Gynecomastia means unilateral or bilateral benign enlargement of the male breast. It can lead to female appearance and consecutively to severe strain of those affected.
The true gynecomastia with actual hypertrophy of glandular tissue is differentiated from the so-called pseudogynecomastia with mainly fatty tissue growth typically associated with adiposity. 
 Both types can result in considerable psychological stress and disturbance of the self-confidence. A  retrospective single center analyses of 35 patients revealed that gynecomastia in adolescents presents a psychological threat to normal self-esteem as well as sexual identity1.
Hence, gynecomastia represents a serious disorder that needs to be treated appropriately.

Distance A = 1.2 + (.28 x length of sternum) + (0.1 x thorax circumference) [cm]
Distance B = 2.4 + (0.09 x thorax circumference) [cm]
modified from Beet et al. - PRS 2001 Dec;108(7):1947-52; discussion 1953. doi: 10.1097/00006534-200112000-00015. [2]

Arterial and venous supply follow the same pattern. Breast parenchyma and skin are supplied by:

Breast innervation is provided by the supraclavicular nerves and by the lateral and median branches of the intercostal nerves - similar to the female breast:

The male breast without gynecomastia mainly consists of fatty tissue with sporadic appearance of ducts and stroma [12]. 
Bannayan et al. histologically classfied the true gynecomastia into florid (ductal hyperplasia and proliferation), fibrous (more stromal fibrosis and fewer ducts) and intermediate gynecomastia [13].
In Contrast to female breast tissue lobules are generally absent [12]. 
Beside the  lipomatous gynecomastia (pseudo-gynecomastia) which is more frequent in older patients, the histological type of the true gynecomastia also seems to be associated with age. Investigations by Fricke et al. showed that the rate of florid gynecomastia increased with the age of patients, while fibrous gynecomastia was more common in adolescents and young adults. The florid one seems to show a higher recurrence rate compared to the fibrous one [14].
Blau et al. demonstrated in their investigations that the male breast gland is composed of a head, body and tail. The head is semicircular medial to the areola, the body is located beneath the areola and the tail goes along to the humeral insertion of the pectoralis major muscle [3]. 

The true gynecomastia is differentiated from the so-called pseudo-gynecomastia (hypertrophy of fatty tissue) and contains true glandular tissue including ducts and stroma (no lobules). It is the most common breast alteration in males and occurs particularly during infancy, puberty and old age [15, 16]. 
The true gynecomastia is often related to a relative or absolute estrogen excess and/or a decrease of circulating androgen respectively a defect in androgen receptors.

Prevalence rates as reported by Johnson et al.:

The physiologic gynecomastia (25%) as part of normal physiologic changes is differentiated from the non-physiologic gynecomastia (50%) which is induced by pathological causes or drugs (see table below). The cause of the idiopathic gynecomastia mostly remains unclear (25%) [17]. Gynecomastia particularly in newborns and adolescents disappears spontaneously within months or years [18].

The histological appearance is reported to change with duration of symptoms[13]:

Spontaneous regression of fibrous gynecomastia is regarded as unlikely. Thus, surgical treatment of gynecomastia is recommended after >12 months of persistence [18, 19].

AA=antiandrogenic; RA=reduced androgens; E=oestrogenic; IAM=increased androgen metabolism; ISHBG=increased concentration of sex hormone binding globulin; IP=increased prolactin; UM=unknown mechanism

Male breast cancer is a very rare disease and represents less than 1-2% of all malignancies in men and less than 1% of all breast cancers [25]:

Due to the low incidence of male breast cancer in patients without high risk factors it seems reasonable to treat gynecomastia using liposuction or surgical excision. In those with high risk factors as BRCA-2 mutation or Klinefelter syndrome excisional techniques are preferred [27]. 

If breast tissue increased gradually and physiological gynecomastia seems reasonable no further investigations are required. For all other cases where no underlying  cause can be determined further investigations are recommended. 

Imaging of the male breast:

Standard: Ultrasound is generally recommended also with regards to the differentiation between true gynecomastia and lipomastia.
In line with US guidelines further imaging investigation is only required where physical examination is unclear or suspicious 12. Therefore Mammography is the method of choice 13. Due to the fact that the incidence of gynecomastia associated breast cancer is reported with 0-2.5% mammography is rarely required 14.


Further Imaging:

The value of a classification is depending on its reproducible clinical implementation as well as on its medical consequences. 
For a reproducible clinical assessment of gynecomastia particular limitations are the grading of skin laxity as well as the grading of fibrosis. 
We stated that skin laxity after massive weight loss is highly reduced, and that one year after massive loss no further skin shrinking is expectable. Thus, we divided gynecomastia patients into two classes: with/without massive weight loss. 
According to our preferred treatment algorithm subclasses with regards to fibrosis and skin excess were defined.
Although biopsy or ultrasound elastography could theoretically verify the grade of fibrosis subjective assessment remains as most practicable in clinical routine.
In patients without massive weight loss skin shrinking is expectable and thus should be awaited over 12 months. 
If the MAC is stretchable 4 cm below the caudal border of the pectoralis major muscle the skin excess is sufficient to perform a horizontal mastectomy with fixation of the planned infrapectoral fold and transfer of the MAC 2 cm above. 
In patients with massive weight loss and just moderate skin excess (not stretchable 4 cm below the pectoralis major muscle) a vertical skin excision is adequate.

