Secretory breast carcinoma with metastatic sentinel lymph node

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DOI: 10.1186/1477-7819-4-88 · Source: PubMed
Abstract
Secretory mammary carcinoma is a rare breast neoplasia originally described in children but sometimes also found in adults. It presents a more favourable outcome than more common histological types of breast carcinoma; published literature in fact reports only a few cases with axillary lymph node metastases and only four cases with distant metastases. In this paper we report a rare case of secretory breast carcinoma with axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin expression. We found positivity for e-cadherin, which would support the hypothesis that this type of tumour is a variant of the infiltrating ductal carcinoma. After a careful analysis of reported data, we have come to the conclusion that the treatment of choice for patients with secretory breast carcinoma should be conservative surgery with sentinel lymph node biopsy, followed by accurate follow-up. We are of the opinion that while post-operative radiotherapy is indicated in adult patients who have undergone quadrantectomy, it should not be used in children. Although several cases of secretory carcinoma have been treated with adjuvant chemotherapy, there are still no reliable data regarding the real value of such a choice.

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World Journal of Surgical Oncology
Open Access
Case report
Secretory breast carcinoma with metastatic sentinel lymph node
Salvatore Vieni*
1
, Daniela Cabibi
2
, Calogero Cipolla
1
, Salvatore Fricano
1
,
Giuseppa Graceffa
1
and Mario Adelfio Latteri
1
Address:
1
Department of Oncology, Division of General and Oncological Surgery, University of Palermo, Palermo, Italy and
2
Institute of
Pathology, University of Palermo, Palermo, Italy
Email: Salvatore Vieni* - salvatorevieni@tiscali.it; Daniela Cabibi - cabibidaniela@virgilio.it; Calogero Cipolla - calogerocipolla@virgilio.it;
Salvatore Fricano - salvatorefricano@hotmail.it; Giuseppa Graceffa - gracet@virgilio.it; Mario Adelfio Latteri - amlatteri@unipa.it
* Corresponding author
Abstract
Background: Secretory mammary carcinoma is a rare breast neoplasia originally described in
children but sometimes also found in adults. It presents a more favourable outcome than more
common histological types of breast carcinoma; published literature in fact reports only a few cases
with axillary lymph node metastases and only four cases with distant metastases.
Clinical presentation: In this paper we report a rare case of secretory breast carcinoma with
axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of
secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin
expression.
We found positivity for e-cadherin, which would support the hypothesis that this type of tumour
is a variant of the infiltrating ductal carcinoma.
Conclusion: After a careful analysis of reported data, we have come to the conclusion that the
treatment of choice for patients with secretory breast carcinoma should be conservative surgery
with sentinel lymph node biopsy, followed by accurate follow-up. We are of the opinion that while
post-operative radiotherapy is indicated in adult patients who have undergone quadrantectomy, it
should not be used in children. Although several cases of secretory carcinoma have been treated
with adjuvant chemotherapy, there are still no reliable data regarding the real value of such a
choice.
Background
Secretory carcinoma was first described in 1966 by McDi-
vitt and Stewart [1]. This is a rare breast neoplasia first
identified in female children and adolescents, at the aver-
age age of nine. Neoplasias with similar features were sub-
sequently observed in male children and young boys, in
adult men and in women of all ages, with the result that
at a certain point this type of tumour was no longer
defined as a "juvenile carcinoma" but was called instead
"secretory carcinoma", since the histological examination
revealed the presence of intracytoplasmic secretory mate-
rial [2-4].
It is not a particularly aggressive tumour and presents an
excellent prognosis. Axillary locoregional lymph node
metastases are uncommon, while only four patients have
shown distant metastases [5,6]. Several authors, therefore,
suggest that treatment should be as conservative and non-
Published: 06 December 2006
World Journal of Surgical Oncology 2006, 4:88 doi:10.1186/1477-7819-4-88
Received: 26 July 2006
Accepted: 06 December 2006
This article is available from: http://www.wjso.com/content/4/1/88
© 2006 Vieni et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
World Journal of Surgical Oncology 2006, 4:88 http://www.wjso.com/content/4/1/88
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aggressive as possible. Nevertheless, since there are very
few reports in literature regarding this rare form of breast
neoplasia, therapeutic approach to it tends to be fairly
flexible.
In this paper, the authors describe the case of a 33-year-
old woman with a secretory breast carcinoma and a meta-
static sentinel lymph node; they analyse the immunophe-
notype pattern with reference to a possible histogenetic
hypothesis and report the most frequently used therapeu-
tic choices, with particular emphasis on use of sentinel
lymph node biopsy, as an alternative to total axillary lym-
phoadenectomy.
