NON-HODGKINS LYMPHOMA:

classification & diagnosis

PRESENTOR: DR. JYOTI RAJPOOT

MODERATOR: DR.AMIT KUMAR
YADAV
 BACKGROUND

• Early classifications: architectural and cytologic

characteristics of the neoplastic elements
• However, with increasing knowledge of the
complexity of the immune system a more functional
approach was sought.
• The integration of immunologic functions with
morphologic descriptions of that era was best
exemplified by the Kiel classification.
 Histologic classification of
non-Hodgkin’s lymphomas

1. Rappaport - 1966
2. Lukes and Collins - 1974
3. Dorfman - 1974
4. Bennet et al., - 1974
5. Lennert - 1974
6. WHO - 1976
7. Working Formulation - 1982
8. REAL - 1994
9. WHO - 1999
Rappaport and Lukes Collins
This classification was developed before lymphoid cells
were divided into B-cells and T-cells. It was developed
in 1966 with the Lukes Collins modifications in 1974

Well-differentiated
lymphocytic lymphoma

Poorly differentiated
lymphocytic lymphoma

Histiocytic lymphoma
 Kiel Classification
This was developed in 1974, the first to
recognize B and T cell subtypes
B-cell T-cell
Low grade Low grade
*Lymphocytic -chronic lymphocytic and
Lymphocytic -chronic lymphocytic and
prolymphocytic leukemia -hairy-cell
prolymphocytic leukemia
leukemia
Small, cerebriform cell -mycosis
-
fungoides, Sézary's syndrome
Lymphoplasmacytic/cytoid (LP
Lymphoepithelioid (Lennert's lymphoma)
immunocytoma)
Plasmacytic Angioimmunoblastic (AILD, LgX)
*Centroblastic/centrocytic - follicular ±
T-zone
diffuse - diffuse
* Centrocytic Pleomorphicm, small cell (HTLV-1
High grade High grade
Pleomorphic, medium and large cell
Centroblastic
(HTLV-1 ±)
*Immunoblastic Immunoblastic (HTLV-1 ±)
*Large cell anaplastic
Large cell anaplastic (Ki-1+)
(Ki-1+
Burkitt's lymphoma -
*Lymphoblastic Lymphoblastic
Rare types Rare types
Working Formulation
This was developed by the National
Cancer Institute in 1982

Low grade Intermediate grade High grade

Large cell
Small lymphocytic Follicular large cell
immunoblastic
Follicular Diffuse small
Lymphoblastic
small-cleaved cell cleaved cell

Follicular mixed Small non-cleaved

Diffuse mixed small
small-cleaved and cell (Burkitt and
and large cell
large cell non-Burkitt type)

Diffuse large cell

WHO Classification:
B-Cell Malignancies
Precursor B-cell neoplasm
• Precursor B-lymphoblastic leukemia/lymphoma

Mature (peripheral) B-cell neoplasms

• B-cell chronic lymphocytic leukemia/ • Hairy cell leukemia
small lymphocytic lymphoma • Plasma-cell myeloma/
• B-cell prolymphocytic leukemia plasmacytoma
• Lymphoplasmacytic lymphoma • Follicular lymphoma
• Splenic marginal-zone B-cell lymphoma • Mantle-cell lymphoma
• Nodal marginal-zone lymphoma • Diffuse large B-cell lymphoma
• Extranodal marginal-zone B-cell (DLBCL)
lymphoma, mucosa-associated • Burkitt's lymphoma/Burkitt's cell
lymphoid tissue (MALT) type leukemia
• Blastic NK-cell leukemia

Harris NL et al. J Clin Oncol. 1999;17:3835-3849.

 WHO Classification:
T-Cell Malignancies
Precursor T-cell neoplasm
• Precursor T-lymphoblastic leukemia/lymphoma

Mature (peripheral) T-cell neoplasms

• T-cell prolymphocytic leukemia • Subcutaneous panniculitis-like T-cell
• T-cell granular lymphocytic leukemia lymphoma
• Aggressive NK-cell leukemia • Mycosis fungoides/Sézary syndrome
• Adult T-cell lymphoma/leukemia (HTLV1+) • Primary cutaneous anaplastic large cell
lymphoma, T/null cell
• Extranodal NK/T-cell lymphoma, nasal type
• Peripheral T-cell lymphoma, unspecified
• Enteropathy-type T-cell lymphoma
• Angioimmunoblastic T-cell lymphoma
• Hepatosplenic gamma-delta T-cell
lymphoma • Primary systemic anaplastic large cell
lymphoma, T/null cell
• Blastic NK lymphoma

Harris NL et al. J Clin Oncol. 1999;17:3835-3849.

