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While tumors of the breast in childhood are rare, enlargements of the breast of all types are sufficiently common that anyone caring for children wall encounter abnormalities, or apparent abnormalities, fairly regularly. The physiologic appearance of breast buds, the development of normal breast tissue at inappropriate times, abnormal diffuse swelling, and discrete masses, both neoplastic and nonneoplastic, are all part of the spectrum of breast enlargement. The clinician must be familiar with all these entities to formulate a rational approach to diagnosis and treatment.
Two factors tend to exaggerate concern about breast lesions. First, the fact that carcinoma of the breast is the most common neoplasm in adult women raises understandable fear about any lump in the breast, even though malignancies of the breast are exceedingly rare in childhood. Second, American culture attaches enormous psychologic significance to the breasts, so any unusual or asymmetric breast development arouses great anxiety in parents and adolescents, if not in younger children. Breast biopsy is an easy procedure but is not without hazards, both physical and psychologic. The clinician must have a thorough understanding of normal and abnormal breast development in order to avoid needless diagnostic evaluation and surgical excision.
This presentation includes a description of the various causes of diffuse and discrete breast enlargement in children, followed by a suggested approach to the child with a breast lesion and further discussion of diagnostic and therapeutic methods.
DIFFUSE ENLARGEMENT OF THE BREAST
Neonatal breast buds. Breast development begins in the sixth week of fetal life and culminates in the formation of a nipple and areola overlying a bud of breast tissue composed of the primary mammary ducts and a loose fibrous stroma. ' The size of this breast bud is used as one index of gestational age. Not palpable before 34 weeks, it measures about 3 mm. at 36 weeks and 4-10 mm. at 40 weeks.2 Further enlargement of this bud, occasionally to several centimeters (Figure 1), occurs in about 60 per cent of normal neonates of both sexes and is frequently associated with secretion of a milklike substance ("witch's milk").3,4 The mass is subareolar, soft, uniform, and not fixed to the chest wall. The ductal hypertrophy and increase in vascular stroma are presumably a result of stimulation by maternal hormones. The breast enlargement may be asymmetric and, therefore, an additional cause for alarm. These nodules, however, are normal and need no further evaluation or treatment. Massage, application of compresses or ointments, or other manipulation may predispose to infection. Although breast buds may be somewhat red and tender, these signs of inflammation are less striking than in mastitis, and fluctuation does not occur. Gradual involution of the hypertrophied breast bud develops over several weeks, although enlargement may persist for many months in breastfed infants. Following involution, a small, palpable breast bud usually remains throughout childhood.
Figure 1. Newborn baby with marked hypertrophy of the breast bud.
Prepubertal breast enlargement. Although this tiny nubbin of breast tissue usually remains quiescent until puberty, it is not uncommon for a child of either sex to develop a nodular enlargement of one or both breasts.4 This may appear at any age. It is frequently asymptomatic, but may cause transient pain or tenderness. The nodule is subareolar, soft, and mobile and has a uniform consistency. Palpation may yield a drop or two of serous fluid from the nipple. The areola and nipple are not developed or pigmented. There are no other signs of sexual maturation. Hormonal abnormalities have not been identified in the few patients studied. Histologically, the lesion is characterized by increased periductal fibrous tissue and slight hypertrophy of the ducts.
Most of these lesions regress spontaneously after a few weeks or months. Occasionally, they persist and grow slowly until puberty. In either case, beast development at puberty is perfectly normal. Further evaluation and treatment are not necessary. Continued observation is advisable, however, since such breast enlargements may be the first manifestation of precocious puberty. Injudicious biopsy or excision of these nodules may prevent or distort subsequent breast development. Careful explanation and reassurance are essential to allay the fears of anxious parents.
Premature breast development. An extension of the foregoing is the appearance of well-developed breasts in prepubertal girls; this is not rare and can be terribly distressing to the child and her parents. The onset of puberty varies widely from person to person and among races, but it is generally assumed that breast development beginning after eight years of age is within the normal range of puberty. To complicate matters, breast development is rarely synchronous; one side usually lags somewhat behind the other, occasionally by several months or even a year. In this case, one breast may be fairly well developed before the other has even begun to mature ("early ripening").5 It is all too easy for child, parents, and physicians to assume that unilateral breast enlargement in an eight- or nine-year-old girl represents an abnormal breast or tumor, particularly since the developing pubertal breast frequently has a vaguely lumpy character owing to the active proliferation of fibrous tissue stroma. Observation and reassurance that this is a normal variation are indicated. By the end of puberty, virtually all of these girls have normally developed, symmetrical breasts.
Premature thelarche, the growth of normal breast tissue before the age of eight years in the absence of other signs of sexual maturation, is a very common clinical problem.6 It is bilateral, although the onset may be asynchronous on the two sides. The breasts feel like normally developing breasts, soft and uniform but slightly nodular at times. Tenderness may be present in the early stages. Most important, there is complete absence of any other signs of sexual maturation. Papanicolaou examination of vaginal cells shows little evidence of estrogen effect. Extensive evaluation is not indicated in these girls; hormonal and histologic abnormalities have not been detected in those who have been studied. Observation is necessary, however, since premature thelarche may be the first manifestation of precocious puberty. In most cases, breast growth reaches a plateau and remains stationary or regresses slightly. Occasionally, continued growth is observed throughout childhood until full development is reached at puberty. In either case, these girls ultimately have normal mature breasts.
