CLASIFICACION DE LINFOMAS

DRA. M. PILAR PAREDES MANRIQUE

HNGAI

Clasificación de la OMS

Neoplasias linfoides son neoplasias clonales de células inmaduras o maduras:– Linfoides B– Linfoides T– Linfoides NK

Tienden a recapitular de estadios normales de diferenciación B, T o NK.

Classification of Lymphoma

Histopathological NHL vs HL B vs T-cell CD20 +ve vs CD20 -ve high grade vs low grade

Clinical aggressive vs indolent stage I vs IV

Molecular c-myc gene translocation

Neoplasias linfoides OMS 2008

Neoplasias de precursores linfoides:– Leucemia/linfoma linfoblástico B, no especificado de otro modo– Leucemia/linfoma linfoblástico B con alteraciones genéticas

recurrentes– Leucemia/linfoma linfoblástico T

Neoplasias de células B maduras Neoplasias de células T y NK maduras

Etiology

The exact etiology is unknown

Immune suppression congenital (Wiskott-Aldrich syndrome) organ transplant (immunosupressants) HIV infection increasing age

DNA repair defects ataxia telangiectasia xeroderma pigmentosum

Etiology

Chronic inflammation Helicobacter pylori (gastric NHL) Chlamydia psittaci (ocular, adrenal LNH)

Viral causes EBV - Burkitt’s lymphoma HTLV-I - T cell leukemia-lymphoma HTLV-V - cutaneous T cell lymphoma Hepatitis C

Diagnosis

Blood tests- FBC, R/L

- LDH, uric acid

- B2 microglobulina

Bone marrow biopsy Imaging

- CXR

- CT N/T/A/P

- PET/CT scan

B cell lymphoma

lymphoblastic leukemia/lymphoma follicular lymphoma chronic lymphocytic leukemia/small lymphocytic lymphoma mantle cell lymphoma prolymphocytic leukemia hairy cell leukemia lymphoplasmacytic lymphoma marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT)-

type nodal marginal zone B cell lymphoma splenic marginal zone B cell lymphoma Burkitt lymphoma diffuse large B cell lymphoma plasmacytoma plasma cell myeloma

WHO classification

Diffuse Large B-cell Lymphoma

Overview: -heterogeneous peripheral B-cell tumor

-20% of all NHL, 60-70% of aggressive lymphoid tumors

Morphology:

-diffuse growth pattern

-large tumor cells

Diffuse Large B-cell Lymphoma

Immunophenotype:

Pos:CD19, CD20, CD22, CD79a, (CD10), sIg

Neg: TdT

Genetics:

t(14;18)(= bcl-2 rearrangement)-- 30% of cases

--- 20 to 30% of cases bcl 6 rearrangement (CH3)

extranodal lesions: negative for bcl 2 rearrangement

Diffuse Large B-cell Lymphoma

Clinical: -wide age range (median age : 60 y/o)-slight male predominance-rapidly enlarging mass

(GI tract, skin, bone, brain, ORL lymphoid tissue, liver, spleen)

-aggressive behavior, but potentially curablePrognosis: responsive to intensive combination chemoRx

better prognosis: limited Dz, small lesionbcl 6 rearrangement

worse prognosis: p53 mutation

Diffuse Large B-cell Lymphoma

Special Subtypes

1. Immunodeficiency-associated large B-cell lymphoma

-with latent EBV infection

2. body cavity large B-cell lymphoma

-mostly seen in advanced HIV(+) patients

-arises as malignant pleural or ascitic effusion

-infected with human herpes virus 8

International Prognostic Index

Age greater than 60 years Stage III or IV disease Elevated serum LDH ECOG/Zubrod performance status of 2, 3, or 4 More than 1 extranodal site

The sum of the points allotted correlates with the following risk groups: Low risk (0-1 points) - 5-year survival of 73% Low-intermediate risk (2 points) - 5-year survival of 51% High-intermediate risk (3 points) - 5-year survival of 43% High risk (4-5 points) - 5-year survival of 26%

Acute Lymphoblastic Leukemia/Lymphoma (ALL)

Overview: B-cell tumor (85%)

T-cell tumors tend to be seen in adolescent males with frequent thymic involvement

differential diagnosis from AML important

Morphology:PAS(+) cytoplasmic granules

absence of peroxidase(+) granules ( AML)

Acute Lymphoblastic Leukemia/Lymphoma (ALL)

Immunophenotype: TdT(+) --- >95% of cases

Genetics: t(12;21) --- preB-cell type

t(9;22) ----- 3% of children, 25% of adults

t(4;11)

hyperdiploidy

pseudodiploidy

Burkitt Lymphoma

Overview: relatively mature B-cell tumor

three(3) subtypes:

1. African(endemic) Burkitt lymphoma

2. sporadic(nonendemic) Burkitt lymphoma

3. HIV-associated neoplasm

Burkitt Lymphoma

Morphology: diffuse infiltrate of

intermediate-size tumor cells

round to oval nucleus coarse chromatin several nucleoli moderate amount of

basophilic cytoplasm with vacuoles

high mitotic rate apoptotic tumor cell death numerous macrophages

(‘starry sky” appearance)

Burkitt LymphomaImmunophenotype:

sIgM, light chainCD19, CD20, CD10CD5 -, CD23 -

Genetics:translocation of c-myc gene

t(8;14)t(2;8)t(8;22)

EBV infection100% of African Burkitt25% of HIV-associated

Burkitt

Burkitt Lymphoma

Clinical:

children and young adults

frequent extranodal involvent African Burkitt: mandible

abdominal organs (kidneys, ovaries, adrenal) nonendemic Burkitt: ileocecum, peritoneum

Prognosis: generally aggressive tumor, but responds well to therapy

Mantle Cell Lymphoma

Overview: peripheral B-cell tumor

3% of NHL in U.S. (7-9% in Europe)

Morphology: two patterns of LN involvement

1. mantle zone pattern

2. diffuse pattern

Normal

Mantle Cell Lymphoma

Morphology:-homogeneous population of small lymphocytes

-absence of centroblast-like cells

nucleus: round to irregular occasionally

cleaved condensed

chromatic inconspicuous

nucleoliscant cytoplasm

Mantle Cell Lymphoma

Immunophenotype:

Pos: CD19, CD20, CD5(aberrant), CD43

sIgM, sIgD

light chain (k or l)Neg: CD10, CD23 ( B-CLL/SLL)

Genetics:t(11;14) (elevated cyclin D1) -- 70% of cases

involving bcl 1 gene loss of cell cycle control

Mantle Cell Lymphoma

Clinical:-males in 40’s, 50’s and older

-generalized lymphadenopathy (widespread)

-BM: para- and non-trabecular aggregates

-extranodal involvement including liver & spleen

“lymphomatoid polyposis”

multifocal entero-colic mucosal involvement

Prognosis: poor (median survival : 3-5 yrs)

not curable with conventional chemotherapy

death due to organ dysfunction