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Case Records of the Massachusetts General Hospital

Founded by RichardC. Cabot

EricS. Rosenberg, M.D., Editor NancyLee Harris, M.D., Editor
JoAnneO. Shepard, M.D., Associate Editor AliceM. Cort, M.D., Associate Editor
SallyH. Ebeling, Assistant Editor EmilyK. McDonald, Assistant Editor

Case 12-2016: An 8-Year-Old Boy

with an Enlarging Mass in the Right Breast
Madhusmita Misra, M.D., M.P.H., Pallavi Sagar, M.D.,
AlisonM. Friedmann, M.D., DanielP. Ryan, M.D., and DennisC. Sgroi, M.D.

Pr e sen tat ion of C a se

Dr. Charumathi Baskaran (Pediatrics): An 8-year-old boy was seen in an outpatient From the Departments of Pediatrics
clinic of this hospital because of an enlarging mass in the right breast. (M.M., A.M.F.), Radiology (P.S.), Pediatric
Surgery (D.P.R.), and Pathology (D.C.S.),
One week before this presentation, the patient was seen by a pediatrician at Massachusetts General Hospital, and the
another medical facility for a routine annual examination. He had a history of a Departments of Pediatrics (M.M., A.M.F.),
mass in his right breast that had been present for 18 months and had recently Radiology (P.S.), Pediatric Surgery (D.P.R.),
and Pathology (D.C.S.), Harvard Medical
enlarged. On examination, a round, mobile mass was palpable under the right School both in Boston.
areola. He was referred to the pediatric endocrinology clinic of this hospital.
N Engl J Med 2016;374:1565-74.
One week later, at the visit to the endocrinology clinic, the patients parents DOI: 10.1056/NEJMcpc1503831
reported that, approximately 18 months earlier, they had noted a mass under the Copyright 2016 Massachusetts Medical Society.

right nipple that was not associated with discharge. The mass had reportedly en-
larged in the 6 months before this presentation, and growth of fine pubic hair was
also noted. The patient had seasonal allergies and eczema and was otherwise well.
He had a history of normal growth and development. His only medication was
topical triamcinolone cream for eczema; his childhood vaccinations were current.
He had no known allergies to medications. He lived with his parents and younger
sibling and was doing well in second grade. His maternal grandfather had asthma,
his maternal grandmother had hypercholesterolemia, and his paternal grand-
mother had breast cancer (which had been diagnosed when she was 70 years of
age); his parents and younger sibling were healthy.
On examination, the patient did not have dysmorphic features. The blood
pressure was 110/70 mm Hg, the pulse 86 beats per minute, the height 131 cm
(68th percentile), the weight 28.4 kg (72nd percentile), and the body-mass index
(BMI; the weight in kilograms divided by the square of the height in meters) 16.5
(66th percentile). The abdomen was soft and had some palpable bowel loops. A firm,
mobile mass (2 cm by 2 cm) was present under the right areola and was not adher-
ent to the skin. A small amount of soft breast tissue was palpable on the left side.
Fine, straight, lightly pigmented hairs were present on the lower mons pubis, and
on close inspection, very scant fine, light axillary hairs were also present. The
testes had an estimated volume of 3 ml; the phallus was prepubertal. The remain-
der of the examination was normal. Findings on a radiograph of the left hand were

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 1. Laboratory Data.

