Annals of Oncology 12 715-718, 2001.
© 2001 KluHer Academic Publishers. Primed in the Netherlands
Clinical case
Rectal metastases from lobular carcinoma of the breast:
Report of a case and literature review
A. Bamias,1 G. Baltayiannis,2 S. Kamina, 3 M. Fatouros,4 E. Lymperopoulos,1 N. Agnanti,3
E. Tsianos2 & N. Pavlidis1
Departments of 'Medical Oncology. 2Gastroenterology. 'Histopathology, 4 Surgery. Ioannina University Hospital, loannina, Greece
Summary
Metastatic involvement of the gastrointestinal (GI) tract secondary to breast cancer is rare. Reported herein is the case of a
74-year-old woman with metastatic lobular breast carcinoma
to the rectum presenting with obstruction. The breast tumour
was diagnosed nine years prior to the presentation of rectal
metastases. Endoscopy was repeated twice until a diagnosis
was established. Examination of endoscopy material revealed
infiltration of the rectum by malignant signet ring cells identi-
Introduction
Breast cancer is the most frequent malignancy in the
female population and a significant cause of morbidity
and mortality. Distant metastases are present in about
60% of the patients at the time of diagnosis, while 30%80% will develop metastatic disease following surgery
and/or chemotherapy, radiotherapy or endocrine therapy
[1]. Breast carcinoma usually metastasizes to lymph
nodes, lung, bone, liver or brain, but GI involvement is
rare [2]. The most frequent sites of the GI tract involved
are the stomach and the small intestine [3-6], while
colonic and rectal metastases are extremely rare. Especially rectal involvement has been mostly reported as
single cases, with only one serie of seven cases published
[2, 4, 7-11]. Nevertheless, recognition of this rare entity is
important, because presentation resembles that of primary rectal carcinoma and different therapeutic modalities may be appropriate. We herein report the case of a
patient with breast cancer metastases to the rectum
presenting with obstruction along with a review of
English published literature.
Case report
A 74-year-old woman had undergone right modified
radical mastectomy and axillary lymph node dissection
in 1991 due to a breast adenocarcinoma. Histopathological examination revealed a 6 cm infiltrating lobular
adenocarcinoma of histological grade 2, with all 10 re-
cal to those of the primary breast tumour. The patient did not
respond to chemotherapy and underwent laparotomy with a
defunctioning colostomy. Literature review revealed only a few
more cases of metastatic breast carcinoma to the rectum.
Awareness of this condition may lead to accurate diagnosis
and early initiation of systemic treatment, thus avoiding surgical
intervention.
Key words: breast cancer, lobular carcinoma, rectal metastases
sected lymph nodes infiltrated by tumour cells (Figure la).
Immunohistochemistry for oestrogen and progesterone
receptors showed weak staining of 20% of cancer cells
for both receptors. There was no evidence of distant
metastases at the time of diagnosis.
The patient received six cycles of adjuvant chemotherapy (cyclophosphamide, mitoxantrone, 5-fluorouracil). Two years after the operation, she was started on
tamoxifen (20 mg daily) due to the development of bone
metastases. Four years later, there was progression of
bone disease with pain in the pelvis and lumbar spine.
The radiographic examination revealed several osteolytic
and osteoblastic lesions in the sacrum. She received
second-line hormone treatment with methoxyprogesterone (160 mg daily) and radiation therapy at the
sacrum (3000 cGy), resulting in significant remission of
her symptoms.
One year later, she complained of progressively
worsening constipation with tenesmus. An abdominal
computerised tomography (CT) scan showed thickness
of the rectal wall and abnormalities of the area between
the rectum and the sacrum consistent with radiation
changes. She underwent rectosigmoidoscopy, which
revealed a diffuse inflammatory area of the lower rectum.
Biopsies were negative for malignant cells. A diagnosis of
postradiation colitis was made and the patient received
cortisone enemas. Because of clinical deterioration and
markedly elevated CA 15-3, a second endoscopy was
performed a year later. At that time, there was an ulcerated area with stenosis of the lumen 7 cm above the anal
verge, just below the lower limit of the radiation field.
