Diagnosing and Managing Breast Disease During Pregnancy and Lactation

, University of Iowa College of Medicine

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Benign Lesions of Pregnancy

Benign breast lesions most likely to develop in pregnant women include lactating adenomas, breast infarcts, and gigantomastia. In addition, benign lesions that are commonly found in women in general--for example, fibroadenoma, breast hamartoma, and axillary breast tissue--may increase in size during pregnancy. The goal in evaluating new breast masses during pregnancy is appropriate diagnosis and confident exclusion of carcinoma by the least invasive but most reliable means possible.

Lactating adenomas. Also termed lactating nodules or nodular lactational hyperplasia, lactating adenomas are discrete, round, well-demarcated masses unique to pregnancy. Despite the name, lactating adenomas are more common during pregnancy than during lactation. Consequently, the alternative term "breast tumor of pregnancy" has been suggested.[4] But this term could also be used to describe other breast lesions--for example, fibroadenomas and hamartomas--that enlarge during pregnancy and lactation. Differentiation among these benign lesions may be difficult and is clinically irrelevant; fibroadenomas and hamartomas that enlarge during lactation both have been included in many series of lactating adenomas.

Lactating adenomas typically present as painless, often rather sizable, palpable masses. The most common location is the breast periphery, often in the upper outer quadrant (where the bulk of breast tissue is distributed). The histology is characteristic; lobulated masses of acini or lobules are densely packed together with little intervening stroma. The basement membrane is intact. Despite abundant proliferative changes, there are no atypia. Pregnancy-associated changes usually are noted, including intracytoplasmic or supranuclear vacuolation and secretions in gland lumens.

The major task is to differentiate these benign masses from breast cancer. Diagnostic fine-needle aspiration cytology (FNAC) is an acceptable method of diagnosis, provided the cytopathologist is informed of the stage of pregnancy and knowledgeable about the changes seen in these lesions. The characteristic FNAC appearance has been well described[5,6]; large numbers of very similar cells are present, with some nuclear enlargement, prominent nucleoli, cellular dispersion against a background suggestive of necrosis, prominent cytoplasmic vacuoles, and a foamy/wispy appearance to the cytoplasm.

Fibroadenomas and mammary hamartomas (Fig. 1) can enlarge significantly during pregnancy, due to proliferation in response to hormonal stimulation or to infarction.

Figure 1. GMammary hamartoma with characteristic mixture of adipose tissue, glandular elements, and stroma

Breast infarcts. Infarcts may occur in fibroadenomas, hamartomas, lactating adenomas, or even in regions of hypertrophic breast tissue. The etiology is believed to be vascular insufficiency related to significantly increased metabolic demands. A pre-existing mass may suddenly increase in size, or a new mass may appear where none was previously palpable. The mass may be ill-defined, or even feel tethered to adjacent breast tissue. Sometimes tenderness, skin fixation, or other skin changes may be noted. The rapid increase in size and physical characteristics of the mass raise concern that the mass may be malignant.

Differentiating these lesions from cancer is more difficult than with lactating adenomas. FNAC is unlikely to be helpful, because it may show only necrotic tissue with some of the proliferative changes noted previously. Generally, biopsy is required. Frozen section may be misleading, especially to the inexperienced pathologist, as the histologic picture of extensive central necrosis with an outer zone of proliferation suggests carcinoma. Sometimes the entire architecture of the underlying fibroadenoma is lost when infarction occurs. Special stains such as Masson's trichrome stain or reticulin stain can be used to demonstrate residual fibrous structure despite extensive necrosis.[7,8,9]

Gigantomastia. In about 1 in 100,000 pregnancies, the normal increase in size and weight of the breasts is exaggerated to enormous proportions.[10,11,12] The resulting hypertrophy is not only grotesquely deforming, but also may preclude ambulation or progress to skin ulceration, infection, or massive bleeding from dilated subcutaneous veins; these complications may be life threatening. Recall that the normal resting weight of the breast--200 grams--typically doubles to 400 grams with pregnancy; in gigantomastia, weights of 4000 to 7000 grams per breast have been recorded.

The etiology is unknown, but the disease is believed to represent an abnormal end-organ (breast) response to the normal rise in progesterone level as pregnancy progresses.[10,11,12] This hypertrophy can occur in any pregnancy, not necessarily the first, but the presence of the condition in one pregnancy essentially guarantees its recurrence in subsequent gestations. There is no racial predilection. It is unnecessary and inadvisable to biopsy the breast tissue when gigantomastia is identified because of the risk of bleeding and infection. Biopsy is recommended only when a discrete, suspicious region of abnormality is detected.[12]

Histology demonstrates an increase in both the glandular and connective tissue elements of the breast, with little or no increase in adipose tissue. There may be a marked histologic resemblance to fibroadenoma. Treatment is bromocriptine, which may arrest continued growth of the breasts.[10,11,12,13] Other hormonal interventions have been used with variable success. Sometimes early delivery and urgent breast surgery are required when life-threatening complications occur, including hemorrhage, infarction, secondary infection, or even hyperparathyroidism.[14] Some involution may occur after delivery. Breast-feeding is not advised, because the hypertrophy may continue to increase. Reduction mammoplasty is generally necessary, because the breasts do not revert to normal size even after involution occurs.

Bloody nipple discharge. During the third trimester of pregnancy, proliferative changes within the ducts of the breasts may lead to bloody discharge from the nipple[15]; this occurs when proliferative spurs of epithelium that extend into the ducts are traumatized, resulting in bleeding.[16,17] Breast-feeding is not contraindicated, and the bleeding often ceases with the onset of nursing. Cytology of the discharge is apt to be misleading, as proliferative changes are typical for pregnancy and may be mistaken for neoplastic alterations. Mammography and biopsy are required only if the bloody discharge persists more than 2 months after delivery, localizes to 1 duct, or is associated with a palpable mass[16,17,18]; mammography is contraindicated during pregnancy.

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