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Korean Journal of Clinical Oncology > Article
Bang, Kim, Choi, Bae, Jung, Min, and Eom: Metastatic breast cancer from a hepatocellular carcinoma: a case report

ABSTRACT

Breast metastases from extramammary malignancies are rare. Here, we report a case of breast metastasis from hepatocellular carcinoma (HCC) after breast mass excision in a 63-year-old woman. A new breast nodule was noticed after transarterial chemoembolization, transarterial radioembolization, and stereotactic body radiation therapy for HCC. Breast ultrasound and core needle biopsy were performed to differentiate between the breast tumors. The biopsy result was invasive breast carcinoma, and wide excision of the breast was performed. The final pathological diagnosis was HCC breast metastasis based on histological findings and immunohistochemical staining results. After 9 months of follow-up, HCC and breast metastasis recurred. Despite palliative treatment, the patient died due to complications and general health deterioration. Although breast metastasis due to HCC is very rare, HCC breast metastasis should be considered when a new breast mass is discovered in a patient with a history of HCC for effective treatment and management.

INTRODUCTION

Metastatic breast cancer from extramammary malignancies is uncommon and accounts for about 0.3% to 2.7% of all breast cancers [1]. Metastasis to the breast occurs via both hematogenous and lymphatic routes. Breast metastases most commonly result from malignant melanoma, sarcoma, lung cancer, ovarian tumors, and renal carcinomas [2,3]. In contrast, breast metastasis from hepatocellular carcinoma (HCC) is rare and difficult to diagnose and differentiate into primary or metastatic neoplasms. To the best of our knowledge, there have been few cases reported in Korea and abroad. Herein, we report a rare case of breast metastasis from HCC and review the related literature. This case was approved by the Institutional Review Board of Eunpyeong St. Mary’s Hospital (IRB No. PC22ZESI0145) and received informed consent from the patient.

CASE REPORT

A 63-year-old woman with diabetic nephropathy and hypothyroidism visited our hospital for further examination of her liver dysfunction. In the liver function test, the level of alkaline phosphatase (ALP) was elevated to 240 U/L (normal ALP <120 U/L), and liver ultrasonography revealed a 7.7 cm lobulated hyperechoic mass in the right hepatic dome. HCC was diagnosed by ultrasound-guided core needle biopsy, and the serum alpha-fetoprotein (AFP) level was elevated to 331.21 ng/mL (normal AFP <10.9 ng/mL). Furthermore, other tumor markers, such as protein induced by vitamin K absence (PIVKA-II) and carbohydrate antigen 19-9 (CA19-9) were elevated to 1,331 mAU/mL (normal PIVKA-II <40 mAU/mL) and 90.65 U/mL (normal CA19-9 range 0–37 U/mL), respectively. Immunohistochemical analysis indicated that the biopsy was positive for CD3, CD20, CD38, CD68, and focally positive in immunoglobulin A.
Moreover, consolidation of 2.4 cm with bubble appearance was observed in the posterior basal segment of the right lower lobe of lungs along with the diaphragm on chest computed tomography consequently, video-assisted thoracic surgery and right lower lobe wedge resection were performed for diagnosis and treatment. After lung surgery, the final pathological result was invasive mucinous adenocarcinoma, the rarest type of lung adenocarcinoma. Therefore, the patient was diagnosed with HCC and lung cancer, i.e., two primary cancers.
Transarterial radioembolization, transarterial chemoembolization (TACE), and stereotactic body radiation therapy were performed for HCC for approximately 3 months. For residual HCC lesions, the therapy lasted for 18 months with two rounds of TACE, radiofrequency ablation, and 10 rounds of hypo-fractional radiotherapy.
A follow-up liver magnetic resonance imaging performed 21 months after the first diagnosis revealed a mass of 1.2 cm in the right upper abdominal wall (Fig. 1). Breast ultrasound and core needle biopsy were performed to differentiate between the breast tumors (Fig. 2). The biopsy result was invasive breast carcinoma; consequently, a wide excision of the right breast was performed. Hepatocyte-specific antigen (HSA)- and AFP-positive results were observed in immunohistochemical staining (Fig. 3). Therefore, the breast mass was diagnosed as HCC breast metastasis based on the histological findings and immunohistochemical staining results.
After 9 months of follow-up with conservative care and without residual HCC, a new lesion in the liver S5 and two new nodules in the right breast were detected. Breast core needle biopsy was performed, and the results indicated recurrent metastatic breast carcinoma from HCC. TACE and palliative breast radiotherapy were performed because surgical treatment was deemed to be difficult. Sorafenib was initiated for HCC refractory to TACE. The breast lesion decreased in size after 5 weeks of breast radiation therapy and was maintained. However, because of severe intrahepatic recurrence, sorafenib was discontinued and hepatic arterial infusion chemotherapy was administered. Unfortunately, after 1 month, she died of esophageal ulcers and deteriorated general health condition.

