---
title: "Transjugular Liver Biopsy–Confirmed Lymphoma Presenting as HLH With Severe Thrombocytopenia: Case"
id: "frontiers-in-immunology-12-case-report-transjugular-liver-biopsy-confirmed-lymphoma-presenting-as"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-12-case-report-transjugular-liver-biopsy-confirmed-lymphoma-presenting-as"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1884908"
published_at: "2026-07-27T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Transjugular Liver Biopsy–Confirmed Lymphoma Presenting as HLH With Severe Thrombocytopenia: Case
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1884908)
- **Published At:** 2026-07-27T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source is a Frontiers in Immunology article titled: Case Report: Transjugular liver biopsy-confirmed lymphoma presenting as hemophagocytic lymphohistiocytosis with severe thrombocytopenia: a case series of three patients. The article type is a case series of three patients. - The title indicates diagnosis of **lymphoma** confirmed by **transjugular liver biopsy**, presenting clinically as **hemophagocytic lymphohistiocytosis (HLH)** with severe **thrombocytopenia**. - The publicly provided source content available here contains only website navigation and journal metadata; the body text of the case series, including patient-level clinical details, laboratory data, imaging, histopathology, treatments, and outcomes, was not present in the source material provided. - Specifics that were not reported in the supplied source include patient demographics, presenting symptoms, diagnostic criteria used for HLH, biopsy technique details, histologic or immunophenotypic findings, staging or lymphoma subtype, therapeutic regimens, complications, and follow-up or outcomes. - Because the supplied source lacked the article content, no clinical data, management recommendations, or study results can be summarized beyond what the title states. Any interpretation of typical practice or expected data would be speculative and is not included. - Readers seeking the full clinical details, histopathology, diagnostic workup, and outcomes should consult the full article on the Frontiers in Immunology website; those elements were not available in the provided source.
## Clinical Analysis & Structured Key Points
Frontiers | Case Report: Transjugular liver biopsy-confirmed lymphoma presenting as hemophagocytic lymphohistiocytosis with severe thrombocytopenia: a case series of three patients CASE REPORT article Front. Immunol. , 27 July 2026 Sec. B Cell Biology Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1884908 Published in Frontiers in Immunology B Cell Biology 7 impact factor 11.3 citescore Part of a Research Topic Endothelium, Innate Immunity and Coagulation in Hematological Disorders - Volume II Submission open 5791 views 8 articles Editor & Reviewers Edited by E G Eleni Gavriilaki Reviewed by S A Sonia Alexiadou A C Abhimanyu Chand Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Figure 5 View in article Table 1 HLH diagnostic criteria fulfilled by three cases. View in article CASE REPORT article Front. Immunol. , 27 July 2026 Sec. B Cell Biology Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1884908 Case Report: Transjugular liver biopsy-confirmed lymphoma presenting as hemophagocytic lymphohistiocytosis with severe thrombocytopenia: a case series of three patients L Z Luocheng Zhang 1,2 † Y D Yang Dai 1,3,4 † X Z Xushu Zhong 1,3,4 X L Xuefeng Luo 5 T N Ting Niu 1,3,4 * A Z Ailin Zhao 1,3,4 * 1. Department of Hematology, Institute of Hematology, and Center for High Altitude Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China 2. West China Medical School, West China Hospital, Sichuan University, Chengdu, China 3. State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China 4. National Facility for Translational Medicine (Sichuan), West China Hospital, Sichuan University, Chengdu, China 5. Division of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China See more Article metrics View details Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can obscure underlying malignancies, particularly aggressive B-cell lymphoma. Severe cytopenias and coagulopathy often preclude conventional biopsy, delaying diagnosis. Objectives: To assess the diagnostic