Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the...
Transcript of Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the...
![Page 2: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/2.jpg)
Lymphoproliferative Disorders
Malignant lymphoma
1. Non-Hodgkin lymphoma (NHL)
2. Hodgkin (disease) lymphoma
3. Multiple myeloma
![Page 3: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/3.jpg)
Lymphomas are solid tumors of the hematopoietic system.
Neoplasms of lymphoid origin, typically causing
lymphadenopathy
leukemia vs. lymphoma
Leukemias as systemically distributed neoplasms of white cells
Basic concepts
![Page 4: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/4.jpg)
lymphomas and leukemias are
clonal expansions of cells at certain
developmental stages
Very important concept……
![Page 5: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/5.jpg)
Follicle / germinal
center (B cell)
NORMAL LYMPH NODE
Mantle zone
(B-cell)
Paracortex
(T-cell)
Medullary cord
(B-cell)
Lymphatic sinus
![Page 6: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/6.jpg)
B-cell development
stem
cell
lymphoid
precursor
progenitor-B
pre-B
immature
B-cell
mature
naive
B-cell
germinal
center
B-cell
memory
B-cell
plasma cell
![Page 7: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/7.jpg)
B-cell development
stem
cell
lymphoid
precursor
progenitor-B
pre-B
immature
B-cell
mature
naive
B-cell
germinal
center
B-cell
memory
B-cell
plasma cell
DLBCL,
FL, BL, HL
LBL, ALL
CLL
MCL
MM
MZL
CLL
![Page 8: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/8.jpg)
A practical way to think of lymphoma
Category Survival of
untreated
patients
Curability To treat or
not to treat
Non-
Hodgkin
lymphoma
Indolent Years Generally
not curable
Generally defer
Rx if
asymptomatic
Aggressive Months Curable in
some
Treat
Very
aggressive
Weeks Curable in
some
Treat
Hodgkin
lymphoma
All types Variable –
months to
years
Curable in
most
Treat
![Page 9: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/9.jpg)
Non-Hodgkin Lymphomas
How do we diagnose and classify these types of
lymphoproliferative disorders?
Architectural pattern
Cytologic (cellular) morphologic appearance
Immunophenotypic (antigenic) characteristics
Molecular / genetic characteristics
![Page 10: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/10.jpg)
Diagnosis requires an adequate biopsy
Diagnosis should be biopsy-proven before treatment is initiated
Need enough tissue to assess cells and architecture
open bx vs core needle bx vs FNA
![Page 11: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/11.jpg)
Lymph Node Protocol
Permanent sectionsMorphologic evaluation
ImmunostainsFlowcytometry Cytogenetics Molecular
![Page 12: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/12.jpg)
CD20
Detection enzyme
AntiCD20 antibody
![Page 13: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/13.jpg)
Flow-cytometry
![Page 14: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/14.jpg)
Flow-cytometryFlow-cytometry
![Page 15: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/15.jpg)
Flow-cytometry
![Page 16: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/16.jpg)
![Page 17: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/17.jpg)
Immunostains
![Page 18: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/18.jpg)
Non-Hodgkin Lymphomas
Neoplasm of the immune system
B-cells, T-cells, histiocytes
Usually begin in the lymph nodes, but may
arise in other lymphoid tissues such as
spleen, bone marrow, or extranodal sites
![Page 19: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/19.jpg)
Clinical Findings
Enlarged, painless lymphadenopathy
B-symptoms-fever, weight loss
Impingement or obstruction of other
structures
![Page 20: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/20.jpg)
Frequency %
I Diffuse Large B cell Lymphoma 422 31
L Follicular Lymphoma 306 22
L Chronic Lymphocytic Leukemia 88 6
I Mantle Cell Lymphoma 83 6
L Marginal Zone B-cell Lymphoma,MALT-type 72 5
L Marginal Zone B-cell Lymphoma,Nodal 20 1
L Lymphoplasmacytic Lymphoma 15 1
H Burkitt Lymphoma 10 <1
H Burkitt-like Lymphoma 29 2
H Lymphoblastic Lymphoma T/B 26 2
I Peripheral T cell Lymphoma 76 6
I Anaplastic Large T-/Null cell Lymphoma 33 2
Subtypes of Non-Hodgkin Lymphoma
![Page 21: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/21.jpg)
Most common types of lymphoma
1. Non-Hodgkin lymphoma (NHL)- SLL/CLL
- Follicular lymphoma
- Diffuse large B cell lymphoma
- Burkitt’s lymhoma
2. Hodgkin lymphoma (HL)
![Page 22: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/22.jpg)
Non-Hodgkin lymphoma
Diffuse
large B-cell
lymphoma
Follicular
lymphoma
Other NHL