716
She received radiotherapy and pamidronate with symptomatic improvement. She remains alive six months
after the operation.
Discussion
Metastatic tumors of the GI tract are unusual but
probably more common than clinically suspected as
shown by autopsy series [4, 5]. Breast cancer is amongst
the commonest primaries metastasising to the GI tract,
along with melanoma, ovary and bladder [4, 8]. Metastases to the stomach and small intestine from breast
cancer have been more frequently reported [2-4, 9-11]
compared to colonic and rectal involvement. Especially
metastases to the rectum are extremely rare and account
for only a minority of large bowel metastases [2, 3, 1116]. We only found two small series and a few case
reports, summarised in Table 1.
Lobular carcinoma represents the commonest breast
cancer metastasising to colon and rectum [2-4], although
it comprises only 10% of breast adenocarcinomas [1].
The reasons for this have not been clarified. The more
common ductal carcinoma has only been reported as the
most frequent primary in one autopsy serie [4], indicating
that metastases from lobular carcinoma possibly become
clinically evident more often or earlier in the course of
(b)
the disease.
Figure 1. (a) Infiltrating lobular carcinoma of the breast with a few
Clinical presentation of metastatic disease to the
'signet-ring'cells (H+E x 400). (b) Metastases of the same carcinoma
GI tract is diverse. Symptoms may be non-specific or
to the rectum with 'signet-ring' morphology. There are no dysplastic
strikingly similar to that of primary GI malignancies [3,
changes in the overlying epithelium or the glands (H + E x 230).
8, 14,15, 17] as it happened in our case. This in combination with the usually long interval after the initial diagThe new biopsy revealed infiltration from malignant nosis [2—4, 8, 11] makes the differential diagnosis between
cells of the signet ring type. Review of the specimen a primary tumour and metastases from a known breast
from the primary lesion confirmed the diagnosis of a carcinoma difficult. The diagnosis of a metastatic lesion
metastatic breast carcinoma to the rectum (Figure lb). to the GI tract becomes even more unlikely on the rare
Immunohistochemical staining for oestrogen and pro- occasion when it represents the first manifestation of
gesterone receptors showed similar results to those of breast cancer [12]. In most series reporting metastases
the primary tumour. Staging investigations revealed no from breast carcinoma to GI tract the median interval
other visceral metastases but a CTscan of her abdomen between diagnosis and presentation of metastases is five
to six years [2^4-]. The interval of 8.5 years in our report
revealed mild bilateral hydronephrosis.
The patient was initially treated with chemotherapy is one of the longest in the literature, although 10 years
consisting of mitomycin-C, mitoxantrone and metho- or more have rarely been reported [2-4, 11].
trexate, while medroxyprogesterone was stopped. After
Although in many cases biopsy obtained during
the first cycle constipation worsened with significant endoscopy will not reveal malignant cells, endoscopy
faecal impaction and pseudo-diarrhea. Due to impend- should be performed in order to accurately detect the
ing obstruction the patient underwent exploratory site of the lesion and because endoscopic appearance
laparotomy. There were several seedings in the pelvic of metastatic lesions may differ from that of a primary
peritoneum, uterus and bladder wall and bilateral carcinoma. Our literature review showed that metastases
hydronephrosis. The bowel wall below the peritoneal to the GI tract may appear as diffuse thickening and
reflection was diffusely thickened. Histopathological rigidity of the colonic wall mimicking plastic linitis,
examination of biopsy specimens from the uterus and Crohn's-like appearance and ulcerated or nodular areas
the right ureter revealed infiltration by malignant cells rather than solitary, discrete masses [2, 3, 9, 12,15, 16]. The
identical to those found by endoscopy. A right ureter- fact that a second endoscopy was required to confirm
ostomy and sigmoid colostomy were performed. The the diagnosis in our case may indicate that follow-up
patient declined any further chemotherapy and she re- endoscopies of such lesions might increase the sensitivity
mained well for four months after the operation, when of this method. Since surgical resection remains the only
she developed pain of her left femur due to osteolysis. other means of establishing a diagnosis, repeated endos-
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Table 1. Rectal metastases from breast carcinoma.
