Ultrasound
Ultrasound Manifestations of Hepatocellular Carcinoma 1 Paul D. Kamin, M.D., Michael E. Bernardino, M.D., and Barry Green, M.D. The ultrasound patterns of primary hepatocellular carcinoma are described. Three types were found: a densely echogenic mass, diffuse disease, and a mixture of the two. These three patterns correspond to the previously reported angiographic and pathological manifestations of disease. The differential diagnosis is discussed. INDEX TERM: Liver neoplasms, ultrasound studies (Liver, biliary system, ultrasonography, 7 [6] .1298; Liver, carcinoma,7 [61] .321) Radiology 131:459-461, May 1979
HILE VARIOUS
patients had computed tomography and 8 had angiography, including the one without histological confirmation. Two patients had cirrhosis. All patients were examined on progressive generations of commercial gray-scale equipment. A 2.25-, 3.5-, or 5-MHz internally focused transducer was used, depending upon the patient's physique. Longitudinal and transverse scans were obtained at intervals of 1 em or less and were recorded on 70mm and radiographic film.
ultrasound patterns have been de-
W scribed for metastatic hepatic disease (1, 2), we know of no reports describing the gray-scale findings in hepatocellular carcinoma. Our experience with primary hepatic carcinomas, their ultrasonographic appearance, and the differential diagnosis are given below. MATERIALS AND METHODS
Seven male and 7 female patients ranging from 16 months to 77 years of age were studied. Two children had hepatoblastoma; the other 12 patients had primary hepatocellular carcinoma (hepatoma). Histological confirmation was obtained in 13. All patients were examined by grayscale ultrasonography and liver/spleen scintigraphy. Four
RESULTS
Three distinct patterns of disease were observed. The most common pattern, seen in 8 patients, was hepatomegaly with diffuse distortion of the normal internal ar-
1a,b
1c
Figure 1. a. Transverse scan of a hepatoma, showing diffuse inhomogeneous echogenic disease throughout the liver. b. Sagittal section through the right lobe demonstrates diffuse, inhomogeneous disease with multiple small, scattered, focal echogenic areas. c. Radionuclide image shows multiple defects corresponding to those seen on the sonogram.
1 From the Department of Diagnostic Radiology, M.D. Anderson Hospital and Tumor Institute, University of Texas System Cancer Center, Houston, Texas. Received Sept. 12, 1978; accepted and revision requested Jan. 3, 1978; revision received Jan. 16. sjh
459
460
PAUL
D. KAMIN AND OTHERS
Figure 2. Transverse scan shows a densely echogenic mass in the right lobe (arrows), corresponding to a focal hepatoma.
May 1979
Figure 3. Transverse scan through the liver of a child with a huge hepatoblastoma. The liver is enlarged and its entire architecture is distorted; in addition, there is a discrete echogenic mass bridging both lobes (arrows). The lesion was deemed unresectable, obviating further studies.
The radionuclide image correlated with the sonogram in all 14 cases, while 3 of the 4 patients examined by CT demonstrated an area of decreased tissue attenuation which correlated with both the sonographic and radionuelide findings. In one patient, CT scans obtained with and without intravenous contrast material showed no lesion; the sonogram showed a diffusely abnormal hepatic parenchymal pattern involving both lobes. Figure 4. Same patient as in figure 2. Sonogram demonstrates a large, complex pelvic mass (arrows), found on biopsy to be hepatoma metastatic to the ovaries (Krukenberg tumor).
chitecture (Fig. 1). Multiple areas of increased echogenicity were noted throughout the distorted portions of the liver, but no distinct masses were identified. Seven lesions involved both lobes; one involved only the right lobe. A second group of 3 patients each demonstrated a large, focal, densely echogenic mass ranging from 2 to 12 em (Fig. 2). One patient had a recurrent hepatoma after a partial hepatectomy. The second patient had a hepatoblastoma in which almost the entire liver was occupied by an echogenic mass and hence inoperable. The third lesion (a hepatoma) presented as an echogenic mass entirely within the right lobe. In all 3 patients the remaining liver appeared normal. The 3 remaining patients exhibited a "mixed pattern" comprising a combination of the first two (Fig. 3). It consisted of a large, densely echogenic mass associated with diffuse hepatic parenchymal disease involving the remaining liver. This particular pattern was noted in both hepatoblastoma and hepatoma. Other sonographic findings included hepatomegaly in 13 patients and ascites in 4. Three patients demonstrated narrowing of the intrahepatic portion of the inferior vena cava, probably secondary to compression by the grossly enlarged liver rather than tumor invasion. One patient had a pelvic mass (Fig. 4), which was found to be an ovarian metastasis from the liver (Krukenberg's tumor).
