Primary hepatic follicular dendritic cell sarcoma: A case study and literature review

Abstract

Follicular dendritic cell sarcoma, a rare malignant tumor arising from specialized antigen-presenting cells, typically occurs in lymph nodes but can also develop at extranodal sites, including the liver. We present a case of a woman in her late 20s with systemic lupus erythematosus who presented with fever as the chief complaint. Imaging revealed a hepatic mass, and pathology confirmed the diagnosis of hepatic follicular dendritic cell sarcoma. The patient showed no recurrence 1 year post-radical surgery. We analyzed a total of 43 cases from 32 previous reports and the present case. Among these, the mean age at onset was 48 years, the median maximum tumor diameter was 87.5 mm, and there was a female predominance. Survival analysis showed that the 5-year disease-free survival of patients was 63.4%. This case and literature review highlight the rarity and diagnostic challenges of primary hepatic follicular dendritic cell sarcoma, especially in patients with atypical presentations such as fever of unknown origin. Early recognition and radical surgery are crucial for a favorable prognosis.

Introduction

Follicular dendritic cell sarcoma (FDCS) is an extremely rare malignant tumor classified under the category of histiocytic and dendritic cell neoplasms. Since its initial documentation in 1986, ¹ the incidence of FDCS has remained very low, and its clinical and pathological characteristics are yet to be completely understood. FDCS originates from follicular dendritic cells, specialized antigen-presenting cells that typically reside within the germinal centers of lymphoid tissues, particularly in the lymph nodes. FDCS can also occur at extranodal sites. ² Extranodal FDCS cases involve sites such as the liver, spleen, tonsil, urinary bladder, ³ and intra-abdominal soft tissue. FDCS can be misdiagnosed as interdigitating dendritic cell sarcoma, thymoma, inflammatory pseudotumor, and gastrointestinal stromal tumor. ⁴ Primary hepatic FDCS is rare in primary liver neoplasms. Primary hepatic FDCS exhibits unique diagnostic challenges due to its clinical and radiological similarity to other tumors. According to the World Health Organization classification of tumors, the diagnosis of FDCS requires pathological confirmation. The characteristic histopathological findings include spindle-to-ovoid tumor cells arranged in storiform, fascicular, or whorled growth patterns; a syncytial cytomorphology; scattered infiltrates of small lymphocytes among tumor cells; immunopositivity for at least two follicular dendritic cell markers; and absence of staining for lymphoid and other specific differentiation markers. ⁵

We report a case of primary hepatic FDCS in a patient with systemic lupus erythematosus, whose initial and predominant clinical manifestation was fever. The reporting of this study conforms to the Case Report (CARE) guidelines. ⁶ We obtained signed consent from the patient for the publication of this report.

Case presentation

Patient information

A Chinese female patient in her late 20s was admitted to the Department of General Surgery of Peking University Third Hospital in mid-2024, due to a fever of unknown origin occurring for more than a month and the detection of a space-occupying lesion in the liver through examinations conducted at another hospital.

Medical history and clinical characteristics

More than a month ago, the patient presented with a fever of unknown origin, with temperature ranging from 38.5°C to 40°C, without nausea, vomiting, abdominal pain, diarrhea, or jaundice of the skin and sclera, leading to admission to a local hospital. Positron emission tomography/computed tomography (PET/CT) revealed a hypermetabolic mass with high glucose density in the posterior inferior segment of the right liver lobe, suggesting a possible infection, with neoplastic lesions remaining to be ruled out. Urine cultures were conducted twice and blood cultures three times, all of which failed to detect any pathogens. Antibiotic therapy was administered without achieving efficacy. Subsequently, the patient was transferred to another local hospital, where magnetic resonance imaging (MRI) of the liver indicated a space-occupying lesion in the right liver lobe, with a possible speculation of an inflammatory myofibroblastic tumor. Since the onset of illness, she had experienced a weight loss of 6 kg. To seek further diagnosis and treatment, the patient presented to our department’s outpatient clinic.

The patient has a 17-year history of systemic lupus erythematosus and has been taking hydroxychloroquine sulfate tablets orally in the morning with satisfactory effects. However, the medication was discontinued for over 40 days. The patient had been found to have anemia for over 40 days, with a hemoglobin level of 70 g/L. After blood transfusion treatment, the hemoglobin level improved to 110 g/L. The patient did not have a familial history of illness. A specialized abdominal examination revealed no abnormalities. A comprehensive physical examination revealed no abnormalities throughout the body.

