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17 May 2023: Articles  Japan

Rapidly Progressing Sarcomatoid Hepatocellular Carcinoma after Needle Biopsy and Radiofrequency Ablation

Unusual clinical course, Rare disease

Masamichi Kimura ORCID logo1ABCDEF*, Ryo Matsuoka1B, Koji Nishikawa1CD, Jun Imamura1CD, Kiminori Kimura ORCID logo1DG

DOI: 10.12659/AJCR.939126

Am J Case Rep 2023; 24:e939126




BACKGROUND: Sarcomatoid hepatocellular carcinoma is a rare, primary malignant liver cancer. Its pathogenesis is unknown, but it often occurs in patients who have undergone repeated antitumor therapies for hepatocellular carcinoma. Sarcomatoid hepatocellular carcinoma is more likely to recur and has a worse prognosis than that of hepatocellular carcinoma. As no specific features have been identified in the symptoms, serological findings, or imaging findings, it is difficult to accurately diagnose the disease before surgical resection or autopsy.

CASE REPORT: An 83-year-old woman was diagnosed with hepatocellular carcinoma 20 years ago. Radiofrequency ablation was initially performed. Thereafter, invasive, non-surgical treatments were repeated. The most recent treatment was 4 years ago, during which computed tomography suggested recurrent hepatocellular carcinoma. However, upon needle biopsy, histological examination revealed spindle-shaped tumor cells and actively mitotic cells. Immunohistochemical analysis showed negative results for Arginase-1, HepPar1, and Glypican3 and positive results for AE1/AE3, CK7, and vimentin. Therefore, sarcomatoid hepatocellular carcinoma was diagnosed, which was treated with radiofrequency ablation but progressed rapidly thereafter. Considering the rapid disease progression, the patient was treated conservatively. However, the patient’s general condition gradually deteriorated, resulting in death.

CONCLUSIONS: Compared with hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma is more prone to recurrence and has a poorer prognosis. Therefore, aggressive surgical resection seems to be the most appropriate treatment for sarcomatoid hepatocellular carcinoma at present. Additional hepatic resection or follow-up imaging in a short period should be considered at the time of diagnosis of sarcomatoid hepatocellular carcinoma by biopsy, considering the risk of seeding or recurrence.

Keywords: alpha-Fetoproteins, radiofrequency ablation, Female, Humans, Aged, 80 and over, Carcinoma, Hepatocellular, Liver Neoplasms, Biopsy, Needle, Catheter Ablation


Sarcomatoid carcinomas are tumors containing sarcomatoid components of malignant epithelial and spindle-shaped cells [1]. A total of 1.8% to 9.4% of hepatocellular carcinomas (HCCs) have sarcomatoid changes and are termed sarcomatoid hepatocellular carcinomas (SHCs) [2]. SHC is a distinct subtype of HCC identified histologically by spindle-shaped, mitotically active cells [3]. However, the pathogenesis of SHC is not completely understood. Antitumor therapies, such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and percutaneous ethanol injection (PEIT) are considered major causes of sarcomatoid changes [4–6], although there are several reported cases with no history of prior antitumor therapy [7,8]. Pathological examination is the only way to diagnose SHC, which is usually performed after surgery or at autopsy. SHC is prone to recurrence and has a poor prognosis. However, surgery remains an effective treatment for SHC and can significantly prolong the overall survival [9]. In this study, we report a case of rapidly progressing SHC that was diagnosed using needle biopsy and treated with RFA.

Case Report

An 83-year-old woman was referred to our hospital 20 years ago because an abdominal ultrasound scan revealed a liver mass. A diagnosis of HCC was made. At initial diagnosis, the tumor-node-metastasis (TNM) classification of the cancer was T2N0M0, and RFA was initially performed. Thereafter, TACE and RFA were repeated, but no chemotherapy was administered. The patient was considered cancer-free for 4 years since the last treatment. Since the initial treatment, regular blood tests and computed tomography (CT) had been performed at intervals of 3 to 6 months in another hospital, liver function was good, and the Child-Pugh classification was grade A. CT suggested the recurrence of HCC after 4 years, with a tumor size of 2.1 cm, and the patient was admitted to our hospital for RFA. RFA was selected in this case because the patient preferred RFA instead of surgical resection. Her medical history included chronic hepatitis C, chronic lymphocytic leukemia, and hypertension. She had no history of smoking or alcohol consumption. The patient underwent a blood transfusion during childbirth.

