Unusual presentations of hepatocellular carcinoma: an iconographic essay

Abstracts

O objetivo deste trabalho foi descrever e ilustrar aspectos incomuns do hepatocarcinoma na tomografia computadorizada e ressonância magnética. A partir da análise retrospectiva de 100 casos de pacientes com hepatocarcinoma diagnosticado por análise combinada de exames de imagem, dosagem de alfa-feto-proteína, biópsia percutânea ou ressecção cirúrgica, selecionamos aqueles com apresentação atípica em um ou mais métodos de imagem ou aqueles com evolução não usual, ilustrando os seus principais aspectos de imagem. Entre os casos apresentados, escolhemos pacientes com hepatocarcinomas císticos, hemorrágicos, rotos e causando hemoperitônio, calcificados, com regressão espontânea, exofíticos, hipovasculares, gigantes e com disseminação não usual. O hepatocarcinoma é o tumor maligno mais comum do fígado e freqüentemente tem apresentação típica e associada à cirrose hepática. Porém, em alguns casos, apresentações atípicas podem retardar o seu diagnóstico.

Hepatocarcinoma; Fígado; Aspectos atípicos; Ultra-sonografia; Tomografia computadorizada; Ressonância magnética

ICONOGRAPHIC ESSAY

Unusual presentations of hepatocellular carcinoma: an iconographic essay^*

Giuseppe D'Ippolito^I; Luiz de Abreu Junior^II; Maria Lucia Borri^II; Mário de Melo Galvão Filho^II; Luiz Guilherme C. Hartmann^II; Angela Maria Borri Wolosker^II; Marcelo Ribeiro^III; Marcelo Zindel Salem^IV; Adriano Misiara^V

^IAdjunct Professor, Department of Imaging Diagnosis, Universidade Federal de São Paulo-Escola Paulista de Medicina, Radiologist responsible for the Service of US/CT/MRI of Hospital São Luiz

^IIMD Radiologists at the Sector of Imaging Diagnosis of the Hospital São Luiz

^IIIPhD in Surgical Gastroenterology by the Universidade Federal de São Paulo-Escola Paulista de Medicina

^IVPhD in Surgical Gastroenterology by the Faculdade de Medicina da Universidade de São Paulo

^VMaster degree in Surgical Gastroenterlogy by the Universidade Federal de São Paulo-Escola Paulista de Medicina

^{Mailing address}

ABSTRACT

In order to evaluate atypical aspects of hepatocellular carcinoma at computed tomography and magnetic resonance imaging, we have retrospectively evaluated 100 patients with diagnosed hepatocellular carcinoma, based on combined imaging studies, laboratory results, biopsy and surgery. We have selected those cases with atypical findings at computed tomography or magnetic resonance imaging, including cystic lesions, bleeding tumors, with calcifications, with spontaneous regression, pedunculated tumors, hypovascular lesions, giant hepatocellular carcinomas, and those with unusual local invasiveness. The hepatocellular carcinoma is the most usual primary malignant lesion of the liver and usually it has a typical aspect and is associated with hepatic cirrhosis. However, in a significant number of cases, some uncommon findings can be responsible for a delayed diagnosis.

Keywords: Hepatocellular carcinoma; Liver; Atypical findings; Ultrasound; Computed tomography; Magnetic resonance imaging.

INTRODUCTION

The hepatocellular carcinoma is the most usual primary malignant tumor of the liver and is frequently associated with hepatic cirrhosis. About 10% of the patients with hepatic cirrhosis develop hepatocellular carcinoma and more than 90% of the patients with this tumor carry some form of chronic hepatopathy^(1,2). The higher prevalence of viral hepatitis has caused an increase in the frequency of hepatocellular carcinoma incidence in our population. Screening Programs in patients with chronic hepatitis virus infection and chronic non-viral hepatitis, have increased the early detection of hepatocellular carcinoma, with the periodical application of alpha-fetoprotein tests and abdominal ultrasound (US) every six months^(3,4).

The hepatocellular carcinoma aspect in imaging studies is well known and is highly specific, allowing a safe diagnosis when this entity is associated with signs of chronic hepatitis. On the other hand, despite some authors consider that any hepatic lesion in a cirrhotic liver not fulfilling the criteria for a cyst or hemangioma should be considered as hepatocellular carcinoma unless contrary proven⁽²⁾, a number of evidences have recently appeared in the literature indicating that certain hypervascular lesions occurring in cirrhotic livers may be reversible perfusion defects, with no pathological meaning^(5,6). Additionally, the previous concept that hemangiomas were unusual in cirrhotic livers has been changed by reports on frequent hemangiomas in patients with chronic hepatopathy⁽⁷⁾.