Beside the division between the pseudo-gynecomastia (lipomatous gynecomastia) and true gynecomastia Bannayan et al. histologically classified the true gynecomastia [13]:

Due to the fact that gynecomastia is transient in 90% of adolescent patients it is recommended to wait until symptoms remain unchanged for 1-2 years before indicating any treatment [16, 18]. In cases where gynecomastia is induced by drugs or pathological reasons causative medication should be withdrawn and pathological findings should be addressed [16-19]. Thereby early acting within the early florid state of gynecomastia is crucial before glandular tissue will be replaced by irreversable fibrosis [16].

As conservative treatment pharmaceuticals can be highly effective before glandular fibrosis occurs. 
Even not licensed for the treatment of gynecomastia Tamoxifen is the most popular medical treatment with response rates up to 95% [42-47].
The main indication for Tamoxifen is breast pain in gynecomastia smaller than 4 cm [19, 43].

Limiting side effects of Tamoxifen are[48]:

Conventional suction assisted liposuction (SAL) or water-jet assisted liposuction (WAL) are suitable to address the fatty tissue around the glandular mass:

If available, the treatment of the glandular mass  by the use of ultrasound assisted liposuction (UAL) is reported to be highly effective [18, 48].

1. Kinsella, C., Jr., et al., The psychological burden of idiopathic adolescent gynecomastia. Plast Reconstr Surg, 2012. 129(1): p. 1-7.2. Beer, G.M., et al., Configuration and localization of the nipple-areola complex in men. Plast Reconstr Surg, 2001. 108(7): p. 1947-52; discussion 1953.3. Agarwal, C.A., et al., Creation of an Aesthetic Male Nipple Areolar Complex in Female-to-Male Transgender Chest Reconstruction. Aesthetic Plast Surg, 2017. 41(6): p. 1305-1310.4. Blau, M., R. Hazani, and D. Hekmat, Anatomy of the Gynecomastia Tissue and Its Clinical Significance. Plast Reconstr Surg Glob Open, 2016. 4(8): p. e854.5. Shulman, O., et al., Appropriate location of the nipple-areola complex in males. Plast Reconstr Surg, 2001. 108(2): p. 348-51.6. Wolter, A., et al., Sexual reassignment surgery in female-to-male transsexuals: an algorithm for subcutaneous mastectomy. J Plast Reconstr Aesthet Surg, 2015. 68(2): p. 184-91.7. Lo Russo, G., S. Tanini, and M. Innocenti, Masculine Chest-Wall Contouring in FtM Transgender: a Personal Approach. Aesthetic Plast Surg, 2017. 41(2): p. 369-374.8. Maas, M., et al., The Ideal Male Nipple-Areola Complex: A Critical Review of the Literature and Discussion of Surgical Techniques for Female-to-Male Gender-Confirming Surgery. Ann Plast Surg, 2020. 84(3): p. 334-340.9. Kasai, S., et al., An anatomic study of nipple position and areola size in Asian men. Aesthet Surg J, 2015. 35(2): p. NP20-7.10. Vaucher, R., et al., [Anatomical study of men's nipple areola complex]. Ann Chir Plast Esthet, 2016. 61(3): p. 206-11.11. Sarhadi, N.S., et al., An anatomical study of the nerve supply of the breast, including the nipple and areola. Br J Plast Surg, 1996. 49(3): p. 156-64.12. Misery, L. and M. Talagas, Innervation of the Male Breast: Psychological and Physiological Consequences. J Mammary Gland Biol Neoplasia, 2017. 22(2): p. 109-115.13. Iuanow, E., M. Kettler, and P.J. Slanetz, Spectrum of disease in the male breast. AJR Am J Roentgenol, 2011. 196(3): p. W247-59.14. Bannayan, G.A. and S.I. Hajdu, Gynecomastia: clinicopathologic study of 351 cases. Am J Clin Pathol, 1972. 57(4): p. 431-7.15. Fricke, A., et al., Gynecomastia: histological appearance in different age groups. J Plast Surg Hand Surg, 2018. 52(3): p. 166-171.16. Cuhaci, N., et al., Gynecomastia: Clinical evaluation and management. Indian J Endocrinol Metab, 2014. 18(2): p. 150-8.17. Johnson, R.E. and M.H. Murad, Gynecomastia: pathophysiology, evaluation, and management. Mayo Clin Proc, 2009. 84(11): p. 1010-5.18. Sansone, A., et al., Gynecomastia and hormones. Endocrine, 2017. 