TABLE 1.
Accelerated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Classical Examples of Richter Transformation
| Case No. | Age, y/Sex | Panel diagnosis | Interesting features |
|---|---|---|---|
| Accelerated CLL/SLL | |||
| 245 | 56/F | Accelerated CLL/SLL (lymph node) | Highly complex karyotype with MYC alterations and a complete TP53 inactivation, unmutated IGHV in a case of accelerated CLL/SLL. Patient responded to ibrutinib and R-venetoclax. |
| 241 | 69/M | Accelerated CLL/SLL (skin) | Multiple cutaneous lesions showing aCLL/SLL, IGHV unmutated. Peripheral blood with numerous prolymphocytes. Despite several poor prognostic factors, the patient responded well to venetoclax with resolution of skin lesions and no evidence of CLL/SLL in bone marrow. |
| Classical Richter transformation | |||
| 152 | 72/M | RT-DLBCL | DLBCL morphology in lymph node in a patient with IGHV-unmutated CLL/SLL; peripheral blood and bone marrow showing both small- to medium-sized and large neoplastic lymphoid cells. Highly complex karyotype; del(17p13.1) and TP53 mutation detected at the time of RT likely contributed to disease progression. |
| 219 | 54/M | RT-DLBCL | Stepwise acquisition of genetic alterations, including BTK C481S, loss of CDKN2A, NOTCH1 rearrangement, and t(2;12)(p12p13.3), IGK::CCND2. The latter is a recurrent alteration described primarily in cyclin D1–negative mantle cell lymphoma and is exceedingly rare in RT. |
| 115 | 65/M | RT-HGBCL, DH | RT with diffuse large B-cell lymphoma morphology and double-hit MYC and BCL2 rearrangements in a patient with a prior diagnosis of unmutated IGHV CLL. |
| 19 | 80/F | RT-HGBCL, DH | Leukemic presentation of double-hit lymphoma with MYC and BCL6 rearrangements without extramedullary involvement. CLL/SLL population was present in a background. |
| 206 | 79/F | 1.RT-HGBCL 2.RT-HGBCL |
Progression of λ light chain–restricted CLL to 2 distinct λ light chain–restricted B-cell lymphomas with distinct immunophenotype and MYC abnormalities. Both lymphomas showed private and shared mutations. The latter included genes involved in DNA repair such as TP53 and MRE11. The heavy chain usage was identical in samples 1 and 2. |
| 103 | 51/F | High-grade blastic transformation with plasmacytoid dendritic cell and T-cell immunophenotype | Aggressive leukemic transformation with unusual immunophenotype during ibrutinib maintenance, in a patient who previously experienced typical RT. Neoplastic cells showed plasmacytoid dendritic cell and T-cell markers and shared the same IgH gene rearrangement with the CLL clone. |
| 62 | 75/M | EBV reactivation in CLL/SLL with morphology of EBV+ DLBCL | EBV reactivation in an immunocompromised patient with CLL/SLL manifesting as EBV+ DLBCL. |
| 41 | 45/F | CLL with focal EBV reactivation | Focal areas of necrosis and EBV positivity in a patient with CLL/SLL, most likely related to immunosuppression. |
| 122 | 50/M | RT-cHL, type I | History of cHL (nodular sclerosis, cervical lymph node) and treatment-refractory CLL/SLL prior to the current presentation. Diagnosis most consistent with EBV-positive type I RT-cHL in a retroperitoneal lymph node. Molecular genetic studies to demonstrate clonal relationship to the original CLL/SLL would be helpful. |
| 127 | 75/M | RT-cHL, type I | Prior diagnosis of untreated CLL/SLL. Patient presented with EBV-positive type I RT-cHL in an inguinal lymph node and was treated with radiotherapy. Three years later presented with recurrence of type I RT-cHL in a cervical lymph node and was treated with systemic immunochemotherapy. |
| 142 | 54/M | RT-cHL with progression from type I to type II | Progression from type I to type II morphology in RT-cHL. EBER in situ hybridization was negative, whereas LMP1 immunostain was positive in HRS cells. |
| 163 | 73/M | cHL, most likely types I and II | Simultaneous presentation with EBV-positive RT-cHL involving lymph nodes and bone marrow, with the latter showing a type II pattern. This case illustrates difficulties in RT-cHL pattern assignment in core needle biopsies. |
| 93 | 57/M | cHL, type II focal (associated with necrosis) | Untreated biclonal CLL/SLL with transformation to EBV-positive RT-cHL, clonally related per IGH gene rearrangement. Lambda light chain–restricted CLL clone expanded over time and gave rise to RT, as demonstrated by the HRS cells positive for λ light chain. |
| 183 | 72/M | RT-cHL transforming from CLL/SLL with subclonal cyclin D1 rearrangement | Initial core needle biopsy specimen suspicious for cHL. Lymph node excision demonstrated EBV-negative cHL and SLL. Three discrete clonal B-cell populations were seen by flow cytometry, including one with CLL/SLL-type immunophenotype. CCND1 rearrangement was demonstrated by FISH in a minor subset of the CLL/SLL clone. IgH/CCND1 translocation in CLL is rare and is more commonly reported after alkylating agent therapy. |
| 78 | 76/F | Coexistent RT-DLBCL and RT-cHL, type II | Previously treated unmutated IGHV CLL (ibrutinib and venetoclax), presenting with lymphadenopathy and lytic lesions in axial and appendicular skeleton. RT-DLBCL in the occipital soft tissue biopsy specimen and both RT-cHL and RT-DLBCL in bone marrow. Sequencing performed on occipital biopsy and bone marrow biopsy specimens showed different IGH-VDJ usage and 2 different DLBCL subtypes (GCB, genetic cluster 3 and ABC, genetic cluster 5, respectively). |
| 73 | 71/F | RT-DLBCL and RT-cHL, type II | Unmutated IGHV CLL, previously treated, transforming to EBV-negative RT-cHL presenting as multifocal bone lesions with subsequent nodal RT-DLBCL and recurrent nodal RT-cHL. |
aCLL, accelerated chronic lymphocytic leukemia; cHL, classic Hodgkin lymphoma; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; DH, double-hit; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; FISH, fluorescence in situ hybridization; HBGCL, high-grade B-cell lymphoma; HRS, Hodgkin and Reed-Sternberg; RT, Richter transformation.