Published online Oct 15, 2026. doi: 10.4251/wjgo.124211
Revised: August 12, 2026
Accepted: September 17, 2026
Published online: October 15, 2026
Processing time: 122 Days and 0.6 Hours
Primary hepatic squamous cell carcinoma (PHSCC) is extremely rare, accounting for approximately 0.2% of all primary liver malignancies. PHSCC lacks specific clinical manifestations and is usually diagnosed at an advanced stage. Currently, no disease-specific diagnostic or therapeutic guidelines are available. Manage
We report the case of a 62-year-old Han Chinese man admitted with a 7-day history of persistent right upper abdominal distension and pain, accompanied by fatigue and loss of appetite. Physical examination revealed right upper abdominal tenderness. Contrast-enhanced abdominal computed tomography demonstrated a large hypodense mass involving the left hepatic lobe and the right anterior hepatic lobe. Ultrasound-guided liver biopsy and subsequent histopathological examination confirmed PHSCC after extrahepatic primary sites were excluded. Following multidisciplinary team (MDT) evaluation, the patient received transarterial interventional therapy combined with an immune checkpoint inhibitor (ICI). Post-treatment imaging demonstrated marked tumor regression. The patient achieved an overall survival of 28 months. We also reviewed the relevant literature to summarize the diagnostic challenges and therapeutic approaches for this rare malignancy.
This case suggests that, for selected patients with unresectable PHSCC, an MDT-guided strategy incorporating transarterial interventional therapy and an ICI may represent a potential individualized therapeutic option.
Core Tip: Primary hepatic squamous cell carcinoma is extremely rare, and no standard treatment has been established. This unresectable, multifocal case was treated with transarterial chemoembolization combined with camrelizumab, followed by hepatic arterial infusion chemotherapy, achieving an overall survival of 28 months. This case suggests that nonsurgical multimodal therapy may provide temporary intrahepatic disease control. However, a single case cannot establish the independent contribution of each treatment or a causal relationship with survival benefit.
- Citation: Qing D, Pan SL, Zhao J, Liu XB, Li WN. Primary squamous cell carcinoma arising in the liver: A case report and review of literature. World J Gastrointest Oncol 2026; 18(10): 124211
- URL: https://www.wjgnet.com/1948-5204/full/v18/i10/124211.htm
- DOI: https://dx.doi.org/10.4251/wjgo.124211
Squamous cell carcinoma (SCC) is a malignant tumor arising from squamous epithelial cells and commonly occurs in tissues such as the skin, esophagus, and bronchi. Because the liver lacks squamous epithelium, primary hepatic SCC (PHSCC) is extremely rare, accounting for only 0.2% of primary hepatic malignancies[1]. The etiology of PHSCC remains unclear, but it is believed to be associated with conditions such as liver cysts, intrahepatic bile duct stones, and hepatic teratomas[1-5]. PHSCC predominantly affects older men[1] and usually presents with nonspecific clinical symptoms; most cases are diagnosed at an advanced stage[2]. The diagnosis of PHSCC relies primarily on pathological examination and careful exclusion of metastatic SCC from extrahepatic sites. Although no standardized treatment guidelines have been established for PHSCC, previously reported treatment options include surgical resection, radiotherapy, chemo
Herein, we report a rare case of unresectable PHSCC evaluated through multidisciplinary team (MDT) discussion and treated with transarterial interventional therapy combined with an immune checkpoint inhibitor (ICI). The patient achieved an overall survival of 28 months. We further discuss the potential therapeutic implications and limitations of this individualized strategy.
A 62-year-old man presented with a 7-day history of right upper abdominal distension and pain.
Seven days before admission, he developed right upper quadrant discomfort without an obvious precipitating factor, accompanied by decreased appetite and fatigue. He denied nausea or vomiting.
He had no history of chronic alcohol use, smoking, regular medication use, hepatitis B infection, hepatic cysts, or intrahepatic bile duct stones.
There was no relevant family history.
Physical examination revealed a palpable liver and right upper quadrant tenderness. A whole-body dermatologic examination showed no suspicious cutaneous lesions suggestive of primary cutaneous SCC, including masses, ulcers, nodules, or scaly lesions. No other abnormal physical findings were noted.