Therefore, it is important to recognize both the typical and atypical findings aspects of the hepatocellular carcinoma in the different methods of imaging diagnosis, mainly computed tomography (CT) and magnetic resonance imaging (MRI), aiming at improving these tools efficacy and allowing a possibly non-invasive and safe diagnosis while reducing the duration of treatment.

Our objective was to demonstrate the main atypical and less frequent findings of the hepatocellular carcinoma, by means of studies selected from 100 cases. The diagnosis of hapatocellular carcinoma was defined by a combination of results of imaging studies, alpha-fetoprotein blood test, percutaneous biopsies and surgical resections.

TYPICAL ASPECTS

At US, the small hepatocellular carcinoma, < 3.0 cm, is shown as a hypoechogenic, homogeneous and well defined lesion (Figure 1A) The lesions > 3.0 cm in diameter usually present hyperechogenic and heterogeneous due the combined presence of necrosis, hemorrhage, fat, fibrosis and sinusoidal dilatation (Figure 1B)⁽⁸⁾. In some cases, it is possible to identify a hypoechogenic halo representing the fibrotic capsule (Figure 2A)⁽²⁾. It is important to remember that only half of hepatocellular carcinomas are identified at US when the cirrhosis process is advanced⁽⁹⁾.

The hepatocellular carcinoma may be classified according to its macroscopic aspect as follows: a) expansile, single nodular type, well defined, encapsulated and with better prognosis⁽¹⁰⁾, representing about 50% of hepatocellular carcinomas (Figure 2); b) infiltrating, consisting of a lesion with irregular although well defined borders, without capsule and frequently presenting vascular invasion (Figure 3); c) multifocal, represented by multiple nodules scattered in many hepatic segments (Figure 4)⁽¹¹⁾. The CT scan and MRI studies allow to characterize each of these findings.

At CT, the expansile hepatocellular carcinoma is a hypodense, isodense or hyperdense lesion, depending on its constitution. The iron or copper accumulation inside the lesion as well as areas of bleeding, give the lesion a hyperdense aspect. The presence of areas of necrosis, fat and glycogen is responsible for the low values of lesion attenuation⁽¹²⁾. After the contrast injection, typically an intense enhancement predominating in the arterial phase is observed, decreasing gradually afterwards. (Figure 5). When the fibrotic capsule is present, an enhancement is observed in the more delayed phases. (Figure 6). In large lesions, it is possible to identify a mosaic enhancement pattern resulting from the presence of areas of fibrosis, hemorrhage, arteriovenous anastomosis and intratumoral necrosis (Figure 7)⁽²⁾. A predominantly arterial enhancement is observed in about 80% of the lesions, representing its irrigation by the hepatic artery and its differentiation degree⁽¹³⁾.

In the last two decades, preceding the advent of the spiral CT and dynamic MRI, the Lipiodol^® arteriography followed by abdominal CT was considered the most sensible pre-surgical method for detection of hepatocellular carcinoma^(14,15). The abdominal CT scan performed between two and four weeks, after intra-arterial injection of liposoluble contrast, demonstrates the contrastation of tumoral nodules (Figure 5B)⁽¹⁶⁾. More recent studies have proved that the spiral and multislice CT, as well as the contrast-enhanced MRI present sensitivity similar or superior to Lipiodol^® CT^(17,18); this method is reserved only for therapeutic indications, combining the use of liposoluble contrast media with the intra-arterial injection of chemotherapic substances⁽¹⁹⁾. It is interesting to observe that, in some cases, the hepatocellular carcinoma can be identified only by Lipiodol^® CT and, in others, only by the spiral CT (Figure 8); in these cases, the arterial CT presents false-negative results due to the preferentially portal irrigation in well differentiated lesions⁽¹⁸⁾.

In the MRI, the expansile hepatocellular carcinoma is usually hyperintense in T1 (61%) and in T2 (75%) (Figures 9 and 10). The T1 signal hyperintensity is due to the presence of Cooper, fat or blood inside the lesion, combined with the presence of zinc in the hepatic parenchyma^(20,21)The hypersignal in the T2 weighted images is due to peliosis and hypervascularization⁽²²⁾.The fibrotic capsule tends to be hypointense in the T1 and T2 weighted images and with delayed enhancement (Figures 2C and 2D). After the injection of paramagnetic contrast media, the hepatocellular carcinoma presents an enhancement pattern similar to that observed in tomographic studies (Figure 9)⁽²⁾.