of the diagnosis. This otherwise healthy 8-year-
old boy presented with a right subareolar mass
Reference 8 Days after that had been present for 18 months and had
Range, Presentation,
Variable Age-Adjusted* 8 a.m.
enlarged during the 6 months before presenta-
tion. When evaluating a boy with breast enlarge-
Thyrotropin (U/ml) 0.504.30 2.81 ment, diagnostic considerations include gyneco-
Free thyroxine (ng/dl) 0.91.6 1.2 mastia, benign breast lesions, and cancer.
Dehydroepiandrosterone sulfate (g/dl) <91 31
Total testosterone (ng/dl) 42 <1 Gynecomastia
Follicle-stimulating hormone (U/liter) <3.00 <0.05 When evaluating this child for possible gyneco-
mastia, we first needed to determine whether
Luteinizing hormone (U/liter) 0.46 <0.02
the mass could be pseudogynecomastia, which
Estradiol (ultrasensitive) (pg/ml) 4 <2
is caused by the accumulation of fatty tissue and
Estrone (serum) (pg/ml) <10 17 little or no glandular breast tissue under the
Human chorionic gonadotropin (mIU/ml) <5 <2 areolae, or true gynecomastia, which is caused
by the benign proliferation of glandular tissue of
* Reference values are affected by many variables, including the patient popu
lation and the laboratory methods used. The ranges used at the commercial the male breast and is typically manifested by
laboratory are age-adjusted for patients who are not pregnant and do not have a rubbery, mobile, and often tender subareolar
medical conditions that could affect the results. They may therefore not be mass.1 Pseudogynecomastia occurs in obese per-
appropriate for all patients.
Reference value is for boys who are 0 to 9 years of age (prepubertal). sons and is usually bilateral; therefore, it is un-
Reference value is for boys who are 8 to 9 years of age. likely in this patient, who had a normal BMI and
a unilateral mass that was firm on palpation and
distinct from adjacent subcutaneous adipose tis-
consistent with a bone age of 8 years. Eight days sue. True gynecomastia may be physiologic or
after this visit, laboratory tests were performed; pathologic1,2 and occurs when the ratio of testos-
the test results are shown in Table1. Thirteen terone to estrogen decreases3; pathologic causes
days after this visit, imaging studies of the chest of this altered hormonal balance include expo-
were performed. sure to certain drugs or herbal compounds, de-
Dr. Pallavi Sagar: Ultrasound examination of the creased testosterone secretion or action, or in-
right breast (Fig.1) revealed a well-circumscribed, creased estrogen production.
oval-shaped, relatively hypoechoic, mobile mass
(measuring approximately 1.4 cm by 1.3 cm by Physiologic Pubertal Gynecomastia
0.8 cm) with through-transmission in the retro Physiologic pubertal gynecomastia occurs in up
areolar region. The mass had smooth peripheral to 65% of boys. It begins during early puberty,
margins and was superficial to the pectoralis peaks at 13 to 14 years of age, and regresses
muscle; its long axis was parallel to the skin and spontaneously in up to 90% of affected boys.
horizontal in orientation. On color Doppler im- The condition may cause tenderness and be
aging, the mass was relatively hypovascular and more marked in one breast than the other. In
had minimal peripheral-blood flow. The mass did patients with pubertal gynecomastia, early mat-
not have irregular spiculated margins, calcifica- uration of aromatase (which catalyzes the con-
tions, or increased vascularity, features that are version of gonadal and adrenal androgens to
typically seen in aggressive cancerous lesions. estrogens) allows estrogen to reach adult levels
Examination of the contralateral breast revealed while androgen levels are still pubertal; conse-
a normal left breast bud. quently, the balance of androgens and estrogens
Dr. Baskaran: Diagnostic procedures were per- favors the proliferation of glandular tissue in the
formed. breast.
Pubertal gynecomastia is common but was
unlikely to be the diagnosis in this patient, who
Differ en t i a l Di agnosis
had not yet begun true puberty. The presence of
Dr. Madhusmita Misra: All the discussants were pubic hair indicated that he had attained adre-
involved in the care of this patient and are aware narche, which is characterized clinically by the

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 Case Records of the Massachuset ts Gener al Hospital

A B

C D

Right Left
Figure 1. Ultrasound Images of the Breasts.
Ultrasound images of the right breast, obtained in transverse and sagittal planes (Panels A and B, respectively), show
a wellcircumscribed, oval mass with smooth margins in the right retroareolar region; the mass is more wide than
tall (i.e., the transverse diameter is greater than the anteroposterior diameter). A color Doppler image (Panel C)
shows that the mass is relatively hypovascular and has minimal peripheralblood flow, as well as throughtransmission
(arrow). A sidebyside comparison of the right breast and the left (normal) breast (Panel D) shows the mass in the
right breast (asterisk) and the normal left breast bud (arrowhead).