Precocious puberty refers to generalized sexual development in girls under eight years of age.4,3 Breast growth is commonly the first manifestation, but is soon followed by pigmentation of the areola, growth and pigmentation of the labia and clitoris, appearance of pubic and axillary hair, and menstruation. True precocious puberty includes gonadal maturation, ovulation, and the possibility of pregnancy. The idiopathic form is by far the most common, but true precocious puberty is also associated with Albright's syndrome (polyostotic fibrous dysplasia) and certain intracranial lesions. These patients have the typical hormonal changes of normal puberty. In pseudoprecocious puberty, the gonads remain immature or develop only partially; ovulation does not occur. Ovarian and adrenal tumors are the most common causes.
A complete discussion of precocious puberty is beyond the scope of this article. These girls need full endocrinologie evaluation and a search for occult tumor. The breasts are composed of normal breast tissue and should not be biopsied or removed.
Gynecomastia. Upon careful examination, at least 70 per cent of normal adolescent boys are found to have a 1-2-cm. firm, disklike nodule of breast tissue on one or both sides, similar to the nodule occasionally seen in prepubertal boys. This usually appears at about age 13 and is gone by the age of 17 or 18 years, although it persists to age 21 in 10 to 15 per cent of males.7 This physiologic enlargement is considered to be an effect of the normal slight increase in estrogen production in the adolescent boy or of some hormonal imbalance.
Figure 2. Typical idiopathic adolescent gynecomastia: 3-cm. mass of breast tissue in a 16-year-old boy.
Figure 3. Extreme gynecomastia in a teenage boy. Subcutaneous mastectomy is clearly indicated.
A greater degree of breast enlargement is called gynecomastia.4,5 This may be an exaggeration of the usual disk or nodule and, on palpation, is a discrete, firm, usually subareolar mass (Figure 2). In other patients, the enlargement is more diffuse and softer but still separable from adjacent soft tissue. In rare instances, the breast with this form of gynecomastia resembles a normal female breast in size, shape, and consistency (Figure 3). Enlargement is bilateral in 15 to 20 per cent of cases.5 Pain and tenderness are not uncommon. Growth is often rapid at first, reaching a peak in about 15 months, then remaining stationary for a year or so before gradually regressing. The histology of gynecomastia is characterized by a marked increase in periductal fibrous tissue and increased size and branching of the ducts without lobule formation (Figure 4). A variety of hormonal abnormalities and imbalances have been described, but no consistent theory of pathogenesis has been established. The great majority of patients have idiopathic gynecomastia, but for a small group a specific cause can be identified. Patients with Klinefelter's syndrome usually have gynecomastia and are readily identified by their female body habitus, small atrophic testes, and characteristic endocrine abnormalities. Some testicular tumors and, rarely, adrenal tumors induce gynecomastia.4 Careful physical examination is therefore indicated in all boys with gynecomastia. At present, it does not seem warranted to perform extensive endocrinologie evaluation in adolescent boys with gynecomastia, as the disorder is so common and, if the rest of the physical examination is normal, almost invariably idiopathic.
Since gynecomastia is a selflimited disorder, observation and reassurance are usually the only required therapy. The physical appearance of breasts can be upsetting and embarrassing to adolescent boys, however, causing them to withdraw from contact with their peers, especially in sports. If the breasts are unusually large or their presence is unduly disconcerting to the boy, subcutaneous mastectomy, with removal of all breast tissue through a circumareolar incision, is readily performed and gives excellent results (Figure 5).
Prepubertal gynecomastia is much less common; about 40 cases have been reported.8,9 As with adolescent gynecomastia, most cases are idiopathic, but a few patients have been reported to have elevated urinary estrogens.9 Because of the rarity of prepubertal gynecomastia, hormone-producing tumors of the testis or adrenal gland are more likely to be the cause of gynecomastia in this age group. Careful examination, complete endocrinologie evaluation, and search for an occult tumor are indicated in these boys.8 The natural history of the idiopathic form is spontaneous regression after a few months or a year. In some cases, the enlargement persists into adolescence or until surgical excision is performed. Indications for operation are the same as for the adolescent type.
Juvenile hypertrophy of the breast. This unusual disorder is characterized by massive breast enlargement in the adolescent girl, most often bilaterally. Onset of breast development occurs normally at puberty but is followed by almost explosive growth, so that in two or three years the breasts may achieve gargantuan proportions. Breast weights of 25-35 pounds and descriptions of breasts reaching to patients' knees have been recorded.4,10 The breast tissue is soft but sometimes has diffuse, ropelike thickenings and may contain discrete masses representing fibroadenomas. Dilatation of subcutaneous veins and stretch marks are common, reflecting rapid growth. Histologically, there is a tremendous increase in periductal fibrous stroma, frequently in a loose myxomatous arrangement characteristic of rapid growth. There is also proliferation and increased branching of the ducts without lobule formation (Figure 6). The histology is almost identical with that seen in gynecomastia and is essentially an exaggeration of the histology of the normally developing adolescent breast.5 Fibroadenomas present a similar picture except that they are more compact and encapsulated and affect only a portion of the breast, while juvenile hypertrophy usually involves all of the breast tissue. Lesser degrees of hypertrophy also occur but - since there is less enlargement, distortion, and asymmetry and the patient may simply appear to be a particularly welldeveloped young woman - are not as likely to come to medical attention. Localized areas of juvenile hypertrophy also occur, but are rare.