UNUSUAL ASPECTS

In our experience, about 20% of the hepatocellular carcinomas do not present the above mentioned aspects and have unusual presentations.

Giant hepatocellular carcinoma – Making systematic use of screening methods, most of hepatocellular carcinomas are diagnosed with diameter of < 5.0 cm⁽²³⁾. However, it is still possible to find large lesions in its initial presentation. (Figure 10). Even when the tumor is large, the patient may benefit from the surgical resection, provided there is no sign of distant dissemination. In these cases, the prognosis is apparently similar to those of patients carrying small, non-disseminated lesions⁽²⁴⁾. But, it is important to remember that large tumors, mainly those occupying four or more hepatic segments, present higher risk of spontaneous disruption⁽²⁵⁾.

Hepatocellular carcinoma with spontaneous regression – There are many papers in the literature, demonstrating about 30 cases of hepatocellular carcinoma with spontaneous regression and disappearance (Figure 11)^(26–28), even in the presence of distant metastases^(29,30). In spite of various hypotheses formulated, for example, tumoral irrigation deficiency^(27,28), none of them seems to be completely satisfactory⁽²⁶⁾.

Cystic hepatocellular carcinoma – The cystic presentation of the hepatocellular carcinoma is extremely rare⁽³¹⁾, only four cases were described in the literature up to 2000⁽³²⁾. In such cases, the lesion had a multilocular aspect in a non-cirrhotic liver^(31–34). The cystic hepatocellular carcinoma should be differentiated from that large and with central necrosis, as apparently they are distinct forms of presentation (Figure 12).

Hypovascular hepatocellular carcinoma – The tumoral lesion is predominantly irrigated by the arterial system; but well differentiated tumors may present preferably portal irrigation, which also is related to the degree of hepatic cirrhosis (Figure 13)⁽¹³⁾.

Bleeding hepatocellular carcinoma – The intratumoral bleeding is not frequent and usually is a result of local ischemia due to the rapid growth of the lesion⁽³⁵⁾. The hemoperitoneum subsequent to bleeding of the hepatocellular carcinoma occurs in 5–15% of the cases (Figure 14)⁽³⁶⁾. The tumors carrying higher risk of bleeding are those located in the left lobe, those of larger diameter, with minimal thickness of the peritumoral parenchyma, with high Child-Pugh score and high transaminases level, and those with high prothrombin time⁽³⁷⁾. The presence of blood inside the lesion can be characterized by hyperdense areas at CT studies and hyperintense in T1 weighted images⁽³⁸⁾.

Calcified hepatocellular carcinoma – As previously mentioned, the hepatocellular carcinoma may necrose and bleed, which leads to the appearance of dystrophic calcifications⁽¹²⁾. Calcifications may occur in 7.5–25% of the hepatocellular carcinomas^(12,39), but, in our studies only 5% of the patients studied presented calcifications (Figure 15). It is important to remember that the presence of liver calcification without textural or local perfusional changes should be considered as being of probable residual origin⁽⁴⁰⁾.

Hepatocellular carcinoma with fat – In spite of the hepatocellular carcinoma lipomatous transformation being frequently described^(8,41)and fat being observed in the tumor cells cytoplasm⁽¹²⁾, its identification is not frequent in imaging studies^(39,42). The presence of focal deposit of fat in the hepatocellular carcinoma can be detected by means of negative density determination inside the lesion region (Figure 16)⁽⁸⁾; on the other hand, the intracellular fat is more easily detected in MRI, using gradient-echo sequences with phase opposition technique (Figure 17)^(43,44).

Exophytic hepatocellular carcinoma – The pedunculated hepatocellular carcinoma is extremely rare⁽⁴⁵⁾and should be considered among the differential diagnoses when a solid mass in contact with a cirrhotic liver is observed (Figure 18).

Unusual dissemination – Some cases of direct gastric infiltration by the hepatocellular carcinoma^(46,47)were described, with extension to the right atrium via inferior vena cava^(48,49), like these presented hereon (Figures 19 and 20).

CONCLUSION

The hepatocellular carcinoma usually presents typical features in imaging studies. But, in a considerable number of cases, it may surprise the radiologist with unusual aspects deserving to be known, aiming at optimizing the efficacy of the available diagnostic tools.

REFERENCES

Received May 2, 2005.

Accepted after revision May 25, 2005.

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*

Study developed at Scopo Diagnóstico, Hospital São Luiz Service of US/CT/MRI, São Paulo, SP.

Publication Dates

• Publication in this collection
  25 May 2006
• Date of issue
  Apr 2006

History

• Received
  02 May 2005
• Accepted
  25 May 2005