Physical examination during her visit to our hospital revealed the following: height, 137 cm; weight, 52 kg; and body mass index, 27.7 kg/m2. Abdominal palpation revealed a mildly distended, soft abdomen. Blood test results showed that the albumin level was slightly low, and a good hepatic reserve was preserved; the Child-Pugh classification was grade A. Several tumor markers were elevated: alpha-fetoprotein (AFP) levels, 14 ng/mL, and protein induced by vitamin K absence-II (PIVKA-II), 104 mAU/mL. Contrast-enhanced CT revealed nodules inside the low-absorption zone of the previously treated area of RFA (Figure 1). Biopsy was performed to confirm the diagnosis, and RFA was performed simultaneously (day 0). Histological examination revealed spindle-shaped tumor cells and actively mitotic cells (Figure 2). Immunohistochemical analysis showed that Arginase-1, HepPar1, and Glypican3 were negative; AE1/AE3, CK7, and vimentin were positive; and CK19 was partially positive (Figure 3).

CT performed on the day after treatment showed no obvious residual lesions (day 1). However, on day 48, she presented to our hospital with the chief concern of worsening leg edema and abdominal distention. Blood tests revealed hepatic and renal dysfunction. AFP and PIVKA-II levels were 4.4 ng/mL and 302 mAU/mL, respectively. CT showed a prominent mass in S8 of the liver, ascites, and numerous disseminated lesions (Figure 4). Ascites puncture revealed bloody fluid. Considering the rapid disease progression, the patient was treated conservatively. However, the patient’s general condition gradually deteriorated, and she died on day 59. An autopsy revealed a white tumor approximately 3 cm in size exposed on the surface of the liver S8, with numerous disseminated nodules up to 45 mm in size in the abdominal wall and abdominal cavity (Figure 4). Numerous seeding nodules of up to 45 mm in size were observed in the omentum and mesentery (Figure 4). Regarding the histology of the disseminated nests in the abdominal cavity, they all had a histology similar to that of tumors on the liver surface. Tumor cells also grew in a multi-nodular fashion and were surrounded by a fibrous capsule in the RFA-treated area, which was presumed to be pre-existing HCC. Thus, we believe that sarcomatoid changes occurred as a result of repeated antitumor therapies, as previously reported, and that SHC was punctured by needle biopsy or RFA, resulting in intraperitoneal dissemination.