DISCUSSION

Metastatic breast cancer is less common than primary breast cancer, and the rate of metastasis from other primary cancers to breast cancer is about 2%. Vergier et al. [4] have suggested that the breast is resistant to metastasis from extramammary malignancy because of the characteristics of breast tissue with a relatively poor blood supply. The most common metastatic breast cancer is contralateral breast cancer, and other metastases occur in primary malignancies such as melanoma, ovarian carcinoma, lung cancer, rhabdomyosarcoma, gastric cancer, colorectal carcinoma, cervical carcinoma, renal cell carcinoma, neuroendocrine tumor, squamous cell carcinoma of the head and neck, and prostate cancer [3].
HCC is the sixth most common cancer and the second leading cause of cancer-related mortality in Korea [5]. HCC can metastasize directly to the adjacent organs through the blood vessels and lymph glands. The most common metastatic organ is the lung; metastasis to the local lymph nodes, adrenal glands, and bone is common, but metastasis to the breast is rare. The exact metastatic pathway to the breast from HCC is still unknown, and further studies are required [6]. Several authors have previously reported the mammographic and ultrasound features of metastatic breast cancer. Most of the lesions were hypoechoic and round in shape with circumscribed margins. Lobular or irregular masses or lesions with indistinct margins may also occur. Some cases showed microcalcifications [1,3]. Similarly, in this case, the breast lesion revealed a hypoechoic, irregular, and lobulated mass on breast ultrasonography. However, it is difficult to diagnose breast metastasis by radiological examination alone; therefore, if a breast mass is found in a patient with a history of cancer in other organs, the possibility of breast metastasis should be considered.
Close surveillance with advanced diagnostic tools for high-risk patients has helped detect HCC at an early stage. Survival rates of HCC patients have improved significantly in recent years due to substantial advances in the treatment of HCC such as surgical resection, percutaneous ablation, TACE, and liver transplantation. However, in the case of extrahepatic metastasis in HCC, the median survival time is approximately 7 months, and the 1-year survival rate is 24.9% [6]. Moreover, the clinical course of patients with extrahepatic metastasis has not yet been fully clarified, and the prognostic factors are also unclear [7]. Along with those mentioned above, primary and metastatic breast cancer have different treatments and prognoses, and the exact diagnosis of metastatic breast cancer is of utmost importance. Routine pathological examination using core needle biopsy is essential for confirmation. Furthermore, because histological diagnosis of breast metastasis can be more difficult than that of primary breast cancer, immunohistochemical studies may be helpful in differentiating breast metastasis. Tumor-specific markers such as ER/PR/BRST-2 for breast cancer, PSA for prostate cancer, AFP for HCC, TTF-1 for lung cancer, and CK7/20 for gastric carcinoma are helpful in diagnosis [1]. In this case, HSA and AFP played a critical role in the differential diagnosis. The breast metastasis pathologic findings include an absence of associated in situ carcinoma, atypical histologic features, periductal and perilobular distribution, multiple microscopic foci of the tumor, and many lymphatic tumor emboli [4]. The amount of tissue we obtained with core needle biopsy was less than that obtained with wide excision, and the pathological characteristics of this tissue did not show significant differences between primary invasive breast cancer and metastatic breast cancer. Metastasis of HCC to the breast is rare than metastasis of breast cancer to the liver; pathologists did not become aware of this rare case. The HCC-specific marker was not performed on the core needle biopsy tissue, which made a difference between the initial core needle biopsy and post-excision pathologic results.
To the best of our knowledge, this is the fourth report in Korea, and approximately 10 cases have been reported worldwide. The first case was diagnosed as HCC breast metastasis by fine-needle aspiration of a breast mass positive for AFP and HSA [8]. The second and third cases were diagnosed as metastatic breast cancer from HCC using core needle biopsy and a final pathological biopsy result after surgery [1]. Similarly, in this case, it was possible to diagnose HCC breast metastasis based on the results of the final pathological biopsy and immunohistochemical staining after surgery.
Accurately diagnosing metastatic breast cancer is difficult and diagnosing metastatic breast cancer from HCC is even more difficult. This is because clinical features are not well differentiated from other benign or malignant breast diseases, and radiologic features are expressed vary depending on the primary tumor [3]. Immunohistochemistry markers could be useful in cases mimicking primary cancers [4]. If immunohistochemistry study revealed a negative breast cancer marker and a positive extramammary cancer marker, it is necessary to consider the diagnosis of metastatic breast cancer [6]. However, if the immunohistochemical study was inconsistent with the findings mentioned above, pathological comparison of the mass and the personal medical and family history could help to differentiate primary and metastatic cancer. In addition, the exact route of metastasis from HCC to the breast remains unclear [6]. In addition, the exact route of metastasis from HCC to the breast is uncertain. Therefore, further studies on this metastasis pathway are needed and consideration of the individual’s clinical history also needed.
In conclusion, breast metastasis should be considered when a new breast mass is discovered in a patient with a history of HCC, because surgical resection of the liver and breast may not be beneficial for breast metastasis of HCC. Therefore, it is necessary to select the most effective treatment based on the patient’s condition through an accurate diagnosis.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