55(1): p. 37-44.19. Rohrich, R.J., et al., Classification and management of gynecomastia: defining the role of ultrasound-assisted liposuction. Plast Reconstr Surg, 2003. 111(2): p. 909-23; discussion 924-5.20. Thiruchelvam, P., et al., Gynaecomastia. BMJ, 2016. 354: p. i4833.21. Akgul, S., N. Kanbur, and O. Derman, Pubertal gynecomastia: what about the remaining 10%? J Pediatr Endocrinol Metab, 2014. 27(9-10): p. 1027-8.22. Biro, F.M., et al., Hormonal studies and physical maturation in adolescent gynecomastia. J Pediatr, 1990. 116(3): p. 450-5.23. LaFranchi, S.H., et al., Pubertal gynecomastia and transient elevation of serum estradiol level. Am J Dis Child, 1975. 129(8): p. 927-31.24. Ma, N.S. and M.E. Geffner, Gynecomastia in prepubertal and pubertal men. Curr Opin Pediatr, 2008. 20(4): p. 465-70.25. Niewoehner, C.B. and F.Q. Nuttal, Gynecomastia in a hospitalized male population. Am J Med, 1984. 77(4): p. 633-8.26. Wu, F.C., et al., Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab, 2008. 93(7): p. 2737-45.27. Smyth, C.M. and W.J. Bremner, Klinefelter syndrome. Arch Intern Med, 1998. 158(12): p. 1309-14.28. Tan, Y.K., C.R. Birch, and D. Valerio, Bilateral gynaecomastia as the primary complaint in hyperthyroidism. J R Coll Surg Edinb, 2001. 46(3): p. 176-7.29. Iglesias, P., J.J. Carrero, and J.J. Diez, Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options. J Nephrol, 2012. 25(1): p. 31-42.30. Hendry, W.S., et al., Ultrasonic detection of occult testicular neoplasms in patients with gynaecomastia. Br J Radiol, 1984. 57(679): p. 571-2.31. Hernes, E.H., K. Harstad, and Fossa, Changing incidence and delay of testicular cancer in southern Norway (1981-1992). Eur Urol, 1996. 30(3): p. 349-57.32. Daniels, I.R. and G.T. Layer, Testicular tumours presenting as gynaecomastia. Eur J Surg Oncol, 2003. 29(5): p. 437-9.33. Harris, M., et al., Testicular tumour presenting as gynaecomastia. BMJ, 2006. 332(7545): p. 837.34. Dundar, B., et al., Leptin levels in boys with pubertal gynecomastia. J Pediatr Endocrinol Metab, 2005. 18(10): p. 929-34.35. Bowman, J.D., H. Kim, and J.J. Bustamante, Drug-induced gynecomastia. Pharmacotherapy, 2012. 32(12): p. 1123-40.36. Dickson, G., Gynecomastia. Am Fam Physician, 2012. 85(7): p. 716-22.37. Karavolos, S., et al., Male central hypogonadism secondary to exogenous androgens: a review of the drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects. Clin Endocrinol (Oxf), 2015. 82(5): p. 624-32.38. Nuttall, F.Q., Gynecomastia. Mayo Clin Proc, 2010. 85(10): p. 961-2.39. Abdelwahab Yousef, A.J., Male Breast Cancer: Epidemiology and Risk Factors. Semin Oncol, 2017. 44(4): p. 267-272.40. Thomas, D.B., Breast cancer in men. Epidemiol Rev, 1993. 15(1): p. 220-31.41. Schanz, S., et al., S1-Leitlinie: Gynakomastie im Erwachsenenalter. J Dtsch Dermatol Ges, 2017. 15(4): p. 465-472.42. Alagaratnam, T.T., Idiopathic gynecomastia treated with tamoxifen: a preliminary report. Clin Ther, 1987. 9(5): p. 483-7.43. Derman, O., et al., Long-term follow-up of tamoxifen treatment in adolescents with gynecomastia. J Pediatr Endocrinol Metab, 2008. 21(5): p. 449-54.44. Derman, O., N.O. Kanbur, and T.E. Tokur, The effect of tamoxifen on sex hormone binding globulin in adolescents with pubertal gynecomastia. J Pediatr Endocrinol Metab, 2004. 17(8): p. 1115-9.45. James, R., F. Ahmed, and G. Cunnick, The efficacy of tamoxifen in the treatment of primary gynecomastia: an observational study of tamoxifen versus observation alone. Breast J, 2012. 18(6): p. 620-1.46. Konig, R., et al., [Treatment of marked gynecomastia in puberty with tamoxifen]. Klin Padiatr, 1987. 199(6): p. 389-91.47. Lawrence, S.E., et al., Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia. J Pediatr, 2004. 145(1): p. 71-6.48. Pemmaraju, N., et al., Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol, 2012. 23(6): p. 1471-4.49. Zocchi, M.L., Ultrasonic assisted lipoplasty. Technical refinements and clinical evaluations. Clin Plast Surg, 1996. 23(4): p. 575-98.