Diagnostic challenge in silent metastatic invasive breast carcinoma: dysphagia as the only symptom

Abstract

Metastatic cancer to the oesophagus is rare. Most cases are diagnosed at autopsy or surgery. The breast is the most common organ bearing a primary tumour. Metastatic oesophageal tumours are nearly always located in the submucosal layer with normal benign-looking mucosa, rendering tissue diagnosis difficult. In the absence of breast-related symptoms, the diagnosis of oesophageal metastasis from breast primary would be very challenging. We report a case of a 50 year-old woman, who was referred to our centre for a second opinion after she was offered an esophagectomy for a suspected oesophageal carcinoma. She presented solely with dysphagia and weight loss. Multiple investigations were performed to investigate her dysphagia which eventually led to the diagnosis of metastatic breast cancer with oesophageal involvement. She underwent excision of right breast invasive lobular carcinoma with axillary dissection. She completed her adjuvant chemoradiotherapy and currently on daily dose of tamoxifen, whereby her dysphagia has dramatically improved.

Background

Metastasis to the oesophagus is very uncommon and hence arriving at the diagnosis is also challenging. In a patient confirmed with breast cancer, worsening dysphagia, typical radiological pattern and negative endoscopic biopsies with apparently normal oesophageal mucosa should raise the suspicion of oesophageal metastasis. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) together with endoscopic submucosal dissection (ESD) may help in establishing the diagnosis. However, negative tissue samples will not exclude the diagnosis. Thus, a diagnosis of ‘breast–oesophagus’ syndrome can only be given after excluding other diseases or after relief of dysphagia with adequate treatment. Given the high risk of perforation from endoscopic procedures, the treatments of choice are currently chemotherapy, radiotherapy and/or hormonal therapy.

Case presentation

We received a referred case of a 50-year-old woman with no previous medical or surgical history, who presented with progressive dysphagia for 9 months duration, from one of the private hospitals. Initially to solid food, and eventually to liquid, to the extent that she could not swallow her saliva. The patient came to us to get a second opinion after she was counselled for a total esophagectomy for a probable oesophageal cancer without proven biopsy result. She lost a significant amount of weight (20 kg) within the 9-month period. On further questioning, she gave a history of intermittent mild gastro-oesophageal (GE) reflux symptoms but did not require any medication. She was neither a smoker nor an alcoholic. There was no history of corrosive ingestion. She did not notice any breast lump previously, but from our clinical examination there was a discrete 2 cm × 1 cm lesion in the right axillary tail. Other physical examinations were unremarkable.

Investigations

Multiple oesophagogastroduodenoscopies (OGDS) performed in the private hospital using the smallest scope diameter showed a long segment oesophageal stricture with normal mucosa. Multiple tissue biopsies were taken which revealed either mild benign reflux disease or normal mucosa. Positron Emission Tomography (PET)-CT scan which was also done in private hospital earlier showed hypermetabolic long segment circumferential thickening of mid and distal oesophagus extending to GE junction and fundus of the stomach suggestive of infiltrative disease (figure 1). There was also mediastinal, hilar and bilateral axillary nodes, as well as an increase in marrow activity in the axial skeleton and incidental finding of an indeterminate bilateral breast lesion. Dilatation of the oesophagus was attempted without success. She was started on a proton pump inhibitor for possible reflux-related symptoms however there was not any improvement.

Figure 1.

PET-CT scan of thorax shows hypermetabolic long segment circumferential thickening along oesophagus suggesting infiltrative disease.

We repeated the OGDS with the smallest scope calibre (nasojejunoscope) and noted the stricture extending from 16 cm to 25 cm from the incisor and from 30 cm to 37 cm with normal mucosa throughout the oesophagus and stomach (figure 2). We attempted dilatation however it failed and was complicated with aspiration pneumonia and respiratory failure which needed intubation and intensive care unit admission. After recovery, nasojejunostomy tube was inserted to optimise her nutrition. High-resolution manometry and pH study were performed as a diagnosis of atypical long segment oesophageal stricture secondary to Gastroesophageal reflux disease (GERD) was considered. However, both tests were inconclusive. EUS and endoscopic mucosal resection (EMR)/ESD to obtain deeper tissue diagnosis were considered as well but due to the severity of the stenosis it was deferred. Tuberculosis (TB) workup and connective tissue disease screening were negative. A bone scan showed indeterminate lesions of the axial skeleton and proximal left femur. Carcinoembryonic antigen (CEA), Ca 125 and Ca 19–9 were normal.

Figure 2.

Upper endoscopic finding of narrowed mid oesophagus, long segment stricture with normal lining mucosa.

Mammogram, breast ultrasound and MRI breast showed indeterminate lesions of bilateral breast and bilateral axillary lymphadenopathy. The largest lymph node seen over the right axilla (measuring 2.2 cm × 1.8 cm) was biopsied and it revealed metastatic carcinoma with a primary lesion likely from the breast. Ultrasound-guided biopsy of a small right breast lesion (measuring 5.4 mm × 3.6 mm × 3.3 mm) was also done and came back as invasive lobular carcinoma, Estrogen-receptor (ER) positive.