appearance of axillary odor, axillary hair, and
pubic hair and biochemically by rising levels of
dehydroepiandrosterone sulfate and androstene-
dione. However, he had not yet entered true or
central puberty (gonadarche). The onset of gona-
darche is marked by an increase in the ampli-
tude and frequency of pulses of gonadotropin-
releasing hormone, which stimulates pulsatile
secretion of follicle-stimulating hormone and
luteinizing hormone from the anterior pituitary,
which in turn stimulate spermatogenesis and
secretion of testosterone from the Leydig cells of
the testes. Consequently, gonadarche is associ-
ated with rising levels of testosterone and with
increased testicular volume (>3 ml), and neither
feature was observed in this patient.
Pseudogynecomastia and physiologic pubertal
gynecomastia have been ruled out on the basis
of the patients history and physical examina-
tion. Therefore, a diagnostic evaluation for causes
of pathologic gynecomastia should be under-
taken (Fig. 2).

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 1568
Take family history and history of drug exposure
Perform examination to determine pubertal status and testicular size and symmetry
Perform laboratory tests of liver function, thyroid function, and serum levels of LH, FSH, hCG, T, E2, E1, DHEAS, and A

Increased hCG Increased LH Decreased or Decreased Increased LH Abnormal liver

Normal results
level and FSH levels, normal LH or normal and T levels function
decreased level, decreased LH level,
T level T and E2 levels increased
E2 and E1 levels Test for TSH Diagnosis: Diagnosis:
and T4 levels liver disease idiopathic
disease
Diagnosis: Diagnosis:
primary hypogonado-
gonadal failure tropic Increased T Normal levels Increased Normal TSH Increased T4
hypogonadism level of T and adrenal DHEAS and and T4 levels level, decreased
androgens A levels TSH level
The

Test for pro-

Perform lactin level and Perform Perform Perform adrenal Diagnosis: Diagnosis:
testicular perform cranial testicular testicular CT or MRI androgen hyperthyroidism
ultrasound imaging study ultrasound ultrasound insensitivity
(if necessary)

Mass present Mass absent Mass present Mass present Mass absent Mass present

Diagnosis: Diagnosis: Diagnosis: Diagnosis: Diagnosis: Diagnosis:

testicular extragonadal Leydig-cell Sertoli- increased adrenal tumor
tumor or cell tumor extraglandular
n e w e ng l a n d j o u r na l

germ-cell tumor germ-cell tumor

Sertoli-cell and aromatase

The New England Journal of Medicine

or hCG-
of

producing non- Leydig-cell activity

trophoblastic tumor
tumor
(hepato-

n engl j med 374;16nejm.org April 21, 2016

blastoma)

Copyright 2016 Massachusetts Medical Society. All rights reserved.

m e dic i n e

Perform
imaging study
of the abdomen,
chest, and head

Figure 2. Diagnostic Evaluation for Nonphysiologic Gynecomastia.

A denotes androstenedione, DHEAS dehydroepiandrosterone sulfate, E1 estrone, E2 estradiol, FSH follicle-stimulating hormone, hCG human chorionic gonadotropin, LH luteiniz
ing hormone, T testosterone, TSH thyroid-stimulating hormone, and T4 thyroxine. Data are adapted from UpToDate.1