utility of transjugular liver biopsy (TJLB) in adult patients presenting with HLH, transfusion-refractory thrombocytopenia, and predominant hepatic involvement, and to explore mechanisms of thrombocytopenia. Methods: Three adult patients with HLH, hepatic lesions, and severe thrombocytopenia unresponsive to platelet transfusions were retrospectively analyzed. Conventional biopsy was contraindicated due to bleeding risk. TJLB was performed for histopathological confirmation, followed by lymphoma-directed therapy. Laboratory, imaging, and histopathological data were reviewed. Results: TJLB established aggressive B-cell lymphoma in all patients, enabling timely chemophagocytic therapy. Platelet counts normalized within 2–4 weeks (case 1 and 2), and HLH-related hyperinflammation resolved. Thrombocytopenia was multifactorial, reflecting hemophagocytosis, immune-mediated platelet destruction, hepatic sequestration, and cytokine-mediated suppression of megakaryopoiesis. Conclusions: HLH may be the first manifestation of occult lymphoma. TJLB is a safe, effective diagnostic strategy in patients with hepatic involvement and high bleeding risk, facilitating early curative therapy. These cases highlight the value of a multidisciplinary, risk-adapted diagnostic approach and provide mechanistic insight into cytopenia in HLH-associated lymphoma. Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled immune activation, hypercytokinemia, and multi-organ dysfunction ( 1 ). The condition encompasses both primary (familial/genetic) forms and secondary (acquired) forms, with the latter predominantly occurring in adults ( 2 , 3 ). Secondary HLH is frequently triggered by infections, autoimmune diseases, or malignancies, among which lymphoma represents one of the most important underlying etiologies in adult patients ( 4 ). Aggressive B-cell lymphoma, particularly, is a well-documented trigger of HLH and often portends a poor prognosis without prompt initiation of curative-directed therapy. Timely identification of the underlying cause is essential for guiding appropriate treatment; however, this is frequently precluded by the patient’s critical condition. HLH patients typically exhibit profound cytopenias and coagulopathy, establishing a bleeding diathesis that contraindicates invasive procedures. In those without superficial lymphadenopathy—where hepatic involvement predominates and percutaneous liver biopsy would be the default diagnostic approach—this hemorrhagic risk leaves tissue diagnosis unattainable. The underlying malignancy may therefore remain occult until the disease advances beyond the window for effective intervention, underscoring the urgent need for alternative diagnostic strategies in this vulnerable population. We herein report a case series of three adult patients with HLH and hepatic lesions presenting with severe, transfusion-refractory thrombocytopenia in whom transjugular liver biopsy—following failure of conventional diagnostic approaches—provided definitive diagnosis of underlying aggressive B-cell lymphoma, thereby enabling transition to curative-directed therapy. Case 1 A 36-year-old male patient presented on September 11, 2025, with a 2-month history of fever, cough, and productive sputum. Initial evaluation at a local hospital identified pancytopenia, coagulopathy, and a hepatic lesion interpreted as a liver abscess. Empiric therapy with clindamycin, moxifloxacin, and eltrombopag yielded no improvement. The patient was then transferred, and laboratory evaluation revealed: reticulocyte count 0.2148 × 10¹²/L, hemoglobin 89 g/L, platelet count 29 × 10 9 /L, WBC 3.47 × 10 9 /L, neutrophils 79.1%; TB 30.1 μmol/L, DB 11.9 μmol/L, triglycerides 5.1 mmol/L, LDH 434 U/L; markedly elevated sCD25 18,830 U/mL, ferritin 1,482 ng/mL; IL-10 3,395.59 pg/mL, IL-6 73.4 pg/mL, with other cytokines relatively normal. AFP 1.74 ng/mL, DCP 24.00 mAU/mL. Imaging revealed multiple hepatic masses: a dominant 10.3 × 6.8 × 12.0 cm lesion in the right posterior lobe and a 3.9 × 3.5 × 3.0 cm lesion in the right anterior lobe, with slight splenomegaly. PET/CT showed intense FDG uptake in the liver and portocaval lymph nodes. Bone marrow examination was unremarkable. The patient met five of eight HLH-2004 criteria ( Table 1 ). ED regimen (etoposide 100 mg twice weekly, dexamethasone 10 mg