Part 2 Nhl

PERIPHERAL B CELL NEOPLASM

NEOPLASM OF MATURE B CELLS

FOLLICULAR LYMPHOMA FOLLICULAR LYMPHOMA

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.

• 10% show Peripheral blood involvement sufficient to produce lymphocytosis (usually <20,000/mm3 )

• 85% have Bone marrow involvement – Paratrabecular lymphoid aggregates.

• Splenic white pulp and hepatic portal triads are also frequently involved.

Features

Reactive LymphoidFollicular Lymphoma Hyperplasia

Majority Small cleaved cellsForm Follicles

7

BCL2 Immunostain

• 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

Immunophenotype and Genetics

Clinical Features.

• Painless lymphadenopathy, which is frequently generalized.

• Uncommon Involvement of extranodal sites–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

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

• Rapidly enlarging mass• Often Symptomatic• Arise in any site

– Waldeyer ring, Oropharyngeal LN, Tonsils

– Liver, spleen• Localized Disease with

extranodal involvement • Rarely present as leukemia

Features

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

Liver -DLCL

• 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

BURKITTS LYMPHOMABURKITTS LYMPHOMA

BURKITTS LYMPHOMABURKITTS LYMPHOMA3 TYPES1. African ( Endemic )2. Sporadic ( Non-endemic )3. Aggressive lymphoma

occuring in HIV patientso Histologically identicalo Genotype & virologic difference

o CD10 Usually seen

FeaturesFeatures

o Cell of originoGerminal center Bcell

o African LATENTLY INFECTED w/ EBV

o All forms associatedoTranslocations c-myc gene on

Chromosome 8 with IgH [t(8,14)]oCommonly

Clinical featuresClinical 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 featuresClinical features Endemic

• Often Mandibular mass

• Unusual predilection to abdominal viscera– Kidneys– Ovary– Adrenals

Sporadic• Often as

Abdominal Mass– Ileocecal– Peritoneum

MorphologyMorphology– Starry sky pattern– High mitotic activity

Burkitts LymphomaStarry sky pattern

High Mitotic IndexMonotonous Cells

Marginal Zone Lymphomas

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• 1. Often arise – Chronic

Inflammatory D/O– Autoimmune

• Sjogrens – Salivary gland• Hashimotos - Thyroid

– Infectious • Helicobacter pylori- Stomach

Unusual Pathogenesis• 2. Remain localized for

prolonged periods – Spread late

• 3. May regress if inciting agent is eradictaed – H. pylori

Chronic inflammati

on

Reactive Polyclonal Immune reaction Acquisition

of mutations

& Chromosom

al aberrations

Monoclonal B cells

neoplasm emerges

Initially dependen

t on T –Helper cell for growth

Continuous mutation

Stage independ

ent of extrinsic stimuli – microbe/antigen

GIT- Maltoma

MULTIPLE MYELOMAMULTIPLE MYELOMA

• 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 lytic lesions

• Punch out lesions• Axial Skeleton• Starts at Medullary

– Gelatinous , soft tumor

MULTIPLE MYELOMA

Mutiple 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%

• Clinicopathologic Dx– Correlation of X-ray & Laboratory Findings

MULTIPLE MYELOMA

BM aspirate- Myeloma

Electrophoresis

IgG k M protein

Clinical Features• Bone pain – axial skeleton

(Vertebrae)• Hypercalcemia ( 25%)• Renal Failure (30-50%)• Myeloma kidney

– Proteinacious tubular cast– Nephrocalcinosis ( metastatic

calcification)

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 MYELOMASOLITARY MYELOMA

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

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

Mycosis fungoides