Laboratory testing showed a white blood cell count of 14.28 × 109/L, an absolute neutrophil count of 11.68 × 109/L (neutrophils, 81.9%), hemoglobin of 103 g/L, and a platelet count of 182 × 109/L. Aspartate aminotransferase (AST) was 63 U/L, and alanine aminotransferase (ALT) was 29 U/L; total, direct, and indirect bilirubin levels were within reference limits. Tumor marker levels were as follows: Alpha-fetoprotein 2.1 μg/L; carcinoembryonic antigen 2.26 μg/L; carbohydrate antigen 19-9 93.7 U/mL; and abnormal prothrombin, 14.13 mAU/mL.
Contrast-enhanced computed tomography (CT) of the upper abdomen demonstrated a large heterogeneous low-density mass involving the left lobe and right anterior segment of the liver, with maximal cross-sectional dimensions of approximately 16.2 cm × 7.2 cm. For retrospective assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, this dominant lesion was selected as the target lesion, and its longest diameter was remeasured as 166.71 mm at baseline. The lesion had an indistinct interface with the stomach and showed heterogeneous contrast enhancement. Multiple rounded low-density lesions were identified in the liver, with the largest measuring approximately 1.9 cm × 2.1 cm and showing ring enhancement in the arterial and venous phases. The portal vein was not dilated. The gallbladder, intra- and extrahepatic bile ducts, pancreas, and spleen were unremarkable (Figure 1).
The MDT included specialists in hepatobiliary surgery, oncology, radiology, and interventional medicine. The 62-year-old patient had an Eastern Cooperative Oncology Group performance status of 3. Imaging revealed multiple intrahepatic tumors, with the dominant lesion being large, poorly defined, and showing an indistinct interface with the gastric wall. After comprehensive evaluation, the MDT deemed the tumor unresectable.
Ultrasound-guided percutaneous liver biopsy was performed. Histomorphological evaluation of the hematoxylin and eosin (H&E)-stained biopsy sections revealed a neoplastic lesion; however, the tumor cells lacked sufficiently characteristic morphological features to allow definitive histological classification, and the lesion could only be classified as a poorly differentiated malignant neoplasm on morphology alone. Immunohistochemical (IHC) staining results were as follows: Cytokeratin 7 (-), cytokeratin 19 (CK19; +), arginase-1 (-), glypican-3 (-), hep-1 (-), cytokeratin 5/6 (CK5/6; +), p63 (+), cluster of differentiation 56 (-), a Ki-67 proliferation index of 40%, Epstein-Barr virus-encoded RNA (-), BRG (+), NUT-1 (-), p40 (+), INI-1 (+), thyroid transcription factor-1 (-), and p16 (-). In particular, positivity for p63, p40, and CK5/6 supported squamous differentiation. Based on the combined histomorphological and immunophenotypic findings, the lesion was diagnosed as poorly differentiated SCC (Figure 2). The diagnosis was reviewed and signed out by a senior pathologist from the hepatobiliary pathology subspecialty group at our institution. The available histomorphological and IHC findings were considered sufficient for pathological classification as poorly differentiated SCC; therefore, no additional diagnostic stains or molecular tests were considered necessary for establishing the pathological diagnosis at that time.
At the time of pathological diagnosis, the findings established SCC involving the liver but could not distinguish a primary hepatic tumor from hepatic metastasis of an extrahepatic SCC. Therefore, the need to exclude an extrahepatic primary lesion was communicated to the clinical team.
To exclude metastatic disease from an extrahepatic primary site, a systematic evaluation was performed. A whole-body skin examination showed no suspicious cutaneous lesions. Chest CT, fiberoptic nasopharyngolaryngoscopy, esophagogastroduodenoscopy, and colonoscopy were performed to investigate potential primary lesions in the head and neck, lungs, and gastrointestinal tract; however, no abnormalities were identified. Whole-body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT demonstrated a large hypodense mass involving the left hepatic lobe and right anterior lobe, with an indistinct interface with the stomach, as well as multiple round hypodense intrahepatic lesions. All lesions showed varying degrees of increased 18F-FDG uptake. No abnormal hypermetabolic lesions were identified outside the liver (Figure 3). Based on the pathological findings and the absence of evidence of an extrahepatic primary tumor, a diagnosis of PHSCC was established.