Figure 4. High-power microphotograph of gynecomastia. Note the proliferation and increased branching of ducts without lobule formation and the marked hypertrophy of periductal fibrous tissue.
Figure 5. Same patient as in Figure 3 one week following bilateral subcutaneous mastectomy through circumareolar incisions.
Endocrine studies in these girls yield normal results. This fact, combined with other indirect evidence, suggests that juvenile hypertrophy represents a marked hypersensitivity of breast tissue to the intense hormonal stimuli of normal puberty.5 Similar pathologic hypertrophy is occasionally seen during pregnancy. Towards the end of adolescence, the hormonal milieu changes and some regression of the hypertrophy occurs as the breast matures. Unfortunately, in the usual case, the enlargement and distortion are so extreme that a little regression affords no real improvement. In girls with lesser degrees of hypertrophy or localized involvement, however, this regression at about age 17 may result in normal, if somewhat large, breasts. A recent patient illustrates this point.
A 16-year-old black girl presented with a 10-cm. firm mass in the upper outer quadrant of the right breast, which was somewhat larger than the left (Figure 7). The clinical impression was giant fibroadenoma, but at operation the mass was not encapsulated and could not be distinguished from the surrounding breast tissue except by palpation. The mass was excised and the remaining breast tissue reconstructed. The lesion had the typical histologic appearance of juvenile hypertrophy (Figure 8). Postoperatively, additional masses appeared in the area of excision, then gradually regressed over the next eight months. Concomitantly, the left breast began to enlarge and several discrete masses became palpable. These have now stabilized, and it is anticipated that they will subside as she reaches full maturity. Her breasts should then be normal and symmetrical.
Figure 5. High-power microphotograph of juvenile hypertrophy. There is moderate proliferation and branching of the ducts and a tremendous increase in periductal and interlobular fibrous tissue.
Figure 7. Sixteen-year-old girl with localized juvenile hypertrophy in the upper outer quadrant of the right breast.
Macromastia may also result from simple overgrowth of normal mature breast tissue. There may be some degree of asymmetry. It is impossible to distinguish this entity from milder degrees of juvenile hypertrophy on clinical grounds, but differentiation is not of great importance since treatment is largely cosmetic. Although Geschickter5 reported that one of his patients with juvenile hypertrophy developed breast cancer in later life, no details are given and there is no good evidence that juvenile hypertrophy is a premalignant lesion. Girls with massive hypertrophy and distortion should be operated on whenever the cosmetic defect or sheer weight of the breasts becomes troublesome. Simple mastectomy is usually necessary, although in selected patients reduction mammoplasty with free nipple transplant may be attempted, with the recognition that there may be a recurrence from hypertrophy of the remaining breast tissue. Sperling and Gold11 and Mayl et al.12 have reported encouraging preliminary results with the use of medroxyprogesterone to arrest further growth of the breasts before and after reduction mammoplasty. Hormone therapy has not been effective in reducing breast size, but it may be helpful in conjunction with surgery. The long-term results and possible complications of medroxyprogesterone treatment have not been established. A decision concerning reduction mammoplasty in girls with lesser degrees of juvenile hypertrophy and/or macromastia should generally be deferred until full skeletal growth and maturity have been achieved, since those with juvenile hypertrophy may have spontaneous regression of breast size and not require surgery at all.
Figure 8. High-power microphotograph of specimen removed from the patient in Figure 7 shows typical juvenile hypertrophy. The loose myxomatous arrangement of the fibrous tissue is common and reflects rapid growth.
Other causes of diffuse breast enlargement. Administration of exogenous estrogen is known to cause mammary hypertrophy. Estrogencontaining drugs are occasionally used therapeutically in children, may be ingested inadvertently, and are present in some proprietary tonics.4,8,9,13-14 Regular application of estrogen-containing creams to the chest wall induces breast growth in human beings.15 Other hormones - including androgens, chorionic gonadotropin, corticosteroids, and insulin - have been incriminated in breast development. Nonhormone drugs that have been reported to cause thelarche include digitalis, isoniazid, and amphetamines. Obviously, a careful drug history should be obtained before establishing a diagnosis of idiopathic gynecomastia, premature thelarche, or any other cause of breast enlargement.
The breast area is normally well endowed with adipose tissue and is not excluded in obesity. Overweight children frequently appear to have breast development that may be quite striking (Figure 9). These "breasts" can be distinguished from true breast tissue by the softer consistency of fat and the inability to distinguish it from surrounding tissue. This pseudogynecomastia or pseudo-premature thelarche regresses with general reduction in body weight.4,16
In advanced cirrhosis (e.g., biliary atresia and cystic fibrosis) the liver is unable to metabolize even the small amount of estrogen produced by the prepubertal child or male adolescent. Gynecomastia or premature thelarche may develop. 4,13,15 The diagnosis should be apparent from history and physical examination.
Breast enlargement due to hormone-secreting gonadal or adrenal tumors has been discussed in the appropriate sections. Breast growth has been reported in association with both hypo- and hyperthyroidism.4
DISCRETE BREAST MASSES
Inflammatory lesions. The child's breast is occasionally the site of inflammation, either cellulitis or abscess. The diagnosis is usually apparent from a history of sudden onset and the presence of swelling, tenderness, erythema, heat, and, in the case of abscess, fluctuation. Occasionally the history is uncertain, and erythema and heat are not prominent; in this situation, an inflammatory mass may be mistaken for a tumor. A few days' observation usually clarifies the diagnosis.
