Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two different primary malignancies. A 51 year-old woman with a previous history of bilateral breast cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune suppression on lymphoid cells by oesophageal carcinoma cells, are discussed

B Scholl

C Paletta

F Levi

FL Ampil

Gary K Atkin

I Jatoi

Jeremy I Livingstone

JO Larkin

K Gohji

K Overstreet

Khalid A El-Gendy

MR Wick

N Mourra

Paul Richman

PJ van Diest

Robert E Brightwell

S Meischer

T Terada

ZK Wade

English

PubMed

Crossref

Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report

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BioMed Central
International Seminars in Surgical 
Oncology
ssOpen AcceCase report
Adjacent thoracic lymph node metastases originating from two 
separate primary cancers: case report
Khalid A El-Gendy†1, Gary K Atkin†1, Robert E Brightwell*†2, Paul Richman3 
and Jeremy I Livingstone1
Address: 1Department of Surgery, Watford General Hospital, Vicarage Rd, Watford, WD18 0HB, Hertfordshire, UK, 2Department of Biosurgery and 
Surgical Technology, Imperial College London, London, UK and 3Department of Histopathology, Mount Vernon Hospital, Rickmansworth Rd, 
Northwood, Middlesex, HA6 2RN, UK
Email: Khalid A El-Gendy - khalid.elgendy@doctors.org.uk; Gary K Atkin - gary.atkin@sky.com; 
Robert E Brightwell* - r.brightwell04@imperial.ac.uk; Paul Richman - paul.richman@whht.nhs.uk; 
Jeremy I Livingstone - jeremy.livingstone@whht.nhs.uk
* Corresponding author    †Equal contributors
Abstract
Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two
different primary malignancies. A 51 year-old woman with a previous history of bilateral breast
cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the
oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent
thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune
suppression on lymphoid cells by oesophageal carcinoma cells, are discussed.
Background
Oesophageal carcinoma cells have been shown to exert a
local immune suppression on regional lymphoid cells [1],
facilitating the metastatic deposit and survival of cancer
cells from a distant malignancy [2]. Reported is an unu-
sual case of adjacent thoracic lymph nodes demonstrating
metastases from two different primary malignancies. As
far as we know this is the first report of such a phenome-
non, and the finding parallels the previously reported 'col-
lision phenomenon' in which two distinct primary
carcinomas metastasise to the same lymph node.
Case presentation
A 51 year-old woman was diagnosed with adenocarci-
noma of the distal third of the oesophagus after present-
ing with dysphagia. She had a past history of recurrent
bilateral breast cancer necessitating bilateral mastectomy
and several courses of radiotherapy to both breasts as well
as the left axilla and left chest wall. She had subsequently
undergone bilateral breast augmentations with silicone
implants.
Preoperative staging CT for the oesophageal malignancy
did not reveal any enlarged abdominal or thoracic lymph
nodes, or any other evidence of metastases, and so she
underwent radical surgery by subtotal oesophagectomy.
At laparotomy, there were no liver or peritoneal metas-
tases and a radical resection was performed incorporating
abdominal and mediastinal lymph node clearances and a
stapled oesphago-gastric anastomosis at the level of the
azygous vein. Post-operatively she developed pneumonia
and she remained in the intensive care unit for 32 days.
She was subsequently discharged after a hospital admis-
sion of 63 days. Three months later she developed a skin
metastasis within the right thoracotomy scar, and she died
soon after.
Published: 2 October 2008
International Seminars in Surgical Oncology 2008, 5:22 doi:10.1186/1477-7800-5-22
Received: 28 August 2008
Accepted: 2 October 2008
This article is available from: http://www.issoonline.com/content/5/1/22
© 2008 El-Gendy 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.Page 1 of 4
(page number not for citation purposes)
International Seminars in Surgical Oncology 2008, 5:22 http://www.issoonline.com/content/5/1/22Histological analysis of the oesophagectomy specimen
revealed a poorly differentiated adenocarcinoma at the
gastro-oesophageal junction. Tumour infiltrated through
the muscularis propria into serosa and adjacent fat. Two
paraoesophageal lymph nodes contained adenocarci-
noma with appearances compatible with metastases from
the oesophageal primary, and which on immunohisto-
chemistry were positive for the epithelial marker cytoker-
atin 7 (CK7) but negative for oestrogen receptor [Figure 1]
and gross cystic disease fluid protein-15 (GCDFP-15),
both of which are breast carcinoma related molecules.
Two further, adjacent lymph nodes contained carcinoma
compatible with metastatic ductal carcinoma of breast ori-
gin [Figure 2]. These expressed oestrogen receptors [Figure
3] and gross cystic disease fluid protein-15 (GCDFP-15).
Several lymph nodes not involved by tumour demon-
strated a silicone-associated reaction [Figure 4].
Conclusion
The present case demonstrates adjacent thoracic lymph
node metastases from two distinct primary malignancies.
Immunohistochemical profiling was used to determine
the site of origin for each metastasis. Two lymph nodes
were positive for GCDFP-15, a highly specific marker for
metastatic breast carcinoma with a specificity and positive
predictive value of 99% [3], whereas the oesophageal
metastases expressed the marker CK7 and were negative