Given the unresectable, multifocal, and liver-confined disease, TACE was selected as a locoregional treatment following MDT discussion. Under local anesthesia and standard sterile conditions, right femoral arterial access was obtained, followed by celiac and hepatic arteriography to delineate the tumor-feeding arteries. A microcatheter was then superselectively advanced into multiple tumor-feeding branches of the left hepatic artery. 5-fluorouracil (5-FU; 0.75 g), lobaplatin (40 mg), epirubicin (30 mg), and lipiodol (10 mL) were administered intra-arterially, followed by embolization with gelatin sponge particles. Repeat angiography demonstrated a marked reduction in tumor staining, which was considered the procedural endpoint. After catheter removal, vascular closure and compression hemostasis were performed. The patient remained supine with immobilization of the puncture-side lower extremity for 6 hours, and the puncture site was monitored for bleeding or hematoma. Camrelizumab (200 mg, intravenous) was administered on December 13, 2022, and March 25, 2023. Owing to financial constraints faced by the patient’s family, camrelizumab was administered only twice, and no further doses were given. For the present report, serial contrast-enhanced CT images were retrospectively reassessed according to RECIST version 1.1. On July 24, 2023, the longest diameter of the selected target lesion in the left hepatic lobe had decreased from 166.71 mm at baseline on October 23, 2022, to 95.38 mm, representing a 42.8% reduction from baseline and meeting the criteria for partial response.
On March 10, 2024, contrast-enhanced liver CT demonstrated intrahepatic tumor progression. The longest diameter of the target lesion had increased to 116.55 mm, representing a 22.2% increase from the nadir of 95.38 mm and an absolute increase of 21.17 mm. In addition, multiple new intrahepatic lesions were identified. Therefore, the overall response was classified as progressive disease according to RECIST 1.1. Because the disease remained confined to the liver despite repeated TACE, hepatic arterial infusion chemotherapy (HAIC) was selected as a subsequent liver-directed treatment following MDT discussion. HAIC was administered from March 14, 2024 to March 16, 2024 and from April 15, 2024 to April 17, 2024, using the same regimen and procedural technique for both cycles. Under local anesthesia and standard sterile conditions, the right femoral artery was punctured, followed by celiac and hepatic arteriography. Angiography demonstrated multiple nodular and mass-like areas of abnormal tumor staining within the liver, with relatively faint enhancement, irregular morphology, and poorly defined margins. A 5-French hepatic catheter was positioned in the common hepatic artery, and a microcatheter was advanced into the right hepatic artery. After catheter position and patency were confirmed, chemotherapy was administered intra-arterially through the catheter system. Oxaliplatin (140 mg) in 100 mL of 5% glucose solution was infused over 2 hours. After completion of the oxaliplatin infusion, the catheter system was flushed with 5% glucose solution before administration of the subsequent agents. Leucovorin (600 mg) in 100 mL of normal saline was then infused over 2 hours. Subsequently, 5-FU (500 mg) in 100 mL of normal saline was infused over 20 min, followed by 5-FU (4000 mg) in 500 mL of normal saline as a continuous intra-arterial infusion over 32 hours. After completion of chemotherapy, the catheters were removed, followed by vascular closure and compression hemostasis. The patient remained supine with immobilization of the right lower extremity for 6-8 hours, and the puncture site was monitored for bleeding or hematoma. No immediate procedure-related complications were observed.