 Lymph node anatomy

• To recognize
lymph node
pathology,
one has to be
familiar with
normal lymph
node anatomy
and cytology
CD 20+
B CELLS
CD3+
T-cells
 WHAT IS NODAL EFFACEMENT

• Loss of normal architecture of lymph node.

• May be Partial or Diffuse.
Normal appearance of a benign reactive lymph node. At the top is the
capsule and just under that a subcapsular sinus where lymphatics
enter that drain tissues peripheral to the node. Beneath the capsule is the
paracortical zone with lymphoid follicles having a pale germinal
center in which the immune responses are often generated.
At high magnification is seen a lymph node follicle with a germinal center
containing larger lymphocytes undergoing activation. At the lower right is the
subcapsular sinus.
This is a more pronounced reactive change in a lymph node, with a
larger follicle and germinal center containing 'tingible body' macrophages.
These large macrophages are involved in phagocytosis of antigenic material
passed from follicular dendritic cells to be processed into peptides.
At high magnification, the germinal center in this reactive lymph node
follicle has prominent macrophages. These macrophages are processing antigen to pass to
lymphocytes to stimulate specific immune responses. Antigen can be brought to the node
via lymphatics or via bloodstream. Specific clones of lymphocytes are attracted to
and migrate through to their respective antigens via high endothelial cells of venules.
• Some of the most common types of NHL's in
the REAL (revised European-American
lymphoma) classification:
Type Histologic Features Immunogenetics Clinical Features
Small Lymphocytic Small and CD19, 5; Bcl-2 and Seen in older adults,
Lymphoma well-differentiated B Bcl-6 expression it is essentially the
lymphocytes, with solid tissue (lymph
diffuse effacement of nodal) component of
nodal architecture chronic lymphocytic
and no follicles leukemia; disease
tends to be
generalized but with
indolent course and
prolonged survival;
some may transform
to more aggressive
lymphomas
Follicular Lymphoma Nodal architecture is CD19, 20, 79a; Most common type,
(predominantly small effaced by t(14:18); Bcl-2 seen in adults, often
cell) monotonous, expression involves multiple
crowded follicles lymph nodes, course
composed of is indolent, with
monomorphous small prolonged survival,
cleaved though some may
B-lymphocytes transform to a large
cell lymphoma
Diffuse Large B-cell Cells are large, with CD19, 20, 79a; some Though often
Lymphoma prominent nucleoli have t(14;18); some localized, they tend
and abundant have Bcl-2 and Bcl-6 to be aggressive
cytoplasm and many expression; linked to extranodal masses;
mitoses. Most are EBV infection; seen in adults and
B-cell, but 20% are negative TdT children, can be seen
T-cell phenotype in HIV infections
Burkitt Lymphoma Intermediate sized CD10, 19, 20, 79a; Endemic in Africa
B-lymphocytes t(8:14) is with mandibular and
(small-noncleaved characteristic; abdominal
cells) African form linked to involvement;
EBV infection; sporadic elsewhere
negative TdT with abdominal
involvement; affects
mainly children and
young adults

High-grade B-cell Intermediate sized CD19, 20 Sporadic; may be

Lymphoma (small B-lymphocytes (small seen with HIV
non-cleaved) non-cleaved cells) infection
Burkitt-like
Lymphoma

