Hepatosplenic γδ T-Cell Lymphoma Masquerading as T Cell Acute Lymphoblastic Leukemia

Hepatosplenic γδ T-Cell Lymphoma (HSTCL) is an uncommon type of Peripheral T cell lymphomas characterized by hepatosplenomegaly without significant lymphadenopathy, with clinically significant cytopenias, predominance in young adult males and an aggressive clinical course. HSTCL have a characteristic immunophenotype CD2+, CD3+, CD4−, CD5−, CD7+, CD8-, TCRγδ+ and are associated with isochromosome 7q cytogenetic abnormality. The predominant laboratory findings are reduced peripheral blood cells ranging from isolated reduction of one lineage to pancytopenia. Lymphocytosis is usually uncommon at the point of diagnosis; however tumor cells may be commonly seen in blood. Two subpopulations of atypical cells are seen – small sized cells with irregular nuclear margins and the medium to large size cells which often resemble blasts. The blast like cells are known to increase with disease progression and a complete blastic transformation though known has been mostly reported in the terminal phase of the disease.

We present three cases of HSTCL, all of which presented with lymphocytosis and increased blast like cells (17%–91%) at diagnosis. These cases included two females and one male in an age group of 13– 17 years. They all presented with generalized systemic complaints, bleeding symptoms and on examination had pedal edema, facial puffiness and moderate to marked hepatosplenomegaly. Immunophenotyping performed on peripheral blood sample using a limited primary panel of antibodies showed a common phenotype: surface CD3+, CD4−, CD8−, CD7+ & CD34−. In addition CD2 and CD5 were positive in two cases, CD56 was positive in one case while CD16 was negative in all three cases. Based on the blast like morphology of tumor cells and an aberrant T cell phenotype, all three cases were initially labeled as T cell Acute Lymphoblastic Leukemia (T-ALL) and treated as per the T-ALL treatment protocol of our institute. However they did not respond to treatment. These cases were reviewed in detail and a repeat Immunophenotypic analysis was done using a more elaborate panel. In addition to the initial Immunophenotypic markers, all three cases were positive for Surface TCR γδ and negative for Tdt. Hence a diagnosis of HSTCL was arrived at. Cytogenetically only one case showed the characteristic finding of isochromosome 7q.

The diagnosis of HSTCL was not considered initially because of the blast like morphology of tumor cells and as surface TCR αβ/γδ is not part of our primary antibody panel. In addition in one case, cytoplasmic CD3 was interpreted as positive without taking into account surface CD3 positivity.

This case series highlights the importance of using a comprehensive antibody panel for the diagnosis of hematolymphoid neoplasms including cytoplasmic markers and Tdt. It re-establishes the importance of assessing cytoplasmic positivity only after the surface positivity has been looked for. Aberrant surface CD3 expression and cytoplasmic γδ positivity is well known in T-ALL and a few cases of Tdt negative T-ALL are also known. However to the best of our knowledge there are no published reports of T-ALL expressing surface TCR γδ and in comparison HSTCL though surface CD3 positive, are Tdt negative. We suggest that in all such cases which are surface CD3 positive, CD34 negative and Tdt negative, Surface TCR γδ should be looked for and if found to be positive a diagnosis of HSTCL can be arrived at in the correct clinical setting. In conclusion, it is important to be aware of this rare entity of HSTCL presenting with leucocytosis & blast like cells and to differentiate it from T-ALL, as these two entities have different treatment and prognosis.