Treatment-related adverse events included transient liver-function abnormalities and poor appetite. The poor appetite improved with symptomatic treatment. Available longitudinal liver-function tests showed transient treatment-associated liver-function abnormalities following transarterial therapy, with varying severity across treatment sessions. The most pronounced aminotransferase elevation occurred after the first TACE session, when AST increased from 63 U/L to 429 U/L and ALT from 29 U/L to 349 U/L, corresponding to grade 3 aminotransferase elevation according to the Common Terminology Criteria for Adverse Events version 5.0. Magnesium isoglycyrrhizinate was administered as hepatoprotective therapy after each transarterial treatment session. After the first TACE session, aminotransferase levels decreased substantially within several days. Grade 1 AST, ALT, and total bilirubin elevations were observed after the second TACE session. Immediate post-treatment laboratory data were not available for the third TACE session, whereas later follow-up after the fourth and fifth TACE sessions showed aminotransferase levels returning toward or within the pretreatment range. Following the first HAIC cycle, AST and ALT increased from 80 U/L and 61 U/L to 215 U/L and 121 U/L, respectively, corresponding to grade 1 elevations relative to the abnormal pretreatment baseline; total bilirubin also showed a grade 1 increase. Following the second HAIC cycle, AST increased from 64 U/L to 126 U/L, corresponding to a grade 1 elevation, whereas total bilirubin did not worsen. Grade 2 hypoalbuminemia was also observed after the second HAIC cycle. Available follow-up laboratory data showed subsequent improvement in the treatment-associated liver-function abnormalities (Supplementary Table 1).
Initially, the patient was optimistic about treatment. However, after being informed of tumor progression, he experienced marked psychological distress and gradually lost confidence in further antitumor therapy. After discussion with the treating team, the patient declined further antitumor treatment after April 17, 2024. In February 2025, the patient was readmitted because of poor appetite and subsequently died of massive gastrointestinal hemorrhage during hospitalization. The exact source of bleeding could not be definitively identified because further diagnostic evaluations, such as emergency endoscopy and an autopsy, were not performed. Therefore, a direct causal relationship between the fatal gastrointestinal hemorrhage and tumor progression or treatment-related complications could not be established (Table 1).
| Date | Treatment and medication | Imaging follow-up/clinical outcome |
| October 23, 2022 | Baseline contrast-enhanced CT: The selected target lesion in the left hepatic lobe measured 166.71 mm in longest diameter | |
| November 4, 2022 | TACE | / |
| December 13, 2022 | Camrelizumab 200 mg | / |
| December 25, 2022 | TACE | / |
| March 22, 2023 | TACE | / |
| March 25, 2023 | Camrelizumab 200 mg | / |
| July 24, 2023 | / | Target lesion decreased to 95.38 mm (-42.8% from baseline); PR according to RECIST 1.1. |
| July 28, 2023 | TACE | / |
| November 6, 2023 | TACE | / |
| March 10, 2024 | / | Target lesion increased to 116.55 mm (+22.2% from nadir; absolute increase, 21.17 mm), with multiple new intrahepatic lesions; PD according to RECIST 1.1. |
| March 14, 2024 to March 16, 2024 | HAIC, FOLFOX-based regimen | / |
| April 15, 2024 to April 17, 2024 | HAIC, FOLFOX-based regimen | / |
| After April 17, 2024 | Patient declined further antitumor treatment | / |
| February 2025 | Supportive care during hospitalization | Presented with loss of appetite; subsequently died of gastrointestinal bleeding; overall survival was 28 months |
PHSCC is a rare malignancy, with only several dozen cases reported since 1970[8]. Because of its rarity, the etiology and pathogenesis of PHSCC remain unclear. Several potential mechanisms have been proposed, but no definitive consensus has been established. Abbas et al[9] reported that most biliary tract tumors are adenocarcinomas, whereas SCCs account for only approximately 2% of cases. Such tumors are usually associated with chronic biliary inflammation, such as primary sclerosing cholangitis, hepatolithiasis, or liver fluke infection, which may drive squamous metaplasia and subsequent carcinogenesis. Lombardo et al[10] described a hepatic cystic lesion lined by squamous epithelium and proposed that recurrent inflammation, hemorrhage, and calcification might induce squamous metaplasia of the cyst lining, ultimately leading to malignant transformation. In this patient, however, none of the previously reported potential predisposing factors, including hepatitis B virus infection, liver cysts, hepatolithiasis, or clonorchiasis, were identified. Therefore, the classical “inflammation-metaplasia-carcinoma” sequence could not fully account for tumorigenesis in this case. Notably, IHC staining showed CK19 positivity. CK19 is commonly regarded as a marker associated with a biliary epithelial phenotype and hepatic progenitor cell-related differentiation[11,12]. Therefore, CK19 positivity may suggest that the tumor exhibits features of biliary epithelial or progenitor cell-associated differentiation, although this finding is insufficient to determine the exact cellular origin of the tumor[13]. Taken together, the pathogenesis of PHSCC in this case remains unclear. Further pathological and molecular investigations are warranted to elucidate the histogenesis and underlying molecular mechanisms of PHSCC.