Precursor T or B-cell Intermediate sized B-cells are CD19, 20, Seen in children and
Lymphoblastic lymphocytes in a sometimes CD10; adolescents; T-cell
Lymphoma/Leukemia diffuse pattern T-cells are CD3 and type often in
(Lymphoblastic 8; all are TdT positive mediastinum; very
Lymphoma) aggressive and can
progress to acute
lymphocytic
leukemia
Mantle Cell Small to medium CD 19, 20, 43; Seen in adults in
Lymphoma sized B cells t(11;14); Bcl-1 middle age; often
(Cyclin D1) advanced at
expression diagnosis and may
be extranodal,
including multifocal
submucosal nodules
in bowel
Marginal Zone Small to medium CD19, 20, 79a; Seen in middle aged
Lymphoma sized B cells negative CD5 and 10 adults; typically
arises in areas of
immune activation
(Hashimoto
thyroiditis, Sjogren
syndrome, Helicobac
ter pylori gastritis);
similar lesions
asociated with
mucosal lymphoid
tissue are called
MALTomas
(mucosa-associated
lymphoid tissue
tumors); may
transform to diffuse
large B-cell
lymphoma
Here is a lymph node involved by lymphoma. The capsule of the node has been
invaded and the lymphomatous cells extend into the surrounding adipose tissue. Note
that the follicles are numerous and irregularly sized. This is a follicular center cell
malignant lymphoma (also described as small cleaved cell type, follicular, or as
malignant lymphoma, poorly differentiated lymphocytic type, nodular).
This pattern of malignant lymphoma is diffuse and no lymphoid follicles are identified in this
lymph node. Note that the normal architecture of the lymph node is obliterated. The lymph
node is replaced by an infiltrate of small (mature-appearing) neoplastic lymphocytes, and
the infiltrate extends through the capsule of the lymph node and into the surrounding fat.
These cells will mark as B lymphocytes. The diagnosis is: small lymphocytic lymphoma
(SLL). This is the tissue equivalent of chronic lymphocytic leukemia (CLL), and both often
occur together (CLL/SLL). Though both are indolent, they are widespread and difficult to
treat.
Many non-Hodgkin's lymphomas seen in adults are large cell lymphomas
such as the one here at medium power, but they can be associated with
immunosuppressed states (such as AIDS), and are typically of B cell origin.
The cells are large, with prominent nucleoli and abundant cytoplasm.
This disease tends to be localized (low stage), but with more rapid enlargement,
and a greater propensity to be extranodal than the low grade lymphomas.
The malignant lymphocytes here are very large with a moderately abundant cytoplasm,
and the nuclei are round to ovoid with prominent nucleoli and occasional mitoses.
The diagnosis is diffuse large B cell lymphoma (also known as immunoblastic lymphoma).
The major differential diagnosis in this case would be a metastatic carcinoma.
The presence of monoclonal immunoglobulin as demonstrated by IHC would help to
confirm this lesion as a malignant lymphoma. Demonstration of CD19 and 20 antigens
would classify it as B cell in origin.
B-cell neoplasms relate to different stages of B-cell differentiation. Precursor B-cell
lymphomas/leukemias are at an antigen-independent stage of differentiation. CD79a is
expressed from early B cells to the plasma cell stage of differentiation. CD20 is acquired at
the time of light-chain gene rearrangement. HCR, heavy-chain rearrangement; κR/D, kappa
light-chain gene rearrangement/deletion; λR/D, lambda light-chain gene rearrangement/
deletion; GC, germinal center; cyto μ, cytoplasmic mu heavy chain.
• The WHO classification represents a significant
achievement in terms of cooperation, communication,
and consensus among pathologists, hematologists, and
oncologists. Furthermore, it recognizes, as in the REAL
classification, that any classification system is an
evolving process and should incorporate new data
resulting from recent technologic advances in the field of
hematopathology and is subjected to periodical review
and revisions.
PRECURSOR B-CELL NEOPLASM:
B-Lymphoblastic Leukemia/Lymphoma

Lymphoblastic lymphoma. Low power (A) and higher power (B)

showing a diffuse infiltrate of intermediate-sized cells with high
mitotic rate and finely dispersed “blastic” nuclear chromatin (C). Touch imprints performed
at the time of the biopsy (D) illustrate the fact that the lymphoma cells are
identical to circulating lymphoblasts seen in acute lymphoblastic leukemia (E).
 B-Lymphoblastic
Leukemia/Lymphoma
• Most B-lymphoblastic leukemia/lymphoma (B-LBL) present
as leukemia
• Lymphomatous presentations: 5% to 10% of cases
• Most common: children and young adults
• Cytologically, it is composed of lymphoblasts that are
usually somewhat larger than a small lymphocyte, but
smaller than the cells of diffuse large B-cell lymphoma.
• The cells have finely stippled chromatin with very sparse
cytoplasm and inconspicuous nucleoli.
• Mitotic figures are frequent, in keeping with the
high-grade nature of this neoplasm.
• The differential diagnosis of B-LBL includes the blastic
variant of a mantle cell lymphoma (MCL).
• The clinical presentation is useful in that MCL is much
more common in adults.
• In some cases immunophenotypic studies will be
required for the differential diagnosis. The blastic
variant of MCL is TDT- and has a mature B-cell
phenotype, in contrast to B-LBL.
MATURE B-CELL NEOPLASMS :
Comprise over 90 percent of lymphoid
neoplasms worldwide. They represent
approximately 4 percent of all new cancers
each year .

