Secretory Carcinoma of the Breast
F. A. TAVASSOLI, MD,’ AND H. J. NORRIS, MDt
Nineteen examples of a very rare type of carcinoma of the breast have been studied. The carcinoma is
unusual in that it has exaggerated secretory features previously reported only (with one exception) in
juveniles. But not all the patients in our series were juveniles; they ranged in age from 9 to 69 years
(median age, 25 years). Six were 30 years of age or older. Eighteen patients were female and 1 was a
9-year-old boy. Treatment varied from local excision of the tumor to radical mastectomy. Four of the
11 patients who had axillary node dissection had metastatic deposits showing the same secretory features
as the primary neoplasm. One of these 4 patients, a 25-year-old woman, died within ten months with
disseminated tumor. Because this distinctive pattern of carcinoma is not limited to children and adoles-
cents, we propose that it be called “secretory carcinoma.” Since, of the 19 patients, 4 (21%) had axillary
node metastases and 1 (5%) died with disseminated tumor, an extended simple mastectomy is recom-
mended as the inital treatment for patients more than 20 years of age.
Cancer 45:2404-2413, 1980.
I common variety of mammary carcinoma in children
which they designated “juvenile car~inoma.”~ Two
distinctive features characterize this neoplasm: 1) the
presence of large amounts of intracellular and extra-
cellular secretions; and 2) the granular eosinophilic
cytoplasm of the cells. These neoplasms had a less
aggressive behavior and a better prognosis in the 7
children reported than the usual breast carcinoma;
hence, a conservative surgical approach (local ex-
cision) was advocated as treatment. Since then, two
reports have described metastasis to axillary nodes and
one local re~urrence.~~~
Also, we have observed the
same pattern in adults. Therefore, we recommend that
the descriptive term “secretory carcinoma” replace
the designation of “juvenile carcinoma.” In order to
better define the clinical spectrum and behavior of this
distinct entity, 19 examples of secretory carcinoma
are described below.
N 1966, MCDIVITT
AND STEWART described an un-
Materials and Methods
Nineteen examples of pure secretory carcinoma of
the breast accessioned at the Armed Forces Institute
From the Department of Gynecologic and Breast Pathology,
Armed Forces Institute of Pathology, Washington, D. C.
* Vice Chairman, Department of Gynecologic and Breast
t Chairman, Department of Gynecologic and Breast Pathology.
Address for reprints: F. A. Tavassoli, MD, Armed Forces
Institute of Pathology, Washington. D. C. 20306.
Accepted for publication May 18, 1979.
The opinions or assertions contained herein are the private views
of the authors and arc not to be construed as official or as reflecting
the views of the Department of the Army or the Department of
of Pathology over a 16-year period were reviewec
Six other carcinomas having the same secretor
features were excluded because of the presence o
small areas of typical infiltrating duct carcinoma
Clinical information was abstracted from the patients
charts, and the gross and microscopic features were
analyzed. Microscopic sections of the primary tumor
were examined in each instance. A variety of special
stains including mucicarmine, periodic acid-Schiff
(PAS) with and without diastase, alcian blue with
sialidase digestion, alcian blue-PAS, and toluidine
blue at pH 1.5 were used in 3 selected cases (cases 4,
9, 18) in order to determine the nature of the secretory
material (Table 1). In two of these (Cases 4,9), staining
with oil red-0 for fat was also done. Staining with
mucicarmine and PAS with and without diastase was
done in two additional cases (Cases 5, 10) (Table 1).
In addition to light microscopic examination, one
neoplasm was studied by transmission and scanning
electron microscopy (SEM). For examination by trans-
mission electron microscopy, samples of tissue were
retrieved from formalin, fixed in 5% glutaraldehyde,
post-fixed in 2% buffered osmium tetroxide, and em-
bedded in Epon after dehydration in graded alcohols
and propylene oxide. The sections were than cut on
an LKB ultratome, stained with uranyl acetate lead
citrate and examined in a Zeiss 9s-2 electron micro-
scope. For examination by SEM, tissue was removed
from formalin, fixed in 2% glutaraldehyde, and after
dehydration through graded acetone, critical point-
dried with liquid CO,. A plasma coating of a 60:40
mixture of go1d:palladium was applied, and the speci-
men was examined in an AMR-1000 SEM at 20kV.
0008-543)3/80/0501/2404 $0.70 D American Cancer Society
Tavassoli and Norris
TABLE 1. Treatment and Follow-up Information
metastasis Case Treatment Recurrence
Mod. radical mast.
+ (8/ 14)
1 . 5
Mod. radical mast.
Simple mast. 3150 rad
Mod. radical mast.
Mod. radical mast.
Mod. radical mast.
NE = not examined. Mast. = mastectomy; Mod. = modified
One case in this study has been the subject of a
recent report, but the other 18 have not been reported
The ages of the patients ranged from 9 to 69 years
(median, age, 25 years). The youngest was a 9-year-old
boy. Only one patient was premenarchal. Seventeen
(89%) of the patients were white and 2 (11%) were
black. In 11 cases, the neoplasm was located in the
right breast and in 8 cases, the left breast. The dis-
tribution within the breast was not unusual, but three
were subareolar in location and one was located in
the axillary tail of the breast. Eighteen of the patients
presented with breast masses; 1 had a bloody dis-
charge from the nipple. Five patients were taking oral
contraceptive steroids; none was pregnant or had any
evidence of an endocrine abnormality, and none had
Gross Pathologic Findings
The tumors ranged in size from 1 to 12 cm (median
size, 3 cm). They were all firm discrete lesions, ap-
pearing as irregular densely fibrous masses, often
simulating fibroadenomas. Typically, they were
grayish-white or yellow to tan in color and were well
delineated, except in 4 cases, in which the neoplasms
each had an infiltrating margin as seen on gross ex-
Microscopic Puthologic Findings
Two cell types could be distinguished and were
arbitrarily designated as Types A and B, on the basis
of variations in the cell cytoplasm and distribution of
secretory material. Type A cells were slightly granular
and there was abundant secretory material within in-
dividual tumor cells and in extracellular lumens (Fig. 1).
