ARTICLE IN PRESS The Breast (2004) 13, 155–158
Breast metastases from colorectal carcinoma Radu Mihaia,*, Jonathan Christie-Brownb, James Bristola a
Department of Surgery, Cheltenham General Hospital, Cheltenham, UK Department of Pathology, Cheltenham General Hospital, Cheltenham, UK
KEYWORDS Breast; Metastases; Colorectal cancer
Summary A case history is presented of a 53-year-old woman with an incidental finding of a breast lump, identified after having had chemotherapy for lung metastases from a rectal carcinoma. Clinical examination, ultrasound, mammography, fine needle aspiration and core biopsies could not prove definitively whether the breast lump represented a metastasis from colorectal carcinoma. Following local excision, the final diagnosis of metastatic colorectal carcinoma to the breast was based on the absence of any site of origin within the breast (i.e. no surrounding DCIS) and on the expression of cytokeratin CK7 and CK20 on immunohistochemistry. Postoperative chemotherapy was initiated. Four months later, although without local recurrence in the breast, the patient developed cutaneous metastatic deposits and active treatment was stopped. A review of other cases of breast metastases from extramammary sources is presented. Possible mechanisms for this rare and unusual phenomenon are discussed. & 2003 Elsevier Ltd. All rights reserved.
Case history A 53-year-old woman presented to the Breast Clinic with a 10-day history of a breast lump discovered incidentally by the patient. She had no increased risk factors for breast cancer, hormonal or familial. A screening mammogram, 3 months prior to referral was normal. Five years earlier she had undergone an anterior resection for a Dukes’ B rectal carcinoma in another hospital, followed by hysterectomy and bilateral oophorectomy 2 years later for local recurrence of rectal carcinoma. Six months prior to the discovery of the breast lump, she received chemotherapy for lung metastases. Examination revealed a palpable nodule in the lower inner left breast, firm, not fixed, measuring *Corresponding author. University Department of Surgery, Bristol Royal Infirmary, Bristol BS2 8HW, UK. Tel.: þ 44-1179701212x1259; fax: þ 44-117-9253726. E-mail address: r [email protected]
1 cm in diameter, with no associated lymphadenopathy. Ultrasound examination demonstrated regular margins, without malignant features. Mammograms showed a well-defined mass lesion, not obviously malignant (Fig. 1). Fine needle aspiration cytology was suspicious of malignancy (C4). Core biopsies showed poorly differentiated infiltrating adenocarcinoma, with no signs of intestinal differentiation. Although the suspicion of a metastasis from her previous colorectal carcinoma was raised, it was not possible to rule out a primary breast carcinoma on morphological criteria on hematoxylin–eosin staining. Immunohistochemistry studies on the core biopsy specimens proved to be negative for oestrogen receptor, progesterone receptor, BCL-2 and HER-2. Blood samples for tumour markers were positive (CEA 38 mg/l, CA125 70 U/ml). Excision biopsy of the breast lump was performed. On standard histological examination the tumour showed features of poorly differentiated
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The patient restarted chemotherapy and 4 months after surgery there were no signs of local recurrence of the breast lesion. Subsequently she developed cutaneous lesions over the left iliac crest and within right groin, which on core biopsy showed identical morphological features with the breast tumour previously excised. Palliative care was instituted. The initial breast tumour was sent for analysis of cytokeratin expression in another centre and the results confirmed a pattern characteristic for colonic tumours: CK20 positive–CK7 negative.
Review of the literature
Figure 1 Imaging studies in a patient with a solitary breast metastasis from a colorectal carcinoma: (a) ultrasound findings; (b) lateral view/ mammogram; (c) cranio-caudal view/mammogram.
adenocarcinoma with focal necrosis. There was no ductal carcinoma in situ in the surrounding breast tissue. There was no evidence of intestinal differentiation. Immunohistochemistry for CEA was positive, as expected in colorectal tumours but also in some breast carcinomas.