Chronic lymphocytic leukemia / small lymphocytic

lymphoma (CLL/SLL) : usually presents in adults with
generalized lymphadenopathy, frequent marrow and
blood involvement, and often hepatosplenomegaly.
• Presentation as leukemia, that is, CLL, is more common
than as lymphoma, SLL.
• Histologically, the lymph nodes show diffuse
architectural effacement
• In this regard, the process may simulate a mantle
cell lymphoma, but usually can be readily
distinguished from MCL on cytologic grounds.
• The predominant cell is a small lymphocyte with
clumped nuclear chromatin, but a spectrum of
nuclear morphology is generally seen.
Small lymphocytic lymphoma (SLL). Low power illustrates a diffuse effacement
of the lymph node. A monotonous population of small lymphocytes is seen at
higher power (B).
These have fairly round nuclear contours, condensed nuclear chromatin, and
inconspicuous or absent nucleoli. Only rare larger cells are present. SLL can
transform to large cell lymphoma (C) and occasionally to Hodgkin lymphoma
(D). Patients can also develop worsening lymphadenopathy as a result of viral
infections such as Herpes Simplex Virus, where the node typically shows focal
necrosis (E).
•Immunophenotype- pan B cell markers CD19
and CD20, as well as CD23 and CD5, the latter a marker that is
found on a small subset of normal B cells.
•Chromosomal translocations rare, most common findings are
deletions of 13q14.3, 11q, and 17p, and trisomy 12q.
 Differential Diagnosis of “Small”
B-Cell Lymphomas

Cyclin
Disease CD5 CD10 CD23 CD43 D1 Ig Class
FL - + +/- - - IgM,
IgG
MCL + - - + + IgM/IgD
CLL/SLL + - + + - IgM/IgD

LPL - - - +/- - IgM (c)

MALT - - - +/- - IgM (c,
s)
SMZL - - - - - IgM/IgD
HCL - - - - -/+ IgG
 Lymphoplasmacytic Lymphoma

• Peripheral blood involvement with an absolute

lymphocytosis is less common in lymphoplasmacytic
lymphoma (LPL) than in B-cell CLL/SLL.
• The tumour consists of a diffuse proliferation of small
lymphocytes, plasmacytoid lymphocytes (cells with
abundant basophilic cytoplasm but lymphocyte-like
nuclei), and plasma cells, with or without Dutcher
bodies. The growth pattern is often interfollicular with
sparing of the sinuses.
A bone marrow aspirate for WM shows the characteristic cell
population
• The neoplastic cells have surface and cytoplasmic
Ig, usually of IgM type, usually lack IgD, and
express B cell-associated antigens (CD19, 20, 22,
79a), CD5-, CD10-, CD43+/-; CD25 or CD11c may be
faintly positive in some cases. Lack of CD5 and
the presence of strong cIg are useful in
distinction from CLL
 Mantle Cell Lymphoma-

• Adults (median age 62)

• High male-to-female ratio
• Gastrointestinal tract involvement is frequent and is
associated with the picture of lymphomatous polyposis.
• The hallmark of MCL is a very monotonous cytologic
composition.
• In the typical case, the cells are slightly larger than a
normal lymphocyte with finely clumped chromatin, scant
cytoplasm, and inconspicuous nucleoli.
• The nuclear contour is usually irregular or cleaved. Some
cytologic variants, blastoid (blastic) and pleomorphic, tend
to be associated with a more aggressive coorse.
IHC-

• The immunophenotype is distinctive (cyclin D1,

IgM/IgD+, CD5+, CD10-, and CD23-).
 Extranodal Marginal-Zone B-Cell
Lymphoma of Mucosa-Associated
Lymphoid Tissue Type

