Hematology Oncology · Year 2 · from Hematology Oncology
Case 2: Diffuse Large B-Cell Lymphoma (DLBCL)
Patient Presentation
Demographics: 65-year-old female
Chief Complaint: Rapidly growing abdominal mass and weight loss
History of Present Illness: The patient noticed abdominal fullness and early satiety 4 weeks ago. She has had progressive abdominal distension with a palpable mass. She reports 18-pound unintentional weight loss, drenching night sweats, and low-grade fevers over the past 6 weeks. She also has fatigue and decreased appetite. She has no history of lymphoma or autoimmune disease.
Physical Examination:
- Vital signs: BP 118/72, HR 92, RR 18, Temp 37.8C
- General: Cachectic-appearing elderly woman
- HEENT: No lymphadenopathy
- Cardiac: Regular rhythm
- Lungs: Decreased breath sounds at right base
- Abdomen: Distended with large palpable right-sided mass (15 cm), mild ascites
- Extremities: 1+ pitting edema bilateral lower extremities
Workup and Results
Laboratory:
- WBC: 6,200/uL
- Hemoglobin: 10.2 g/dL
- Platelets: 145,000/uL
- LDH: 1,250 U/L (markedly elevated)
- Creatinine: 1.8 mg/dL (elevated)
- Uric acid: 10.5 mg/dL (elevated)
CT Abdomen/Pelvis:
- 18 cm heterogeneous retroperitoneal mass
- Moderate ascites
- Right hydronephrosis from ureteral compression
- Mesenteric lymphadenopathy
PET-CT:
- Intensely FDG-avid retroperitoneal mass (SUV max 28)
- Additional FDG-avid lymph nodes in mediastinum
- No bone marrow involvement
Core Needle Biopsy:
- Diffuse infiltrate of large atypical lymphoid cells
- High mitotic rate
- Areas of necrosis
Immunohistochemistry:
- CD20: Positive (strong)
- CD10: Positive
- BCL6: Positive
- MUM1: Negative
- BCL2: Positive
- Ki-67: 85%
- MYC: 40% (not rearranged)
FISH:
- BCL2 rearrangement: Positive
- MYC rearrangement: Negative
- BCL6 rearrangement: Negative
Cell of Origin: Germinal Center B-cell (GCB) subtype
IPI Score:
- Age >60: 1 point
- LDH elevated: 1 point
- Stage III/IV: 1 point
- ECOG ≥2: 1 point
- Extranodal sites >1: 0 points
- Total: 4 points (High-intermediate risk)
Clinical Image
Histologic section of diffuse large B-cell lymphoma showing diffuse infiltrate of large atypical lymphoid cells with high nuclear-to-cytoplasmic ratio, prominent nucleoli, and frequent mitotic figures.
Diagnosis
Diffuse Large B-Cell Lymphoma - GCB Subtype, Stage III, IPI High-Intermediate
Key features:
- Aggressive B-cell lymphoma
- GCB subtype (better prognosis than ABC)
- Not double-hit (MYC not rearranged)
- Advanced stage with B symptoms
Treatment Plan
- Pre-treatment:
- Ureteral stent placement for hydronephrosis
- Aggressive hydration for tumor lysis prevention
- Allopurinol or rasburicase
- First-line therapy:
- R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)
- 6 cycles, every 21 days
- Consider addition of polatuzumab vedotin (Pola-R-CHP)
- Interim assessment:
- PET-CT after 2-4 cycles
- End-of-treatment PET for response
- CNS prophylaxis:
- Consider intrathecal methotrexate or high-dose MTX given high LDH and renal involvement
- Relapsed/refractory:
- Salvage chemotherapy + autologous transplant if chemosensitive
- CAR-T cell therapy (axicabtagene ciloleucel or tisagenlecleucel) if refractory
- Prognosis:
- IPI 4 points: ~50% 5-year survival
- GCB subtype is favorable
- Response to initial therapy is most important prognostic factor
Teaching Points
- DLBCL is the most common non-Hodgkin lymphoma (~30% of NHL)
- Aggressive behavior requires prompt diagnosis and treatment
- Cell of origin (GCB vs ABC) impacts prognosis; GCB is more favorable
- Double-hit lymphoma (MYC + BCL2/BCL6) requires more intensive therapy
- R-CHOP has been standard for 20+ years; new additions like polatuzumab improving outcomes
- IPI score predicts prognosis based on 5 clinical factors
- CAR-T therapy has transformed outcomes in relapsed/refractory disease