Introduction:

• These are clonal proliferation of  mature B-cells at various stages of differentiation

Epidemiology

• Account for 90% of lymphoid neoplasms
• 4% of new cancers each year

Etiology

• Immunologic problems
  • Immunodeficiency disorders
  • Autoimmunity
• Infections
  • EBV-Burkitt lymphoma
  • HHV-8- Primary effusion lymphoma
  • HCV- Lympho-plasmacytic lymphoma 
  • H. Pylori – Gastric MALT lymphoma
  • B. Burgdorferi – cutaneous MALT lymphoma
  • Mixed bacterial infection – Intestinal MALT lymphoma with immunoproliferative small intestinal disease, alfa heavy chain disease 
• Cytogenetic abnormalities
  • t(11:14)- Mantle cell lymphoma
  • t(14:18)- Follicular lymphoma
  • t(8:14)- Burkitt lymphoma
  • t(11:18)- MALT lymphoma

WHO Classification of mature B-cell neoplasms

• Chronic lymphocytic leukemia / small lymphocytic lymphoma
  • Monoclonal B-cell lymphocytosis
• B-cell prolymphocytic leukemia
• Splenic marginal zone lymphoma
• Hairy cell leukemia
• Splenic B-cell lymphoma/leukaemia, unclassifiable
  • Splenic diffuse red pulp small B-cell lymphoma
  • Hairy cell leukaemia variant
• Lymphoplasmacytic lymphoma 
• lgM Monoclonal gammopathy of undetermined significance
• Heavy chain diseases
  • Mu heavy chain disease
  • Gamma heavy chain disease
  • Alpha heavy chain disease
• Plasma cell neoplasms
  • Non-lgM monoclonal gammopathy of undetermined significance
  • Plasma cell myeloma
  • Smouldering (asymptomatic) plasma cell myeloma
  • Plasma cell leukaemia
  • Plasmacytoma
  • Monoclonal immunoglobulin deposition diseases- Primary amyloidosis and Light chain and heavy chain deposition diseases
  • Plasma cell neoplasms with associated paraneoplastic syndrome- POEMS syndrome, TEMPI syndrome
• Extra nodal marginal zone B cell lymphoma (MALToma)
• Nodal marginal zone B-cell lymphoma
• Follicular lymphoma
• Large B-cell lymphoma with IRF4 rearrangement
• Primary cutaneousfollicle centre lymphoma
• Mantle cell lymphoma
• Diffuse large B-cell lymphoma
• T-cell/histiocyte-rich large B-cell lymphoma
• Primary diffuse large B-cell lymphoma of the CNS
• Primary cutaneous diffuse large B-cell lymphoma, leg type
• EBV-positive diffuse large B-cell lymphoma, NOS
• EBV-positive mucocutaneous ulcer
• Diffuse large B-cell lymphoma associated with chronic inflammation
• Lymphomatoidgranulomatosis
• Mediastinal large B-cell lymphoma
• Intravascular large B-cell lymphoma
• ALK-positive large B-cell lymphoma
• Plasmablastic lymphoma
• Primary effusion lymphoma
• HHV8-associated lymphoproliferative disorders- MulticentricCastleman disease, HHV8-positive diffuse large B-cell lymphoma, NOS, HHV8-positive germinotropiclymphoproliferative disorder
• Burkitt lymphoma / leukemia
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma

Immunoglobulin secreting neoplasms

• Malignant lymphomas- Usual SLL
• Plasmacytoma
• SLL with part undergoing plasmacytic differentiation
• Large cell lymphomas composed of B-immunoblasts
• Lymphoplasmacytic lymphoma

Recent Advances:

Infection with Neoehrlichiamikurensis promotes the development of malignant B-cell lymphomas

This study investigated five patients with malignant B-cell lymphoma and concurrent Neoehrlichia (N.) mikurensis infection to understand the clinical characteristics and potential impact of the infection. N. mikurensis is a tick-borne pathogen known to persistently infect the vascular endothelium. The study found that B cells play a crucial role in host defense against this infection, but chronic stimulation of B cells can lead to B-cell transformation and lymphoma. After treating the patients with doxycycline to eliminate N. mikurensis, three of them showed significant improvement and discontinued lymphoma treatment. Analysis of the B-cell lymphoma IGHV genes revealed a preference for specific gene families, namely IGHV1 (IGHV1-2 and -69) and IGHV3 (IGHV3-15, -21, -23). 

https://doi.org/10.1111/bjh.18652

Pirtobrutinib: a new hope for patients with BTK inhibitor–refractory lymphoproliferative disorders

Pirtobrutinib, a noncovalentBruton tyrosine kinase inhibitor (BTKi), has shown promise in treating patients with lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) who are resistant to covalent BTKis. It has demonstrated high response rates even in patients who are refractory to covalent BTKis and venetoclax. As a result, pirtobrutinib recently received accelerated approval from the US Food and Drug Administration for MCL. Early studies indicate a favorable toxicity profile, suggesting potential for combination therapies. 

https://doi.org/10.1182/blood.2023020240