Background
Methods
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Bone metastases (17 cases)The most common site of bone metastases was the ribs (6 cases) followed by the mandible (4 cases). The remaining cases were located in the humerus, femur, iliac bone and vertebral bodies (Fig. 1) (one or two cases for each site). They were clinically and radiologically suspected as primary or secondary malignant neoplasm. Biopsies were taken from all lesions.×
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Lymph node metastases (9 cases)Six cases were located in the abdominal lymph nodes and 3 were situated in the retroperitoneal, inguinal and supraclavicular lymph nodes. Guided needle or excisional biopsies from these sites were performed.
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Soft tissue metastases (7 cases)These metastases were located in the anterior chest wall (4 cases), shoulder (1 case), back, deep to angle of scapula (1 case) and forearm (1 case). CT scan revealed a large soft tissue mass with no underlying bone destruction. Needle biopsies were taken for pathological assessment.
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Omental metastases (7 cases)The main complaint of these cases was abdominal pain, CT scan showed hypoechoic solitary mass in 2 patients and multiple nodules in 5 patients.
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Adrenal gland metastases (2 cases)The patients presented with lumbar pain. Abdominal ultrasound detected a retroperitoneal mass close to the kidney. CT scan with contrast was done and revealed an enhancing adrenal mass from which needle biopsy was taken.
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Brain metastases (2 cases)Both patients complained of headache and vomiting, CT scan showed a space occupying lesion in the left parietal lobe and right fronto-temporal area with homogeneous enhancement. Craniotomy was done and the tumor was excised.
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Maxillary sinus metastases (2 cases)One of the two patients presented with severe bleeding after tooth extraction. The other had felt pain on occlusion and movement of the right upper molar, CT examination of both cases revealed soft tissue density infiltrating the adjacent bones and muscles.
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Skin metastases (1 case)One patient presented with a cutaneous non ulcerating nodule on his hand. Radiography and CT scan of the hand suggested a subcutaneous metastasis.
Histologic and immunohistochemical examination
Antibody | Code no. | Dilution | Type | Company | Country |
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HepPar-1 | MS-18100-R7 | Ready to use | Monoclonal Mouse | Lab Vision | CA, USA |
AFP | A 0008 | 1:400–1:800 | Polyclonal rabbit | Dako | Denmark |
CD34 | M7165 | 1:50 | Monoclonal Mouse | Dako | Denmark |
CK7 | M7018 | 1:100 | Monoclonal Mouse | Dako | Denmark |
CK20 | M7019 | 1:50 | Monoclonal Mouse | Dako | Denmark |
Retrograde data collection
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Clinical data: Patients age, gender, history of liver disease, presence of hepatomegaly or other manifestations of HCC.
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Radiologic data: Abdominal ultrasonography and/or CT were performed.
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Laboratory data: Serum AFP level as measured by radioimmunoassay (cut off level 20 ng/ml), hepatitis B surface antigen (HBsAg), hepatitis C antibody and serum virus C RNA which was detected by real time PCR.Finally, the diagnosis of primary HCC was based on the presence of hepatic focal lesion(s) with typical hypervascular radiological features and/or high serum AFP level or pathologic examination of liver biopsy [21]. The study was carried out with full local ethics approval.
Results
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Clinical findings: All 47 patients had no clinical features suggestive of HCC. Their initial presentation was in the form of extrahepatic mass lesion as described in the material and methods.
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Radiologic examination of the liver: Thirty six patients (76.6 %) had cirrhosis. Hepatic focal lesions were detected in all patients. These lesions were solitary in 38 patients (80.9 %) ranging from 8 mm to 2.5 cm in diameter. The remaining 9 patients, (19.1 %) had multiple focal lesions varying between 5 mm and 1.5 cm.
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Laboratory findings: All patients were positive for HCV by real time PCR and one patient was also positive for hepatitis B virus antigen. Twenty two of the 47 patients (46.8 %) showed elevated serum AFP level.
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Histology: All metastatic lesions showed malignant tumor tissue which consists of large hepatocyte-like cells with moderate nuclear atypia and prominent mitotic activity. The cells are mostly arranged in trabecular or sinusoidal pattern, which is very reminiscent to that seen in primary HCC (Fig. 2). So, the histologic diagnosis was metastatic carcinoma of possible hepatocellular origin.
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Immunohistochemistry : In all cases, the tumor cells showed granular cytoplasmic positivity for HepPar-1 (Fig. 3) and/or AFP (Fig. 4). For HepPar-1, the staining was diffuse and strong in 28(59.6 %) cases while AFP revealed focal and weak staining in 15 (32 %) cases. CD34 highlighted the rich vasculature of the tumor tissue and staining of the sinusoidal endoethelial cells. Staining for CK7 and CK20 yielded negative results (Fig. 5).
Number | Percent | |
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Male/Female | 38/9 | |
Age range | 40–80 years | |
Median age | 60 years | |
HCV | 47 | 100 |
HBV | 1 | 2.1 |
Elevated AFP | 22 | 46.8 |
Cirrhosis | 36 | 76.6 |
Hepatic focal lesion: | ||
-Solitary | 38 | 80.9 |
-Multiple | 9 | 19.1 |
Site of metastases: | ||
- Bones | 17 | 36.2 |
-Lymph nodes | 9 | 19.1 |
- Soft tissue | 7 | 15 |
- Omentum | 7 | 15 |
-Maxillary sinus | 2 | 4.2 |
-Adrenal gland | 2 | 4.2 |
-Brain | 2 | 4.2 |
-Skin | 1 | 2.1 |
Pattern of HCC growth : | ||
-Trabecular (plate like) | 8 | 17 % |
- Pseudoglandular (acinar) | 2 | 4.3 % |
-Solid | 10 | 21.3 % |
-Mixed patterns | 27 | 57.4 % |
Grade: | ||
- Well differentiated | 0 | 0 % |
- Moderately differentiated | 17 | 36.2 % |
- Poorly differentiated | 30 | 63.8 % |
Discussion
Authors name | Year of publication | No of patients | Age range (Median) | Male/Female | Pattern of growth of HCC | Metastatic anatomic region |
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Liaw et al. [20] | 1989 | 20 | 26–64 (50) | 16/4 | Predominantly trabecular pattern | Spines, ribs, skull, scapula, pelvis, long bone, sternum, clavicle. |
Uka et al. [22] | 2007 | 151 | 21–82 (64) | 117/34 | Not mentioned | Lung, lymph nodes, bones, adrenal gland, peritoneum, pancreas, nasal passages. |
Yoo et al. [21] | 2011 | 251 | 18–85 (51) | 212/39 | Not mentioned | Lung, lymph node, bones, adrenal gland, others. |
The present study | 2015 | 47 | 40–80 (60) | 38/9 | Predominantly mixed pattern | Bones, lymph nodes , soft tissue, omentum, maxillary sinus, adrenal gland, brain, skin. |