Mastalgia as an atypical presentation of hepatocellular carcinoma: a case report
© The Author(s). 2017
Received: 7 October 2016
Accepted: 6 March 2017
Published: 9 March 2017
As the incidence of hepatocellular carcinoma (HCC) diagnoses in Saudi Arabia has recently increased due to better diagnostic techniques, the incidence of diagnosed HCC metastasis has also increased. Here, we report a case of HCC metastasis to the rib with an initially atypical presentation of mastalgia caused by extrahepatic metastasis.
A 31-year-old woman with a prior hepatitis B viral infection presented with a mass in the left breast accompanied by mastalgia for a 6-month duration. The patient’s liver enzymes were elevated, and her serum α-fetoprotein level was particularly high. Computed tomography of her chest and abdomen showed a soft-tissue mass adhering to the upper chest wall, rib deterioration, and multiple hepatic lesions. A needle biopsy was immunohistochemically analyzed for Glypican-3, Pan-CK, and CK7 and was confirmed to be metastatic HCC.
This metastatic HCC case is unique because it initially presented as mastalgia. We should consider the possibility of metastatic disease when assessing patients with unusual presentations who have risk factors for metastatic carcinoma.
KeywordsMetastatic hepatocellular carcinoma Extrahepatic Bone metastasis Liver cancer
Hepatocellular carcinoma (HCC) is the 3rd most common carcinoma worldwide. In Saudi Arabia, it accounts for approximately 4.8% of all tumors. HCC is the 4th most common cancer in men and the 8th most common cancer in women  and is defined as an epithelial tumor that arises from the malignant transformation of hepatocytes. HCC is the most common primary liver malignancy and is often discovered in patients who present with cirrhosis or other chronic liver diseases . Extrahepatic metastasis (Em) of HCC (EmHCC) is usually seen in a terminal stage and has an aggressive progression . EmHCC manifests in approximately half of HCC cases and is most commonly found in the lung, lymph nodes, or bones . Bone metastasis accounts for 1.6–16% of HCC metastasis. Em occurs most commonly to the ribs (six reported cases), followed by the mandible, the humerus, the femur, the iliac bone, and the vertebral bodies [5, 6]. The prognosis of Em is poor, with a 1-year survival rate of approximately 40% [7–9]. In this report, we present an unusual metastatic HCC case that initially presented as mastalgia caused by an EmHCC to the rib cage.
Biochemical test results and tumor marker levels
Result (normal range)
11.8 (13.0–18.0) g/dL
8.7 (4.0–11.0) k/μL
150 (140–450) k/μL
Serum total protein
6.1 (6–8) g/dL
2.3 (3.5–5) g/dL
651 (15–37) U/L
94 (14–63) U/L
726 (81–234) U/L
376 (5–55) U/L
238 (46–116) U/L
402.5 (0–40) ng/mL
1.20 (5–25) mlU/mL
27.7 (<35) U/mL
605.57 (0–37) U/mL
0.50 (≤3) ng/mL
Accurate diagnosis is the 1st step in optimal cancer care. However, because EmHCC often presents atypically, patients might be misdiagnosed and not receive appropriate treatment in a timely manner. Moreover, distinguishing a primary cancer from secondary metastatic lesions can be challenging. Fortunately, the evolution of diagnostic imaging modalities can assist the physician in accurate diagnostic practices.
In our study, a contrast-enhanced CT scan of the chest showed a destructive lesion on the left 3rd rib as a large soft-tissue mass that anteriorly invaded the ipsilateral pectoralis muscle, causing localized invasion of the breast tissue. Moreover, a contrast-enhanced CT scan of the abdomen showed multifocal hypodense hepatic lesions with centralized necrosis that surrounded an enhanced pseudocapsule and distal branches of the portal vein, all of which are features suggestive of HCC .
Nevertheless, a noninvasive approach to diagnose EmHCC might not be sufficiently precise. Undoubtedly, immunohistochemical diagnosis from needle aspiration biopsy is the gold standard because it provides details about the neoplastic cells involved in the malignant disease process (e.g., arrangement pattern and stain confirmation). Our patient was diagnosed with stage IV HCC with a metastatic epithelial tumor to the 3rd rib. This diagnosis was confirmed by specialized immunohistochemical stains including Glypican-3, cytokeratin pan-antibody (Pan-CK), and cytokeratin 7 (CK7). Glypican-3 is a membrane-bound heparin sulfate proteoglycan that is expressed only in HCC cells and their metastases (Fig. 5) .
Interestingly, hepatocytes can grow in trabecular structures that are surrounded by tissue expressing high levels of ECM proteins such as laminin, vitronectin, collagen, and fibronectin . The defective cell adhesion and migration and proteolysis of extracellular matrix proteins are necessary steps in metastatic development . However, EmHCC can be disseminated either hematogenously or lymphatically to form new neoplastic foci in sites other than the original tumor .
The clinical course and prognosis of EmHCC are not entirely clear. However, recently developed management options can prolong the life expectancy of HCC patients. Furthermore, systemic therapy with sorafenib combined with 5-fluorouracil has shown promising effects for HCC treatment .
In summary, although EmHCC diagnosis can be challenging, physicians should be alert to the possibility of encountering this disease in their differential diagnoses. Regardless of AFP levels, EmHCC requires meticulous evaluation to reach an appropriate diagnosis and to provide suitable treatment.
