Likely Diagnosis: Diffuse Large B-Cell Lymphoma (DLBCL), Germinal Center B-Cell Type
Based on the immunohistochemistry profile showing CD45+, BCL6+, Cyclin D1-, and CD30-, the most likely diagnosis is Diffuse Large B-Cell Lymphoma (DLBCL) of germinal center origin, particularly in a patient with autoimmune disorders or immunosuppression. 1, 2
Diagnostic Interpretation
Key Immunophenotypic Features
- CD45 positivity confirms hematopoietic origin and excludes non-hematopoietic malignancies 1
- BCL6 positivity is characteristic of germinal center-derived B-cell lymphomas, including DLBCL (germinal center B-cell type) and follicular lymphoma 1, 3
- Cyclin D1 negativity effectively excludes mantle cell lymphoma (MCL), including blastoid and pleomorphic variants, which are characteristically Cyclin D1+ 1, 4, 5
- CD30 negativity excludes anaplastic large cell lymphoma and primary mediastinal B-cell lymphoma with features overlapping classical Hodgkin lymphoma 1
Critical Missing Information Needed
You must obtain the following additional markers immediately to complete the diagnosis and guide treatment:
- CD20, CD79a, or PAX5 to confirm B-cell lineage 1, 6
- CD10 to distinguish germinal center DLBCL (CD10+/BCL6+) from non-germinal center type 1
- BCL2 and MYC by IHC to identify "double-expressor" lymphomas with poor prognosis 1, 2
- Ki-67 proliferation index to assess aggressiveness and distinguish from indolent lymphomas 1, 2, 7
- FISH for MYC, BCL2, and BCL6 rearrangements to identify "double-hit" or "triple-hit" lymphomas, which require more intensive therapy than standard R-CHOP 1, 2
Differential Diagnosis to Exclude
Pleomorphic Mantle Cell Lymphoma
- While Cyclin D1 negativity argues strongly against MCL, rare CD5-/Cyclin D1- pleomorphic MCL exists 4, 8
- Order SOX11 immunostain: SOX11+ would suggest pleomorphic MCL, while SOX11- favors DLBCL 4
- If SOX11 is positive, perform FISH for IGH-CCND1 translocation to confirm cyclin D1-negative MCL 4
Follicular Lymphoma
- BCL6+ can occur in follicular lymphoma, but this typically shows low-grade cytology 1
- Check Ki-67: if <20%, consider follicular lymphoma; if >40%, favors DLBCL 1, 2
- 85% of follicular lymphomas are BCL2+ or have t(14;18) translocation 1
Angioimmunoblastic T-Cell Lymphoma (AITL)
- AITL can express BCL6, but would show T-cell markers (CD3+, CD4+) rather than B-cell markers 1, 3
- In immunosuppressed patients, AITL may present with concurrent EBV+ DLBCL, requiring EBER-ISH testing 1
Essential Workup for Immunosuppressed/Autoimmune Patients
Infectious Screening
- EBV testing by EBER in-situ hybridization is mandatory, as immunosuppressed patients can develop EBV+ DLBCL 1
- HHV-8 testing if there is history of HIV or features suggesting Castleman's disease 1
- HIV, HBV (HBsAg, anti-HBs, anti-HBc), and HCV serology 1
Staging Workup
- PET/CT scan is the gold standard for staging DLBCL 1
- Bone marrow biopsy is NOT required if PET/CT shows bone marrow involvement indicating stage IV disease 1
- Complete blood count, comprehensive metabolic panel, LDH, and uric acid 1
- Multigated acquisition scan or echocardiogram before anthracycline-based chemotherapy 1
Treatment Implications
Standard Therapy
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) every 21 days is standard for CD20+ DLBCL 1, 6
- If CD20 is negative (rare), rituximab should be omitted 1
Intensive Therapy Considerations
- If FISH confirms "double-hit" lymphoma (MYC + BCL2 or BCL6 rearrangements): standard R-CHOP is inadequate 2
- Consider dose-adjusted EPOCH-R or Burkitt-type regimens (CODOX-M/IVAC, hyper-CVAD) for younger, fit patients with double-hit lymphoma 1, 2
- Mandatory CNS prophylaxis with intrathecal chemotherapy for double-hit cases due to high CNS relapse risk 2
Special Considerations for Immunosuppressed Patients
- Optimize antiretroviral therapy if HIV-positive before starting chemotherapy 1
- G-CSF support for all patients to prevent neutropenic complications 1
- Consider reduced-intensity regimens if performance status is poor, but avoid compromising cure rates 1
Critical Pitfalls to Avoid
- Do not assume Cyclin D1 negativity completely excludes MCL: rare cases of Cyclin D1-/SOX11+ pleomorphic MCL exist and require FISH confirmation 4, 8
- Do not rely solely on BCL2/MYC IHC expression ("double-expressors") to guide therapy: FISH for genetic rearrangements is mandatory, as IHC expression only partially correlates with genetic abnormalities 1, 2
- Do not skip EBV testing in immunosuppressed patients: EBV+ DLBCL has distinct biology and may require different management 1
- Do not perform bone marrow biopsy if PET/CT already shows stage IV disease: this is unnecessary and delays treatment 1