ULTRA-RARE CANCERLymphomaWHO 5th Edition Classification

Hepatosplenic T-cell Lymphoma (HSTCL)

Ultra-Rare Malignancy (< 1 case per 1,000,000 / year) • Clinical Staging, Genomic Targets & Vetted Specialists

A rare and aggressive lymphoma of gamma-delta T cells that infiltrates the liver, spleen and bone marrow sinusoids without forming enlarged lymph nodes. A recognised subset arises in people on long-term immunosuppression, particularly thiopurines with anti-TNF therapy for inflammatory bowel disease.

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Emergent Referral AdvisoryImmediate Action

Certain rare malignancies progress rapidly or carry acute risk of airway obstruction, acute spinal compression, hydrocephalus, or biopsy-seeding. Do not perform needle biopsy or surgery outside of an NCI-designated specialty sarcoma or neuro-oncology unit without multidisciplinary tumor board review.

Report immediately to an emergency department or tertiary oncologist upon:

  • Hepatosplenomegaly with cytopenias and no lymphadenopathy
  • History of long-term thiopurine plus anti-TNF therapy
Who It Affects

Adolescents and young adults, median around 35; strong male predominance

Annual Incidence

Fewer than 1 per million per year

Clinical Evidence Review

Last audited: 2026-08-13 against NCCN, ESMO, and WHO 5th ed. guidelines.

Clinical Presentation & Hallmark Symptoms

Presenting signs most frequently observed across clinical case series

Marked enlargement of the spleen and liver
Fever, night sweats and weight loss
Low platelets, anaemia and low white cells
Abdominal pain and fullness
Notably absent peripheral lymph node enlargement

Genomic Profiling & Defining Molecular Lesions

Critical diagnostic fusions, somatic mutations, and therapeutic targets

Rare malignancies frequently depend on distinct oncogenic drivers rather than conventional environmental carcinogens. Comprehensive Next-Generation Sequencing (NGS comprehensive panel) and FISH/IHC are mandatory to establish the true diagnosis and screen for basket trial agents.

Isochromosome 7qTrisomy 8SETD2STAT5BINO80gamma-delta TCR

Standard-of-Care Treatment Protocol

Frontline and multimodal strategies established under international consensus guidelines

1

Intensive induction chemotherapy (ICE, IVAC or hyper-CVAD style regimens)

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

2

Allogeneic stem cell transplant in first remission - the only curative route

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

3

Splenectomy in selected cases for diagnosis or symptom control

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

4

Withdrawal of the implicated immunosuppressant where relevant

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

5

Clinical trial enrolment

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

Clinical Trial Advisory: For rare and ultra-rare malignancies, enrollment in an active clinical trial or expanded-access program is widely considered the preferred standard of care by ASCO and NCCN panels.

Prognosis & Disease Trajectory

Objective clinical outlook without false reassurance

Poor, with median survival historically under two years using conventional chemotherapy alone. Patients who proceed to allogeneic transplant in first remission have the best reported long-term outcomes.

Note: Statistics reflect cohort averages. Individual outcomes depend heavily on performance status, resectability, biomarker expression, and timely access to specialized tertiary care.

Active Research, Biomarkers & Clinical Trials

Novel investigational agents, phase I/II trials, and international rare disease consortia

Epigenetic agents including romidepsin and azacitidine, and JAK/STAT pathway inhibition, are being explored given the recurrent SETD2 and STAT5B lesions.

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Expert Clinicians

Verified Specialists for Hepatosplenic T-cell Lymphoma

Browse All Oncologists

Dr. Steven Horwitz

Medical Oncologist

20+ yrs exp

MSKCC

New York, USA

T-cell LymphomaHSTCLNovel Immunotherapies
Vetted DirectoryConsult Specialist

Dr. Lim Soon Thye

Medical Oncologist

25+ yrs exp

NCCS

Singapore, Singapore

Lymphoma ServiceT-cell LymphomasHSTCL
Vetted DirectoryConsult Specialist

Prof. Marie José Kersten

Hematologist

20+ yrs exp

NKI/AVL

Amsterdam, Netherlands

T-cell LymphomasHSTCLEuropean Outcomes
Vetted DirectoryConsult Specialist

Dr. Lalit Kumar

Medical Oncologist, Former Head of Medical Oncology

30+ yrs exp

AIIMS, New Delhi

New Delhi, India

Hemato-OncologyBlood CancersHSTCLT-cell Lymphomas
Vetted DirectoryConsult Specialist
Hospital Network

Designated Cancer Centers with Dedicated Programs

Search All 72 NCI Centers

Memorial Sloan Kettering Cancer Center

NY

NCI-Designated Comprehensive Cancer Center

World-leading rare tumor board & pediatric solid tumor protocols

Proton TherapyCAR-T Cell TherapyRobotic Surgery
1,000+ Active Clinical TrialsView Center Profile

University of Texas MD Anderson Cancer Center

TX

NCI-Designated Comprehensive Cancer Center

Largest specialized rare cancer and sarcoma multidisciplinary program

Proton TherapyCAR-T Cell TherapyCyberKnife SBRT
1,200+ Active Clinical TrialsView Center Profile

Dana-Farber / Harvard Cancer Center

MA

NCI-Designated Comprehensive Cancer Center

Pioneering genomic molecular tumor boards & rare histologies

Proton TherapyCAR-T Cell TherapyPhase I Unit
1,100+ Active Clinical TrialsView Center Profile

Mayo Clinic Comprehensive Cancer Center

MN

NCI-Designated Comprehensive Cancer Center

High-volume surgical oncology & rare endocrine/neuroendocrine expertise

Proton TherapyCAR-T Cell TherapyCyberKnife SBRT
600+ Active Clinical TrialsView Center Profile

Frequently Asked Clinical Questions

Authoritative guidance on diagnosis, tumor boards, genomic markers, and care options

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Independent Tumor Board Review

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