for the breast carcinoma related molecules. This rare case
is, to the authors' knowledge, the first report of mixed
metastatic disease involving metastases from two distinct
primary cancers occurring within adjacent lymph nodes.
Metastasis within a single lymph node from two distinct
primary cancers has previously been documented. This is
termed the 'collision phenomenon' and has been seen
with bladder and prostate, prostate and colon, urothelial
and prostate, and prostate and gastric cancers [4-8]. All of
these reported cases used immunohistochemical charac-
terisation of the lymph node to confirm the tumour of ori-
gin.
Thoracic lymph node metastasis from a primary breast
cancer is an uncommon occurrence [9], and several mech-
anisms may be postulated to explain the present case, as
well as the collision phenomenon. Regional immune sup-
pression by oesophageal squamous carcinoma has been
Oesophageal metastasis in paraoesophageal lymph node staining neg tiv ly for oestrogen receptor (magnification × 100)Figure 1
Oesophageal metastasis in paraoesophageal lymph 
node staining negatively for oestrogen receptor 
(magnification × 100).
Paraoesophageal lymph node containing metastatic ductal bre st carcinoma ( agnification × 100)Figur  2
Paraoesophageal lymph node containing metastatic 
ductal breast carcinoma (magnification × 100).
Lymph node metastasis demonstrating oestrogen receptor-expressing breast carcinoma (magnification × 100)Figure 3
Lymph node metastasis demonstrating oestrogen 
receptor-expressing breast carcinoma (magnification 
× 100).Page 2 of 4
(page number not for citation purposes)
International Seminars in Surgical Oncology 2008, 5:22 http://www.issoonline.com/content/5/1/22reported [1] and O'Mahony et al [10] proposed the exist-
ence of a soluble factor released by oesophageal tumour
cells which induces apoptosis in lymphoid cells. It may
be, therefore, that a local immune suppression exerted by
the oesophageal malignancy facilitated the metastatic
deposit and survival of cancer cells from a distant breast
malignancy. In vitro work, however, suggests this mecha-
nism may be active only for squamous carcinoma of the
oesophagus, as a suppression of regional immune func-
tion by oesophageal adenocarcinoma cells was not seen
[10]. Other mechanisms facilitating regional metastases
from distant cancers include the role of tumour infiltrat-
ing lymphocytes, which have been shown to have a poor
cytotoxic effect on tumour cells compared with standard
lymphocytes [11]. In the present case, there was no radio-
logical evidence of thoracic lymph node disease demon-
strated throughout the follow-up of the breast cancer.
However, breast cancer is often considered as a systemic
disease [12] and it may be that development of an
oesophageal malignancy subsequently led to the deposit
of circulating breast carcinoma cells within an adjacent
thoracic lymph node. However, it may have been that the
thoracic lymph node metastases were present initially and
were too small for detection by CT.
An increased risk of oesophageal cancer has been seen in
breast cancer patients treated with radiotherapy [13-16].
Squamous cell carcinomas are most commonly reported,
but breast cancer patients treated with radiotherapy are
four times more likely to suffer from oesophageal adeno-
carcinoma compared to those not treated with radiother-
apy [15]. The risk is greatest ten years or more following
radiotherapy and there is no increased risk in breast can-
cer patients not receiving radiotherapy [15,16].
Another pathological point of interest in the present case
was the silicone-associated reaction evident in several tho-
racic lymph nodes. Silicone dissemination is well recog-
nised following insertion of silicone prostheses, and has
been reported in blood and lymphatic tissue as well as tis-
sues adjacent to the prosthesis [17]. Leakage of silicone
after breast augmentation has been implicated in the
development of conditions such as Kikuchi's disease (his-
tiocytic necrotising lymphadenitis), as well as systemic
disorders such as autoimmune and connective tissue dis-
ease [17]. Debate continues over the oncological safety of
silicone implants following early reports of breast adeno-
carcinoma and squamous cell carcinoma in patients with
previous silicone breast augmentation [18]. Uncertainty
over the safety of silicone implants led to the Food and
Drug Administration (FDA) restricting their use in the
United States in 1992. Recent studies with long term fol-
low up have failed to demonstrate a link with the devel-
opment of breast cancer, however, and the FDA's position
may be revised in the near future.
Consent
Verbal informed consent was obtained from the patient in
the presence of 3 of the authors prior to death for the pub-
lication of this case report and any accompanying images.
The patient was unable to provide written consent due to
illness and there is no available next of kin from which we
could obtain written consent. This has been discussed and
approved with the Editor-in-Chief.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
All authors have read and approved the final manuscript.
KE, GA, and RB all contributed significantly towards arti-
cle generation and subsequent revision. PR provided the
histological figures and JL oversaw the project and offered
critical analysis.
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Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report

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