Gamma-delta T-cell acute lymphoblastic lymphoma/leukemia: a report of a rare entity.

Gamma delta (γδ) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is a rare, aggressive subtype of T-lymphoid leukemia that accounts for only 9-12% of all T-ALL cases. Herein, we report the case of an 8-year-old boy who presented with facial swelling, shortness of breath, and progressive cervical and axillary lymphadenopathy. Pathological examination, flow cytometry (Navios, Beckman Coulter ClearLLab 10C 10-color T-cell panel [containing FITC-labeled TCR γδ antibody]), chromosomal analysis, interphase FISH, and targeted DNA-based NGS (34-gene Illumina TruSeq Myeloid Panel) were performed. Flow cytometry evaluation of a lymph node biopsy specimen revealed an immature T-cell population positive for CD4, CD3, CD2 (subset positive), CD5, CD7, CD38, CD1a, cytoplasmic terminal deoxynucleotidyl transferase (cyto-TdT), CD30 (subset positive), and T-cell receptor (TCR) gamma delta (γδ). Microscopic examination of an enlarged lymph node and bone marrow showed involvement by a dense, diffuse, neoplastic infiltrate. Interphase FISH revealed a copy number loss of PDGFRB (5q32) in 90.5% of interphase nuclei. Targeted DNA-based NGS detected a tier II oncogenic variant in NOTCH1 (c.7375C > T, p.Gln2459Ter) at a VAF of 21%. This case of γδ T-ALL highlights a rare entity and adds to the literature, albeit scant, which may aid in better recognition and classification.

The role of splenectomy in management of splenic B-cell lymphomas.

INTRODUCTION: Splenic B-cell lymphomas are rare and understudied entities. Splenectomy is frequently required for specific pathological diagnosis in patients with splenic B-cell lymphomas other than classical hairy cell leukemia (cHCL), and can be effective and durable therapy. Our study investigated the diagnostic and therapeutic role of splenectomy for non-cHCL indolent splenic B-cell lymphomas. METHODS: Observational study of patients with non-cHCL splenic B-cell lymphoma undergoing splenectomy between 1 August 2011 and 1 August 2021 at the University of Rochester Medical Center. The comparison cohort was patients categorized as having non-cHCL splenic B-cell lymphoma who did not undergo splenectomy. RESULTS: Forty-nine patients (median age 68 years) had splenectomy (SMZL n = 33, HCLv n = 9, SDRPL n = 7) with median follow up of 3.9 years post splenectomy. One patient had fatal post-operative complications. Post-operative hospitalization was ≤ 4 days for 61% and ≤ 10 days for 94% of patients. Splenectomy was initial therapy for 30 patients. Of the 19 patients who had previous medical therapy, splenectomy changed their lymphoma diagnosis in 5 (26%). Twenty-one patients without splenectomy were clinically categorized as having non-cHCL splenic B-cell lymphoma. Nine required medical treatment for progressive lymphoma and of these 3 (33%) required re-treatment for lymphoma progression compared to 16% of patients following first line splenectomy. CONCLUSION: Splenectomy is useful for the diagnosis of non-cHCL splenic B-cell lymphomas with comparable risk/benefit profile and remission duration to medical therapy. Patients with suspected non-cHCL splenic lymphomas should be considered for referral to a high-volume center with experience in performing splenectomies for definitive diagnosis and treatment.

Utility of Select Gene Mutation Detection in Tumors by the Idylla Rapid Multiplex PCR Platform in Comparison to Next-Generation Sequencing.

Testing of tumors by next generation sequencing (NGS) is impacted by relatively long turnaround times and a need for highly trained personnel. Recently, Idylla oncology assays were introduced to test for BRAF, EGFR, KRAS, and NRAS common hotspot mutations that do not require specialized trained personnel. Moreover, the interpretation of results is fully automated, with rapid turnaround time. Though Idylla testing and NGS have been shown to have high concordance in identifying EGFR, BRAF, KRAS, and NRAS hotspot mutations, there is limited experience on optimal ways the Idylla system can be used in routine practice. We retrospectively evaluated all cases with EGFR, BRAF, KRAS, or NRAS mutations identified in clinical specimens sequenced on two different NGS panels at the University of Rochester Medical Center (URMC) molecular diagnostics laboratory between July 2020 and July 2021 and assessed if these mutations would be detected by the Idylla cartridges if used. We found that the Idylla system could accurately identify Tier 1 or 2 actionable genomic alterations in select associated disease pathologies if used. Yet, in a minority of cases, we would have been unable to detect NGS-identified pathogenic mutations due to their absence on the Idylla panels. We derived algorithmic practice guidelines for the use of the Idylla cartridges. Overall, Idylla molecular testing could be implemented either as a first-line standalone diagnostic tool in select indications or for orthogonal confirmation of uncertain results.