Author
[reference]
Number of
patients
Age
Subtype
Taal et al. [2]
7
60" (median)
Lobular* 15
Ductal" 1
NR" 1
Asch ct al. [5]
3
58
75
NR
NR
NR
NR
Klein and
Sherlock [11]
2
68
77
Lobular
NR
Time from
diagnosis
(months)
53* (median)
78
18
NR
56
276
Haubrich [7]
1
56
Ductal
36
Present report
1
74
Lobular
108
Treatment
Outcome
Resection+systemic" 3
Radiotherapy" 2
Systemic treatment" 12
Median survival 16 months"
Colostomy
Colostomy
NR
Died (2 months)
Died postoperatively
Radiotherapy
Radiotherapy + hypophysectomy
Died shortly after diagnosis
Alive ( > 1 year)
Supportive
Died(l month)
Chemotherapy
Resection
Alive (4 months)
Abbreviation. NR - not reported
° Data of colonic and rectal metastases together (17 patients).
copies might prevent unnecessary surgical procedures in
many of these patients.
Histologically, metastases often do not form glands
or tubular structures but infiltrate as small nests and
strands of tumour cells, which are usually of the signet
ring type. Histopathological diagnosis can be difficult,
particularly for pathologists who are unaware of the
patient's history. In addition, the 'signet-ring' morphology
of lobular carcinoma may mimic other primary tumours,
i.e., gastric carcinoma. The lack of dysplasia or atypia
of the rectal epithelium and the glands surrounding
the malignant cells is often helpful in the differential
diagnosis between a primary and a metastatic lesion.
Immunohistochemistry may also be useful in reaching
the correct diagnosis. The most informative markers are
gross cystic disease fluid protein-15 (GCDFP-15) and
oestrogen (ER) and progesterone (PgR) receptors. Metastatic breast carcinomas are usually positive for
GCDFP-15 and often for ER and/or PgR, in contrast to
most colorectal or gastric carcinomas, which are negative [18-20].
Systemic treatment (chemotherapy, endocrine treatment or both) is usually employed in patients with
metastases to the GI tract, since patients usually present
with involvement of multiple organs [2, 3]. Results are
variable and improvement in more than 50% of the
patients was reported in the only series, where results of
treatment were analysed in detail [2]. Survival after
diagnosis of GI metastases is poor with few patients
surviving beyond two years [2, 3], although survival up
to nine years has also been reported [21]. We also used
chemotherapy as the initial treatment for our patient.
Nevertheless, progression of stenosis prompted surgical
removal of the tumour. Patients with rectal metastases
commonly present having already developed stenosis and
obstruction requiring urgent correction, which usually
cannot be achieved by systemic treatment. This underlines the importance of early diagnosis, which would
enable prompt initiation of systemic treatment, thus
avoiding surgical intervention. Not surprisingly, laparotomy revealed more extensive disease than shown by
preoperative investigations. In most cases reported,
colorectal metastases are part of widespread metastatic
disease [2, 11] and this should be taken into account in
management decisions.
Conclusion
Rectal metastases from breast carcinoma are very rare
and represent the least frequent metastatic site in the GI
tract. Nevertheless, in patients with lobular carcinoma
this possibility should be suspected in the case of symptoms suggesting a rectal lesion. Endoscopy can be helpful but will not confirm the diagnosis in a significant
percentage of cases. A high level of suspicion for metastatic breast cancer, a detailed pathological analysis and
repetition of endoscopy are necessary for early diagnosis,
which might help to avoid surgical treatment.
Acknowledgement
The authors are grateful to Dr A. Skopelitou (Histopathology Department, loannina University Hospital)
for the preparation of the figures.
References
1. Harris JR, Morrow M, Norton L. Malignant tumours of the
breast. In DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer:
Principles & Practice of Oncology, 5th edition. Philadelphia,
Pennsylvania: Lippincott-Raven 1997; 1457-616.
