Clinical Radiology (2005) 60, 271–274
Metastatic manifestations of invasive lobular breast carcinoma D.J. Doylea,*, N. Relihanb, H.P. Redmondb, J.E. Barrya Departments of aRadiology and bSurgery, Cork University Hospital, Cork, Ireland Invasive lobular breast carcinoma (ILC) is the second most common breast cancer. ILC has a wide range of imaging appearances. The pattern of metastatic spread differs significantly between ILC and ductal carcinoma.1 Metastases to the gastrointestinal tract, genitourinary system and peritoneum/retroperitoneum are more prevalent with ILC than with ductal carcinoma.2 We describe the case of a 50-year-old woman with ILC, detailing her metastatic manifestations and the imaging limitations we encountered in demonstrating these metastases. Clinicians evaluating patients with ILC presenting with gastrointestinal or genitourinary symptoms should have a high index of suspicion of metastasis.
Introduction Invasive lobular carcinoma (ILC) accounts for 10– 15% of all breast cancers. It is bilateral in 6–28% of cases.3 Given the high incidence of breast carcinoma worldwide, the incidence of ILC is greater than that of invasive cervical cancer and two thirds that of ovarian cancer.4 Research has suggested that the use of combined oestrogen and progesterone hormone replacement therapy (CHRT) increases the risk of breast cancer.5 ILC is often difficult to detect by breast palpation or mammography, and the tumour is often significantly larger than non-lobular invasive carcinoma.6 Locally advanced disease at time of presentation is common. The risk of bilateral synchronous or metachronous tumours is approximately twice that of invasive ductal carcinoma.7 Metastatic disease from invasive ductal carcinoma most commonly affects lung, liver, bone and * Guarantor and correspondent: D.J. Doyle, Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. Tel.: C353 214922253; fax: C353 214922857. E-mail address: [email protected]
brain. ILC also metastasizes to these sites, but also is more often found in the gastrointestinal tract (GIT), pelvic organs, peritoneum/retroperitoneum and genitourinary tract (GIT) than infiltrating ductal carcinoma.2 By describing a specific case, we aim to discuss the spectrum of metastatic disease peculiar to ILC.
Case report A 50-year-old woman presented in December 1998, with a clinically suspicious, palpable mass superior to her right nipple. Her past medical history included non-insulin dependent diabetes mellitus, hypothyroidism and hepatitis C. A mammogram at the time demonstrated asymmetric density at the 12 o’clock position in the right breast (Fig. 1). Breast ultrasound was not performed. Fine needle aspiration of the lesion demonstrated uniform epithelial cells, and no malignant cells were seen. In view of the clinically suspicious features, a diagnostic excision biopsy was carried out. This confirmed a moderately well differentiated invasive lobular carcinoma with the margin of the specimen involved. The tumour measured approximately 2 cm in diameter. Definitive cancer surgery included a wider local excision, sentinel node mapping and level 2 axillary clearance. On histology, 17/17 lymph nodes were positive and the tumour was oestrogen receptor positive. Preoperative staging examinations with an isotope bone scan and ultrasound of the liver were normal. The tumour was pathologically staged at P T2 N1. The woman received adjuvant ECMF chemotherapy, followed by 45 Gy of radiotherapy to the right breast and right supraclavicular fossa. This was given in 20 fractions. She commenced tamoxifen 20 mg daily following completion of chemotherapy. In July 2002, 3 years after initial presentation, the woman was found to have a skin nodule on the anterior abdominal wall overlying the liver. An
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excision biopsy of this nodule confirmed metastatic lobular carcinoma, and the tamoxifen was changed to anastrozole 1 mg daily. After approximately 6 weeks, the patient complained of altered bowel habit, namely constipation and tenesmus. A rectal examination revealed the presence of a mass on the posterior wall of the rectum. A rigid sigmoidoscopy biopsy demonstrated a submucosal infiltrate of atypical epithelial cells consistent with metastatic lobular carcinoma. CT performed for restaging showed a normal liver, no significant lymphadenopathy and asymmetrical thickening of the rectal wall with perirectal stranding (Fig. 2). MRI of the pelvis confirmed circumferential thickening of the rectal wall with a thickness of 2 cm extending over a length of 3 cm (Fig. 3). An isotope bone scan was normal. Before radiotherapy the woman underwent a laparoscopy which showed no evidence of peritoneal carcinomatosis, and a defunctioning sigmoid loop colostomy was performed. Three months later, in December 2002, the woman complained of one episode of bleeding from the stoma and also vaginally. Rectal examination under anaesthesia suggested that the rectal metastatic tumour was adherent to the vagina and uterus anteriorly. Hysteroscopy showed grossly abnormal endometrium but no biopsies were taken at this time. It was considered that the appearances of the endometrium could be due to radiotherapy or direct extension of the rectal tumour. Repeat MRI did not show any convincing evidence of vaginal wall invasion and no endometrial thickening. The woman had no further episodes of bleeding. In March 2003, elective hysteroscopy and biopsy showed features indicative of metastatic lobular carcinoma. PET demonstrated low activity in the pelvis, in keeping with mild inflammatory reaction,
Figure 1 Craniocaudal mammographic views of (a) right and (b) left breast showing asymmetrical density at the 12 O’clock position in the right breast, but no definite mass or malignant microcalcifications.
Figure 2 Axial contrast-enhanced CT of the pelvis showing asymmetrical thickening of the left lateral rectal wall with perirectal stranding.
