Craniocerebral Metastases of Hepatocellular Carcinoma

Brain metastases are the natural outcome of any cancerous process. However, the susceptibility of cancers to be the cause of brain metastases varies according to the primary site and the histological nature of the tumor. They are currently considered the most common malignant brain tumors seen in adults and therefore deserve particular attention. As the primary cancer is still far from known, CBM poses a twofold problem: confirming the secondary nature of the neoformation and guiding the search for the primary site, bearing in mind that in 15 to 20 % of cases, the primary tumor remains unknown. Although extrahepatic metastases from hepatocellular carcinoma are not uncommon, intracranial metastases are relatively rare and have an inferior prognosis. Diagnosis is straightforward, based firstly on diagnosing the primary lesion (hepatocellular carcinoma) and then correlating it with the histopathology of the brain metastasis. In the Neurosurgery Department of the Fann University Hospital, we conducted a retrospective descriptive study of three cases of craniocerebral metastases of hepatocellular carcinoma over 2 years from January 2019 to December 2022. This study aimed to investigate the epidemiological, clinical, paraclinical, therapeutic, and evolutionary aspects.


Introduction
Hepatocellular carcinoma (HCC) is one of the world's most common cancers. Its incidence is increasing and is closely associated with advanced liver disease [1]. In 2008, hepatocellular carcinoma was the 5th and 7th most common cancer in adult men and women, respectively. It is the 2nd and 6th most common cause of cancer death in men and women worldwide [2]. Cirrhosis, whatever its origin, increases the risk of HCC, especially if it is due to hepatitis C (HCV), hepatitis B (HBV), or hereditary hemochromatosis (HH) [3,4].
HCC can be diagnosed with certainty based on radiological criteria, with or without biological data (alpha-feto-protein assay), without histology, which is only carried out when these methods are inconclusive [5]. Craniobrain metastases (CBM) of HCC are very rare. Even in endemic regions, brain metastases from HCC are so rare that their incidence is only around 0.2 % [6]. The diagnosis of CBM is suspected based on clinical and paraclinical data with brain imaging, particularly magnetic resonance imaging. The diagnosis is confirmed by histology. Once the diagnosis of brain metastases has been established, the choice of treatment takes into account several parameters, the most important of which are the patient's general condition, the single or multiple appearance of the brain lesion, its topography, histology, the existence of other extra-cerebral metastatic locations and the treatment of the primary cancer. The treatment options are surgery, conventional radiotherapy, radiosurgery, chemotherapy, and recently trans-arterial chemo-embolization (TACE) [6,7]. The prognosis in cases of CBM is still not fully understood. Only a few exclusive studies have reported that the forecast is so unfavorable when HCC spreads to intracranial structures, including the skull and brain, that the median survival time was only 1 to 2 months [7,8]. We report the case of 3 patients followed in our department for cranioencephalic metastases whose etiological investigation revealed an HCC carcinoma.

Case N° 1
The patient was 30 years old and was admitted to the hospital for management of confusion with intracranial hypertension that had been evolving for 1 month in the presence of a left frontoparietal swelling for which no further medical consultation had been carried out. An investigation carried out with the parents revealed generalized tonic-clonic convulsive seizures. The patient was known to be a chronic carrier of HBsAg. The clinical examination revealed a relatively good general condition with a Karnofski index of 70 %. The conjunctiva and mucous membranes were normal-colored and not icteric. The abdominal investigation revealed a slight tenderness in the right hypochondrium with no palpable mass or ascites. On palpation, there was also a soft left frontoparietal swelling of firm consistency with healthy, painless skin. The neurological examination concluded that there was an intracranial hypertension syndrome, a cortical irritation syndrome with persistent disturbance of consciousness in the late post-critical phase. Cerebral CT scan

Case N° 2
This was a young man, aged 35, whom we followed up on for a painless, non-inflammatory right parietal swelling associated with headaches and no vomiting. The history-taking revealed no specific pathological history. His general condition was poor, with a Karnofski index (KI) of 60 %, but he was hemodynamically stable. He had a distended abdomen with a nonpalpable liver, abdominal curvature, and collateral venous circulation. There was also a firm right parietal swelling with little pain on palpation and healthy skin. The neurological examination was in favor of intracranial hypertension syndrome. Analysis of the other systems was unremarkable, apart from the conjunctivae and mucous membranes, which were icteric ( Figures A, B, C). The stools were discolored, and the urine was dark.  Given the craniocerebral lesion and liver lesions, the diagnosis of CM on probable HCC was retained, and he underwent total removal of the tissue portion of the tumor and a biopsy of the tumor mass. The patient also underwent conservative treatment due to his poor general condition. He was transferred to digestive surgery to manage ascites and hepatomegaly, where he died 15 days later.

Case N° 3
The patient was a 66-year-old woman with altered consciousness associated with a language disorder of the aphasic type and weakness of the right hemisphere, with no evidence of vomiting or convulsive seizures. Questioning revealed no particular pathological history. She

Epidemiological aspect
In this work, we report the case of 3 patients diagnosed in our department with metastatic HCC. Of these, 2 were male, with a sex ratio of 2. Although the size of our sample was small to allow comparison, some data in the literature show that the predominance is often male (Table I).   Extra-neurological signs pointing to primary cancer were found in two patients with digestive symptoms (cholestasis syndrome, portal hypertension syndrome, hepatomegaly, and tenderness in the right hypochondrium).
In the Senegalese series by Doualeh Ali [14], extra-neurological symptoms pointing to a primary were found in 30 % of his patients.

Etiological investigation
An etiological investigation in search of digestive cancer in general and hepatic cancer, in particular, responsible for the CM studied, was carried out with a thoracic-abdominal-pelvic CT scan in one of our patients, an abdominal ultrasound in two of our patients, a chest Xray in two of our patients and, biologically, hepatocellular insufficiency was found in two of our patients, and the alpha-

Anatomopathology
Pathological examination of the surgical specimen confirmed the diagnosis of craniocerebral metastasis of HCC. A scan biopsy of the liver lesion confirmed the nature of the primary lesion (hepatocellular carcinoma) in all 3 patients.

Evolutionary aspects
The short-term evolution of all our patients was unfavorable, with a

Conclusion
Despite the malignancy and high frequency of hepatocellular carcinoma, craniobrain metastases are rare, with a high mortality rate.
The prognosis is poor, with death in this case. The forecast is poor,