HSTCL in children and adolescents is rare, with incidence estimated at 0.05 cases per million person-years.

The disease shows a strong predominance in male adolescents and is associated with immune system suppression, dysregulation, and IEIs.

Symptoms may include fatigue, fever, and weight loss.

Examination typically reveals massive hepatosplenomegaly and absence of peripheral lymphadenopathy.

Secondary HLH may complicate and obscure presentation.

Identification relies on biopsies (liver, spleen, and bilateral bone marrow), which reveal sinusoidal infiltrates of malignant lymphocytic cells.

Chromosome 7 abnormalities are common cytogenetic findings.

NGS should be sent, if feasible, to identify potentially targetable mutations.

Both CT and PET contribute important staging information and should be obtained if feasible.

Bilateral bone marrow biopsies should be pursued for staging because up to 70% of pediatric patients with HSTCL have bone marrow involvement.

Controversies on staging and determining response to treatment currently exist for HSTCL.

There is no current consensus standard treatment approach for HSTCL in children and adolescents.

Patients receiving highly cytotoxic induction chemotherapy followed by consolidative allogeneic HSCT seem to have superior outcomes based on small retrospective cohorts, case series, and case reports.

Autologous HSCT and successful salvage treatment have been reported.

5-y OS estimates are dismal at 9.6% to 13%, based on limited data