Clinical case report
A 33-year-old woman with no family history of breast car-
cinoma presented with a nodule in the upper outer quad-
rant of the right breast wich had been discovered about
four mounth previously and had gradually increased
slightly in volume during the intervening period. Clinical
examination showed the presence of a hard, mobile, non-
painful nodule with regular margins, a smooth surface
and about 1,5 cm in diameter. No clinical alterations were
found either in the ipsi- or contralateral lymph nodes.
Ultrasound examination of the breast showed an ovular
hypoechogenic formation with regular margins and 1,5
cm in diameter, diagnosable as a fibroadenoma of the
breast.
Not only for this reason, but also following the patient's
specific request, core biopsy of the tumour was not per-
formed and the patient therefore immediately underwent
surgical removal of the nodule under local anaesthetic.
The histopathological examination of the surgical piece
showed the presence of a secretory carcinoma the lesion
had no capsule, since one of the resection margins was not
very clear, and showed small, glistening, mucus-like foci
on the cut surface.
For microscopic examination, 5 micron sections were
obtained from formalin-fixed, paraffin- embedded mate-
rial and stained with hematoxylin-eosin and Alcian PAS.
The lesion showed solid cell nests, intermingled with
tubular structures and separated by fibrous bundles. The
neoplastic nests consisted of small, uniform, well-differ-
entiated cells, with granular or vacuolated cytoplasm and
vescicular nuclei containing small nucleoli. Mitoses were
scanty and atypia was mild. Eosinophilic, PAS-positive
secretory material was frequently observed in the ductular
lumina and, in the form of globular structures, in the
intracytoplasmic vacuoles of many neoplastic cells (fig
1a). Peripherally, in the more ductular areas, extracellular
Alcian blue-positive material (reminiscent of a mucinous
carcinoma) was present. Vascular invasion was not evi-
dent. Immunohistochemically the neoplastic cells
showed a strong positive stain for cytokeratins (MNF116,
CK7) EMA, S100 (fig 1b) and e-cadherin (fig 1c). In addi-
tion, an extremely focal, weak stain for 34beta E12 and
CD10 was observed.
Chromogranin, sinaptophysin, NSE, smooth muscle
actin, p63, Her-2, oestrogen and progesterone receptors
were negative, Mib1 (Ki67) and P53 were positive in less
than 5% of the cells. The histological diagnosis was G1
secretory breast cancer.
Analysis of the DNA cell content of the secretory carci-
noma proves to be diploid with low proliferative activity
[19-23] and, in fact, in our own case, flow cytometry per-
formed on the cell DNA (65,520 cells) also showed a dip-
loid-type histogram (DI = 1.0) with low proliferative
activity (S-phase = 4.5%).
After an interdepartmental discussion, an upper outer
quadrantectomy of the right breast on the previous site of
removal of the nodule was proposed to the patient,
together with a biopsy of the ipsilateral axillary sentinel
lymph node.
The sentinel lymph node was identified with the use of a
radiocolloid and intravital stain.
The day before the operation, the sentinel lymph node
was observed by means of lymphoscintigraphy after an
intradermal injection into the surgical scar of human
albumin (Nanocoll) bound to technetium 99 (0,2 mCi of
99 mTc in a volume di 0,4 ml). Ten minutes before the
start of the operation 0.5 ml of intravital stain was injected
subdermically into the same site. A portable radioisotope
detector was a further help in the intraoperative identifica-
tion of the sentinel lymph node, which showed up as
bright blue and was therefore removable without any dif-
ficulty. Frozen section of the sentinel nodes was not per-
formed since at the time when this case was observed
(1999) the extemporary histological examination of the
sentinel lymph node was not well-codified in our depart-
ment and was therefore not in routine use.
The subsequent histological analysis performed on the
removed quadrant showed the presence of some small
areas of "in situ" secretory carcinoma, mixed with focal
aspects of ductal papillomatosis with atypia of the epithe-
lial cells.
The lymph node defined as the sentinel had a maximum
diameter of 1 cm. It was fixed in formalin, paraffin-
embedded, completely sectioned and histologically ana-
lysed. It presented metastases with a maximum diameter
of 0,3 cm (fig 1d); the metastatic cancer cells showed
World Journal of Surgical Oncology 2006, 4:88 http://www.wjso.com/content/4/1/88
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intracytoplasmic vacuoles containing secretory globules
similar to those of the primary tumour cells (Fig 2A–B)
A total axillary lymphoadectomy under general anaes-
thetic was therefore performed during a subsequent oper-
ation. Histological examination of the 18 axillary lymph
nodes removed showed no signs of metastases. The
patient was given adjuvant chemotherapy consisting of six
cycles of CMF and radiotherapy of the residual mammary
gland.