Type B cells were round to polygonal in shape with
finely granular or vacuolated cytoplasms (Fig. 2). An
admixture of the two kinds of cells was always present;
in 4 cases, the neoplasms were predominantly com-
posed of Type A cells and in 7, of Type B cells. In
the remaining 8 cases, the neoplasms were composed
of equal admixtures of both cell types.
Cellular atypism and mitotic activity were minimal
or absent in both Type A and B tumor cells. Seventeen
tumors each had an admixture of an intraductal com-
ponent and sheets and cords of tumor cells (Fig. 3).
Two other neoplasms had basically a lobular configura-
tion. In these, multiple lobules were distended by
tumor cells with coalescence of lobules in some areas.
Two neoplasms'were multifocal. Although all but four
were grossly circumscribed, microscopically all neo-
plasms had irregular margins and focal areas of in-
filtration with irregular extension of tumor cells into
the stroma. Seven neoplasms each had a prominent
SECRETORY CARCINOMA . Tavassoli and Norris
TABLE 2. Patients with Axillary Node Metastasis
Size of tumor
(cm) Case Race Follow-up, timc after diagnosis
3 of 11
8 of 14
1 of 20
Well, 6 years
Died with metastatic tumor, 10 months
Local recurrence, 8 months; NED, 18 months
Well, 5 years
NED = no evidence of disease; B = black; W = white. Cell types described in Materials and Methods.
tions in the intracellular and extracellular secretory
material. The possible presence of casein in these
tumors should also be investigated in the future.
Secretory carcinoma is a separate entity from the
lipid-rich (lipid-secreting) carcinoma because two neo-
plasms stained with oil red-0 did not contain stainable
fat and ultrastructural examination showed only an
occasional lipid droplet in the tumor cells.9 Further-
more, the neoplastic cells contained PAS, alcian blue,
or mucicarmine-positive material, features contrary to
Secretory carcinomas are distinct from mucin-pro-
ducing carcinomas (mucoid carcinoma, signet ring cell
carcinoma, and mucin-producing papillary carcinoma)
by the absence of membrane-bound mucin droplets.
In lobular carcinomas, the mucin is confined mainly
to intracytoplasmic lumens,3 but they are not as abun-
dant as in secretory carcinomas. Furthermore, secretory
carcinomas also have an abundance of secretory ma-
terial in the extracellular lumens. Harris c ~ t ~
proposed a possible derivation of the intracytoplasmic
lumens from the Golgi apparatus. They demonstrated
varying degrees of dilatation of the Golgi cisternae
associated with concentric fibrils in the adjacent cyto-
plasm and suggested that, as the Golgi becomes pro-
gressively dilated, the cytoplasmic strands separating
the cisternae become attenuated and transformed into
microvilli. Our findings also support such B derivation.
By means of SEM, the cellular pleomorphism may
distinguish this lesion from some noncancerous lesions
of the breast,h the cell surface pattern, however, cannot
be reliably distinguished from that atypical of apocrine
hyperplasias or various papillary carcinomas.x The
presence of some large cells bulging with secretory
material and about to rupture suggests cell disruption
as a possible mechanism for at least partial discharge
of the secretory material into the extracellular spaces.
Undoubtedly other mechanisms are also involved.
Steroid receptor studies of these tumors would be
of interest for determining whether there is any dif-
ferences between the tumors occurring in the pre-
pubertal patients and those occurring in adult patients
and for determining whether the receptor concentration
is related to prognosis.
Since this neoplasm is capable of axillary node and
distant metastasis. in adult patients, a conservative
surgical approach such as local excision is insufficient
for controlling the progression of the disease. A simple
mastectomy with axillary node dissection will probably
be adequate as the initial treatment for patients more
than 20 years of age, with the necessity for further
treatment dependent on the results of this initial pro-
cedure. Since metastases are so rare in children,
wide excision probably is adequate. As our knowledge
in the field of cancer therapy increases, other means of
controlling the progression of this neoplasm will be-
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helpful histopathologic feature. Arch. Parhol. 99:614-617, 1975.
2. Byrne, M. P., Fabey, M. M., and Gooselaw, J. G.: Breast
cancer with axillary metastasis in an 8-112 year old girl. Canrer
3 1:726-728, 1972.
3. Harris, M., Vasudev, K. S., Anfield, C.. and Wells, S.:
Mucin-producing carcinomas of the breast: Ultrastructural observa-
tions. Histopathology 2: 177- 188, 1978.
4. McDivitt, R. W., and Stewart, F. W.: Breast carcinoma in
children. JAMA 195:388-390, 1966.
5. Salazar, H., Tobon, H. H.. and Josimovich, J. B.: Develop-
mental gestational and postgestational modifications of the human
breast. Clin. Ohstet. Gjvzecol. 18: 113- 137, 1975.
6. Spring-Mills, E., and Elias, J. J.: Cell surface differences in
ducts from cancerous and noncancerous human breasts. Science
7. Sullivan, J. J., Mayee, H. R., and Donald, K. J.: Secretory
(Juvenile) carcinoma of the breast. Puthology 9:341-346, 1977.
8. Tavassoli, F. T., and Norris, H. J.: Unpublished data.
9. Van Bogaert, L. H., and Maldague, P.: Histologic variants
of lipid-secreting carcinoma of the breast. Virch. Arch. Parhol.
Anar. 375:345-353, 1977.