Introduction: 

• It is a B-cell neoplasm comprising of small lymphocytes which surround and replace the splenic white pulp germinal centers, efface the follicle mantle and merge with a peripheral zone of larger cells including scattered transformed blasts; both small and large cell infiltrate the red pulp. 
• It is also called as splenic lymphoma with villous lymphocytes. 

Epidemiology: 

• <1% of lymphoid neoplasms 
• Median age- 69 years 
• M:F- 1:1 

Etiology: 

• ? HCV infection 

Clinical Features: 

• Splenomegaly 
• B Symptoms  

Investigations: 

• Peripheral smear- Small lymphoma cells which have a characteristic short polar villi (confined to  one pole) & irregular membrane outline. Nucleolus is seen in half of cases 
• Bone marrow aspiration: 
  • Similar cells infiltrate in nodular/ interstitial pattern 
  • Intrasinusoidal lymphocytic infiltration is characteristic 
• Immunophenotype 
  • Positive - Surface IgM& IgD, CD20, CD79a, CD11c 
  • Negative - CD5, CD10, CD23,  Annexin A1, Nuclear Cyclin D1, CD103, CD10 
  • Variable- CD23, CD43 
  • Ki 67 staining- Targetoid pattern with increased growth fraction in both germinal and marginal zones 
• Molecular studies
  • Rearrangement of Ig heavy and light chain genes. 
  • Loss of Chr. 7q 21-32 which leads to inactivation of p53 
  • Dysregulation of CDK gene on 7q21  
• S. Protein electrophoresis- Some may have small monoclonal M protein 

Criteria for Diagnosis: 

• Definitive diagnosis can be done only after splenectomy, as immunophenotype is non-specific and morphology on BM may not be diagnostic. 
• Diagnosis is made if 
  • Small lymphoid cells in PS/BM 
  • Ig light chain restriction and lack markers of other B cell neoplasms i.e. negative for CD5, CD10 and cyclin D1 
  • Intra-sinusoidal lymphocytic infiltration within bone marrow 

Prognosis: 

• It has an indolent course 

Differential Diagnosis: 

• CLL 
• HCL 
• Mantle cell lymphoma 
• Follicular lymphoma 
• Lymphoplasmacytic lymphoma 

Indications for Treatment (Even at relapse): 

• Symptomatic patient 
• Progressive cytopenia 
• Hepatitis C positive with splenomegaly 

Pretreatment Work-up: 

• History  
  • B-Symptoms  
• Examination  
  • LN:  
  • Spleen:  
• WHO P. S.  
• BSA  
• IHC/Flow cytometry  
• BMA and Bx  
• CT (CAP)  Or Whole body PET 
• Stage  
• Hemoglobin  
• TLC, DLC  
• Platelet count  
• LFT:  Bili- T/D      SGPT:         SGOT:  Albumin:         Globulin:  
• SPEP/ IFEP 
• Creatinine  
• Electrolytes: Na:     K:    Ca:  Mg:       PO4:        
• Uric acid:  
• LDH  
• HIV:                         
• HBsAg:                                
• HCV:  
• UPT  
• Sperm banking
• Cytogenetics  
• ECHO(If anthracyclines planned)- LVEF-              %
• Chemotherapy consent after informing about disease, prognosis, cost of therapy, side effects, hygiene, food and contraception
• Fertility preservation
• PICC line insertion and Chest X ray after line insertion
• Tumor board meeting and decision
• Attach supportive care drug sheet
• Inform primary care physician

Treatment Plan: 

Response Criteria: 

• Complete response: 
  • Recovery of counts 
  • Normal bone marrow with no excess lymphocytes 
  • Regression of splenomegaly 

Monitoring After Treatment/ Follow-up: 

• Once in 3-6 months for 5 years, then once a year  

Related Disorders: 

• Splenic diffuse red pulp small B cell lymphoma (SMZL-Diffuse variant) 
  • Diagnosis is made after excluding CLL, HCL, LPL, PLL, vHCL 
  • Present with massive splenomegaly 
  • Peripheral smear shows villous lymphocytes (Similar to seen with SMZL) with leucopenia and thrombocytopenia 
  • BM shows intrasinusoidal infiltration 
  • Spleen- Diffuse pattern with red pulp involvement. Both cord and sinusoidal infiltration are present.
  • TRAP- Negative 
  • Immunophenotyping 
    • Positive- CD20, DBA.44, IgG 
    • Negative- IgD, Annexin 1, CD25, CD5, CD103, CD123, CD11c, CD10, CD23
  • Molecular studies
    • Hypermutation in IgHV genes 
    • t(9:14) involving PAX5 and IgH @genes 
    • TP53 mutations 
  • Prognosis: Indolent course