A Late Recurrent Metastatic Breast Cancer Mimicking Primary Pancreatic Cancer: Case Report

Abstract

Metastasis to the pancreas from malignant tumors is a rare event, representing only 1% to 2% of all pancreatic neoplasms. They occur in 2 different clinicopathological settings: as a manifestation in widespread metastatic disease or as an isolated mass in the pancreas. We report the case of a 41-year-old woman who had a history of invasive lobular breast cancer treated with radical surgery, chemotherapy, and radiotherapy. After 21 years of total remission, she presented for severe lower back pain with jaundice, nausea, and loss of 9 kg in 3 months. Abdominal computed tomography demonstrated a hyper vascularized, irregular solid lesion of 2.6 cm × 2.1 cm in the head of the pancreas with discreet biliary duct dilatation and coelio-mesenteric enlarged lymph nodes measuring 2 cm. The diagnosis of pancreatic metastasis from a lobular breast carcinoma was made by percutaneous biopsy of pancreatic lesion. The multidisciplinary committee decided a palliative treatment. The patient received chemotherapy. The take home message from his case is that we should keep in mind the hypothesis of a solitary metastasis to the pancreas, when the pancreatic lesion develops in a patient who had a clinical history of previous neoplasm especially in those which is known to potentially metastasize to pancreas.

Introduction

Metastasis to the pancreas from malignant tumors is a rare event, representing only 1% to 2% of all pancreatic neoplasms. ¹ They occur in 2 different clinicopathological settings: as a manifestation in widespread metastatic disease or as an isolated mass in the pancreas. In the context of widespread metastatic disease, the incidence at autopsy ranges from 1.6% to 11%.^2,3

The pancreas can be affected by direct invasion from cancers in neighboring organs or by lymphatic and hematogenous spread, which is most common in lung and kidney cancer. Less common are carcinomas of thyroid, colon, skin, esophagus, gall bladder, urinary bladder, and gynecological cancers. However, breast cancer metastases form only a minority of an already small patient population. ⁴ In fact, breast cancer mainly metastasizes to the bones, lungs, and liver. Metastases to the pancreas are extremely rare. The incidence of pancreatic lesions, such as solitary metastases from primary breast cancer, is less than 3%. However, the occurrence of isolated metastases in the pancreas is even rare.^2,4

Case Presentation

In December 1994, a 41-year-old woman refereed to our institute for a mass in her upper outer quadrant of the left breast, associated with palpable axillary lymph node. The tumor size was 1 cm × 2 cm. A mammography and ultrasound imaging were done; they showed 2 suspected masses in the outer quadrant of the left breast distant a 3-cm classified ACR 5. No distant metastases were revealed thorough the evaluation including computed tomography (CT) scan. Pathology showed invasive lobular breast carcinoma after fine-needle aspiration. The patient presented with a normal level of CA 153 (4 U/mL). The disease was staged T1mN0M0. She underwent modified radical mastectomy. The histological examination of the specimen concluded to breast invasive lobular carcinoma measuring 2 and 1 cm and estrogen receptor (ER)/progesterone receptor (PR) negative, KI67 = 30%. Human epidermal growth factor receptor 2 (HER2) was negative. One metastatic lymph node was found in a level 1 axillary clearance (1N+/15). She had received adjuvant radiotherapy and chemotherapy. The patient was then followed up every 6 months for 5 years and then every year with serial examinations (mammography, bone scintigraphy, and CT scans) for locoregional and distant recurrence. After 21 years of total remission, she presented in June 2020 to our emergency for severe lower back pain with jaundice, nausea, and loss of 9 kg in 3 months. The abdomen was painful to deep palpation and the physical examination revealed frank cutaneous mucosal jaundice. However, there was no palpable mass in the right breast. An abdominal CT scan showed a hypervascular, irregular solid lesion measuring 2.6 cm × 2.1 cm in the head of the pancreas with subtle dilatation of the biliary tree and coelio-mesenteric enlarged lymph nodes measuring 2 cm (Figure 1). Mammography was free of suspected lesion. Total bilirubin was 70 μmol/L (normal <20), raised alanine transaminase (ALT) at 400 U/L (normal <34), and aspartate transaminase (AST) at 500 U/L (normal <31). Alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were also mildly raised at 200 U/L for ALP (normal = 30-110) and 230 U/L for GGT (normal <38). CA 125, ACE and CA 19.9, both markers of pancreatic cancer, were not raised. A percutaneous biopsy was performed. Histology demonstrated a poorly differentiated tumors and epithelial cells with abundant cytoplasm, hyperchromatic pleomorphic nuclei, and distinct nucleoli, arranged in columns and glandular-like structures (Figure 2). Immunohistochemistry (IHC) analysis revealed GATA and ER nuclear expression (Figure 3). Poorly differentiated lobular breast carcinoma was the final diagnosis.