The diagnosis of PHSCC requires both histopathological confirmation of SCC and careful exclusion of an extrahepatic primary tumor because metastatic SCC involving the liver is far more common than primary hepatic disease[14,15]. H&E staining typically shows tumor cells arranged in nests or sheets, with marked nuclear atypia and hyperchromasia; in well-differentiated cases, keratin pearl formation may also be observed. Immunohistochemically, strong nuclear positivity for p63 and p40 indicates squamous differentiation[4], and CK5/6 positivity may provide additional support for a squamous phenotype. In the present case, the histopathological morphology and IHC profile supported a diagnosis of poorly differentiated SCC, whereas comprehensive systemic evaluation revealed no evidence of an extrahepatic primary lesion. Together, these findings supported the diagnosis of PHSCC.
Currently, no standardized treatment guidelines are available for PHSCC. Published reports indicate that the median overall survival times for patients undergoing radical surgery and palliative treatment are 17 months and 5 months, respectively[1], suggesting that surgical resection remains the preferred option when feasible[16]. In this case, the patient was not a candidate for radical resection. Therefore, after MDT discussion, an individualized treatment strategy com
The rationale for this strategy was to enhance local drug exposure within the liver while reducing systemic toxicity. TACE combines selective intra-arterial delivery of chemotherapeutic agents with vascular embolization, which may increase intratumoral drug concentrations and reduce systemic adverse effects. In addition, embolization can induce tumor ischemia and hypoxia, leading to tumor necrosis and the potential release of tumor-associated antigens[17]. These antigens may promote antitumor immune activation, whereas blockade with ICIs may further enhance cytotoxic T-cell-mediated tumor destruction[18]. This potential immunologic complementarity provided a mechanistic rationale for combining TACE with an ICI. The specific selection of camrelizumab was based primarily on MDT judgment and indirect evidence from previous studies showing its antitumor activity and acceptable safety profile in advanced hepatocellular carcinoma[19-23].
The use of platinum-based agents and 5-FU was also supported by limited published evidence. Several case reports have described favorable responses of PHSCC or hepatic SCC to these agents. Lee et al[4] reported a substantial response to 5-FU combined with carboplatin in PHSCC; Iimuro et al[24] found that cisplatin combined with 5-FU was effective in PHSCC; Boscolo et al[25] reported a favorable response of hepatic SCC to cisplatin and 5-FU; and Xiao et al[8] described a patient with PHSCC who achieved long-term survival after hepatectomy followed by TACE and two cycles of gem
After TACE, the hepatic lesion initially decreased in size. However, subsequent imaging showed enlargement of the existing lesions and an increased number of intrahepatic lesions, indicating inadequate intrahepatic tumor control. Because the disease remained confined to the liver, HAIC was selected as a subsequent locoregional treatment. HAIC allows direct intra-arterial infusion of chemotherapeutic agents into the hepatic circulation, thereby increasing local drug exposure within intrahepatic tumors while potentially reducing systemic exposure. In this case, a leucovorin, 5-FU, and oxaliplatin (FOLFOX)-based regimen was selected after MDT discussion. This decision was based on experience with FOLFOX-based HAIC in unresectable hepatocellular carcinoma[21] and on the previously reported use of platinum agents and 5-FU in PHSCC[4,24,25]. Nevertheless, the patient received only two cycles of HAIC and subsequently discontinued treatment; therefore, the therapeutic effect of HAIC could not be adequately evaluated in this case.
Tumor progression appeared to substantially affect the patient’s psychological well-being and confidence in further treatment. After being informed of disease progression, he experienced marked psychological distress and ultimately declined further antitumor therapy. Psychological distress, including anxiety, depression, and demoralization, is common among patients with advanced or rare cancers and may influence treatment adherence and end-of-life decision-making[26-28]. Previous evidence suggests that appropriate psychosocial interventions may improve certain psychological and end-of-life experiences in patients with advanced cancer[29]. In light of this evidence and the clinical course of the present case, timely psychological assessment, communication with patients and their families, and appropriate psychosocial and supportive care should be considered important components of comprehensive management for patients with advanced PHSCC.