2. Taal BG, den Hartog Jager FCA, Steinmetz R, Peterse H. The
spectrum of gastrointestinal metastases of breast carcinoma.
Gastrointest Endosc 1992: 38: 136-41.
718
3. Schwartz RE, Klimstra DS, Turnbull ADM Metastatic breast
cancer masquerading as gastrointestinal primary. Am J Gastroenterol 1998; 93. 111-4.
4. Washington K, McDonagh D. Secondary tumours of the gastrointestinal tract: Surgical pathologicfindingsand comparison with
autopsy series. Mod Pathol 1995; 8 (4): 427-33.
5 Asch J, Wiedel PD, Habif DV. Gastrointestinal metastases from
carcinoma of the breast. Autopsy study and 18 cases requiring
operative intervention. Arch Surg 1968; 96- 840-3.
6 Graham WP, Goldman L Gastro-intestinal metastases from
carcinoma of the breast. Ann Surg 1964; 159: 477-80.
7. Haubrich WS. Adenocarcinoma of the breast metastatic to the
rectum. Gastrointest Endosc 1985; 31: 403-4.
8. Meyers M, McSweeney J. Secondary neoplasms of the bowel.
Radiology 1972; 105: 1-11.
9. Koos L, Field RE Metastatic carcinoma of breast simulating
Crohn's disease. Int Surg 1980; 65: 359-62.
10 Hansen RM, Lewis JD, Janjan NA, Komorowski RA Occult
carcinoma of the breast masquerading as primary adenocarcinoma of the small intestine. A case report. J Clin Gastroenterol
1988; 10: 213-7.
11. Klein MS, Sherlock P. Gastric and colonic metastases from
breast cancer. Am J Dig Dis 1972; 17- 881-4.
12. Van Halteren HK., Peters H, Gerlag PGG: Large bowel mucosal
metastases from breast cancer. J Clin Oncol 1998; 16-3711-13
13 Smith JL, Painter RW, Bermann MM Breast carcinoma: Colonic
metastases with perforation - report of two cases. Contemp Surg
1989; 35. 47-52.
14. Nyberg B, Sonnefeld T. Metastatic breast cancer causing intestinal obstruction. Acta Chir Scan 1986; 530: 95-6.
15. Fayemi AO, Ali M, Braun EV Metastatic carcinoma simulating
16.
17
18.
19.
20.
21.
linitis plastica of the colon. A case report. Am J Gastroenterol
1979; 71. 311-4.
Rabau MY, Alon RJ, Werbin N, Yossipov Y. Colonic metastases
from lobular carcinoma of the breast. Dis Colon Rectum 1988- 31401-2.
Kanoh T, Shirai Y, Wakai T, Hatakeyama K. Malignant fibrous
histiocytoma metastases to the small intestine and colon presenting as an intussusception. Am J Gastroenterol 1998; 93: 2594-5.
Raju U, MaCK, Shaw A. Signet ring variant of lobular carcinoma
of the breast: A clinicopathologic and immunohistochemical
study. Mod Pathol 1993; 6 (5)- 516-20.
Kaufman O, Deidesheimer T, Muehlenberg M et al. Immunohistochemical differentiation of metastatic breast carcinomas from
metastatic adenocarcinomas of other common primary sites
Histopathology 1996; 29 (3): 233-40
Lagendijk JH, Mullink H, van Diesl PJ et al. Immunohistochemical differentiation between primary adenocarcinoma of the ovary
and ovarian metastases of colonic and breast origin. Comparison
between a statistical and an intuitive approach. Clin Pathol 1999;
52 (4): 283-90.
Hattori T, Mine H, Abe Yet al. Metastatic involvement of the
stomach from breast cancer. Jpn J Surg 1973; 3- 98-105.
Received 28 July 2000; accepted 10 November 2000.
Correspondence to:
Dr A. Bamias
Oncology Department
Ioannina University Hospital
Ioannina 45110, Greece
E-mail: [email protected]