Metastatic manifestations of invasive lobular breast carcinoma
Figure 4 Axial contrast-enhanced CT showing hydronephrosis, mesenteric stranding and lymphadenopathy in the retroperitoneum and mesentery.
Figure 3 Sagittal MRI confirming thickening of the rectal wall with narrowing of the lumen extending over 3 cm.
and no evidence of metastases elsewhere. Ultrasound of the liver was normal. It was therefore planned that the patient should have a hysterectomy and anterior resection. However, at laparotomy in June 2003 the patient was found to have multiple involved lymph nodes within the mesentery, with encasement of the superior mesenteric vessels and abnormal soft tissue within the small bowel mesentery. Metastatic deposits were confirmed on frozen section. The loop colostomy was excised and was subsequently confirmed on paraffin section to have been involved with tumour in all the margins. An end colostomy was formed. Repeat CT did not show any change in the appearance of the rectum but demonstrated small lymph nodes in the retroperitoneum and small bowel mesentery, and a left hydronephrosis (Fig. 4). The patient continued with palliative chemotherapy, achieving good symptom control. In February 2004 she was readmitted with small bowel obstruction. A repeat laparotomy showed obstruction of the terminal ileum with widespread intra-abdominal metastases. An ileotransverse, side-to-side, anastomosis was formed. Her condition deteriorated and she died on February 7, 2004.
Discussion ILC spreads through the breast parenchyma by
means of diffuse infiltration with single rows of malignant cells, causing little disruption and generating little tissue reaction.8 ILC accounts for a significant proportion of mammographically occult breast cancers. In one retrospective study of ILC, 46% of the false negative results on mammograms failed to show any suspicious findings even in retrospect.9 Positive mammographic findings include a spiculated mass in up to 40%.3 A higher incidence of subtle mammographic signs, such as asymmetrical density (3–25%) or architectural distortion (10–25%) has been reported.9 Microcalcifications are not a typical feature.3 The majority of tumours are oestrogen receptor positive.7 It has been suggested that loss of expression of the cell–cell adhesion molecule E-cadherin in ILC may contribute to the differences in metastatic pattern when compared with infiltrating ductal carcinoma.4 In one series of 57 women, bone was the most frequent site of metastasis from ILC (81%). However, gastrointestinal involvement (32%) was as frequent as liver involvement and appeared as bowel wall thickening.4 This study was a retrospective review of CT: the conclusions were based predominantly on imaging findings, often without histological confirmation. Another series of 2605 patients, comparing rates of metastasis from ILC and ductal carcinoma, showed statistically significant differences for metastases in the GIT (4.5% vs 0.2%), gynaecological organs (4.5% vs 0.8%) and peritoneum/retroperitoneum (3.1% vs 0.6%), respectively.1 These cases were reviewed using the tumour registry and therefore had pathologically proven ILC metastases. In general, metastatic tumours to the GIT are rare (1–4%) and typically originate from lung, renal, melanoma and breast primaries.10 ILC can metastasise to the oesophagus, stomach and small and
large bowel, with 50% of metastases affecting the small bowel.1 Spread to the lower GIT is infrequent and often multifocal, as in our case.11 Bowel involvement can occasionally present with obstruction, haemorrhage or perforation. Involvement of the peritoneum usually manifests as small nodules, which may become confluent.12 Retroperitoneal involvement may result in ureteric obstruction and hydronephrosis. Our case demonstrated multifocal involvement of the large bowel and ultimately small bowel, as well as peritoneal metastatic spread. Metastatic spread from ILC to gynaecological organs, including uterus, ovary, vagina and parametrium, has been described. Breast cancer, particularly ILC, is the commonest extragenital neoplasm to metastasise to the uterus.7 The uterus and ovary account for 80% of gynaecological metastases from ILC.8 Metastases to the neck and body of the uterus and endometrial polyps have been reported. This case demonstrates metastatic lobular carcinoma involving skin, rectum, endometrium, peritoneum and retroperitoneum in a single case. Involvement of the uterus and particularly the endometrium is rare. We were unable to find previous case reports of ILC metastasizing to a stoma. There are documented cases of metastasis to either GIT or (GUT), but no specific case documenting metastases to both organ systems. Our case, however, demonstrates a significant number of the metastatic manifestations of ILC in a single patient. Our case also emphasizes the potential limitations of imaging in detection of metastases. MRI did not demonstrate the endometrial involvement. Lack of deep myometrial invasion or superficial involvement may have contributed to our false negative result. Contrast-enhanced MR is clinically useful in excluding deep endometrial invasion. However, with grade 1 endometrial cancers there is only a 13% frequency of deep myometrial invasion.13 PET did not reveal extensive peritoneal or retroperitoneal disease. The recognized limitations of PET include reduced sensitivity with small lesions, particularly those taking up too little FDG to be detectable where the tumour background ratio is not sufficiently high. A recent study comparing PET with axillary lymph node dissection and sentinel lymph node mapping found high specificity (0.97) and positive predictive value. However, sensitivity was low (0.40), and it was concluded that a negative PET does not accurately reflect nodal status.14 Knowledge of the pattern of disease spread is essential for accurate image interpretation, to aid detection and to minimize the possibility of mistaking metastatic disease for a second primary malignancy.4
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Our case demonstrates that lack of positive imaging findings does not exclude metastasis. The somewhat unexpected and atypical pattern of metastatic spread of ILC makes it imperative that clinicians exclude metastatic disease when patients with ILC present with any GIT or GUT symptoms.
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