What is the diagnosis and treatment for a patient with CD3 (cluster of differentiation 3) and CD20 (cluster of differentiation 20) positive lymphoid cells?

CD3 and CD20 Positive Lymphoid Cells: Diagnosis and Treatment

The most likely diagnosis for a patient with CD3 and CD20 positive lymphoid cells is a T-cell lymphoma with aberrant CD20 expression, which requires immunohistochemical confirmation and treatment with rituximab-containing chemotherapy regimens.

Diagnostic Approach

Immunophenotypic Considerations

• CD3 is typically a T-cell marker while CD20 is a B-cell marker; co-expression is uncommon and requires careful diagnostic evaluation 1
• The Reed-Sternberg cells of Classical Hodgkin Lymphoma express CD30 in all patients and CD15 in most patients, but are usually negative for CD3 and CD45, with CD20 detectable in fewer than 40% of patients 1
• Immunohistochemistry is mandatory for proper diagnosis with a minimum antibody panel including CD45, CD20, and CD3 1

Required Diagnostic Testing

• Excisional lymph node biopsy or adequate tissue biopsy providing sufficient material for formalin-fixed samples is essential 1
• Core biopsies may be appropriate only in rare patients requiring emergency treatment 1
• Additional immunohistochemical markers should include CD15, CD30, CD45, CD79a, and PAX5 to help distinguish between various lymphoma types 1
• Flow cytometry can help confirm the diagnosis, especially when CD20 expression is weak or variable 2

Differential Diagnosis

• Diffuse Large B-cell Lymphoma (DLBCL) with aberrant CD3 expression
• T-cell lymphoma with aberrant CD20 expression (rare but reported in the literature) 3, 4
• T-cell prolymphocytic leukemia with CD20 expression 3
• Composite lymphoma (both T and B-cell components)
• Hodgkin lymphoma with variable CD20 expression 1

Staging and Risk Assessment

Initial Workup

• Complete blood count, routine blood chemistry including LDH and uric acid 1
• Screening tests for HIV and hepatitis B and C 1
• CT scan of chest, abdomen, and pelvis 1
• PET/CT scan (skull base to mid-thigh or vertex to feet in selected cases) 1
• Bone marrow aspirate and biopsy 1
• Performance status assessment and cardiac function evaluation (left ventricular ejection fraction) 1

Prognostic Assessment

• International Prognostic Index (IPI) and age-adapted IPI should be calculated 1
• Ann Arbor staging system should be used 1

Treatment Approach

General Principles

• Treatment strategies should be stratified according to age, age-adapted IPI, and feasibility of dose-intensified approaches 1
• For CD20-positive lymphomas, rituximab-containing regimens are the standard of care, even in cases with aberrant marker expression 1
• Enrollment in clinical trials should be considered whenever available 1

First-Line Treatment

• For young low-risk patients (aaIPI ≤1): 6-8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 21 days 1
• For young high-risk patients (aaIPI ≥2): 6-8 cycles of R-CHOP given every 14-21 days; consider CNS prophylaxis 1
• For patients older than 60 years: 8 cycles of R-CHOP given every 21 days or 6 cycles if given every 14 days 1
• Dose reductions due to hematological toxicity should be avoided; consider prophylactic use of growth factors for febrile neutropenia 1

Special Considerations

• In cases with very low CD20 expression, the efficacy of rituximab may be limited, potentially resulting in poorer outcomes 2
• For CD20-positive T-cell lymphomas, the treatment approach should still include rituximab as it may target the aberrant CD20 expression 5, 3
• In cases with high tumor load, precautions such as corticosteroid pre-phase treatment are required to avoid tumor lysis syndrome 1

Response Evaluation and Follow-up

Response Assessment

• Abnormal radiological tests at baseline should be repeated after 3-4 cycles and after the last cycle of treatment 1
• PET scan is highly recommended for post-treatment assessment to define complete remission according to revised response criteria 1
• Bone marrow aspirate and biopsy should be repeated at the end of treatment if initially involved 1
• In case of therapeutic consequences based on PET positivity, histological confirmation is strongly recommended 1

Follow-up Schedule

• History and physical examination every 3 months for 1 year, every 6 months for 2 more years, and then once a year 1
• Blood count and LDH at 3,6,12, and 24 months, then only as needed 1
• CT scans at 6,12, and 24 months after end of treatment 1
• Routine surveillance with PET scan is not recommended 1
• High-risk patients with curative options may require more frequent monitoring 1

Management of Relapsed Disease

Diagnostic Approach for Relapse

• Histological verification should be obtained whenever possible, especially in relapses occurring >12 months after initial diagnosis 1
• Confirm CD20 positivity to ensure potential benefit from rituximab 1

Treatment of Relapsed Disease

• For suitable patients (adequate performance status, age <65-70 years): salvage regimens with rituximab plus chemotherapy followed by high-dose therapy with stem cell support 1
• Common salvage regimens include R-DHAP (rituximab, cisplatin, cytarabine, dexamethasone) or R-ICE (rituximab, ifosfamide, carboplatin, etoposide) 1
• For patients not suitable for high-dose therapy: alternative salvage regimens such as R-GEMOX (rituximab, gemcitabine, oxaliplatin) 1
• Consider allogeneic transplantation for patients with refractory disease, early relapse, or relapse after autologous stem cell transplantation 1