DISCUSSION
Hepatoma formation has been thought to be related to predisposing diseases such as cirrhosis, hepatitis, hemochromatosis, and syphilis: however, this was true of only 2 of our patients, both of whom had cirrhosis. This may be due to the referral base from which our population of patients is drawn. In addition, African blacks and Chinese have a higher incidence of hepatocellular carcinoma than other racial groups (3). The tumor has a poor prognosis, with some series reported to exhibit a median survival of only 3.8 months. However, longevity has increased with aggressive therapy, such as hepatic artery ligation and (when possible) hepatic resection (3). Other methods of treatment include irradiation and chemotherapy. Early detection and accurate evaluation of the extent of disease are extremely important with these more effective therapeutic measures. Pre-gray-scale ultrasonographic reports of hepatomas have described discrete masses with variable internal echo patterns, some large enough to leave little normal hepatic parenchyma (4, 5). Since the advent of gray-scale sonography, there have been only a few sporadic reports of primary hepatic tumors (6), and these too were described as discrete masses. The wider range of sonographic manifestations reported in this series is probably due to the improved image quality and accuracy of gray-scale equipment. Okuda et a/. (7) recently showed an excellent correlation between the vascular angiographic pattern and the gross
Vol. 131
ULTRASOUND MANIFESTATIONS OF HEPATOCELLULAR CARCINOMA
461
Ultrasound
5a
5b
Fig. 6. Longitudinal scan demonstrates subtle diffuse alterations in the liver architecture in another patient with surgically proved multifocal hepatoma. This would be difficult to differentiate from lymphoma, cirrhosis, or fatty infiltration.
Although the radionuclide results correlated extremely well with the sonographic findings in this brief study, ultrasonography offers the distinct advantage of showing additional disease elsewhere in the abdomen. Tumor invasion of the inferior vena cava, ascites, and the presence of pelvic metastases (Fig. 4) has definite therapeutic implications. Also, when sonography demonstrates disease in both lobes of the liver, it obviates an invasive staging procedure such as angiography, especially in the pediatric age group (8). Finally, sonography may be more sensitive than CT in detecting diffuse hepatic parenchymal disease such as cirrhosis, lymphoma, or hepatoma lacking discrete areas of beam attenuation. Figure 5. A. Sonogram of a patient with hepatocellular carcinoma illustrates diffuse increased echogenicity. Other scans showed a similar appearance throughoutthe liver. This can be difficult to distinguishfrom cirrhosis, fatty infiltration, hemochromatosis, or poor scanning technique. B. Selective hepatic arteriogram reveals a diffuse hypervascular hepatoma.
pathological extent of disease. In their series, three vascular patterns were noted: a discrete hypervascular mass, diffuse, irregular, tortuous vessels, and a mixture of the two. In our patients who had angiography, there was good correlation between the sonographic pattern and the type of vascularity noted. However, our numbers are too small for any definitive statement in this regard, and a future prospective study correlating sonographic patterns and vascularity is needed. It must be stressed that these patterns are not unique to primary hepatocellular carcinoma. Any of these patterns may be seen with metastatic disease. In fact, we have seen the diffuse pattern (Figs. 5 and 6) in lymphoma, cirrhosis, hemochromatosis, and fatty infiltration of the liver. We have also noted a diffuse echogenic pattern of the liver in patients with ascites, probably due to increased sound transmission through the ascitic fluid. Thus adequate evaluation of the liver is difficult in the presence of significant ascites.
REFERENCES 1. Green B, Bree RL, Goldstein HM, et al: Gray scale ultrasound evaluation of hepatic neoplasms: patterns and correlations. Radiology 124:203-208, Jul 1977 2. McArdle CR: Ultrasonic diagnosis of liver metastases. J Clin Ultrasound 4:265-268, Aug 1976 3. Tien-yu L: Tumors of the liver. Part I. Primary malignant tumors. [In] Bockus HL, ed: Gastroenterology. Philadelphia, Saunders, 3d Ed, 1976, Vol 3, pp 522-534 4. Melki G: Ultrasonic patterns of tumors of the liver. J Clin Ultrasound 1:306-314, Dec 1973 5. DuncanJG: The diagnostic value of ultrasoundin hepatomegaly and upper abdominal masses. J R Coil Surg Edinb 20: 107-114, Mar 1975 6. GoldbergBB: AbdominalGray Scale Ultrasonography. New York, Wiley, 1977, Chapt 5, pp 127-128 7. Okuda K, Obata H, Jinnouchi S, et al: Angiographic assessment of gross anatomy of hepatocellular carcinoma: comparison of celiac angiograms and pathology in 100 cases. Radiology 123:21-29, Apr 1977 8. Exelby PR, Filler RM, Grosfeld JL: Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey1974. J Pediatr Surg 10:329-337, Jun 1975
Department of Diagnostic Radiology M.D. Anderson Hospital and Tumor Institute University of Texas System Cancer Center Houston, Texas 77030
Ultrasound Manifestations of Hepatocellular Carcinoma 1 Paul D. Kamin, M.D., Michael E. Bernardino, M.D., and Barry Green, M.D. The ultrasound patterns of primary hepatocellular carcinoma are described. Three types were found: a densely echogenic mass, diffuse disease, and a mixture of the two. These three patterns correspond to the previously reported angiographic and pathological manifestations of disease. The differential diagnosis is discussed. INDEX TERM: Liver neoplasms, ultrasound studies (Liver, biliary system, ultrasonography, 7 [6] .1298; Liver, carcinoma,7 [61] .321) Radiology 131:459-461, May 1979
HILE VARIOUS
patients had computed tomography and 8 had angiography, including the one without histological confirmation. Two patients had cirrhosis. All patients were examined on progressive generations of commercial gray-scale equipment. A 2.25-, 3.5-, or 5-MHz internally focused transducer was used, depending upon the patient's physique. Longitudinal and transverse scans were obtained at intervals of 1 em or less and were recorded on 70mm and radiographic film.