Ductal obstruction is presumably the immediate cause of inflammation, although it is not always documented. There may be a history of trauma. Infection may arise in a pre-existing cyst. In one series, duct ectasia was found in 24 per cent of surgical specimens from patients with breast abscess, but it is not clear whether the ectasia was a cause or an effect.17
Hormonal stimulation is thought to be one of the most important factors in the etiology of breast infection. Breast tissue that is actively proliferating under the influence of increased hormones is particularly prone to duct obstruction and secondary infection. Abscess in the lactating breast is a common and well-known entity. Not surprisingly, inflammatory processes of the breast in children are most common at times of unusual hormonal activity - namely, the neonatal period and adolescence. Mastitis neonatorum usually appears in the second or third week of life. The usual subareolar breast bud becomes hard and tender, with erythema and increased heat in the surrounding tissues. Fluctuation due to abscess formation is common. The infant may develop generalized sepsis with positive blood culture. Alternatively, breast abscess in the neonate may be a manifestation of sepsis from another source. In either case, these infants can be extremely ill and require prompt, vigorous therapy.
Figure 9. Obese 12-year-old boy with marked "breast" development from deposition of adipose tissue in the mammary area. Careful palpation revealed no evidence of enlargement of the true breast tissue.
Infection in the breast of the older child or adolescent tends to be a more localized process. Sepsis is uncommon, although there may be some fever and enlargement of the regional lymph nodes.
Treatment is initiated with warm compresses and systemic antibiotics. Staphylococcus is by far the most common offending organism, so a penicillinase-resistant penicillin is the antibiotic of choice. If fluctuation is present when the child is first seen or develops during the course of treatment, prompt incision and drainage should be performed, usually under local anesthesia. Abscess in the neonatal breast or in peripheral areas of the developed breast usually responds well to surgical drainage; recurrence is uncommon. In contrast, subareolar abscess in the developed breast is notoriously difficult to treat. Recurrence rates of 40 to 50 per cent have been reported after simple incision and drainage. Excision of all affected tissue gives somewhat better results.17 Following resolution of infection by medical or surgical means, a small mass of scar tissue may remain palpable indefinitely. Unless it begins to enlarge, biopsy is not indicated.
Trauma may produce inflammatory masses. The child's breasts are constantly exposed to injury during normal active play and sports. The appearance of a localized but poorly defined firm, tender mass following trauma almost certainly represents a deep contusion that will gradually resolve over several weeks. More extensive trauma results in a hematoma, which may be more sharply defined. There is usually ecchymosis of the skin over the breast and considerable pain and tenderness. Application of ice in the first 24 hours, then hot pads or compresses for several days, may hasten resolution of the inflammation. Infection may supervene during this acute stage. Complete resolution of the process may take several months, and a palpable mass of scar tissue may be present permanently.
Fat necrosis from trauma may appear as a firm, usually circumscribed mass in or adjacent to the breast. Typically, the patient notices nothing unusual following the injury but after a few months realizes that a painless mass has grown rapidly in the area. A substantial percentage of patients cannot recall any significant trauma.18 The mass is mobile but may be fixed to the skin. The rapid growth and skin fixation suggest carcinoma, while the mobility and sharp delineation of the mass are reassuring.19 Despite the rarity of carcinoma in children, most of these lesions come to excisional biopsy, particularly if history of trauma is vague or absent.
Finally, trauma may simply call attention to a pre-existing lesion. A firm, discrete, nontender mass discovered immediately after relatively minor trauma has almost certainly been present for some time and is unrelated to the injury.
Nonneoplastic discrete masses. A variety of mastopathies may produce masses in any area of the breast of postmenarchal girls. These lesions are usually small, somewhat circumscribed, and mobile. They are sometimes tender, and pain and tenderness may increase with menses. They may be multiple or bilateral, and they may be difficult to distinguish clinically from fibroadenomas. If they remain small and show a clear relationship to the menstrual cycle, observation is proper. Slow, steady growth usually leads to surgical excision. Histologic findings in this heterogeneous group of lesions include periductal fibrosis, cystic ductal hyperplasia, sclerosing adenosis, and lobular hyperplasia.18,20
Solitary cysts of the breast may appear at any age. They tend to be small, firm or obviously cystic, subareolar, and mobile except for some fixation to the undersurface of the nipple. They may be asymptomatic or painful and tender. A watery, milky, brownish, or even frankly bloody discharge, is not uncommon. Simple cysts, blue-domed cysts, and galactoceles, as well as other types of cysts, have been reported.18,21,22 Excision is generally advisable.
Fibrocystic disease (cystic mastitis), a common lesion among young adult women, is infrequently seen in adolescent girls, never in boys or prepubertal girls. The disease is characterized by diffuse bilateral lumpiness, cordlike thickenings, and distinct areas of more prominent enlargement representing one or more cysts. The disease may be unilateral or even localized to one segment of a breast, particularly in the early stages. Pain and tenderness tend to increase before each menses. Physical findings may also change from month to month as cysts enlarge and collapse. The inflammatory nature of this disease and its relationship to the menstrual cycle are clearly established. Some sort of hormonal imbalance is postulated but not documented. The cyclic nature of the process and the changing physical signs usually make the diagnosis obvious. Biopsy or excision is indicated if a particular area is unusually hard or fixed or enlarges progressively, since there is evidence that the disease, if not truly premalignant, is associated with an increased risk of cancer. The rarity of malignancy among teenagers supports an even more conservative approach of prolonged observation in this age group than is appropriate for the adult woman. An alternative approach to an expanding breast mass in a patient with fibrocystic disease is to attempt aspiration of the mass. If clear fluid is obtained and the mass disappears, surgery can be avoided. Absence of malignant cells on cytologic examination of the fluid is reassuring.
