Aggressive T-LGL or indolent Hepatosplenic T-cell lymphoma: case with a difficult differential diagnosis

Abstract

T-cell large granular lymphocytic leukemia (T-LGL) is an indolent lymphoproliferative disorder characterized by persist en t (>6 months ) i nc rease in pe r iphe ra l b lood immunophenotypically distinct, clonal population of large granular lymphocytes, usually between 2–20×10^9/L, without a clearly identifiable cause [1]. Hepatosplenic T-cell lymphoma (HSTL), on the other hand, is a uniformly aggressive disease with a fulminant systemic clinical presentation with massive hepatosplenomegaly, bone marrow involvement, thrombocytopenia and anemia, and B symptoms with survival counted in months (6–16 months) from the time of diagnosis [1]. More indolent variants are not recognized. This is a case with clinical presentation more compatible with T-large granular lymphocytic leukemia (T-LGL) and clinically followed as such, until it manifested clinically aggressively with B symptoms, splenomegaly, lymphadenopathy, and morphologically compatible with HSTL. This case continued to challenge us with the differential of a case of T-LGL with aggressive transformation or a HSTL with indolent presentation. This is a case of a 65-year-old lady, with a 10-year history of Raynaud’s disease, who presented with a mild viral syndrome associated with a slight leucopenia in September of 2007. In 2008, due to persistent cytopenia, a bone marrow biopsy was obtained. Her CBC at that time showed a wbc 1.4 k/uL, with absolute neutropenia, Hg 13gm/dl, and platelets 137 K/uL. There were no B symptoms (fever, weight loss, night sweats). The peripheral smear failed to show an abnormal lymphocyte or large granular lymphocytic population. The bone marrow biopsy showed a small inter-trabecular nodular CD3-positive T-lymphocytic aggregate without significant interstitial T-cell infiltrates. Flow analysis showed an aberrant T-cell phenotype CD3+/CD8dim+/CD7dim+/ CD56dim+/CD2+/CD16+/CD4−/CD5−/CD57− suspicious for a T-cell lymphoproliferative disorder. In 2009, the patient presented with pancytopenia, marked splenomegaly and mild hepatomegaly. The CBC showed wbc 1.7 (Neutrophil 340/ uL), Hg 10.8, and plt 80. The bone marrow was hypercellular marrow (70 %) with decreased granulocytes, increased erythroid precursors, and normal-appearing megakaryocytes. There was an interstitial and moderate intrasinusoidal T-cell infiltrate containing small lymphocytes with round to slight irregular nuclear profiles and ample cytoplasm (HE, CD3+, TIA1+, Granzyme B equivocal negative) Fig. 1 (a–c). Flow analysis showed a similar aberrant phenotype CD3+/ CD8dim+/CD7dim+/ CD56dim+/ CD2+/CD16+/CD4−/ CD5−/CD57− and γδ T-cell receptor-positive. Molecular studies were performed, and TCR beta and gamma gene rearrangements were seen. Cytogenetic studies showed a normal karyotype. FISH studies performed showed no chromosome 7 abnormalities. She was treated with G-CSF for her cytopenias. Unfortunately, this caused a splenic rupture (Fig. 1d). The spleen showed a diffuse red pulp disease with atrophic follicles. In June of 2010, she presented with B symptoms with fevers, night sweats, and a 10-pound weight loss and paraaortic and inguinal lymphadenopathy. There were persistent cytopenias: wbc 2.8, rbc 3.18, plt 204 k. A lymph node biopsy was obtained. The lymph node architecture was effaced by a diffuse population of large transformed lymphocytes (Fig. 1e). By immunostains, they marked as CD3+, CD8+, TIA+ T-cell infiltrate with flow analysis showing a similar phenotype as reported earlier. A peripheral smear reviewed at this time showed numerous large granular lymphocytes (Fig. 1f). She * Prabhjot Kaur prabhjot.kaur@hitchcock.org