Extrahepatic metastasis of hepatocellular carcinoma
The authors thank Dr. Abdullatif M. Almousa and Dr. Liga A. Almulla for providing the pathology images for this case presentation.
The authors declare that no funds have been received.
Availability of data and materials
The availability of the data and materials concerning the case report is related to the diagnostic examinations that were recorded during patient hospitalization. The publication of these data was authorized by the Affiliated King Fahd Hospital at the University of Dammam.
AMA-S wrote the original manuscript. MAES reported the pathology and interpreted the immunocytochemistry. Radiology image reporting was performed by AHA-A and IAA, and the revision of the final manuscript was performed by AMA-S and FAK. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of their clinical details and radiological studies. A copy of the consent form is available for review by the editor of this journal.
Ethics approval and consent to participate
As per the University of Dammam Institutional Review Board, case reports do not need ethical approval or patient consent, as long as there is no intervention and no patient identifiers appear in the report. Therefore, neither ethical approval nor patient consent was required for this case report; however, written informed consent was obtained from the patient involved in this study.
The authors declare that no new software has been used.
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- Ministry of Health National Cancer Registry. Cancer Incidence Report-Saudi Arabia 1994–2010. 2014. ISSN: 1658-0559. http://www.chs.gov.sa/Ar/mediacenter/NewsLetter/2010%20Report%20(1).pdf.Google Scholar
- Goldman L, Ausiello DA, editors. Cecil medicine. Philadelphia: Saunders Elsevier; 2008.Google Scholar
- Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2. doi:10.1002/hep.24199.View ArticlePubMedPubMed CentralGoogle Scholar
- Si MS, Amersi F, Golish SR, Ortiz JA. Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg. 2003;69(10):879.PubMedGoogle Scholar
- Woo KM, Kim BC, Cho KT, Kim EJ. Spontaneous epidural hematoma from skull base metastasis of hepatocellular carcinoma. J Korean Neurosurg Soc. 2010;47(6):461–3.View ArticlePubMedPubMed CentralGoogle Scholar
- El Thanaa AH, Radwan NA, Shaker M. Extrahepatic metastases as initial manifestations of hepatocellular carcinoma: an Egyptian experience. Diagn Pathol. 2015;10(1):82. doi:10.1186/s13000-015-0313-1.View ArticleGoogle Scholar
- Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K, Hiramatsu A, Kodama H, Takahashi S, Chayama K. Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol. 2007;13(3):414. doi:10.3748/wjg.v13.i3.414.View ArticlePubMedPubMed CentralGoogle Scholar
- Yang Y, Nagano H, Ota H, Morimoto O, Nakamura M, Wada H, Noda T, Damdinsuren B, Marubashi S, Miyamoto A, Takeda Y. Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery. 2007;141(2):196–202. http://dx.doi.org/10.1016/j.surg.2006.06.033.View ArticlePubMedGoogle Scholar
- Natsuizaka M, Omura T, Akaike T, Kuwata Y, Yamazaki K, Sato T, Karino Y, Toyota J, Suga T, Asaka M. Clinical features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol. 2005;20(11):1781–7. doi:10.1111/j.1440-1746.2005.03919.x.View ArticlePubMedGoogle Scholar
- Silverman PM, Szklaruk J. Controversies in imaging of hepatocellular carcinoma: multidetector CT (MDCT). Cancer Imaging. 2005;5(1):178–87. doi:10.1102/1470-7330.2005.0105.View ArticlePubMedPubMed CentralGoogle Scholar
- Zaakook M, Ayoub M, Sinna EA, El-Sheikh S. Role of glypican-3 immunocytochemistry in differentiating hepatocellular carcinoma from metastatic carcinoma of the liver utilizing fine needle aspiration cytology. J Egypt Natl Canc Inst. 2013;25(4):173–80. http://dx.doi.org/10.1016/j.jnci.2013.07.004.View ArticlePubMedGoogle Scholar
- Bianchi FB, Biagini G, Ballardini G, Cenacchi G, Faccani A, Pisi E, Laschi R, Liotta L, Garbisa S. Basement membrane production by hepatocytes in chronic liver disease. Hepatology. 1984;4(6):1167–72. doi:10.1002/hep.1840040612.View ArticlePubMedGoogle Scholar
- Murphy G, Gavrilovic J. Proteolysis and cell migration: creating a path? Curr Opin Cell Biol. 1999;11(5):614–21. http://dx.doi.org/10.1016/S0955-0674(99)00022-8.View ArticlePubMedGoogle Scholar
- Katyal S, Oliver III JH, Peterson MS, Ferris JV, Carr BS, Baron RL. Extrahepatic metastases of hepatocellular carcinoma 1. Radiology. 2000;216(3):698–703. http://dx.doi.org/10.1148/radiology.216.3.r00se24698.View ArticlePubMedGoogle Scholar
- Deng L, Ren Z, Jia Q, Wu W, Shen H, Wang Y. Schedule-dependent antitumor effects of 5-fluorouracil combined with sorafenib in hepatocellular carcinoma. BMC Cancer. 2013;13(1):363. doi:10.1186/1471-2407-13-363.View ArticlePubMedPubMed CentralGoogle Scholar