Peripheral B cell Neoplasm Neoplasm of Mature B cells
FEATURES Follicular lymphoma is the most common form of indolent NHL in the United States Middle age men and women equally. Arise from germinal center B cells. Strongly associated with translocation involving BCL2
hallmark Translocation( 14; 18) This translocation is seen in most but not all follicular lymphomas Leads to overexpression of BCL2 protein. BCL2, = is an antagonist of apoptotic cell death and appears to promote the survival of follicular lymphoma cells.
Features 10% show Peripheral blood involvement sufficient to produce lymphocytosis (usually <20,000/mm3 ) 85% have Bone marrow involvement Paratrabecularlymphoid aggregates. Splenic white pulp and hepatic portal triads are also frequently involved.
Reactive LymphoidFollicular Lymphoma Hyperplasia Majority Small cleaved cells Form Follicles
BCL2 Immunostain 7
Immunophenotype and Genetics Express CD19, CD20, CD10 Like Normal follicular center B cells, CD5 is NOT Expressed In contrast to CLL and SLL and mantle cell lymphoma, CD5 is expressed. OverExpression of BCL2 protein - > 90% Versus Normal Follicular center B cells, which are BCL2 negative
Clinical Features. Painless lymphadenopathy, which is frequently generalized. Uncommon Involvement of extranodalsites GIT, CNS, Testis Often follows an indolent waxing and waning course.
Survival Overall median survival is 7 to 9 years Is not improved by aggressive therapy The usual clinical approach is to palliate patients with low-dose chemotherapy or radiation when they become symptomatic.
Transformation Retain t(14;18) Somatic Hypermutation promote transformation Occurs in 30 to 50% of follicular lymphomas, Most commonly to diffuse large B-cell lymphoma. Median survival is less than 1 year after transformation.
DIFFUSE LARGE CELL LYMPHOMA
Most common form of NHL 60-70% Aggressive lymphoid neoplasm M>F , Median age 60y/o DIFFUSE LARGE B-CELL LYMPHOMA
Features Rapidly enlarging mass Often Symptomatic Arise in any site Waldeyerring, Oropharyngeal LN, Tonsils Liver, spleen Localized Disease with extranodal involvement Rarely present as leukemia
Immunophenotype Mature B cell Express CD19 & CD20 Variably Express Germinal Center Markers Have surface Ig Negative Tdt
Molecular Pathogenesis 30% Dysregulation of BCL6 Repress germinal center B-cell Differentiation Growth Arrest Holds cell in Undifferentiated Proliferative state Silence the expression of p53 Prevent the activation of DNA repair mechanism
Morphology Diffuse pattern of growth Large Neoplastic cells 4-5x small lymphocytes DIFFUSE LARGE CELL LYMPHOMA
Diffuse Large Cell
Therapy 60-80% Complete remission with combination Chemotherapy 50% remain free from disease for years Immunotherapy with Anti-CD20 improves outcome especially elderly
Subtype Immunedeficiency-associated large B cell Lymphoma T cell immunodeficiency ( HIV ) (+) EBV Neoplastic B cell Restoration of immunity Regression of proliferation
Translocations c-myc gene on Chromosome 8 with IgH [t(8,14)]
Clinical features Adolescent or Young Adult w/ jaw or extranodal abdominal mass Very aggressive Respond well to chemotx Outcome guarded in Older adults UNCOMMON BM or peripheral blood
Clinical features Endemic Often as Abdominal Mass Ileocecal Peritoneum Often Mandibular mass Unusual predilection to abdominal viscera Kidneys Ovary Adrenals Sporadic
Morphology Starry sky pattern High mitotic activity
BurkittsLymphomaStarry sky pattern
High Mitotic IndexMonotonous Cells
Marginal Zone Lymphomas
Features LOW grade lesions Encompass a heterogenous group of B cell tumors Arise in LN, Spleen, Extranodal Tissues Tumor cell resemble normal Marginal Zone B cells Initially recognized at mucosal sites MALTOMA
Unusual Pathogenesis 2. Remain localized for prolonged periods – Spread late 3. May regress if inciting agent is eradictaed – H. pylori
Multiple bone involvement Can also spread to LN & Extranodal 1% in Western countries Higher incidence Men>Women Older Patients Radiation exposure African decent MULTIPLE MYELOMA
Pathogenesis IL-6 Proliferation of tumor cells are DEPENDENT on Cytokione Active Disease and Poor Prognosis MIP 1 alpha & RANK Ligand Mediate Bone Destruction Karyotyping Deletions of 13q IgH MULTIPLE MYELOMA
X-ray Multiple lyticlesions Punch out lesions Axial Skeleton Starts at Medullary Gelatinous , soft tumor MULTIPLE MYELOMA
Laboratory High M proteins Rouleaux 55% IgG Monoclonal Ab Proliferation of Neoplastic plasma cells 30% of bone marrow cellularity (Plasma cell Leukemia ) Bence Jones proteins in urine Myeloma kidney Seen in 60-80% ClinicopathologicDx Correlation of X-ray & Laboratory Findings MULTIPLE MYELOMA
Clinical Features Hematologic findings Normocytic anemia with rouleaux Prolonged bleeding due to defect in platelet aggregation Radiculopathy due to bone compression and vertebral fracture Recurrent infection – Most common cause of death
Prognosis Variable but Generally Poor Median survival is 6 months without treatment
Solitary Myeloma Lesions either in the Bone or Soft Tissue Axial Skeleton Lungs, Oropharynx, Nasal Sinuses Minority show (+) M protein Progression to Multiple Myeloma Common in solitary Osseous myeloma ( 10-20 yrs) Less common in Extraosseous
PERIPHERAL T-CELL and NK-CELL NEOPLASMS NEOPLASM OF MATURE T CELLS AND NK CELLS
EXTRANODAL NK/T-CELL LYMPHOMA
EXTRANODAL NK/T-CELL LYMPHOMA PREVIOUSLY MIDLINE GRANULOMA 3% OF NHL IN ASIA DESTRUCTIVE MIDLINE MASS INVADE SMALL VESSELS EXTENSIVE ISCHEMIC NECROSIS NEOPLASTIC ELEMENTS MIXTURE OF SMALL & LARGE LYMPHOID CELLS