Jie Wang

The discrimination of benign from malignant lymphoproliferative disorders is sometimes difficult because there can be overlap in their histological and immunophenotypic features. In such situations, molecularly based clonality testing is often used to discriminate benign (polyclonal) from malignant (monoclonal) processes. Clonality testing by polymerase chain reaction (PCR) has a number of pitfalls that may result in spurious results. Here we report the case of a woman diagnosed by 2 major academic institutions with hepatosplenic T-cell lymphoma based on a dense infiltration of the spleen by a γδ T-cell population with mild cytologic atypia, resulting in expansion of the splenic red pulp, and a positive T-cell receptor clonality test by PCR. There was likewise mild involvement of the liver and bone marrow by the "atypical" T-cell population. Close attention to her uncharacteristically well clinical appearance led to repeat T-cell receptor clonality testing using next-generation sequencing. Definitive demonstration of polyclonality by this test showed that she in fact did not have hepatosplenic T-cell lymphoma but rather a reactive condition, and allogeneic stem cell transplantation could be safely avoided. As molecular clonality testing is widely used in the practice of hematology, this case brings attention to the pitfalls of clonality testing by PCR that practitioners may encounter. It is therefore a cautionary tale highlighting the need for critical interpretation of test results in full clinical context.