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 Case Records of the Massachuset ts Gener al Hospital
Gynecomastia Due to Exposure to Drugs or Herbal
Compounds
Drugs and herbal compounds that cause gyneco-
mastia include estrogens and estrogen-like com-
pounds (e.g., tea tree and lavender oils and weak
estrogens and antiandrogens that are found in
certain lotions, soaps, and shampoos),4 drugs
that inhibit testosterone secretion or action (e.g.,
ketoconazole, spironolactone, androgen-receptor
blockers, metronidazole, cimetidine, and alkyl-
ating agents), drugs that increase endogenous
estrogen production (e.g., fertility-inducing ther-
apies), and other agents that operate through
unclear mechanisms (e.g., marijuana, heroin,
growth hormone, calcium-channel blockers, iso-
niazid, and tricyclic antidepressants).5 This pa-
tient had no history of exposure to any of these
compounds.
Gynecomastia Due to Decreased Testosterone
Secretion or Action
In patients with gynecomastia associated with
decreased testosterone secretion, the ratio of
testosterone to estrogen is decreased because
testosterone levels are low while aromatization
of adrenal androgens to estrogens occurs nor-
mally. Conditions that cause hypogonadotropic
hypogonadism (low gonadotropin levels) are
associated with low testosterone levels and are
typically diagnosed in patients who are older
than the normal age of pubertal onset (i.e., >14
years of age in boys). Earlier diagnosis is possible
in boys with microphallus or multiple pituitary-
hormone deficiencies, features that were not pres-
ent in this patient. Other causes of decreased
testosterone secretion include conditions associ-
ated with hypergonadotropic hypogonadism
(high gonadotropin levels), such as anorchia,
testicular trauma, mumps orchitis, use of alkyl-
ating agents, radiation to the testes, and disor-
ders of testosterone biosynthesis. Klinefelters
syndrome is another cause of hypergonadotropic
hypogonadism; when elevated gonadotropin lev-
els are found in a patient with gynecomastia, a
karyotype analysis should be performed to rule
out this sex-chromosome disorder. This patients
history and physical examination did not sug-
gest any of these causes of hypergonadotropic
hypogonadism, and the levels of follicle-stimu-
lating hormone and luteinizing hormone were
not elevated.
The androgen insensitivity syndrome is also
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associated with gynecomastia. However, unlike
patients with hypogonadotropic or hypergonado-
tropic hypogonadism, patients with the andro-
gen insensitivity syndrome have normal-to-high
testosterone levels. In the androgen insensitivity
syndrome, the decrease in the ratio of testoster-
one to estrogen is a consequence of aromatization
of increased testicular androgens to estrogens.
Similar to disorders of testosterone biosynthesis,
the partial androgen insensitivity syndrome may
cause genital ambiguity, which was not present
in this patient.
Gynecomastia Due to Increased Estrogen Production
Increased testicular production of estrogen and
resultant gynecomastia may occur in patients
with testosterone-secreting Leydig-cell tumors,
Sertoli-cell tumors (because of increased aroma-
tase expression), or human chorionic gonadotro-
pin (hCG)secreting germ-cell tumors (because
of increased testosterone secretion from Leydig
cells and increased aromatase activity). These
conditions are associated with reduced or sup-
pressed gonadotropin levels. This patient did not
have testicular asymmetry on examination, but
Leydig-cell tumors are typically small and their
detection may require ultrasonography. In addi-
tion, extragonadal hCG-secreting tumors (germi-
nomas, teratomas, and hepatoblastomas) can
cause gynecomastia. However, the normal estra-
diol, hCG, and gonadotropin levels in this pa-
tient rule out these causes.
In persons with ovotesticular disorder of sex
development, who have both ovarian and testic-
ular tissue, gynecomastia develops because of
pubertal activation of estrogen secretion from
functional ovarian tissue. This patient had un-
ambiguous external genitalia and a prepubertal
estradiol level, features that essentially rule out
the diagnosis of ovotesticular disorder of sex
development.
Increased extragonadal aromatization of an-
drogens can also lead to increased estrogen
levels and gynecomastia. This can occur in per-
sons with hyperthyroidism, obesity (since adipose
tissue is a site of aromatization), increased avail-
ability of androgenic substrates for peripheral
aromatization (e.g., due to the presence of femi-
nizing adrenal tumors that produce adrenal an-
drogens or the presence of liver disease with
decreased extraction of androgens), or exposure
to exogenous aromatizable androgens (e.g., the
1569
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anabolic agents used by bodybuilders). This pa-
tient did not have the phenotypic or biochemical
profiles suggestive of any of these conditions.
Finally, activating mutations of the aromatase
gene cause familial prepubertal gynecomastia,
which occurs at adrenarche and is associated
with a markedly elevated estrone level.6-9 The
estrone level in this patient was only minimally
elevated.
Benign Breast Lesions
Benign breast lesions, which occur rarely in chil-
dren, include breast abscesses (which are char-
acterized by induration, erythema, tenderness,
and fluctuance), intraductal cysts and papillo-
mas (which are associated with bloody nipple
discharge), fibroadenomas (which most fre-
quently occur in the upper outer quadrant of the
breast and are firm and well-circumscribed),
and phyllodes tumors (which typically enlarge
rapidly and are painless and may be either be-
nign or malignant). Although the findings on
this patients imaging studies were consistent
with a benign lesion, the mass was located be-
hind the areola, had not increased rapidly in
size, and was not associated with signs of in-
flammation or nipple discharge, and thus all
these conditions were unlikely. Lipomas, hem-
angiomas, and lymphangiomas may also be Unilateral breast mass, possibly due to breast
manifested by breast masses and should be cancer.
considered.
Breast Cancer
Primary breast cancer in children is exceedingly
rare; only 0.1 to 0.3% of all breast cancers occur
in the pediatric age group. Approximately 80%
of primary breast cancers in children are secre-
tory carcinomas, which is an unusual histologic
tumor type among adults with breast cancer.10,11
Secretory carcinomas are slow-growing, and al-
though approximately 10% of affected patients
have nodal involvement at the time of diagnosis,
the prognosis is typically good. Primary breast
cancers that occur in children less commonly
and behave more aggressively than secretory
carcinomas include medullary and inflamma-
tory carcinomas. In addition, metastases from
other primary cancers may cause breast masses;
in fact, this occurs more commonly than does
primary breast cancer in pediatric patients. The
risk of breast cancer in children is increased
after exposure of the chest to ionizing radiation,
including the radiation therapy that is adminis-
tered for the treatment of Hodgkins lymphoma;
this risk is higher among girls than among boys.
Gynecomastia has been associated with a slight
increase in the risk of breast cancer; however,
the overall risk among children with gyneco-
mastia remains low.12 In one case series, the
presence of unilateral gynecomastia increased
the risk of breast cancer,13 but other studies have
shown a lower risk.14,15 The risk of breast cancer
is increased among male patients with Klinefel-
ters syndrome16,17 and among persons with a
family history of BRCA2 gene mutations.17 This
patient did not have elevated gonadotropin levels,
which would suggest the presence of Klinefel-
ters syndrome, and his paternal grandmother was
the only relative known to have breast cancer.
The patients unilateral mass felt more firm
and circumscribed than would be expected with
pubertal gynecomastia, and an extensive endo-
crinologic evaluation was negative. Therefore, I
was concerned that this patient had breast can-
cer, and I referred him to a pediatric surgeon at
this hospital for an excisional biopsy.
Dr . M a dhusmi ta Misr as
Di agnosis
Pathol o gic a l Discussion
Dr. Nancy Lee Harris (Pathology): Dr. Ryan, would
you tell us what you found when you performed
the biopsy?
Dr. Daniel P. Ryan: We made an incision at the
junction of the areola and the skin and raised
the skin off the mass; the skin did not seem to
be infiltrated. There was a clear plane around the
mass and no extension into the deep muscle.
There were no palpable lymph nodes in the
axilla or supraclavicular area. The excised mass
was submitted for histopathological examination.
Dr. Dennis C. Sgroi: Gross inspection of the ex-
cised mass revealed a well-circumscribed, rubbery-
to-firm, vaguely lobulated mass, measuring 1.8 cm
by 1.2 cm by 0.8 cm, that abutted the surgical
resection margin (Fig.3A). On microscopic ex-
amination, the mass was fairly well defined and
consisted of a moderately differentiated invasive
ductal carcinoma showing a predominant solid