Differential diagnosis

The initial provisional diagnosis for this patient was oesophageal carcinoma based on the history and PET- CT imaging even though we did not have a proven biopsy. We considered lymphoma as a differential due to the diffuse infiltrative nature of this disease. Other differentials include atypical GERD, oeosinophilic oesophagitis, TB and autoimmune diseases such as sarcoidosis.

Treatment

She underwent hook wire localisation and wide local excision of her right breast lesion and axillary dissection. Full histopathology of the right breast was reported as invasive lobular carcinoma of T1b, N3a. She completed her adjuvant radiotherapy and a 5-month course of doxorubicin and cyclophosphamide chemotherapy regime. She is currently on tamoxifen 20 mg daily.

Outcome and follow-up

At present, she can tolerate soft diet. She is on tamoxifen 20 mg daily. CT thorax was done post completion of chemotherapy which showed a slight reduction in oesophageal thickening (figure 3).

Figure 3.

Contrast-enhanced CT scan of thorax shows a slight reduction in oesophageal thickening after completed chemoradiotherapy.

Discussion

Most often a complete history, description of the patient’s symptoms, and physical examination will lead the examiner to the diagnosis. However sometimes, making the diagnosis can be exceptionally challenging, necessitating a high index of suspicion and extensive investigations in order to reach the diagnosis. Very often this will lead to a delayed diagnosis and unfortunately poorer prognosis for the patient.

Oesophageal stricture due to metastases arising from distant organs is rare. The breast is one of the most common organs bearing a primary tumour, which accounts for 7.4%–22% of all metastatic oesophageal tumours.¹ Metastasis from lungs, endometrium, colorectal, ovarian, renal carcinoma, prostate, and melanoma have also been reported.

In oesophageal metastasis, OGDS would reveal an oesophageal stricture with apparently smooth and benign-appearing overlying mucosa.^{1 2} The intramural or submucosal nature of the lesions renders tissue biopsy difficult. Superficial biopsy of the mucosa is non-diagnostic. A CT scan would typically detect thickening of the oesophageal wall without any extrinsic or endoluminal mass. Arriving at a plausible diagnosis in a patient who does not have any breast symptoms is rather demanding akin to looking for a needle in a haystack.

Metastasis to the oesophagus can be via hematogenous or lymphatic spread. Direct contiguous invasion from an adjacent organ is more common. For metastatic breast cancer, periesophageal lymph nodes involvement through intramammary lymphatic channels may cause obstruction at the level of mid and distal oesophagus. Meanwhile, the reason for submucosal location of metastatic oesophageal disease is most likely attributed to the extensive lymphatic plexus found in the oesophageal submucosa.^{3 4}

In metastatic cancer to the oesophagus, the time of onset of progressive dysphagia is dependent on the primary cancer. Oesophageal disease from breast primaries tends to occur much later, with reports ranging between 4 and 10 years after diagnosis of breast cancer was made.^5–7 To our knowledge, our patient is the third reported case with dysphagia as the initial symptom that brings to the diagnosis of metastatic breast cancer. One of them had undergone total esophagectomy in view of suspicion of primary oesophageal malignancy.

From the literature, a few methods have been reported to obtain tissue diagnosis. However, complications including perforation and bleeding have to be considered. The diagnosis of metastasis to the oesophagus may be aided by EUS and FNA.⁷ EUS will provide visualisation of the lesions in the submucosa or muscularis propria as well as enlarged paraesophageal lymph nodes. FNA can be targeted to yield cytological diagnosis of metastatic disease. Such approach has been evaluated with success in metastatic breast cancer. As of now, it is not a widely known or adopted practice in the evaluation of metastatic oesophageal strictures due to the relatively small specimens obtained using this method making it difficult to differentiate benign from malignant tumours. Normal findings also do not exclude the possibility of malignancy.

EMR also was introduced as one of the diagnostic tools. EMR using a capping method with the injection of 20 mL of saline underneath the mucosa was reported as a successful method to diagnose metastasis to the oesophagus by the aid of immunohistochemistry.

The diagnosis of oesophageal metastasis from primary breast cancer in this patient is crucial because the treatment includes chemotherapy, radiotherapy and/or hormonal therapy without the need for extensive surgery/esophagectomy⁸

Learning points.

• Metastatic cancer to oesophagus is rare. Most cases are diagnosed at autopsy or major surgery.

• Breast is one of the most common organs bearing a primary tumour.

• In the absence of breast lump or breast-related symptoms, diagnosis of oesophageal metastasis from breast primary would be very challenging and often delayed.

• Careful history, physical examination and extensive investigations are needed in the diagnosis of metastatic cancer to oesophagus including oesophagogastroduodenoscopies, CT scan, PET scan, endoscopic ultrasound and fine needle aspiration and endoscopic mucosal resection. Negative tissue sample however will not exclude the diagnosis.

• A ‘breast–oesophagus’ syndrome can only be diagnosed after excluding other diseases or after relief of dysphagia with adequate therapy.

• The diagnosis is of clinical importance because oesophageal metastasis from breast cancer can be treated by chemotherapy, radiotherapy and/or hormonal therapy without the need for extensive surgery. This ensures the patient receives the appropriate treatment without unnecessary morbidity and mortality. Multidisciplinary team discussions are important.

Ethics statements

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