Secretory Carcinoma of the
Male Breast:
Correlation of Aspiration Cytology
and Pathology
Cristina Alenda, M.D.,1* F. Ignacio Aranda, M.D.,
1
F. Javier Seguı́,
and Juan Laforga, M.D.2
Secretory carcinoma (SC) is a rare variant of breast carcinoma,
which was first described in children and adolescents but it can
occur at all ages. Very few cases have been reported in male
patients. We describe the cytological and histopathological fea-
tures of SC in a 79-yr-old man. Cytological findings demonstrated
cohesive sheets of monotonous cells with round nuclei and small
nucleoli. Most cells contained intracytoplasmic vacuoles, which
are the key feature of an accurate diagnosis. Differential diagnosis
with other tumors is discussed briefly. Diagn. Cytopathol. 2005;
32:47–50. © 2005 Wiley-Liss, Inc.
Key Words: secretory carcinoma; male breast; fine-needle aspira-
tion
Less than 1% of all breast cancers occur in men, represent-
ing less than 0.17% of all cancers in men.1 The histological
types of male and female breast cancer are identical and
similar in frequency, and the majority are infiltrating ductal
carcinoma.2 Special histological types represent less than
10% of all cases.2 Secretory carcinoma (SC) of the breast
was first described in 19663 and designated as juvenile
carcinoma. Tavassoli et al.4 observed the same pattern in
adults and recommended replacing the designation of juve-
nile carcinoma. SC is a distinctive and rare variant of breast
carcinoma with a favourable prognosis.5 SC is characterized
by the presence of large amounts of intracellular and extra-
cellular secretions and a granular eosinophilic cytoplasm of
the cells.4 These features can be recognized on fine-needle
aspiration (FNA).6 –9 There are only 15 cases reported in
men5 and only 2 cases were diagnosed by FNA.7,10
1
Department of Pathology, Hospital General Universitario de Alicante,
Alicante, Spain
2
Department of Pathology, Hospital Marina Alta, Alicante, Spain
*Correspondence to: Cristina Alenda, M.D., Department of Pathology,
Hospital General Universitario de Alicante, Pintor Baeza s/n 03010 Ali-
cante, Spain. E-mail: alenda_cri@gva.es
Received 29 January 2004; Accepted 6 July 2004
DOI 10.1002/dc.20157
Published online in Wiley InterScience (www.interscience.wiley.com).
© 2005 WILEY-LISS, INC.
M.D.,
1
We describe the radiological, cytological, pathological,
and immunohistochemical (IHC) features of a secretory
breast carcinoma in a 79-yr-old man.
Case Reports
A 79-yr-old man presented with a left palpable breast tumor
mass in a background of bilateral gynecomastia. Nipple
discharge was not observed. Clinical history was not rele-
vant. Ultrasound and mammographic studies showed a
high-density lesion suspicious for malignancy. An FNA of
the mass was performed, followed by a mastectomy and
axillary lymph node dissection.
Cytological Findings
The slides showed irregular large sheets of polygonal cells
in a colloid-like background material. The cells often con-
tained prominent cytoplasmic vacuoles and some signet-
ring cells were found. Cells with nonvacuolated cytoplasm
appeared granular. The nuclei were atypical, round, central,
and with fine chromatin. (Fig. 1A–D) A diagnosis of posi-
tive for carcinoma was rendered, and SC was considered in
the differential diagnosis.
Pathological Findings
A mastectomy with lymph node dissection was performed.
A 30-mm circumscribed tumor mass was identified in a
subareolar location. Margins were free of tumor.
Microscopically, the neoplasm had pushing and partially
infiltrating margins and was composed of microglandular,
glandular, solid, and papillary areas. The tumor cells, glands,
and microcystic spaces contained abundant secretion (Fig. 1E,
F). The secretory material was PAS positive and diastase
resistant. No necrosis or vascular invasion was observed. There
was no metastasis at the lymph node dissection. The surround-
ing breast tissue showed gynecomastia.
An IHC study was performed by the streptavidin-biotin
method (Dako ChemMate Detection kit; Dakocytomation,
Diagnostic Cytopathology, Vol 32, No 1 47
ALENDA ET AL.

Fig. 1. (A) Cohesive groups of cells with background secretory material (Papanicolaou stain, ⫻40). (B) Cytologically bland, ovoid nuclei cells were seen
in association with groups of epithelial cells (Papanicolaou stain, ⫻200). (C) Epithelial cells showed vacuolated cytoplasm with frayed margins
(Papanicolaou stain, ⫻400). (D) Some signet-ring cells were seen (Papanicolaou stain, ⫻400). (E) SC with solid and microacinar patterns (hematoxylin
and eosin, ⫻100). (F) Epithelial cells with finely vacuolated cytoplasm and nuclei with uniform nucleoli and intratubular secretory material (hematoxylin
and eosin, ⫻400).