A focused narrative literature review was conducted using PubMed, Web of Science, and Google Scholar to identify previously reported cases of PHSCC. The databases were searched from inception through August 6, 2026, and the search was restricted to English-language publications. No restrictions were imposed on publication year or article type. In PubMed, the primary search combined the terms “primary hepatic squamous cell carcinoma”, “primary squamous cell carcinoma of the liver”, “primary squamous cell carcinoma of liver”, “primary liver squamous cell carcinoma”, “PHSCC”, and “PSCCL” in the title/abstract fields. Additional targeted searches combined these disease-related terms with treatment-related terms, including “immunotherapy”, “immune checkpoint inhibitor”, “PD-1”, “PD-L1”, “camrelizumab”, “pembrolizumab”, “nivolumab”, “sintilimab”, “tislelizumab”, “TACE”, “transarterial chemoembolization”, “transcatheter arterial chemoembolization”, “TAI”, “arterial infusion”, “HAIC”, “hepatic arterial infusion chemo
Records retrieved from the literature search were first screened based on titles and abstracts, followed by full-text review of potentially relevant reports. Reports were eligible for inclusion if they described PHSCC and provided individual-patient information on diagnosis, treatment, and follow-up. For the comparative summary in Table 2, we specifically included cases treated with immunotherapy, locoregional therapy, or both[1,5,6,8,16,30-37]. Duplicate publications involving the same patient and reports in which hepatic SCC was considered metastatic from an extrahepatic primary site were excluded. In addition, the reference lists of eligible articles were manually reviewed to identify further potentially relevant reports.
| Ref. | Age/sex | Tumor characteristics | Treatment | Molecular or immune biomarkers | Follow-up duration | Status at last follow-up |
| Arase et al[30], 1988 | 69/M | Right hepatic lobe; 8 cm at detection and 13 cm at autopsy; portal vein tumor thrombus | Single transarterial infusion of mitomycin C (16 mg) | - | 1 month | Deceased (acute myocardial infarction) |
| Kaji et al[36], 2003 | 67/F | Bilobar hepatic lesions; maximum diameter approximately 10 cm; hilar lymph-node metastasis | HAIC with low-dose cisplatin (10 mg/day) and 5-FU (250 mg/day) | - | 23 months | Deceased |
| Yuki et al[35], 2006 | 63/M | Segment VI; 6 cm at diagnosis, increasing to 13 cm; underlying cirrhosis | Transarterial infusion of epirubicin, 5-FU, and mitomycin C followed by TAE; subsequent continuous intra-arterial cisplatin | - | 8 months | Deceased |
| Zhao et al[37], 2012 | 60/F | Junction of the left medial and right anterior hepatic segments; recurrent lesion 1.5 cm × 1.2 cm × 0.5 cm with extrahepatic extension | Prior hepatic resection; radiofrequency ablation and local radiotherapy (36 Gy/20 fractions) for recurrence | - | NR | Alive at publication |
| Wilson et al[5], 2013 | 34/M | Segments IV, V, and VIII; 10 cm on initial imaging and 14 cm at resection; ciliated hepatic foregut cyst-associated | TACE followed by PVE and right trisectionectomy; carboplatin plus paclitaxel after recurrence | - | 6 months | Alive with lung and abdominal recurrence |
| Zhang et al[1], 2015, case 2 | 70/F | Multiple lesions involving both lobes; maximum diameter 15 cm | Three sessions of TACE with 5-FU, cisplatin, doxorubicin, and lipiodol, followed by SOX chemotherapy | - | 9 months | Deceased |
| Zhang et al[1], 2015, case 4 | 73/F | Multiple cystic lesions involving the whole liver; maximum diameter 11 cm | Palliative unroofing of four large cysts with intralesional injection of alcohol (20 mL) and 5-FU (0.4 g) | - | 4 months | Deceased |
| Tuminello et al[34], 2020 | 79/M | Segments IV-VIII; 15 cm × 12 cm; multiple hepatic cysts | Percutaneous microwave ablation combined with TACE/arterial embolization | - | 9 months | Deceased |
| Xiao et al[8], 2021, case 2 | 47/M | Solitary lesion in segments VI/VII; 10 cm | Right hepatectomy and cholecystectomy, followed by TACE and two cycles of gemcitabine plus 5-FU | PD-L1 positive in tumor cells | 35 months1 | Alive at last follow-up |