Benign tumors. Fibroadenoma is by far the most common breast mass in childhood; it occurs more frequently than all other breast masses combined. In one series of children, fibroadenoma accounted for over 90 per cent of excised breast lesions.This tumor occurs primarily in young adult women, but it has been reported in girls a year or two before the onset of puberty and is seen with increasing frequency through the teenage years.23,24 Fibroadenomas are firm, freely mobile, and clearly demarcated from the surrounding breast tissue. They are most commonly located in the upper outer quadrant but can occur anywhere in the breast.23 They are asymptomatic except for occasional tenderness. The tumor is usually discovered accidentally by the girl or by her physician during routine physical examination. Ten to 25 per cent of patients have multiple or bilateral tumors, which may be concomitant or occur serially.18,23,24 Growth is usually slow but steady; the average size at time of discovery is 2-3 cm. Enlargement may be very rapid at times, especially in adolescent girls, and these tumors may become very large, as great as 10-15 cm., and involve an entire quadrant of the breast.18·23,25·26 Large, rapidly growing tumors may appear to be fixed to the skin but never to the pectoral fascia. Hemorrhage may occur into the rapidly enlarging lesion.
Fibroadenomas are well encapsulated and easily distinguished from the surrounding breast tissue. The surface is firm, bulging, grayish white, and homogeneous. Histologically, there is proliferation of the periductal and perilobular fibrous tissue and proliferation and increased branching of the ducts, all forming a compact encapsulated mass (Figure 10). Lobule formation is usually absent. The large, rapidly growing tumors are characterized by more marked increase in the fibrous tissue stroma, which may have a loose myxomatous appearance. The similarity to juvenile hypertrophy is striking; at times the lesions can be separated only by the clinical observation that fibroadenomas are discrete and encapsulated, while juvenile hypertrophy is almost always diffuse and nonencapsulated. At the other end of the spectrum, rapidly growing fibroadenomas may be hard to distinguish from cystosarcoma phylloides.25
The cause of fibroadenoma is unknown, but it is clearly related to hormonal activity. There is clinical and experimental evidence that these tumors are stimulated by estrogen.23 Endocrine evaluation yields consistently normal results, however; as with so many breast lesions, an increased sensitivity to hormonal action is postulated. Administration of various hormones has not altered the course of fibroadenoma or prevented recurrence.
Fibroadenomas should be excised when they are discovered, primarily because continued growth causes marked asymmetry and distortion of the breasts. Excision of the mass and cosmetic reconstruction of the breast are then much more difficult. Small tumors are easily excised, with a margin of normal breast tissue, through a short incision in the skin lines overlying the lesion. There is little cosmetic deformity. A second indication for early excision is to prevent the development of fibrosarcoma, which has been reported in adults - usually in long-standing, neglected tumors.
In some cases, a young girl will have multiple bilateral fibroadenomas, which recur at the rate of several a year (fibroadenomatosis). To avoid frequent and repeated operations, it may be reasonable to follow such a patient carefully and remove only those tumors that grow rapidly. At the end of adolescence, a period of quiescence can be expected; at this time all or most of the remaining tumors can be excised.
Cytosarcoma phylloides is closely related to fibroadenoma. Despite its ominous name, it is usually a benign tumor. Treves and Sunderland27 reported 77 patients; 41 tumors were benign, 18 borderline, and 18 malignant. Cystosarcoma phylloides is even more likely to be benign in the teenage girl. About 40 cases have been reported in girls under 20 years of age; only two have been malignant.28 Neither patient had metastases, and both were cured by surgical removal of the tumor. This lesion has not been reported in boys or prepubertal girls, although in a few cases the mass first appeared several months before menarche.
Figur· 10. High-power microphotograph of a fibroadenoma. Note the marked hypertrophy and hyperplasia of the ducts, increased fibrous tissue, and compact fibrous capsule.
In the adolescent, cystosarcoma phylloides tends to be a rapidly growing tumor, often reaching a size of 15-20 cm. in a few months.23·28 Size and growth alone do not distinguish it from fibroadenoma, however, since giant fibroadenomas may have grown rapidly and some cystosarcomas may grow slowly or be discovered and removed before becoming large. The tumors are hard and often irregular, but they are discrete and not fixed to the deep fascia. Some degree oí skin fixation may occur, and rapid growth may produce skin stretching, desquamation, and dilatation of cutaneous veins. Actual skin involvement and ulceration are seen only in longstanding, neglected cases.28 Lymphadenopathy is rare. A serous or even bloody discharge from the nipple is not uncommon and does not imply malignancy. The tumor may be multiple or trilateral; more commonly, a second mass in the same or opposite breast proves to be a fibroadenoma.28
The diagnosis of cystosarcoma phylloides can be made only by the pathologist. The histologic appearance is similar to that of fibroadenoma but is characterized by greater hypertrophy and more marked cellularity of the fibrous tissue stroma.27 Malignant change. when present, is confined to the connective tissue, and only these elements metastasize, usually by the hematogenous route.
