretory carcinoma of the male breast. J Clin Pathol 2004;57:894.
21. Norris HJ, Taylor HB. Carcinoma of the male breast. Cancer 1969;23:
1428–1435.
22. Olsson H. Estrogen receptor content in malignant breast tumors in men – a review. J Mammary Gland Biol Neoplasia 2000;5:283–287.
23. Roth JA, Discafani C, O’Malley M. Secretory breast carcinoma in a man. Am J Surg Pathol 1988;12:150–154.
24. Sneige N, Holder PD, Katz RL, et al. Fine needle aspiration cytology of the male breast in a cancer center. Diagn Cytopathol 1993;9:691–
697.
25. Tavassoli FA, Norris HJ. Secretory carcinoma of the breast. Cancer 1980;45:2404–2413.
26. Westenend PJ. Core needle biopsy in male breast lesions. J Clin Pathol 2003;56:863–865.
27. Willshir PC, Leach ICH, Ellis IO, et al. Male breast cancer: patholog- ical and immunohistochemical features. Anticancer Res 1997;173:
2335–2338.
Chapter 13 367
Male Breast Lesions
13
Fig. 89: Gynecomastia.
Case history: A 36-year-old man presented with bi- lateral diffuse enlargement of his breasts.There was no palpable mass.
Figs. 89.1 and 892: Excisional biopsy showing pro- liferation of ductal epithelial cells and periglandular mesenchymal cells resembling fibroadenomatous hyperplasia or pericanalicular growth pattern of fibroadenoma.
Figs. 89.3 and 89.4: The florid phase of prolifera- tion showing ductal hyperplasia with tufting growth pattern.
Fig. 89.5: Ductal hyperplasia with intraluminal tufts mimicking micropapillary growth pattern of DIN (DCIS). In contrast to DIN (DCIS), however, the cell population of proliferating cells in gynecomas- tia is heterogeneous.
Figs. 89.6, 89.7, and 89.8: Immunohistochemistry for CK5/6 reveals in several ducts a heterogeneous positive reaction, which is typical for usual ductal hyperplasia.
Fig. 89: Final remarks
●
The cytologic features and growth pattern of
intraductal proliferation in gynecomastia may
appear to be atypical. The tufting growth pat-
tern of gynecomastia should not be confused
with micropapillary DIN (DCIS). In a difficult
case of gynecomastia, immunostaining for
high molecular weight cytokeratin (such as
CK5/6) can be helpful for identifying the be-
nign nature of proliferating luminal cells.
Chapter 13 369
Male Breast Lesions
13
Fig. 90a: Gynecomastia associated with pseudo- angiomatous stromal hyperplasia (PASH).
Case history: A 70-year-old man presented with a unilateral right breast tumor. He had a history of prostate cancer and antiandrogen hormonal treat- ment. The breast tumor was firm and clinically sus- picious for malignancy (breast cancer? metastatic prostate cancer?).
Figs. 90a.1 and 90a.2: Excisional biopsy of the breast shows gynecomastia with periductal stromal proliferation (pericanalicular growth pattern). Some ducts reveal intraluminal proliferation with typical features of intraductal hyperplasia.
Figs. 90a.3 and 90a.4: In addition, several sections show periductal empty spaces or vascular-like channels.
Figs. 90a.5 and 90a.6: The anastomosing spaces are lined by spindle cells closely mimicking endo- thelial cells.The immunohistochemistry of the spin- dle cells was negative for endothelial markers (CD31, CD34; not shown). Note significant stromal fibrosis associated with some edematous/myxoid changes.
Fig. 90a: Final remarks
●
This is a typical example of pseudoangioma-
tous stromal hyperplasia (PASH). which is a
benign proliferation of fibroblasts and myo-
fibroblasts. The clinical impression of malig-
nancy in this case was due to gynecomastia
associated with PASH.
Chapter 13 371
Male Breast Lesions
13
Fig. 90b: Male breast carcinoma
(infiltrating ductal carcinoma) associated with intraductal papillary carcinoma.
Case history: A 23-year-old man with a history of bloody nipple discharge presented with a firm tu- mor close to the nipple of his left breast. There was a positive family history of ovarian and breast carci- noma (mother). Excisional biopsy of the tumor was performed.
Fig. 90b.1: Low magnification shows an intraduc- tal papillary tumor. The tumor is within 1.5 mm of the inked margin.
Figs. 90b.2 and 90b.3: Several areas of the papil- lary tumor show a monotonous cell population of mildly atypical cells with cribriform growth pattern.
Fig. 90b.4: In addition to the intraductal papillary carcinoma, there is a focus of infiltrating carcinoma.
Figs. 90b.5 and 90b.6: Higher magnification re- veals invasive ductal carcinoma that is character- ized by solid and cordlike epithelial clusters with haphazard arrangement. The tumor cells show mild to moderate nuclear atypia.
Fig. 90b.7: The neoplastic cells of intraductal papil- lary carcinoma are positive for estrogen receptors.
Fig. 90b.8: Infiltrating carcinoma showing positive reaction for estrogen receptors.
Fig. 90b: Final remarks
●
This is a remarkable case of breast carcinoma occurring in a young man. While the invasive component of the tumor is 3 mm in diameter (pT1a), the lesion is predominantly a low- grade intraductal papillary carcinoma (low- grade papillary DIN).
●
Note that intraductal papillary carcinoma is
the most common type or growth pattern of
male breast cancer.
Chapter 13 373
Male Breast Lesions