Primary breast cancer is the leading cause of death from malignant disease in women. Every year over 32,000 new cases are diagnosed in the UK. Metastases to the breast from extramammary carcinomas are extremely rare. In about 40% of such patients, the breast lesion is the first manifestation of disease. The correct diagnosis is therefore crucial in these patients so that unnecessary surgical interventions can be avoided. Our patient presented to Breast Clinic when known to have loco-regional and widespread metastatic colorectal cancer. In this clinical context, the suspicion that her breast lump represented a further metastatic deposit was very high. Unfortunately, slides of the primary rectal tumour were not available for histological comparison. Furthermore, the findings on ultrasound and mammography (well-defined mass with regular margins) were in contrast with those reported by others. In a previous study of patients with metastatic tumours to the breast, mammography revealed poorly defined lesions with obscured margins, which on ultrasound examination appeared superficially located, poorly defined, irregular and heterogeneous.1 In the presence of widespread disease, the prognosis for this patient was poor when she presented to our unit. It can be argued that once the diagnosis of a poorly differentiated infiltrating adenocarcinoma was proven on core biopsy, surgical intervention could have been avoided. However, in the absence of definitive proof that the breast lesion represented disseminated disease from the colorectal carcinoma, it was considered that the possibility of a primary breast carcinoma could not be excluded. Because at that stage the clinical condition of the patient was not severely affected, active management was pursued. This was stopped when she developed further cutaneous metastatic lesions.
ARTICLE IN PRESS Breast metastases from colorectal carcinoma
Table 1 Source of primary tumour in patients with breast metastases.10–25 Lymphoma Melanoma Rhabdomyosarcoma Lung tumours Ovarian tumours Renal cell carcinoma Cervix carcinoma Leukaemia Thyroid Prostatic carcinoma Leiomyosarcoma Intestinal carcinoid Pancreatic adenocarcinoma Mesothelioma Gastric carcinoma Plasma cell myeloma Individual cases:
23 21 15 11 11 8 7 5 5 5 5 4 3 2 2 2 retroperitoneal sarcoma, cholangiocarcinoma, squamos cell carcinoma of the skin peripheral neuroblastoma Meckel cell carcinoma
For our patient the diagnosis was finally reached after studying the pattern of cytokeratin (CK) expression. Recently, expression of CK with different molecular weight has been found to help identify the origin of adenocarcinomas whose morphological features do not allow to specify the initial origin. Expression of CK7 and CK20 is considered to be most helpful in this algorithm. Some tumours express none of these cytokeratins (renal), some tumours express both cytokeratins (mucinous ovarian carcinoma, pancreatic carcinoma, transitional cell carcinoma of the bladder). Importantly, the great majority of breast tumours are CK7-positive and CK20-negative while colorectal carcinomas are usually CK7-negative and CK20-positive.2 A review published in 1981 quoted that only about 200 cases of metastases to the breast were described in the literature at the time.3 A literature search identified a further 145 cases reported in 46 studies performed between 1980 and 2000 (Table 1). It appears therefore that the total number of patients reported in the English literature to have metastases to the breast is under 400. The real incidence is difficult to know and is probably much higher. This is suggested by data from an autopsy study that reported incidental
findings of breast metastases in patients with known melanomas, ovarian, renal cell and gastric adenocarcinomas.4 Patients with breast secondaries from a colorectal primary neoplasm are extremely rare. Only six such patients have been reported in the last 20 years, two of them being in men.5–8 This rare incidence of metastases to the breast from tumours without any anatomical connection to the breast raises questions about the possible underlying mechanisms for such events. According to the widely accepted model, micrometastatic foci arise from dissemination of clonogenic cells possessing essentially similar characteristics to the primary tumour. The spread of such cells is mediated by systemic circulation, lymphatic circulation or transcoelomic migration. This model does not explain the occurrence of solitary metastases in unusual sites such as the breast. An alternative hypothesis of metastasis has been proposed recently.9 Following death by apoptosis of existing cancer cells, discrete fragments of cellular genome may be released into the circulation and subsequently taken up by cells of the reticuloendothelial system. Such fragments of genetic material may be passed to other cells of the reticulo-endothelial system and possibly to other normal cells via transfection. This could lead to expression of oncogenic sequences and development of cancer cell phenotypes in unexpected locations. Such a mechanism could explain involvement of breast tissue in metastatic processes not explained otherwise by the ‘‘classical mechanisms’’. Further studies might shed more light on this unorthodox hypothesis.
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