Gynecomastia: differential diagnosis for male breast cancer
Breast cancer in males in uncommon, accounting for less than 0.8 % of all breast cancers. However, there is some evidence to suggest that incidence rates are on the rise. Of course men do not develop milk-producing breasts, but they still have a small amount of breast tissue, and anyone who has breast tissue is at a small risk for breast cancer development. Men who are ultimately diagnosed with breast cancer tend to have tumors of a more advanced stage than women. This is likely because symptoms are either ignored, or assumed to be a benign condition like gynecomastia.
What is gynecomastia?
Essentially, gynecomastia is abnormally large breast development in males. More specifically it may be defined as an abnormal increase in the ductal and stromal elements of the male breast. Men with gynecomastia may have a disk or button-like growth under the nipple and areola that can be felt, and is sometimes also visible.The development of gynecomastia will be unique for each patient, depending on the patterns and sizes of the glandular tissues involved, and the extent to which these tissues are intermixed with fibrous and adipose tissue.
puffy nipples is a common symptom
Gynecomastia can be bilateral or unilateral, and symmetrical or asymmetrical. But the most common and recognizeable feature of early gynecomastia is a 'concentric' distribution of new fibroglandular growth located directly under the nipple. A wide range of physically apparent 'aesthetic' abnormalities may arise. "Puffy nipples" is probably the most common manifestation, the result of accumulations of glandular tissue under and confined to the areola. Sometimes the abnormal growth extends just outside the areola, giving a characteristic 'dome-shaped' appearance.
pure glandular gynecomatia common with bodybuilders
The 'pure glandular' form of gynecomastia is common with lean men and bodybuilders, and is sometimes brought on by the use of anabolic steroids. Since the level of body fat (adipose tissue) is so low, the abnormal growth is purely of glandular tissues and not mixed with fat tissues. With 'pure glandular' gynecomastia, the only possible treatment is surgical excision of the abnormal breast tissue, which leaves the undesired cosmetic result of a 'flat nipple-areola complex'.
Phases of gynecomastia
Normally, the male breast has only major mammory ducts which almost never branch. True 'acinar lobules' ( berry-like glands ) are usually absent. But in early gynecomastia, sometimes called the 'florid' phase, the breast ducts experience proliferative growth, which also causes a richly vascular ( blood delivery ) network of connective tissues to develop around them. As the condition progresses, the breast ducts involved dilate and lengthen, and increase in the number of branches. Epithelial hyperplasia is also typical at this stage.
late 'fibrous' phase gynecomatia
In the late phase, sometimes called the 'fibrous' phase, the breast duct structures become less defined as fibrosis and hyalinization gradually begin to take over. ('Hyalinization' means that cell tissues gradually become glassy and 'transparent') Collagen surrounds the breast ducts and becomes more and more densely packed, which essentially destroys the ducts.
In the image above one notes dilated breast ducts and 'loose' collagen collagen along the right edge. Gradually the collagen become more densely packed around the breast ducts, damaging them. But in early stages it is termed 'florid' gynecomastia.
In advance stages, such as in the image below, collagen becomes densely packed around the breast ducts, constricting them and eventually blocking them entirely. This is termed late-phase or 'fibrous' gynecomastia.
There is another manifestation of gynecomastia in a 'diffuse glandular' pattern, which is most commonly linked to patients who have received endrogen therapy.
Certain age groups are more susceptible to gynecomastia
Suprisingly, gynecomastia actually affects about one third of males at some point in their lives. Sometimes a small percentage of males develop gynecomastia when they reach puberty, but this is most often temporary and resolves on its own as the rest of the body 'catches up'. But generally speaking, gynecomastia occurs most commonly with men in their mid sixties.
What causes gynecomastia?
In cases of benign gyecomastia, the condition is thought to be caused by a hormonal imbalance of some kind. However, the condition may also arise as a result of breast tumor development, and that's why it always has to be fully checked out, usually with ultrasound and possibly a biopsy.
decreasing testosterone in eldery men may be a contributing factor
In elderly men the main cause of gynecomastia is thought to be decreasing testosterone production. Medications a patient may have been taking over the years can also play a role. Hormonal medications including androgens, anabolic steroids, antiandrogens, and estrogens can certainly help bring it on, but nonhormonal medications can also be a contributing factor. Of course, some of these ideas remain more in the category of 'urban myths', but the consumption of alcholol, marijuana use, and amphetamines have been suggested as agents. Other drugs like tricyclic antidepressents, thiazide diuretics, phenytoin, digoxin, and ketoconazole, taken over many years, are also thought to contribute to the condition.