ultrasound patterns have been de-
W scribed for metastatic hepatic disease (1, 2), we know of no reports describing the gray-scale findings in hepatocellular carcinoma. Our experience with primary hepatic carcinomas, their ultrasonographic appearance, and the differential diagnosis are given below. MATERIALS AND METHODS
Seven male and 7 female patients ranging from 16 months to 77 years of age were studied. Two children had hepatoblastoma; the other 12 patients had primary hepatocellular carcinoma (hepatoma). Histological confirmation was obtained in 13. All patients were examined by grayscale ultrasonography and liver/spleen scintigraphy. Four
RESULTS
Three distinct patterns of disease were observed. The most common pattern, seen in 8 patients, was hepatomegaly with diffuse distortion of the normal internal ar-
1a,b
1c
Figure 1. a. Transverse scan of a hepatoma, showing diffuse inhomogeneous echogenic disease throughout the liver. b. Sagittal section through the right lobe demonstrates diffuse, inhomogeneous disease with multiple small, scattered, focal echogenic areas. c. Radionuclide image shows multiple defects corresponding to those seen on the sonogram.
1 From the Department of Diagnostic Radiology, M.D. Anderson Hospital and Tumor Institute, University of Texas System Cancer Center, Houston, Texas. Received Sept. 12, 1978; accepted and revision requested Jan. 3, 1978; revision received Jan. 16. sjh
459
460
PAUL
D. KAMIN AND OTHERS
Figure 2. Transverse scan shows a densely echogenic mass in the right lobe (arrows), corresponding to a focal hepatoma.
May 1979
Figure 3. Transverse scan through the liver of a child with a huge hepatoblastoma. The liver is enlarged and its entire architecture is distorted; in addition, there is a discrete echogenic mass bridging both lobes (arrows). The lesion was deemed unresectable, obviating further studies.
The radionuclide image correlated with the sonogram in all 14 cases, while 3 of the 4 patients examined by CT demonstrated an area of decreased tissue attenuation which correlated with both the sonographic and radionuelide findings. In one patient, CT scans obtained with and without intravenous contrast material showed no lesion; the sonogram showed a diffusely abnormal hepatic parenchymal pattern involving both lobes. Figure 4. Same patient as in figure 2. Sonogram demonstrates a large, complex pelvic mass (arrows), found on biopsy to be hepatoma metastatic to the ovaries (Krukenberg tumor).
chitecture (Fig. 1). Multiple areas of increased echogenicity were noted throughout the distorted portions of the liver, but no distinct masses were identified. Seven lesions involved both lobes; one involved only the right lobe. A second group of 3 patients each demonstrated a large, focal, densely echogenic mass ranging from 2 to 12 em (Fig. 2). One patient had a recurrent hepatoma after a partial hepatectomy. The second patient had a hepatoblastoma in which almost the entire liver was occupied by an echogenic mass and hence inoperable. The third lesion (a hepatoma) presented as an echogenic mass entirely within the right lobe. In all 3 patients the remaining liver appeared normal. The 3 remaining patients exhibited a "mixed pattern" comprising a combination of the first two (Fig. 3). It consisted of a large, densely echogenic mass associated with diffuse hepatic parenchymal disease involving the remaining liver. This particular pattern was noted in both hepatoblastoma and hepatoma. Other sonographic findings included hepatomegaly in 13 patients and ascites in 4. Three patients demonstrated narrowing of the intrahepatic portion of the inferior vena cava, probably secondary to compression by the grossly enlarged liver rather than tumor invasion. One patient had a pelvic mass (Fig. 4), which was found to be an ovarian metastasis from the liver (Krukenberg's tumor).
