What is the most likely diagnosis and recommended immediate work‑up and treatment for an adult presenting with diffuse large B‑cell lymphoma causing jaundice, anemia and thrombocytopenia?

Diffuse Large B-Cell Lymphoma with Jaundice, Anemia, and Thrombocytopenia

This presentation suggests primary bone marrow or hepatosplenic involvement of DLBCL, a rare and aggressive variant requiring immediate tissue diagnosis, comprehensive staging, and urgent initiation of R-CHOP chemotherapy with tumor lysis syndrome prophylaxis.

Most Likely Diagnosis

The triad of jaundice, anemia, and thrombocytopenia in DLBCL indicates one of two aggressive presentations:

• Primary bone marrow DLBCL – characterized by lymphoma cells confined to bone marrow with pancytopenia and hyperbilirubinemia, often without lymphadenopathy or organomegaly 1
• Primary hepatosplenic DLBCL – an extremely rare variant (only 4 documented cases) presenting with hepatosplenomegaly, thrombocytopenia, abnormal liver function tests, and frequently associated hemophagocytic syndrome 2

Both variants demonstrate stem cell characteristics (HOXA9, NANOG expression) that promote aggressive behavior and bone marrow/hepatosplenic infiltration 3. These presentations are more common in females over 60 years and typically have <2 months of symptom evolution prior to diagnosis 2.

Immediate Diagnostic Work-Up

Tissue Diagnosis (Highest Priority)

• Core biopsy may be appropriate as the only diagnostic test in patients requiring emergency treatment rather than waiting for excisional biopsy 4
• Mandatory immunohistochemistry panel must include CD45, CD20, and CD3 to confirm B-cell lineage and CD20 positivity (essential for rituximab eligibility) 4, 5
• Bone marrow aspirate, flow cytometry, biopsy, and immunohistochemistry are required to confirm bone marrow involvement 1

Laboratory Assessment

• Complete blood count to document cytopenias 4
• Comprehensive metabolic panel including LDH and uric acid – elevated LDH is a prognostic factor and uric acid guides tumor lysis syndrome risk 4
• Liver function tests to assess degree of hepatic involvement 2
• Screening for HIV, hepatitis B, and hepatitis C is required as these infections impact treatment decisions 4
• Protein electrophoresis is recommended 4

Imaging Studies

• CT scan of chest and abdomen is the minimum required imaging for all patients amenable to curative therapy 4, 5
• PET scanning is strongly recommended to better delineate disease extent and for subsequent treatment response evaluation 4, 5

Additional Required Assessments

• Performance status (ECOG) and cardiac function (left ventricular ejection fraction) must be assessed before treatment 4
• Calculate International Prognostic Index (IPI) and age-adjusted IPI using age, elevated LDH, ECOG performance status, Ann Arbor stage, and number of extranodal sites 4, 5
• Evaluate for hemophagocytic syndrome – present in two of three reported hepatosplenic cases and frequently associated with BLS-type DLBCL 2

Immediate Treatment Approach

Tumor Lysis Syndrome Prophylaxis (Critical First Step)

In cases with high tumor load, precautions are required to avoid tumor lysis syndrome – administer prednisone 100 mg orally for several days as "prephase" treatment before initiating chemotherapy 4, 5. This is particularly critical given the pancytopenia and elevated uric acid risk in bone marrow involvement.

Definitive Chemotherapy

The standard treatment is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regardless of age or risk category:

• For patients ≤60 years: Six to eight cycles of R-CHOP-21 (every 21 days) combined with eight doses of rituximab 4, 5
• For patients >60 years: Eight cycles of R-CHOP-21 is the current standard 4, 5
• Dose reductions due to hematological toxicity should be avoided – use prophylactic hematopoietic growth factors to maintain dose intensity 4, 5

Special Considerations for This Presentation

• Rituximab dose: 375 mg/m² for adult B-cell NHL 6
• Blood transfusion support will likely be required given the pancytopenia 1
• Case reports demonstrate that blood cell counts and hyperbilirubinemia improve after 2 cycles of R-CHOP in primary bone marrow DLBCL 1

Critical Management Pitfalls

• Do not delay treatment for complete staging – core biopsy is sufficient to initiate therapy in emergency situations 4
• Never reduce chemotherapy doses due to cytopenias – instead use growth factor support to maintain dose intensity, as dose reductions compromise survival 4, 5
• Monitor for infusion reactions – rituximab carries risk of fatal infusion-related reactions, particularly with first infusion; administer only with appropriate medical support 6
• Screen for hepatitis B reactivation – rituximab can cause HBV reactivation resulting in fulminant hepatitis and death 6
• Recognize the aggressive nature – primary bone marrow and hepatosplenic DLBCL are distinct, aggressive variants with variable prognoses requiring immediate recognition and treatment 1, 2

Prognosis

Prognoses for primary bone marrow DLBCL vary, but patients can survive at least 3 years after chemotherapy with supportive care 1. The presence of stem cell characteristics (HOXA9, NANOG) correlates with inferior outcomes and poor prognostic parameters 3. Primary hepatosplenic DLBCL is particularly aggressive with <2 months typical evolution prior to diagnosis 2.