Notes

FUNDING
None.

REFERENCES

1. Lee SK, Kim WW, Kim SH, Hur SM, Kim S, Choi JH, et al. Characteristics of metastasis in the breast from extramammary malignancies. J Surg Oncol. 2010; 101:137–40.
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3. Abbas J, Wienke A, Spielmann RP, Bach AG, Surov A. Intramammary metastases: comparison of mammographic and ultrasound features. Eur J Radiol. 2013; 82:1423–30.
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4. Vergier B, Trojani M, de Mascarel I, Coindre JM, Le Treut A. Metastases to the breast: differential diagnosis from primary breast carcinoma. J Surg Oncol. 1991; 48:112–6.
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7. Uchino K, Tateishi R, Shiina S, Kanda M, Masuzaki R, Kondo Y, et al. Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer. 2011; 117:4475–83.
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8. Woo SJ, Shin JW, Park JW, Jo JH, Lee GY, Kim YM, et al. Breast metastasis from a hepatocellular carcinoma. Korean J Med. 2007; 72:306–10.

Fig. 1
Magnetic resonance imaging of the breast. (A, B) An enhancing irregular nodule of size 1.2 cm is observed in the right upper abdominal wall (arrow).
kjco-18-2-93f1.jpg
Fig. 2
Ultrasound-guided core needle biopsy. (A, B) Core needle biopsy is performed on an irregular, hypoechoic mass of 1.2 cm with increased blood vessels in the right lower middle breast as observed on the breast ultrasound.
kjco-18-2-93f2.jpg
Fig. 3
Pathological findings of excision (immunohistochemistry, ×20). Tumor cells are positive for both hepatocyte-specific antigen (A) and alpha-fetoprotein (B).
kjco-18-2-93f3.jpg
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