Hepatosplenic T-cell lymphoma: a rare but challenging entity

Abstract

Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell neoplasm that most commonly arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. HSTCL is more common in adolescent and young adults and has a rapidly progressive clinical course and poor outcome due to its refractoriness to conventional chemotherapy regimens. Approximately 20% of the cases arise in the background of chronic immunosuppression or immune dysregulation. Patients commonly present with constitutional symptoms, hepatic and liver enlargement, and cytopenias; hematophagocytic syndrome can also occur. The most frequent chromosomal aberrations associated with HSTCL are isochromosome 7q and trisomy 8, and most cases harbor mutations in genes involved in chromatin modification or the JAK/STAT pathway. The rarity of this disease, along with lack of nodal involvement and presenting symptoms that mimic different entities including infectious etiologies, makes this lymphoma a significant diagnostic challenge. In this review, we highlight the clinical and pathologic features of HSTCL. Moreover, we summarize the results of recent molecular studies suggesting potential targets for novel therapeutics strategies.

Graphical abstract

Figure 1.

Morphologic features of different cases of HSTCL. (A) Spleen involvement with sheets of small neoplastic lymphoid cells involving cords and sinuses of spleen (hematoxylin and eosin [H&E] stain; original magnification ×600). (B) Bone marrow aspirate in a patient with progressive HSTCL (Wright-Giemsa stain; original magnification ×1000). The neoplastic T cells in this case (highlighted with thin tall arrows) are medium sized and demonstrate fine chromatic, resembling blasts. A rare neoplastic cell is demonstrating hemophagocytosis (highlighted with a thick short arrow). (C) Bone marrow core biopsy showing sinusoidal expansion by medium-sized lymphoid cells (H&E stain; original magnification ×600). (D) CD3 immunohistochemical stain in bone marrow core biopsy, highlighting the sinusoidal expansion by neoplastic T cells (original magnification ×1000).