17 May 2023: Articles
Rapidly Progressing Sarcomatoid Hepatocellular Carcinoma after Needle Biopsy and Radiofrequency Ablation
Unusual clinical course, Rare diseaseMasamichi Kimura 1ABCDEF*, Ryo Matsuoka1B, Koji Nishikawa1CD, Jun Imamura1CD, Kiminori Kimura 1DG
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
Sarcomatoid carcinomas are tumors containing sarcomatoid components of malignant epithelial and spindle-shaped cells . A total of 1.8% to 9.4% of hepatocellular carcinomas (HCCs) have sarcomatoid changes and are termed sarcomatoid hepatocellular carcinomas (SHCs) . SHC is a distinct subtype of HCC identified histologically by spindle-shaped, mitotically active cells . 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 . In this study, we report a case of rapidly progressing SHC that was diagnosed using needle biopsy and treated with RFA.
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 . 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 . A previous study reported sarcomatoid changes in 3.9% of 355 HCC autopsies . In a WHO-sponsored working group, spindle cell-type HCC, such as SHC, is classified as a subtype of HCC . 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 . 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 . Several genetic mutations have been found frequently in SHC, including mutations in
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.
FiguresFigure 1.. Contrast-enhanced computed tomography (CT) 4 years before radiofrequency ablation (RFA), showing a tumor (red arrow) in the liver S8 (A) enhancement in the early phase and (B) washout in the late phase. (C, D) Contrast-enhanced CT showing nodules (red arrow) inside the low-absorption zone of the previously treated area of RFA. Figure 2.. Hematoxylin and eosin staining of cancerous specimens showing spindle-shaped tumor cells (red arrow) and actively mitotic cells (yellow arrow). Figure 3.. Immunohistochemical staining showing positive AE1/AE3, CK7, and vimentin; positive CK19 (in some cells); and negative HepPar1, Arginase-1, and Glypican3. Figure 4.. (A) Simple computed tomography (CT) showing a prominent mass (red arrow) in hepatic S8 and ascites (yellow arrow) with high CT values. (B) Simple CT showing numerous disseminated lesions (red arrows) in the abdominal cavity. (C, D) In the diaphragm, numerous lumpy tumors (red arrows) and disseminated nodules (red arrows) up to 13 cm in size, adherent to the right lobe capsule of the liver, are observed. A 3-cm large mass (yellow arrow) that is exposed on the surface of the liver S8 is observed. A clot is also observed near the right subdiaphragm. The ascites appeared pale and bloody and was an amount of 3300 mL, but the source of the hemorrhage was unknown.
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