| Sun and Jin[33], 2021 | 73/M | Right hepatic lobe; 7.3 cm × 3.8 cm at diagnosis, increasing to 10.1 cm × 5.2 cm after 2 months | Argon-helium cryoablation | - | NR | Alive with clinical deterioration at last report |
| Kang et al[16], 2022 | 73/M | Left caudate lobe; approximately 3.8 cm | Laparoscopic left caudate lobectomy followed by sintilimab (200 mg every 3 weeks) | - | 8 months | Alive without recurrence |
| Zhao et al[6], 2023 | 60/F | Right posterior lobe; 6.3 × 6.8 cm; segments V, VII, and VIII; right portal vein branch involvement and lymph-node metastases | Gemcitabine plus cisplatin, followed by pembrolizumab plus nab-paclitaxel | PD-L1 TPS 1%; TMB 24.93 mutations/Mb; MSI-H | 15 months | Deceased |
| Jiang et al[31], 2025 | 72/M | Multiple right-lobe lesions; largest 8.2 cm × 7.8 cm; portal vein tumor thrombus; lymph-node and bone metastases | Envafolimab plus nab-paclitaxel and cisplatin | PD-L1 CPS 5 | 18 months | Alive with sustained partial response |
| Antzoulas et al[32], 2025 | 50/M | Central liver; 10.5 cm × 9.8 cm; segments IVa, IVb, V, and VIII; subsequent peritoneal metastases | Five cycles of carboplatin plus paclitaxel, followed by pembrolizumab | PD-L1 positive; MMR proteins retained | 4 months | Deceased |
| Present case | 62/M | Left lobe and right anterior segment; 16.2 cm × 7.2 cm; multiple intrahepatic lesions; indistinct interface with the gastric wall | Repeated TACE and camrelizumab, followed by HAIC after intrahepatic progression | PD-L1, TMB, MSI status, and NGS not assessed | 28 months | Deceased |
Only a small number of patients received immunotherapy, including postoperative sintilimab, pembrolizumab-based regimens, envafolimab-based therapy, and, in the present case, camrelizumab. The available evidence remains limited to individual case reports and small case series, and the marked heterogeneity in disease extent, treatment sequence, biomarker assessment, and follow-up precludes direct comparisons of treatment efficacy.
The present case provides a detailed longitudinal record of the initial radiologic response following repeated TACE and camrelizumab treatment, subsequent intrahepatic disease progression, and later treatment with HAIC. The patient achieved an overall survival of 28 months. Overall, this case suggests that nonsurgical combination therapy may provide short-term disease control in patients with unresectable or multifocal PHSCC, although the response may not be durable. The longitudinal imaging and treatment data presented in this case further expand the limited evidence base for nonsurgical multimodal management of this rare malignancy.
This case has several limitations. First, as a single-patient report, the observed clinical outcome and prolonged survival cannot be causally attributed to any specific treatment. The patient’s baseline clinical condition, disease extent and biological behavior, as well as the sequential use of TACE, camrelizumab, and HAIC, may all have influenced the outcome. Second, PD-L1 expression, tumor mutational burden, microsatellite instability status, and genomic profiling by next-generation sequencing were not assessed in this patient. Therefore, the absence of predictive molecular and immune biomarker data limits interpretation of the contribution of camrelizumab to the observed therapeutic response. Finally, although the pathological diagnosis was supported by histomorphological and IHC findings and specialist pathological review, the use of a percutaneous biopsy specimen inherently limited the extent of tumor sampling. In addition, radiologic response was assessed retrospectively rather than according to a prospectively predefined imaging protocol.
PHSCC is extremely rare and should be diagnosed only after extrahepatic primary lesions have been carefully excluded. This case suggests that TACE combined with an ICI may provide temporary disease control in patients with unresectable or multifocal disease. However, the response was not durable, and the efficacy of this treatment strategy cannot be established from a single case.
The authors thank all participants in this study.
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