Periodic follow-up examinations after completion of the
surgical, medical and radiotherapy treatment have shown
no evidence of either local regression or distant metastases
and seven years later, the patient is still free of the disease.
Discussion
Secretory carcinoma is a rare form of breast cancer, gener-
ally with a favourable prognosis, since literature reports
few cases with locoregional or distant metastases.
Although this disease represents 84% of all the histologi-
cal variants of infant breast carcinoma [7], secretory carci-
noma can also occur in adults, both in men and women.
The tumour has been found in patients ranging from three
to eighty-seven years of age [1,8,9]. Most of the cases
reported in literature involve female patients of the aver-
age age of 40 years and a median of 33 [10]. Only 15 cases
have been observed in males (average age 17) with a
male:female ratio of 1:6, which is relatively high com-
pared with the distribution of other histological types of
breast carcinoma in males [11,12].
(A) PAS positive secretory material in ductular lumina and, as globular structures, in intracytoplasmic vacuoles (arrows)Figure 1
(A) PAS positive secretory material in ductular lumina and, as globular structures, in intracytoplasmic vacuoles (arrows). (B)
Positive immunostain for S100 antibody, (C) Positive immunostain for E-cadherin, (D) Metastasis to sentinel lymph node.
(Original magnification: A 400X; B and C 200X; D 100X).
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The correlation between known risk factors for breast car-
cinoma and secretory carcinoma is not yet fully under-
stood. Since the presence of oestrogen and progesterone
receptors is extremely variable in patients with secretory
breast carcinoma, the etiopathogenesis of such tumours is
probably not linked to female sex hormones.
Many authors have shown the presence of several chro-
mosomic anomalies in secretory carcinomas, although
the significance of such genetic alterations has still to be
clarified [7,10,13]. Our own case showed the two more
distinctive pathological characteristics of such tumours:
intracellular and extracellular secretion and granular eosi-
nophilic cytoplasm of the neoplastic cells.
Immunohistochemically the negative stain for oestrogen
and progesterone receptors and the positive stain for S100
are in agreement with previous reports [9,14,15].
The primary tumour showed a low risk factor (diameter <
2 cm, low histological grade, absence of vascular invasion,
low proliferation rate assessed by Ki67, Her-2 negative
immunostain), with the exception of the hormone recep-
tors, which proved to be negative.
In our case we found strong membranous immunostain
for e-cadherin. Previous studies reported that e-cadherin is
present in infiltranting ductal carcinoma and its loss has
been reported in most of infiltranting lobular carcinoma
High power view of metastatic lymph node cancer cellsFigure 2
High power view of metastatic lymph node cancer cells.(A) globular structures, in intracytoplasmic vacuoles (arrows), that are
positive with alcian-PAS stain (B) (Alcian)(Original magnification: A and B 400X)
World Journal of Surgical Oncology 2006, 4:88 http://www.wjso.com/content/4/1/88
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[16,17]. This supports the hypothesis that the secretory
carcinoma might originate from the ductal component of
the mammary gland and might therefore be considered as
a variant of ductal carcinoma.
To our knowledge, this is the first report of secretory carci-
noma in which the e-cadherin expression has been inves-
tigated. On the other hand, positivity for S100 and,
focally, for CD10 and negativity for oestrogens and pro-
gesterone suggests that the tumour might originate in the
basal cells of the duct, whose immunophenotype has
recently been described by Kesse-Adu R and Shousha S
[18]. If this view is correct, oestrogen and progesterone
negativity should not be considered as the indication of
an unfavourable outcome, but merely as a feature linked
to the histogenetic origin of the tumour. The analysis of
the DNA cell content of the secretory carcinoma proves to
be diploid with a low proliferative activity [19-23]. In our
case, flow cytometry performed on the cell DNA (65,520
cells) also showed a diploid-type histogram (DI = 1.0)
with a low proliferative activity (S-phase = 4.5%).
Whatever the age or sex of the patient, the secretory carci-
noma can usually be felt at palpation. Reported dimen-
sions of the tumour range from a minimum of 1 cm to a
maximum of 16 cm [2,21].