Figure 1.

Axial (A) contrast-enhanced CT images which show a poorly defined tissue mass of the cephalic pancreas with intense enhancement (arrow). Coronal (B) contrast-enhanced CT images which show a poorly defined tissue mass of the cephalic pancreas with intense enhancement (arrow). Sagittal (C) contrast-enhanced CT images which show a poorly defined tissue mass of the cephalic pancreas with intense enhancement (arrow).

Figure 2.

(A) Pancreatic parenchyma (arrow) massively invaded by a poorly differentiated carcinoma (H&E stain, ×100). (B) Epithelial cells with abundant cytoplasm, hyperchromatic pleomorphic nuclei, and distinct nucleoli, arranged in columns and glandular-like structures (arrow) (H&E stain, 2100).

Figure 3.

(A) Immunohistochemistry (IHC) analysis revealed GATA3 n (×200). (B) Immunohistochemistry (IHC) analysis estrogen receptor nuclear expression (×200).

The multidisciplinary committee decided a palliative treatment; our patient underwent endoscopic biliary stent and then chemotherapy with paclitaxel, but she received only 2 courses due to the deterioration of general condition and then she lost of follow-up.

Discussion

In the literature, breast cancer commonly metastasizes to the liver, bones, and lungs. Renal cell carcinoma is the most common primary tumor which metastasize to the pancreas. ³ However, pancreatic involvement in solitary metastases from a primary breast cancer is rare, occurring in less than 3% of cases. ⁵

A review of literature done by Apodaca-Rueda et al showed that most frequent histological type (18 cases from 28 cases of pancreatic metastasis) was lobular carcinoma, in 23 cases was a solitary disease, and in the majority of cases, the disease affected the head of the pancreas (22 cases). The mean time between the diagnosis of a primary breast neoplasm and a metastasis in the pancreas was 43.3 months.^5,6

Other series also showed a long time interval between primary and the appearance of metastasis disease; in the series of Eidt et al, ⁷ patients developed metastasis between 9 and 20 years after surgery of the primary (median 13 years). In our case, the asymptomatic interval was 21 years, and the patient presented with metastases in the region of the head of the pancreas, with a histopathological diagnosis of tubular carcinoma.

In the literature, the clinical signs of metastatic disease are not specific; the main signs are abdominal pain and obstructive jaundice. ⁵ Our patient presented with severe lower back pain with jaundice, nausea, and loss of 9 kg; these symptoms are the same as primitive pancreatic cancer.

Diagnosis is often made using ultrasound, CT, and magnetic resonance imaging. They may support the clinical suspicion of metastatic disease especially in case of multiple lesions in the pancreas; they appear as hypervascular lesions. Distinguishing primary endocrine pancreatic tumors from pancreatic metastases is often difficult. Using serum markers, such as CA 15.3, can help to make the diagnosis, although in some cases, its serum elevation is not relevant and does not always significant ³ likely our case which the lesion was isolated and located in the head of pancreas.

To confirm the metastatic disease, and to response to the relevant clinical question if the lesion is a primary pancreatic neoplasm or an isolated metastasis which would change the operative management. Pancreatic biopsy remains the most accurate method; many methods for diagnosis such as fine-needle biopsies guided by endoscopic ultrasound or percutaneously. This can help to establish the correct diagnosis. It is particularly useful in the case of inoperable disease to assess the type of chemotherapy. In some cases, only the operation revealed the histological nature of the lesion.^2,4,5

Immunohistochemistry remains the best method to distinguish between a primary and metastatic tumor. GATA3 is the most sensitive marker of mammary differentiation; positivity has been reported in 73% to 96% cases of metastatic breast. ⁸

The non-availability of endoscopic ultrasound at our institution precluded its use in the present case. Therefore, the patient underwent percutaneous biopsy of the pancreatic lesion.