SHC is a rare malignant liver tumor, and its definition was proposed by the World Health Organization (WHO) in 2000 [1]. According to the WHO’s definition, (1) SHC tumors contain both carcinomatous and sarcomatous components, (2) tumors show cell morphologies of sarcomatous components varying from spindled to epithelioid and pleomorphic, and (3) positive epithelial and mesenchymal markers, identified using immunohistochemical staining, are present. Sarcomatoid components are considered to originate from a de-differentiated or undifferentiated process in HCC [10]. A previous study reported sarcomatoid changes in 3.9% of 355 HCC autopsies [10]. In a WHO-sponsored working group, spindle cell-type HCC, such as SHC, is classified as a subtype of HCC [11]. SHC has an aggressive clinical course and poor prognosis regardless of treatment since it is more prone to local recurrence and distant metastasis than is HCC [4–6]. Currently, surgery is the only treatment that has shown efficacy [9]. No proven effective treatments are available for patients with recurrence after surgical resection. Patients with SHC who undergo treatment with RFA, TACE, and radiation therapy have a limited therapeutic effect, resulting in poor outcomes [4,12,13]. To date, the efficacy of chemotherapy for SHC remains uncertain, although there have been some reports of chemotherapy being effective [14]. Several genetic mutations have been found frequently in SHC, including mutations in CDKN2A, EPHA5, FANCM, and MAP3K1 genes, which are involved in cell cycle regulation and DNA damage response, and their mutation rates are high; CDKN2A gene mutations are associated with low probability of survival in patients with SHC [15]. The frequency of mutations in TP53, TERT, and KRAS genes, which are involved in cancer development and progression, are also reported to be extremely high [16]. These results provide important insights into the pathogenesis of SHC and its targeted therapeutic strategies. Particularly, the involvement of CDKN2A mutation in the pathogenesis of SHC suggests that CDK4/6 inhibitors are promising therapeutic targets with important implications for future therapeutic development. The pathogenesis of SHC remains unclear, but it often occurs in patients with HCC who have undergone recurrent interventional treatments [4–6]. This suggests that repeated treatment for HCC may induce or promote sarcomatous changes. In the present case, repeated cancer treatment such as TACE, RFA, and PEIT induced sarcomatoid changes, resulting in the degeneration, necrosis, and regeneration of tumor cells [6,7]. SHC may be misdiagnosed as HCC because few specific features have been identified in the symptoms, serological findings, or imaging findings [9]. One of the few features of HCC with sarcomatoid changes is a low blood AFP level [5]. In most cases, SHC is precisely diagnosed after surgical resection or autopsy. In the present case, local recurrence of HCC was initially diagnosed, based on imaging findings and elevated tumor markers such as AFP and PIVKA-II, but in retrospect, the blood AFP level decreased in response to cancer progression, such as the appearance of disseminated lesions, which may have suggested the presence of SHC. Contrarily, the imaging features of SHC on CT and gadoxitate-weighted magnetic resonance imaging (MRI) often present as a subcapsular mass with hypovascularity and rim-like or heterogeneous enhancement on the arterial phase and a progressive dynamic pattern on CT, and with a high frequency of T2-weighted areas on gadoxetic acid-enhanced MRI due to extensive necrosis and vascular invasion [17–19]. MRI was not performed in this case; however, in retrospect, CT imaging did show heterogeneous enhancement on the arterial phase and a progressive dynamic pattern (Figure 1). These imaging features were different from the typical HCC imaging findings present at the time of HCC recurrence 4 years ago; we speculate that these differences were due to the sarcomatoid changes in the HCC. Liver biopsy can be used to diagnose liver cancer but is not necessary in all cases. For example, biopsy should be considered when imaging studies cannot determine whether the cancer is benign or malignant or when the patient’s treatment options require an accurate assessment of the type and progression of the liver cancer. In this case, the patient was initially thought to have recurrent HCC; however, the imaging findings were not typical of HCC. Consequently, liver biopsy and RFA for SHC were performed, and contrast-enhanced CT performed the following day showed no obvious residual disease. Thus, the patient was scheduled for follow-up imaging within 3 months. The diagnosis of SHC is usually confirmed by surgical resection or autopsy, with only a few reported cases diagnosed by liver biopsy [20]. The median disease-free survival and overall survival have been reported to be 3 and 5 months, respectively [9]. Furthermore, even if surgical resection or liver transplantation is performed, the 3-year survival rates are 14.3% and 37.5%, respectively [4,13]. Therefore, in this case, we should have considered additional hepatic resection and chemotherapy, or follow-up imaging in a short period during diagnosis of SHC by needle biopsy, considering the risk for seeding or recurrence.


SHC is clearly more prone to recurrence and has a poorer prognosis than HCC; therefore, it is unlikely that invasive non-surgical treatments such as TACE, RFA, and PEIT can be expected to cure SHC. Therefore, aggressive surgical resection or liver transplantation seems to be the most appropriate treatment for SHC currently. When SHC is diagnosed using needle biopsy, aggressive surgical resection or follow-up imaging at an interval shorter than that for HCC is necessary. The possibility of SHC should also be considered when the blood AFP level decreases contrary to disease progression.


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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923