The treatment of cystosarcoma phylloides is surgical excision at the time of discovery. Recurrences have been reported, and there is clearly a possibility of malignancy, so enucleation is inadequate. On the other hand, complete sacrifice of the adolescent's breast is inappropriate for this usually benign tumor. Local excision, with a generous margin of normal breast tissue, is preferred and has been adequate in reported cases.25·28 The tumors are usually encapsulated or well demarcated from the surrounding breast tissue. Careful follow-up to detect recurrences is essential. Appropriate treatment of histologically malignant cystosarcoma is unknown. Of the two reported cases, one patient was alive and free of disease one year after radical mastectomy;29 the other underwent local excision, followed in six months by excision of a recurrence, and was alive and well three years later.30 Simple mastectomy is probably the best choice. Radical mastectomy is not logical, since metastases, when they occur, are almost exclusively hematogenous.
Intraductal papillomas are occasionally seen in adolescent girls,18 rarely in prepubertal children.31 A bloody nipple discharge or a small vague mass usually calls attention to the lesion. The mass is generally subareolar but may be more peripheral. Pain and tenderness are uncommon. Local excision of the involved duct, sparing the rest of the ductal system, is curative.
Other benign tumors of the breast or adjacent tissue are occasionally encountered. Lipomas, which may arise within the breast or from the soft tissue overlying the breast, are recognized by their soft and spongy character. Keratomas and papillomas may develop from the squamous epithelium at the nipple or areola. Hemangiomas and lymphangiomas of the breast or adjacent tissue are present at birth or appear early in infancy. Hemangiomas, which tend to enlarge for a few months and then gradually involute over a period of years, should not be excised. Lymphangiomas may require removal, but the dissection should be very limited to avoid permanent injury to the breast bud.
Granular cell myoblastoma is a bizarre benign tumor of neural origin that characteristically appears as a rock-hard, irregular soft- tissue mass. The breast area is a common site of these tumors in adult women.32,33 A few have been reported in adolescent girls. I have seen a six-year-old girl with a typical granular cell myoblastoma arising in the areola. The stony hardness of these tumors and their unusual histologic appearance, especially on frozen section, has led to the erroneous diagnosis of malignancy and unnecessary mastectomy in a number of patients.32 The origin of the tumor from the soft tissue over the breast and the lack of fixation to deep structures are clues to the diagnosis, which should be made by examination of permanent histologic sections. Wide local excision is adequate therapy.
Malignant tumors. Cancer of the breast in children is very uncommon. Table 1 summarizes the 33 cases that have been described in reasonable detail in the literature from England.18·34·57 The rarity of this lesion is also illustrated by perusal of several large series of breast cancer. Harrington found only five girls under age 20 among 5,105 patients with breast cancer at the Mayo Clinic;58 Norris, only two of 5,000 women;59 and McDivitt, seven of 10,000. 51 Williams reported only one child with a malignant breast tumor among 181 cases of childhood cancer in London.45 We have not seen a child with breast cancer at our hospital in the past 10 years, although we operate on about 15 patients a year under the age of 20 for various breast lesions.
CARCINOMA OF THE BREAST IN CHILDREN
CARCINOMA OF THE BREAST IN CHILDREN
Although the total number is small, certain conclusions can be drawn from the data in Table 1. Children of almost any age, except infants, can be affected. The youngest child was three years old. If one arbitrarily chooses age 12 as the approximate average age of puberty, slightly more than half of the cases (19 of 33) occurred in prepubertal children. Right and left breasts were equally affected. One patient had bilateral synchronous disease, and two patients developed recurrences, or second primaries, in the opposite breast. All patients had a hard mass that was most commonly subareolar and frequently fixed to the deep tissues. Symptoms were uncommon, although a few patients complained of pain and tenderness. Axillary lymphadenopathy was present in a few cases. No patient had clinical evidence of endocrine dysfunction, precocious puberty, or any other abnormal physical or laboratory findings. The mass had been present for one day to seven years. Obvious metastatic disease was present in only one patient at the time of diagnosis. About half the patients were operated on within six months of discovery of the lesion. Masses that had been present for several years were said to have grown slowly; sudden, rapid enlargement sometimes prompted the patient to seek medical attention. Presumably, tumors that grew rapidly from the outset were removed earlier. Twelve per cent (four of 33) of the patients were male, a much higher percentage than among adults. The most common cell type was adenocarcinoma (27 of 33). The remaining six patients had a variety of carcinomas.
Treatment of these patients varied greatly, no doubt reflecting physician bias and local standards of the time. Primary therapy consisted of local excision in 14, simple mastectomy in seven, radical or modified radical mastectomy in 10, and biopsy and irradiation only in two patients with advanced disease. Radiotherapy was added initially in two patients in each mastectomy group. Several patients received radiotherapy and/or combination chemotherapy for treatment of recurrences without any consistent beneficial effect.
Adequate follow-up information of at least three years' duration was recorded for 23 of the 33 patients, and all the survival statistics are based on this group. Fifteen of the 23 patients (65 per cent) survived during follow-up periods of three to 27 years. One woman died of a primary pleural mesothelioma 27 years after mastectomy for breast carcinoma, but is counted as a survivor because of the long disease-free interval and the absence of any breast cancer at autopsy. Seven children died of their disease - most within a year of diagnosis, although one died at four and a half years and one at 10 years. One boy died suddenly shortly after local excision of an adenocarcinoma. An autopsy was not obtained, and the cause of death is not known.