Incidence
![Page 23: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/23.jpg)
General Features Low Grade Lymphomas
Adult population affected (median age, 50-70 years)
Rare in children
High stage disease (III/IV) is most common
Indolent course with relatively long survival
Generally incurable
Transformation to higher grade NHL may occur
![Page 24: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/24.jpg)
Small Lymphocytic Lymphoma
Low grade B-cell malignancy
Similar to chronic lymphocytic leukemia (CLL)
Frequency - ~ 4% of NHL
Older age group (median, 60.5 years)
Bone marrow involvement: Common
Indolent course
![Page 25: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/25.jpg)
![Page 26: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/26.jpg)
![Page 27: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/27.jpg)
Flow cytometry
![Page 28: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/28.jpg)
Follicular Lymphomas
Frequency -~40% of NHL (most common)
Older age group (median, 55 years)
Often asymptomatic
Bone marrow involvement: Common
Indolent Course
Chromosomal translocation, t(14;18)
![Page 29: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/29.jpg)
Follicular Lymphomas
Several chemotherapy options if symptomatic
Median survival: years
Transformation to more aggressive B-cell lymphoma
![Page 30: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/30.jpg)
Follicular Lymphoma
![Page 31: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/31.jpg)
Reactive Follicular Hyperplasia
![Page 32: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/32.jpg)
Architectural Features Distinguishing Reactive Follicular Hyperplasia and Follicular NHL
Reactive Follicular
Hyperplasia
Follicular NHL
Nodal Architecture Preserved Effaced
Germinal Center
Size & Shape
Marked variation Slight to moderate
variation
Capsular infiltration None or minimal Invasion with extension
into pericapsular fat
Density of follicles Low, with intervening
lymphoid tissue
High, with back to back
follicles
Morphology of follicles Sharply defined, mantle
zone
Ill defined, no mantle
zone
![Page 33: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/33.jpg)
Intermediate Grade/Aggressive
Mantle cell lymphoma
t(11;14) translocation results in
over- expression of cyclin D1 protein
Diffuse large cell lymphoma
![Page 34: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/34.jpg)
Diffuse Large Cell
60-70% derived from B-cells
Often stage I or II at diagnosis
More likely to have extranodal sites
Peripheral blood involvement is rare
![Page 35: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/35.jpg)
Diffuse large B-cell lymphoma
![Page 36: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/36.jpg)
Diffuse Large B-cell Lymphoma
CD20
H & E
![Page 37: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/37.jpg)
MIB-1
![Page 38: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/38.jpg)
High Grade (small non-cleaved)
Burkitt lymphoma
Endemic in Africa
Seen in children and related to
Epstein-Barr virus
Usually extranodal
AIDS associated lymphoma
![Page 39: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/39.jpg)
Clinical Findings
• Enlarged painless lymphadenopathy
• B-symptoms, fever, sweats, weight loss
• Impingement or obstruction of adjacent
structures (mass effect)
• Extranodal presentation (30% of cases)
GI tract, spleen, salivary gland
![Page 40: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/40.jpg)
Burkitt lymphoma
involving jaw
![Page 41: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/41.jpg)
Burkitt lymphoma - Starry-sky pattern
![Page 42: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/42.jpg)
Burkitt lymphoma tingible-body macrophages
![Page 43: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/43.jpg)
High grade Burkitt lymphoma
- Endemic in Africa
- Seen in children and related to Epstein-Barr virus
- B-cell phenotype
- t(8:14) MYC/IgH
- Usually extranodal
-High mitotic rate (starry-sky)
Lymphoblastic lymphoma
![Page 44: Lymphoma Diagnostic Work-up from a Lab Perspective - revis… · Lymphomas are solid tumors of the hematopoietic system. Neoplasms of lymphoid origin, typically causing lymphadenopathy](https://reader034.fdocuments.us/reader034/viewer/2022042210/5eadc4e3a32fc41d0f5edd3f/html5/thumbnails/44.jpg)
Sum…
Indolent Lymphomas
Very slow growing, over years.
Follicular lymphoma, grades I/II is prototype.
If can’t cure, goal is to control disease/symptoms.
Decision of WHEN to treat is important.
Aggressive Lymphomas
Rapidly growing, over days, months.
Diffuse large B cell lymphoma is prototype.
Cure is possible.
About 50% with multi-agent chemotherapy.