DISCUSSION
Hepatoma formation has been thought to be related to predisposing diseases such as cirrhosis, hepatitis, hemochromatosis, and syphilis: however, this was true of only 2 of our patients, both of whom had cirrhosis. This may be due to the referral base from which our population of patients is drawn. In addition, African blacks and Chinese have a higher incidence of hepatocellular carcinoma than other racial groups (3). The tumor has a poor prognosis, with some series reported to exhibit a median survival of only 3.8 months. However, longevity has increased with aggressive therapy, such as hepatic artery ligation and (when possible) hepatic resection (3). Other methods of treatment include irradiation and chemotherapy. Early detection and accurate evaluation of the extent of disease are extremely important with these more effective therapeutic measures. Pre-gray-scale ultrasonographic reports of hepatomas have described discrete masses with variable internal echo patterns, some large enough to leave little normal hepatic parenchyma (4, 5). Since the advent of gray-scale sonography, there have been only a few sporadic reports of primary hepatic tumors (6), and these too were described as discrete masses. The wider range of sonographic manifestations reported in this series is probably due to the improved image quality and accuracy of gray-scale equipment. Okuda et a/. (7) recently showed an excellent correlation between the vascular angiographic pattern and the gross
Vol. 131
ULTRASOUND MANIFESTATIONS OF HEPATOCELLULAR CARCINOMA
461
Ultrasound
5a
5b
Fig. 6. Longitudinal scan demonstrates subtle diffuse alterations in the liver architecture in another patient with surgically proved multifocal hepatoma. This would be difficult to differentiate from lymphoma, cirrhosis, or fatty infiltration.
Although the radionuclide results correlated extremely well with the sonographic findings in this brief study, ultrasonography offers the distinct advantage of showing additional disease elsewhere in the abdomen. Tumor invasion of the inferior vena cava, ascites, and the presence of pelvic metastases (Fig. 4) has definite therapeutic implications. Also, when sonography demonstrates disease in both lobes of the liver, it obviates an invasive staging procedure such as angiography, especially in the pediatric age group (8). Finally, sonography may be more sensitive than CT in detecting diffuse hepatic parenchymal disease such as cirrhosis, lymphoma, or hepatoma lacking discrete areas of beam attenuation. Figure 5. A. Sonogram of a patient with hepatocellular carcinoma illustrates diffuse increased echogenicity. Other scans showed a similar appearance throughoutthe liver. This can be difficult to distinguishfrom cirrhosis, fatty infiltration, hemochromatosis, or poor scanning technique. B. Selective hepatic arteriogram reveals a diffuse hypervascular hepatoma.
pathological extent of disease. In their series, three vascular patterns were noted: a discrete hypervascular mass, diffuse, irregular, tortuous vessels, and a mixture of the two. In our patients who had angiography, there was good correlation between the sonographic pattern and the type of vascularity noted. However, our numbers are too small for any definitive statement in this regard, and a future prospective study correlating sonographic patterns and vascularity is needed. It must be stressed that these patterns are not unique to primary hepatocellular carcinoma. Any of these patterns may be seen with metastatic disease. In fact, we have seen the diffuse pattern (Figs. 5 and 6) in lymphoma, cirrhosis, hemochromatosis, and fatty infiltration of the liver. We have also noted a diffuse echogenic pattern of the liver in patients with ascites, probably due to increased sound transmission through the ascitic fluid. Thus adequate evaluation of the liver is difficult in the presence of significant ascites.
REFERENCES 1. Green B, Bree RL, Goldstein HM, et al: Gray scale ultrasound evaluation of hepatic neoplasms: patterns and correlations. Radiology 124:203-208, Jul 1977 2. McArdle CR: Ultrasonic diagnosis of liver metastases. J Clin Ultrasound 4:265-268, Aug 1976 3. Tien-yu L: Tumors of the liver. Part I. Primary malignant tumors. [In] Bockus HL, ed: Gastroenterology. Philadelphia, Saunders, 3d Ed, 1976, Vol 3, pp 522-534 4. Melki G: Ultrasonic patterns of tumors of the liver. J Clin Ultrasound 1:306-314, Dec 1973 5. DuncanJG: The diagnostic value of ultrasoundin hepatomegaly and upper abdominal masses. J R Coil Surg Edinb 20: 107-114, Mar 1975 6. GoldbergBB: AbdominalGray Scale Ultrasonography. New York, Wiley, 1977, Chapt 5, pp 127-128 7. Okuda K, Obata H, Jinnouchi S, et al: Angiographic assessment of gross anatomy of hepatocellular carcinoma: comparison of celiac angiograms and pathology in 100 cases. Radiology 123:21-29, Apr 1977 8. Exelby PR, Filler RM, Grosfeld JL: Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey1974. J Pediatr Surg 10:329-337, Jun 1975
Department of Diagnostic Radiology M.D. Anderson Hospital and Tumor Institute University of Texas System Cancer Center Houston, Texas 77030