Currently, breast metastasis can be detected by positron emission tomography (PET)/CT and fluorodeoxyglucose (FDG)-PET, by becoming a standard part of breast cancer staging and surveillance in the future. ⁶ But, in some series, 18-FDG-PET was negative; it showed increased focal uptake of 18-FDG within the pancreas. ² Unfortunately, in our case, PET scan has not been carried out because of the long waiting time.

Because there is no standardized treatment every case should be discussed in the committee in the presence of oncology and surgery teams and surgery should be recommended in cases without widespread disease. ⁵ There were a few guidelines for the management of these lesions. Some authors, especially in medical centers with experienced surgeons, recommend surgery as the first choice.

However, authors recommended palliative treatment because the worse prognosis and the mortality and morbidity of the surgery. ² The reviewing of the previous series concluded that pancreatic resections for primary tumor were associated with high morbidity and mortality, and metastatic disease to the pancreas was considered the terminal stage of the disease, so palliative treatment is considered in first intension. ² Recently, pancreatic resection has been shown to significantly reduce operative risk, extending the indication for surgery to patients with metastatic disease. ² Unfortunately, only a minority of patients presented with isolated pancreatic metastasis because most patients diagnosed in stage of extrapancreatic metastases, so the interpretation of these data is difficult and concise treatment recommendations are not standardized. Therefore, these patients are less likely to be candidates for surgical resection. ¹

The benefit of pancreatic resection is depending of the site of primitive tumor, and in fact, Crippa et al found that patients with kidney cell carcinoma had better prognosis than other metastatic tumors to the pancreas; indeed, recurrence rate was 40% in kidney carcinoma group and 83.5% in other primitive tumors. Also he found that 80% of kidney carcinoma patients are still alive after a mean time of 40.8 months, whereas the mean survival time of non-kidney carcinoma and radical surgical resection has been proven to be associated with improved survival and a better quality of life. ²

Other authors demonstrated the benefit of pancreatic surgery in fact; the median disease-free interval (DFI) was 75 months, compared to 12 months for those who were not offered resection (P < .05). This most likely reflects the tumor biology; a favorable biology will likely have an extended DFI and a favorable survival. Also, symptomatic disease is related to a worse prognosis. ¹

The patients who can benefit from the surgery should be well selected; the original tumor biology could be favorable, such as isolated metastases from lobular carcinoma of the breast and an isolated metastatic lesion in the pancreas. But the lack or the impossibility of biopsy should not rule an attempt at a curative surgery.^5,6

Some authors recommended chemotherapy after surgery for resectable disease because metastatic. ⁴ Systemic therapy can be indicated first if pancreatic metastasis occurs many years after primary tumor.^1,8

If the disease is unresectable, surgery and chemotherapy may improve the quality of life, but not the survival rate; in rare cases of renal cell metastases, surgery may improve the survival rate after palliative surgery. ⁹ Unfortunately, our patient presented with deterioration of general condition so unfit for surgery and ever for chemotherapy.

In the literature, patients with metastatic pancreatic cancer usually have a better prognosis than those with primary pancreatic cancer, with 2- and 5-year survival rates of 57.1% and 34.3%, respectively, which is better than primary pancreatic carcinoma.^4,5 Also survival in patients with isolated breast cancer metastases is prolonged after an R0 pancreatic resection. ⁶

Despite the benefit of surgical resection which was demonstrated in the literature, until now there is no consensus for the management in pancreatic metastases because of the small number of patients included in these series.

Conclusion

Despite the rarity of this disease, we should keep in mind the hypothesis of a solitary metastasis to the pancreas, when the pancreatic lesion develops in a patient who had a clinical history of previous neoplasm especially in those which is known to potentially metastasize to pancreas. The treatment should be discussed in team including an oncologist and a surgeon. It should be personalized, and the decision should be depending on the site and the histologic type of metastases and the clinical status of the patient.