• MALT lymphomas are characterized by a heterogeneous

cellular composition that includes marginal-zone or
centrocyte-like cells, monocytoid B cells, small
lymphocytes, and plasma cells.
• The follicles usually contain reactive germinal centers,
but the germinal centers may become colonized by
neoplastic cells. When follicular colonization occurs, the
process may simulate follicular lymphoma. The plasma
cells are usually found in the subepithelial zones and are
monoclonal in up to 50% of cases.
Marginal-zone lymphomas commonly occur at extranodal sites from
mucosa associated lymphoid tissue (MALT). MALT-lymphomas are
composed of small- to intermediate-sized cells with abundant cytoplasm.
These typically infiltrate or invade into epithelial structures resulting
in lymphoepithelial lesions (A). Normal lymph nodes do not have a
marginal zone, but primary nodal marginal-zone lymphomas (NMZL)
can occur. They infiltrate the node in what would be a marginal-zone
(peripheral to mantle cells) pattern (B). The spleen does have a normal
marginal zone, and this can give rise to a splenic marginal-zone lymphoma
(SMZL). Early on, these show expansion of the marginal-
zone areas (C) but later can become more diffuse, infiltrating the red pulp.
 .

❖ Diffuse large B cell lymphoma-

most common form of NHL.
morphology- large tumour cells (4-5 times size of
small lymphocyte), having round to oval nucleus
appearing vesicular owing to margination of
chromatin at nuclear membrane.
Diffuse pattern of growth
IHC- express CD 19, CD 20
variable expression of CD 10 and Bcl-6,
positive for SIg, all negative for Tdt.
 Diffuse large B Cell Lymphoma

Diffuse pattern of
growth
Lymphoblastic lymphoma. Low power (A) and higher power (B)
showing a diffuse infiltrate of intermediate-sized cells with high
mitotic rate and finely dispersed “blastic” nuclear chromatin (C).
Touch imprints performed at the time of the biopsy (D)
illustrate the fact that the lymphomacells are identical to
circulating lymphoblasts seen in acute lymphoblastic leukemia (E).
❖Follicular Lymphoma –
Follicular lymphoma is the most common
form of indolent NHL. Term follicular means
cells tend to grow in circular pattern in
lymph node.
Morphology- nodular or nodular and diffuse
growth pattern in the involved lymph node.

Two principal cell types- (1) small cells with

irregular or cleaved nuclear contours and scant
cytoplasm, referred to as centrocytes (small
cleaved cells); and
(2) larger cells with open nuclear chromatin,
several nucleoli, and modest amounts of
cytoplasm, referred to as centroblasts.
Bone marrow involvement in 85% cases.
Immunophenotype-
The neoplastic cells closely resemble normal
germinal center B cells, expressing CD19, CD20,
CD10, surface Ig, and BCL6.

Unlike CLL/SLL and mantle cell lymphoma, CD5

is not expressed. BCL2 is expressed in more
than 90% of cases, in distinction to normal
follicular center B cells, which are
BCL2-negative.
.
Hallmark of follicular lymphoma ( in 90%
cases)- t(14; 18) leading to overexpression
of BCL2 which antagonizes apoptosis
Three major grades according to
the current WHO classification
GRADE centroblasts/hpf

grade 1 <5

grade 2 5–15

grade 3 >15

3a >15 centroblasts/hpf
but centrocytes still
present

3b solid sheet of
centroblasts)
Follicular lymphoma-showing nodular pattern
 Difference between reactive follicular
hyperplasia and lymphoma
Reactive follicular Follicular lymphoma
hyperplasia

Low density of follicles

Reactive follicular High densitylymphoma
• Follicular of follicles
hyperplasia
Follicles usually limited to subcortical Follicles distributed evenly
region throughout nodal parenchyma
Follicles often extend beyond
Follicles rarely extend beyond capsule
capsule
Follicles usually of similar size and
Follicles of uneven size and shape
shape
Monomorphic or polymorphic
Mixture of cell types in germinal center
population
Tingible-body macrophages usually
Tingible-body macrophages present
rare
Follicular hyperplasia Follicular lymphoma
Reactive follicular Follicular lymphoma
hyperplasia
Usually moderate to high mitotic rate Usually low to moderate mitotic rate

Mantle zone usually distinct Mantle zone usually indistinct or absent

Cell polarization often seen Cell polarization usually absent

Large interfollicular areas evident Compressed interfollicular areas

May contain Areas of nodal
Areas of nodal effacement not seen
effacement
Burkitt Lymphoma-
1-2% of all lymphomas. 90% cases are males and affects children
and young adults.
Within this category fall (1) African (endemic, children, mandible
or maxilla mass) Burkitt lymphoma, (2) sporadic (nonendemic)
Burkitt lymphoma, and (3) a subset of aggressive lymphomas
occurring in individuals infected with HIV.
.
Morphology-Involved tissues are effaced by a diffuse
infiltrate of intermediate-sized lymphoid cells 10 to 25 μm in
diameter with round or oval nuclei, coarse chromatin,
several nucleoli, and a moderate amount of cytoplasm