In agreement with reports published by several other
authors [24], the tumour observed by us also presented
clinical and ultrasound features similar to those of a
fibroadenoma – clear margins, smooth surface and
mobile on both the upper and the lower levels. Partly as a
result of the clinical and echographic features of the nod-
ule, and also following the specific request of the patient,
who preferred to undergo nodulectomy only, we did not
perform a core biopsy of the nodule, which would most
certainly have led to a more accurate therapeutic approach
and made it possible to avoid the second surgical inter-
vention.
Breast X-rays have rarely been performed in patients with
secretory carcinomas; in a multicentre study, Richard et al.
described a few cases where there was radio-opacity with
defined margins and the presence of microcalcifications
[23].
Since this type of tumour is extremely rare, there is still no
unanimous consensus about treatment choice. Many
authors maintain that the frequency of local disease
relapse after the simple surgical removal of the neoplasia
only would suggest that mastectomy should always be
performed [8,14].
According to Richard et al [23] about 33% of adult
women treated with extensive surgery of the tumour site
presented local disease relapse.
Whenever possible, prepubertal girls should be treated
initially by wide local excision. Preservation of the breast
bud should be attempted, but as this is not always possi-
ble, breast development may sometimes be impaired
[14].
When the neoplasia is large, mastectomy should be per-
formed in order to avoid the probability of local relapse
[9].
Post-operative radiotherapy should be proposed after
conservative surgery in adult patients, but is not advised
for children because of the possible secondary effects such
as fibrosis of the lung, rib damage and the consequent
asymmetry of the rib cage [15,25]. In our own case, since
the patient was an adult woman with a tumour of less
than 2 cm, and since the histological examination of one
of the nodule resection margins was not sufficiently clear,
we decided on quadrantectomy followed by subsequent
radiotherapy.
Although locoregional and distant metastases from the
secretory carcinoma are extremely rare, they are neverthe-
less possible. For the correct staging of the disease, there-
fore, it is necessary to verify the possible presence of
sytemic and/or axillary lymph node metastases.
There is still considerable discussion about the indications
for a complete axillary lymph node dissection. Since the
secretory carcinoma has a reduced metastatic capacity, it is
obvious that a total axillary lymphoadenectomy per-
formed on principle would be in fact a form of over-treat-
ment for this particular disease stage. The frequently-
reported post-operative complications of axillary dissec-
tion, such as pain, parasthesia, seroma, difficulty of shoul-
der movements and lymphedema of the upper arm are all
further valid reasons for a cautious approach towards this
therapeutic choice.
In the last few years, in order to avoid where possible the
complete dissection of the axillary fossa in ductal and lob-
ular breast cancer, a biopsy of the sentinel lymph node is
usually performed. In our own case we also tried to use
this technique, which had never been reported in litera-
ture at the time of surgery (1999). We used both intravital
stain and a radiotracer with a portable radioisotope detec-
tor for the intraoperative identification and subsequent
removal of the lymph node without any difficulty, even
though these substances were injected directly into the
surgical scar.
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The histological examination of the sentinel lymph node
was performed on formalin-fixed, paraffin-embedded
material and showed the presence of metastases; this
made it imperative to perform further surgery for total
axillary lymphoadectomy. Reported data show that in
40% of cases, the other lymph nodes removed after senti-
nel lymph node positivity have not undergone metastatic
colonisation [26] and this proved to be true in our patient.
Although several cases of secretory carcinoma have been
treated with adjuvant chemotherapy, there are no pub-
lished data about the real effectiveness of this therapeutic
choice. Herz et al have reported non-responsiveness of the
tumour to chemotherapy [6]. In our own case, since we
had found axillary metastases, we administered adjuvant
chemotherapy consisting of six cycles of CMF.
Conclusion
Since very few cases of secretory carcinoma have been
described in literature, it is imperative to report any new
cases observed in order to establish the most suitable ther-
apeutic approach. In this report the hypothesis that secre-
tory carcinoma might be considered a variant of ductal
carcinoma has been stressed, based on e-cadherin expres-
sion, suggesting that it might originate from the ductal
component of the mammary gland. Moreover, we
hypothesize that oestrogen- and progesterone-negative
immunostain should not be considered as markers of an
unfavourable outcome but, together with S100 and Cd10
positive immunostain, might be linked to the histogenetic
origin of the tumour from the basal cells of the duct.
