Hepatosplenic T-cell lymphoma in children and adolescents.

abstractHepatosplenic T-cell lymphoma (HSTCL) is an aggressive mature T-cell lymphoma characterized by significant hepatosplenomegaly, bone marrow involvement, and minimal or no lymphadenopathy. Primarily affecting young adults, it is exceptionally rare in children and adolescents. This makes diagnosis and treatment particularly challenging for pathologists and pediatric oncologists. Diagnosis typically relies on bone marrow, spleen, or liver biopsy, with histopathologic features including small/medium lymphoid cells with irregular nuclear contours that obstruct the sinuses or sinusoids of the spleen or liver. Immunophenotyping usually reveals CD2/3/7 positivity and CD4/8 negativity, with γδ T-cell receptor rearrangements in most cases. Some genetic distinctions described in pediatric and adolescent patients include chromosome 7 and 8 abnormalities and mutations involving SETD2 and STAT5B. Given the lack of standardized approaches, childhood and adolescent patients with HSTCL are often treated with adult protocols, such as intensive cytotoxic chemotherapy regimens followed by allogeneic hematopoietic stem cell transplantation. Despite these highly intensive treatments, the prognosis for HSTCL remains poor in children and adolescents, with an estimated 5-year overall survival of <15%. HSTCL's rarity in children and adolescents limits accurate epidemiological estimates, clinical experience, data collection, treatment advances, and surveillance recommendations. Data on relapsed/refractory disease are even more limited. This review summarizes known clinical and histopathologic features as well as outcomes specific to children and adolescents with HSTCL, highlighting potential distinctions from adults. We will also discuss future strategies to acquire additional biologic and molecular data, streamline diagnosis, and advance treatment approaches to ultimately improve outcomes for young patients with this deadly disease.