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 Case Records of the Massachuset ts Gener al Hospital

A B

1.8 cm

C D

Figure 3. Excisional-Biopsy Specimen of the Mass in the Right Breast.

A gross photograph of the excisional specimen shows a wellcircumscribed, tannish white, glistening, rubberyto
firm mass, measuring 1.8 cm by 1.2 cm by 0.8 cm, that abuts the resection margin (Panel A). The tumor consists of
a moderately differentiated invasive ductal carcinoma showing a predominant solid growth pattern with inter
spersed fibrous septae (Panel B, hematoxylin and eosin) and a minor microcystic and microglandular pattern (Panel
C, hematoxylin and eosin). The tumor cells have small nuclei with small nucleoli and abundant paletopink cyto
plasm (Panel C). The tumor cells, gland lumina, and microcystic spaces contain eosinophilic and amphophilic se
cretions with no glycogen (Panel D, arrows; periodic acidSchiff with diastase). Rather than sidebyside (intact)
NTRK3 signals, separate signals are visible, thus indicating the presence of a t(12;15)(p13;q25) translocation and
ETV6-NTRK3 gene fusion (Panel E, arrows; dualcolor breakapart fluorescence in situ hybridization in which the 3
end of the NTRK3 gene is labeled with a red fluorescent probe and the 5 end with a green fluorescent probe); this
finding supports the diagnosis of secretory carcinoma.