The fact that this neoplasia is not very aggressive suggests
that surgical treatment should be kept as conservative as
possible. Nevertheless, the lack of secure data regarding
the real potential of the secretory carcinoma to bring
about local relapse leads us to the conclusion that a con-
ventional, conservative approach, such as quadrantec-
tomy followed by radiotherapy, used for all other types of
infiltrating breast carcinomas, should also be used for this
type of tumour. Furthermore, since reports in literature
have shown optimal results regarding the value of bioptic
staging of the sentinel lymph gland, we are therefore of
the opinion that this treatment choice is particularly valid
in order to avoid axillary lymphadenectomy, useless in
patients affected by neoplasias which are not particularly
aggressive, such as the secretory breast carcinoma.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
SV and CC carried out the surgical procedure and contrib-
uted to the design of the study. SF and GG gathered the
data from the literature search and made the first draft of
the manuscript. DC performed the histological analysis of
the surgical specimen and provided histological sections
as figures for the manuscript. MAL, SV and DC revised
and finally approved the manuscript for been published.
All authors approved the final manuscript.
Acknowledgements
The written consent of the patient was obtained for publication of this case
report in WJSO.
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    • "SBC is also known to occur in both sexes with prior literature showing a male to female ratio of 1:6 [6], our review of the NCDB demonstrated a ratio of 1:31. Multiple case reports have been reported in the literature [7,[8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Li et al. reported histopathological features of 15 patients diagnosed with SBC. "
    [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Invasive secretory breast carcinoma (SBC) is a rare subtype of breast malignancy. Methods: Cases of SBC and infiltrating ductal carcinoma (IDC) from the National Cancer Database (1998-2011) were queried. Results: Patients with SBC (n = 246) and IDC were identified (n = 1,564,068). The group with SBC was younger (age 56.4 ± 16.0 vs. 60.4 ± 13.9 years, P < 0.001), had similar tumor size (19.9 ± 17.8 vs. 21.6 ± 25.5 mm, P = 0.297), more frequently African-Americans (24.1 vs. 14.8 vs. 13.7; P = 0.004), more well-differentiated (32 vs. 18%, P < 0.001) and less likely to be hormone receptor positive (ER: 64 vs. 76%, P = 0.001; PR: 43 vs. 65%, P < 0.001). No differences were found for incidence of node-positivity (32 vs. 34%, P = 0.520) and stage IV presentation (2.4 vs. 3.6%, P = 0.372). Breast conserving surgery (60 vs. 58%, P = 0.405) and hormonal therapy (67 vs. 71%, P = 0.489) rates were similar. Systemic chemotherapy was used less often for SBC (38 vs. 45%, P = 0.035). The overall survival of all patients with SBC was better than all patients with IDC (median not reached vs. 14.8 years, P = 0.025). Conclusion: SBC is an uncommon tumor that is often well-differentiated and seen in younger women. Contrary to prior reports, they are frequently hormone receptor-positive. Compared to IDC, overall survival is improved. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
    Article · Apr 2016
    • "Minimal surgical procedures have been proposed due to non-aggressive course of the tumor. [7] There are various methods available for surgical treatment from modified radical mastectomy to local excision. Complete total excision and gradual axillary lymph node dissection can be suitable if the tumor is smaller than 2 cm whereas axillary lymph node dissection along with simple mastectomy must be considered if the tumor is bigger than 2 cm. "
    [Show description] [Hide description] DESCRIPTION: Secretory breast carcinoma is a rare variant of invasive breast cancers. This tumor was first classified in juvenile age breast tumors category and, however, with the increase in the incidences of these tumoral structures in adults, it was included in adult breast cancers classification. This paper presents a 38 year old female patient who admitted with complaints of palpable mass in the right breast and reported as 'malignant epithelial tumor' as a result of excisional biopsy and diagnosed with 'secretory carcinoma' following a right modified radical mastectomy in the continued process and axillary dissection.
    File · Research · Dec 2015 · Case Reports in Oncological Medicine
    • "The mean tumor size is 3 cm. The literature mentions nodal involvement in 15% of the patients at presen- tation [8]. Although rare, metastatic disease at presentation has also been reported [9]. "
    [Show abstract] [Hide abstract] ABSTRACT: Secretory carcinoma of the breast is an extremely rare subtype of breast cancer characterized by intracellular or extracellular secretion and granular eosinophilic cytoplasm of the neoplastic cells. The disease which was considered to be predominant in younger age group has been recognized in adult population too and tends to show slow growth and indolent behavior. The disease occurs preferentially in females and only 27 cases have been reported amongst males. An optimal treatment for the disease subtype has been debated because of the paucity of data. We report two cases (one female and one male) of this rare disease that underwent treatment at our institution.
    Full-text · Article · Aug 2015
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