daily) was initiated. Imaging and labs suggested lymphoma rather than hepatocellular carcinoma. Hepatic lesions were the sole measurable site, but thrombocytopenia remained refractory to ED therapy, eltrombopag, and transfusions, precluding percutaneous biopsy. Table 1 HLH-2004 diagnostic criteria Case 1 Case 2 Case 3 Fever (>38.5 °C) Yes (Maximum 38.5 °C, >1 week) Yes (Maximum 39.8 °C; >1 week) Yes (Maximum 38.7 °C; >1 week) Splenomegaly Yes (on abdominal CT) Yes (on abdominal CT) Yes (on abdominal CT) Cytopenias (Affecting >=2 lineages) Hemoglobin ( =3.0 mmol/L or >=265 mg/dL) Yes (Triglycerides 5.1 mmol/L) No No or Hypofibrinogenemia (Fibrinogen =500 ng/mL) Yes (1,482 ng/mL) Yes (1,160 ng/mL) Yes (12,459 ng/mL) sCD25 (>=2,400 U/mL) Yes (18,830 U/mL) Yes (3,533 U/mL) Yes (15,838 U/mL) Hemophagocytosis (bone marrow, spleen, or lymph nodes) No Yes (bone marrow) No Decreased or absent natural killer (NK) cell activity NA NA NA HLH diagnostic criteria fulfilled by three cases. Following multidisciplinary discussion, transjugular liver biopsy (TJLB) was performed on October 17, 2025, via the right internal jugular vein using the Seldinger technique. On the day of the procedure, the platelet count was 15 × 10 9 /L. Multiple core samples were obtained under fluoroscopic guidance; the introducer sheath was retained temporarily. The procedure was successful and well tolerated, with no complications. The sheath was removed on post-operative day three without bleeding. Histopathology revealed medium-to-large atypical lymphoid cells: CD20+, CD19+, CD22+, CD3-, CD5-, CD30-, CD10-, BCL-6+, MUM-1+, BCL-2+ (>90%), c-MYC+ (10–20%), Ki-67+ (80–85%), EBER negative. Clonal IGH and IGK rearrangements confirmed non-GCB DLBCL; FISH showed no c-MYC, BCL-2, or BCL-6 rearrangements. NGS revealed no actionable variants. ED therapy was discontinued, and R-CHOP was initiated (rituximab 800 mg day 1, cyclophosphamide 1,400 mg day 2, epirubicin 120 mg day 2, vindesine 4 mg day 2, prednisone 50 mg twice daily day 2–6). Platelets recovered to 142 × 10 9 /L within two weeks. Four cycles of R-CHOP achieved complete metabolic response (Deauville 1) on PET/CT, with no HLH relapse. The patient remains on ongoing chemophagocytic therapy ( Figure 1 ). Figure 1 Pathological and PET/CT images of case 1. (A–C) Immunohistochemophagocyticical staining of liver biopsy specimens (original magnification ×20): (A) CD20 showing diffuse strong positivity in tumor cells; (B) CD3 negative in tumor cells; (C) Ki-67 demonstrating a high proliferation index. (D) Baseline whole-body 18 F-FDG PET/CT showing intense hypermetabolic activity in the liver and lymph nodes. (E) Post-treatment 18 F-FDG PET/CT demonstrating a marked reduction in metabolic activity. Case 2 A 60-year-old male patient presented on December 17, 2025 with a 3-month history of recurrent fever (maximal 39.8 °C) and recent-onset melena. Initial laboratory studies at an outside institution revealed: hemoglobin 78 g/L, platelets 52 × 10 9 /L, WBC 9.19 × 10 9 /L, alkaline phosphatase 171 U/L. Contrast-enhanced CT of the abdomen demonstrated normal hepatic morphology with homogeneous parenchymal attenuation; a hypodense mass measuring approximately 10.2 × 7.4 cm in the left hepatic lobe with confluent appearance; and a hypodense nodule measuring approximately 1.8 × 1.4 cm in the caudate lobe. Mild splenomegaly was also noted. Surgical intervention had originally been planned but was deferred due to persistent fever. Whole-body PET/CT was then performed and demonstrated abnormal FDG uptake in the anterior wall of the left maxillary sinus, liver, ascending colon, small intestine, and bilateral cervical/axillary/abdominal lymph nodes, highly suggestive of hemophagocytic atologic malignancy. On December 4, 2025, an ultrasound-guided axillary lymph node biopsy was attempted but failed to obtain diagnostic tissue. The patient was subsequently transferred to our hospital. Laboratory studies revealed a hemoglobin level of 78 g/L, platelet count of 52 × 10 9 /L, and white blood cell count of 9.19 × 10 9 /L, with neutrophils of 80%. Biochemophagocyticistry showed elevated alkaline phosphatase at 171 U/L. The coagulation profile was normal. Ferritin 1,374 ng/mL, sCD25 3,533 U/mL; IL-10 1514.48pg/mL, IL-6 48.40pg/mL, while the rest of the cytokines were normal; Tumor