Primary Testicular and Cutaneous Philadelphia Chromosome Positive B-Cell Lymphoblastic Lymphoma: A Rare Case and Review

Abstract

Philadelphia chromosome positive B cell lymphoblastic lymphoma (Ph+ B-LBL) is an extremely rare disease. We report a 27-year-old patient diagnosed with primary testicular and cutaneous Ph+ B-LBL without bone marrow involvement. The CCCG-LBL-2016 regimen (https://ichgcp.net/clinical-trials-registry/NCT02845882) was initially administered due to the fast pathological diagnosis as B-LBL that was first obtained. To identify potential therapeutic targets, RNA sequencing (RNAseq) was also performed on lymph node specimens as a part of the routine diagnostic workup in our center. Unexpectedly, IKZF1 deletions and BCR-ABL1 fusion transcripts were detected. Based on these results, we retrospectively performed fluorescence in situ hybridization (FISH) for BCR/ABL1 rearrangements in the same lymph node specimen, and a 70% positive signal was detected. The patient subsequently received the CCCG-LBL-2016 protocol combined with the BCR-ABL tyrosine kinase inhibitor (TKI) dasatinib, along with prophylactic intrathecal infusion. Then, the patient underwent TBI-based haploidentical (haplo) allogeneic hematopoietic stem cell transplantation (haplo-allo-HSCT) as consolidation following the achievement of remission and continued taking dasatinib as maintenance therapy. The patient was still in complete remission 1 year after diagnosis. This case indicates that the detection of potential molecular targets, especially those targets that can be pharmacologically treated, such as BCR/ABL1 fusion transcripts, is of important value to both LBL diagnosis and therapeutic strategy choices. FISH, reverse transcriptase polymerase chain reaction (RT-PCR) and/or RNAseq should be routinely carried out in lymphoma specimens to depict its genetic landscape for the further execution of a precise therapy strategy.

Keywords: B-cell lymphoblastic lymphoma; Philadelphia chromosome; hematopoietic stem cell transplantation; tyrosine kinase inhibitor.

Conflict of interest statement

The authors report no conflicts of interest in this work.

© 2022 Yu et al.

Figures

Figure 1

Representative of patient’s PET imaging. (A and B) PET scan images revealed that FDG uptake was high in multiple lymph nodes (SUV max: 9.4) and bones (SUV max: 6.2), posterior wall of nasopharynx (SUV max: 6.5), bilateral ethmoid sinuses (SUV max: 5.0), bilateral testicle and right spermatic cord (SUV max: 7.3) and subcutaneous nodules on bilateral cheeks (SUV max: 2.8) before therapy. (C and D) PET/CT evaluation was carried out before Protocol M of CCCG-LBL-2016 beginning, and it showed complete remission. (E and F) Repeat PET/CT scan more than five months after transplantation showed normal metabolic activity. FDG, fluorodeoxyglucose; PET, positron emission tomography.

Figure 2

Morphologic features of the skin lesion. (A) The core needle biopsy specimen is extensively replaced with tumor cells characterized by nucleoli and scant cytoplasm (H&E, 400x). (B–D) Immunohistochemical stains show that tumor cells were positive for CD20 ((B), 100x), PAX5 ((C), 100x), and TdT ((D), 100x). (E) Immunohistochemical stains show that tumor cells were negative for CD34 (100x). (F) About 90% of the neoplastic cells display nuclear Ki67 staining (100x). TDT, terminal deoxynucleotidyl transferase.

Figure 3

FISH analysis was approached on suspension samples in interphase cells of fresh swelling lymph node specimen using commercial probe (LSI BCR/ABL DS probe, Vysis). (A) Cells with a signal pattern of 1 red, 1 green, and 2 yellow (fusion signal) are positive for BCR/ABL1 rearrangement. (B) Cells with 2 red and 2 green are normal. FISH, Fluorescence in situ hybridization.