48 Diagnostic Cytopathology, Vol 32, No 1


Glostrup, Denmark) using the following antibodies: S100
protein; carcinoembryonic antigens (CEAs); estrogen recep-
tors; progesterone receptors; and androgen receptors gross
cyst disease fluid protein (GCDFP15), bcl2, Her2/neu,
Ki67, and p53. Tumor cells were positive for S100 protein
and CEA, and very focal reactivity was observed for GC-
DFP15. On the other hand, tumor cells were negative for
progesterone; estrogen; and androgen receptors bcl-2, p53,
and Her2/neu. Proliferative activity determined by Ki67
was low (1%).
Discussion
SC was first described as juvenile breast carcinoma because
it was thought to occur only in childhood.11 However, it has
been described in all age groups, and the majority of the
patients are adults.4 Bree et al.5 reported 15 cases of male
patients with SC, resulting in a male/female ratio of approx-
imately 1:6. As far as we know, our patient is the oldest man
reported in the English literature. On mammographic stud-
ies features such as benign opacity, asymmetric densities, or
microcalcifications might be seen.12
The most characteristic findings in FNA specimens of SC
are large vacuoles containing proteinaceous material that is
abundant also in the background of the smears.7,8,10 The FNA
specimen is composed of cohesive sheets and loosely cohesive
groups of monotonous cells with round nuclei and homoge-
neous chromatin. Most cells have abundant granular cytoplasm
with or without intracytoplasmic vacuolted, including a com-
ponent with signet-ring cells, morphology.7,9,13–16
Histological patterns observed include solid, microcystic,
and ductal, with many neoplasms containing all three pat-
terns.5 The presence of abundant intra- and extracellular
secretion of a material containing mucin and a vacuolated or
granular eosinophilic cytoplasm is characteristic.4 This ma-
terial always stains with Alcian blue and periodic acid-schi
(PAS).
In the histological differential diagnosis, cystic hyperse-
cretory carcinoma, cystic hypersecretory hyperplasia, sig-
net-ring-cell breast carcinoma, and lactational changes
should be ruled out.12 Microscopically, all cystic hyperse-
cretory lesions have cysts that contain eosinophilic secretion
that bears a striking resemblance to thyroid colloid. The
cells in cystic hypersecretory hyperplasia have uniform cy-
tologically bland nuclei and scant cytoplasm, and in cystic
hypersecretory carcinoma, the epithelium grows as micro-
papillary intraductal carcinoma.17 Signet-ring cells can oc-
cur in ductal carcinomas, but usually are associated with
lobular carcinomas. Signet-ring cells have eccentric nuclei,
which abuts on the cytoplasmic mucin vacuole. In the
secretory changes associated with pregnancy, the cytoplasm
of lobular epithelial cells becomes vacuolated, and secretion
is progressively accumulated in distended lobular glands.
Nuclei are hyperchromatic and often have small nucle-
oli.18,19 FNA cytological findings show marked overlap with
SECRETORY CARCINOMA OF THE MALE BREAST
features described as characteristic of lactation changes and
emphasizes that the clinical information is very important in
this distinction.7
Other entities to be considered in the cytological differ-
ential diagnosis include those breast tumors in which vacu-
oles also are seen, such as ductal, lobular, lipid rich, glyco-
gen rich, and mucinous.10 Lipid- and glycogen-rich
carcinoma can be ruled out with specific staining. In ductal,
lobular, and mucinous carcinoma, the vacuoles are always
smaller and not as numerous as in SC.10 Cases with prom-
inent signet-ring cells may be mistaken with signet-ring-cell
carcinoma. Sometimes, aggregates of cells or tissue frag-
ments with an acinar pattern containing small centrally
placed mucoid structures resembling adenoid cystic carci-
noma are the main differential diagnosis.
Few reports of SC appear in the cytology literature, with
only two cases reported on FNA findings in the male
breast.7,10 The risk factors reported for breast cancer include
exposure to carcinogens, genetic factors, hormonal disor-
ders, and gynecomastia.2,20 Only 4 of 15 male patients with
SC had gynecomastia,5 as in our case. In general, there is no
evidence that atypical proliferative changes in gynecomastia
are associated with an increased risk of the development of
carcinoma, although there may be increased risk in associ-
ation with gynecomastia.21 In the majority of patients with
gynecomastia, the estrogen receptor status is positive; how-
ever, its positivity in SC is variable. Hormonal abnormality
that would explain the prominent secretory activity in this
type of carcinoma is unknown.22 It has been suggested that
the pathogenesis of this tumor type may not be related to
female sex hormones,22 in agreement with the findings of
the present case. In addition, androgen receptors also were
negative in the case under discussion, which argues against
a hormonal male sex modulation. Tumor cells also showed
positive IHC staining with S100 protein and CEA.6,11,23,24
SC is considered a variant of infiltrating ductal carci-
noma, but recently it was demonstrated that SC expresses
the ETV6-NTRK3 gene fusion as a primary event in human
breast carcinogenesis, but it is not expressed in infiltrating
ductal carcinoma.25–27
The treatment of SC is surgical. Local excision alone may
not be an adequate therapy, because many cases demon-
strate local recurrent disease.12 An alternative approach is to
perform a breast-conserving surgery.
In summary, we reported the clinicopathological findings
of an SC carcinoma in a male breast studied by FNA. The
cytological features may be a challenge; however, it is
important to make this diagnosis preoperatively because of
the low malignant behaviour of this special variant of breast
cancer.
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