Survival was clearly related to age. Eleven of 12 children (92 per cent) under age 12 survived, while only four of 11 teenagers (36 per cent) lived. A significant difference in survival according to mode of therapy was also apparent. Local excision led to survival in seven of nine (78 per cent), simple mastectomy in five out of five, and radical mastectomy in three out of eight (38 per cent); irradiation alone was unsuccessful in one patient. There was, however, a preponderance of radical mastectomies among the teenagers; within this age group no significant difference in survival was found between radical mastectomy and local excision. Thus, the advantage of local excision is probably not real. Further examination oí the data also reveals that, of the total group, eight patients had recurrences several months to four years after the original treatment. In six cases, recurrence followed initial locai excision, and all of these patients then underwent mastectomy. Two patients had recurrence after radical mastectomy, and both died within months. There were no recurrences following simple mastectomy.
Cell type also has a bearing on survival. Fourteen of 19 patients (74 per cent) with adenocarcinoma survived, but only one of four with other cell types lived. Of interest in this regard is a report by McDivitt51 of seven girls with adenocarcinoma of the breast, all of whom survived. AU tumors had a similar histologic pattern, characterized by intensely eosinophilic cytoplasma and an abundance of eosinophilic secretory material in the cells and ductlike spaces among the cells. Subsequent authors have also emphasized the favorable prognosis of tumors with this histologic appearance.18·53'56
It is difficult and hazardous to base therapeutic decisions on such fragmentary data. Certain conclusions do seem warranted, however. The prognosis of carcinoma of the breast in prepubertal children is clearly better than in adults. Among teenagers, survival is about the same as for adults. Generous excisional biopsy of hard breast masses should be performed promptly. Considering the rarity of the lesion, the diagnosis of carcinoma should be made only by examination of permanent histologic sections. Evaluation by two or more pathologists is desirable. If the patient is prepubertal or if the histology shows a typical glandular pattern with prominent eosinophilic secretory material, as described by McDivitt, no further treatment may be necessary. Simple mastectomy has consistently given the best results, however, and is the procedure of choice for most patients, including all teenagers. If the patient or family refuses mastectomy, adequate local excision with careful follow-up is an acceptable alternative, although about half of these patients will ultimately require mastectomy as a result of recurrence. Radical mastectomy has not afforded any better results and, since it is such a mutilating procedure, has little place in the treatment of breast tumors in children.
The role of radiotherapy in childhood breast cancer cannot be determined from the available data. Radiotherapy has proved to be a valuable adjunct in the treatment of breast cancer in adults. Although it is risky to apply data from adult experience to children, it seems reasonable to consider the use of radiation in older children and those who refuse mastectomy.
The treatment of metastatic disease is also largely speculative and based on experience with adults. Combination chemotherapy, oophorectomy, adrenalectomy, and hypophysectomy should be considered in selected patients, although the longterm effects of such ablative procedures in children are unknown.
Primary sarcomas of the breast are even rarer than carcinomas; about 20 cases have been reported in children.4*60,61 Fibrosarcoma and liposarcoma are the most common types, but sarcomas may arise from any mesodermal element. They tend to be large, bulky, hard, slowgrowing tumors. Fixation to surrounding tissues occurs late. Wide local excision of small tumors and simple mastectomy for large lesions are probably the most appropriate procedures. As with carcinoma, the prognosis appears to be better than in adults.60
The breast may be affected by systemic malignancies, including lymphoma, Hodgkin's disease, leukemia, and multiple myeloma.4*62·63 Usually the diagnosis is already apparent, but occasionally unilateral or bilateral breast masses are the first manifestation.62 Excisional biopsy and histologic examination will lead to the correct diagnosis and treatment. Extensive resection of the breast lesions is not indicated.
The breast may also be the site of metastatic deposits from various cancers, especially melanoma and rhabdomyosarcoma.18·64 The breast lesion is rarely the first manifestation of an occult primary.
CLINICAL EVALUATION OF THE CHILD WITH BREAST ENLARGEMENT
The breasts have great psychologic significance, and the possibility of an abnormality in breast development arouses great anxiety. Gentle and patient questioning, examination, and explanation are essential to allay unnecessary fear. The child and parents should be encouraged to ask questions and vent their feelings.
A careful history should be obtained about the onset of the mass or enlargement, rate of growth, nipple discharge, local or systemic symptoms, and the possibility of trauma. A history of exposure to drugs or hormones (including birth control pills) should be sought. In older girls, the age of menarche and the menstrual history are important.
A complete physical examination should be performed. Girls over the age of about 10 years should be appropriately gowned and examined in a private room in the presence of the mother or another woman. The location and character of the breast lesion should be carefully defined, and the opposite breast examined and compared. Lymphadenopathy, other masses, and any evidence of sexual maturation are especially important to note. Extensive laboratory and radiologic examinations are not necessary except in certain situations to be noted below.
The child's age and sex are helpful in formulating a preliminary differential diagnosis, which can be refined on the basis of the history and physical examination. Table 2 lists the various causes of breast enlargement by age and sex in descending order of frequency. Soft subareolar swelling of the infant's breast is almost certainly an effect of maternal hormones and is a transient phenomenon. Local or systemic signs of inflammation suggest mastitis. Tumors are very rare and are typically discrete and hard.
RELATIVE FREQUENCY OF BREAST ENLARGEMENTS BY SEX AND AGE
In preschool and school-age children, soft subareolar swelling of one or both breasts is also most likely to be transient overgrowth of normal breast tissue and requires no treatment. The family can be reassured that this is a common event of no great significance. Trauma and infection may cause more acute and localized breast enlargement in this age group.