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 The n e w e ng l a n d j o u r na l
growth pattern with interspersed fibrous septae
and a minor microcystic and microglandular
pattern (Fig.3B). On cytologic examination, the
tumor consisted of cells with abundant pale-to-
pink cytoplasm and small, round nuclei contain-
ing small nucleoli and open chromatin. The tu-
mor cells, gland lumina, and microcystic spaces
contained eosinophilic and amphophilic secre-
tions (Fig.3C) that were positive on periodic
acidSchiff staining and resistant to diastase,
thus indicating the lack of glycogen and the
presence of mucopolysaccharide (Fig.3D).18 The
tumor had slight mitotic activity and did not
have lymphovascular invasion. Ductal carcinoma
in situ with cytomorphologic features identical to
those of the invasive carcinoma was present in
the excision specimen.
On immunohistochemical staining, the tumor
cells were positive for estrogen-receptor protein,
negative for progesterone protein, and negative
for HER2/neu overexpression; on fluorescence in
situ hybridization (FISH), HER2/neu gene ampli-
fication was not present. Taken together, the
cytomorphologic features were characteristic of
invasive secretory carcinoma, a rare variant of
invasive ductal carcinoma that accounts for less
than 0.15% of all diagnosed breast cancers.19-22
Because secretory carcinomas frequently harbor
the t(12;15)(p13;q25) translocation and ETV6-
NTRK3 gene fusion,23,24 dual-color break-apart
FISH24 was performed and revealed the charac-
teristic translocation (Fig.3E).
Discussion of M a nagemen t
Dr. Alison M. Friedmann: Because breast cancer is a
very rare diagnosis in pediatric patients, we con-
ferred with colleagues from the breast oncology
service at this hospital when planning this
childs care. Together we considered the need for
additional surgery and staging evaluation, the
role of adjuvant treatments such as radiation
therapy and systemic therapy, and eventually, the
best surveillance strategy for recurrence.
The available literature on secretory carcinoma
suggests that local excision is the preferred ini-
tial treatment in children.25 Because of the
positive margin in the excisional biopsy speci-
men, it was clear that further surgery was neces-
sary; we decided to proceed with mastectomy for
definitive surgical management. In the staging
evaluation, sentinel-lymph-node biopsy was indi-
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of m e dic i n e
cated for evaluation of the regional lymph
nodes, which would be the first possible sites of
metastasis.
Dr. Ryan: During this patients second opera-
tion, we removed skin and tissue around the
previous biopsy site. We performed a simple
mastectomy, removing all the subcutaneous tis-
sue, including the muscle fascia, but sparing the
muscle itself.
No studies have defined the optimal approach
for the staging of breast cancer in children, but
sentinel-lymph-node biopsy has become the
standard of care in adults without palpable axil-
lary lymph nodes. The method was developed to
allow less extensive removal of lymphatic tissue
in the axilla than that required for complete
lymphadenectomy, thus avoiding the complica-
tions of arm swelling, sensory loss, and shoul-
der problems. Sentinel-lymph-node biopsy has a
low rate of false negativity in the detection of
metastatic disease; rates of local control, overall
survival, and disease-free survival during 8 years
of follow-up have been reported to be equivalent
among patients who undergo sentinel-lymph-
node biopsy and those who undergo lymphade-
nectomy.26 The sentinel-lymph-node biopsy tech-
nique27 involves injecting a radiolabeled colloid
into the breast tumor or biopsy site; a gamma
detector is then used to identify the node with
the highest counts for removal. Some surgeons
also inject vital blue dye at the time of surgery to
add a visual aid to help identify the draining
node. In this patient, the sentinel lymph node
was identified with a gamma detector, and the
biopsy specimen was submitted for histopatho-
logical analysis. If metastatic carcinoma were to
be found in the biopsy specimen, lymphadenec-
tomy would be indicated to allow full disease
staging and inform a plan for adjuvant therapy.
Dr. Sgroi: Histopathological examination of the
mastectomy specimen revealed no residual in-
vasive or in situ secretory carcinoma, and there
was no evidence of carcinoma in the sentinel-
lymph-node biopsy specimen.
Dr. Friedmann: Because cancer was not identi-
fied in the sentinel-lymph-node biopsy specimen,
additional staging evaluation for distant meta-
static disease was not indicated. This form of
breast cancer has a natural history associated
with a favorable prognosis and there was no re-
sidual disease after the second surgery, and thus
we did not see a need for adjuvant therapy.28
 Case Records of the Massachuset ts Gener al Hospital