markers (AFP, CEA, NSE, SCC, CYFRA21-1) were all within normal limits. This patient presented with persistent fever, splenomegaly, bicytopenia (hemoglobin 74 g/L, platelets 54 × 10 9 /L) as well as markedly elevated ferritin and sCD25, which prompted the diagnosis of HLH ( Table 1 ). The ED regimen (etoposide 100 mg twice weekly, dexamethasone 10 mg daily) was initiated. Concurrently, gastrointestinal bleeding required fasting, acid suppression, somatostatin, and repeated platelet transfusions. Additionally, romiplostim and thrombopoietin receptor agonists were administered to improve the platelet count. Similar to the preceding case, this patient presented with HLH and hepatic lesions, with lymphoma strongly suspected as the underlying etiology and severe thrombocytopenia refractory to platelet transfusion and multiple treatments. However, in contrast to Case 1, the dominant mass was located in the left hepatic lobe, rendering transjugular liver biopsy (TJLB), typically optimized for right lobe sampling, technically more challenging. This anatomical consideration created an additional diagnostic challenge. Following extensive multidisciplinary discussion involving interventional gastroenterology, TJLB was ultimately attempted with external ultrasound guidance to direct the biopsy needle toward the left hepatic lesion, thereby maximizing the probability of obtaining diagnostic tissue from the pathological site. On December 30, 2025, a TJLB was performed using the same technique as previously described. The biopsy needle was advanced through the left hepatic vein wall into the liver parenchyma to obtain multiple tissue samples. A transabdominal ultrasound was used to confirm the position of the needle tip within the mass, and hemostasis was achieved with manual compression at the puncture site. The procedure was well tolerated, with no hemorrhagic complications. Histopathological analysis of the liver biopsy specimen established the diagnosis of diffuse large B-cell lymphoma, non-germinal center B-cell-like subtype, with BCL-2 and c-MYC double expression, according to the Hans algorithm. Immunohistochemophagocyticistry demonstrated CD20+, CD79a+, CD3-, CD10-, BCL-6+, MUM-1+, cyclin-D1-, TDT-, PCK-, CD34-, S100-, CD23-, CD30-, CD5-, BCL-2+ (>80%), c-MYC+ (~40%), Ki-67+ (70–80%), with clonal IGH and IGK rearrangements. EBER was negative. FISH analysis yielded no BCL-2, BCL-6, or c-MYC rearrangements. Once the diagnosis was established, the ED regimen was discontinued and CR-CHOP (chidamide 20mg twice weekly, rituximab 600mg day 1, cyclophosphamide 1000mg day 2, epirubicin 80mg day 2, vindesine 4mg day 2, prednisone 50mg bid day2-6) was initiated on January 20, 2026 ( 5 ). The patient was discharged in stable condition following platelet recovery to 86 × 10 9 /L, with resolution of melena and afebrile status. The patient is currently receiving ongoing chemotherapy and has not yet reached the mid-treatment evaluation. Platelet counts remained within the normal range during the inter-treatment intervals ( Figure 2 ). Figure 2 Pathological and baseline PET/CT images of case 2. (A–E) Immunohistochemophagocyticical staining of liver biopsy specimens (all images at original magnification ×20): (A) CD20 showing diffuse strong positivity in tumor cells; (B) CD3 negative in tumor cells; (C) BCL-2 demonstrating strong expression (>80%); (D) c-MYC showing partial positivity (~40%); (E) Ki-67 indicating a high proliferation index. (F) Baseline whole-body 18 F-FDG PET/CT demonstrating intense hypermetabolic activity in the liver and lymph nodes. Case 3 A 61-year-old woman presented on March 30, 2026, with a 2-month history of fever, worsening over the past week, accompanied by anorexia, fatigue, abdominal distension, and diarrhea. Initial evaluation revealed ANA 1:320, IL-10 >1000 pg/mL, IL-6–24 pg/mL, TNF-α 12.8 pg/mL, IFN-γ 12.1 IU/mL, ferritin >2000 ng/mL, and sCD25–7086 U/mL. A diagnosis of undifferentiated connective tissue disease was considered and methylprednisolone administered, leading to symptomatic improvement. Fever recurred a week prior to admission, with pallor on examination. Laboratory studies showed hemophagocyticoglobin 77 g/L, WBC 15.19 × 10 9 /L, platelets 21 × 10 9 /L; PT 21.0 s, APTT 54.1 s, fibrinogen 0.9 g/L; TB 68.3 μmol/L, DB 52.9 μmol/L, triglycerides 