Aberrations or Diseases of Lobular Development

Before the peri-menarchal period, the mammary gland consists of only a few ducts. During peri-menarchal development, the principal changes are duct sprouting and the addition of lobular structures. Estrogen induces connective tissue and vascular growth, which is required for new duct development. The lobules develop particularly during early reproductive life, between 15 and 25 years of age, and the different types have been described by Russo and coworkers. Each period of reproductive life (such as pregnancy, breastfeeding or menopause) is associated with increasingly more differentiated lobules. This explains the frequency of fibroadenoma during early reproductive life, which is an exaggerated development of various lobule structures.

Fibroadenomas are classified as benign, since they can almost be considered as aberrations of normal development.

Fibroadenoma Simplex: Aberration of Normal Development
The lobular origin explains many features of fibroadenoma, for instance its frequency during the menarchal period, which is a time of maximal lobular development. Fibroadenoma is the most common breast tumor of adolescence.

Indeed, its discovery is certainly less frequent by clinical examination than by ultrasound, which usually detects deeper fibroadenomas. The characteristics of adolescent fibroadenoma are accurate enough to be diagnosed certainly after only clinical examination. Often, the tumor is noticed accidentally by the adolescent herself. It is a firm, smooth, round or bosselated, painless and very mobile tumor. Its encapsulation explains this mobility.

The size of a fibroadenoma is generally from 1 to 3 cm. During the growth phase, the tumor doubles in size in 6 - 12 months and is then likely to remain static for the rest of the patient’s life; it may even gradually decrease in size or disappear. In one study, Dent et al. followed 99 young women with clinical and cytological diagnoses of single or multiple fibroadenoma. They found that 107 lumps disappeared out of the 279 tumors followed over 7 to 9 years. In this work, the probability of fibroadenoma disappearance depended only on the young age of the patient. Fibroadenoma development is hormonedependent.

This dependence rapidly diminishes with the lesion’s age and the appearance of fibrosis without hormonal receptors, a further possible explanation for the plateauing in the fibroadenoma’s growth curve. Ultrasound confirms the evident clinical diagnosis. The ultrasonic features are round or oval sharp contour, weak internal echoes in a uniform distribution and intermediate attenuation, which is more evident if the tumor is young.

The histological features of fibroadenoma are an exaggeration of normal lobular development. The proliferation of stromal and epithelial elements is regular, maintaining a normal relationship as in a normal lobule. There is then a progressive sclerosis of the stromal element and the epithelial element disappears.

For some authors, fibroadenoma occurs in women with an estrogen-progesterone imbalance that leads to an ‘unopposed estrogen effect’.

Progesterone appears to oppose the estrogen effects on breast epithelial cells. Based on this rationale, some clinicians, at least in our country, propose progestin treatment for various benign breast disorders; for example, for fibroadenoma.

19-Nortestosterone derivatives, used 15 - 20 days per cycle, have been proposed with good clinical and ultrasound results.

Removal of all fibroadenomas is a classical response, but for an adolescent, a few points argue for a more flexible approach: (a) Recurrence after surgery at the site of previous removal or near it -  in the same breast or in the contralateral one -  is possible. (b) Fibroadenomas are often multiple. Repeated surgery is not recommended for an adolescent in an aesthetic approach. (c) The lumps may spontaneously become smaller or disappear. (d) Medical treatment with progestins provides good results. (e) The risk of malignancy is negligible for women younger than 20, so progestins can be used as a conservative approach without fear.

A conservative approach can be chosen if clinical and ultrasound examinations show unequivocally benign characteristics. Fine needle aspiration can be used for confirmation if clinical or ultrasound features are not entirely typical. After the triple assessment (clinical, ultrasound and cytology), the diagnosis is confirmed, but sometimes the cytological features can be florid if the fibroadenoma is young. Patients can be discharged after 6 months if the lesion remains stable or regressed. Only standard clinical surveillance is necessary.
The conservative policy should be reconsidered if the tumor increases in size.

If there is doubt regarding the nature of the presumed fibroadenoma or if the patient wishes to be rid of it, surgery is chosen. The surgical approach must be as aesthetic as possible. The peri-areolar excision is better from this point of view.

Giant Fibroadenoma: Disease
Although fibroadenoma simplex is considered as an aberration of normal lobular development, giant fibroadenoma is a disease. The tumor is >5 cm at onset of menarche or soon after. This encapsulated breast mass with rapid enlargement compresses the adjacent breast tissue with the development of skin ulcers and prominent veins. This sudden growth argues against the hypothesis that giant fibroadenoma arises from the continued progression of small fibroadenoma. It is possible that giant fibroadenoma is a separate de novo condition. The clinical feature is a large well-demarcated breast mass, firmer than the rest of the breast, as opposed to breast asymmetry or unilateral hypertrophy.

A giant fibroadenoma in this age group may be associated with multiple smaller fibroadenomas in the same breast or in the opposite one.

Giant fibroadenoma has been described as being more common in the black population. On the basis of clinical diagnosis, surgery should be recommended as its size imposes this. A cosmetic approach is recommended. Tumor fragmentation is possible.

The histological features are the same as for fibroadenoma simplex, with a normal relationship between epithelial and stromal elements. The florid feature of this proliferation can lead to considerable confusion with cystosarcoma phyllodes, which are very rare under the age of 20. The phyllode tumor is distinct from the giant fibroadenoma by both macroscopic and histological criteria; the diagnosis is essentially histological.

To diagnose the phyllode tumor, both epithelial and fibrous stromal elements must be present, with the stroma showing cellularity, irregularity, hyperchromatism and significant mitosis. The stroma are notably more cellular than in fibroadenoma and are dominant in relation to the epithelial component. Under the age of 20, they almost invariably behave in a benign manner. All should be treated by enucleation. This tumor shows no local recurrence if completely excised. Many diagnoses of phyllode tumor are certainly made in excess.

Multiple Fibroadenomas
Fibroadenomas are often multiple, occurring concurrently or successively in both breasts. Haagensen showed an incidence of 16% in his experience.

The development of multiple fibroadenomas, some of them >5 cm in size, has been reported to be at times brutal, with the breast invaded by the fibroadenomatous disease. It is, like giant fibroadenoma, a true disease. The treatment of these multiple fibroadenomas is not surgical due to the risk of aesthetic damage.

Medical treatment can be discussed. The use of progestin 19-nortestosterone derivatives, if given early, has shown a diminution of fibroadenoma size and sometimes the disappearance of some tumors.

Provided by ArmMed Media
Revision date: July 3, 2011
Last revised: by Andrew G. Epstein, M.D.