Barbara Nelson is the current Laboratory Genetics and Genomics Fellow at Vanderbilt University training in molecular genetics and cytogenetics for the diagnosis of constitutional and somatic diseases (mentors: Cindy Vnencak-Jones, PhD and Ashwini Yenamandra, PhD). She received her PhD from the University of Michigan in Cancer Biology studying the defining roles of metabolic reprogramming in pancreatic tumorigenesis and tumor maintenance (mentors: Costas Lyssiotis, PhD and Howard Crawford, PhD). Subsequently, she was a post-doctoral fellow at the University of Michigan in a CLIA-certified lab that sequences and studies metastatic and rare cancers (mentor: Arul Chinnaiyan, MD, PhD).
Barbara Nelson, Rebecca Smith, Cindy Vnencak-Jones, Laura Lee, Aaron Shaver, Mary Ann Thompson Arildsen, Barbara Sommer, Yingda Wang, Ashwini Yenamandra
Vanderbilt University Medical Center, Nashville, TN, United States
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive subtype of peripheral T-cell lymphoma (PTCL), accounting for 1-2% of all PTCLs. Neoplastic HSTCL lymphocytes are usually positive for isochromosome 7q and gamma-delta T-cell receptor (TCR) expression.
We present a case of a 33-year-old female with a recent diagnosis of HSTCL from an outside institution referred to Vanderbilt University Medical Center (VUMC) in late 2022. Bone marrow (BM) biopsies from VUMC and the outside institution-performed 16 days apart-had similar immunophenotypic and morphologic findings: an abnormal T-cell lymphocyte population positive for CD3, CD56, and gamma delta, negative for CD5 and alpha beta, and an intrasinusoidal distribution.
While histopathological findings were similar between institutions, cytogenetic and molecular analyses were conflicting. The outside institution reported a normal karyotype and TCR clonality. Conversely, VUMC testing at presentation revealed a complex karyotype of 43,X,-X-1,i(7)(q10),der(10;16)(q10;p10),add(21)(p11.2),der(22)t(9;22)(q13;q13) in 6/20 cells with no evidence of TCR clonality.
To investigate this discordance, we examined sequentially collected BM aspirates (second and final pulls) used for VUMC testing as a potential source of the variability. Cytogenetic testing that revealed isochromosome 7q was performed on the second pull, whereas TCR clonality testing that was negative was performed on the final pull. In contrast, subsequent testing of the second aspirate pull demonstrated TCR clonality. These findings highlight the potential for disparity of sequential BM aspirate samplings in the context of molecular testing. Furthermore, this case demonstrates the integration of multiple testing modalities for achieving a diagnosis of a rare cancer.