There are no data suggesting that radiation
therapy would be beneficial in this situation,
and radiation is associated with greater long-
term risks in children than in adults, both be-
cause it impairs the growth of normal musculo-
skeletal tissues and because children have a
longer period during which they are at risk for
radiation-induced second cancers. There are lim-
ited data regarding the role of systemic therapy
for secretory carcinoma, and systemic therapy
was not indicated in this patient with a favorable
prognosis and no evidence of systemic disease.
Three years after the patient received the diag-
nosis of breast cancer, he is doing well and has
no evidence of recurrent disease. He was seen
for follow-up every 3 months for the first year
after diagnosis and every 6 months for the sec-
ond and third years; we now plan to see him
annually. In addition to performing physical ex-
aminations at these visits, we have also checked
the serum levels of CA 15-3 and carcinoembry-
onic antigen; the levels of these tumor markers
were not measured before excision of the mass,
and pretherapy values are unknown, but the re-
sults have been stable and within the normal
reference ranges. Relapses after mastectomy are
very uncommon in patients with secretory carci-
noma, but when they do occur, they usually occur
at the local site within the first few years after
mastectomy.29,30 However, very late recurrences,
occasionally with distant metastases, have been
reported.31,32 In these cases, chemotherapy was
not effective.
Dr. Ronald E. Kleinman (Pediatrics): Can the
translocation that was seen in this patients
tumor be found in other tissues? Is he at risk
for tumors at other sites?
Dr. Sgroi: This translocation was actually first
identified in congenital fibrosarcomas and in
congenital cellular mesoblastic nephroma. It is a
sporadic genetic event rather than a germ-line
transmission event, and to my knowledge, it is
not seen in other tissues.
Dr. Ryan: Which patients with gynecomastia
should undergo endocrinologic evaluation?
Dr. Misra: Patients with prepubertal gyneco-
mastia, gynecomastia associated with delayed
pubertal onset, or gynecomastia with a pheno-
type that raises concerns about pathologic causes
should be evaluated by a pediatric endocrinolo-
gist. Pubertal gynecomastia is very common, so
we do not need to see every patient with gyneco-
mastia that develops shortly after the onset of
puberty. However, endocrinologic evaluation may
be warranted in boys whose pubertal gyneco-
mastia is pronounced.
Dr. Sgroi: Would you comment further on the
ultrasound findings? In my limited radiologic
experience, if the medial-to-lateral axis of a
mass is greater in length than the anterior-to-
posterior axis, then there is a greater likelihood
that we are dealing with a fibroadenoma than
with breast cancer.
Dr. Sagar: Ultrasonographic features that can
help differentiate benign masses from breast can-
cers include margins and orientation. Smooth,
well-circumscribed margins are indicative of be-
nign causes, whereas microlobulated, irregular,
spiculated margins raise concerns about cancer.
As you point out, a mass that is oriented with its
long axis parallel to the skin and that is more
wide than tall (i.e., has a greater transverse
diameter than anteroposterior diameter) is more
likely to be benign. The features observed in this
case on ultrasound examination were more typi-
cal of those seen with benign breast masses
than of those seen with breast cancers.
A nat omic a l Di agnosis
Secretory carcinoma of the breast.
Fina l Di agnosis
Secretory carcinoma of the breast.
This case was presented at Pediatric Grand Rounds.
Dr. Misra reports receiving grant support to her institution
from Genentech. No other potential conflict of interest relevant
to this article was reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.

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