The primary abnormal results of the preoperative blood examination are as follows: C-reactive protein, 6.53 mg/dL (↑); alanine aminotransferase, 540 U/L (↑); albumin, 30.4 g/L (↓); alkaline phosphatase, 133 U/L (↑); aspartate aminotransferase, 485 U/L (↑); lactate dehydrogenase, 369 U/L (↑); urea, 2.4 mmol/L (↓); sodium, 136 mmol/L (↓); glucose, 2.9 mmol/L (↓); creatinine (enzymatic method), 28 umol/L (↓); gamma-glutamyl transferase, 97 U/L (↑); white blood cells, 12.48 × 10⁹/L (↑); red blood cells, 3.67 × 10¹²/L (↓); hemoglobin, 101 g/L (↓); hematocrit, 0.32 (↓); lymphocyte percentage, 8.9% (↓); neutrophil percentage, 85% (↑); absolute neutrophil count, 10.61 × 10⁹/L (↑); eosinophil percentage, 0% (↓); and absolute monocyte count, 0.74 × 10⁹/L (↑). Tumor markers, including alpha-fetoprotein, carbohydrate antigen (CA) 199, CA724, abnormal prothrombin, carcinoembryonic antigen, CA125, and CA242, were normal.

Enhanced abdominal and pelvic CT revealed a mass-like hypodense shadow in the right lobe of the liver, approximately 6.9 × 5.6 cm in size (Figure 1(a)). This mass demonstrated significant enhancement during the arterial phase of the enhanced scan (Figure 1(b)), with reduced enhancement observed during the portal venous phase (Figure 1(c)). Enhanced MRI of the liver revealed an abnormal mass-like signal shadow in the right lobe, displaying iso- to slightly long T1 and slightly long T2 signals (Figure 1(d) and (e)), with a size of approximately 6.9 cm ×5.4 cm × 7.0 cm and a clear boundary. On diffusion-weighted imaging (DWI) (Figure 1(f)), the mass showed a high signal, while the apparent diffusion coefficient (ADC) demonstrated a low signal. During the arterial phase of the enhanced scan, the mass exhibited significant enhancement; however, this enhancement decreased during the portal venous phase and delayed phase, appearing lower than that of the surrounding liver parenchyma. A pseudocapsule-like enhancement was observed around the mass. No uptake was noted during the hepatobiliary phase. The out-of-phase images suggested a slight reduction in the signal intensity compared with the in-phase images. Additionally, a patchy low enhancement was visible at the anterior inferior margin of the lesion.

Figure 1.

(a) Plain CT scan; (b) CT-enhanced arterial phase; (c) CT-enhanced venous phase; (d) MRI T1WI and (e) MRI T2WI and (f) MRI DWI. CT: computed tomography; MRI: magnetic resonance imaging; DWI: diffusion-weighted imaging.

Preoperative puncture pathological biopsy indicated the presence of hepatic FDCS. Immunohistochemical findings revealed that the tumor cells were strongly positive for CD35; weakly positive for CD21, CD31, and Melan-A; and negative for CD34, SMA, Desmin, HMB45, ALK-1A4, CD117, and S-100. Epstein–Barr-encoded RNA (EBER) in situ hybridization was negative.

Treatment

We obtained signed consent to treatment from the patient. The patient underwent laparoscopic exploration, right hemihepatectomy, and caudate lobe resection under general anesthesia. The gross sarcoma images are shown in Supplementary Material 1 (Figure S1).

Postoperative pathology

The sarcoma measured 7 cm × 6.5 cm ×6 cm in size, involving the vascular walls of the surrounding liver tissue and gallbladder wall. A mixture of spindle cells was present in the tumor, along with small lymphocytes and plasma cells (Figure 2(a)). The portal areas demonstrate the infiltration of numerous lymphocytes and monocytes, accompanied by fibrous connective tissue proliferation.

Figure 2.

HE staining, immunohistochemical staining, and in situ hybridization (20×). (a) HE staining; (b) CD23 (positive); (c) CD35 (positive) and (d) EBER (negative). HE: hematoxylin–eosin; EBER: Epstein–Barr-encoded RNA.

The results of immunohistochemical staining showed that the tumor cells were positive for CD23 (Figure 2(b)), CD35 (Figure 2(c)), CD68, and CD163; slightly positive for S-100; and negative for CD21 and CD1a (Supplementary Material 1, Figure S2). In situ hybridization revealed that the tumor cells were negative for EBER (Figure 2(d)). Based on the morphological and immunohistochemical findings, the diagnosis was consistent with FDCS of the liver.

Outcome and follow-up

One year later, the patient underwent a follow-up abdominal B-ultrasound examination, and no recurrence was found. The patient had no symptoms of discomfort, and the hematologic examination was normal. The patient believes that she has recovered well and resumed a normal life.

Literature review

Materials and methods

A literature review of 32 case reports of FDCS was conducted, involving a total of 42 cases.^7–38 The specific information about these studies is presented in the Supplementary Material 2. PubMed was systematically searched from the establishment of the database up to September 2025.

Based on the case reported in this study and 42 previous cases, a total of 43 cases were used to analyze the characteristics of FDCS. For normally or non-normally distributed data, continuous variables were expressed as mean ± SD or median and interquartile range, respectively, while categorical variables were expressed as frequency or percentage. The survival analysis derived from published case reports is descriptive in nature due to the inherent limitations of case report data. All data analyses and plotting were performed using R Statistical Software (4.2.2). A P-value <0.05 was considered to indicate statistical significance.

