B-cell

Non Hodgkin Lymphoma

Endang SR Hardjolukito
Kursus Kolegium –KSPHL
PPDS-PA Kelas B
Surabaya 12-14 Mei 2023
INTRODUCTION
 Objectives

Recognized
Able to work- lymphoma Understand
Recognized
up lympho- entities based how to use
the differential
proliferative on WHO and interpret
diagnosis and
lesions based classification IHC to
it’s clinical
on histological 2017 diagnose
impact.
pattern frequently Lymphoma
found
 WHO 2017 - 2022
LYMPHOMA CLASSIFICATION
D
I
S
E
A
MALIGNANT LYMPHOMA
S
E

E
N
NON HODGKIN HODGKIN
T
I
T NLPHL
I
PRECURSOR MATURE
E B CELL & T CELL B CELL & T CELL CLASSIC
S
 MATURE B CELL NEOPLASM
CLL/SLL *
B prolymphocytic leuk.
Splenic marginal zone lymphoma
Hairy cell leuk.
Splenic lymphoma/leuk, unclass
Lymphoplasmacytic lymphoma *
Heavy chain diseases
Plasma cells neoplasms
Extranodalmarginal zone lymphoma*
(MALT lymphoma)
Nodal marginal zone lymphoma*
Follicular lymphoma *
Primary cutaneous follicle centre
lymphoma
Mantle cell lymphoma*
Diffuse large B cell lymphoma, NOS**
T cell /histiocyte rich large B cell
Lymphoma *
Primary DLBCL of the CNS
Primary cutaneous DLBCL, leg type
EBV positive DLBCL of the elderly
DLBCL ass with chronic inflammation
Lymphomatoid granulomatosis
Primary mediastinal (thymic) large B cell *
lymphoma
Intravascular large B cell lymphoma
ALK positive large B cell lymphoma
Plasmablastic lymphoma *
Large B cell lymphoma arising in HHV8
ass multicentric Castleman disease
Primary effusion lymphoma
Burkitt lymphoma *
B cell lymphoma, unclass. Wf
intermediate between DLBCL and *
Burkitt lymphoma
B cell lymphoma, unclass wf
intermediate between DLBCL and
Hodgkin lymphoma *
 Abbreviation
• SLL = small lymphocytic lymphoma
• MZL = marginal zone lymphoma
• ENMZL = extranodal MZL
• SMZL = splenic MZL
• MCL = mantle cell lymphoma
• B-MCl = blastoid MCL
• P-MCL = pleomorphic MCL
• LPL = lymphoplasmacytic lymphoma
• LB = lymphoblastic lymphoma
• BL = Burkitt lymphoma
• FL= follicular lymphoma
• D-FL= diffuse FL
• DLBCL-NOS= diffuse large B –cell
lymphoma, not otherwise specified
• Hi gr-BCL = high grade B-cell lymphoma
• T/HRLBCL = T-cell/histiocyte rich large B
cell lymphoma
• PB= plasmablastic lymphoma
• HL= Hodgkin lymphoma
• TCL= T-cell lymphoma
• ALCL= anaplastic large cell lymphoma
• ALK= anaplastic lymphoma kinase
• LBCL = large B-cell lymphoma
• IRF4 = interferon regulatory factor 4
 Diagnostic steps & components
Robust technique Diagnosis
& interpretation
Right panel
& interpretation Genetic/
molecular

Morphology
clues IHC
Complete
Relevant data
Morphology

Clinic WHO 2008, 2017

 Diagnostic approach

Growth pattern
Diffuse
Nodular Cell size
Sinusoidal Small
Medium
Large
Mixed
Algoritma Diagnosis Morfologik Limfoma berdasarkan pola
pertumbuhan tumor
Growth
pattern Ann Lymphoma 2019;3:3. doi: 10.21037/aol.2019.03.01 PATHOLOGICA 2019;111:1-16;

Modern Pathology (2021) 34:922–933

Cell Size
small : nucleus =/< HN
med : nucleus = HN
large : nucleus > HN
or >2x SL
( HN = histiocyte nucleus)
( SL = small lymphocyte)
Jaffe E ed. Hematopathology 2011

Rizzo K and Nassiri M. Lymphome Volume 2012, Article ID 346084 Hindawi Publishing Corporation
( Jaffe E et al, Hematopathology, 2017)
Marcus Hentrich Stefan K. Barta Editors . HIV-associated Hematological
Malignancies, Springers, 2016
Algoritma Diagnosis Morfologik Limfoma berdasarkan pola
pertumbuhan tumor
SMALL CELL
SLL / CLL
 SLL/CLL :