2.2 mmol/L, LDH 992 U/L, albumin 22.7 g/L, globulin 17.8 g/L, ferritin 12,459 ng/mL, sCD25 15,838 U/mL. Abdominal CT revealed diffuse hepatic changes with hepatosplenomegaly, ascites, and multiple enlarged lymph nodes. Given persistent fever, splenomegaly, bicytopenia, and markedly elevated ferritin and sCD25, HLH was diagnosed ( Table 1 ). ED therapy (etoposide 80 mg twice weekly, dexamethasone 10 mg daily) was initiated. EBV-DNA was undetectable; bone marrow studies were unremarkable. PET/CT showed hepatosplenomegaly with diffuse FDG uptake and small lymph nodes with intense FDG avidity (SUVmax 13.15; Figure 3 ), raising suspicion for lymphoma. Due to high hemophagocytic risk, TJLB was performed. Post-procedure, platelets fell to 2 × 10 9 /L. Histopathology revealed focal atypical cells: CD20+, CD3-, CD5 (partial), Bcl-6+, MUM-1+, Bcl-2+ (majority), c-MYC+ (few), Ki-67 40–50%, EBER1/2 negative, and clonal IGH/IGK rearrangements, consistent with non-GCB DLBCL. Figure 3 Baseline PET/CT image of case 3. Baseline whole-body 18 F-FDG PET/CT demonstrating intense hypermetabolic activity in the liver, spleen and lymph nodes. While awaiting pathology, ED therapy improved fever, ferritin, sCD25, and bilirubin, but cytopenias persisted and progressed to agranulocytosis. Etoposide was discontinued and G-CSF was administered; however, a severe pulmonary infection developed, requiring ICU care. Consequently, lymphoma-directed treatment was temporarily deferred due to infection, and the platelet count remained below normal at the end of the observation period (19 × 10 9 /L on April 23, 2026; Figure 4 ). Figure 4 Laboratory parameters following therapy in three cases. Ferritin (red) and sCD25 (blue) levels are shown on a logarithmic scale (left y-axis), while platelet counts (green, right y-axis) are presented over time. Platelet transfusions are indicated by orange dots with corresponding units administered. In all three cases, patients presented with hyperinflammatory features consistent with HLH, including persistently elevated ferritin and sCD25. Despite repeated platelet transfusions, severe thrombocytopenia remained refractory. Transjugular liver biopsy (TJLB) was performed in each case, leading to the definitive diagnosis of underlying lymphoma. Following initiation of lymphoma-directed chemotherapy (Case 1: R-CHOP ×6 cycles; Case 2: CR-CHOP), platelet counts recovered and inflammatory markers gradually declined. Discussion Liver involvement in lymphoma-associated HLH has been previously documented, including a case of primary hepatic lymphoma presenting as HLH and diagnosed by laparoscopic liver biopsy ( 6 ). However, in the context of HLH, this procedure remains associated with a substantial risk of bleeding. TJLB is a safe and less invasive alternative to laparoscopic liver biopsy, with proven effectiveness in patients who have bleeding tendencies from various causes, including Fontan-associated liver disease and unexplained liver dysfunction ( 7 , 8 ). Despite these advantages, its use in lymphoma-associated HLH with predominant hepatic involvement—where conventional percutaneous biopsy is contraindicated—has been rarely described. Several aspects of these cases merit attention. The profound, transfusion-refractory thrombocytopenia observed exceeds typical HLH coagulopathy, reflecting multifactorial causes including immune-mediated destruction, splenic/hepatic sequestration, and cytokine-driven impaired megakaryopoiesis. Aggressive B-cell lymphomas, especially with extranodal or sinusoidal involvement, can present as a “masked” syndrome dominated by systemic inflammation. The present cases highlight the critical role of TJLB in this high-risk setting, demonstrating that a multidisciplinary, risk-adapted biopsy strategy can achieve timely tissue diagnosis without incurring major hemorrhagic complications ( Figure 4 ). Mechanisms of thrombocytopenia in hepatic lymphoma-associated HLH In this setting, thrombocytopenia is likely multifactorial. We hypothesize that thrombocytopenia potentially reflects consumption, immune-mediated destruction, sequestration, and impaired production. In HLH, activated macrophages engulf platelets and other blood cells, contributing to cytopenias and poor response to transfusion. In B-ce
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