Statistical description

Age data followed a normal distribution, with an average age of 48 ± 15 years (mean ±SD; range: 19–82 years; Supplementary Material 1, Figure S3(A)). The maximum diameter of tumors in all cases did not follow a normal distribution, with the median (lower quartile, upper quartile) being 87.5 mm (42 mm–130 mm; Supplementary Material 1, Figure S3(B)). Most cases occurred in China (Supplementary Material 1, Figure S3(C)). A higher number of female patients was observed compared with male patients (27 vs. 16; Figure 3(a)). The tumors were more commonly observed to occur in the left hepatic lobe (Figure 3(b)). Most patients presented with abdominal pain, were asymptomatic, and experienced weight loss (Figure 3(c)).

Figure 3.

Analysis of the 44 hepatic FDCS cases. (a) Sex comparison; (b) tumor location and (c) clinical symptoms. FDCS: follicular dendritic cell sarcoma.

Survival analysis

The median disease-free survival time was 95 months. Among the 41 patients with survival information, 34 survived disease-free and 1 patient died. The 1-year survival of patients was 87.4%. The 3-year disease-free survival of patients was 76.1%. The 5-year disease-free survival of patients was 63.4%. No effect of sarcoma diameter, sex, age, and country on disease-free survival was found (P > 0.05; Supplementary Material 2, Figure S4).

Immunohistochemical features

Most FDCSs express CD21, CD23, and CD35. Vimentin, clusterin, CD68, S-100 protein, D-20, CD138, and SMA have been reported previously (Supplementary Material 2, Table S1). Novel markers FDC-secreted protein, serglycin, and SSTR2 can provide evidence for FDCS. The incidence of EBV infection in patients with hepatic FDCS was 53.3%; it was especially high (82.1%) in patients with inflammatory pseudotumor-like-FDCS, which was consistent with a previous study. ³⁹

Discussion

Novelty

This study is the first to report the occurrence of hepatic FDCS in patients with a history of systemic lupus erythematosus, and high fever is the main clinical symptom. In this case, the most significant hematological finding was the elevated C-reactive protein level prior to surgery, which returned to normal after surgery. C-reactive protein is a potential screening marker. In this case, the discrepancy between CD21 and S-100 staining in biopsy versus resection is attributed to sarcoma heterogeneity, indicating that different regions or subpopulations within the same sarcoma can exhibit varying biological characteristics. This article provides a comprehensive and systematic summary and comparison of previous relevant researches.

Potential mechanisms and further research

The potential mechanisms underlying hepatic FDCS are as follows: 1. Fever as the primary manifestation: FDCS may secrete substances with pyrogenic effects. FDCS stimulates the immune response of the body. 2. Association between autoimmune disease and FDCS: Prolonged immune activation and cytokine release in autoimmune settings may create a microenvironment conducive to the proliferation and transformation of follicular dendritic cells, ultimately leading to the development of FDCS. Additionally, autoimmune diseases are often associated with genetic predispositions that could also confer susceptibility to FDCS, suggesting a shared genetic background or molecular pathways underlying both conditions. However, the above potential needs to be tested and verified in future studies.

Treatment strategy

Surgical resection is the primary treatment for early-stage follicular dendritic cell sarcoma (FDCS) and is often curative; however, patients remain at risk for both local recurrence and distant metastasis ²⁷ In previous studies, FDCS was characterized by a low- to intermediate-grade malignant sarcoma that has a chance of local recurrence and distant metastasis. ⁴⁰ Early detection, early diagnosis, and early treatment are crucial to improve the prognosis. Targeted therapy and immune checkpoint inhibitors could be promising therapeutic approaches for patients with refractory FDCS. ⁴¹

Limitation of this study

First, the results of the data analysis based on previously reported case data require more rigorous cohort studies and randomized controlled trials for confirmation. Second, despite a detailed search of previous literature and screened cases according to the World Health Organization Classification of FDCS, the retrospective nature of the literature review can cause potential selection bias in the reported outcomes and complications.

Conclusion

Due to the rarity of hepatic FDCS and nonspecific clinical presentation, this case report holds significant clinical value. It not only enhances our understanding of this rare sarcoma but also alerts clinicians to consider the possibility of hepatic FDCS and other rare diseases when encountering patients with unexplained fever. This ensures a timely and accurate diagnosis and treatment for patients, enabling a positive prognosis.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605251405692 - Supplemental material for Primary hepatic follicular dendritic cell sarcoma: A case study and literature review

Supplemental material, sj-pdf-1-imr-10.1177_03000605251405692 for Primary hepatic follicular dendritic cell sarcoma: A case study and literature review by Junjie Zhu, Ying Liang, Li Zhang, Bingqi Li, Danfeng Zheng and Hangyan Wang in Journal of International Medical Research

Supplemental Material

sj-xlsx-2-imr-10.1177_03000605251405692 - Supplemental material for Primary hepatic follicular dendritic cell sarcoma: A case study and literature review

Supplemental material, sj-xlsx-2-imr-10.1177_03000605251405692 for Primary hepatic follicular dendritic cell sarcoma: A case study and literature review by Junjie Zhu, Ying Liang, Li Zhang, Bingqi Li, Danfeng Zheng and Hangyan Wang in Journal of International Medical Research