• 6-7% NHL in western, less in Asia

• M>F (1,5-2 : 1), median age 65-70 yo
• First diagnosed incidentally ( CLL)
• Less often Lymphadenopathy, anemia, thrombocytopenia, liver, spleen,
autoimmune, pulmonary infection
• 10% Paraprotein IgM, 30% hypo γ glob-emia
• Lymphocytosis
• Severe allergic reaction to insect bites
• Able to transform to DLBCL ( Richter syndrome )

WHO classification of Tumours of Haematopoeietic and lymphoid tissues, 2008

WHO classification of Tumours of Haematopoeietic and lymphoid tissues, Revised 2017
Jaffe ES, Arber DA, Campo E, Harris NL, Martinez LQ
Hematopathology 2nd ed, Elsevier 2017.
Jaffe ES, Arber DA, Campo E, Harris NL, Martinez LQ
Hematopathology 2nd ed, Elsevier 2017.
SLL : GROWTH CENTER
(pseudo-growth/ pseudo-follicle/proliferation center)

AFIP 3rd series fasc 14 , 1995, 2004

SLL JKC CHAN HK IAP 2004
 SLL/CLL

PROLIFERATION CENTER /

GROWTH CENTER / PSEUDO FOLLICLE

MCL
 MCL

• 3-10% NHL
• M>F (>2:1), middle age , median 60s
• LN, spleen, BM, Waldeyer ring, GI tract ( polyposis) , pleura
• Most present stg III-IV
• Lymphocytosis mimicking pro-lymphocytic leukemia
• Nodal considered aggressive
• Leukemic, non nodal , in situ are Indolent
• Relapse, as CNS-MCL
WHO classification of Tumours of Haematopoeietic and lymphoid tissues, 2008
WHO classification of Tumours of Haematopoeietic and lymphoid tissues revised 2017
 Monotonous small –medium sized
cells

Centrocyte-like cells

Scattered histiocytes ; starry sky like

Hialinized vascular

JKC, HK-IAP 2004

MCL : CC-LIKE

AFIP 3rd series fasc 14 , 1995

MCL

W KLAPPER, KIEL 2007, LYFE PATH

 C D

(C) Blastoid mantle cell lymphoma with a monotonous proliferation of medium-sized tumor cells, with slightly
irregular nuclei, open and vesicular chromatin, inconspicuous nucleoli and scant cytoplasm. Mitosis are
also observed. (D) Pleomorphic mantle cell lymphoma, composed of a heterogeneous population of large atypical
cells with irregular cleaved nuclei, vesicular chromatin and distinct nucleoli. Abundant mitoses are seen. All
stained with H&E, 40×.
Veloza L, Ribera-Cortada I, Campo E. Mantle cell lymphoma pathology update in the 2016 WHO classification. Ann Lymphoma 2019;3:3. doi: 10.21037/aol.2019.03.01
 MCL
CC-like cells
NAKED DENDRITIC NUCLEI /
EPITHELIOID HISTIOCYTE
HYALINIZED VASCULAR
 IHC profile
of MCL

Hindawi Publishing Corporation

Lymphoma
Volume 2012, Article ID 346084, 15 pages
doi:10.1155/2012/346084
Hindawi Publishing Corporation
Lymphoma
Volume 2012, Article ID 346084, 15 pages
doi:10.1155/2012/346084
Hindawi Publishing Corporation
Lymphoma
Volume 2012, Article ID 346084, 15 pages
doi:10.1155/2012/346084
 A, CD20 B, CD5

C, Cyclin D1 D, SOX 11

Figure 4 Typical immunophenotypic features of mantle cell lymphoma. (A) Tumor cells express CD20. (B) Co-expression of the T-
cell associated antigen CD5 is seen in all neoplastic cells. (C) Strong nuclear expression of cyclin D1 is seen in virtually all tumor
cells. (D) This case is SOX11-positive. All stained by immunohistochemical techniques, 40×.
Veloza L, Ribera-Cortada I, Campo E. Mantle cell lymphoma pathology update in the 2016 WHO classification. Ann Lymphoma 2019;3:3. doi: 10.21037/aol.2019.03.01
 MCL growth pattern
Nodular pattern

mantle zone pattern

Diffuse pattern

W KLAPPER, KIEL 2007, LYFE PATH

MCL
extranodal manifestation

W KLAPPER, KIEL 2007, LYFE PATH