The tumor exhibits a high mitotic index and contains

numerous apoptotic cells, the nuclear remnants of which are
phagocytosed by interspersed benign macrophages. These
phagocytes have abundant clear cytoplasm, creating a
characteristic “starry sky” pattern.
This cytologic preparation of a Burkitt lymphoma shows the
characteristic basophilic cytoplasm with vacuoles, the and the
prominent nucleoli.
Hairy Cell Leukemia
This rare but distinctive B-cell neoplasm constitutes about 2%
of all leukemias.
Morphology-
On routine peripheral blood smears, hairy cells have round,
oblong, or reniform nuclei and moderate amounts of pale blue
cytoplasm with threadlike or bleblike extensions.
Immunophenotype- positive for CD 19, 20, 11C, CD 25 and
CD103.
• Classic hairy cell with a smoothly contoured, round
nucleus, moderate amount of cytoplasm with
circumferential hairlike projections.
The “pale” appearance of the marrow is due the presence of abundant
cytoplasm in leukemic cells. This may give rise to the typical “fried
egg” appearance in some cells (arrow)
 Precursor T cell neoplasm –
T Cell Lymphoblastic
Lymphoma/Leukemia
• Cytologically indistinguishable from their B-cell
counterparts.
• The cells have finely distributed chromatin, inconspicuous
nucleoli, and sparse, pale cytoplasm. Nuclear irregularity
is variable.
• 50-80% : anterior mediastinal mass(usually with
involvement of the thymus gland)
• This is a high-grade lymphoma
• Bone marrow involvement is common
Mature T cell neoplasm- rare
neoplasm.
• Mycosis Fungoides/Sézary Syndrome-
tumor f CD4+ helper T cells that home to the
skin.
• Histologically, the epidermis and upper
dermis are infiltrated by neoplastic T cells,
which often have a cerebriform appearance
due to marked infolding of the nuclear
membrane.
• Cerebriform Sézary Cell (convulated nucleus of
T cell)
Extranodal NK/T-Cell
Lymphoma

Rare in US & Europe but 3% of NHLs in Asia

Presents as destructive nasopharyngeal mass.
Tumor cells are of variable size usually includes cell large
component.
Necrosis is commonly present and may obscure the true identity
of tumor in small biopsy specimens
invasion of a small sized artery/arteriole by tumor cells
 What should we do ?
when we meet a patient with
suspected non-Hodgkin’s lymphoma
PAST HISTORY
• A personal or family history malignancy,
radiation therapy,
immunosuppressive agents,
chemotherapy,
organ transplantation， etc.

• Relevant infectious illnesses HIV-I,

HTLV-I,
Epstein-Barr virus (EBV),
hepatitis C virus,
Pyothorax-associated
lymphoma.

• Connective tissue diseases, immunodeficiency

disorders etc.
• Agricultural to pesticides and Agent Orange
 CHIEF COMPLAINTS
Systemic complaints (B symptoms)
* Fever — temperature >38ºC
* Weight loss >10 percent over the past six
months
* Sweats — the presence of drenching night
sweats
Lymphadenopathy
* Rapid and progressive or Waxing and waning
* The duration, observed sites, and extent
* Peripheral lymphocytosis
 ONCOLOGIC EMERGENCIES
• Spinal cord compression
• Pericardial tamponade
• Hypercalcemia (adult T cell lymphoma)
• Superior or inferior vena cava obstruction
• Hyperleukocytosis (lymphoblastic lymphoma)
• Acute airway obstruction (mediastinal lymphoma)
• Lymphomatous meningitis and/or CNS mass
• Hyperuricemia and tumor lysis syndrome
• Hyperviscosity syndrome
• Intestinal obstruction, intussusception
• Ureteral obstruction, unilateral or bilateral
• Severe hepatic dysfunction
• Venous thromboembolic disease
• Severe autoimmune hemolytic anemia and/or thrombocytopenia
PHYSICAL EXAMINATION
• Waldeyer's ring
• Standard lymph node sites
• Liver and spleen
• Abdominal nodal sites (mesenteric,
retroperitoneal)
• Less commonly involved nodal sites (eg,
occipital, preauricular, epitrochlear,
popliteal)
PHYSICAL EXAMINATION： Head and Neck
Chest and lungs
• ~ 20% of pts with NHL present with mediastinal
adenopathy.
• A superior vena caval syndrome is part of the clinical
presentation (3 to 8 %).
• Pleural disease is seen in about 10 percent of all
patients with NHL at diagnosis.
• The differential diagnosis of mediastinal presentation
includes

