Diagnosis: Non-Hodgkin Lymphoma
A malignant round cell tumor that is LCA (CD45) positive and cytokeratin negative is virtually diagnostic of a hematolymphoid malignancy, specifically non-Hodgkin lymphoma, and should be treated accordingly with lymphoma-directed chemotherapy rather than carcinoma protocols. 1
Immunohistochemical Interpretation
The immunophenotype you describe is pathognomonic for lymphoma:
- LCA (CD45) positivity is expressed in virtually all hematolymphoid malignancies and is highly specific for non-Hodgkin lymphoma 1
- Cytokeratin negativity effectively excludes carcinoma, as carcinomas are usually positive for anticytokeratin antibodies like CAM5.2 1
- This immunoprofile distinguishes lymphoma from the other major differential diagnoses in round cell tumors (carcinoma, melanoma, sarcoma) 1
Critical Diagnostic Pitfall to Avoid
While the classic teaching is that cytokeratin marks carcinomas and LCA marks lymphomas, rare cases of cytokeratin-positive lymphomas exist (including plasmablastic lymphomas, anaplastic large cell lymphoma, and some acute lymphoblastic leukemias), which can lead to misdiagnosis as carcinoma 2, 3, 4, 5. However, your case shows the opposite and more reliable pattern: LCA-positive/cytokeratin-negative, which is diagnostic for lymphoma without significant diagnostic overlap 1.
Required Additional Workup
To subclassify the lymphoma and guide treatment, perform:
- CD20 immunostaining to identify B-cell lineage 6
- CD3 immunostaining to identify T-cell lineage 6
- CD99 (MIC2) if Ewing sarcoma/PNET remains in differential (though LCA positivity makes this unlikely) 6
- Flow cytometry on fresh tissue if available for more detailed immunophenotyping 1
Treatment Approach
Treatment should follow lymphoma protocols, NOT carcinoma chemotherapy regimens 1. The specific regimen depends on:
- Lymphoma subtype (B-cell vs T-cell, determined by CD20/CD3 staining) 6
- Stage of disease (localized vs disseminated) 1
- Patient performance status and comorbidities 1
For aggressive B-cell lymphomas, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is standard first-line therapy. For T-cell lymphomas, CHOP-based regimens without rituximab are typically used 1.
Why This Matters for Mortality and Morbidity
Misdiagnosing this as carcinoma and treating with carcinoma-directed chemotherapy would result in inappropriate therapy and worse outcomes 2, 3. Lymphomas are generally more chemosensitive than carcinomas, and many subtypes are potentially curable with appropriate lymphoma-directed therapy 1, 6. The 5-year survival for appropriately treated non-Hodgkin lymphoma varies by subtype but can exceed 70% for some aggressive B-cell lymphomas treated with R-CHOP, whereas treating lymphoma as carcinoma would likely result in treatment failure 1.