Greater degrees of soft and diffuse breast development, whether bilateral or unilateral, in girls over eight years of age should be assumed to be normal pubertal growth. Reassurance and periodic re-examination are all that is necessary. In a younger girl, such development is considered to be premature thelarche. If there are no other signs of physical maturation and Papanicolaou examination of vaginal epithelial cells shows little estrogen effect, these girls can be safely followed. There is no specific therapy for premature thelarche; surgery is contraindicated. These girls may require considerable emotional support, since they are so obviously different from their playmates.
If other signs of sexual maturation are present or appear subsequently, a diagnosis of precocious puberty is made. Complete endocrine evaluation and a search for occult adrenal or ovarian tumor are indicated. Most cases are idiopathic, and no specific therapy is available. Emotional support and education are of utmost importance, especially for girls who ovulate and could become pregnant. Diffuse breast enlargement in the prepubertal male (gynecomastia) should also prompt complete evaluation, because of the possibility of occult tumor. Surgical resection of the hypertrophied breast tissue may be indicated.
Tumors, benign or malignant, are the least common cause of breast enlargement in this age group. They are usually identifiable as discrete hard masses and should be removed.
Gynecomastia is overwhelmingly the most common cause of breast enlargement in the adolescent boy. It is so common that endocrine evaluation is not indicated unless there are other physical findings to suggest another diagnosis, such as Klinefelter' s syndrome. Although the disorder is self-limited, boys with pronounced breast enlargement may benefit from subcutaneous mastectomy. Inflammatory lesions and tumors are infrequently noted.
SURGICALLY REMOVED BREAST LESIONS IN ADOLESCENT GIRLS
Adolescent girls have the greatest incidence of significant breast lesions, no doubt reflecting the intense hormonal stimulation associated with maturation. Table 3 summarizes the relative frequency of breast masses in adolescent girls in three reported series and our own experience. Fibroadenoma was by far the most common lesion. Intraductal papillomas and other benign tumors were occasionally seen. Various mastopathies, including cysts and fibrocystic disease, formed the second largest group. Inflammatory masses from infection, fat necrosis, and trauma were less common. Juvenile hypertrophy and malignant tumors were rare.
A rational plan for treatment of breast masses in adolescent girls can be formulated on the basis of these observations. Benign tumors should be excised, since they tend to enlarge and distort the breast and have a small - but real - malignant potential. Most forms of mastopathy, except fibrocystic disease, should* also be excised, to relieve symptoms and prevent further growth. Inflammatory lesions are usually selflimited and need not be removed. Fibrocystic disease, which may be increasing in frequency among teenagers, is a diffuse chronic disease that cannot be controlled surgically. All too often, these patients undergo several operations as new areas of disease appear. Every effort should be made to avoid unnecessary procedures.
Since there is considerable overlap in the clinical presentation of these lesions, a single examination may not suffice to ensure a correct diagnosis. Frequent re-examination over a period of two or three months will often clarify the diagnosis. Benign tumors and most mastopathies remain unchanged or grow slowly, so nothing is lost by the delay in removing them. Malignant tumors are rare and tend to be less aggressive in children. A brief period of observation is not likely to affect the prognosis. Infections will either resolve or become obvious, and they can be treated appropriately. Masses resulting from trauma or fat necrosis may gradually subside. If a mass persists, excision is indicated. Fibrocystic disease characteristically waxes and wanes, with an increase in symptoms and the size of masses before each menses. Masses may disappear as cysts collapse, while new lesions appear in other areas of either breast. Aspiration of suspected cysts may be helpful in establishing the diagnosis. Mammography, xeroradiography, and thermography have not been used extensively in young girls, but they have proved useful in distinguishing fibrocystic disease from tumors in adults. Despite these precautions. many patients with fibrocystic disease will come to biopsy. Excision of persistent or enlarging masses is indicated.
Massive diffuse enlargement of the breasts in adolescent girls is most likely juvenile hypertrophy. Because of the huge size of these breasts, reduction mammoplasty or mastectomy is frequently necessary. Lesser degrees of enlargement may represent juvenile hypertrophy or macromastia. These girls may seek reduction mammoplasty for cosmetic reasons, but the procedure should be deferred until full skeletal growth is achieved, since, at the end of adolescence, juvenile hypertrophy may regress somewhat and obviate the need for operation.
Alteration in the hormonal milieu is a recurrent theme in breast lesions in children. Abundant circumstantial evidence suggests a cause-and-effect relationship. Our knowledge of the hormonal regulation of normal breast development is rudimentary, however, and concepts of abnormalities or imbalances causing specific disease are largely speculative. A few preliminary reports suggest that hormone therapy may be helpful in certain breast lesions, but at present no specific drug or hormone therapy can be recommended.
The vast majority of breast enlargements in children and adolescents can thus be managed by reassurance and careful follow-up or by simple local excision after a brief period of observation. Whenever possible, excision should be performed through a circumareolar incision, which leaves virtually no cosmetic defect. Gynecomastia in the male, central masses, and virtually all lesions in the undeveloped breast can be resected adequately through a curved incision along the junction of the areola with the skin overlying the ...
CARCINOMA OF THE BREAST IN CHILDREN
CARCINOMA OF THE BREAST IN CHILDREN
RELATIVE FREQUENCY OF BREAST ENLARGEMENTS BY SEX AND AGE
SURGICALLY REMOVED BREAST LESIONS IN ADOLESCENT GIRLS