infections,
sarcoidosis,
Hodgkin's
lymphoma, other
neoplasms.
Abdomen and pelvis
• Retroperitoneal, mesenteric, and pelvic
involvement is common in most histologic
subtypes of NHL.
• Diffuse hepatosplenomegaly is common in the
indolent lymphomas,
• Hepatic masses are more commonly seen in
the aggressive or highly aggressive
lymphomas.
• Not all focal liver lesions in a patient with
NHL are due to lymphoma.
• Ascites may be present
PHYSICAL EXAMINATION： Abdomen and Pelvis
Extranodal sites
• Patients with NHL will have primary extranodal
lymphoma at initial Diagnosis (10~35 %).
• The most common site of primary extranodal disease is
the GI tract, followed by skin.
• Symptoms due to extralymphatic disease are usually
associated with aggressive NHL.
• The skin should be carefully examined for lesions; all
suspicious areas should be biopsied.
INITIAL LABORATORY STUDIES
• CBC with differential
• Renal and hepatic function
• Serum calcium, electrolytes, and uric acid
• Serum protein electrophoresis
• the tumor markers
beta-2 microglobulin
lactate dehydrogenase
etc
LYMPH NODE AND TISSUE BIOPSY
• Peripheral lymphonodes
• CT-guided core needle biopsies
• Bone marrow examination
•Laparoscopic multiple biopsies
• Surgical operation
Lymph node selection
• Size:
* Significant enlargement
* Persistence for more than four to six
weeks
• Site:
* Supraclavicular nodes — 75 to 90 percent
* Cervical and axillary nodes — 60 to 70
percent
* Inguinal nodes — 30 to 40 percent
Studies on excised tissue
• An intact lymph node is critical for histologic,
immunologic, molecular biologic assessment.
• The FNA findings of "lymphoma" requires to be
confirmed.
• Immunologic, cytogenetic, and molecular studies are
useful for making therapeutic decisions and assessing
prognosis.
Bone marrow examination
• BM involvement occurs commonly in the
indolent histologies.
• BM aspirates / BM biopsy
This is the appearance of normal bone marrow at medium magnification.
Note the presence of megakaryocytes, erythroid islands, and
granulocytic precursors. This marrow is taken from the posterior iliac
crest in a middle aged person, so it is about 50% cellular, with
steatocytes admixed with the marrow elements
• ]. A normal marrow is said to show trilineage hematopoiesis (TLH) meaning that elements of all three
major cell lines are represented. These cell lines include myelomonocytic cells, erythroid cells, and
megakaryocytic cells. However, other cells types are also present including lymphocytes, plasma
cells, connective tissue cells and stromal cells. Two histiocytes are present (arrowheads) engulfing
cellular debris. The nucleated erythroid precursors are also dispersed (two long arrows) throughout
the marrow. Two normal megakaryocytes are apparent in this field (two big arrows). A binucleated
eosinophil is identified with an arrow with tai
This is the appearance of normal bone marrow smear
at high magnification. Note thepresence of an eosinophilic myelocyte,
abasophilic myelocyte, and a plasma cell.
• Peritrabecular lymphomatous infiltrate
CLINICAL EVALUATION
"B" symptoms
• “B” symptoms are more common in
aggressive/ highly aggressive histologies (47%)
.
• < 25 % with indolent lymphomas have B
symptoms.
International Prognostic Index

• Age >60
• Serum LDH
• ECOG performance status 2
• Ann Arbor clinical stage III or IV
• Number of involved extranodal disease sites
>1
ECOG Performance Status
Performance Status Definition

0 Fully active; able to carry on all pre-disease performance witout restrictions

1 Strenuos physical activity restricted; fully ambulatory and

able to carry out light work

2 Capable of all selfcare but unable to carry out any work

activities, Up and about more than 50 percent of waking hours

3 Capable of only limited selfcare; confined to bed or chair,

less than50% of waking hours

4 Completely disabled; cannot carry out any selfcare; totally

confined to bed or chair

5 Dead
THANKS