gynecomastia may be caused by endocrine-gland tumors
While uncommon, gynecomastia may also be caused by tumors or diseases of certain endocrine (hormone-producing) glands or the liver, which increases estrogen production in men. (Estrogen is primarily a female hormone). Liver disease may be the cause of either gynecomastia or possibly even breast cancer, as it has an essential role in hormonal metabolism and balance.
treatment is usually through medication
Treaments for gynecomatia will vary, but hormonal medications
aimed at restoring hormonal balance are usually given. Depending on the amount
of fat tissue involved, the condition might be treated (reduced) with liposuction,
or surgically removed.
Differential diagnosis of gynecomastia versus breast cancer
Typical physical symptoms of male breast cancer may include nipple retraction, nipple discharge, redness and scaling of the breast skin or nipple, a breast lump, skin dimpling or puckering, and breast swelling. For this reason, whenever there is gynecomastica the patient should have an mammogram and ultrasound to determine whether it looks like normal tissue or breast cancer. If those findings are uncertain or not in typical gynecomastia patterns, an excisional biopsy should be undertaken.
male breast cancer tumors might include a hard, immobile mass
When the breast enlargement is the result of a breast cancer tumor, clinical signs might include a hard or immobile mass under the skin. On a mammogram one might find a thickening of overlying skin layers, or an eccentric mass relative to the nipple, and possibly clustered microcalcifications. Mammograms of male breast cancer with gynecomastia would also typically reveal a lipoma, with a thin capsule surrounding radiolucent lipomatous tissue. On ultrasound, this would appear as a solid, well-circumscribed and echogenic tumor. Fat necrosis might also be apparent, which tends to be associated with trauma. Evidence of fat necrosis should be followed up with a core biopsy at least.
treatment of male breast cancers is basically the same as for women
Treatment of male breast cancer will tend to follow the same recommendations as for the treatment of female breast cancers, and the survival rates tend to be similar. However, male breast cancer patients do appear to be more likley to have estrogen receptor-positive tumors, which is a good prognostic indicator for the succesful treatment with chemical therapy.
Ongoing Genetic research on male breast cancer and gynecomastia
As breast cancer is essentially a genetic disease, research into the relationships and interactions caused by various gene expressions holds perhaps the most promise for ultimately curing and preventing breast cancer. In the case of male breast cancer, one branch of current genetic research focuses on 'micro-RNA's, (miRNA or micro Ribonucleic acid ) which is a molecule in the category of 'post-transcriptional regulator'.
genetic research into the 'benignity' of gynecomastia
By using gynecomastia as a potentially 'benign counterpart' for abnomalities in male breast glands, studying the difference between miRNA gene expression profiles in men with breast cancer as opposed to men with gynecomastia might provide some insight into the potential genetic causes. Ultimately, it is hoped that such investigations may lead to genetically oriented treatments for male breast cancer.
- Chantra PK, So GJ, Wollman JS, Bassett LW. Mammography of the Male Breast. AJR 1995; 164: 853-858.
- Rissanen TJ, Makarainen HP, Kallioinen MJ, Kiviniemi HO, Salmela PI. Radiography of the Male Breast In Gynecomastia. Acta Radiologica 33, 1992, Fasc. 2: 110-114
- Stewart RAL, Howlett DC, Hearn FJ. Pictorial Review: The Imaging Features of Males Breast Disease. Clinical Radiology, 1997; 52: 739-744.
- Braunstein, GD (Feb 18 1993). "Gynecomastia". N Engl J Med 328
- Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY.; MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008 Nov;14(11):2348-60. Epub 2008 Sep 23.
- Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM.MicroRNA gene expression deregulation in human breast cancer.Cancer Res. 2005 Aug 15;65(16):7065-70.
- Ma L, Teruya-Feldstein J, Weinberg RA.; Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007 Oct 11;449(7163):682-8. Epub 2007 Sep 26.
- Giordano, Sharon H., Buzdar, AU., Hortobagyi, GN. Breast Cancer in Men. Ann Intern Med August 19, 2003 139:305
- Lee, R. C., Feinbaum, R. L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854.
- Kusenda, B., Mraz, M., Mayer, J., and Pospisilova, S. (2006). MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 150, 205-215.
Copyright Steven B. Halls, MD Last edited 23-August-2011